BACKGROUND:The influence of left ventricular ejection fraction (LVEF) on clinical outcomes in patients treated with drug-coated balloons (DCBs) versus drug-eluting stents (DES) for de novo coronary lesions remains uncertain. METHODS:REC-CAGEFREE I was an investigator-initiated, non-inferiority trial conducted at 43 sites in China, randomizing 2272 patients to paclitaxel-coated balloons with optional rescue stenting or to sirolimus-eluting stents. In this pre-specified subgroup analysis, 2194 patients with available baseline LVEF were stratified into LVEF <55% and LVEF ≥55%. The primary endpoint was the device-oriented composite endpoint (DoCE; including cardiovascular death, target-vessel myocardial infarction, and clinically and physiologically indicated target lesion revascularization) at 3 years. RESULTS:Among 2194 patients, 402 (18.3%) had an LVEF <55%, and 1792 (81.7%) had an LVEF ≥55%. At 3 years, the risk of DoCE was numerically higher in patients with an LVEF <55% versus LVEF ≥55% (9.0% vs. 6.1%; P=0.237). A significant treatment-by-LVEF interaction was observed for DoCE (Pinteraction=0.033). In patients with an LVEF <55%, DoCE occurred in 28/206 (13.7%) and 8/196 (4.2%) patients in the DCB and DES groups (DifferenceIPTW: 7.19%, 95% CI: 1.89% to 12.48%, P=0.008), respectively; in patients with an LVEF ≥55%, DoCE occurred in 62/886 (7.0%) and 47/906 (5.2%) patients in the DCB and DES groups (DifferenceIPTW: 1.93%, 95% CI: -0.37% to 4.23%, P=0.101), respectively. CONCLUSIONS:Baseline LVEF may modify clinical outcomes after DCB versus DES for de novo coronary artery disease, with excess risk of DoCE with DCB mainly observed in patients with LVEF <55%. These exploratory findings should be interpreted cautiously. CLINICAL TRIAL REGISTRATION:www. CLINICALTRIALS:gov; number, NCT04561739.

The anatomical and pathophysiological characteristics of coronary artery disease vary between the sexes. This study investigated the impact of sex on outcomes in patients with de novo coronary artery lesions treated with drug-coated balloons (DCB) or drug-eluting stents (DES). REC-CAGEFREE I was an investigator-initiated, non-inferiority trial conducted at 43 sites in China from Feb 5, 2021, to May 1, 2022, which randomized 2,272 patients for treating de novo coronary lesions, regardless of vessel diameter. After successful lesion pre-dilatation, eligible patients were randomized (1:1) to either DCB angioplasty with the option of rescue stenting or intended DES deployment. In this prespecified subgroup analysis, patients were analyzed by sex based on their medical records. The primary endpoint was device-oriented composite endpoint (DoCE), including cardiovascular death, target-vessel myocardial infarction, and clinically and physiologically indicated target lesion revascularization at 2 years. Between-group differences were compared by Cox proportional-hazards models, and imbalances in baseline characteristics were adjusted with inverse probability of treatment weighting (IPTW). The analyses were conducted in the intention-to-treat population. A total of 2,272 participants underwent randomization, of which 698 (30.7

We investigate the impact of pulse pressure on long-term outcomes for patients treated with drug-coated balloons (DCBs) or drug-eluting stents (DESs). REC-CAGEFREE I was an investigator-initiated, non-inferiority trial conducted at 43 sites in China from Feb 5, 2021, to May 1, 2022, which randomized 2272 participants to DCB or DES treatment for de novo, non-complex lesions. In this post hoc analysis, participants were stratified into three groups based on pulse pressure tertiles (< 46, 46–60, and > 60 mmHg). The primary outcome was the 2-year device-oriented composite endpoint (DoCE), including cardiovascular death, target-vessel myocardial infarction, and clinically and physiologically indicated target lesion revascularization. 2272 participants were included in the analysis. At 2 years, DoCE occurred in 35/723 (4.9

BACKGROUND:For long coronary lesions, drug-coated balloons (DCBs) might be an attractive alternative compared with drug-eluting stents (DES); however, supporting evidence remains scarce. AIMS:To compare the efficacy of DCBs versus DES for treating long de novo coronary lesions. METHODS:REC-CAGEFREE I was a non-inferiority trial conducted at 43 sites in China, which randomized 2272 patients to paclitaxel-coated balloon angioplasty with the option of rescue stenting or sirolimus-eluting stents for treating de novo lesions, regardless of vessel diameter. In this pre-specified subgroup analysis, patients were stratified by quantitative coronary angiography-assessed lesion length into short (< 20 mm) and long (≥ 20 mm) groups. The primary endpoint was a device-oriented composite endpoint (DoCE, including cardiovascular death, target vessel myocardial infarction, or clinically and physiologically-indicated target lesion revascularization) at 3 years. RESULTS:2,223 (97.8%) participants with available angiograms were included, of which 302 (13.6%) had long lesions and 1921 (86.4%) had short lesions. At 3 years, DoCE occurred in 24/302 (8.0%) and 121/1921 (6.3%) patients in long and short groups, respectively. In the long lesions group, DoCE occurred in 14/121 (11.6%) and 10/181 (5.6%) in the DCBs and DES groups, respectively (HRIPTW: 2.46, 95% CI: 1.07-5.67, p = 0.034). In the short lesions group, DoCE occurred in 75/983 (7.7%) and 46/938 (4.9%) in the DCBs and DES groups, respectively (HRIPTW: 1.52, 95% CI: 1.03-2.22, p = 0.033). No significant interaction was observed between lesion length and DES/DCBs (Pinteraction = 0.460). CONCLUSION:DCBs were associated with a higher risk of DoCE compared to DES for treating de novo lesions, regardless of lesion length.

BACKGROUND:Drug-coated balloons (DCBs) are attractive for treating de novo coronary lesions, especially when involving bifurcations; however, their efficacy compared with drug-eluting stents (DES) remains uncertain. OBJECTIVES:The aim of this study was to assess the prognosis of DCBs vs DES in patients with noncomplex bifurcation and nonbifurcation lesions. METHODS:This was a prespecified subgroup analysis of the REC-CAGEFREE I (Paclitaxel-Coated Balloon for Treatment of De-Novo Non-Complex Coronary Artery Lesions) trial, which was an investigator-initiated, noninferiority trial conducted at 43 sites in China that randomized 2,272 participants to paclitaxel-coated balloons (the DCB group) or sirolimus-eluting stents (the DES group) for the treatment of de novo lesions, regardless of vessel diameter. The primary outcome was a device-oriented composite endpoint (DoCE) at 24 months. Participants were stratified according to the presence vs absence of bifurcation, and inverse probability of treatment weighting (IPTW) was performed to adjust for between-group imbalances. RESULTS:A total of 2,257 of 2,272 participants (99.3%) with available angiographic results were included. At 24 months, the DoCE had occurred in 46 of 773 patients in the bifurcation group (6.0%) and 64 of 1,484 patients in the nonbifurcation group (4.3%) (HRIPTW: 1.39; 95% CI: 0.87-2.21; P = 0.164). Of the 798 bifurcation lesions, 719 (90.1%) had DCB or DES treatment in the main vessel. A significant interaction for the DoCE was observed between bifurcation or nonbifurcation and assigned treatment (Pinteraction = 0.031). In the nonbifurcation group, the DoCE occurred in 46 of 735 patients with DCBs (6.3%) and 18 of 749 (2.4%) with DES (HRIPTW: 2.67; 95% CI: 1.64-4.33; P < 0.001); the in bifurcation group, the DoCE occurred in 26 of 394 patients with DCBs (6.7%) and 20 of 379 (5.3%) with DES (HRIPTW: 1.03; 95% CI: 0.53-2.01; P = 0.934). CONCLUSIONS:DCBs were associated with a numerically comparable risk for DoCE compared with DES in noncomplex bifurcations at 2 years. However, these findings should be interpreted as hypothesis generating only. (Paclitaxel-Coated Balloon for Treatment of De-Novo Non-Complex Coronary Artery Lesions; NCT04561739).

BACKGROUND:The safety and efficacy of drug-coated balloon (DCB) angioplasty for the treatment of proximal left anterior descending (LAD) lesions remain unclear. We aim to assess the prognosis of DCB versus drug-eluting stent (DES) in treating de novo proximal LAD lesions. METHODS:In this prespecified, exploratory subgroup analysis of the investigator-initiated, multicenter, randomized, non-inferiority REC-CAGEFREE I trial, 2272 patients were stratified into two groups based on whether target lesion was located in proximal LAD. The primary endpoint was device-oriented composite endpoint (DoCE, a composite of cardiovascular death, target vessel myocardial infarction, and clinically and physiologically indicated target lesion revascularization) at 2 years. RESULTS:Of 2272 patients randomized, 688 (30.3%) had target lesion in proximal LAD. In patients with proximal LAD lesions, compared to DES treatment, DCB treatment had a higher risk of 2-year DoCE (8.8% versus 3.4%, HRIPTW:2.68, 95%CI:1.34-5.35, P = 0.008). Similar results were observed in patients with non-proximal LAD lesions (DCB versus DES: 5.4% versus 3.3%, HRIPTW:1.72, 95%CI:1.04-2.85, P = 0.038). No significant interaction was observed between the lesion location and the treatment strategy (DES/DCB) (Pinteraction = 0.257). In patients with DCB treatment, proximal LAD had a higher risk of DoCE compared to non-proximal LAD (8.8% vs. 5.4%, HRIPTW:1.68, 95%CI:1.01-2.81, P = 0.049). CONCLUSIONS:For patients with de novo, non-complex coronary artery disease, DCB was associated with a higher 2-year risk of DoCE than DES across all lesion locations, with a numerically larger effect in proximal LAD. Due to the exploratory nature of the analysis, the results should be interpreted cautiously and considered hypothesis-generating.

OBJECTIVES:To investigate whether a less intense antiplatelet regimen could be used for people receiving drug coated balloons. DESIGN:Multicentre, randomised, open label, assessor blind, non-inferiority trial (REC-CAGEFREE II). SETTING:41 hospitals in China between 27 November 2021 and 21 January 2023. PARTICIPANTS:1948 adults (18-80 years) with acute coronary syndrome who received treatment exclusively with paclitaxel-coated balloons according to the international drug coated balloon consensus. INTERVENTIONS:Participants were randomly assigned (1:1) to either the stepwise dual antiplatelet therapy (DAPT) de-escalation group (n=975) consisting of aspirin plus ticagrelor for one month, followed by five months of ticagrelor monotherapy, and then six months of aspirin monotherapy, or to the standard DAPT group (n=973) consisting of aspirin plus ticagrelor for 12 months. MAIN OUTCOME MEASURES:The primary endpoint was net adverse clinical events (all cause death, stroke, myocardial infarction, revascularisation, and Bleeding Academic Research Consortium (BARC) type 3 or 5 bleeding) at 12 months in the intention-to-treat population. Non-inferiority was established if the upper limit of the one sided 95% confidence interval (CI) for the absolute risk difference was smaller than 3.2%. RESULTS:The mean age of participants was 59.2 years, 74.9% were men, 30.5% had diabetes, and 20.6% were at high bleeding risk. 60.9% of treated lesions were in small vessels, and 17.8% were in-stent restenosis. The mean drug coated balloon diameter was 2.72 mm (standard deviation 0.49). At 12 months, the primary endpoint occurred in 87 (8.9%) participants in the stepwise de-escalation group and 84 (8.6%) in the standard group (difference 0.36%; upper boundary of the one sided 95% CI 2.47%; Pnon-inferiority=0.013). In the stepwise de-escalation versus standard groups, BARC type 3 or 5 bleeding occurred in four versus 16 participants (0.4% v 1.6%, difference -1.19% (95% CI -2.07% to -0.31%), P=0.008), and all cause death, stroke, myocardial infarction, and revascularisation occurred in 84 versus 74 participants (8.6% v 7.6%, difference 1.05% (95% CI -1.37% to 3.47%), P=0.396). Treated as having hierarchical clinical importance by the win ratio method, more wins were noted with the stepwise de-escalation group (14.4% wins) compared with the standard group (10.1% wins) for the predefined hierarchical composite endpoint of all cause death, stroke, myocardial infarction, BARC type 3 bleeding, revascularisation, and BARC type 2 bleeding (win ratio 1.43 (95% CI 1.12 to 1.83), P=0.004). Results from the per-protocol and the intention-to-treat analysis were similar. CONCLUSIONS:Among participants with acute coronary syndrome who could be treated by drug coated balloons exclusively, a stepwise DAPT de-escalation was non-inferior to 12 month DAPT for net adverse clinical events. TRIAL REGISTRATION:Clinicaltrials.gov NCT04971356.

BACKGROUND:Data regarding the efficacy and safety of drug-coated balloons (DCBs) versus drug-eluting stents (DES) in patients with chronic kidney disease (CKD) remains limited. AIMS:To assess the prognosis of DCB versus DES in patients with and without CKD. METHODS:REC-CAGEFREE I was an investigator-initiated, non-inferiority trial conducted at 43 sites in China, which randomized 2272 patients to paclitaxel-coated balloons with the option of rescue stenting (DCB group) or second-generation sirolimus-eluting stents (DES group) for treating de novo lesions, regardless of vessel diameter. In this pre-specified subgroup analysis, patients were stratified based on the presence of CKD (kidney damage or estimated glomerular filtration rate < 60 mL/min per 1.73 m²) at baseline. The primary outcome was the device-oriented composite endpoint (DoCE; including cardiovascular death, target vessel myocardial infarction, and clinically and physiologically-indicated target lesion revascularization) at 2 years. RESULTS:Of 2272 patients enrolled, 203 (8.9%) had CKD, with 95 and 108 treated with DCB and DES, respectively. At 2 years, the risk of DoCE was significantly higher in CKD versus non-CKD patients (22/203 [10.9%] vs. 88/2069 [4.3%], HRIPTW: 2.14, 95% CI: 1.13-4.07, p = 0.022). There was no significant interaction between CKD and treatment allocation (pinteraction = 0.352). Among CKD patients, DoCE occurred in 12/95 (12.7%) and 10/108 (9.3%) patients in the DCB and DES groups (HRIPTW: 1.57, 95% CI: 0.66-3.71, p = 0.317), respectively. Among non-CKD patients, DoCE occurred in 60/1038 (5.8%) versus 28/1031 (2.7%) patients in the DCB and DES groups (HRIPTW: 2.27, 95% CI: 1.38-3.72, p = 0.002), respectively. CONCLUSION:Patients with CKD had worse outcomes compared to those without. DCBs were associated with a higher risk of DoCE than DES, irrespective of CKD status. TRIAL REGISTRATION:Unique Identifier: NCT04561739; URL: https://www. CLINICALTRIALS:gov.

Background Patients treated with drug-coated balloons (DCB) have the theoretical advantage of adopting a low-intensity antiplatelet regimen due to the absence of struts and polymers. Nevertheless, the optimal antiplatelet strategy for patients undergoing DCB-only treatment remains a topic of debate and has not been investigated in randomized trials. Methods The REC-CAGEFREE II is an investigator-initiated, prospective, open-label, multi-center, randomized, non-inferiority trial aimed to enroll 1908 patients from ≥ 40 interventional cardiology centers in China to evaluate the non-inferiority of an antiplatelet regimen consisting of Aspirin plus Ticagrelor for one month, followed by five months Ticagrelor monotherapy, and then Aspirin monotherapy for six months (Experimental group) compared to the conventional treatment of Aspirin plus Ticagrelor for 12 months (Reference group) in patients with acute coronary syndrome (ACS) who have undergone percutaneous coronary intervention (PCI) using paclitaxel-coated balloons (DCB) exclusively. Participants will be randomly assigned to the Experimental or Reference group in a 1:1 ratio. The randomization will be stratified based on the center and the type of lesion being treated (De novo or in-stent restenosis). The primary endpoint is net adverse clinical events (NACE) within 12 months of PCI, which includes the composite of all-cause death, any stroke, any myocardial infarction, any revascularization and Bleeding Academic Research Consortium (BARC) defined type 3 or 5 bleeding. The secondary endpoint, any ischemic and bleeding event, which includes all-cause death, any stroke, MI, BARC-defined type 3 bleeding, any revascularization, and BARC-defined type 2 bleeding events, will be treated as having hierarchical clinical importance in the above order and analyzed using the win ratio method. Discussion The ongoing REC-CAGEFREE II trial aims to assess the efficacy and safety of a low-intensity antiplatelet approach among ACS patients with DCB. If non-inferiority is shown, the novel antiplatelet approach could provide an alternative treatment for ACS patients with DCB. Trial registration ClinicalTrials.gov identifier: NCT04971356.

Background: Taking thrombosis and bleeding risks into consideration, little real world study data is available to dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) in elderly Chinese chronic total occlusion (CTO) patients. Objective: This study was designed to investigate the effectiveness and safety of Ticagrelor in comparison with Clopidogrel as an add-on therapy to Aspirin for elderly Chinese CTO patients who underwent elective PCI. Materials and Methods: We retrospectively enrolled 504 CTO patients (aged ≥75 years) who received PCI from December 2009 to May 2020 and DAPT for up to 12 months. The effectiveness endpoints were evaluated by major adverse cardiac events (MACE) including all-cause death, nonfatal myocardial infarction (MI) and clinically driven revascularization. The safety endpoints were recorded as the incidence of Bleeding Academic Research Consortium (BARC) bleeding. Results: Patients in Clopidogrel group, as was evidenced in our study, were older, and had a higher percentage of BMI, diastolic blood pressure and HDL-C than those in Ticagrelor group. Clopidogrel group had a lower percentage of hyperlipidemia, prior PCI, glucose, TG and LDL-C. No significant difference was found as to the Angiographic and procedural characteristics (P＞0.05 for all). After 12 months' follow-up, the incidence of MACE (12.19% vs. 11.04%, P=0.763) and bleeding (9.38% vs. 13.64%, P=0.205) showed no significant difference. After clinical characteristics balanced matching by inverse probability of treatment weighting (IPTW) model, we found that Ticagrelor had an unfavorable effect on reducing the incidence of bleeding with the IPTW model (IPTW-OR, 1.81, 95% CI: 1.18-2.76, P=0.006). Conclusions: Clopidogrel and Ticagrelor present similar effectiveness and safety to elderly Chinese CTO-PCI patients, yet Ticagrelor should be prescribed with caution to patients with a high bleeding risk.

The aim of this study was to evaluate whether patients with nonalcoholic fatty liver disease (NAFLD) have more myocardial malperfusion on CT myocardial perfusion imaging (CT-MPI), as well as to further assess if NAFLD is a predictor of myocardial ischemia independently. A total of 310 consecutive patients were included for analysis. All patients were divided into two groups according to the presence or absence of NAFLD, which was diagnosed by noncontrast cardiac CT partially covered liver and spleen. Clinical characteristics as well as imaging features including coronary artery calcium score, CCTA, and CT-MPI findings were analyzed. Univariable and multivariable logistic regression analyses were used to find out the relationship between NAFLD and myocardial ischemia. NAFLD (unadjusted hazard ratio [HR]: 2.4, 95 • NAFLD patients had higher calcium score, incidence of obstructive coronary artery disease, grade of CAD-RADS, quantitative plaque characteristics, and incidence of fat attenuation index ≥ −70.1 HU. • NAFLD patients had a higher incidence of myocardial ischemia, myocardial hypoperfusion, and hypoperfusion myocardial segments ratio. • NAFLD was a predictor of myocardial ischemia, independent of traditional cardiovascular risk factors, and CCTA characteristics.

Taking ischemic and bleeding risks into consideration, insufficient data exist on dual antiplatelet therapy after percutaneous coronary intervention in elderly Chinese patients with coronary artery disease. We aimed to investigate the effectiveness and safety of ticagrelor in comparison with clopidogrel on a background of aspirin for elderly Chinese patients with coronary artery disease 12 months after percutaneous coronary intervention. A single-center retrospective cohort study was conducted. Selected from patients with coronary artery disease aged ≥ 75 years from January 2010 to July 2019, 908 eligible subjects receiving dual antiplatelet therapy after percutaneous coronary intervention for up to 12 months were consecutively enrolled in the study. The included patients received ticagrelor in combination with aspirin (n = 264) or clopidogrel in combination with aspirin (n = 644). Effectiveness endpoints were evaluated by the major adverse cardiovascular events, encompassing all-cause death, non-fatal myocardial infarction, and clinically driven revascularization. The safety endpoints were recorded as the incidence of Bleeding Academic Research Consortium bleeding. The patients who were treated with ticagrelor were slightly younger than those who were treated with clopidogrel (79.1 ± 3.7 vs 80.7 ± 4.5 years, p < 0.01). The ticagrelor cohort contained a higher percentage of patients undergoing a prior percutaneous coronary intervention (37.9% vs 24.5%, p < 0.01), and a lower percentage of smokers (19.3% vs 27.2%, p < 0.05), compared with the clopidogrel cohort. The levels of glucose, total cholesterol, and low-density lipoprotein-cholesterol in the ticagrelor group were higher while the level of triglycerides and high-density lipoprotein-cholesterol were lower (p < 0.05) than those in the clopidogrel group. Left main percutaneous coronary intervention was performed more frequently among the ticagrelor-treated patients (23.5% vs 9.3%, p < 0.01), while patients in the clopidogrel group underwent more left circumflex percutaneous coronary intervention (34.3% vs 23.1%, p < 0.01). We found that ticagrelor was associated with a lower incidence of major adverse cardiovascular events than clopidogrel using the inverse probability of treatment weighting model (odds ratio, 0.493; 95% confidence interval 0.356–0.684). There was no difference in terms of the risk of Bleeding Academic Research Consortium bleeding between the two groups (p > 0.05). Ticagrelor was associated with a lower incidence of major adverse cardiovascular events than clopidogrel at 12 months in elderly Chinese patients with coronary artery disease, without a significant increase of Bleeding Academic Research Consortium bleeding events.

Low adhesion between emulsified asphalt mortar and aggregate can enormously result in poor properties of emulsified asphalt mixture. The adhesion performance can also be directly influenced by the viscosity of cement emulsified asphalt mortar (CEAM). In this work, Brookfield viscometer was used to test the viscosity of CEAM with different cement content, temperature and mixing time. Then, influence degree of each factor on viscosity was determined by gray correlation analysis (GCA) and significance test. Furthermore, dynamic mechanical analysis (DMA) was used to quantitatively evaluate the adhesion between CEAM and aggregate. Besides these, scanning electron microscope (SEM), energy dispersive X-ray (EDX), alkali content test, Fourier transform infrared spectroscopy (FT-IR) were adopted to analyze the interaction between cement and emulsified asphalt. The results show that the viscosity of CEAM increases with the increase of the cement content, mixing time and temperature. The cement content has the highest effect on the viscosity of CEAM, followed by mixing time; and temperature has a lowest effect. When the cement content is less than 50%, hydration products in the mixture can improve the fatigue life of CEAM. While it is higher than 50%, the adhesion is weakened and the fatigue life is shortened. Cement hydration and asphalt emulsion demulsification can mutually promote, which generates a network structure and improves the adhesion performance of CEAM to aggregate.

The purpose of this observational study was to investigate the feasibility, initial safety, and efficacy of the SeQuent® Please DCB (B. Braun Melsungen, Germany) for patients with de novo coronary lesions in vessels exceeding 3.0 mm in a consecutive series of all comer percutaneous coronary intervention. A total of 120 patients (135 lesions) with de novo coronary lesions in vessels ≥ 3.0 mm treated with DCB were enrolled in this single-centre prospective observational study. The primary endpoint was target lesion failure (TLF), a composite endpoint of cardiac death, target vessel-myocardial infarction (TV-MI), and clinically driven target vessel revascularization (TLR) at 12 months. Safety endpoints included cardiac death, TV-MI, and definite target vessel thrombosis. 45.9% of the lesions were classified as complex (type B2/C). The reference vessel diameter was 3.09 ± 0.31 mm measured via quantitative coronary angiography analysis. Coronary dissections occurred in 42 patients (35.0%; Type A-B 14.1%; Type C 19.1%; Type D: 1.6%), two of which [1.6%; (type D dissection)] underwent bail-out stent implantation. 12-month follow-up was completed in 100% patients. The 12-month incidence of TLF was 3.4%. The clinically driven TLR occurred in four patients (3.4%). The incidence of TLR was low in patients without any detectable dissections, similar to those with dissections (3.8% vs. 2.5%; p = 0.146). No patient suffered cardiac death, TV-MI, or target vessel thrombosis. The study shows the feasibility, initial safety, and efficacy of coronary intervention using SeQuent® Please DCB for the treatment of patients with de novo lesion in vessels exceeding 3 mm. The study highlights that the coronary dissection (Type A–C) post DCB treatment occurs frequently but is safe at follow up.

Hypoxia-induced pulmonary hypertension, which is characterized by vascular remodeling of blood vessels, is an important complication in COPD. In this study, we found that the expression of miR-214 was differentially expressed by screening 13 candidate miRNAs in pulmonary artery smooth muscle cells (PASMCs). Additionally, using luciferase assay in PASMCs, we found that phosphatase-and-tensin homolog (PTEN) was a target of miR-214. Furthermore, the expression of PTEN was found to be substantially downregulated in PASMCs from COPD patients with pulmonary hypertension (PH) compared with normal controls by using real-time polymerase chain reaction (PCR), immunohistochemistry, and Western blot. In addition, we transfected PASMCs with miR-214 mimics, using real-time PCR and Western blotting, to confirm the miRNA/mRNA relationship. Furthermore, the introduction of miR-214 significantly promoted the proliferation of PASMCs by suppressing apoptosis of the cells, which was mediated by the downregulation of PTEN. Exposure to hypoxia significantly increased the expression of miR-214 and decreased the expression of PTEN in PASMCs, and its proliferation was significantly promoted. Such effects could be significantly attenuated by the introduction of miR-214 inhibitors, which significantly downregulated miR-214 expression and upregulated the expression of PTEN. In conclusion, hypoxia-induced upregulation of miR-214 was found to promote PH development by targeting PTEN in PASMCs, and miR-214 could be a promising diagnostic tool and novel therapeutic target in the management of hypoxia-induced PH in COPD.

Mesenchymal stem cells (MSCs) hold great promise as cell therapy candidate in clinics. However, the underlying mechanisms remain elusive due to the lack of effective cell tracking approaches during therapeutic processes. In this study, we successfully synthesized and utilized NaYF4:Yb3+,Er3+ upconversion nanoparticles (UCNPs) to label and track rabbit bone marrow mesenchymal stem cells (rBMSCs) during the osteogenic differentiation in vitro. To improve their biocompatibility and cellular uptake, we modified the UCNPs with negatively-charged poly(acrylic acid) and positively-charged poly(allylamine hydrochloride) in turns (i.e., PAH-PAA-UCNPs). The effect of cellular uptake of UCNPs on the osteogenic differentiation of rBMSCs was systematically evaluated, and no significant difference was found between rBMSCs labeled with UCNPs (concentration range of 0-50 mu g/mL) and UCNPs-free rBMSCs in terms of cell viability, ALP activity, osteogenic protein expressions and production of mineralized nodules. Moreover, the PAH-PAA-UCNPs at a concentration of 50 mu g/mL exhibited the highest biocompatibility and stability, which could well track rBMSCs during the osteogenesis process. These results would provide a positive reference for the application of these lanthanide-doped UCNPs as fluorescent nanoprobes for stem cell tracking to further understand the mechanism of stem cell fate in tissue engineering and stem cell therapy.Statement of SignificanceUpconversion nanoparticles (UCNPs) have attracted increasing attention as alternative probes for tracking various types of cells including stem cells. The reported fluorapatite-based UCNPs with the needle-like morphology showed a little poor performance on stem cell tracking, which was possibly attributed to the low upconversion efficiency and cell labeling efficiency potentially due to nanomaterial composition, crystal structure and shape. Here, we synthesized the positively-charged NaYF4:Yb3+,Er3+ UCNPs with hexagonal phase and sphere-like morphology to enhance their upconversion efficiency, biocompatibility and cellular uptake, leading to a successful tracking of rBMSCs in osteogenesis process without impairing cell viability and differentiation capacity. This study provided a necessary reference for the application of UCNPs in stem cell tracking to better understand the mechanism of stem cell fate in tissue engineering, stem cell therapy, etc. (C) 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

The functions of the binders, cement and emulsified asphalt, in cement emulsified asphalt mixture are quite different from the situation where they are used in cement concrete or asphalt mixture. In addition, reasonable curing ages for the mixture are not well determined, especially in severe weather conditions. It is desirable to recommend the ranking about effects of binder’s content and curing age on properties, such as indirect tensile strength (IDT), dynamic stability (DS), IDT at low temperature and dry shrinkage of the mixture to the asphalt pavement engineering. This study was performed to compare effects of binders and curing ages on the properties of the mixture using gray relation entropy analysis. In addition, Zeta potential, viscosity, microstructures, hydration heat of the binders and absorption between cement and emulsified asphalt were also tested to analyze the mechanism. The results indicate that IDT and DS values of the mixture increase remarkably with the increase of cement content. Emulsified asphalt content has a direct relation with IDT at low temperature. The dry shrinkage shows an abrupt increase at the 28-curing day. It is recommended the ranking of the following correlation degrees through the results from the gray correlation degree analyses: cement content>emulsified asphalt content>curing age (IDT); cement content>curing age>emulsified asphalt content (DS); emulsified asphalt content>cement content>curing age (IDT at low temperature) and curing age>cement content>emulsified asphalt content (dry shrinkage).

Cement emulsified asphalt mixture is a kind of composite materials, which is comprised of organic and inorganic materials, such as emulsified asphalt and cement, and has both advantages of cement concrete and asphalt concrete. Aiming at the problems of cement emulsified asphalt mixture that adhesion decline and road performance down in the using of process, the Discrete Element Method (DEM) was used to simulate two different kinds of aggregate used in the mixture. Through comparing the splitting strength, stress-strain curve, fracture development situation, and so on, suitable aggregate type, limestone aggregate, was obtained, which had higher adhesion property with cement emulsified asphalt binders.