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Background: Intravascular ultrasound-guided percutaneous coronary intervention has been shown to result in superior clinical outcomes compared with angiography-guided percutaneous coronary intervention. However, insufficient data are available concerning the advantages of intravascular ultrasound guidance for patients with an acute coronary syndrome. This trial aimed to investigate whether the use of intravascular ultrasound guidance, as compared with angiography guidance, improves the outcomes of percutaneous coronary intervention with contemporary drug-eluting stents in patients presenting with an acute coronary syndrome., Methods: In this two-stage, multicentre, randomised trial, patients aged 18 years or older and presenting with an acute coronary syndrome at 58 centres in China, Italy, Pakistan, and the UK were randomly assigned to intravascular ultrasound-guided percutaneous coronary intervention or angiography-guided percutaneous coronary intervention. Patients, follow-up health-care providers, and assessors were masked to random assignment; however, staff in the catheterisation laboratory were not. The primary endpoint was target vessel failure, a composite of cardiac death, target vessel myocardial infarction, or clinically driven target vessel revascularisation at 1 year after randomisation. This trial is registered at ClinicalTrials.gov, NCT03971500, and is completed., Findings: Between Aug 20, 2019 and Oct 27, 2022, 3505 patients with an acute coronary syndrome were randomly assigned to intravascular ultrasound-guided percutaneous coronary intervention (n=1753) or angiography-guided percutaneous coronary intervention (n=1752). 1-year follow-up was completed in 3504 (>99·9%) patients. The primary endpoint occurred in 70 patients in the intravascular ultrasound group and 128 patients in the angiography group (Kaplan-Meier rate 4·0% vs 7·3%; hazard ratio 0·55 [95% CI 0·41-0·74]; p=0·0001), driven by reductions in target vessel myocardial infarction or target vessel revascularisation. There were no significant differences in all-cause death or stent thrombosis between groups. Safety endpoints were also similar in the two groups., Interpretation: In patients with an acute coronary syndrome, intravascular ultrasound-guided implantation of contemporary drug-eluting stents resulted in a lower 1-year rate of the composite outcome of cardiac death, target vessel myocardial infarction, or clinically driven revascularisation compared with angiography guidance alone., Funding: The Chinese Society of Cardiology, the National Natural Scientific Foundation of China, and Jiangsu Provincial & Nanjing Municipal Clinical Trial Project., Translation: For the Mandarin translation of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests GWS reports speaker fees from Medtronic, Pulnovo, Infraredx, Abiomed, Abbott, Amgen, and Boehringer Ingelheim; has served as a consultant to Daiichi Sankyo, Ablative Solutions, CorFlow, Apollo Therapeutics, Cardiomech, Gore, Robocath, Miracor, Vectorious, Abiomed, Valfix, TherOx, HeartFlow, Neovasc, Ancora, Elucid Bio, Occlutech, Impulse Dynamics, Adona Medical, Millennia Biopharma, and Oxitope; has equity or options from Ancora, Cagent, Applied Therapeutics, Biostar family of funds, SpectraWave, Orchestra Biomed, Aria, Cardiac Success, Valfix, and Xenter; research support from Abbott, Abiomed, Bioventrix, Cardiovascular Systems, Phillips, Biosense-Webster, Shockwave, Vascular Dynamics, Pulnovo, and V-wave paid directly to institution; and his daughter is an employee at IQVIA. S-LC reports speaker fees from Microport, Pulnovo, Boston International Scientific, Medtronic, Sanofi, and BioMed; and grants from the National Scientific Foundation of China. GSM received honorarium from Boston Scientific. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Hypochlorous acid (HClO) is an important biomarker for inflammation, cardiovascular disease, and even cancer. It is of great significance to accurately monitor and quantitatively analyze the fluctuations of HClO to better understand their physiological functions. Traditional HClO detection methods such as high-performance liquid chromatography (HPLC), and mass spectrometry are preferred, but are costly and unsuitable in vivo. Near-infrared (NIR) fluorescence imaging has the advantages of high sensitivity, high temporal and spatial resolutions, minimal autofluorescence, and deep tissue penetration, which facilitates its application in biological systems. Therefore, the development of sensitivity and simple NIR fluorescence monitoring HClO methods in vivo and in vitro is essential and desirable., Results: Herein, we present a NIR probe NOF3 by integrating the rhodamine scaffold and HClO-triggered moiety for the real-time detection of HClO in vitro and in vivo. NOF3 reacts with the HClO and releases the NOF-OH fluorophore of emitted signals at 730 nm, which is in the NIR region. The designed probe detected concentrations of HClO ranging from 0 to 17 μM with a low detection limit of 0.146 μM, presenting excellent sensitivity and selectivity toward HClO over other species. NOF3 manifests significantly turn-on NIR fluorescent signals in response to HClO concentration, which makes it favorable for monitoring dynamic HClO distribution in vivo. We exemplify NOF3 for the tracking of endogenously overexpressed HClO distribution in RAW 264.7 cells, and further realize real-time in vivo bioimaging of HClO activity in inflammation mice., Significance: The facile NIR NOF3 probe was successfully applied to visualize endogenous and exogenous HClO in living cells and mice. This study provides not only an effective tool for spatial and temporal resolution HClO bioimaging in vivo but also possesses great potential for use in future research on HClO-related biology and pathology., Competing Interests: Declaration of competing interest We declare that we have no financial and personal relationships with other people ororganizations that can inappropriately influence our work, there is no professional or other personal interest of any nature or kind in any product, service and company that could beconstrued as influencing the position presented in, or the review of, the manuscript entitled., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: The differential treatment effect of pulmonary artery denervation (PADN) in pulmonary arterial hypertension (PAH) patients with different risk burdens remains unclear. This study aimed to determine the effectiveness of PADN in low vs intermediate-high-risk PAH patients., Methods: In total, 128 patients with treatment naive PAH included in the PADN-CFDA trial were categorized into low-risk and intermediate-high-risk patients. The primary endpoint was the between-group difference in the change in 6-min walk distance (6 MWD) from baseline to 6 months., Results: In the intermediate-high-risk group, those treated with PADN and PDE-5i had a greater improvement in 6 MWD from baseline to 6 months as compared to those treated with sham plus PDE-5i. From baseline to 6 months, pulmonary vascular resistance (PVR) was reduced by -6.1 ± 0.6 and -2.0 ± 0.7 Wood units following PADN plus PDE-5i and sham plus PDE-5i, respectively, along with the significant reduction of NT-proBNP in the intermediate-high-risk group. However, there were no significant differences in 6 MWD, PVR, and NT-proBNP between the PADN plus PDE-5i and sham plus PDE-5i groups among low-risk patients. Moreover, the right ventricular function was equally improved by PADN treatment across the low-, intermediate-, and high-risk groups. Clinical worsening was less with PADN plus PDE-5i treatment during the 6-month follow-up., Conclusions: In patients with pulmonary arterial hypertension, pulmonary artery denervation plus PDE-5i improved exercise capacity, NT-proBNP, hemodynamic, and clinical outcomes during the 6-month follow-up among intermediate-high risk patients., (Copyright © 2023 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: World Health Organization (WHO) group 1 pulmonary arterial hypertension (PAH) is a progressive, debilitating disease. Previous observational studies have demonstrated that pulmonary artery denervation (PADN) reduces pulmonary artery pressures in PAH. However, the safety and effectiveness of PADN have not been established in a randomized trial., Objectives: The aim of this study was to determine the treatment effects of PADN in patients with group 1 PAH., Methods: Patients with WHO group 1 PAH not taking PAH-specific drugs for at least 30 days were enrolled in a multicenter, sham-controlled, single-blind, randomized trial. Patients were assigned to receive PADN plus a phosphodiesterase-5 inhibitor or a sham procedure plus a phosphodiesterase-5 inhibitor. The primary endpoint was the between-group difference in the change in 6-minute walk distance from baseline to 6 months., Results: Among 128 randomized patients, those treated with PADN compared with sham had a greater improvement in 6-minute walk distance from baseline to 6 months (mean adjusted between-group difference 33.8 m; 95% CI: 16.7-50.9 m; P < 0.001). From baseline to 6 months, pulmonary vascular resistance was reduced by -3.0 ± 0.3 WU after PADN and -1.9 ± 0.3 WU after sham (adjusted difference -1.4; 95% CI: -2.6 to -0.2). PADN also improved right ventricular function, reduced tricuspid regurgitation, and decreased N-terminal pro-brain natriuretic peptide. Clinical worsening was less (1.6% vs 13.8%; OR: 0.11; 95% CI: 0.01-0.87), and a satisfactory clinical response was greater (57.1% vs 32.3%; OR: 2.79; 95% CI: 1.37-5.82) with PADN treatment during 6-month follow-up., Conclusions: In patients with WHO group 1 PAH, PADN improved exercise capacity, hemodynamic status, and clinical outcomes during 6-month follow-up. (Safety and Efficacy of Pulmonary Artery Denervation in Patients With Pulmonary Arterial Hypertension [PADN-CFDA]; NCT03282266)., Competing Interests: Funding Support and Author Disclosures This trial was supported by the National Scientific Foundation of China (grants NSFC 91639303, and NSFC 81770441, and NSFC 82121001). Nanjing First Hospital funded this trial, and Pulnovo Medical provided all PADN catheters through the study period. Dr Stone has received speaker honoraria from Medtronic, Pulnovo Medical, and Infraredx; has served as a consultant to Valfix, TherOx, Robocath, HeartFlow, Ablative Solutions, Vectorious, Miracor, Neovasc, Abiomed, Ancora, Elucid Bio, Occlutech, CorFlow, Apollo Therapeutics, Impulse Dynamics, Vascular Dynamics, Shockwave, V-Wave, Cardiomech, Gore, and Amgen; and has equity or options in Ancora, Cagent, Applied Therapeutics, the Biostar family of funds, SpectraWave, Orchestra Biomed, Aria, Cardiac Success, Valfix, and Xenter. Dr Stone’s daughter is an employee at Medtronic. Dr Stone’s employer, Mount Sinai Hospital, has received research support from Abbott, Abiomed, Bioventrix, Cardiovascular Systems, Phillips, Biosense Webster, Shockwave, Vascular Dynamics, and V-Wave. Dr S.-L. Chen is the inventor of PADN but not the owner of the PADN patent; has received speaker honoraria from Microport, Pulnovo Medical, Boston Scientific, Medtronic, Sanofi, and BioMed; is a fellow at the Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, Nanjing Medical University; and has received grants from the National Scientific Foundation of China. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

The effect of vegetation seasonal cycle alterations to aerosol dry deposition on PM 2.5 concentrations (hereafter referred as the VSC effect) in China was investigated using a numerical modelling system (WRF/CUACE). Two simulation experiments using the vegetation parameters in particle dry deposition schemes typical for January and July revealed an absolute increase in surface PM 2.5 concentrations of about 2.4 μg/m 3 and a 5.5% relative increase in China (within model domain 2). The effect in non-urban areas was more significant than that in urban areas. The increases in PM 2.5 concentrations in Beijing-Tianjin-Hebei (BTH), Yangtze River Delta (YRD), Pearl River Delta (PRD), Sichuan Basin (SCB), and Central China (CC) were calculated as 1.9 μg/m 3 , 3.4 μg/m 3 , 3.1 μg/m 3 , 4.3 μg/m 3 , and 4.9 μg/m 3 , respectively, corresponding to relative increases of 2.9%, 4.5%, 5.4%, 5.8%, and 5.9%. These results demonstrate that the effect of decreased particle dry deposition due to reduced vegetation in southern areas was stronger, which was partially attributed to the increased vegetation cover and more significant seasonal changes in those regions. Furthermore, the increased PM 2.5 concentrations caused by the VSC effect were transported from north to south via the winter northerly winds, which weakened the effect in North China Plain and enhanced the effect in parts of central and southern China, such as the south of CC. Although the surface PM 2.5 concentration was relatively high in North China Plain, the effects of the northerly wind and relatively small dry deposition velocity meant that the removal of PM 2.5 in that region was relatively less than in southern areas of China. These results will contribute to understanding of the underlying mechanisms of PM 2.5 enhancement during winter in China., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier B.V.)

Background: Machine learning (ML) may be helpful to simplify the risk stratification of coronary artery disease (CAD). The current study aims to establish a ML-aided risk stratification system to simplify the procedure of the diagnosis of CAD., Methods and Results: 5819 patients with coronary artery angiography (CAG) from July 2015 and December 2018 in our hospital, 2583 patients (aged 56 ± 11, <50% stenosis) and 3236 patients (aged 60 ± 10, ≥50% stenosis), available on age, sex, history of smoking, systolic and diastolic blood pressure, total cholesterol level, low- and high-density lipoprotein, triglyceride level, glycosylated hemoglobin A1c and uric acid were included in the ensemble model of ML. Receiver-operating characteristic curves showed that area-under-the-curve of the training data (90%) and the testing data (10%) were 0.81 and 0.75 (P = 0.006483). The validation data of 582 patients with CAG from July 2019 to September 2019 in our hospital showed the same predictive rate of the testing data. The low-risk group (risk probability<0.2) without the treatment of hypertension, diabetes and CAD could be probably excluded the diagnosis of CAD, the moderate-risk group (risk probability 0.2-0.8) would need further examination, and high-risk group (risk probability>0.8) would suggested to perform CAG directly., Conclusion: Machine learning-aided detection system with the clinical data of age, sex, history of smoking, systolic and diastolic blood pressure, total cholesterol level, low- and high-density lipoprotein, triglyceride level, glycosylated hemoglobin A1c and uric acid could be helpful for the risk stratification of prediction for the coronary artery disease., Competing Interests: Declaration of Competing Interest he authors report no relationships that could be construed as a conflict of interest., (Copyright © 2020. Published by Elsevier B.V.)

The study was to investigate the anti-inflammatory effect of Cyclocarya paliurus polysaccharides (CP) on carbon tetrachloride (CCl 4 ) induced mice and explore its underlying mechanism. Based on a mouse model of CCl 4 induced liver inflammation and pretreatment with CP. Results showed that CP significantly decreased the levels of the proinflammatory cytokines (NO, TNF-α, IL-1β) as well as the proteins expression levels of COX-2 and iNOS in the liver. TLR4 and MAPK pathways were down-regulated after CP administration. Furthermore, 16S rDNA showed that CP increased the Firmicutes/Bacteroidetes ratio and the abundance of probiotics (Unclassified Clostridiales) as well as decreased abundances of pathogenic bacteria (Proteobacteria, Helicobacter and Aerococcus) compared to model group. Moreover, CP treatment increased the SCFAs levels in CCl 4 induced mice. These findings suggested that CP act as prebiotics in ameliorating the liver inflammation in mice caused by CCl 4 through regulating the gut microbiota composition and increasing the concentration of SCFAs., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Progressive thinning and dilation of the LV due to ischemic heart failure (IHF) increases wall stress and myocardial oxygen consumption. Injectable biopolymers implanted in the myocardial wall have been used to increase wall thickness to reduce chamber volume, decrease wall stress, and improve cardiac function. We sought to evaluate the efficacy of a biopolymer (Algisyl-LVR) to prevent left ventricular (LV) remodeling in a swine model of IHF., Methods: IHF was induced in 11 swine by occluding the marginal obtuse branches of the left circumflex artery. Eight weeks later, Algisyl-LVR was injected into the LV myocardial free wall in five of the 11 animals. Echocardiographic examinations were done every 2weeks for 16weeks., Results: Within eight weeks of treatment, the ejection fraction increased from 30.5%±7.7% to 42.4%±3.5% (treated group) vs. 37.3%±3.8% to 34.3%±2.9% (control), p<0.01. Stroke volume increased from 18.5±9.3mL to 41.3±13.3mL (treated group) vs. 25.4±2.3mL to 31.4±5.3mL (control), p<0.05. Wall thickness in end-diastole of the infarcted region changed from 0.69±0.06cm to 0.81±0.13cm (treated group) vs. 0.73±0.09cm to 0.68±0.11cm (control), p<0.05. Sphericity index remained almost unchanged after treatment, although differences were found at the end of the study between both groups (p<0.001). Average myofiber stress changed from 16.3±5.8kPa to 10.2±4.0kPa (treated group) vs. 15.2±4.8kPa to 17.9±5.6kPa (control), p<0.05., Conclusions: Algisyl-LVR is an effective strategy that serves as a micro-LV assist device to reduce stress and hence prevent or reverse maladaptive cardiac remodeling caused by IHF in swine., (Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.)

Background: Gene variants contribute to variability in individual responsiveness to clopidogrel and influence cardiovascular outcomes in Caucasian patients with acute coronary syndrome (ACS). However, limited data is available in Asian populations., Methods: We resequenced 14 genes in metabolizing and activity pathway of clopidogrel in 138 patients with ACS and prospectively assessed the modulating effects of 13 variants possibly related to clopidogrel efficacy on one-year cardiovascular event occurrence in 5820 ACS patients after percutaneous coronary intervention (PCI). In addition, platelet aggregation rate was measured in 1084 participants and plasma levels of active metabolite were determined in 15 patients to test whether increasing clopidogrel maintenance doses increases active metabolite exposure., Results: No significant associations were found between any of the tested variants and risk of cardiovascular events (P>0.05), although CYP2C19*2 carriers had slightly higher on-treatment platelet aggregation rate and lower active metabolite exposure compared with that of non-carriers (Median [IQR] 51.49 [35.43-66.75] vs. 49.05 [32.36-63.38], P=0.012) (means±SD AUC, 22.84±5.00 vs. 35.05±12.34, P=0.008). Switching from 75mg daily clopidogrel to 150mg daily fully overcomes low exposure to clopidogrel active metabolite in CYP2C19*2 carriers (means±SD AUC, 32.35±8.65 vs. 35.05±12.34, P=0.314)., Conclusion: Different from Caucasian populations, genetic variants have no significant influence on clinical outcomes and have much milder effects on inhibition of platelet and active clopidogrel metabolite levels in Chinese patients with ACS after PCI, an effect which could be overcome with a dose escalation to 150mg daily., (Copyright © 2017. Published by Elsevier B.V.)

To explore the variations in atmospheric environment over mountainous areas, measurements were made from an intensive field observation at the summit of Mt. Huang (30.13°N, 118.15°E, 1841m above sea level), a rural site located in East China, from June to August 2011. The measurements revealed a diurnal change of surface O3 with low concentrations during the daytime and high concentrations during the nighttime. The causes of diurnal O3 variations over the mountain peak in East China were investigated by using a fairly comprehensive WRF-Chem and HYSPLIT4 modeling approach with observational analysis. By varying model inputs and comparing the results to a baseline modeling and actual air quality observations, it is found that nearby ozone urban/anthropogenic emission sources were contributing to a nighttime increase in mountaintop ozone levels due to a regional transport lag and residual layer effects. Positive correlation of measured O3 and CO concentrations suggested that O3 was associated with anthropogenic emissions. Sensitivity modeling experiments indicated that local anthropogenic emissions had little impact on the diurnal pattern of O3. The diurnal pattern of O3 was mainly influenced by regional O3 transport from the surrounding urban areas located 100-150km away from the summit, with a lag time of 10h for transport., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Mitofusin 2 (Mfn2) inhibits atherosclerotic plaque formation, but the underlying mechanism remains elusive. This study aims to reveal how Mfn2 functions in the atherosclerosis. Mfn2 expression was found to be significantly reduced in arterial atherosclerotic lesions of both mice and human compared with healthy counterparts. Here, we observed that Mfn2 increased cellular cholesterol transporter expression in macrophages by upregulating peroxisome proliferator-activated receptor-γ, an effect achieved at least partially by inhibiting extracellular signal-regulated kinase1/2 (ERK1/2) and p38 mitogen-activated protein kinases (MAPKs) pathway. These findings provide insights into potential mechanisms of Mfn2-mediated alterations in cholesterol transporter expression, which may have significant implications for the treatment of atherosclerotic heart disease., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objective: Mitofusin 2 (Mfn2) is an important suppressor of vascular smooth muscle cell (VSMC) proliferation. It contains a protein kinase A (PKA) phosphorylation site at serine 442 (S442) and can be phosphorylated by PKA. This study examined the role of phosphorylating specific sites on the regulation of Mfn2 protein activity in vitro and in vivo., Methods and Results: We introduced two mutations at S442 in rat Mfn2, and investigated their effects using cultured rat VSMCs and the balloon injury model. Our results indicated that, in VSMCs, Mfn2 expression and mitochondrial morphology are affected by adenoviral-mediated overexpression of the two Mfn2 mutant proteins in the same way as the wild-type Mfn2 protein. Specifically, overexpression of the protein harboring the phospho-deficient mutation Mfn2-S442A (serine replaced by alanine at residue 442) increased the inhibitory effects of Mfn2 on proliferation of VSMCs in culture, and neointimal hyperplasia and restenosis in the rat carotid artery balloon injury model at days 14 after injury. On the other hand, the phospho-mimetic mutation Mfn2-S442D (serine replaced by aspartic acid at residue 442) led to loss of growth suppressor activity., Conclusions: These results suggest that this specific PKA phosphorylation site plays a key role in Mfn2-mediated suppression of VSMC growth, which is independent of its effects on modulation of mitochondrial morphology., (Copyright (c) 2010 Elsevier Ireland Ltd. All rights reserved.)

Background: The prevalence of obesity is growing worldwide and has reached epidemic proportions. Vertical sleeve gastrectomy, which requires irreversible removal of gastric tissue, is considered an effective weight loss treatment of severe obesity. The aim of the present study was to evaluate the feasibility of a reversible gastric sleeve magnetic implant that mimics the vertical sleeve gastrectomy without the gastrectomy for weight loss in a group of normal and obese rats., Methods: A group of Zucker fatty rats either underwent surgical implantation or a sham operation and were followed up for 6 weeks. Also, a group of Wistar rats underwent surgical implantation for 6 weeks, followed by surgical implant removal at 6 weeks, and recovery for an additional 4 weeks. Food intake and body weight were monitored after surgery to determine the efficacy of the device. A histologic examination for all rats was made to evaluate the change in the gastric wall in response to gastric sleeve magnetic implantation., Results: The implanted Zucker fatty and Wistar rats showed a statistically significant decrease in food intake and weight gain rate compared with the sham-operated rats (approximately 3%/wk of body weight loss in the treated group). Moreover, the decrease in the weight gain rate was sustained for 4 weeks after removal of the magnetic implant. The histologic evidence revealed an inflammatory mononuclear cell infiltration and mild fibrosis and hyperplasia of blood vessels, as expected for any implant. No significant structural damage, tissue ischemia, hemorrhage, or necrosis was found in the gastric wall., Conclusion: Our results have shown that the device is feasible in rats, results in effective weight loss, and can be easily removed. These findings, along with the lack of the need for resection of the native stomach, provide a compelling basis for additional development of the device in large animal models.