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The previous first-in-human study established the preliminary safety and effectiveness of the novel thin-strut iron bioresorbable scaffold (IBS). The current study aims to directly compare the imaging and physiological efficacy, and clinical outcomes of IBS with contemporary metallic drug-eluting stents (DES). A total of 518 patients were randomly allocated to treatment with IBS (257 patients) or metallic DES (261 patients) from 36 centers in China. The study is powered to test noninferiority of the IBS compared with the metallic everolimus-eluting stent in terms of the primary endpoint of in-segment late lumen loss at 2 years, and major secondary endpoints including 2-year quantitative flow ratio and cross-sectional mean flow area measured by optical coherence tomography (OCT) (limited to the OCT subgroup, 25 patients in each group). This will be the first powered randomized trial investigating the safety and efficacy of the novel thin-strut IBS compared to a contemporary metallic DES. The findings will provide valuable evidence for future research of this kind and the application of metallic bioresorbable scaffolds. [ABSTRACT FROM AUTHOR]

Few methods have been reported to demonstrate real-time effects during vein of Marshall (VOM) ethanol infusion in persistent atrial fibrillation (PeAF). This study was to evaluate the impact of left atrial (LA) monitoring using intracardiac echocardiography (ICE) during VOM ethanol infusion. Seventy-four consecutive patients with PeAF who underwent VOM ethanol infusion followed by radiofrequency (RF) ablation were included. Patients with findings on ICE consistent with echogenic streaming in the LA and with increased myocardial local echogenicity along the VOM area were placed into one group (group A) and those without into the other group (group B). Outcomes between the 2 groups were compared. Forty-six patients (62%) were placed into group A. A new ethanol-induced low-voltage area in group A was larger than that in group B (8.5 cm2 [5.5–10.2 cm2] and 4.0 cm2 (2.4–6.3 cm2]; P <.001). The RF ablation time required to achieve MI block was reduced in group A patients (263.0 seconds [196.0–351.0 seconds] vs 417.0 seconds [315.0–709.5 seconds] in group B patients; P <.001). MI block was achieved in 46 patients (100%) via an endocardial approach in group A and 27 patients (96.4%) in group B (extra coronary sinus ablation in 4 patients). One patient developed clinically significant pericardial effusions and required pericardiocentesis in group B. Presence of increased myocardial local echogenicity at the ridge and consistent echogenic streaming in the LA detected by ICE-based imaging during VOM ethanol infusion suggests increased ablated tissue in that region and lower RF ablation time during ablation for PeAF. [Display omitted] [ABSTRACT FROM AUTHOR]

Intimal hyperplasia is a common lesion that can be observed in diverse vascular diseases. Drug-eluting stents and drug-coated balloons, which can release anti-proliferative agents to inhibit smooth muscle cell (SMC) proliferation, are developed to prevent intimal hyperplasia. However, these intervention devices still cannot achieve satisfactory clinical outcomes. In contrast to endovascular drug delivery, vascular adventitial drug delivery is a new strategy. To develop a vascular adventitial drug delivery system to treat intimal hyperplasia post vascular injuries, we loaded miR-145-5p-agomir (miR-145) into an injectable and in-situ self-assembling RAD peptide hydrogel. In vitro data showed that the miR-145 could be well incorporated into the RAD peptide hydrogels and released in a slow and controlled manner. The released miR-145 could transfect SMCs successfully, and the transfected SMCs exhibited a reduced migration capacity and higher expressions of SMC contractile biomarkers as compared to the non-transfected SMCs. In vivo data showed that the retention of the miR-145 was greatly elongated by the RAD peptide hydrogels. In addition, the application of the miR-145-loaded RAD peptide hydrogels surrounding injured arteries decreased the proliferative SMCs, promoted the regeneration of endothelium, reduced the macrophage infiltration, inhibited the neointimal formation and prevented adverse ECM remodeling via downregulation of KLF4 expression. The RAD peptide hydrogels loaded with miR-145 can successfully inhibit intimal hyperplasia after vascular injuries and thus hold great potential as an innovative extravascular drug delivery approach to treat vascular diseases. Intimal hyperplasia is a common lesion that can be observed in diverse vascular diseases. Drug-eluting stents and drug-coated balloons, which can release anti-proliferative agents to inhibit smooth muscle cell (SMC) proliferation, are developed to prevent intimal hyperplasia. However, these intervention devices still cannot achieve satisfactory clinical outcomes. In contrast to endovascular drug delivery, vascular adventitial drug delivery is a new strategy. Our work here demonstrates that the RAD peptide hydrogels loaded with miR-145-5p-agomir (miR-145) can successfully reverse intimal hyperplasia after vascular injuries and thus hold great potential as an innovative vascular adventitial drug delivery approach to treat vascular diseases. Our work proposes a possible paradigm shift from endovascular drug delivery to extravascular drug delivery for vascular disorder treatment. [Display omitted] [ABSTRACT FROM AUTHOR]

Computed tomography-derived fractional flow reserve (CT-derived FFR) algorithms have emerged as promising noninvasive methods for identifying hemodynamically significant coronary artery disease (CAD). However, its broad adaption is limited by the complex workflow, slow processing, and supercomputer requirement. Therefore, CT-derived FFR solutions capable of producing fast and accurate results could help deliver time-sensitive results rapidly and potentially alter patient management. The current study aimed to determine the diagnostic performance of a novel CT-derived FFR algorithm, esFFR, on patients with CAD was evaluated. 329 patients from 6 medical centers in China were included in this prospective study. CT-derived FFR calculations were performed on 350 vessels using the esFFR algorithm using patients' presenting coronary computed tomography angiography (CCTA) images, and results and processing speed were recorded. Using invasive FFR measurements from direct coronary angiography as the reference standard, the diagnostic performance of esFFR and CCTA in detecting hemodynamically significant lesions were compared. Post-hoc analyses were performed for patients with calcified lesions or stenoses within the CT-derived FFR diagnostic "gray zone." The esFFR values correlated well with invasive FFR. The sensitivity, specificity, accuracy, positive and negative predictive value for esFFR were all above 90%. The overall performance of esFFR was superior to CCTA. Coronary calcification had minimal effects on esFFR's diagnostic performance. It also maintained 85% of diagnostic accuracy for "gray zone" lesions, which historically was <50%. The average esFFR processing speed was 4.6 ± 1.3 minutes. The current study demonstrated esFFR had high diagnostic efficacy and fast processing speed in identifying hemodynamically significant CAD. [ABSTRACT FROM AUTHOR]

Although use of drug-coated balloons (DCB) is a promising technique, little is known about the clinical efficacy of the Dissolve DCB in drug-eluting stent (DES) in-stent restenosis (ISR). This study sought to evaluate the efficacy and safety of the Dissolve DCB in patients with DES ISR. This was a prospective, multicenter, randomized, noninferiority trial comparing Dissolve DCB with SeQuent Please DCB in patients with DES ISR. Angiographic and clinical follow-up was planned at 9 months in all patients. The primary endpoint was 9-month in-segment late loss. A total of 260 patients with ISR from 10 Chinese sites were included (Dissolve DCB, n = 128; SeQuent Please DCB, n = 132). Nine-month in-segment late loss was 0.50 ± 0.06 mm with Dissolve DCB vs 0.47 ± 0.07 mm with SeQuent Please DCB; the 1-sided 97.5% upper confidence limit of the difference was 0.18 mm (P for noninferiority = 0.03). Rates of target lesion failure and binary restenosis were numerical higher in the Dissolve DCB cohort compared with the SeQuent Please DCB cohort at 9 months (17.5% vs 10.7%; P = 0.12; 23.4% vs 16.4%; P = 0.19, respectively). At 9 months, major adverse cardiac and cerebrovascular events occurred in 36 patients (28.3%) vs 30 patients (22.9%) in the Dissolve DCB and SeQuent Please DCB groups, respectively. In this head-to-head randomized trial, the Dissolve DCB was noninferior to the SeQuent Please DCB for 9-month in-segment late loss. However, Dissolve DCB with its numerical increase in target lesion failure and binary restenosis warrants assessment in larger clinical trials (A Safety and Efficacy Study of Dissolve™ in Treatment of Coronary In-Stent Restenosis; NCT03373695) [Display omitted] [ABSTRACT FROM AUTHOR]

Background: Atrioventricular nodal ablation (AVNA) combined with biventricular pacing (BVP) improves outcomes in patients with persistent atrial fibrillation (AF), adequate rate control, and reduced left ventricular ejection fraction (LVEF). His-bundle pacing (HBP) delivers physiological ventricular activation and is a promising alternative to BVP.Objective: The purpose of this trial was to compare HBP with BVP following AVNA.Methods: In this multicenter, prospective, randomized crossover trial, we recruited patients with persistent AF and reduced LVEF (≤40%). All patients underwent AVNA and received both HBP and BVP. Patients were randomized to either HBP or BVP for 9 months (phase 1), then were switched to the alternative pacing modality for the next 9 months (phase 2). The primary endpoint was change in LVEF.Results: Fifty patients (age 64.3 ± 10.3 years; ventricular rate 93.1 ± 19.9 bpm; 72% male) were enrolled. Thirty-eight patients completed the 2 phases and were included in the crossover analysis. A significant improvement in LVEF was observed with HBP compared to BVP (phase 1: ΔLVEFHBP 21.3% and ΔLVEFBVP 16.7%; phase 2: ΔLVEFHBP 3.5% and ΔLVEFBVP -2.4%; Pgeneralizedadditivemodel = 0.015). Significant improvements in left ventricular end-diastolic diameter, New York Heart Association functional class, and B-type natriuretic peptide level were observed with both pacing modalities compared with baseline, whereas no significant differences were observed between HBP and BVP.Conclusion: HBP delivers a modest but significant improvement in LVEF in patients with persistent AF, impaired ventricular function, and narrow QRS duration post-AVNA compared with BVP. Larger long-term trials are required to confirm the additional improvements in function with HBP. [ABSTRACT FROM AUTHOR]

The existing fly ash-slag foaming geopolymer materials generally have the shortcomings of low fly ash content and low porosity. It is urgent to develop geopolymer foaming materials with high fly ash content and high porosity. Using fly ash and slag as the main raw materials, geopolymer foaming materials were prepared by alkali activation. The effects of activator content and sodium silicate modulus on the macroscopic mechanical properties, pore structures and microstructures of geopolymer foaming materials were studied. The experimental results showed that when the activator content was 21% (wt.) and the modulus of sodium silicate was 1, the specimen exhibited the best performance. The compressive strength of the specimen reached 2.18 MPa at 28 d, the porosity was 63.07%, and the average pore sizes of macroscopic pores were 920 μm. Inductively Coupled Plasma-Optical Emission Spectroscopy (ICP-OES) and Scanning Electron Microscopy and Energy Dispersive Spectrometer (SEM-EDS) analysis showed that when the content of activator was 21% and the modulus of sodium silicate was 1, the reaction grade of the system was the highest, reached 55.12%, meanwhile the main product Sodium silicate hydrate (N-A-S-H) gel produced the largest amount. The fractal dimension calculations showed that the spatial complexity of a specimen with large pores was greater than that of a specimen with small pores. This study can provide a basis for the design of geopolymer foaming materials with high proportion of fly ash and high porosity. [Display omitted] • Using fly ash and slag as raw materials, geopolymer foaming materials were successfully prepared by alkali activation method. • The geopolymer foaming material is conducive to the green production of foaming materials and reduces people's dependence on cement. • The fractal characteristics of pore are directly related to the stress state of pore evolution in slurry. • High or low dosage of activator and modulus of sodium silicate will reduce the compressive strength of geopolymer foam materials. • Influence of sodium silicate modulus on polymer order and degree of polymerization was greater than the dosage of activator. [ABSTRACT FROM AUTHOR]

Drug-coated balloons are a safe and effective option for patients undergoing percutaneous coronary intervention, but prior randomized studies have exclusively used paclitaxel-coated devices. The aim of this study was to assess for the first time the safety and efficacy of a novel biolimus-coated balloon (BCB) in patients with small-vessel coronary disease. In a prospective trial conducted at 10 centers in China, 212 patients with small-vessel native coronary disease (reference vessel diameter 2.0-2.75 mm, lesion length ≤25 mm) were randomized to receive a BCB or an uncoated balloon. The primary endpoint was in-segment late lumen loss at 9 months. In the per-protocol population, angiographic late lumen loss at 9 months was 0.16 ± 0.29 mm in the BCB group vs 0.30 ± 0.35 mm with the plain balloon (P = 0.001). Late luminal enlargement (positive remodeling) occurred in 29.7% of patients in the BCB group vs 9.8% of patients with plain balloons (P = 0.007). In the full analysis set population, after 12 months, target lesion failure rates were 6.7% in the BCB group vs 13.9% with the plain balloon (HR: 0.47; 95% CI: 0.19-1.16), and rates of the patient-oriented clinical outcome were 14.3% with the BCB vs 21.8% with the plain balloon (HR: 0.64; 95% CI: 0.33-1.24). In this first-in-human study, a novel BCB showed superior efficacy to plain balloon angioplasty in patients with small-vessel coronary disease undergoing percutaneous coronary intervention. Positive vascular remodeling was more frequent, and there was a trend toward improved clinical outcomes. (A Randomized Trial of a Biolimus-Coated Balloon Versus POBA in Small Vessel Coronary Artery Disease [Brave]; NCT03769623) [Display omitted] [ABSTRACT FROM AUTHOR]

Background and Aims: Serum uric acid (SUA) levels have been reported to be associated with an increased risk of coronary artery disease (CAD) among patients with diabetes in observational study. Whether this relationship is causal remains unclear. The current study aimed to explore the causal association between SUA and the risk of CAD in patients with diabetes.Methods and Results: A two-sample Mendelian randomization (MR) approach was employed to evaluate the causal effect of SUA on the risk of CAD in patients with diabetes. A total of 28 single nucleotide polymorphisms (SNPs) related to SUA were identified as instruments. Genetic association with CAD were obtained from a recently published genome-wide association study (GWAS) of 15,666 patients with diabetes (3968 CAD cases and 11,696 controls). The fixed-effects inverse variance-weighted method was employed to estimate the causal effect for the primary analysis, and other robust methods were employed for sensitivity analyses. In addition, the whole analyses were repeated using 9 non-pleiotropic SNPs. Genetic determined SUA levels were not significantly associated with the risk of CAD in patients with diabetes in the primary analysis (odds ratio = 1.13, 95% confidence interval: 0.98-1.16, P = 0.09). Consistent results were observed in the sensitivity analyses using various robust methods. In addition, this finding was confirmed by the repeated analyses using 9 non-pleiotropic SNPs.Conclusions: This two-sample MR study does not support a causal effect of genetically predicted SUA levels on the risk of CAD in patients with diabetes. [ABSTRACT FROM AUTHOR]

Abstract We propose a novel high-order HDG method for the Biot's consolidation model in poroelasticity. We present optimal h -version error analysis for both the semi-discrete and full-discrete (combined with temporal backward differentiation formula) schemes. Numerical tests are provided to demonstrate the performance of the method. [ABSTRACT FROM AUTHOR]

Background: There remains some confusion delineating the accurate location and the detailed anatomical relationship between atrioventricular accessory pathways (APs) located in the superoparaseptal region.Objective: The purpose of this article was to detail the anatomical relationship and accurate location of APs located in the superoparaseptal region.Methods: Between May 1, 2009 and November 30, 2016, 11 patients with superoparaseptal APs (SPS-APs) were identified in 129 consecutive patients who underwent catheter ablation for APs in our center.Results: A single SPS-AP was detected in all patients (manifest, n = 5; concealed, n = 6). The location of all 11 APs were precisely identified at the region millimeters superior to the His bundle recording site at the tricuspid annulus (S-HB, n = 6; manifest, n = 4); the area millimeters behind the His bundle recording site, adjacent to the right atrial aspect of the noncoronary aortic cusp (B-HB, n = 2; manifest, n = 1); and the true para-His bundle region (P-HB, n = 3). The electrocardiogram of all 5 manifest APs conformed to the typical "anteroseptal AP" pattern: a positive delta wave in leads I, II, avF, and avL; a narrow positive delta wave in lead V1; and a precordial QRS transition at lead V3. All APs were successfully eliminated by catheter ablation. After 54 ± 26 months of follow-up, all patients were free of arrhythmia.Conclusion: Three distinct regions are identified for localization of SPS-APs. Careful mapping and a detailed understanding of the anatomy of this region as well as distinct electrocardiographic characteristics are essential to eliminate such APs safely and effectively. [ABSTRACT FROM AUTHOR]

We present a novel hybridizable discontinuous Galerkin (HDG) method on unfitted meshes for single-phase Darcy flow in a fractured porous medium. In particular we apply the HDG methodology to the recently introduced reinterpreted discrete fracture model (RDFM) that use Dirac- δ functions to model both conductive and blocking fractures. Due to the use of Dirac- δ function approach for the fractures, our numerical scheme naturally allows for unfitted meshes with respect to the fractures, which is the major novelty of the proposed scheme. Moreover, the scheme is locally mass conservative. In particular, our scheme has a simple form, which is a novel modification of an existing regular Darcy flow HDG solver by adding the following two components: (i) locate the co-dimension one fractures in the background mesh and add the appropriate surface integrals associated with these fractures into the stiffness matrix, (ii) adjust the penalty parameters on cells cut through conductive and blocking fractures (fractured cells). Despite the simplicity of the proposed scheme, it performs quite well for various benchmark test cases in both two and three dimensions. To the best of our knowledge, this is the first time that an unfitted finite element scheme been applied to complex fractured porous media flow problems in 3D with both blocking and conductive fractures without any restrictions on the meshes. • Introduce line Dirac delta functions into the discrete fracture model for fracture and barrier networks. • The model works for both blocking and conductive fractures without any restrictions on the meshes. • The hybridizable discontinuous Galerkin methods for the model is conservative and easy to implement. • Prove the well-posedness of the proposed scheme. [ABSTRACT FROM AUTHOR]

Background: Catheter ablation in the right ventricular outflow tract (RVOT) may modify the electrophysiologic substrate for recurrent ventricular tachycardia/ventricular fibrillation (VT/VF) in patients with Brugada syndrome (BrS).Objective: The purpose of this study was to investigate the mechanism and arrhythmogenic substrate of VT/VF and to evaluate the long-term outcomes of catheter ablation in patients with BrS.Methods: Eleven consecutive patients with BrS referred to 2 academic medical centers underwent combined epicardial-endocardial electroanatomic mapping. Catheter ablation was performed in regions of localized conduction slowing. Transmural dispersion of late activation was calculated as the difference between the latest activation between epicardium and endocardium, and low-voltage areas were analyzed.Results: Eleven patients met diagnostic criteria for BrS (spontaneous type 1, n = 9; Na channel provocation = 2). All patients were found to have a localized region in the anterior epicardial RVOT with conduction slowing evidenced by prolonged electrogram duration (78.79 ± 19.87 ms vs 58.93 ± 10.11 ms in epicardial right ventricle, and 59.87 ± 12.61 ms in endocardial RVOT, P <.005, respectively) with variable low voltage (0.97 ± 0.48 mV; median scar area 19.8 ± 25.9 cm2). Epicardial ablation resulted in normalization of spontaneous type 1 Brugada ECG pattern in all patients, and 73% were free from VT/VF at 25 ± 11 months.Conclusion: Prolonged electrograms localized to epicardial RVOT with variable low voltage were identified in all patients with BrS. J-point and ST-segment elevation correlated with greater transmural dispersion of late activation and was independent of total low-voltage area. Despite normalization of spontaneous type 1 pattern in all patients after ablation, recurrence was still observed, suggesting the implantable cardioverter-defibrillator as the cornerstone therapy for BrS. [ABSTRACT FROM AUTHOR]

[Display omitted] • Using MSWI fly ash for mine filling and providing a resettlement approach for it. • Automatic foaming using aluminum of the material itself without extra foaming agent. • According to different depth of goaf, different material ratio was proposed. • Fluidity loss, rheological properties of slurry were studied directed to work. • Pore distribution complexity was positively with material compressive strength. To solve the problems of MSWI fly ash with no place stacking and the lack of filling materials in goaf, a scheme using MSWI fly ash for goaf filling is proposed. Using MSWI fly ash and slag as the main raw materials, geopolymer foaming materials with different proportions were prepared after alkali excitation to meet the differential filling requirements of goafs with different depths. The effects of curing temperature, activator dosage and MSWI fly ash content on the indexes of filling materials were investigated. The results showed that when the curing temperature was increased from 20 °C to 40 °C, the 28 d compressive strength of the material increased by approximately 31.9 %. The increase in curing temperature significantly improved the degree of polymerization and heavy metal curing rate of the material, resulting in more polymerization products in the system and promoting the conversion of calcium silicate hydrate (C S H) to calcium aluminosilicate hydrate (C-A S H) with a higher degree of polymerization. The pore structure of the material was mainly affected by the amount of activator used and the MSWI fly ash content. The higher the MSWI fly ash content was, the less round the pores and the more complex the spatial distribution. Scanning electron microscopy (SEM) showed that increasing the curing temperature and activator dosage made the raw material particles more compact and improved the integrity of the polymeric materials. Finally, three proportions involving an activator dosage of 20 % and a fly ash content of 40 %, an activator dosage of 15 % and a fly ash content of 40 % and an activator dosage of 10 % and a fly ash content of 60 % were selected for goaf filling at 20 °C, 30 °C and 40 °C, respectively. [ABSTRACT FROM AUTHOR]

We present and analyze a first order least squares method for convection dominated diffusion problems, which provides robust L 2 a priori error estimate for the scalar variable even if the given data f ∈ L 2 ( Ω ) . The novel theoretical approach is to rewrite the method in the framework of discontinuous Petrov–Galerkin (DPG) method, and then show numerical stability by using a key equation discovered by Gopalakrishnan and Qiu (2014). This new approach gives an alternative way to do numerical analysis for least squares methods for a large class of differential equations. We also show that the condition number of the global matrix is independent of the diffusion coefficient. A key feature of the method is that there is no stabilization parameter chosen empirically. In addition, Dirichlet boundary condition is weakly imposed. Numerical experiments verify our theoretical results and, in particular, show our way of weakly imposing Dirichlet boundary condition is essential to the design of least squares methods—numerical solutions on subdomains away from interior layers or boundary layers have remarkable accuracy even on coarse meshes, which are unstructured quasi-uniform. [ABSTRACT FROM AUTHOR]

Objectives: The intention of the PEPCAD China ISR (A Prospective, Multicenter, Randomized Trial of Paclitaxel-Coated versus Paclitaxel-Eluting Stent for the Treatment of Drug-Eluting Stent In-Stent Restenosis) was to demonstrate the efficacy of paclitaxel-coated balloon (PCB) angioplasty in a non-European patient population with coronary drug-eluting stent in-stent restenosis (DES-ISR). Background: The treatment of DES-ISR is still challenging with no established best strategy. Moreover, there is no study on the effect of PCB in the treatment of ISR in the Chinese population. Methods: PEPCAD China ISR was a 220-patient randomized (1:1), single-blind prospective multicenter trial conducted in China. Patients with coronary DES-ISR received either PCB (SeQuent Please, B. Braun Melsungen AG, Melsungen, Germany) or paclitaxel-eluting stent (Taxus Liberté, Boston Scientific, Natick, Massachusetts) treatment. The primary endpoint was in-segment late lumen loss at 9 months. Results: There were no significant baseline differences between both treatment groups in terms of patient, lesion, or procedural characteristics. At 9 months, in-segment late lumen loss in the PCB group was noninferior to that of the paclitaxel-eluting stent group (0.46 ± 0.51 mm vs. 0.55 ± 0.61 mm; difference: −0.06 mm with 95% confidence interval: −0.23 to 0.10; p for noninferiority = 0.0005). The 9-month rate of binary restenosis and 12-month composite clinical event rates were not significantly different between groups. Conclusions: In a randomized trial of 220 patients, angioplasty with a PCB was noninferior to paclitaxel-eluting stent implantation when used to treat DES-ISR. On the basis of these, as well as previous randomized trial data, PCB angioplasty offers an effective treatment for DES-ISR without the necessity of implanting additional metal layers for drug release. (A Safety and Efficacy Study of Paclitaxel-Eluting Balloon to Paclitaxel-Eluting Stent [PEPCAD]; NCT01622075) [Copyright &y& Elsevier]

We present a hybrid-mixed finite element method for a novel hybrid-dimensional model of single-phase Darcy flow in a fractured porous media. In this model, the fracture is treated as a (d − 1) -dimensional interface within the d -dimensional fractured porous domain, for d = 2 , 3. Two classes of fracture are distinguished based on the permeability magnitude ratio between the fracture and its surrounding medium: when the permeability in the fracture is (significantly) larger than in its surrounding medium, it is considered as a conductive fracture; when the permeability in the fracture is (significantly) smaller than in its surrounding medium, it is considered as a blocking fracture. The conductive fractures are treated using the classical hybrid-dimensional approach of the interface model where pressure is assumed to be continuous across the fracture interfaces, while the blocking fractures are treated using the recent Dirac- δ function approach where normal component of Darcy velocity is assumed to be continuous across the interface. Due to the use of Dirac- δ function approach for the blocking fractures, our numerical scheme allows for nonconforming meshes with respect to the blocking fractures. This is the major novelty of our model and numerical discretization. Moreover, our numerical scheme produces locally conservative velocity approximations and leads to a symmetric positive definite linear system involving pressure degrees of freedom on the mesh skeleton only. As an application, we extend the idea to a simple transport model. The performance of the proposed method is demonstrated by various benchmark test cases in both two- and three-dimensions. Numerical results indicate that the proposed scheme is highly competitive with existing methods in the literature • Combine the interface model with the reinterpreted discrete fracture model. • Solve the blocking fractures on nonconforming meshes. • Use hybridized method to reduce the degrees of freedom. • The scheme is locally conservative. [ABSTRACT FROM AUTHOR]

We present two cases of spontaneous left main stem coronary artery dissection. One was underdiagnosed with suboptimal percutaneous coronary artery intervention followed by acute vessel occlusion again during the hospitalization. The other one was identified and confirmed by intravascular ultrasound, followed by conservative medical treatment, with completed healing of SCAD during two-month follow up. [ABSTRACT FROM AUTHOR]

[Display omitted] • We proposed optimal harvesting strategies for edible and medicinal purpose of Chaenomeles speciosa fruit. • The metabolism and gene expression pattern of Chaenomeles speciosa fruit was investigated during maturation. • Further identified putative key enzymes involved in quality-associated primary and secondary metabolites biosynthesis. • Our findings laid the foundation for the further investigations of the potential regulatory mechanisms in harvest times, and provided a new possibility for the development and utilization in products. Chaenomeles speciosa fruit is a homologous medicine and food plant with a long history of multiple uses. It could be harvested near maturity and last for a long time. However, the optimal harvest strategy of Chaenomeles speciosa for various uses is currently unavailable. Here, untargeted metabolome at different harvest times during maturation was investigated for the first time, and 896 metabolites, including sugars, organic acids, amino acids, and phenylpropanoids, were identified. Optimal harvesting methods were proposed for different purposes. During the early maturation stages (before 105 days after full bloom), Ch. speciosa fruit could be harvested as Chinese medicine. Whereas as snacks and food, Ch. speciosa fruit might be harvested at late maturity (after 120 days after full bloom). In addition, the overall network was revealed by integrating full-length Iso-seq and transcriptomics (RNA-seq) to investigate the association between quality-associated metabolites and Chaenomeles speciosa fruit gene expression during maturation. A few putative genes were captured via screening, dissecting and correlation analysis with the quality-associated metabolites (including d-glucose, catechin, gallocatechin, and succinic acid). Overall, in addition to providing a harvesting strategy for food and medicine, we also investigated the metabolism and gene expression pattern of Chaenomeles speciosa fruit during maturation. This comprehensive data and analyses laid the foundation for further investigating potential regulatory mechanisms during harvest and provided a new possibility for its development and utilization. [ABSTRACT FROM AUTHOR]

Deferred revascularization of mildly stenotic coronary vessels based exclusively on physiological evaluation is associated with up to 5% residual incidence of future adverse events at 1 year. We aimed to evaluate the incremental value of angiography-derived radial wall strain (RWS) in risk stratification of non–flow-limiting mild coronary narrowings. This is a post hoc analysis of 824 non–flow-limiting vessels in 751 patients from the FAVOR III China (Comparison of Quantitative Flow Ratio Guided and Angiography Guided Percutaneous Intervention in Patients With Coronary Artery Disease) trial. Each individual vessel had ≥1 mildly stenotic lesion. The primary outcome was vessel-oriented composite endpoint (VOCE), defined as the composite of vessel-related cardiac death, vessel-related myocardial infarction (nonprocedural), and ischemia-driven target vessel revascularization at 1-year follow-up. During 1-year follow-up, VOCE occurred in 46 of 824 vessels, with a cumulative incidence of 5.6%. Maximum RWS (RWS max) was predictive of 1-year VOCE with an area under the curve of 0.68 (95% CI: 0.58-0.77; P < 0.001). The incidence of VOCE was 14.3% in vessels with RWS max >12% vs 2.9% in those with RWS max ≤12%. In the multivariable Cox regression model, RWS max >12% was a strong independent predictor of 1-year VOCE in deferred non–flow-limiting vessels (adjusted HR: 4.44; 95% CI: 2.43-8.14; P < 0.001). The risk of deferred revascularization based on combined normal RWS max and Murray–law-based quantitative flow ratio (μQFR) was significantly reduced compared with μQFR alone (adjusted HR: 0.52; 95% CI: 0.30-0.90; P = 0.019). Among vessels with preserved coronary flow, angiography-derived RWS analysis has the potential to further discriminate vessels at risk of 1-year VOCE. (Comparison of Quantitative Flow Ratio Guided and Angiography Guided Percutaneous Intervention in Patients With Coronary Artery Disease [FAVOR III China Study]; NCT03656848) [Display omitted] [ABSTRACT FROM AUTHOR]

Background: In the multicenter, randomized, sham-controlled FAVOR (Comparison of Quantitative Flow Ratio Guided and Angiography Guided Percutaneous Intervention in Patients with Coronary Artery Disease) III China trial, quantitative flow ratio (QFR)-based lesion selection improved 1-year clinical outcomes compared with conventional angiographic guidance for percutaneous coronary intervention (PCI).Objectives: The purpose of this study was to determine whether the benefits of QFR guidance persist at 2 years, particularly for patients in whom QFR changed the revascularization strategy.Methods: Eligible patients were randomized to a QFR-guided strategy (PCI performed only if QFR ≤0.80) or a standard angiography-guided strategy. Major adverse cardiac events (MACE), a composite of all-cause death, myocardial infarction (MI), or ischemia-driven revascularization occurring within 2 years were analyzed in the intention-to-treat population.Results: Among 3,825 randomized participants, 2-year MACE occurred in 161 of 1,913 (8.5%) patients in the QFR-guided group and in 237 of 1,912 (12.5%) patients in the angiography-guided group (HR: 0.66; 95% CI: 0.54-0.81; P < 0.0001), driven by fewer MIs (4.0% vs 6.8%; HR: 0.58; 95% CI: 0.44-0.77; P = 0.0002) and ischemia-driven revascularizations (4.2% vs 5.8%; HR: 0.71; 95% CI: 0.53-0.95; P = 0.02) in the QFR-guided group. Landmark analysis showed consistent results within the first year and between 1-2 years (Pint = 0.99). Although the 2-year MACE rate was lower in the QFR-guided group in both patients with and without revascularization strategy changes, the extent of outcome improvement was greater (Pint = 0.009) among those patients in whom the preplanned PCI strategy was modified by QFR.Conclusions: QFR-guided lesion selection improved 2-year clinical outcomes compared with standard angiography guidance. The benefits were most pronounced among patients in whom QFR assessment altered the planned revascularization strategy. (FAVOR III China Study [The Comparison of Quantitative Flow Ratio Guided and Angiography Guided Percutaneous Intervention in Patients with Coronary Artery Disease] NCT03656848). [ABSTRACT FROM AUTHOR]

Background: The clinical utility of the quantitative flow ratio (QFR), a novel angiography-based index for the functional assessment of coronary stenoses, has recently been demonstrated in patients undergoing percutaneous coronary intervention (PCI).Objectives: This study aimed to ascertain whether the beneficial outcomes of QFR guidance for lesion selection during PCI is affected by diabetes status.Methods: This substudy from the FAVOR III China trial, in which diabetes was one of the prespecified factors for stratified randomization, compared clinical outcomes of QFR-guided vs angiography-guided PCI lesion selection according to the presence of diabetes. The primary endpoint was the 1-year risk of major adverse cardiac events (MACE) (a composite of all-cause death, myocardial infarction, or ischemia-driven revascularization).Results: Among 3,825 patients enrolled, 1,295 (33.9%) had diabetes, 347 (26.8%) of whom were treated with insulin. Baseline characteristics were well balanced between treatment arms in both diabetic and nondiabetic patients. Compared with standard angiography-based lesion selection, the QFR-guided strategy consistently reduced the risk of 1-year MACE in both diabetic patients (6.2% vs 9.6%; HR: 0.64; 95% CI: 0.43-0.95) and nondiabetic patients (5.6% vs 8.3%; HR: 0.66; 95% CI: 0.49-0.89) (Pinteraction = 0.88). Among patients in whom PCI was deferred after QFR, the risk of 1-year MACE was similar in patients with and without diabetes (4.5% vs 6.2%; P = 0.51).Conclusions: A QFR-guided lesion selection strategy improves PCI outcomes compared with standard angiography guidance in patients both with and without diabetes. (The Comparison of Quantitative Flow Ratio Guided and Angiography Guided Percutaneous Intervention in Patients with Coronary Artery Disease [FAVOR III China Study]; NCT03656848). [ABSTRACT FROM AUTHOR]

Abstract A glutathione (GSH)-sensitive supramolecular nitric oxide (NO) nanogenerator is developed as an all-rounder for enhanced photodynamic therapy (PDT). By integrating GSH-sensitive NO prodrug into the system via LEGO-like host-guest interaction, the nanocarrier could not only deplete intracellular GSH, but also relieve hypoxia at tumor sites through NO mediated blood vessel relaxation. Furthermore, reactive nitrogen species (RNS) with enhanced biocidal activity could be produced by the reaction between NO and reactive oxygen species (ROS), generated from α-cyclodextrin (α-CD) conjugated S-nitrosothiol and light-activated chlorin e6 (Ce6) respectively. Due to multiple combined effects between NO and PDT, the NO acts as the loaded gunpowder inside a 'grenade', 'explosively' amplifying the therapeutic effects that the light responsive 'fuse' Ce6 could exert. The present work may well serve as an inspiration for future creative approaches of photodynamic cancer therapy. [ABSTRACT FROM AUTHOR]