Comparison of machine learning-based CT fractional flow reserve with cardiac MR perfusion mapping for ischemia diagnosis in stable coronary artery disease.

OBJECTIVES: To compare the diagnostic performance of machine learning (ML)-based computed tomography-derived fractional flow reserve (CT-FFR) and cardiac magnetic resonance (MR) perfusion mapping for functional assessment of coronary stenosis. METHODS: Between October 2020 and March 2022, consecutive participants with stable coronary artery disease (CAD) were prospectively enrolled and underwent coronary CTA, cardiac MR, and invasive fractional flow reserve (FFR) within 2 weeks. Cardiac MR perfusion analysis was quantified by stress myocardial blood flow (MBF) and myocardial perfusion reserve (MPR). Hemodynamically significant stenosis was defined as FFR ≤ 0.8 or > 90% stenosis on invasive coronary angiography (ICA). The diagnostic performance of CT-FFR, MBF, and MPR was compared, using invasive FFR as a reference. RESULTS: The study protocol was completed in 110 participants (mean age, 62 years ± 8; 73 men), and hemodynamically significant stenosis was detected in 36 (33%). Among the quantitative perfusion indices, MPR had the largest area under receiver operating characteristic curve (AUC) (0.90) for identifying hemodynamically significant stenosis, which is in comparison with ML-based CT-FFR on the vessel level (AUC 0.89, p = 0.71), with comparable sensitivity (89% vs 79%, p = 0.20), specificity (87% vs 84%, p = 0.48), and accuracy (88% vs 83%, p = 0.24). However, MPR outperformed ML-based CT-FFR on the patient level (AUC 0.96 vs 0.86, p = 0.03), with improved specificity (95% vs 82%, p = 0.01) and accuracy (95% vs 81%, p < 0.01). CONCLUSION: ML-based CT-FFR and quantitative cardiac MR showed comparable diagnostic performance in detecting vessel-specific hemodynamically significant stenosis, whereas quantitative perfusion mapping had a favorable performance in per-patient analysis. CLINICAL RELEVANCE STATEMENT: ML-based CT-FFR and MPR derived from cardiac MR performed well in diagnosing vessel-specific hemodynamically significant stenosis, both of which showed no statistical discrepancy with each other. KEY POINTS: • Both machine learning (ML)-based computed tomography-derived fractional flow reserve (CT-FFR) and quantitative perfusion cardiac MR performed well in the detection of hemodynamically significant stenosis. • Compared with stress myocardial blood flow (MBF) from quantitative perfusion cardiac MR, myocardial perfusion reserve (MPR) provided higher diagnostic performance for detecting hemodynamically significant coronary artery stenosis. • ML-based CT-FFR and MPR from quantitative cardiac MR perfusion yielded similar diagnostic performance in assessing vessel-specific hemodynamically significant stenosis, whereas MPR had a favorable performance in per-patient analysis.

PPARγ Agonist Rosiglitazone and Antagonist GW9662: Antihypertensive Effects on Chronic Intermittent Hypoxia-Induced Hypertension in Rats.

The increased incidence of hypertension associated with obstructive sleep apnea (OSA) presents significant physical, psychological, and economic challenges. Peroxisome proliferator-activated receptor gamma (PPARγ) plays a role in both OSA and hypertension, yet the therapeutic potential of PPARγ agonists and antagonists for OSA-related hypertension remains unexplored. Therefore, we constructed a chronic intermittent hypoxia (CIH)-induced hypertension rat model that mimics the pathogenesis of OSA-related hypertension in humans. The model involved administering PPARγ agonist rosiglitazone (RSG), PPARγ antagonist GW9662, or normal saline, followed by regular monitoring of blood pressure and thoracic aorta analysis using staining and electron microscopy. Intriguingly, our results indicated that both RSG and GW9662 appeared to potently counteract CIH-induced hypertension. In silico study suggested that GW9662's antihypertensive effect might mediated through angiotensin II receptor type 1 (AGTR1). Our findings provide insights into the mechanisms of OSA-related hypertension and propose novel therapeutic targets.

Comparison of CT-derived Plaque Characteristic Index With CMR Perfusion for Ischemia Diagnosis in Stable CAD.

BACKGROUND: Coronary computed tomography angiography (CCTA) and cardiac magnetic resonance (CMR) have been used to diagnose lesion-specific ischemia in patients with coronary artery disease. The aim of this study was to investigate the diagnostic performance of CCTA-derived plaque characteristic index compared with myocardial blood flow (MBF) and myocardial perfusion reserve (MPR) derived from CMR perfusion in the assessment of lesion-specific ischemia. METHODS: Between October 2020 and March 2022, consecutive patients with suspected or known coronary artery disease, who were clinically referred for invasive coronary angiography were prospectively enrolled. All participants sequentially underwent CCTA and CMR and invasive fractional flow reserve within 2 weeks. The diagnostic performance of CCTA-derived plaque characteristics, CMR perfusion-derived stress MBF, and MPR were compared. Lesions with fractional flow reserve ≤0.80 were considered to be hemodynamically significant stenosis. RESULTS: Nighty-two patients with 141 vessels were included in this study. Plaque length, minimum luminal area, plaque area, percent area stenosis, total atheroma volume, vessel volume, lipid-rich volume, spotty calcium, napkin-ring signs, stress MBF, and MPR in flow-limiting stenosis group were significantly different from nonflow-limiting group. The overall accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of lesion-specific ischemia diagnosis were 61.0%, 55.3%, 63.1%, 35.6%, and 79.3% for stress MBF, and 89.4%, 89.5%, 89.3%, 75.6%, 95.8% for MPR; meanwhile, 82.3%, 79.0%, 84.5%, 65.2%, and 91.6% for CCTA-derived plaque characteristic index. CONCLUSIONS: In our prospective study, CCTA-derived plaque characteristics and MPR derived from CMR performed well in diagnosing lesion-specific myocardial ischemia and were significantly better than stress MBF in stable coronary artery disease.

Fully automated pixel-wise quantitative CMR-myocardial perfusion with CMR-coronary angiography to detect hemodynamically significant coronary artery disease.

OBJECTIVES: We applied a fully automated pixel-wise post-processing framework to evaluate fully quantitative cardiovascular magnetic resonance myocardial perfusion imaging (CMR-MPI). In addition, we aimed to evaluate the additive value of coronary magnetic resonance angiography (CMRA) to the diagnostic performance of fully automated pixel-wise quantitative CMR-MPI for detecting hemodynamically significant coronary artery disease (CAD). METHODS: A total of 109 patients with suspected CAD were prospectively enrolled and underwent stress and rest CMR-MPI, CMRA, invasive coronary angiography (ICA), and fractional flow reserve (FFR). CMRA was acquired between stress and rest CMR-MPI acquisition, without any additional contrast agent. Finally, CMR-MPI quantification was analyzed by a fully automated pixel-wise post-processing framework. RESULTS: Of the 109 patients, 42 patients had hemodynamically significant CAD (FFR ≤ 0.80 or luminal stenosis ≥ 90% on ICA) and 67 patients had hemodynamically non-significant CAD (FFR ˃ 0.80 or luminal stenosis < 30% on ICA) were enrolled. On the per-territory analysis, patients with hemodynamically significant CAD had higher myocardial blood flow (MBF) at rest, lower MBF under stress, and lower myocardial perfusion reserve (MPR) than patients with hemodynamically non-significant CAD (p < 0.001). The area under the receiver operating characteristic curve of MPR (0.93) was significantly larger than those of stress and rest MBF, visual assessment of CMR-MPI, and CMRA (p < 0.05), but similar to that of the integration of CMR-MPI with CMRA (0.90). CONCLUSIONS: Fully automated pixel-wise quantitative CMR-MPI can accurately detect hemodynamically significant CAD, but the integration of CMRA obtained between stress and rest CMR-MPI acquisition did not provide significantly additive value. KEY POINTS: • Full quantification of stress and rest cardiovascular magnetic resonance myocardial perfusion imaging can be postprocessed fully automatically, generating pixel-wise myocardial blood flow (MBF) and myocardial perfusion reserve (MPR) maps. • Fully quantitative MPR provided higher diagnostic performance for detecting hemodynamically significant coronary artery disease, compared with stress and rest MBF, qualitative assessment, and coronary magnetic resonance angiography (CMRA). • The integration of CMRA and MPR did not significantly improve the diagnostic performance of MPR alone.

Energy partitioning in laser-induced millimeter-sized spherical cavitation up to the fourth oscillation.

To investigate the energy partitioning up to the fourth oscillation of a millimeter-scale spherical cavitation bubble induced by laser, we used nanosecond laser pulses to generate highly spherical cavitation bubbles and shadowgraphs to measure the radius-time curve. Using the extended Gilmore model and considering the continuous condensation of the vapor in the bubble, the time evolution of the bubble radius, bubble wall velocity, and pressure in the bubble is calculated till the 4th oscillation. Using Kirkwood-Bethe hypothesis, the evolution of velocity and pressure of shock wave at the optical breakdown, the first and second collapses are calculated. The shock wave energy at the breakdown and bubble collapse is directly calculated by numerical method. We found the simulated radius-time curve fits well with experimental data for the first four oscillations. The energy partition at the breakdown is the same as that in previous studies, the ratio of shock wave energy to bubble energy is about 2:1. In the first collapse and the second collapse, the ratio of shock wave energy to bubble energy is 14.54:1 and 2.81:1 respectively. In the third and fourth collapses, the ratio is less, namely than 1.5:1 and 0.42:1 respectively. The formation mechanism of the shock wave at the collapse is analyzed. The breakdown shock wave is mainly driven by the expansion of the supercritical liquid resulting from the thermalization of the energy of the free electrons in the plasma, and the collapse shock wave is mainly driven by the compressed liquid around the bubble.

Impact of Pressure Wire on Fractional Flow Reserve and Hemodynamics of the Coronary Arteries: A Computational and Clinical Study.

OBJECTIVE: Noninvasive fractional flow reserve (FFR) has been extensively studied and gained clinical recognition. However, the effect of an interventional catheter and a pressure wire in the arteries on the noninvasive FFR was not considered in previous studies. We provide quantitative analysis of how a catheter and a pressure wire can affect the estimation of noninvasive FFR using computational fluid dynamics (CFD) techniques. METHODS: Six patients are studied. We calibrate our CFD model with patient-specific conditions so that the noninvasive FFR matches the FFR measured by the pressure wire. Then, we numerically remove the pressure wire and compute the noninvasive FFR again. This allows us to analyze the effect of the pressure wire on FFR. RESULTS: The presence of a catheter and a pressure wire can reduce distal pressure from -0.1 mmHg to -8.1 mmHg, resulting in a reduction of FFR by 5.8 % in average (0.012 to 0.107 or -1.2 % to -16.8 %). The insertion also reduces the time-averaged flow rate at the stenosis by up to 16.2 % (4.9 % in average). CONCLUSION: The impact of the pressure wire on the measured FFR depends on the characteristics of the patient-specific lesion. Significant linear correlations are found between the minimum diameter of the stenotic arteries and the reduction in FFR. SIGNIFICANCE: The impact we found may contribute to provide a correction and improve the estimation of the noninvasive FFR technique for use in clinical practice.

Validation of a Novel Renal Denervation System With Cryoablation: A Preclinical Study and Case Series.

Recently, we designed a renal denervation with cryoablation (Cryo-RDN) system using liquid nitrogen and proved its short-term safety and effectiveness. In this study, we first conducted a 6-month follow-up in a swine model. Renal sympathetic nerve activity remained at a significantly lower level than that of the control group after 6 months. In patients with resistant hypertension, Cryo-RDN demonstrated preliminary safety. Renal function fluctuations and vascular-related complications were not detected. In addition, the average 24-hour systolic and diastolic blood pressure decreased by 12.17 ± 8.35 mm Hg and 8.50 ± 3.83 mm Hg at the 6-month follow-up, respectively, compared with their baseline values.

The lncRNA ZFAS1 regulates lipogenesis in colorectal cancer by binding polyadenylate-binding protein 2 to stabilize SREBP1 mRNA.

Colorectal cancer (CRC) is the fourth leading cause of cancer-related mortality globally. Therefore, a better understanding of the early molecular events of this disease is needed. Long noncoding RNAs (lncRNAs) play a critical role in the regulation of tumorigenesis and cancer progression. In this study, we investigated the characteristics of ZFAS1 in CRC. We analyzed three independent microarray datasets of CRC tissues from GEO and found that ZFAS1 expression was remarkably upregulated in all three datasets. Moreover, we validated the overexpression of ZFAS1 in CRC tissues compared with normal tissues and found that ZFAS1 was positively correlated with tumor size and metastasis in CRC. Knockdown of ZFAS1 significantly suppressed the malignant phenotype and lipogenesis of CRC cells. Mechanistically, ZFAS1 binds polyadenylate-binding protein 2 (PABP2) to stabilize SREBP1 mRNA, thereby increasing the expression of SREBP1 and its target genes stearoyl-CoA desaturase (SCD1) and fatty acid synthase (FASN), thus promoting CRC lipid accumulation. These data demonstrated that ZFAS1 could act as an oncogene for CRC and that ZFAS1 reprograms lipid metabolism by binding with PABP2 to stabilize SREBP1 mRNA accumulation, implicating it as a novel and potent target for the treatment of CRC.

[Roles of long non-coding RNAs in prostate cancer and their action mechanisms].

Prostate cancer (PCa) is one of the most common male malignancies as well as one of the frequent causes of tumor-induced death. Long non-coding RNAs (lncRNAs) are RNA transcripts that are more than 200 nucleotides in length, lack an open reading frame, and do not encode proteins. LncRNAs are abnormally expressed in most tumors including PCa and closely related to the recurrence, metastasis and prognosis of PCa. LncRNAs regulate gene expressions at multiple levels such as epigenetics, transcription and post-transcription, change metabolic pathways, and play a carcinogenic or anti-tumor role in the development and progression of PCa. Continuous androgen receptor (AR) signal transduction is one of the key features of castration-resistant PCa. This review briefly introduces the role of lncRNAs as oncogenes or tumor suppressor genes in the development and progression of PCa, and expounds the possible molecular mechanisms of lncRNAs mediating PCa through the AR signaling pathway, post-transcriptional regulation represented by ceRNA, and tumor metabolism, aiming to provide potential biomarkers and therapeutic targets for the clinical diagnosis and treatment of PCa.

A Simple Model to Predict Repeat Revascularization After Drug-Eluting Stent Implantation in Patients With Stable Coronary Artery Disease.

Repeat revascularization is still common in the era of drug-eluting stents (DES), especially for non-target lesions. However, few validated models exist to predict the need for revascularization. We aimed to develop and validate an easy-to-use predictive model for repeat revascularization after DES implantation in patients with stable coronary artery disease (CAD). A total of 1,653 stable CAD patients with angiographic follow-up after DES implantation were consecutively enrolled. Split-sample testing was adopted to develop and validate the model. In the training set, male, diabetes, number of target lesions, occlusion lesion, number of non-target lesions, recurrent angina, suboptimal low density lipoprotein-cholesterol level, and high lipoprotein (a) level were independent predictors of repeat revascularization using logistic regression analyses. The established model (Model 1) yielded a bias-corrected concordance index of 0.700 (95% confidence interval: 0.667 to 0.735), with good calibration. It also performed well in the validation set. Compared with the traditional empirical model only including recurrent angina (Model 2), Model 1 had better discriminative ability and clinical usefulness. In conclusion, we established and validated a simple model including 8 easily accessible variables to predict repeat revascularization after DES implantation in stable CAD patients, contributing to better risk stratification, decision making, and patient consultation.

Nanosecond resolution photography system for laser-induced cavitation based on PIV dual-head laser and industrial camera.

The detailed study of the initial and collapse processes of the laser-induced cavitation requires nanosecond resolution (both nanoseconds exposure and nanoseconds interframe time) of the photography measurement system. The high-speed video cameras are difficult to achieve nanoseconds interval time. The framing and streak cameras are able to reach the nanosecond resolution, but their complex technology and expensive prices make them far from being commercially available. The present study builds a nanosecond resolution photography system based on PIV dual-head laser and conventional industrial camera. The exposure time of the photography system is controlled by the laser pulse width, which is 5 ns. The two heads of the PIV laser are operated independently thus the smallest time interval between two laser pulses can be set to less than 10 ns. A double-pulse per-exposure imaging technique is used to record the information from two laser pulses on single frame on a low-speed industrial camera. The nanosecond resolution photography system was applied to the laser-induced cavitation experiments to verify the reliability of the measurement results. The measurement of the shock wave velocity demonstrates the ability of the system to capture ultrafast phenomena, which reduces from 3611 m/s to approximately 1483 m/s within 400 ns. The experimental results also reveal the asymmetric evolution of laser-induced cavitation bubbles. The major axis of the ellipsoidal bubble has twice reversals along the laser propagation and perpendicular direction from the laser-induced breakdown to the first collapse.

The prevalence, relative risk factors and MTHFR C677T genotype of H type hypertension of the elderly hypertensives in Shanghai, China: a cross-section study : Prevalence of H type hypertension.

BACKGROUND: H type hypertension is defined as homocysteine (Hcy) ≥ 10 µmol/L in combination with primary hypertension. Studies demonstrated that the existence of hyperhomocysteine (HHcy) in hypertensive exacerbates the poor outcome of cardiocerebral incidents. This study was to investigate the current epidemic situation of H type hypertension and determine the risk factors in order to find intervention targets for H type hypertensives. METHODS: We conducted a cross-sectional study using cluster sampling design in Shanghai, China from July 2019 and April 2020. 23,652 patients with primary hypertension were enrolled in this study. Their medical information was recorded, and the level of Hcy concentrations and methylenetetrahydrofolate reductase (MTHFR) C677T polymorphisms were detected. RESULTS: In total, 22,731 of 23,652 patients were recorded. The mean age was 68.9 ± 8.6 y and 43% were men. 80.0% of the enrolled patients had H type hypertension. The frequency of allele T was 40.9%, and the proportions of the CC, CT, and TT genotypes were 36.1%, 46.0%, and 17.9%, respectively. Compared with the TT genotype, the plasma Hcy concentration levels were lower in patients with the CC/CT genotype (18.96 ± 13.48 µmol/L vs. 13.62 ± 5.20/14.28 ± 5.36, F = 75.04, p < 0.01). The risk for H type hypertension was higher in elderly people. Men had ~ 5.55-fold odds of H type hypertension compared with women. Patients with CT genotype and TT genotype had ~ 1.36- and ~ 2.76-fold odds of H type hypertension compared with those with CC genotype, respectively. Smoking and diabetes were not significantly associated with H type hypertension. CONCLUSIONS: The prevalence of H type hypertension in patients with primary hypertension was 80.0%, which was higher than the 75% found in prior report in China. Age, gender, and MTHFR C677T polymorphisms rather than smoking and diabetes were independently associated with H type hypertension.

PCSK9 (Proprotein Convertase Subtilisin/Kexin 9) Enhances Platelet Activation, Thrombosis, and Myocardial Infarct Expansion by Binding to Platelet CD36.

BACKGROUND: PCSK9 (proprotein convertase subtilisin/kexin 9), mainly secreted by the liver and released into the blood, elevates plasma low-density lipoprotein cholesterol by degrading low-density lipoprotein receptor. Pleiotropic effects of PCSK9 beyond lipid metabolism have been shown. However, the direct effects of PCSK9 on platelet activation and thrombosis, and the underlying mechanisms, as well, still remain unclear. METHODS: We detected the direct effects of PCSK9 on agonist-induced platelet aggregation, dense granule ATP release, integrin αIIbß3 activation, α-granule release, spreading, and clot retraction. These studies were complemented by in vivo analysis of FeCl3-injured mouse mesenteric arteriole thrombosis. We also investigated the underlying mechanisms. Using the myocardial infarction (MI) model, we explored the effects of PCSK9 on microvascular obstruction and infarct expansion post-MI. RESULTS: PCSK9 directly enhances agonist-induced platelet aggregation, dense granule ATP release, integrin αIIbß3 activation, P-selectin release from α-granules, spreading, and clot retraction. In line, PCSK9 enhances in vivo thrombosis in a FeCl3-injured mesenteric arteriole thrombosis mouse model, whereas PCSK9 inhibitor evolocumab ameliorates its enhancing effects. Mechanism studies revealed that PCSK9 binds to platelet CD36 and thus activates Src kinase and MAPK (mitogen-activated protein kinase)-extracellular signal-regulated kinase 5 and c-Jun N-terminal kinase, increases the generation of reactive oxygen species, and activates the p38MAPK/cytosolic phospholipase A2/cyclooxygenase-1/thromboxane A2 signaling pathways downstream of CD36 to enhance platelet activation, as well. Using CD36 knockout mice, we showed that the enhancing effects of PCSK9 on platelet activation are CD36 dependent. It is important to note that aspirin consistently abolishes the enhancing effects of PCSK9 on platelet activation and in vivo thrombosis. Last, we showed that PCSK9 activating platelet CD36 aggravates microvascular obstruction and promotes MI expansion post-MI. CONCLUSIONS: PCSK9 in plasma directly enhances platelet activation and in vivo thrombosis, and MI expansion post-MI, as well, by binding to platelet CD36 and thus activating the downstream signaling pathways. PCSK9 inhibitors or aspirin abolish the enhancing effects of PCSK9, supporting the use of aspirin in patients with high plasma PCSK9 levels in addition to PCSK9 inhibitors to prevent thrombotic complications.

A novel risk assessment model of contrast-induced nephropathy after percutaneous coronary intervention in patients with diabetes.

The purpose of our study was to develop a simple clinical pre-procedure risk model based on clinical characteristics for the prediction of contrast-induced nephropathy (CIN) and major adverse cardiac events (MACEs) after percutaneous coronary intervention (PCI) in patients with diabetes. A total of 1113 patients with diabetes who underwent PCI with contrast exposure were randomized into a development group (n = 742) and a validation group (n = 371) in a 2:1 ratio. CIN was defined as an increase of either 25% or 0.5 mg/dL (44.2 µmol/L) in serum creatinine within 72 hours after contrast infusion. A simple CIN risk score based on independent predictors was established. Four variables were identified for our risk score model: LVEF < 40%, acute coronary syndrome (ACS), eGFR < 60, and contrast volume > 300 mL. Based on this new CIN risk score, the incidence of CIN had a significant trend with increased predicting score values of 5.9%, 32.9% and 60.0%, corresponding to low-, moderate- and high-risk groups, respectively. The novel risk assessment exhibited moderate discrimination ability for predicting CIN, with an AUC of 0.759 [95% CI 0.668-0.852, P = .001] in the validation cohort. It also had similar prognostic values for one-year follow-up MACE (C-statistic: 0.705 and 0.606 for new risk score and Mehran score, respectively). This novel risk prediction model could be effective for preventing nephropathy in diabetic patients receiving contrast media during surgical procedures.

MiR-223 levels predicting perioperative bleeding in off-pump coronary artery bypass grafting.

BACKGROUND: To investigate the predictive value of platelet-related microRNAs (miRNAs) for bleeding during and after off-pump coronary artery bypass grafting (OPCABG) and the influence of dual antiplatelet therapy (DAPT) on miRNAs. METHODS: This prospective study included 59 patients scheduled for OPCABG. The plasma miR-126 and miR-223 levels were measured and platelet aggregation was determined by thromboelastography during DAPT. The plasma miRNA levels were compared between patients treated with ticagrelor or clopidogrel. Multivariable logistic regression analysis was performed to determine the independent risk factors for bleeding during and after surgery. Active bleeding was defined as a blood loss >1.5 mL/kg/h for 6 consecutive hours within the first 24 hours or in case of reoperation during the first 12 postoperative hours. Severe perioperative bleeding was defined using the universal definition of perioperative bleeding in adult cardiac surgery. RESULTS: Higher circulating miR-223 levels [odds ratio (OR) =1.348, 95% confidence interval (CI): 1.001-1.814, P=0.047] and lower body mass index (OR =0.648, 95% CI: 0.428-0.980, P=0.040) were independent predictors for severe perioperative bleeding in OPCABG. Ticagrelor treatment led to significant increases in circulating miR-223 levels compared with clopidogrel treatment. CONCLUSIONS: The plasma miR-223 levels served as a predictor for bleeding during and after OPCABG. Circulating miR-223 levels were significantly elevated with ticagrelor treatment compared with clopidogrel treatment. MiR-223 may be a novel biomarker for bleeding in cardiac surgery and can help explain the different efficacies of ticagrelor and clopidogrel.

Three-year clinical outcomes of a sirolimus-eluting bioresorbable scaffold (XINSORB) and a metallic stent to treat coronary artery stenosis.

BACKGROUND: Recent studies have shown increased risks of late target lesion failure (TLF) and thrombosis using a bioresorbable scaffold (BRS). However, the results of the ABSORB China study offered a different means of understanding the long-term performance of BRSs. We tested the 3-year clinical outcome of the XINSORB BRS in a multicenter, randomized controlled clinical trial (ChiCTR1800014966). METHODS: Eligible patients with one or two de novo coronary lesions were randomly assigned 1:1 to be treated with XINSORB scaffolds and metallic sirolimus-eluting stents (SESs). The clinical endpoints include TLF [cardiac death, target vessel-related myocardial infarction (TV-MI), or ischemia-driven target lesion revascularization (ID-TLR)], its components, and devised thrombosis. RESULTS: Three hundred ninety-five patients were enrolled and randomized to the XINSORB (N=200) and SES (N=195) arms. The clinical 3-year follow-up included 95.5% of the XINSORB-treated patients and 92.8% of the SES-treated patients. Dual antiplatelet therapy was at 59.0% of the XINSORB-treated and 52.8% of the SES-treated patients (P=0.34). There were no significant differences in the clinical outcomes between the XINSORB and SES arms, including in TLF (4.0% vs. 6.2%, P=0.29), cardiac death (1.0% vs. 0%, P=NA), TV-MI (1.0% vs. 0%, P=NA), and ID-TLR (3.5% vs. 6.2%, P=0.19). The rate of confirmed/probable device thrombosis in the XINSORB-treated patients was only 1.0% (2/200). CONCLUSIONS: In this XINSORB randomized clinical trial, the XINSORB scaffolds and SESs showed similar efficacy and safety up to the 3-year follow-up. The rates of TLF and device thrombosis were low and comparable between the two arms.

[Long noncoding RNA Linc00662 promotes the tumorigenesis of prostate cancer cells].

OBJECTIVE: To investigate the expression of Linc00662 in PCa and its influence on the biological function of PCa cells. METHODS: Using qRT-PCR, we detected the expression of Linc00662 in the PCa tissue and cell lines and that in the adjacent normal prostatic tissue and epithelial WPMY-1 cells and analyzed the correlation between the expression of Linc00662 and the clinicopathological features of the PCa tissue. We transfected PC-3 and DU145 cells with siRNA, and verified the interference efficiency by qRT-PCR. We examined the effects of interfering with the Linc00662 expression on the proliferation, apoptosis, migration and invasiveness of PC-3 and DU145 cells by CCK-8 assay, Caspase 3/9 activity assay, wound-healing assay and Transwell invasion assay. RESULTS: The expression of Linc00662 in the PCa tissue and cell lines was significantly up-regulated compared with that in the adjacent normal prostatic tissue and epithelial cells (P < 0.01), and the high expression of Linc00662 was positively correlated with the tumor stage (P = 0.002), primary tumor size (P = 0.006), lymph node metastasis (P = 0.001) and distant metastasis (P = 0.001). Transfection of si-Linc00662 into the PC-3 and DU145 cells significantly reduced the expression of Linc00662 (P < 0.01). Compared with the normal control, the PC-3 and DU145 cells in the Linc00662 interference group showed remarkably decreased proliferation, invasion and migration abilities (P < 0.01), but an increased rate of apoptosis (P < 0.01). CONCLUSIONS: Linc00662 is highly expressed in PCa tissues and cells relatively. Knockdown of the Linc00662 expression may inhibit the proliferation, migration and invasiveness and promote the apoptosis of PCa cells. Therefore, Linc00662 could be considered as a new marker of PCa.

Final report of the 5-year clinical outcomes of the XINSORB bioresorbable sirolimus-eluting scaffold in the treatment of single de novo coronary lesions in a first-in-human study.

BACKGROUND: We aimed to report the 5-year outcomes of XINSORB bioresorbable sirolimus-eluting scaffolds in the treatment of single de novo coronary lesions in a first-in-human (FIM) study. This is the final report of the long-term clinical outcomes of the study. Recent studies have shown that bioresorbable scaffolds (BRSs) increase the risks of late target lesion failure (TLF) and thrombosis. METHODS: In this prospective, single-arm study, eligible patients with single de novo coronary lesions were enrolled and treated with XINSORB scaffolds. The scaffolds measured 3.0 mm in diameter and 12, 15, and 18 mm in length. The clinical endpoints included TLF [cardiac death, target vessel-related myocardial infarction (TV-MI), or ischaemia-driven target lesion revascularization (ID-TLR)], its components, major adverse cardiac events (MACE), and scaffold thrombosis. RESULTS: From September 2013 to January 2014, 30 patients were enrolled and treated with XINSORB scaffolds. The procedure had a 100% success rate. None of the patients died during the 5 years of follow-up. The primary endpoint of TLF occurred in 4 patients (13.3%). Six patients were recanalized by intervention, including 4 by ID-TLR. The rate of MACE was 16.7% (5/30). One very late case of scaffold thrombosis was recorded, which led to TV-MI. No more cases of thrombosis were recorded beyond 2 years of follow-up. The rates of clinical endpoints remained steady with no changes after 3 years of follow-up. CONCLUSIONS: Considering that this FIM study was launched at an early stage of the BRS era and without optimal implantation techniques, the clinical outcomes of TLF during the 5-year follow-up were acceptable. The rate of thrombosis was relatively low.

Effect of the Inclination Angle on Premixed Flame Dynamics in Half-Open Ducts.

The propagation of premix methane/air flames in long half-open ducts with different inclination angles θ between the sidewall and the horizon was numerically investigated using the laminar model. The numerical result was compared with the experimental and theoretical ones to validate the numerical model. The results show that the numerical results are in good agreement with them. The investigation provides the basic understanding of the effects on changing the shape of the ducts to promote the premixed flame combustion. For methane/air, the position where the flame front begins to concave is pushed back with the increase in angle θ. The so-called "tulip" flame even disappeared, if the angle θ is bigger than one certain value. Moreover, the flame propagation speed and pressure are enhanced as the angle θ increases. In addition, the numerical simulation indicates that the burning gas creates an eddy near the tip of the flame, altering the flow field and causing the tulip flame to appear. However, with the angle θ increased, the flame propagation is restrained by the change in sidewalls, resulting in the different flow patterns to suppress the formation of tulip flames and promote flame combustion.

High nitrogen stainless steel drug-eluting stent - Assessment of pharmacokinetics and preclinical safety in vivo.

Pharmacokinetic analyses were performed using 20 pigs for 120-days implantation, while one sirolimus-eluting stent was implanted into one of their coronary artery. At different time points, the residual sirolimus on the stent, delivered locally (to artery wall), regionally (to adjacent and downstream muscle) and systemically (to plasma and visceral organs), was detected throughout 120 days. Preclinical safety evaluation was performed using 32 pigs for 180-days implantation to study the safety of metal platform material and the effectiveness of sirolimus eluting coating on the HNS stent. The neointima area, restenosis rate and inflammatory grade for HNS and control group stents were detected and analyzed. Approximately 80% sirolimus was eluted from the sirolimus-eluting stents after 30-days implantation in vivo. Additionally, there was sustained sirolimus in the artery wall, cardiac muscle and heart throughout 120-days implantation, and sirolimus accumulated to the peak at 90-days implantation. It was inferred that the sirolimus eluting stent in this study was covered by neointima before 90-days implantation, indicating that the sirolimus eluting coating on the HNS stent was safe and effective. Very little sirolimus was distributed in visceral organs after 14-days implantation. HNS sirolimus-eluting stent exhibited lower restenosis rate and lower inflammatory grade than control group, which verified that the sirolimus-eluting coating design in this study was reasonable and practical. In addition, there were no significant difference in restenosis rate and inflammatory score between HNS bare-metal stent and drug-eluting stents, illustrating that HNS has good bio-compatibility and is suitable to use as coronary artery stent material.