A two-center study of a combined nomogram based on mammography and MRI to predict ALN metastasis in breast cancer.

OBJECTIVES: To develop and validate a predictive method for axillary lymph node (ALN) metastasis of breast cancer by using radiomics based on mammography and MRI. MATERIALS AND METHODS: A retrospective analysis of 492 women from center 1 (The affiliated Hospital of Qingdao University) and center 2 (Yantai Yuhuangding Hospital) with primary breast cancer from August 2013 to May 2021 was carried out. The radscore was calculated using the features screened based on preoperative mammography and MRI from the training cohort of Center 1 (n = 231), then tested in the validation cohort (n = 99), an internal test cohort (n = 90) from Center 1, and an external test cohort (n = 72) from Center 2. Univariate and multivariate analyses were used to screen for the clinical and radiological characteristics most associated with ALN metastasis. A combined nomogram was established in combination with radscore that predicted the clinicopathological and radiological characteristics. Calibration curves were used to test the effectiveness of the combined nomogram. The receiver operating characteristic (ROC) curve was used to evaluate the performance of the combined nomogram and then compare with the clinical and radiomic models. The decision curve analysis (DCA) value was used to evaluate the combined nomogram for clinical applications. RESULTS: The constructed combined nomogram incorporating the radscore and MRI-reported ALN metastasis status exhibited good calibration and outperformed the radiomics signatures in predicting ALN metastasis (area under the curve [AUC]: 0.886 vs. 0.846 in the training cohort; 0.826 vs. 0.762 in the validation cohort; 0.925 vs. 0.899 in the internal test cohort; and 0.902 vs. 0.793 in the external test cohort). The combination nomogram achieved a higher AUC in the training cohort (0.886 vs. 0.786) and the internal test cohort (0.925 vs. 0.780) and similar AUCs in the validation (0.826 vs. 0.811) and external test (0.902 vs. 0.837) cohorts than the clinical model. CONCLUSION: A combined nomogram based on mammography and MRI can be used for preoperative prediction of ALN metastasis in primary breast cancer.

Assessment of right ventricular diastolic function in pediatric patients with repaired tetralogy of Fallot by cardiovascular magnetic resonance and echocardiography.

OBJECTIVES: Cardiovascular magnetic resonance (CMR) imaging is routinely performed for assessing right ventricular (RV) systolic but not diastolic function. We aimed to investigate CMR-based assessment of RV diastolic function in pediatric patients with repaired tetralogy of Fallot (rTOF), compared to transthoracic echocardiography (TTE) measurements. METHODS: A total of 130 consecutive pediatric patients with rTOF who underwent clinically indicated CMR and same-day TTE were included. Forty-three controls were recruited. Phase-contrast images were used to measure trans-tricuspid valve flow velocities during early (E) and late diastolic (A) phases (measured in cm/s). Feature tracking of the tricuspid annulus was performed to derive early (e') and late diastolic (a') myocardial velocities (measured in cm/s). RV diastolic function was evaluated by E/A ratio, E/e' ratio, and E-wave deceleration time (measured in milliseconds). Regression analyses were utilized to identify potential variables associated with RV diastolic dysfunction (DD). The performance of CMR-derived parameters in diagnosing RV DD was assessed using receiver-operating characteristic analyses. RESULTS: Good agreement was found between CMR and TTE measurements (ICC 0.70-0.89). Patients with RV DD (n = 67) showed significantly different CMR-derived parameters including E and e' velocities, and E/A and E/e' ratio, compared to patients without DD (n = 63) (all p < 0.05). CMR-derived E and e' velocities and E/e' ratio were independent predictors of RV DD. E/e' of 5.8 demonstrated the highest discrimination of RV DD (AUC 0.76, sensitivity 70%, specificity 86%). CONCLUSIONS: CMR-derived parameters showed good agreement with TTE parameters in determining RV DD. CMR-derived E/e' was proved to be the most effective in identifying RV DD. CLINICAL RELEVANCE STATEMENT: This study demonstrated the feasibility and efficacy of CMR in assessing diastolic function in pediatric patients. RV DD was presented in over half of patients according to current TTE guidelines, highlighting the need for assessing RV diastolic function during follow-up. KEY POINTS: • Routinely acquired cine and phase-contrast cardiovascular magnetic resonance (CMR) images yielded right ventricular (RV) diastolic parameters which demonstrated good agreement with transthoracic echocardiography (TTE) measurements. • There was a high prevalence of RV diastolic function impairment in pediatric patients with repaired tetralogy of Fallot (rTOF). • CMR is a reliable complementary modality of TTE for RV diastolic function evaluation.

Novel, high accuracy models for hepatocellular carcinoma prediction based on longitudinal data and cell-free DNA signatures.

BACKGROUND & AIMS: Current hepatocellular carcinoma (HCC) risk scores do not reflect changes in HCC risk resulting from liver disease progression/regression over time. We aimed to develop and validate two novel prediction models using multivariate longitudinal data, with or without cell-free DNA (cfDNA) signatures. METHODS: A total of 13,728 patients from two nationwide multicenter prospective observational cohorts, the majority of whom had chronic hepatitis B, were enrolled. aMAP score, as one of the most promising HCC prediction models, was evaluated for each patient. Low-pass whole-genome sequencing was used to derive multi-modal cfDNA fragmentomics features. A longitudinal discriminant analysis algorithm was used to model longitudinal profiles of patient biomarkers and estimate the risk of HCC development. RESULTS: We developed and externally validated two novel HCC prediction models with a greater accuracy, termed aMAP-2 and aMAP-2 Plus scores. The aMAP-2 score, calculated with longitudinal data on the aMAP score and alpha-fetoprotein values during an up to 8-year follow-up, performed superbly in the training and external validation cohorts (AUC 0.83-0.84). The aMAP-2 score showed further improvement and accurately divided aMAP-defined high-risk patients into two groups with 5-year cumulative HCC incidences of 23.4% and 4.1%, respectively (p = 0.0065). The aMAP-2 Plus score, which incorporates cfDNA signatures (nucleosome, fragment and motif scores), optimized the prediction of HCC development, especially for patients with cirrhosis (AUC 0.85-0.89). Importantly, the stepwise approach (aMAP -> aMAP-2 -> aMAP-2 Plus) stratified patients with cirrhosis into two groups, comprising 90% and 10% of the cohort, with an annual HCC incidence of 0.8% and 12.5%, respectively (p <0.0001). CONCLUSIONS: aMAP-2 and aMAP-2 Plus scores are highly accurate in predicting HCC. The stepwise application of aMAP scores provides an improved enrichment strategy, identifying patients at a high risk of HCC, which could effectively guide individualized HCC surveillance. IMPACT AND IMPLICATIONS: In this multicenter nationwide cohort study, we developed and externally validated two novel hepatocellular carcinoma (HCC) risk prediction models (called aMAP-2 and aMAP-2 Plus scores), using longitudinal discriminant analysis algorithm and longitudinal data (i.e., aMAP and alpha-fetoprotein) with or without the addition of cell-free DNA signatures, based on 13,728 patients from 61 centers across mainland China. Our findings demonstrated that the performance of aMAP-2 and aMAP-2 Plus scores was markedly better than the original aMAP score, and any other existing HCC risk scores across all subsets, especially for patients with cirrhosis. More importantly, the stepwise application of aMAP scores (aMAP -> aMAP-2 -> aMAP-2 Plus) provides an improved enrichment strategy, identifying patients at high risk of HCC, which could effectively guide individualized HCC surveillance.

A meta-analysis of the effect of endoscopic submucosal dissection compared with gastrectomy on the wound infection in early stomach cancer subjects.

We conducted a meta-analysis to assess the effect of endoscopic submucosal dissection compared with gastrectomy on the wound infection in early stomach cancer subjects. A systematic literature search up to November 2022 was performed and 2765 related studies were evaluated. The chosen studies comprised 7842 early stomach cancer subjects participated in the selected studies' baseline trials; 3308 of them used the endoscopic submucosal dissection, while 4534 used gastrectomy. Odds ratio (OR) with 95% confidence intervals (CIs) were calculated to assess the wound infection in endoscopic submucosal dissection versus gastrectomy for early stomach cancer by the dichotomous methods with a random or fixed effect model. The use of endoscopic submucosal dissection resulted in significantly lower wound infection (OR, 0.45; 95% CI, 0.34-0.60, P < .001) with no heterogeneity (I2  = 8%) compared with the gastrectomy for early stomach cancer. The use of endoscopic submucosal dissection resulted in significantly lower wound infection compared with the gastrectomy for early stomach cancer. The small sample size of some studies in the comparison calls for care when analysing the results.

Nanopore-based metagenomic sequencing for the rapid and precise detection of pathogens among immunocompromised cancer patients with suspected infections.

Cancer patients are at high risk of infections and infection-related mortality; thereby, prompt diagnosis and precise anti-infectives treatment are critical. This study aimed to evaluate the performance of nanopore amplicon sequencing in identifying microbial agents among immunocompromised cancer patients with suspected infections. This prospective study enlisted 56 immunocompromised cancer patients with suspected infections. Their body fluid samples such as sputum and blood were collected, and potential microbial agents were detected in parallel by nanopore amplicon sequencing and the conventional culture method. Among the 56 body fluid samples, 47 (83.9%) samples were identified to have at least one pathogen by nanopore amplicon sequencing, but only 25 (44.6%) samples exhibited a positive finding by culture. Among 31 culture-negative samples, nanopore amplicon sequencing successfully detected pathogens in 22 samples (71.0%). Nanopore amplicon sequencing showed a higher sensitivity in pathogen detection than that of the conventional culture method (83.9% vs. 44.6%, P<0.001), and this advantage both existed in blood samples (38.5% vs. 0%, P=0.039) and non-blood samples (97.7% vs. 58.1%, P<0.001). Compared with the culture method, nanopore amplicon sequencing illustrated more samples with bacterial infections (P<0.001), infections from fastidious pathogens (P=0.006), and co-infections (P<0.001). The mean turnaround time for nanopore amplicon sequencing was about 17.5 hours, which was shorter than that of the conventional culture assay. This study suggested nanopore amplicon sequencing as a rapid and precise method for detecting pathogens among immunocompromised cancer patients with suspected infections. The novel and high-sensitive method will improve the outcomes of immunocompromised cancer patients by facilitating the prompt diagnosis of infections and precise anti-infectives treatment.

Left Atrial Dysfunction in Children with Repaired Pulmonary Artery Atresia with Ventricular Septal Defect: A Cardiovascular Magnetic Resonance Imaging Study.

(1) Background: The left atrium (LA) is much more than a reservoir for left ventricular filling. The aim of this study was to assess the LA volume and function in patients with repaired pulmonary artery atresia with ventricular septal defect (rPA/VSD) using CMR. (2) Methods: 31 pediatric patients with rPA/VSD and 30 healthy controls were prospectively recruited. Left atrial ejection fraction (EF), strain and strain rate of three phases (reservoir, conduit, and pump) and left atrial volume were measured with cardiac function analysis software. (3) Results: Patients with rPA/VSD had decreased maximal volume index (p = 0.008). Compared to controls, LA reservoir strain and strain rate, conduit strain and strain rate, booster pump strain rate, total EF and passive EF were significantly lower (p = 0.001, p < 0.001, p = 0.001, p = 0.02, p = 0.03, p < 0.001, p < 0.001); the patients with preserved but lower RVEF(<50%) had lower reservoir strain, reservoir strain rate and pump strain rate (p = 0.01, p = 0.02, p = 0.04, respectively) than the patients with higher RVEF (≥50%). (4) Conclusions: In patients with rPA/VSD, LA function was altered when biventricular EF was preserved, which may provide an early indication of left ventricular diastolic dysfunction. CMR can detect LA dysfunction at an early stage, even before LA enlargement.

Efficacy of TACE+Radiofrequency Ablation+Sorafenib in the Treatment of Patients with Recurrent Liver Cancer and Construction of Prediction Model.

Objective: This study is aimed at exploring the efficacy of transarterial chemotherapy embolization (TACE)+radiofrequency ablation+sorafenib in the treatment of patients with recurrent liver cancer and at constructing its prediction model. Methods: A total of 60 patients with recurrent liver cancer treated in our hospital from March 2020 to March 2022 were enrolled and divided into two groups according to treatment methods, with 30 patients in each group. Group A adopted TACE+radiofrequency ablation+sorafenib therapy while group B adopted TACE+radiofrequency ablation therapy. Clinical efficacy, complications, and adverse reactions of the two groups were observed. A total of 30 patients with nonrecurrent liver cancer in the same period were enrolled. 60 patients with recurrent liver cancer and 30 patients with nonrecurrent liver cancer were taken as the recurrence group and the nonrecurrence group, respectively. The baseline data and clinical data of the patients were queried by the Hospital Information System. The data included age, gender, Child-Pugh grade, HBV/HCV infection, portal vein tumor thrombus, degree of differentiation, vascular invasion, serum alpha fetal protein (AFP) level, number of tumors, maximum diameter of tumors, and number of nodules. The logistic regression analysis was used to analyze the independent risk factors for liver cancer recurrence. The Hosmer-Lemeshow test was used to analyze the degree of fitting between the prediction model and the standard curve. The ROC curve was used to analyze the predictive value of the model for liver cancer recurrence. Results: The objective effective rate and disease control rate in group A (33.33% and 70.00%) were higher than those in group B (10.00% and 43.33%), and the differences were statistically significant (both P < 0.05). There were no significant differences in the incidence of complications such as embolism syndrome, hand and foot skin reaction, gastrointestinal reaction, hypertension, diaphragmatic injury and bleeding, and biliary leakage and fever between the two groups (all P > 0.05). The proportions of patients in the recurrence group with portal vein tumor thrombus (PVTT), medium and high degree of differentiation, combined with vascular invasion, serum AFP level ≥ 400 ng/dL, multiple tumors, maximum tumor diameter ≥ 5 cm, combined with cirrhosis, and polynodules were all higher than those in the nonrecurrence group; the differences were statistically significant (all P < 0.05). Complication of PVTT, the degree of medium and high differentiation, and the maximum tumor diameter ≥ 5 cm were independent risk factors for recurrence of liver cancer (all P < 0.05). The prediction model of liver cancer recurrence was obtained by multiple regression analysis, P = 1/[1 + e -(-5.441 + 6.154∗PVTT + 3.475∗differentiateddegree + 3.001∗maximumdiameteroftumor)]. The Hosmer-Lemeshow test showed that χ 2 = 1.558 (P = 0.992). According to the ROC curve analysis, the AUC, SE, and 95% CI value of the prediction model for liver cancer recurrence were 0.977, 0.012, and 0.953-1.000, respectively. Conclusion: TACE+radiofrequency ablation+sorafenib is effective in the treatment of recurrent liver cancer, and the prediction model established based on the risk factor has high predictive value for patients with recurrent liver cancer.

Cardiac Computed Tomography-Derived Left Atrial Strain and Volume in Pediatric Patients With Congenital Heart Disease: A Comparative Analysis With Transthoracic Echocardiography.

Purpose: This study aimed at exploring the feasibility and reproducibility of CCT for the measurement of Left Atrial (LA) strain and volume compared with transthoracic echocardiography (TTE) in pediatric patients with congenital heart disease (CHD). Materials and Methods: The present study included 43 postoperative patients with CHD (7.39 ± 3.64 years, 56% male) who underwent clinically indicated CCT, and all patients underwent additional TTE on the same day. LA strain and volume parameters were measured by dedicated software. The correlation and agreement of LA strain and volume parameters were assessed using Pearson's correlation coefficient and Bland-Altman analysis. Intra-class correlation coefficients (ICC) were used to assess CCT intra-observer and inter-observer reproducibility. Results: All strain parameters of CCT were lower compared to TTE (reservoir strain: 28.37 ± 6.92 vs. 32.15 ± 8.15, respectively; conduit strain: 21.33 ± 6.46 vs. 24.23 ± 7.75, respectively; booster strain: 7.04 ± 2.74 vs. 7.92 ± 3.56). While the volume parameters of CCT were higher compared to TTE (LAV: 29.60 ± 19.01 vs. 25.66 ± 17.60, respectively; LAVi: 30.36 ± 22.31 vs. 28.63 ± 19.25, respectively). Both LA strain and volume measurements showed good correlation and agreement between the two modalities (r = 0.63-0.87, p < 0.001). CT-derived LA strain and volume measurements showed good intra- and inter-observer reproducibility using prototype software (ICC = 0.78-0.96). Conclusions: CCT was feasible for measuring LA strain and volume with good correlation and high reproducibility as compared with TTE. As a complementary modality, CCT can regard as an accepted method in the evaluation of LA function in pediatric patients with CHD.

Right and left ventricular function and flow quantification in pediatric patients with repaired tetralogy of Fallot using four-dimensional flow magnetic resonance imaging.

BACKGROUND: To assess the accuracy and reproducibility of right ventricular (RV) and left ventricular (LV) function and flow measurements in children with repaired tetralogy of Fallot (rTOF) using four-dimensional (4D) flow, compared with conventional two-dimensional (2D) magnetic resonance imaging (MRI) sequences. METHODS: Thirty pediatric patients with rTOF were retrospectively enrolled to undergo 2D balanced steady-state free precession cine (2D b-SSFP cine), 2D phase contrast (PC), and 4D flow cardiac MRI. LV and RV volumes and flow in the ascending aorta (AAO) and main pulmonary artery (MPA) were quantified. Pearson's or Spearman's correlation tests, paired t-tests, the Wilcoxon signed-rank test, Bland-Altman analysis, and intraclass correlation coefficients (ICC) were performed. RESULTS: The 4D flow scan time was shorter compared with 2D sequences (P < 0.001). The biventricular volumes between 4D flow and 2D b-SSFP cine had no significant differences (P > 0.05), and showed strong correlations (r > 0.90, P < 0.001) and good consistency. The flow measurements of the AAO and MPA between 4D flow and 2D PC showed moderate to good correlations (r > 0.60, P < 0.001). There was good internal consistency in cardiac output. There was good intraobserver and interobserver biventricular function agreement (ICC > 0.85). CONCLUSIONS: RV and LV function and flow quantification in pediatric patients with rTOF using 4D flow MRI can be measured accurately and reproducibly compared to those with conventional 2D sequences.

Feasibility of Cardiac Computed Tomography for the Evaluation of Ventricular Function in Postoperative Children With Congenital Heart Disease: Comparison With Cardiac Magnetic Resonance Imaging.

OBJECTIVE: We explored the feasibility of cardiac computed tomography (CCT) to evaluate postoperative ventricular function in children with congenital heart disease (CHD) and evaluated the accuracy and reproducibility of CCT using cardiac magnetic resonance (CMR) as a reference. METHODS: Thirty-two postoperative children with CHD (20 boys and 12 girls) who underwent CMR and CCT were enrolled. Left and right ventricular ejection fraction, end-diastolic volume, end-systolic volume, stroke volume, and cardiac index were measured using cardiac function analysis software. Cardiac function data were compared between CMR and CCT. The agreement between the 2 modalities was assessed using a Bland-Altman analysis. Intraclass correlation coefficients were used to assess intraobserver and interobserver reproducibility in CCT functional measurements. RESULTS: All functional parameters showed no significant difference (P > 0.05) and were well-correlated (r > 0.5, P < 0.05) between CMR and CCT. The mean values of all ventricular function parameters in CCT were higher compared with CMR. As indicated by 95% limits of agreement, left ventricular function parameters showed a better level of agreement compared with right ventricular function parameters between the 2 modalities. Intraobserver and interobserver reproducibility were excellent in CCT measurements for all functional parameters (intraclass correlation coefficient > 0.9). CONCLUSIONS: Compared with the criterion standard of CMR, CCT is feasible for assessing postoperative ventricular function with sufficient diagnostic accuracy and reproducibility in children with CHD. In addition to its important role regarding anatomical characterization, CCT is a suitable alternative and convenient follow-up tool that can be used to functional evaluation in children who are intolerant with CMR or have contraindications to CMR.

Feasibility of Three-Dimensional Balanced Steady-State Free Precession Cine Magnetic Resonance Imaging Combined with an Image Denoising Technique to Evaluate Cardiac Function in Children with Repaired Tetralogy of Fallot.

OBJECTIVE: To investigate the feasibility of cine three-dimensional (3D) balanced steady-state free precession (b-SSFP) imaging combined with a non-local means (NLM) algorithm for image denoising in evaluating cardiac function in children with repaired tetralogy of Fallot (rTOF). MATERIALS AND METHODS: Thirty-five patients with rTOF (mean age, 12 years; range, 7-18 years) were enrolled to undergo cardiac cine image acquisition, including two-dimensional (2D) b-SSFP, 3D b-SSFP, and 3D b-SSFP combined with NLM. End-diastolic volume (EDV), end-systolic volume (ESV), stroke volume (SV), and ejection fraction (EF) of the two ventricles were measured and indexed by body surface index. Acquisition time and image quality were recorded and compared among the three imaging sequences. RESULTS: 3D b-SSFP with denoising vs. 2D b-SSFP had high correlation coefficients for EDV, ESV, SV, and EF of the left (0.959-0.991; p < 0.001) as well as right (0.755-0.965; p < 0.001) ventricular metrics. The image acquisition time ± standard deviation (SD) was 25.1 ± 2.4 seconds for 3D b-SSFP compared with 277.6 ± 0.7 seconds for 2D b-SSFP, indicating a significantly shorter time with the 3D than the 2D sequence (p < 0.001). Image quality score was better with 3D b-SSFP combined with denoising than with 3D b-SSFP (mean ± SD, 3.8 ± 0.6 vs. 3.5 ± 0.6; p = 0.005). Signal-to-noise ratios for blood and myocardium as well as contrast between blood and myocardium were higher for 3D b-SSFP combined with denoising than for 3D b-SSFP (p < 0.05 for all but septal myocardium). CONCLUSION: The 3D b-SSFP sequence can significantly reduce acquisition time compared to the 2D b-SSFP sequence for cine imaging in the evaluation of ventricular function in children with rTOF, and its quality can be further improved by combining it with an NLM denoising method.

Postoperative evaluation of left ventricular global strain using cardiac computed tomography in pediatric patients with congenital heart disease: A comparison with echocardiography.

PURPOSE: We explored the feasibility and reproducibility of cardiac computed tomography (CCT)-derived left ventricular (LV) global strain in postoperative childrenwith congenital heart disease (CHD) and compared its correlation and agreement with transthoracic echocardiography (TTE). METHODS: Fifty-one patients (28 males, 23 females) were included who underwent clinically indicated retrospective electrocardiography-triggered CCT. and all patients underwent additional TTE on the same day. LV global longitudinal strain (GLS), global circumferential strain (GCS), and global radial strain (GRS) were measured. Correlations of global strains between CCT and TTE were assessed using Pearson's correlation coefficient. Intra-class correlation coefficients (ICC) were used to assess CCT intra-observer and inter-observer reproducibility. RESULTS: GLS and GCS were not significantly different between CCT and TTE (GLS: -23.54 ± 3.24 vs. -23.85 ± 3.72, respectively, p = 0.415; GCS: -28.21 ± 3.55 vs. -28.79 ± 3.69, respectively, p = 0.155). GRS was significantly different between CCT and TTE (60.79 ± 15.11 vs. 41.73 ± 4.27, respectively, p < 0.001). There was good correlation between CCT- and TTE-derived GLS (r = 0.70, p < 0.001) and GCS (r = 0.68, p < 0.001), but GRS showed no correlation between CCT and TTE (r = 0.09, p = 0.54). CCT-derived global strain showed good intra- and inter-observer reproducibility (ICC = 0.86-0.92), except the inter-observer reproducibility for GRS (ICC = 0.77). CONCLUSIONS: CCT was feasible for postoperative evaluation of LV global strain in pediatric patients with CHD with sufficient reproducibility. CCT-derived global strain can provide additional information in selected CHD patients with poor acoustic windows and who are intolerant to or have contraindications for cardiac magnetic resonance.

Enhancement of interferon gamma stability as an anticancer therapeutic protein against hepatocellular carcinoma upon interaction with calycosin.

The stability of IFN-γ as a therapeutic protein can play a key role on its anticancer effects. Herein, we explored the thermodynamic parameters and conformational stability of IFN-γ in the presence of calycosin, the main active compound of Radix astragali, by different biophysical and theoretical analysis. Afterwards, the improved anticancer effects of IFN-γ-calycosin interaction relative to IFN-γ alone were assessed on hepatocellular carcinoma (HepG2) cell line by MTT and caspase assays. ITC data indicated that upon interaction of calycosin with IFN-γ the binding and thermodynamic parameters were as follows: Kd = 1.9 µM, ΔG° = -32.45 kJ/mol, ΔH° = -11.91 kJ/mol, and TΔS° = 20.54 kJ/mol. ANS/synchronous fluorescence, CD and UV-Vis spectroscopy studies indicated that the interaction between calycosin and IFN-γ caused the folding of the IFN-γ backbone in to a more packed structure with enhanced α-helix content and higher melting temperature (Tm) value. The spectroscopic outcomes were then verified by molecular docking and molecular dynamic analysis. It was also shown that after incubation of the IFN-γ samples at 50 °C for 60 min in the presence of calycosin (5 µM), the IFN-γ-calycosin system showed a significant antiproliferative effects against hepatocellular carcinoma (HepG2) cells through caspase-9/3 activation and this anticancer effect was more pronounced than free IFN-γ. This data may provide useful information about the development of IFN-γ-based therapeutic platforms.

Feasibility of using a non-sedation protocol for evaluation of neonatal congenital heart disease by using a 16-cm wide-detector computed tomography with a low radiation dose: preliminary experience from a single pediatric medical center.

The aim of this study is to explore the feasibility of using a non-sedation protocol for the evaluation of neonatal congenital heart disease by using 16-cm wide-detector CT with a low radiation dose. Thirty-four neonates (group 1) were enrolled to undergo cardiac CT without sedation between August 2018 and March 2019. The control group (group 2) comprising 20 inpatient neonates was sedated. Cardiac CT was performed using 16-cm area detector 320-row CT with free breathing and prospective ECG-triggering scan mode. The examination completion time, radiation dose, and image quality were compared between the groups. The results of cardiac CT for patients in group 1 who underwent surgery were compared with surgical findings. Intergroup differences in body weight, age, examination completion time, radiation dose, and image quality evaluation were not significant. There was no significant difference in oxygen saturation before and after the examination in group 1. In all, 98 separate cardiovascular abnormalities in 27 group 1 patients were confirmed using surgical reports. The overall sensitivity, specificity, positive predictive value, and negative predictive value of cardiac CT were 94.90%, 100.0%, 100.0%, and 98.53%. The non-sedation protocol can be applied in neonates with congenital heart disease by using 16-cm wide-detector CT with a low radiation dose. Based on the image quality obtained, non-sedative examination did not extend the examination completion time and helped avoid the possible side effects of sedative drugs.

Detection of persistent systolic and diastolic abnormalities in asymptomatic pediatric repaired tetralogy of Fallot patients with preserved ejection fraction: a CMR feature tracking study.

OBJECTIVES: A fast cardiovascular magnetic resonance (CMR) feature tracking was applied to assess ventricular systolic and diastolic function. This study sought to detect right ventricular (RV) systolic and diastolic abnormalities in asymptomatic pediatric repaired tetralogy of Fallot (rTOF) patients with preserved RV ejection fraction (EF). METHODS: One hundred asymptomatic pediatric rTOF patients with preserved RVEF ≥ 45% and 52 control subjects underwent cine CMR examinations. Tricuspid annular plane systolic excursion (TAPSE); peak tricuspid annular systolic (Sm), early diastolic (Em), and late diastolic (Am) velocities; and biventricular global radial (GRS), circumferential (GCS), and longitudinal strains (GLS) were analyzed using CMR feature tracking. RESULTS: TAPSE, Sm, Em, Am, and RV GLS were significantly lower in rTOF patients compared with controls (all p < 0.01). The lower limits (mean-2·standard deviations) of TAPSE, Sm, Em, and Am among controls were 10.9 mm, 6.3 cm/s, 8.9 cm/s, and 2.4 cm/s, respectively, and 78%, 75%, 75%, and 19% of rTOF patients had corresponding measurements below these thresholds. Among rTOF patients, RV GLS was significantly lower in females than in males (p < 0.05). CONCLUSIONS: Despite preserved RVEF, there was a high prevalence of RV systolic and diastolic dysfunction among pediatric rTOF patients, which was detected using fast CMR feature tracking. KEY POINTS: • There was high prevalence of systolic and diastolic dysfunction in asymptomatic pediatric repaired tetralogy of Fallot (rTOF) patients despite preserved right ventricular (RV) ejection fraction (EF). • Significant correlations were observed between right ventricular (RV) measurements (strains, tricuspid annular plane systolic excursion (TAPSE), peak tricuspid annular early diastolic velocity (Em), peak tricuspid annular late diastolic velocity (Am)), and left ventricular (LV) strain measurements, which indicates ventricular-ventricular interactions at systolic and diastolic function level. • Right ventricular (RV) global longitudinal strain (GLS) was lower in female repaired tetralogy of Fallot (rTOF) patients than in males, suggesting females with rTOF may be at a higher risk of developing RV systolic dysfunction than males.

Pulmonary artery hemodynamic assessment of blood flow characteristics in repaired tetralogy of Fallot patients versus healthy child volunteers.

BACKGROUND: This study aimed to assess the severity of helix and vortex flow in pulmonary artery hemodynamic using 4-dimensional flow cardiac magnetic resonance (4D flow CMR) in patients with repaired tetralogy of Fallot (rTOF) and healthy child volunteers and to explore the relationship between pulmonary hemodynamic changes and right heart function. METHODS: CMR studies were performed in 25 rTOF patients (15 M/10 F; 8.44±4.52 years) and 10 normal child volunteers (7 M/3 F; 8.2±1.22 years) on 3.0T MR scanners. Cardiac function was calculated in the patient and control groups. Systolic diameter, peak velocity, net flow, and regurgitation was quantified in the main pulmonary artery (MPA) plane, left pulmonary artery (LPA) plane, and right pulmonary artery (RPA) plane. The relationship between the hemodynamic parameters and quantitative flow indices and right ventricular (RV) function were analyzed through simple linear regression analysis using Pearson R-values. We analyzed differences in flow patterns between the 2 groups for the same slice. According to the severity of the helix and vortex flow in the 4D flow CMR, we categorized rTOF patients into the following groups: group 1, severe flow grading; group 2, mild flow grading; group 3, no flow grading; the control cases with no flow grade were included in group 4. We compared RV cardiac function, wall shear stress (WSS), and viscous energy loss (EL) between group 1+2 and group 3+4 using unpaired t-test analysis for normally distributed data and the Mann-Whitney test for non-normally distributed continuous variables. RESULTS: RV end-diastolic volume index (EDVi) (127.8±36.13 vs. 83.11±6.18, respectively; P<0.001), RV end-systolic volume index (ESVi) (65.14±27.02 vs. 36.13±5.95, respectively; P<0.001), and ejection fraction (EF) (49.97±6.39 vs. 56.71±4.56, respectively; P=0.006,) were significantly different between the groups. The rTOF diameters of the MPA and RPA were significantly larger than those of the control group (19.74±4.01 vs. 14.97±2.37 for MPA, P=0.001; 12.04±3.28 vs. 8.99±1.23 for RPA, P=0.004, respectively). There were correlations between peak WSS and pulmonary regurgitation (PR) in the MPA (R=0.48, P=0.014), correlations between peak systolic EL and RVEDV (R=0.51, P=0.008), and between peak systolic EL and RVESV (R=0.51, P=0.009). The peak systole and diastole WSS of group 1+2 were significantly different compared to group 3+4 in the MPA (P<0.05). The peak systole and diastole EL of group 1+2 was significantly different from group 3+4 in the MPA (P<0.05). The peak systole EL of group 1+2 was significantly different from group 3+4 in the RPA (P<0.01). CONCLUSIONS: Increased peak WSS and EL were associated with pulmonary hemodynamic changes in the MPA and RPA. There might be an earlier marker of evolving hemodynamic inefficiency than that in traditional parameters. The better understanding of pulmonary artery hemodynamic assessment in rTOF may lead to a greater insight into pulmonary artery (PA)-RV interactions and how they ultimately impact RV function.

Systemic ventricular strain and torsion are predictive of elevated serum NT-proBNP in Fontan patients: a magnetic resonance study.

BACKGROUND: This study aimed to investigate the associations between cardiac strain, cardiac torsion, ventricular volumes, and ventricular ejection fraction, with N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels in Fontan patients who were age- and gender-matched with healthy control subjects. METHODS: Cardiovascular magnetic resonance (CMR) studies performed in 22 (15 male, 7 female) patients with single-ventricle physiology (all morphological left ventricles) palliated with Fontan and 17 (10 male, 7 female) age- and gender-matched healthy children volunteers were retrospectively analyzed. Serum NT-proBNP levels were obtained in Fontan subjects. Standard post-processing of CMR images included systemic ventricular end-diastolic and end-systolic volumes, stroke volume, cardiac mass, atrioventricular regurgitation, and ejection fraction. CMR tissue tracking (TT) software was used to quantify global longitudinal strain (GLS), global radial strain (GRS), and global circumferential strain (GCS) and torsion of the systemic ventricle. Pearson and Spearman correlation coefficients were used in comparisons of correlations between NT-proBNP and functional parameters in repair Fontan patients. Intra-observer and inter-observer variability of CMR strain and torsion values were determined from 10 randomly selected Fontan subjects and 10 randomly selected control subjects. RESULTS: GLS was significantly lower in Fontan patients than in control subjects (-15.19±2.94 vs. -19.97±1.70; P<0.001). GLS was not significantly different between normal NT-proBNP levels and high NT-proBNP levels in Fontan patients (-15.59±2.72 vs. -14.62±3.32; P=0.462). The GCS of repair Fontan patients was not significantly lower than that of the control group (-16.76±3.27 vs. -17.88±2.26; P=0.235). GCS was significantly different between normal and high NT-proBNP levels group in Fontan patients (-17.95±2.43 vs. -15.04±3.67; P=0.036). The peak systolic torsion and peak systolic torsion rates were significantly lower in Fontan patients than in control subjects (0.81±0.41 vs. 1.07±0.36, P=0.044; 7.36±3.41 vs. 9.85±2.61, P=0.017). Peak systolic torsion was significantly lower in Fontan patients with normal NT-proBNP levels than in high NT-proBNP subjects (0.67±0.43 vs. 1.01±0.29; P=0.036). GCS and torsion were more strongly correlated with NT-proBNP in the patient group (r=0.541 for GCS; r=0.588 for torsion, P<0.01). The parameters of strain and torsion could be reproduced with sufficient accuracy by intra-observer agreement(biases =0.04 for GLS; biases =0.66 for GCS; biases =1.03 for GRS; biases =0.04 for torsion) and inter-observer agreement (biases =0.32 for GLS; biases =0.85 for GCS; biases =1.52 for GRS; biases =0.18 for torsion). CONCLUSIONS: GLS is an earlier marker of contractile dysfunction in repair Fontan patients. Peak systolic torsion may be a biomarker for determining subclinical dysfunction, as it is more strongly correlated with serum biomarkers of ventricular function than ventricular size or ejection fraction.

Quantitative comparison of two-dimensional and three-dimensional strain measurement using MRI feature tracking in repair Fontan patients and normal child volunteers.

BACKGROUND: The accuracy of 2D and 3D strain analyses was evaluated by comparing strain and cardiac function parameters in Fontan repair patients and normal child volunteers. METHODS: We retrospectively enrolled 32 patients with Fontan circulation and 32 child volunteers who had undergone clinical cardiac magnetic resonance (CMR) assessment of the dominant ventricle with a 1.5-Tesla MRI scanner. Global and regional strain (2D and 3D) of the dominant ventricle in both groups was assessed using CMR feature-tracking. Correlations between cardiac function and strain data were assessed using Pearson's correlation coefficient values. The intraclass correlation coefficient (ICC) and coefficient of variation (CoV) were determined to evaluate repeatability and agreement. RESULTS: The 2D GLS showed significant differences between the Fontan repair patients and volunteers (- 16.49 ± 5.00 vs. -19.49 ± 2.03; p = 0.002). The 2D GRS and 2D GCS showed no significant differences between two groups. 2D GRS: 38.96 ± 14.48 vs. 37.46 ± 7.77; 2D GCS: - 17.64 ± 5.00 vs. -16.89 ± 2.96, respectively; p > 0.05). The 3D global radial strain (GRS), global circumferential strain (GCS), and global longitudinal strain (GLS) showed significant differences between the Fontan repair patients and volunteers (3D GRS: 36.35 ± 16.72 vs. 44.96 ± 9.98; 3D GLS: - 8.86 ± 6.84 vs. -13.67 ± 2.44; 3D GCS: - 13.70 ± 7.84 vs. -18.01 ± 1.78; p < 0.05, respectively). The ejection fraction (EF) and 3D GCS were significantly associated (r = - 0.491, p = 0.004). The 3D GCS showed correlations with the indexed end-diastolic volume (EDV) (r = 0.523, p = 0.002) and indexed end-systolic volume (ESV) (r = 0.602, p < 0.001). 3D strain showed good reproducibility, with GCS showing the best inter-observer agreement (ICC = 0.87 and CoV = 5.15), followed by GLS (ICC = 0.84 and CoV = 5.36). CONCLUSIONS: 3D GCS is feasible, highly reproducible, and strongly correlated with conventional cardiac function measures. 3D GCS assessments may be useful for monitoring abnormal myocardial motion in patients with Fontan circulation.

Knockdown of CTCF reduces the binding of EZH2 and affects the methylation of the SOCS3 promoter in hepatocellular carcinoma.

The epigenetic silencing mechanism of suppressor 3 of cytokine signaling (SOCS3) in cancers has not been fully elucidated. Polycomb repressive complexes 2 (PRC2), an important epigenetic regulatory factors, exerts a critical role in repressing the initial phase of gene transcription. Whether PRC2 participates the down- regulation of SOCS3 in Hepatocellular carcinoma (HCC) remains unclear and how does PRC2 be recruited target gene still needs to explore. In this study, Using TCGA HCC dataset, and detecting HCC tissue specimens and cell lines, we found that SOCS3 expression in HCC was inversely related to that of EZH2, and depended on its promoter methylation status. CTCF, vigilin, EZH2 and H3K27me3 were enriched at CTCF and EZH2 binding sites on the methylated SOCS3 gene promoter. The depletion of CTCF did not affect expression of EZH2 and DNMT1, but decrease recruitment of CTCF, vigilin, EZH2 and H3K27me3. Further, knockdown of CTCF led to a loss of methylation of the methylated SOCS3 promoter, which sequentially increased the expression of SOCS3 and decreased the expression of pSTAT3, the downstream effector. These findings suggest that the CTCF dependent recruitment of EZH2 to the SOCS3 gene promoter is likely to participate in the epigenetic silencing of SOCS3 and in regulating its gene expression.

Assessment of global and regional strain left ventricular in patients with preserved ejection fraction after Fontan operation using a tissue tracking technique.

To evaluate the use of the tissue tracking (TT) technique to measure myocardial strain left ventricular in post-Fontan children with preserved ejection fraction (pEF). Nineteen (male/female, 10/9) patients with univentricular hearts after completion of the Fontan circulation (post-Fontan group) and 19 age- and gender-matched healthy children (control group) were retrospectively enrolled. Cardiovascular magnetic resonance (CMR) imaging was conducted on a 1.5-T MRI scanner. Global and regional strains of the left ventricle in post-Fontan patients (EF > 55%) and controls were obtained using CMR-TT software. The Mann-Whitney U test was used to compare parameters between the two groups. Correlation between EF and strain was investigated using Pearson correlation coefficients. The Bland-Altman method was used to identify the inter- and intra-observer agreement in measurement of global strain. Global longitudinal strain was lower in post-Fontan patients than in healthy controls (- 18.87 ± 4.61 vs. -19.72 ± 1.58; P = 0.54), though the difference was not statistically significant. Global circumferential strain and global radial strain were significantly lower in post-Fontan patients than in healthy controls (- 14.55 ± 3.79 vs. -19.91 ± 1.97; P < 0.001; and 29.62 ± 8.41 vs. 36.85 ± 5.95; P = 0.01; respectively). The regional circumferential strain (RCS) decrease was marked in regional segments compare with post-Fontan patients and controls (basal, - 11.81 ± 2.98 vs. - 16.21 ± 2.72, P < 0.001; mid, - 15.05 ± 3.31 vs. - 20.17 ± 2.28, P = 0.005; apical, - 16.86 ± 3.09 vs. - 23.37 ± 2.62, P < 0.001). All circumferential and longitudinal parameters had an inter-observer ICC of ≥ 0.85, but this coefficient was lower for radial parameters. CMR-TT appears to be a feasible technique for identification of early myocardial dysfunction in post-Fontan with pEF.