Rational design and synthesis of triazene-amonafide derivatives as novel potential antitumor agents causing oxidative damage towards DNA through intercalation mode.

In this work, we rationally designed and synthesized two novel triazene-amonafide derivatives 2-(2-(diisopropylamino)ethyl)-5-(3,3-dimethyltriaz-1-en-1-yl)-1H-benzo[de]isoquinoline-1,3(2H)-dione (D-11) and 5-(3,3-diethyltriaz-1-en-1-yl)-2-(2-(diisopropylamino)ethyl)-1H-benzo[de]isoquinoline-1,3(2H)-dione (D-12) as potential antitumor agents. The DNA damage induced by the intercalation mode of D-11 (D-12) towards DNA was electrochemically detected through the construction of efficient biosensors. The consecutive processes of reversible redox of naphthylimide ring and irreversible oxidation of triazene moiety were elucidated on the surface of glassy carbon electrode (GCE) by CV, SWV, and DPV methods. Electrochemical biosensors were obtained through the immobilization of ctDNA, G-quadruplexes, poly(dG), and poly(dA), respectively, on the clean surface of GCE. After the incubation of biosensors with D-11 or D-12, the peaks of dGuo and dAdo decreased prominently, and the peak of 8-oxoGua appeared at +0.50 V, suggesting that the interaction between D-11 (D-12) and DNA could result in the oxidative damage of guanine. Unexpected, the as-prepared DNA biosensor possessed satisfactory anti-interference property and good practicability in real samples. UV-vis and fluorescence spectra, and gel electrophoresis assays were employed to further confirm the intercalation mode of D-11 (D-12) towards DNA base pairs. Moreover, D-11 was proved to exhibit stronger anti-proliferation activity than mitionafide and amonafide against both A549 and HeLa cell lines.

Machine learning based ischemia-specific stenosis prediction: A Chinese multicenter coronary CT angiography study.

OBJECTIVES: To evaluate the performance of coronary computed tomography angiography (CCTA) derived characteristics including CT derived fractional flow reserve (CT-FFR) with FFR as a reference standard in identifying the lesion-specific ischemia by machine learning (ML) algorithms. METHODS: The retrospective analysis enrolled 596 vessels in 462 patients (mean age, 61 years ± 11 [SD]; 71.4 % men) with suspected coronary artery disease who underwent CCTA and invasive FFR. The data were divided into training cohort, internal validation cohort, external validation cohorts 1 and 2 according to participating centers. All CCTA-derived parameters, which contained 10 qualitative and 33 quantitative plaque parameters, were collected to establish ML model. The Boruta and unsupervised clustering algorithm were implemented to select important and non-redundant parameters. Finally, the eight features with the highest mean importance were included for further ML model establishment and decision tree building. Five models were built to predict lesion-specific ischemia: stenosis degree from CCTA, CT-FFR, ΔCT-FFR, ML model and nested model. RESULTS: Low-attenuation plaque, bend and lesion length were the main predictors of ischemia-specific lesions. Of 5 models, the ML model showed favorable discrimination for ischemia-specific lesions in the training and three validation sets (area under the curve [95 % confidence interval], 0.93 [0.90-0.96], 0.86 [0.79-0.94], 0.88 [0.83-0.94], and 0.90 [0.84-0.96], respectively). The nested model which combined the ML model and CT-FFR showed better diagnostic efficacy (AUC [95 %CI], 0.96 [0.94-0.99], 0.92 [0.86-0.99], 0.92 [0.86-0.99] and 0.94 [0.91-0.98], respectively; all P < 0.05), and net reclassification improvement (NRI) and integrated discrimination improvement (IDI) were significantly higher than CT-FFR alone. CONCLUSIONS: Comprehensive CCTA-derived multiparameter model could better predict the ischemia-specific lesions by ML algorithms compared to stenosis degree from CTA, CT-FFR and ΔCT-FFR. Decision tree can be used to predict myocardial ischemia effectively.

The incremental value of CCTA-derived myocardial radiomics signature for ischemia diagnosis with reference to CT myocardial perfusion imaging.

OBJECTIVES: To explore the incremental value of myocardial radiomics signature derived from static coronary computed tomography angiography (CCTA) for identifying myocardial ischemia based on stress dynamic CT myocardial perfusion imaging (CT-MPI). METHODS: Patients who underwent CT-MPI and CCTA were retrospectively enrolled from two independent institutions, one used as training and the other as testing. Based on CT-MPI, coronary artery supplying area with relative myocardial blood flow (rMBF) value <0.8 was considered ischemia. Conventional imaging features of target plaques which caused the most severe narrowing of the vessel included area stenosis, lesion length (LL), total plaque burden, calcification burden, non-calcification burden, high-risk plaque (HRP) score, and CT fractional flow reserve (CT-FFR). Myocardial radiomics features were extracted at three vascular supply areas from CCTA images. The optimized radiomics signature was added to the conventional CCTA features to build the combined model (radiomics + conventional). RESULTS: There were 168 vessels from 56 patients enrolled in the training set, and the testing set consisted of 135 vessels from 45 patients. From either cohort, HRP score, LL, stenosis ≥50% and CT-FFR ≤0.80 were associated with ischemia. The optimal myocardial radiomics signature consisted of nine features. The detection of ischemia using the combined model was significantly improved compared with conventional model in both training and testing set (AUC 0.789 vs 0.608, p < 0.001; 0.726 vs 0.637, p = 0.045). CONCLUSIONS: Myocardial radiomics signature extracted from static CCTA combining with conventional features could provide incremental value to diagnose specific ischemia. ADVANCES IN KNOWLEDGE: Myocardial radiomics signature extracted from CCTA may capture myocardial characteristics and provide incremental value to detect specific ischemia when combined with conventional features.

Optimal Measurement Sites of Coronary-Computed Tomography Angiography-derived Fractional Flow Reserve: The Insight From China CT-FFR Study.

OBJECTIVES: To investigate the optimal measurement site of coronary-computed tomography angiography-derived fractional flow reserve (FFR CT ) for the assessment of coronary artery disease (CAD) in the whole clinical routine practice. MATERIALS AND METHODS: This retrospective multicenter study included 396 CAD patients who underwent coronary-computed tomography angiography, FFR CT , and invasive FFR. FFR CT was measured at 1 cm (FFR CT -1 cm), 2 cm (FFR CT -2 cm), 3 cm (FFR CT -3 cm), and 4 cm (FFR CT -4 cm) distal to coronary stenosis, respectively. FFR CT and invasive FFR ≤0.80 were defined as lesion-specific ischemia. The diagnostic performance of FFR CT to detect ischemia was obtained using invasive FFR as the reference standard. Reduced invasive coronary angiography rate and revascularization efficiency were calculated. After a median follow-up of 35 months in 267 patients for major adverse cardiovascular events (MACE), Cox hazard proportional models were performed with FFR CT values at each measurement site. RESULTS: For discriminating lesion-specific ischemia, the areas under the curve of FFR CT -1 cm (0.91) as well as FFR CT -2 cm (0.91) were higher than those of FFR CT -3 cm (0.89) and FFR CT -4 cm (0.88), respectively (all P <0.05). The higher reduced invasive coronary angiography rate (81.6%) was found at FFR CT -1 cm than FFR CT -2 cm (81.6% vs. 62.6%, P <0.05). Revascularization efficiency did not differ between FFR CT -1 cm and FFR CT -2 cm (80.8% vs. 65.5%, P =0.019). In 12.4% (33/267) MACE occurred and only values of FFR CT -2 cm were independently predictive of MACE (hazard ratio: 0.957 [95% CI: 0.925-0.989]; P =0.010). CONCLUSIONS: This study indicates FFR CT -2 cm is the optimal measurement site with superior diagnostic performance and independent prognostic role.

Cardiovascular Imaging in China: Yesterday, Today, and Tomorrow.

The high prevalence and mortality of cardiovascular diseases in China's large population has increased the use of cardiovascular imaging for the assessment of conditions in recent years. In this study, we review the past 20 years of cardiovascular imaging in China, the increasingly important role played by cardiovascular computed tomography in coronary artery disease and pulmonary embolism assessment, magnetic resonance imaging's use for cardiomyopathy assessment, the development and application of artificial intelligence in cardiovascular imaging, and the future of Chinese cardiovascular imaging.

Functional CAD-RADS using FFRCT on therapeutic management and prognosis in patients with coronary artery disease.

OBJECTIVES: To propose a novel functional Coronary Artery Disease-Reporting and Data System (CAD-RADS) category system integrated with coronary CT angiography (CCTA)-derived fractional flow reserve (FFRCT) and to validate its effect on therapeutic decision and prognosis in patients with coronary artery disease (CAD). METHODS: Firstly, we proposed a novel functional CAD-RADS and evaluated the performance of functional CAD-RADS for guiding treatment strategies with actual clinical treatment as a reference standard in a retrospective multicenter cohort with CCTA and invasive FFR performed in all patients (n = 466). Net reclassification improvement (NRI) of functional CAD-RADS over anatomical CAD-RADS was calculated. Secondly, the prognostic value of functional CAD-RADS in a prospective two-arm cohort (566 [FFRCT arm] vs. 567 [CCTA arm]) was calculated, after a 1-year follow-up, functional CAD-RADS in FFRCT arm (n = 513) and anatomical CAD-RADS in CCTA arm (n = 511) to determine patients at risk of adverse outcomes were compared with a Cox hazard proportional model. RESULTS: Functional CAD-RADS demonstrated superior value over anatomical CAD-RADS (AUC: 0.828 vs. 0.681, p < 0.001) and comparable performance to FFR (AUC: 0.828 vs. 0.848, p = 0.253) in guiding therapeutic decisions. Functional CAD-RADS resulted in the revision of management plan as determined by anatomical CAD-RADS in 30.0% of patients (n = 140) (NRI = 0.369, p < 0.001). Functional CAD-RADS was an independent predictor for 1-year outcomes with indexes of concordance of 0.795 and the corresponding value was 0.751 in anatomical CAD-RADS. CONCLUSION: The novel functional CAD-RADS gained incremental value in guiding therapeutic decision-making compared with anatomical CAD-RADS and comparable power in 1-year prognosis with anatomical CAD-RADS in a real-world scenario. KEY POINTS: • The novel functional CAD-RADS category system with FFRCT integrated into the anatomical CAD-RADS categories was originally proposed. • The novel functional CAD-RADS category system was validated superior value over anatomical CAD-RADS (AUC: 0.828 vs. 0.681, p < 0.001) in guiding therapeutic decisions and revised management plan in 30.0% of patients as determined by anatomical CAD-RADS (net reclassification improvement index = 0.369, p < 0.001). • Functional CAD-RADS was an independent predictor with an index of concordance of 0.795 and 0.751 in anatomical CAD-RADS for 1-year prognosis of adverse outcomes.

Influence of diabetes mellitus on the diagnostic performance of machine learning-based coronary CT angiography-derived fractional flow reserve: a multicenter study.

OBJECTIVES: To examine the diagnostic accuracy of machine learning-based coronary CT angiography-derived fractional flow reserve (FFRCT) in diabetes mellitus (DM) patients. METHODS: In total, 484 patients with suspected or known coronary artery disease from 11 Chinese medical centers were retrospectively analyzed. All patients underwent CCTA, FFRCT, and invasive FFR. The patients were further grouped into mild (25~49 %), moderate (50~69 %), and severe (≥ 70 %) according to CCTA stenosis degree and Agatston score < 400 and Agatston score ≥ 400 groups according to coronary artery calcium severity. Propensity score matching (PSM) was used to match DM (n  = 112) and non-DM (n  = 214) groups. Sensitivity, specificity, accuracy, and area under the curve (AUC) with 95 % confidence interval (CI) were calculated and compared. RESULTS: Sensitivity, specificity, accuracy, and AUC of FFRCT were 0.79, 0.96, 0.87, and 0.91 in DM patients and 0.82, 0.93, 0.89, and 0.89 in non-DM patients without significant difference (all p > 0.05) on a per-patient level. The accuracies of FFRCT had no significant difference among different coronary stenosis subgroups and between two coronary calcium subgroups (all p > 0.05) in the DM and non-DM groups. After PSM grouping, the accuracies of FFRCT were 0.88 in the DM group and 0.87 in the non-DM group without a statistical difference (p > 0.05). CONCLUSIONS: DM has no negative impact on the diagnostic accuracy of machine learning-based FFRCT. KEY POINTS: • ML-based FFRCT has a high discriminative accuracy of hemodynamic ischemia, which is not affected by DM. • FFRCT was superior to the CCTA alone for the detection of ischemia relevance of coronary artery stenosis in both DM and non-DM patients. • Coronary calcification had no significant effect on the diagnostic accuracy of FFRCT to detect ischemia in DM patients.

Phytosterols in hull-less pumpkin seed oil, rich in ∆7-phytosterols, ameliorate benign prostatic hyperplasia by lowing 5α-reductase and regulating balance between cell proliferation and apoptosis in rats.

BACKGROUND: Pumpkin seed oil is widely used to treat benign prostatic hyperplasia (BPH), a common disease in elder men. However, its active components and mechanism have remained to be elucidated. OBJECTIVE: The objective of the present study was to investigate the active components of pumpkin seed oil and its mechanism against BPH. DESIGN: Total phytosterol (TPS) was isolated from hull-less pumpkin (Cucurbita pepo L. var. Styriaca) seed oil and analyzed by gas chromatography/mass spectrometry (GC/MS). Three phytosterols were purified by preparative HPLC (high performance liquid chromatography) and confirmed by NMR (nuclear magnetic resonance). TPS (3.3 mg/kg body weight, 1 mL/day/rat) was administered intragastrically to the testosterone propionate-induced BPH rats for 4 weeks. The structure changes of prostate tissues were assessed by hematoxylin & eosin (H&E) staining. The expression of androgen receptor (AR) and steroid receptor coactivator 1 (SRC-1) was analyzed by immunohistochemistry, while that of 5α-reductase (5AR), apoptosis, or proliferation-related growth factors/proteins was detected by real-time quantitative polymerase chain reaction or western blotting. RESULTS: The ∆7-phytosterols in TPS reached up to 87.64%. Among them, 24ß-ethylcholesta-7,22,25-trienol, 24ß-ethylcholesta-7,25(27)-dien-3-ol, and ∆7-avenasterol were confirmed by NMR. TPS treatment significantly ameliorated the pathological prostate enlargement and restored histopathological alterations of prostate in BPH rats. It effectively suppressed the expressions of 5AR, AR, and coactivator SRC-1. TPS inhibited the expression of proliferation-related growth factor epidermal growth factor, whereas it increased the expressions of apoptosis-related growth factor/gene transforming growth factor-ß1. The proliferation-inhibiting effect was achieved by decreasing the ERK (extracellular signal-regulated kinase) phosphorylation, while apoptosis was induced by Caspase 3 activation through JNK (c-Jun N-terminal kinase) and p38 phosphorylation. CONCLUSION: TPS from hull-less pumpkin seed oil, with ∆7-phytosterols as its main ingredients, is a potential nutraceutical for BPH prevention.

The effect of coronary calcification on diagnostic performance of machine learning-based CT-FFR: a Chinese multicenter study.

OBJECTIVE: To investigate the effect of coronary calcification morphology and severity on the diagnostic performance of machine learning (ML)-based coronary CT angiography (CCTA)-derived fractional flow reserve (CT-FFR) with FFR as a reference standard. METHODS: A total of 442 patients (61.2 ± 9.1 years, 70% men) with 544 vessels who underwent CCTA, ML-based CT-FFR, and invasive FFR from China multicenter CT-FFR study were enrolled. The effect of calcification arc, calcification remodeling index (CRI), and Agatston score (AS) on the diagnostic performance of CT-FFR was investigated. CT-FFR ≤ 0.80 and lumen reduction ≥ 50% determined by CCTA were identified as vessel-specific ischemia with invasive FFR as a reference standard. RESULTS: Compared with invasive FFR, ML-based CT-FFR yielded an overall sensitivity of 0.84, specificity of 0.94, and accuracy of 0.90 in a total of 344 calcification lesions. There was no statistical difference in diagnostic accuracy, sensitivity, or specificity of CT-FFR across different calcification arc, CRI, or AS levels. CT-FFR exhibited improved discrimination of ischemia compared with CCTA alone in lesions with mild-to-moderate calcification (AUC, 0.89 vs. 0.69, p < 0.001) and lesions with CRI ≥ 1 (AUC, 0.89 vs. 0.71, p < 0.001). The diagnostic accuracy and specificity of CT-FFR were higher than CCTA alone in patients and vessels with mid (100 to 299) or high (≥ 300) AS. CONCLUSION: Coronary calcification morphology and severity did not influence diagnostic performance of CT-FFR in ischemia detection, and CT-FFR showed marked improved discrimination of ischemia compared with CCTA alone in the setting of calcification. KEY POINTS: • CT-FFR provides superior diagnostic performance than CCTA alone regardless of coronary calcification. • No significant differences in the diagnostic performance of CT-FFR were observed in coronary arteries with different coronary calcification arcs and calcified remodeling indexes. • No significant differences in the diagnostic accuracy of CT-FFR were observed in coronary arteries with different coronary calcification score levels.

Low-dose CT perfusion with combined use of CTP and CTP-derived coronary CT angiography at 70 kVp: validation with invasive fractional flow reserve.

OBJECTIVES: To investigate the diagnostic performance of 70-kVp stress dynamic myocardial CT perfusion (CTP) as a low-dose, one-stop cardiac CT examination in clinical application. MATERIALS AND METHODS: Consecutive symptomatic patients were prospectively recruited and scanned with stress dynamic myocardial CTP. The CTP phase with the best enhancement of the coronary arteries was selected and extracted as the CTP-derived single-phase coronary CT angiography (SP-CTA). The diagnostic performance of CTP and CTP+SP-CTA for functionally significant CAD was assessed. Invasive coronary angiography and fractional flow reserve were used as the reference standard for the myocardial ischemia evaluation. RESULTS: In total, 71 patients (43 men and 28 women; 63.6 ± 8.8 years old) underwent the stress dynamic myocardial CTP; 63 vessels (36.2%) from 42 of the patients (59.2%) were identified as causing ischemia. On a per-vessel basis, the sensitivity, specificity, PPV, NPV, and diagnostic accuracy for CTP and CTP+SP-CTA were 77.8%, 93.7%, 87.5%, 88.1%, and 87.9% and 84.1%, 93.7%, 88.3%, 91.2%, and 90.2%, respectively. The area under the curve (AUC) of CTP+SP-CTA (AUC = 0.963; 95%CI, 0.938-0.989) was significantly superior to that of CTP (AUC = 0.922; 95%CI, 0.880-0.964) and that of SP-CTA (AUC = 0.833; 95%CI, 0.765-0.900) alone (all p < 0.01). The mean radiation dose of the CTP examination was 3.8 ± 1.4 mSv. CONCLUSION: CTP-derived SP-CTA improved the diagnostic value of CTP. With a promising performance of myocardial ischemia detection and low radiation dose, the innovative low-dose, one-stop CTP examination is clinically feasible for patients who need to receive a myocardial perfusion assessment. KEY POINTS: • Myocardial CTP performed well in the evaluation of hemodynamically significant CAD. • CTP-derived single-phase CCTA improved the diagnostic value of CTP. • The combined use of low-dose CTP and CTP-derived CCTA at 70 kVp is clinically feasible for CAD patients who need to receive a myocardial perfusion assessment.

Stress dynamic myocardial CT perfusion for symptomatic patients with intermediate- or high-risk of coronary artery disease: Optimization and incremental improvement between the absolute and relative myocardial blood flow analysis.

BACKGROUND: The optimization of myocardial CT perfusion (CTP) assessment remains inconsistent and uncertain. Our aim was to explore the superior analysis selection and incremental improvement of myocardial blood flow (MBF) assessment on CTP in diagnosing hemodynamically significant coronary artery disease (CAD). METHODS: Sixty patients (43 men and 17 women; 61.38 ± 8.01 years) were prospectively recruited and underwent stress dynamic myocardial CTP examinations. Absolute and relative MBF was used for ischemia evaluation with the invasive coronary angiography and fractional flow reserve were used as the reference standard. Areas under the receiver operating characteristic curves (AUCs) and cutoff values were calculated and compared. RESULTS: There were 151 vessels in 60 patients finally enrolled for analysis. The sensitivity, specificity, PPV, NPV and diagnostic accuracy for the absolute MBF value and relative MBF ratio were 82.76%, 98.92%, 97.96%, 90.20%, and 92.72% and 74.14%, 93.56%, 87.76%, 85.29%, and 86.09%, respectively. The absolute MBF value was superior than the relative MBF ratio in detecting ischemia (AUC, 0.955 [95%CI: 0.919-0.990] vs.0.906 [95%CI:0.857-0.954])(P = 0.02). For territories with both sensitivity and specificity ≤90%, the diagnostic accuracy increased from 79.1% to 88.4% when the specific data were assessed using the absolute MBF value instead of the relative MBF ratio. CONCLUSIONS: The absolute MBF value from the endocardial myocardium on stress dynamic myocardial CTP showed superior diagnostic performance compared to the relative MBF ratio for the detection of myocardial ischemia in intermediate-to-high risk patients. The absolute MBF value provides an incremental benefit toward diagnostic performance for the relative MBF ratio evaluation.

The influence of image quality on diagnostic performance of a machine learning-based fractional flow reserve derived from coronary CT angiography.

OBJECTIVE: To investigate the effect of image quality of coronary CT angiography (CCTA) on the diagnostic performance of a machine learning-based CT-derived fractional flow reserve (FFRCT). METHODS: This nationwide retrospective study enrolled participants from 10 individual centers across China. FFRCT analysis was performed in 570 vessels in 437 patients. Invasive FFR and FFRCT values ≤ 0.80 were considered ischemia-specific. Four-score subjective assessment based on image quality and objective measurement of vessel enhancement was performed on a per-vessel basis. The effects of body mass index (BMI), sex, heart rate, and coronary calcium score on the diagnostic performance of FFRCT were studied. RESULTS: Among 570 vessels, 216 were considered ischemia-specific by invasive FFR and 198 by FFRCT. Sensitivity and specificity of FFRCT for detecting lesion-specific ischemia were 0.82 and 0.93, respectively. Area under the curve (AUC) of high-quality images (0.93, n = 159) was found to be superior to low-quality images (0.80, n = 92, p = 0.02). Objective image quality and heart rate were also associated with diagnostic performance of FFRCT, whereas there was no statistical difference in diagnostic performance among different BMI, sex, and calcium score groups (all p > 0.05, Bonferroni correction). CONCLUSIONS: This retrospective multicenter study supported the FFRCT as a noninvasive test in evaluating lesion-specific ischemia. Subjective image quality, vessel enhancement, and heart rate affect the diagnostic performance of FFRCT. KEY POINTS: • FFRCTcan be used to evaluate lesion-specific ischemia. • Poor image quality negatively affects the diagnostic performance of FFRCT. • CCTA with ≥ score 3, intracoronary enhancement degree of 300-400 HU, and heart rate below 70 bpm at scanning could be of great benefit to more accurate FFRCTanalysis.

CT FFR for Ischemia-Specific CAD With a New Computational Fluid Dynamics Algorithm: A Chinese Multicenter Study.

OBJECTIVES: The aim of this study was to validate the feasibility of a novel structural and computational fluid dynamics-based fractional flow reserve (FFR) algorithm for coronary computed tomography angiography (CTA), using alternative boundary conditions to detect lesion-specific ischemia. BACKGROUND: A new model of computed tomographic (CT) FFR relying on boundary conditions derived from structural deformation of the coronary lumen and aorta with transluminal attenuation gradient and assumptions regarding microvascular resistance has been developed, but its accuracy has not yet been validated. METHODS: A total of 338 consecutive patients with 422 vessels from 9 Chinese medical centers undergoing CTA and invasive FFR were retrospectively analyzed. CT FFR values were obtained on a novel on-site computational fluid dynamics-based CT FFR (uCT-FFR [version 1.5, United-Imaging Healthcare, Shanghai, China]). Performance characteristics of uCT-FFR and CTA in detecting lesion-specific ischemia in all lesions, intermediate lesions (luminal stenosis 30% to 70%), and "gray zone" lesions (FFR 0.75 to 0.80) were calculated with invasive FFR as the reference standard. The effect of coronary calcification on uCT-FFR measurements was also assessed. RESULTS: Per vessel sensitivities, specificities, and accuracies of 0.89, 0.91, and 0.91 with uCT-FFR, 0.92, 0.34, and 0.55 with CTA, and 0.94, 0.37, and 0.58 with invasive coronary angiography, respectively, were found. There was higher specificity, accuracy, and AUC for uCT-FFR compared with CTA and qualitative invasive coronary angiography in all lesions, including intermediate lesions (p < 0.001 for all). No significant difference in diagnostic accuracy was observed in the "gray zone" range versus the other 2 lesion groups (FFR ≤0.75 and >0.80; p = 0.397) and in patients with "gray zone" versus FFR ≤0.75 (p = 0.633) and versus FFR >0.80 (p = 0.364), respectively. No significant difference in the diagnostic performance of uCT-FFR was found between patients with calcium scores ≥400 and <400 (p = 0.393). CONCLUSIONS: This novel computational fluid dynamics-based CT FFR approach demonstrates good performance in detecting lesion-specific ischemia. Additionally, it outperforms CTA and qualitative invasive coronary angiography, most notably in intermediate lesions, and may potentially have diagnostic power in gray zone and highly calcified lesions.

Diagnostic Performance of Machine Learning Based CT-FFR in Detecting Ischemia in Myocardial Bridging and Concomitant Proximal Atherosclerotic Disease.

BACKGROUND: The diagnostic performance of coronary computed tomography angiography-derived fractional flow reserve (CT-FFR) in detecting ischemia in myocardial bridging (MB) has not been investigated to date. METHODS: This retrospective multicentre study included 104 patients with left anterior descending MBs. MB was classified as either superficial or deep, short, or long, whereas all MB vessels were further divided into <50%, 50% to 69%, and ≥70% groups, according to proximal lumen stenosis on invasive coronary angiography. Diagnostic performance and receiver operating characteristics (ROC) of CT-FFR to detect lesion-specific ischemia was assessed on a per-vessel level, using invasive FFR as reference standard. Intraclass correlation coefficient (ICC) and Bland-Altman plots were used for agreement measurement. RESULTS: Forty-eight MB vessels (46.2%) showed ischemia by invasive FFR (≤0.80). Sensitivity, specificity, and accuracy of CT-FFR to detect functional ischemia were 0.96 (0.85 to 0.99), 0.84 (0.71 to 0.92), and 0.89 (0.81 to 0.94), respectively, in all MB vessels. There were no differences in diagnostic performance between superficial and deep MB or between short and long MB (all P > 0.05). The accuracy of CT-FFR was 0.96 (0.85 to 0.99) in ≥70% stenosis, 0.82 (0.67 to 0.91) in 50% to 69% stenosis, and 0.89 (0.51 to 0.99) in <50% stenosis (P = 0.081). Bland-Altman analysis showed a slight mean difference between CT-FFR and invasive FFR of 0.014 (95% limit of agreement, -0.117 to 0.145). The ICC was 0.775 (95% confidence interval, 0.685-0.842, P < 0.001). CONCLUSIONS: CT-FFR demonstrated high diagnostic performance for identifying functional ischemia in vessels with MB and concomitant proximal atherosclerotic disease when compared with invasive FFR. However, the clinical use of CT-FFR in patients with MB needs further study for stronger and more robust results.

A protocol of homozygous haploid callus induction from endosperm of Taxus chinensis Rehd. var. mairei.

Obtainment and characterization of the novel endosperm callus of Taxus chinensis Rehd. var. mairei are valuable for haploid breeding, genome, and functional genome in Taxus. Callus was obtained by hydropriming with sterile water for 3 days and suitable medium composition. The highest callus induction (70.89 %) and lower browning ratio (7.95 %) were obtained from Gamborg (B5) medium supplemented with 30 g l(-1) of sucrose, 2.5 mg l(-1) of 2,4-dichlorophenoxyacetic (2,4-D), 0.5 mg l(-1) of 6-benzylademine (6-BA) and 7 g l(-1) of agar under dark conditions. The auxin of 2,4-D had a better efficiency of callus induction than naphthylacetic acid, and over 1 mg l(-1) of 6-BA was inhibitory to the callogensis of endosperm. The endosperm callus was haploid which was detectable by the flow cytometry. The genome block of homozygosity of callus was homozygous which was indicated by PCR-based SNP marks. The homozygous haploid of endosperm callus in vitro culture may be useful tools for taxoid-metabolism of gene engineering and bio-fermentation engineering.

Photodynamic Therapy Mediated by Upconversion Nanoparticles to Reduce Glial Scar Formation and Promote Hindlimb Functional Recovery After Spinal Cord Injury in Rats.

Glial scar formation is one of the major consequences of spinal cord injury, which prevents the regenerated axons passing the injured area and forming effective synaptic connection. In this paper, we used photodynamic therapy (PDT), which was mediated by the upconversion nanoparticles coated with polyethylene glycol (PEG) and photosensitizer (UCNPs-PEGM540), to reduce the glial scar formation after spinal cord injury. The in vitro experimental results indicated that cultured astrocytes could be killed by using upconversion nanoparticles after excitation with near infrared light. By transplanting UCNPs-PEG-M540 into the margin area of injured epicenter of spinal cord, the recovery of rat's hindlimb function was evaluated in Basso, Beattie, Bresnahan locomotor rating scale, respectively. The improvement in microenvironment of the injured spinal cord was also evaluated by glial fibrillary acidic protein staining, neurofiliment staining, biotinylated dextran amine anterograde tracing and western blotting. Our results demonstrated that more regenerative axons of corticospinal tract were found to surround and pass through the injured cavity to the caudal cord with transplanting UCNPs-PEG-M540 into the injured spinal cord. In conclusion, our results strongly suggested that upconversion nanoparticles combined with photodynamic therapy can promote functional recovery in rats' hindlimbs by reducing the formation of glial scar and promoting remyelination of injured axons.

[Influence of Electroacupuncture Intervention on Glutamic Acid and Ca2+ Contents and Expression of NMDA Receptor Protein in Hippocampus in Vascular Dementia Rats].

OBJECTIVE: To observe the influence of electroacupuncture (EA) intervention on hippocampal glutamate (Glu) and Ca2+ contents, and expression of Glu-N-methyl-D-aspartic acid receptor(NMDAR) and the learning-memory ability in vascular dementia (VD) rats, so as to reveal its mechanisms underlying improvement of VD. METHODS: SD rats were rando-mized into sham operation (sham) group (n=9), model group (n=11) and EA groups (n=10). The VD model was established by repeated bilateral common carotid arteries occlusion and reperfusion plus intraperitoneal injection of sodium nitroprusside. EA (2 Hz, 2 mA) was applied to "Baihui" (GV 20)-"Housanli" (ST 36) and "Geshu" (BL 17)-"Dazhui" (GV 14) for 10 min, once a day for 15 consecutive days. The neurological function was assessed by using stroke index (0-10 points) and neurological deficit scaling(0-10 points). The learning-memory ability was evaluated by using step-down tests. The contents of Glu and Ca2+ in the right hippocampal tissue were determined by using aspectrophotometer and the expression of NMDAR protein in the right hippocampus was detected by immunoblotting. RESULTS: Compared with the sham group, the stroke index and neurological deficit scores, and the reaction latency and the error times of step-down tests, as well as the contents of Glu and Ca2+ and the expression level of NMDAR in the right hippocampus were significantly increased in the model group (P<0.05, P<0.01), while the step-through latency was considerably decreased (P<0.01), suggesting a neurological disorder and a cognitive decline. After EA intervention, the reaction latency and error times of step-down tests, the contents of Glu and Ca2+ and the expression level of NMDAR in the right hippocampus were significantly down-regulated, and the step-through latency was notably increased in comparison with the model group (P<0.01). CONCLUSIONS: EA intervention is able to improve the cognitive ability of VD rats, which may be associated with its effects in reducing the excitatory neurotoxicity of hippocampal Glu-NMDAR and lowering cellular Ca2+ load to resist neuronal injury.

A preliminary investigation of computed tomographic angiography in the assessment of coronary artery distensibility.

OBJECTIVE: To test 2 hypotheses: first, that coronary distensibility can be measured noninvasively using 64-slice computed tomographic angiography (CTA); and second, that the extent of coronary artery disease (CAD) in any individual patient is related to the degree of distensibility detected by CTA. MATERIALS AND METHODS: Computed tomographic angiography was performed in 30 healthy adults and in 30 patients. All subjects were younger than 55 years. The main lesion located in the left anterior descending branch in patients with CAD. The cross-sectional coronary area of the left main and the left anterior descending arteries were measured in each phase (5%-95%, 10% each), and any change in the ratio was quantified. A distensibility value (D value) was determined for each artery. RESULTS: Compared with healthy subjects, the coronary area of the patients with CAD was significantly decreased in 65% to 85% (P < 0.05). There was a significant difference in the D value between healthy subjects and patients with both single-vessel and 2-vessel disease (P < 0.05). CONCLUSIONS: Coronary artery distensibility can be measured noninvasively using data obtained from CTA. The distensibility of the coronary artery decreased with the increasing number of involved pathological coronary vessels. The distensibility of the coronary artery correlated with the extent of CAD.

Prevalence of unruptured cerebral aneurysms in Chinese adults aged 35 to 75 years: a cross-sectional study.

BACKGROUND: The reported prevalence of unruptured cerebral aneurysms (UCAs) varies widely. OBJECTIVE: To measure the prevalence of UCAs by using 3-dimensional time-of-flight magnetic resonance angiography in adults aged 35 to 75 years. DESIGN: Cross-sectional study done between June 2007 and June 2011. SETTING: Two communities chosen at random from 2 districts (1 urban and 1 suburban) in Shanghai, China. PARTICIPANTS: 4813 adults aged 35 to 75 years. MEASUREMENTS: Three-dimensional time-of-flight magnetic resonance angiography, interpreted by 3 observers blinded to the participants' information, was used to identify the location and size of UCAs and to estimate the overall, age-specific, and sex-specific prevalence. RESULTS: 369 UCAs were found in 336 participants (130 men and 206 women); 4477 participants had no evidence of UCAs. The prevalence was 7.0% overall (95% CI, 6.3% to 7.7%), with 5.5% for men (CI, 4.6% to 6.4%) and 8.4% for women (CI, 7.3% to 9.5%). The overall prevalence of UCAs was higher in women than in men (P < 0.001) and peaked at ages 55 to 64 years in men and women. The UCAs were mostly located in the internal carotid artery (81%), and 90.2% had a maximum diameter less than 5 mm. Mean diameter was larger in women than in men (3.7 mm vs. 3.2 mm; P < 0.009). LIMITATION: Participants were from 2 communities selected from 2 districts in Shanghai, and adults older than 75 years were not studied. CONCLUSION: The overall prevalence of UCAs was 7.0% in Chinese adults aged 35 to 75 years, and most lesions had a diameter less than 5 mm. PRIMARY FUNDING SOURCE: National Natural Science Foundation of China.