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.

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.

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.

[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.

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.

[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.

Research Progress on Long Non-Coding RNA and Radiotherapy.

d_abstr_R Long non-coding RNAs (lncRNAs), a group of non-protein-coding RNAs longer than 200 nucleotides, are involved in multiple biological and pathological processes, such as proliferation, apoptosis, migration, invasion, angiogenesis, and immune escape. Many studies have shown that lncRNAs participate in the complex network of cancer and play vital roles as oncogenes or tumor-suppressor genes in a variety of cancers. Moreover, recent research has shown that abnormal expression of lncRNAs in malignant tumor cells before and after radiotherapy may participate in the progression of cancers and affect the radiation sensitivity of malignant tumor cells mediated by specific signaling pathways or cell cycle regulation. In this review, we summarize the published studies on lncRNAs in radiotherapy regarding the biological function and mechanism of human cancers, including esophageal cancer, pancreatic cancers, nasopharyngeal carcinoma, hepatocellular carcinoma, cervical cancer, colorectal cancer, and gastric cancer.

Early Visual Detection of Wheat Stripe Rust Using Visible/Near-Infrared Hyperspectral Imaging.

Wheat stripe rust is one of the most important and devastating diseases in wheat production. In order to detect wheat stripe rust at an early stage, a visual detection method based on hyperspectral imaging is proposed in this paper. Hyperspectral images of wheat leaves infected by stripe rust for 15 consecutive days were collected, and their corresponding chlorophyll content (SPAD value) were measured using a handheld SPAD-502 chlorophyll meter. The spectral reflectance of the samples were then extracted from the hyperspectral images, using image segmentation based on a leaf mask. The effective wavebands were selected by the loadings of principal component analysis (PCA-loadings) and the successive projections algorithm (SPA). Next, the regression model of the SPAD values in wheat leaves was established, based on the back propagation neural network (BPNN), using the full spectra and the selected effective wavelengths as inputs, respectively. The results showed that the PCA-loadings⁻BPNN model had the best performance, which modeling accuracy (RC²) and validation accuracy (RP²) were 0.921 and 0.918, respectively, and the RPD was 3.363. The number of effective wavelengths extracted by this model accounted for only 3.12% of the total number of wavelengths, thus simplifying the models and improving the rate of operation greatly. Finally, the optimal models were used to estimate the SPAD of each pixel within the wheat leaf images, to generate spatial distribution maps of chlorophyll content. The visualized distribution map showed that wheat leaves infected by stripe rust could be identified six days after inoculation, and at least three days before the appearance of visible symptoms, which provides a new method for the early detection of wheat stripe rust.

Mechanism-based QSAR Models for the Toxicity of Quorum Sensing Inhibitors to Gram-negative and Gram-positive Bacteria.

Quorum sensing inhibitors (QSIs) are a promising alternative to the antibiotics and unlikely to induce drug resistance. However, toxicity studies on the QSIs remain limited; therefore in this paper we investigated the acute (15 min) and chronic (24 h) toxicity of some potential QSIs on both gram-negative (V. fischeri) and gram-positive bacteria (B. subtilis). It was found that the toxicity of the QSIs differed with the toxicity test periods. QSAR models were developed for both the acute and chronic toxicity, using the interaction energies between QSIs and the relevant proteins, and the frontier orbital energies. Based on the QSAR models, it was suggested that QSIs primarily bind with the luciferase at 15 min, but LuxR at 24 h in V. fischeri; whereas in B. subtilis, the QSIs mainly bind with LuxS. Our study provided an insight into the toxicity mechanism for QSIs during different exposure periods.

[Integrated Development of Full-automatic Fluorescence Analyzer].

In view of the fact that medical inspection equipment sold in the domestic market is mainly imported from abroad and very expensive, we developed a full-automatic fluorescence analyzer in our center, presented in this paper. The present paper introduces the hardware architecture design of FPGA/DSP motion controlling card+PC+ STM32 embedded micro processing unit, software system based on C# multi thread, design and implementation of double-unit communication in detail. By simplifying the hardware structure, selecting hardware legitimately and adopting control system software to object-oriented technology, we have improved the precision and velocity of the control system significantly. Finally, the performance test showed that the control system could meet the needs of automated fluorescence analyzer on the functionality, performance and cost.

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.

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.

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.

Model of hormesis and its toxicity mechanism based on quorum sensing: a case study on the toxicity of sulfonamides to Photobacterium phosphoreum.

During the past two decades, the phenomenon of hormesis has gained increasing recognition in environmental and toxicological communities. However, the mechanistic understanding of hormesis, to date, is extremely limited. Herein is proposed a novel parametric model with a mechanistic basis and two model-based parameters for hormesis that was successfully applied to the hormetic dose-response observed in the chronic toxicity of sulfonamides on Photobacterium phosphoreum. On the basis of the methods of molecular docking and quantitative structure-activity relationships (QSARs), we proposed a mechanistic hypothesis for hormesis that introduces for the first time the concept of quorum sensing in toxicological studies and explains the mechanism at the level of the receptors. The mechanistic hypothesis stated that (1) specific target binding like interaction with LuxR may contribute to transcriptional activation leading to enhanced luciferase activity at low dose exposure of sulfonamides, and (2) as the dose of sulfonamides increases, more sulfonamides competitively bind to dihydropteroate synthase, which inhibit the biosynthesis of folic acid and thus provoke toxicity. This mechanistic hypothesis, which explains both the dose-dependent and time-dependent features of hormesis, could give new insight into the mechanistic study of hormesis.

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.

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.

Effects of extracellular environment factors on the motility in Japanese eel spermatozoa.

We have examined the effects in vitro of the ionic composition, pH and temperature on the motility by the spermatozoa of the Japanese eel (Anguilla japonica). Milt was obtained from 10 males that had been artificially matured by repeated injections of hCG. Sperm motility was monitored with a VHS video recorder and a video camera connected to a microscope. The results showed that most of the sperm were highly motile in 250-700 mM NaCl, 250-650 mM KCl and 350-550 mM CaCl2 solution. The longest duration of sperm motility recorded in 500 mM NaCl, 250 mM KCl and 350 mM CaCl2 solution. Sperm was not motile when suspended at pH 2, sperm motility was observed at pH 3, there was a relatively higher percentage of motile sperm in solutions at pH 4-12 (above 80%). The motility and duration increased within 18-24°C and decreased at the range of 24-30°C. Appropriate K+ ion concentration in the active medium could enhance the percent motility and duration of eel spermatozoa.

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.