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Research question : What is the expression pattern of inflammatory mRNA profiles of dehydroepiandrosterone (DHEA) plus high-fat diet (HFD)-induced polycystic ovary syndrome (PCOS) mouse model? Design : In this study, RNA sequencing was performed to investigate the mRNA expression profiles in the ovarian tissues of a DHEA plus HFD-induced PCOS mouse model. Six samples were divided into two groups (control and PCOS), with three biological replicates in each group. This was followed by hierarchical clustering, gene ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. The relative expression levels of nine inflammatory genes were validated via quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Results : A total of 436 genes were differentially expressed between the control and PCOS mice. Out of these, 137 genes were up-regulated while 299 genes were down-regulated. Gene ontology analysis indicated that differentially expressed mRNAs were associated with T cell-mediated cytotoxicity and homocysteine metabolic processes. Pathway analysis further showed that these abnormally expressed mRNAs were associated with signaling pathways, such as NF-kB signaling, tyrosine metabolism, and phenylalanine metabolism. All these pathways are involved in chronic inflammation and PCOS. Conclusion : The differentially expressed genes are potentially involved in the inflammation that is evident in PCOS, and so could serve as therapeutic options against the disease. Nevertheless, prospective studies are needed to test this hypothesis.

Background Macro-reentrant atrial tachycardias (MATs) are a common complication after cardiac valve surgery. The MAT types and the effectiveness of MAT ablation might differ after different valve surgery. Data comparing the electrophysiological characteristics and the ablation results of MAT post-tricuspid or mitral valve surgery are limited. Methods Forty-eight patients (29 males, age 56.1 ± 13.3 years) with MAT after valve surgery were assigned to tricuspid valve (TV) group (n = 18) and mitral valve (MV) group (n = 30). MATs were mapped and ablated guided by a three-dimensional navigation system. The one-year clinical effectiveness was compared in two groups. Results Nineteen MATs were documented in TV group, including 16 cavo-tricuspid isthmus (CTI)-dependent AFL and 3 other MATs at right atrial (RA) free wall, RA septum and left atrial (LA) roof. Thirty-nine MATs were identified in MV group, including15 CTI-dependent AFL, 8 RA free wall scar-related, 2 RA septum scar-related, 8 peri-mitral flutter, 3 LA roof-dependent, 2 LA anterior scar-related, and 1 right pulmonary vein-related MAT. Compared with TV group, MV group had significantly lower prevalence of CTI-dependent AFL (38.5% vs. 84.2%), higher prevalence of left atrial MAT (35.9 vs.5.3%) and higher proportion of patients with left atrial MAT (40 vs. 5.6%), P = 0.02, 0.01 and 0.01, respectively. The acute success rate of MAT ablation (100 vs. 93.3%) and the one-year freedom from atrial tachy-arrhythmias (72.2 vs. 76.5%) was comparable in TV and MV group. No predictor for recurrence was identified. Conclusion Although the types of MATs differed significantly in patients with prior TV or MV surgery, the acute and mid-term effectiveness of MAT ablation was comparable in two groups. Trial registration: This study was registered as a part of EARLY-MYO-AF clinical trial at the website ClinicalTrials. gov (NCT04512222).

Aim To evaluate the safety, visual and anatomic outcomes of fourier-domain optical coherence tomography (FD-OCT)-guided excimer laser phototherapeutic keratectomy (PTK) combined with photorefractive keratectomy (PRK) surgery in treating anterior corneal scarring. Methods Clinical data of 23 eyes of 21 patients with anterior corneal scarring underwent FD-OCT-guided PTK and PRK from Dec. 2014 to Jul. 2016 were reviewed. Patients were assessed for preoperative and postoperative uncorrected visual acuity (UCVA), best spectacle-corrected visual acuity (BSCVA), contrast sensitivity (CS), FD-OCT, corneal topography and colour figures of anterior segments. Results The preoperative corneal pathologic conditions included viral keratitis (7 patients, 7 eyes), band keratopathy (2 patients, 4 eyes), corneal dystrophy (4 patients, 4 eyes), traumatic corneal disease (2 patients, 2 eyes) and corneal chemical injury (6 patients, 6 eyes). Mean follow-up time was 10.65 (range, 3-19)mo. UCVA (in logMAR) improved from a mean of 0.79 (95%CI, 0.28-1.29) preoperatively to a mean of 0.45 (95%CI, 0.29-0.62) postoperatively (P=0.021). BSCVA (in logMAR) improved from 0.57 (95%CI, 0.27-0.88) preoperatively to a mean of 0.28 (95%CI, 0.15-0.41) postoperatively (P=0.001). Corneal topographic indices postoperatively showed significant improvement in corneal cylinder (P=0.009), the surface regularity index (P=0.007) and surface asymmetry index (P=0.00). Postoperative spherical equivalent averaged -0.53 diopters (-1.49 to 0.42). No complications were associated with the treatment. Conclusion FD-OCT-guided PTK combined with PRK is safe and effective for the treatment of anterior corneal scarring by eliminating or reducing corneal opacities.

BACKGROUND Acute myocardial infarction (AMI) is a disease with high morbidity and mortality worldwide and the evaluation of myocardial injury and perfusion status following myocardial ischemia and reperfusion is of clinical value. PURPOSE To assess the diagnostic utility of simplified perfusion fraction (SPF) in differentiating salvage and infarcted myocardium and its predictive value for left ventricular remodeling in patients with reperfusion ST-segment elevation myocardial infarction (STEMI). STUDY TYPE Prospective. POPULATION Forty-one reperfused STEMI patients and 20 healthy volunteers. FIELD STRENGTH/SEQUENCE 3.0T MRI. The MR examination included cine, T2 -short tau inversion recovery (T2 -STIR), first pass perfusiong (FPP)，phase sensitive inversion recovery (PSIR), and diffusion-weighted imaging (DWI). ASSESSMENT SPF values among different myocardium regions (infarcted, salvaged, remote, and MVO) and stages of reperfused STEMI patients as well as normal controls were measured. The diagnostic utility of SPF values in differentiating salvaged and infarcted myocardium was assessed. STATISTICAL ANALYSIS Independent t-test and the Mann-Whitney U-test. Logistic regression. RESULTS SPF values in healthy controls were not significantly different than SPF values in the remote myocardium of patients (40.09 ± 1.47% vs. 40.28 ± 1.93%, P = 0.698). In reperfusion STEMI patients, SPF values were lower in infarcted myocardium compared to remote and salvaged myocardium (32.15 ± 2.36% vs. 40.28 ± 1.93%, P

Aims Facial features were associated with increased risk of coronary artery disease (CAD). We developed and validated a deep learning algorithm for detecting CAD based on facial photos. Methods and results We conducted a multicentre cross-sectional study of patients undergoing coronary angiography or computed tomography angiography at nine Chinese sites to train and validate a deep convolutional neural network for the detection of CAD (at least one ≥50% stenosis) from patient facial photos. Between July 2017 and March 2019, 5796 patients from eight sites were consecutively enrolled and randomly divided into training (90%, n = 5216) and validation (10%, n = 580) groups for algorithm development. Between April 2019 and July 2019, 1013 patients from nine sites were enrolled in test group for algorithm test. Sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) were calculated using radiologist diagnosis as the reference standard. Using an operating cut point with high sensitivity, the CAD detection algorithm had sensitivity of 0.80 and specificity of 0.54 in the test group; the AUC was 0.730 (95% confidence interval, 0.699–0.761). The AUC for the algorithm was higher than that for the Diamond–Forrester model (0.730 vs. 0.623, P Conclusion Our results suggested that a deep learning algorithm based on facial photos can assist in CAD detection in this Chinese cohort. This technique may hold promise for pre-test CAD probability assessment in outpatient clinics or CAD screening in community. Further studies to develop a clinical available tool are warranted.

Background Left atrial (LA) dysfunction is associated with morbidity and mortality. To the knowledge of the authors, the relationship of LA strain to long-term prognosis in participants with ST-segment elevation myocardial infarction (STEMI) is unknown. Purpose To evaluate LA strain as a long-term outcome predictor in STEMI in a prospective, multicenter cardiac MRI cohort. Materials and Methods Participants with STEMI who underwent primary percutaneous coronary intervention and cardiac MRI from 10 sites (EARLY-MYO-CMR registry, clinical trial number NCT03768453) were included. The parent study took place between August 2013 and December 2018. LA longitudinal strain and strain rate parameters were derived from cine cardiac MRI by using an in-house semiautomated method. Major adverse cardiac events (MACEs) were defined as cardiovascular death, myocardial reinfarction, hospitalization for heart failure, and stroke. The association between LA performance and MACE was evaluated by using time-dependent receiver operating characteristic analysis, Kaplan-Meier analysis, and multivariable Cox regression analysis. Results A total of 321 participants (median age, 59 years; age range, 27-75 years; 90% men) were included in this study. During median follow-up of 3.7 years, MACE occurred in 76 participants (23.7%). Participants with impaired reservoir (≤22%) and conduit strain (≤10%) had a higher risk of MACE than those with reservoir strain greater than 22% and conduit strain greater than 10% (P < .001). Reservoir strain (hazard ratio, 0.84; 95% confidence interval: 0.77, 0.91; P < .001) and conduit strain (hazard ratio, 0.81; 95% confidence interval: 0.73, 0.89; P < .001) were independent predictors for MACE after adjustment for known risk factors. Finally, LA reservoir and conduit strains provided incremental prognostic value over traditional outcome predictors (Uno C statistic comparing models, 0.75 vs 0.68; P = .04). Conclusion Assessment of left atrial strain, as a measure of left atrial function, provided incremental prognostic information to established predictors in ST-segment elevation myocardial infarction. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Kawel-Boehm and Bremerich in this issue.

There is increasing evidence linking plasma homocysteine levels and atrial fibrillation (AF). The association between an elevated level of plasma homocysteine and AF was examined by meta-analysis in this study.The PubMed and ScienceDirect databases until August 2019 were utilized to collect previous literature on homocysteine and the potential relation to AF. The pooled effects were evaluated depending on standardized mean differences (SMDs) or odds ratios (ORs) with 95% confidence intervals (CIs), and the calculation was performed using Stata 12 software.A total of 11 validated articles were included in the meta-analysis. For pooled effect, the results confirmed that AF patients had higher homocysteine levels than control subjects (SMD: 0.58, 95%CI: 0.09-1.06). Compared with control subjects, homocysteine levels were higher in paroxysmal AF (SMD: 0.45, 95%CI: 0.18-0.72) and persistent AF patients (SMD: 1.21, 95%CI: 0.50-1.92). The pooled analysis suggested that patients with elevated homocysteine levels had markedly higher risk of AF compared with lower homocysteine levels in the categorical variable (OR: 2.21, 95%CI: 1.16-4.21) and continuous variable analyses (OR: 1.13, 95%CI: 1.00-1.27), respectively. In addition, the pooled analysis indicated that recurrent AF patients had significantly higher homocysteine levels than those without recurrence (SMD: 0.65, 95%CI: 0.42-0.88). The pooled analysis of the categorical variables indicated that elevated homocysteine levels were associated with increased risk of AF recurrence (OR: 3.81, 95%CI: 3.11-4.68). However, the association was weak in the pooled analysis of continuous variables (OR: 1.88, 95%CI: 0.74-4.81).Our meta-analysis identified that plasma homocysteine levels were significantly elevated in AF and recurrent AF patients. Elevated homocysteine is associated with increased risk of AF and AF recurrence.

Background Mitral isthmus (MI) ablation was limited due to technical challenges in the index ablation for long‐standing persistent atrial fibrillation (LPeAF). The role of adjunctive MI ablation was controversial. Hypothesis MI block could be achieved in most patients undergoing repeat LPeAF ablation and was associated with favorable clinical outcomes. Methods Of 87 consecutively patients undergoing reablation for recurrent atrial tachyarrhythmias (ATa), 41 patients with residual MI conduction but without pulmonary vein reconnection or left atrial roof conduction were enrolled to treat recurrent atrial flutter (AFL) (n = 20) and AF (n = 21). After AFL ablation and AF cardioversion, MI conduction gaps (CGs) were mapped and closed. Results MI line was successfully blocked in 37 (90.2%) of 41 patients after closing 1.4 ± 0.5 CGs (31 endocardial CGs and 16 epicardial ones) in the initial MI lines. CGs were more often located at the endocardial sites close to the lateral ridge between left atrial appendage and left‐sided PVs, midportion of MI and at the epicardial breakthroughs within coronary sinus. At the end of 16.0 ± 1.9 months' follow‐up, 31 (83.8%) of 37 patients with MI block and 1 of 4 patients without MI block were free of further recurrence of ATa off anti‐arrhythmic drugs. MI block was positively associated with ATa‐free survival by Cox's regression analysis (hazard ratio [HR]: 0.012, 95% confidence interval [CI]: 0.000‐0.456, P = .02). Conclusions MI block could be achieved in the majority of patients during repeat ablation for LPeAF. MI block was associated with favorable clinical outcomes after LPeAF reablation.

Direct stenting (DS) without pre-dilatation of the culprit lesion might improve myocardial perfusion and prognosis in patients undergoing percutaneous coronary intervention for ST-elevation myocardial infarction (STEMI); however, some studies report conflicting results. We investigated whether DS provides incremental myocardial benefits over conventional stenting (CS) in STEMI patients based on cardiac magnetic resonance imaging (CMR) measures. Reperfused patients who underwent CMR examinations within 1 week of STEMI onset were selected from a multicenter CMR registry of STEMI (NCT: 03768453). Patients were stratified into either a DS or CS group. Each group comprised 137 patients after 1:1 propensity score matching. Major adverse events (MACEs), including death, myocardial re-infarction, re-admission for heart failure, and stroke were noted during a median period of 44 months (interquartile range 32-58 months). DS was associated with larger (p = 0.007) and shorter (p = 0.005) stent sizes than CS. DS and CS achieved comparable angiographic TIMI-3 flow grades (p = 0.86) and myocardial blush grades (p = 0.70). There were no group differences regarding the incidence of CMR manifestations of microvascular dysfunction, including microvascular obstruction (MVO) (p = 0.89) and intramyocardial hemorrhage (p = 0.47), the extent of MVO (p = 0.21), infarction size (p = 0.83), or left ventricular ejection fraction (p = 0.57). Kaplan-Meier analysis revealed similar risks of MACEs (log rank p = 0.909), which occurred in 23.4% of DS and 26.3% of CS patients (p = 0.576). DS did not show any incremental benefits over CS on myocardial impairments as evaluated using CMR.Clinical Trial Registration: Clinicaltrials.gov, NCT: 03768453.

Background The presence of late gadolinium enhanced (LGE), which may enable better evaluation of myocardial impairment, would help predict the occurrence of life-threatening arrhythmias and major adverse cardiovascular events (MACE) in patients suffering from ischemic cardiomyopathy (ICM) and nonischemic cardiomyopathy (NICM) patients and who underwent a process of implantable cardioverter-defibrillator (ICD). Purpose To evaluate the prognostic value of cardiac MR-LGE for ICM and NICM patients with ICD. Study type Systematic review and meta-analysis. Population A total of 33 studies of 3457 patients were included. Field strength 1. 5T and 3.0T, LGE. Assessment PubMed, Cochrane Library, EMBASE, and Web of Science were systematically searched for studies reporting LGE in ICM or NICM patients with ICD implantation with several kinds of endpoints: MACE, life-threatening arrhythmia, cardiovascular mortality, and all-cause mortality. Statistical tests A meta-analysis was performed using a random-effects model to calculate odds ratios or standard mean differences (SMDs) for binary and continuous data. Results MR-LGE was positive in 1923 (55.6%) of ICM and NICM patients. LGE-present patients were more likely to have life-threatening arrhythmia (odds ratio [OR]: 5.1; 95% confidence interval [CI]: 3.8-6.8), MACE (OR: 5.2; 95% CI: 3.8-6.9), cardiovascular mortality (OR: 2.4; 95% CI: 1.2-4.6), and all-cause mortality (OR: 2.1; 95% CI: 1.3-3.4) compared with those without LGE. Moreover, ICM and NICM patients with LGE both had increased life-threatening arrhythmia (OR: 4.6; 95% CI: 2.7-8.0; OR: 5.2; 95% CI: 3.6-7.8, respectively) and MACE (OR: 4.7; 95% CI: 2.8-7.9; OR: 4.7; 95% CI: 2.7-8.1, respectively). Data conclusion The presence of MR-LGE may worsen the prognosis for adverse cardiovascular events in both ICM and NIMC patients who benefit more from ICDs. Level of evidence 3 Technical Efficacy Stage: 3 J. Magn. Reson. Imaging 2020;51:1422-1439.

Background Sodium-glucose cotransporter 2 (SGLT2) inhibitors lowered the risk of cardiovascular events in patients with diabetes or heart failure (HF) with reduced ejection fraction, whether they directly promote cardiac function remains unclear. Therefore, we sought to determine whether SGLT2 inhibitors could improve left ventricular (LV) function in these patients. Methods A literature search was conducted using MEDLINE, EMBASE, and Cochrane Library databases from their inception to July 9, 2021. Randomized clinical trials and cohort studies that reported LV function-related variables were included. Results Thirteen studies comprising 1437 patients (830 SGLT2 inhibitor-treated and 607 non-SGLT2 inhibitor-treated patients) and representing 7 randomized controlled trials with 640 individuals and 6 cohort studies with 797 individuals were included in this meta-analysis. LV regression [LV mass (LVM)], LV ejection fractions (LVEF), LV volumes [LV end-diastolic volumes and systolic volumes (LVEDV and LVESV, respectively], and LV diastolic function [mitral inflow E velocity to tissue Doppler e’ ratio, E/e’ and left atrial volume index (LAVI)] were all significantly improved in patients treated with SGLT2 inhibitors (weighted mean differences, 95% CI, LVM: −6.319 g, −10.850 to −1.789; LVEF: 2.458%, 0.693 to 4.224; LVEDV: −9.134 mL, −15.808 to −2.460; LVESV: −8.440 mL, −15.093 to −1.787; LAVI: −2.791 mL/m2, −.554 to −1.027; E/e’: −1.567, −2.440 to −0.698). Subgroup analysis further confirmed the improvement of LV function mainly in patients with HF or those receiving empagliflozin treatment. Conclusions Treatment with SGLT2 inhibitors can significantly improve LV function in patients with or without diabetes (especially those with HF or undergoing empagliflozin treatment).

Background Sepsis is a significant cause of mortality, and cardiac dysfunction is one of the vital predictors for mortality of sepsis. However, the factors associated with the susceptibility to sepsis-induced cardiac dysfunction remain unclear. Disruption of circadian rhythms can profoundly influence cardiac health; however, to the knowledge of the authors, the relationship of circadian disruption to cardiac involvement in patients with sepsis is unknown. Purpose We aim to investigate the impact of circadian disruption on the susceptibility to sepsis-induced cardiac dysfunction. Methods Study patient data were obtained from the image database of EARLY-MYO-SEPSIS (EARLY assessment of MYOcardial tissue characteristics by multi-modal imaging in SEPSIS) registry, which was a prospective, multi-center registry of sepsis patients who have undergone cardiac magnetic resonance imaging (MRI) and echocardiography from 8 sites (clinical trial number NCT04513795). Cardiac involvement was evaluated using a comprehensive assessment comprising of echocardiography (with global longitudinal strain calculation), cardiac MRI and cardiac biomarker evaluation. Logistic regression was performed to identify independent predictors of left ventricular systolic dysfunction in sepsis. Results A total of 216 intensive care unit patients with sepsis was enrolled in the present analysis. Septic patients with a history of circadian disruption (i.e., sleep insufficiency Conclusions Our data from EARLY-MYO-SEPSIS registry demonstrated a previously unappreciated circadian sensitivity to sepsis-induced cardiac dysfunction. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): This work was supported by grants from the National Science Fund for Distinguished Young Scholars (81625002) and National Natural Science Foundation of China (81930007)

Background: Walking, as the most common campaign in older people, is recommended to improve their cardiovascular health. However, the direct association between weekly walking activity and asymptomatic hypertensive mediated organ damage (HMOD) remains unclear.Methods: 2,830 community-dwelling elderly subjects (over 65 years) in northern Shanghai were recruited from 2014 to 2018. Weekly walking activity was assessed by International Physical Activity Questionnaires (IPAQ). Within the framework of comprehensive cardiovascular examinations, HMOD, including left ventricular mass index, peak transmitral pulsed Doppler velocity/early diastolic tissue Doppler velocity, creatinine clearance rate, urinary albumin–creatinine ratio, carotid-femoral pulse wave velocity (cf-PWV), carotid intima–media thickness (CIMT), arterial plaque, and ankle-brachial index (ABI), were all evaluated.Results: 1,862 (65.8%) participants with weekly walking activity showed lower CIMT, lower cf-PWV, fewer abnormal ABI, and lower prevalence of hypertension and coronary heart disease (p < 0.05). Walking activity was negatively correlated with age and smokers (correlation coefficient: −0.066, −0.042; both p < 0.05). After adjusting for cardiovascular risk factors and concomitant diseases, walking activity was significantly associated with better indicator of most vascular HMOD in multivariate logistic regressions, including arterial stiffness [odds ratio (OR) = 0.75, p = 0.01], increased CIMT (OR = 0.70, p = 0.03), and peripheral artery disease (OR = 0.72, p = 0.005), but not cardiac or renal HMOD. Subgroup analysis further showed that walking duration ≥1 h/day was significantly associated with decreased risk of most vascular HMOD after adjustment for confounders and moderate-to-vigorous physical activity based on IPAQ (all p < 0.05).Conclusions: In the community-dwelling elderly Chinese, there was a significant negative association of weekly walking activity with vascular HMOD, but not cardiac or renal HMOD. Increased daily walking duration, but not walking frequency, was significantly associated with improved vascular HMOD. Hence, increasing daily walking duration seems to encourage a healthy lifestyle in terms of vascular protection.Clinical Trial Registration:ClinicalTrials.gov, identifier: NCT02368938.

Summary Background Compared with visual angiographic assessment, pressure wire-based physiological measurement more accurately identifies flow-limiting lesions in patients with coronary artery disease. Nonetheless, angiography remains the most widely used method to guide percutaneous coronary intervention (PCI). In FAVOR III China, we aimed to establish whether clinical outcomes might be improved by lesion selection for PCI using the quantitative flow ratio (QFR), a novel angiography-based approach to estimate the fractional flow reserve. Methods FAVOR III China is a multicentre, blinded, randomised, sham-controlled trial done at 26 hospitals in China. Patients aged 18 years or older, with stable or unstable angina pectoris or patients who had a myocardial infarction at least 72 h before screening, who had at least one lesion with a diameter stenosis of 50–90% in a coronary artery with a reference vessel of at least 2·5 mm diameter by visual assessment were eligible. Patients were randomly assigned to a QFR-guided strategy (PCI performed only if QFR ≤0·80) or an angiography-guided strategy (PCI based on standard visual angiographic assessment). Participants and clinical assessors were masked to treatment allocation. The primary endpoint was the 1-year rate of major adverse cardiac events, a composite of death from any cause, myocardial infarction, or ischaemia-driven revascularisation. The primary analysis was done in the intention-to-treat population. The trial was registered with ClinicalTrials.gov ( NCT03656848 ). Findings Between Dec 25, 2018, and Jan 19, 2020, 3847 patients were enrolled. After exclusion of 22 patients who elected not to undergo PCI or who were withdrawn by their physicians, 3825 participants were included in the intention-to-treat population (1913 in the QFR-guided group and 1912 in the angiography-guided group). The mean age was 62·7 years (SD 10·1), 2699 (70·6%) were men and 1126 (29·4%) were women, 1295 (33·9%) had diabetes, and 2428 (63·5%) presented with an acute coronary syndrome. The 1-year primary endpoint occurred in 110 (Kaplan-Meier estimated rate 5·8%) participants in the QFR-guided group and in 167 (8·8%) participants in the angiography-guided group (difference, –3·0% [95% CI –4·7 to –1·4]; hazard ratio 0·65 [95% CI 0·51 to 0·83]; p=0·0004), driven by fewer myocardial infarctions and ischaemia-driven revascularisations in the QFR-guided group than in the angiography-guided group. Interpretation In FAVOR III China, among patients undergoing PCI, a QFR-guided strategy of lesion selection improved 1-year clinical outcomes compared with standard angiography guidance. Funding Beijing Municipal Science and Technology Commission, Chinese Academy of Medical Sciences, and the National Clinical Research Centre for Cardiovascular Diseases, Fuwai Hospital.

Background Abdominal aortic aneurysm (AAA) is a life‐threatening vascular disorder characterized by chronic inflammation of the aortic wall, which lacks effective pharmacotherapeutic remedies and has an extremely high mortality. Nuclear receptor NR4A1 (Nur77) functions in various chronic inflammatory diseases. However, the influence of Nur77 on AAA has remained unclear. Herein, we sought to determine the effects of Nur77 on the development of AAA. Methods and Results We observed that Nur77 expression decreased significantly in human and mice AAA lesions. Deletion of Nur77 accelerated the development of AAA in mice, as evidenced by increased AAA incidence, abdominal aortic diameters, elastin fragmentation, and collagen content. Consistent with genetic manipulation, pharmacological activation of Nur77 by celastrol showed beneficial effects against AAA. Microscopic and molecular analyses indicated that the detrimental effects of Nur77 deficiency were associated with aggravated macrophage infiltration in AAA lesions and increased pro‐inflammatory cytokines secretion and matrix metalloproteinase (MMP‐9) expression. Bioinformatics analyses further revealed that LOX‐1 was upregulated by Nur77 deficiency and consequently increased the expression of cytokines and MMP‐9. Moreover, rescue experiments verified that LOX‐1 notably aggravated inflammatory response, an effect that was blunted by Nur77. Conclusions This study firstly demonstrated a crucial role of Nur77 in the formation of AAA by targeting LOX‐1, which implicated Nur77 might be a potential therapeutic target for AAA.

Background: Recent studies have suggested that soluble suppression of tumorigenicity-2 (sST2), an inflammation-related protein receptor, is associated with atherosclerotic diseases. This study aimed to investigate the potential predictive value of sST2 on plaque vulnerability by assessing whether elevated serum levels of sST2 are associated with vulnerable plaque features in patients with non-ST-elevation acute coronary syndrome (ACS).Methods: A total of 120 patients with non-ST-elevation ACS (167 lesions) were prospectively enrolled and evaluated by standard coronary computed tomography angiography (CCTA) and coronary angiography in this study. Serum sST2 levels were measured by ELISA (Presage® ST2 Assay Kit, Critical Diagnostics), and semiautomated software (QAngioCT, Medis) was used to quantify coronary plaques.Results: The included patients were divided into 4 groups by serum sST2 level quartiles. Volumetric analysis of the whole lesion revealed that patients with higher sST2 levels had a larger absolute necrotic core (NC) volume (Quartile 4 vs. Quartile 1, 86.16 ± 59.71 vs. 45.10 ± 45.80 mm3, P = 0.001; Quartile 4 vs. Quartile 2, 86.16 ± 59.71 vs. 50.22 ± 42.56 mm3, P = 0.002) and a higher NC percentage (Quartile 4 vs. Quartile 1, 35.16 ± 9.82 vs. 23.21 ± 16.18%, P < 0.001; Quartile 4 vs. Quartile 2, 35.16 ± 9.82% vs. 22.50 ± 14.03%, P < 0.001; Quartile 4 vs. Quartile 3, 35.16 ± 9.82% vs. 25.04 ± 14.48%, P < 0.001). Correlation analysis revealed that serum sST2 levels were positively correlated with the NC (r = 0.323, P < 0.001) but negatively correlated with dense calcium (r = −0.208, P = 0.007). Furthermore, among those with plaque calcification, patients with spotty calcification exhibited higher serum sST2 levels than those with large calcification (26.06 ± 16.54 vs. 17.55 ± 7.65 ng/mL, P = 0.002). No significant differences in plaque components at the level of the minimal lumen area (MLA) were found among the groups.Conclusions: Serum sST2 levels were correlated with different coronary plaque components in patients with non-ST-elevation ACS. A higher serum level of sST2 was correlated with plaque vulnerability.Clinical Trial Registration:www.ClinicalTrials.gov, identifier: NCT04797819.

Methicillin-resistant Staphylococcus aureus (MRSA), a leading cause of infections in human being and is usually associated with a multidrug-resistant profile, represents a significant health threat and public burden globally. The limited options of effective antibiotics motivate the search for novel anti-MRSA agents. Aminoglycoside antibiotics have been extensively applied in the medical field due to their desirable broad-spectrum antibacterial activity, especially for systemic infections caused by Gram-negative organisms. Recent studies demonstrated that aminoglycosides also possessed potential activity against MRSA, so aminoglycosides may be useful weapons to fight against MRSA. The present work aims to summarize the current scenario of aminoglycosides with anti- MRSA potential, covering articles published between 2010 and 2020. The structure-activity relationship and the mechanism of action are also discussed for the further rational design of novel potential drug candidates.

Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): the National Key Research and Development Program of China OnBehalf Renji Hospital Affiliated to Medical College of Shanghai Jiaotong University Background：The prognostic value of Peak Early Diastolic Strain Rate (PEDSR) measured by Cardiac Magnetic Resonance (CMR) in ST-Elevation Myocardial Infarction (STEMI) is not clear. Methods：420 first-STEMI patients from the EARLY Assessment of MYOcardial Tissue Characteristics by CMR in STEMI (EARLY-MYO-CMR) registry (NCT03768453) and 40 normal people were enrolled and followed up. The patients received timely percutaneous coronary intervention (PCI) within 12h and CMR within 1 week (median,5 days; range, 2-7 days) after infarction. LV circumferential, radial, longitudinal PEDSR and other routine CMR parameters were measured. Clinical end point was a composite major adverse cardiovascular events (MACEs) including cardiovascular death, re-infarction and re-hospitalization for heart failure. Results：During follow-up (median: 52 months, inter-quartile range: 29–78 months), 73 (17.4%) patients experienced a MACE event. Compared with normal people, STEMI patients had lower PEDSR (circumf. PEDSR 0.77 vs. 1.27%/s, P 50.28% (P = 0.003) but not in reduced LVEF patients (P = 0.204). PEDSR is also incremental to LVEF (Continuous NRI 0.515 [95%CI 0.268-0.763], P Conclusions：CMR-derived PEDSR can significantly predict MACEs with the discriminative power not inferior to LVEF, LVIS and LVMVO. Circumf. PEDSR ≤ 0.665%/s is an independent predictive factor of MACEs and is incremental in the prognostic risk stratification of STEMI.

Although mass spectrometry (MS) of metabolites has the potential to provide real‐time monitoring of patient status for diagnostic purposes, the diagnostic application of MS is limited due to sample treatment and data quality/reproducibility. Here, the generation of a deep stabilizer for ultra‐fast, label‐free MS detection and the application of this method for serum metabolic diagnosis of coronary heart disease (CHD) are reported. Nanoparticle‐assisted laser desorption/ionization‐MS is used to achieve direct metabolic analysis of trace unprocessed serum in seconds. Furthermore, a deep stabilizer is constructed to map native MS results to high‐quality results obtained by established methods. Finally, using the newly developed protocol and diagnosis variation characteristic surface to characterize sensitivity/specificity and variation, CHD is diagnosed with advanced accuracy in a high‐throughput/speed manner. This work advances design of metabolic analysis tools for disease detection as it provides a direct label‐free, ultra‐fast, and stabilized platform for future protocol development in clinics., Mass spectrometry (MS) based metabolic analysis has the potential to provide real‐time monitoring of patient status for diagnostic purposes, whereas the diagnostic application is limited due to sample treatment and data quality/reproducibility. Here, the generation of a deep stabilizer is developed for ultra‐fast, label‐free MS detection in serum metabolic diagnosis of coronary heart disease.

Background. Gamma-glutamyl transferase (GGT) has been detected in coronary plaques. However, the association between serum GGT levels and coronary atherosclerotic plaque vulnerability in patients with coronary artery disease (CAD) as detected by optical coherence tomography (OCT) has not been investigated.Methods. We performed a retrospective study of consecutively enrolled CAD patients undergoing preintervention OCT examination during coronary angiography. Plaque vulnerability was defined as the presence of ruptured plaques or thin-cap fibroatheroma (TCFA) upon OCT. The association between serum GGT levels and coronary plaque vulnerability was evaluated using multivariate logistic regression analysis.Results. A total of 142 patients were included in our analysis. OCT examination detected ruptured plaques in 16 patients, nonruptured plaques with TCFA in 17 patients, and nonruptured plaques and non-TCFA in 109 patients. Univariate analyses showed that gender, diabetes, Apolipoprotein A1 (ApoA1) and high-density lipoprotein cholesterol (HDL-c), and diagnosis of acute coronary syndrome (ACS) were associated with plaque vulnerability (P all < 0.05). Patients grouped according to serum GGT tertiles did not differ statistically in baseline characteristics or OCT findings. Results of multivariate logistic analyses showed that diabetes and diagnosis of ACS were associated with plaque rupture and TCFA (P < 0.05).Conclusions. GGT serum levels were not associated with OCT detected coronary vulnerability in our cohort of CAD patient.

BACKGROUND & AIMS Cirrhotic cardiomyopathy is a major complication and cause of morbidity in end-stage primary biliary cholangitis (PBC). However, it is unclear whether there is clinically silent myocardial involvement at the early stage of PBC before cirrhosis and cardiac manifestations. This prospective, three-center, multi-modality cardiac imaging study on the early identification of myocardial impairment in PBC (EARLY-MYO-PBC) was designed to identify silent myocardial impairment in PBC patients without cardiac manifestations. METHODS A total of 112 subjects (56 with PBC and 56 age- and sex-matched controls) undergoing cardiovascular magnetic resonance (CMR) were enrolled. Demographic, serologic, and cardiac imaging data were prospectively collected. All participants had no cardiac discomfort or previous heart disease and had normal electrocardiographic findings. RESULTS Subclinical myocardial involvement, as evidenced by cardiac morphologic, functional, and tissue characterization changes on CMR, including hyperdynamic left ventricular (LV) ejection fraction (median, 75% in PBC patients vs 69% in controls, P = .029), subclinical myocardial edema by T2-short tau inversion recovery (21% vs 2% in controls, P = .001), elevated extracellular matrix indices (30% vs 26% in controls, P < .001), and impaired myocardial viability by positive late gadolinium enhancement (LGE) (36%), was detected in PBC patients. Importantly, a mid-wall "stripe" at the LV septum was identified as a PBC-specific LGE pattern that differs from other known cardiomyopathies. In multivariate analysis, gp210 positivity (odds ratio [OR] = 9.909, P = .010), lower hemoglobin (OR = 0.919, P = .004), and body mass index (OR = 0.638, P = .005) were independent predictors of cardiac abnormalities in PBC. CONCLUSIONS This study demonstrates clinically silent cardiac impairment with specific CMR patterns in PBC, allowing optimal screening for early myocardial impairment and potentially timely therapies. (Trial registration no.: NCT03545672).

To assess a novel approach for automatic flow velocity computation in deriving quantitative flow ratio (QFR) from coronary angiography. QFR is a novel approach for assessment of functional significance of coronary artery stenosis without using pressure wire and induced hyperemia. Patient-specific coronary flow is estimated semi-automatically by frame count method, which is subjective and inconvenient in the workflow of QFR analysis. The vascular structures were automatically delineated from coronary angiogram. Subsequently, the centerline of the interrogated vessel was extracted from the delineated lumen on each image frame and the change in the length of centerline was used to compute the flow velocity, which provided patient-specific flow for computation of QFR (QFR auto ). A parameter derived from the increase in centerline length was used to automatically quantify the stability of contrast flow. From the two angiographic image runs used for three-dimensional angiographic reconstruction, the one with better stability was used to compute QFR auto . QFR auto was assessed in all patients enrolled in the FAVOR II China study, and compared with the commercialized QFR computational method based on frame count (QFR count ), using pressure wire-based fractional flow reserve (FFR) as the reference standard. Out of 328 vessels with paired FFR data, QFR auto was successfully computed on 325 (99%) vessels with acceptable stability in filling of contrast flow. The flow velocity computed by the proposed approach had a weak to moderate correlation with the frame count method (r = 0.37, p < 0.001), with mean differences of − 0.02 ± 0.07 m/s (p < 0.001). QFR auto had good correlation (r = 0.96, p < 0.001) and agreement (mean difference: − 0.01 ± 0.04, p < 0.001) with QFR count . Good correlation (r = 0.83, p < 0.001) and agreement (mean difference: 0.01 ± 0.06, p = 0.016) were also observed between QFR auto and FFR. Using FFR ≤ 0.80 to define functional significance of coronary stenosis, the overall diagnostic accuracy for QFR auto was 93.2% (95% CI 90.5–96.0%). The area under the receiver-operating characteristic curve did not differ significantly between QFR count and QFR auto (difference: 0.00; 95% CI − 0.01 to 0.01; p = 0.529). Sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio for QFR auto were 92.4% (95% CI 86.0–96.5%), 93.7% (95% CI 89.5–96.6%), 14.7 (95% CI 8.7–25.0), and 0.1 (95% CI 0.0–0.2), respectively. Automatic computation of patient-specific coronary flow velocity based on coronary angiography is feasible. Assessment of QFR based on this novel approach had good diagnostic accuracy in determining the functional significance of coronary stenosis.

This study aimed to evaluate left atrial (LA) remodeling and fibrosis in paroxysmal atrial fibrillation (AF) using speckle tracking echocardiography (STE) based on the findings with radiofrequency catheter ablation (RFCA) so as to predict atrial remodeling prior to ablation. A total of 40 patients with paroxysmal AF were enrolled and divided into two groups based on LA bipolar voltage detected during RFCA: those with low-voltage zone (LVZ) (LV group, n = 19) and those without LVZ (non-LV group, n = 21). The segmental and global LA reservoir, conduit and contractile strain (es, ee, ea) were analyzed using two-dimensional STE before RFCA. The segmental and global es, ee, ea (%) decreased in the LV group. Especially, the es in anteroseptal upper (18.32 ± 7.94 vs. 31.61 ± 9.39) and lower segments (16.60 ± 7.23 vs. 29.23 ± 9.81), posteroseptal upper (22.24 ± 6.65 vs. 32.23 ± 10.57) and lower segments (18.24 ± 6.49 vs. 26.40 ± 7.12), and the global es (23.85 ± 6.74 vs. 30.48 ± 8.67) significantly decreased in the LV group than in the non-LV group (all P

Atherosclerosis is a progressive vascular wall inflammatory disease, and the rupture of atherosclerotic vulnerable plaques is the leading cause of morbidity and mortality worldwide. This study intended to explore the potential mechanisms behind plaque rupture and thrombosis in ApoE knockout mice. The spontaneous plaque rupture models were established, and left carotid artery tissues at different time points (1-, 2-, 4-, 6-, 8-, 12-, and 16-week post-surgery) were collected. By the extent of plaque rupture, plaque was defined as (1) control groups, (2) atherosclerotic plaque group, and (3) plaque rupture group. Macrophage (CD68), MMP-8, and MMP-13 activities were measured by immunofluorescence. Cytokines and inflammatory markers were measured by ELISA. The left carotid artery sample tissue was collected to evaluate the miRNAs expression level by miRNA-microarray. Bioinformatic analyses were conducted at three levels: (2) vs. (1), (3) vs. (2), and again in seven time series analysis. The plaque rupture with thrombus and intraplaque hemorrhage results peaked at 8 weeks and decreased thereafter. Similar trends were seen in the number of plaque macrophages and lipids, the expression of matrix metalloproteinase, and the atherosclerotic and plasma cytokine levels. MiRNA-microarray showed that miR-322-5p and miR-206-3p were specifically upregulated in the atherosclerotic plaque group compared with those in the control group. Meanwhile, miR-466h-5p was specifically upregulated in the plaque rupture group compared with the atherosclerotic plaque group. The highest incidence of plaque rupture and thrombosis occurred at 8 weeks post-surgery. miR-322-5p and miR-206-3p may be associated with the formation of atherosclerotic plaques. miR-466h-5p may promote atherosclerotic plaque rupture via apoptosis-related pathways.

Background: Catheter ablation for parahisian ventricular arrhythmias (PHVA) is technically challenging and associated with risks of atrioventricular block (AVB). We developed a stepwise approach to improve the efficacy and safety of PHVA ablation. Methods: Forty-three patients (26 males; average age 65.8 ±10.4 years) with PHVAs were enrolled. A stepwise approach comprising differential electrocardiogram, sequential mapping and ablation beneath/above the septal leaflet of the tricuspid valve (SLTV) and at the neighboring/contralateral regions (the aortic root and sub-aortic valve region) was applied for PHVA. The effectiveness and safety of the stepwise approach was evaluated at the end of one year’s follow-up. Results: Sequential ablation beneath the SLTV (B-SLTV) succeeded in 24 (66.7 %) of 36 with right PHVA and ablation above the SLTV succeeded in 6 of the remaining12 with failed B-SLTV ablation. Target-His bundle (HB) distance > 4.5 mm significantly predicted successful right PHVA ablation (OR 1.703; 95% CI 1.084-2.676, P=0.02). “Seeming” right PHVA by electrocardiogram in 4 and apparent left PHVA in 3 was successfully ablated at the sub-aortic parahisian region. At the end of one year’s follow-up, 27 (75%) of 36 patients with right PHVA and 6 (85.7%) of 7 patients with left PHVA were free of PHVA recurrence off anti-arrhythmic drugs. The total success rate was 76.7% by using the stepwise approach for PHVA. One patient with A-SLTV ablation underwent pacemaker implantation due to complete AVB. Conclusions: The stepwise approach was effective and safe for treating PHVA. The target-HB distance was a significant predictor for right PHVA ablation

Background: Emerging studies have described and analyzed epidemiological, clinical, laboratory, and radiological features of COVID-19 patients. Yet, scarce information is available regarding the association of lipid profile features and disease severity and mortality.Methods: We conducted a prospective observational cohort study to investigate lipid profile features in patients with COVID-19. From 9 February to 4 April 2020, a total of 99 patients (31 critically ill and 20 severely ill) with confirmed COVID-19 were included in the study. Dynamic alterations in lipid profiles were recorded and tracked. Outcomes were followed up until 4 April 2020.Results: We found that high-density lipoprotein-cholesterol (HDL-C) and apolipoprotein A-1 (apoA-1) levels were significantly lower in the severe disease group, with mortality cases showing the lowest levels (p < 0.0001). Furthermore, HDL-C and apoA-1 levels were independently associated with disease severity (apoA-1: odds ratio (OR): 0.651, 95% confidence interval (CI): 0.456–0.929, p = 0.018; HDL-C: OR: 0.643, 95% CI: 0.456–0.906, p = 0.012). For predicting disease severity, the areas under the receiver operating characteristic curves (AUCs) of HDL-C and apoA-1 levels at admission were 0.78 (95% CI, 0.70–0.85) and 0.85 (95% CI, 0.76–0.91), respectively. For in-hospital deaths, HDL-C and apoA-1 levels demonstrated similar discrimination ability, with AUCs of 0.75 (95% CI, 0.61–0.88) and 0.74 (95% CI, 0.61–0.88), respectively. Moreover, patients with lower serum concentrations of apoA-1 (p < 0.001). Notably, levels of apoA-1 and HDL-C were inversely proportional to disease severity. The survivors of severe cases showed significant recovery of apoA-1 levels at the end of hospitalization (vs. midterm apoA-1 levels, p = 0.02), whereas the mortality cases demonstrated continuously lower apoA-1 levels throughout hospitalization. Correlation analysis revealed that apoA-1 and HDL-C levels were negatively correlated with both admission levels and highest concentrations of C-reactive protein and interleukin-6.Conclusions: Severely ill COVID-19 patients featured low HDL-C and apoA-1 levels, which were strongly correlated with inflammatory states. Thus, low apoA-1 and HDL-C levels may be promising predictors for severe disease and in-hospital mortality in patients suffering from COVID-19.

Background There is controversy regarding the efficacy of different treatment strategies for acute left malignant colonic obstruction. This study investigated the 5-year overall survival (OS) and disease-free survival (DFS) of several treatment strategies for acute left malignant colonic obstruction. Methods We searched for articles published in PubMed, Embase (Ovid), MEDLINE (Ovid), Web of Science, and Cochrane Library between January 1, 2000, and July 1, 2020. We screened out the literature comparing different treatment strategies. Evaluate the primary and secondary outcomes of different treatment strategies. The network meta-analysis summarizes the hazard ratio, odds ratio, mean difference, and its 95% confidence interval. Results The network meta-analysis involved 48 articles, including 8 (randomized controlled trials) RCTs and 40 non-RCTs. Primary outcomes: the 5-year overall survival (OS) and disease-free survival (DFS) of the CS-BTS strategy and the DS-BTS strategy were significantly better than those of the ES strategy, and the 5-year OS of the DS-BTS strategy was significantly better than that of CS-BTS. The long-term survival of TCT-BTS was not significantly different from those of CS-BTS and ES. Secondary outcomes: compared with emergency resection (ER) strategies, colonic stent-bridge to surgery (CS-BTS) and transanal colorectal tube-bridge to surgery (TCT-BTS) strategies can significantly increase the primary anastomosis rate, CS-BTS and decompressing stoma-bridge to surgery (DS-BTS) strategies can significantly reduce mortality, and CS-BTS strategies can significantly reduce the permanent stoma rate. The hospital stay of DS-BTS is significantly longer than that of other strategies. There was no significant difference in the anastomotic leakage levels of several treatment strategies. Conclusion Comprehensive literature research, we find that CS-BTS and DS-BTS strategies can bring better 5-year OS and DFS than ER. DS-BTS strategies have a better 5-year OS than CS-BTS strategies. Without considering the hospital stays, DS-BTS strategy is the best choice.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has become global pandemic and resulted in considerable morbidity and mortality since December 2019. Information on the incidence of myocardial injury remains scarce. METHODS: English-language databases (PubMed, Embase, Cochrane), Chinese-language databases (CNKI, VIP, WANFANG), and preprint platform were searched to identify studies that reported the myocardial injury data in COVID-19 patients. Random-effects meta-analyses were used to derive the pooled incidence and relative risks (RRs) of myocardial injury. Variations by disease severity were examined by subgroup analyses. Sensitivity analyses were performed to strengthen the results. Meta-regression was applied to explore the risk factors associated with myocardial injury. RESULTS: A total of 53 studies involving 7,679 patients were included. The pooled incidence of myocardial injury was 21% [95% confidence interval (CI), 17–25%; I(2), 96.5%]. The highest incidence of myocardial injury was found in non-survivors (66%; 95 CI%, 54–78%; I(2), 85.7%), followed by severe patients (43%; 95 CI%, 33–53%; I(2), 93.0%) and non-severe patients (11%; 95 CI%, 7–15%; I(2), 95.2%). Higher risk of myocardial injury was detected in severe patients than non-severe patients (RR, 5.74; 95% CI, 3.74–8.79; I(2), 86.8%). All the sensitivity analyses confirmed the robustness of primacy results. CONCLUSIONS: This meta-analysis showed that myocardial injury occurred in 21% of COVID-19 patients. An elevated rate was observed in non-survivors (66%) and severe patients (43%). Severe patients had a 4.74-fold increase in the risk of myocardial injury than non-severe patients. Aggressive strategy may be considered for COVID-19 patients at high risk of myocardial injury.

Background Double kissing (DK) crush approach for patients with coronary bifurcation lesions, particularly localized at distal left main or lesions with increased complexity, is associated with significant reduction in clinical events when compared with provisional stenting. Recently, randomized clinical trial has demonstrated the net clinical benefits by intravascular ultrasound (IVUS)-guided implantation of drug-eluting stent in all-comers. However, the improvement in clinical outcome after DK crush treatment guided by IVUS over angiography guidance for patients with complex bifurcation lesions have never been studied in a randomized fashion. Trial design DKCRUSH VIII study is a prospective, multicenter, randomized controlled trial designed to assess superiority of IVUS-guided vs angiography-guided DK crush stenting in patients with complex bifurcation lesions according to DEFINITION criteria. A total of 556 patients with complex bifurcation lesions will be randomly (1:1 of ratio) assigned to IVUS-guided or angiography-guided DK crush stenting group. The primary end point is the rate of 12-month target vessel failure, including cardiac death, target vessel myocardial infarction, or clinically driven target vessel revascularization. The secondary end points consist of the individual component of primary end point, all-cause death, myocardial infarction, and in-stent restenosis. The safety end point is the incidence of definite or probable stent thrombosis. An angiographic follow-up will be performed for all patients at 13 months and clinical follow-up will be continued annually until 3 years after the index procedure. Conclusions DKCRUSH VIII trial is the first study designed to evaluate the differences in efficacy and safety between IVUS-guided and angiography-guided DK crush stenting in patients with complex true bifurcation lesions. This study will also provide IVUS-derived criteria to define optimal DK crush stenting for bifurcation lesions at higher complexity.

BACKGROUNDIncreasing attention has been paid to cardiac involvement in patients with coronavirus disease 2019 (COVID-19). Yet, scarce information is available regarding the morphological and functional features of cardiac impairments in these patients.METHODSWe conducted a prospective and serial echocardiographic study to investigate the structural and functional cardiac changes among COVID-19 patients admitted to the intensive care unit (ICU). From January 21 to April 8, 2020, a total of 51 ICU patients (31 critically ill and 20 severely ill) with confirmed COVID-19 were monitored by serial transthoracic echocardiography examinations. Outcomes were followed up until April 8, 2020.RESULTSOf 51 ICU patients, 33 (64.7%) had cardiovascular comorbidities. Elevations of levels of cardiac biomarkers including high-sensitivity cardiac troponin-I (hs-cTnI) and brain natriuretic peptide were observed in 62.7% and 86.3% of patients, respectively. Forty-two (82.3%) had at least one left-heart and/or right-heart echocardiographic abnormality. The overall median left ventricular ejection fraction (LVEF) was 65.0% (IQR 58.0–69.0%), with most (44/86.3%) having preserved LVEF. Sixteen patients (31.4%) had increased pulmonary artery systolic pressure, and 14 (27.5%) had right-ventricle (RV) enlargement. During the study period, 12 (23.5%) patients died. LVEF was comparable between survivors and non-survivors, while non-survivors had more often pulmonary hypertension (58.3% vs. 23.1%; P=0.028) and RV enlargement (58.3% vs. 17.9%, P=0.011). Kaplan-Meier analysis demonstrated similar survival curves between patients with vs. without echocardiographic left-heart abnormalities (P=0.450 by log-rank test), while right-heart abnormalities had adverse impact on mortality (P=0.012 by log-rank test).CONCLUSIONSTypical cardiac abnormality in ICU patients with COVID-19 was right-heart dysfunction with preserved LVEF. Echocardiographic right-heart dysfunction was associated with disease severity and increased mortality in patients affected by COVID-19.CLINICAL TRIAL REGISTRATIONUnique identifier: NCT04352842.

Background Farnesoid X receptor (FXR) is a nuclear receptor that plays a critical role in controlling cell apoptosis in diverse diseases. Previous studies have shown that knocking out FXR improved cardiac function by reducing cardiomyocyte apoptosis in myocardial ischemic mice. However, the role of FXR after cerebral ischemia remains unknown. In this study, we explored the effects and mechanisms of FXR knockout (KO) on the functional recovery of mice post cerebral ischemia-reperfusion. Methods Adult male C57BL/6 wild type and FXR KO mice were subjected to 90-min transient middle cerebral artery occlusion (tMCAO). The mice were divided into five groups: sham, wild-type tMCAO, FXR KO tMCAO, wild-type tMCAO treated with calcium agonist Bayk8644, and FXR KO tMCAO treated with Bayk8644. FXR expression was examined using immunohistochemistry and Western blot. Brain infarct and brain atrophy volume were examined at 3 and 14 days after stroke respectively. Neurobehavioral tests were conducted up to 14 days after stroke. The protein levels of apoptotic factors (Bcl-2, Bax, and Cleaved caspase-3) and mRNA levels of pro-inflammatory factors (TNF-α, IL-6, IL-1β, IL-17, and IL-18) were examined using Western blot and RT-PCR. TUNEL staining and calcium imaging were obtained using confocal and two-photon microscopy. Results The expression of FXR was upregulated after ischemic stroke, which is located in the nucleus of the neurons. FXR KO was found to reduce infarct volume and promote neurobehavioral recovery following tMCAO compared to the vehicle. The expression of apoptotic and pro-inflammatory factors decreased in FXR KO mice compared to the control. The number of NeuN+/TUNEL+ cells declined in the peri-infarct area of FXR KO mice compared to the vehicle. We further demonstrated that inhibition of FXR reduced calcium overload and addition of ionomycin could reverse this neuroprotective effect in vitro. What is more, in vivo results showed that enhancement of intracellular calcium concentrations could aggravate ischemic injury and reverse the neuroprotective effect of FXR KO in mice. Conclusions FXR KO can promote neurobehavioral recovery and attenuate ischemic brain injury, inflammatory release, and neuronal apoptosis via reducing calcium influx, suggesting its role as a therapeutic target for stroke treatments.

To explore the strategy of acute cerebral artery embolism after radiofrequency catheter ablation (RFA) for atrial fibrillation (AF). Reporting two cases with acute cerebral infarction after RFA for AF. Two patients were both with AF, and intracardiac thrombus was excluded through transesophageal echocardiogram (TEE) before procedure. Approach of ablation: circumferential pulmonary vein ablation in left atrium to isolate pulmonary vein plus linear ablation in the top and bottom of left atrium (BOX procedure). They both received Dabigatran Etexilate 110 mg twice daily, starting 6 hr after ablation. Symptoms of major stroke appeared 30 hr after ablation in Case 1. Occlusion was detected in M1 segment of the left middle cerebral artery by MRI 2 hr after symptoms onset. Intravenous thrombolysis was given immediately. In Case 2, the patient presented symptoms of major stroke 34 hr after ablation and occlusion in the basilar artery was confirmed by MRI 4.5 hr after symptoms onset. Although it was beyond the thrombolysis time window, mechanical thrombectomy was taken 7 hr after the symptoms onset. The culprit artery was successfully revascularized in both cases. In Case 1, NIHSS score was reduced from 8 (before thrombolysis) to 0 (24 hr after thrombolysis). In Case 2, NIHSS score decreased from 18 (before embolectomy) to 3 (24 hr after embolectomy). Both of the patients live a normal life without brain function impairment and hemorrhage until the last follow‐up. Timely recanalization could attained a good cure effect when acute stoke was happened after RFA for AF.

Disruptions of the circadian rhythm and reduced circulating levels of the circadian hormone melatonin predispose to ischemic stroke. Although the nuclear receptor RORα is considered as a circadian rhythm regulator and a mediator of certain melatonin effects, its potential role in cerebral ischemia-reperfusion (CI/R) injury and in the neuroprotective effects of melatonin remain undefined. Here, we observed that CI/R injury in RORα-deficient mice was associated with greater cerebral infarct size, brain edema, and cerebral apoptosis compared with wild-type model. In contrast, transgenic mice with brain-specific overexpression of RORα versus non-transgenic controls exerted significantly reduced infarct volume, brain edema and apoptotic response induced by CI/R. Mechanistically, RORα deficiency was found to exacerbate apoptosis pathways mediated by endoplasmic-reticulum stress and mitochondria and aggravate oxidative/nitrative stress after CI/R. Further studies revealed that RORα deficiency intensified the activation of nuclear factor-κB signaling induced by CI/R. Given the emerging evidence of RORα as an essential melatonin activity mediator, we further investigated the RORα roles in melatonin-exerted neuroprotection against acute ischemic stroke. Melatonin treatment significantly decreased infarct volume and cerebral apoptosis; mitigated endoplasmic reticulum stress and mitochondrial dysfunction; and inhibited CI/R injury-induced oxidative/nitrative stress and nuclear factor-κB activation, which was eradicated in RORα-deficient mice. Collectively, current findings suggest that RORα is a novel endogenous neuroprotective receptor, and a pivotal mediator of melatonin's suppressive effects against CI/R injury.

Our study sought to explore the prognostic value of radiomic TA (texture analysis) on quantitative ECV (extracellular volume) fraction mapping to differentiate between reversible and irreversible myocardial damage and to predict left ventricular adverse remodeling in patients with reperfused STEMI (ST-elevation myocardial infarction). This observational prospective cohort study identified 70 patients (62 ± 9 years, 62 men [85.70%]) with STEMI for TA who consecutively performed native and contrast T1 mapping. Texture features were extracted from each stack of ECV mapping based on ROI (region of interest) analysis. After texture feature selection and dimension reduction, five selected texture features were found to be statistically significant for differentiating the extent of myocardial injury. ROC (receiver operating characteristic) curve analysis for the differentiation of unsalvageable infarction and salvageable myocardium demonstrated a significantly higher AUC (area under the curve) (0.91 [95% CI, 0.86–0.96], p

OBJECTIVES This study evaluated quantitative flow ratio (QFR) to predict microvascular dysfunction (MVD) in patients with ST-segment elevation myocardial infarction (STEMI). BACKGROUND QFR is a novel approach for the rapid computation of fractional flow reserve based on three-dimensional quantitative coronary angiography. We hypothesized that QFR computation could be used to predict MVD after STEMI. METHODS Indexes such as contrast-flow QFR (cQFR), fixed-flow QFR (fQFR), and hyperemic flow velocity (HFV) were calculated in 130 STEMI patients with culprit lesion with ≥50% diameter stenosis and TIMI flow grade 2/3 in the spontaneously recanalized culprit artery on initial angiography. MVD was defined as microvascular obstruction determined by contrast-enhanced cardiac magnetic resonance at a median of 5 days after percutaneous coronary intervention. RESULTS Patients were divided into the MVD group (76/130, 58.5%) and non-MVD group (54/130, 41.5%). Patients with MVD had higher cQFR-fQFR value (0.080 ± 0.058 vs. 0.038 ± 0.039, p

Background Papillary thyroid cancer (PTC) is the most common epithelial thyroid tumor, accounting for more than 80% of all thyroid cancers. Though the fine needle aspiration biopsy (FNAB) represents as the golden standard for the diagnostics of thyroid nodules, there is a ∼25% risk of indeterminate cytological features. TMPRSS4 is a newly found transmembrane serine protease which was overexpressed in papillary thyroid cancer (PTC). Aims The aim of this study was to determine its potential as a diagnostic marker to improve the diagnostic accuracy of thyroid cancer. Methods We used pyrosequencing and quantitative real-time PCR (qRT-PCT) approaches to examine BRAFV600E mutation and TMPRSS4 mRNA level in FNAB specimens of thyroid nodules. The detection and analysis were respectively applied to training group with 91, and test group with 88 samples. Results We demonstrated that PTC patients had an increased TMPRSS4 mRNA level as compared with benign subjects. The diagnostic sensitivity, specificity, and accuracy of TMPRSS4 were 93.33, 100, and 96.70%, respectively. Notably, compared with BRAFV600E mutation testing alone, combining with TMPRSS4 mRNA level significantly increased the diagnostic sensitivity and accuracy. Conclusions Our findings indicated BRAFV600E mutation combination with TMPRSS4 mRNA analysis can dramatically improve the sensitivity and accuracy of preoperative diagnosis of thyroid nodules.

Background and aims Protein S-sulfhydration mediated by H2 S has been shown to play important roles in several diseases. However, its precise role in liver disease and the related mechanism remain unclear. Approach and results We showed that in streptozotocin (STZ)-treated and high-fat diet (HFD)-treated low-density lipoprotein receptor-negative (LDLr-/- ) mice, the H2 S donor GYY4137 ameliorated liver injury, decreased serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, mitigated lipid deposition, and reduced hepatocyte death. Strikingly, S-sulfhydration of Kelch-like ECH-associated protein 1 (Keap1) was decreased in the livers of patients with fatty liver under diabetic conditions. In STZ+HFD-treated LDLr-/- mice and in high glucose-treated and oxidized low-density lipoprotein (ox-LDL)-treated primary mouse hepatocytes, the GYY4137-mediated increase in Keap1 S-sulfhydration induced nuclear erythroid 2-related factor 2 (Nrf2) dissociation from Keap1, which enhanced the nuclear translocation of Nrf2 itself and the consequent expression of antioxidant proteins. Keap1 Cys151 mutation significantly reduced Keap1 S-sulfhydration and abolished the hepatoprotective effects of H2 S both in vivo and in vitro. Nrf2 deficiency inhibited the H2 S-induced beneficial impacts in Nrf2-/- mice. Similarly, in CCl4 -stimulated mice, GYY4137 increased Keap1 S-sulfhydration, improved liver function, alleviated liver fibrosis, decreased hepatic oxidative stress, and activated the Nrf2 signaling pathway; and these effects were abrogated after Keap1 Cys151 mutation. Moreover, H2 S increased the binding of Nrf2 to the promoter region of LDLr-related protein 1 (Lrp1) and consequently up-regulated LRP1 expression, but these effects were disrupted by Keap1 Cys151 mutation. Conclusions H2 S-mediated Keap1 S-sulfhydration alleviates liver damage through activation of Nrf2. Hence, administration of exogenous H2 S in the form of the H2 S donor GYY4137 may be of therapeutic benefit in the context of concurrent hyperlipidemia and hyperglycemia-induced or CCl4 -stimulated liver dysfunction.

BACKGROUND The relationship between dynamic changes of myocardial injury in ST-elevation myocardial infarction (STEMI) patients and long-term prognosis is still unclear. PURPOSE To evaluate the extracellular volume fraction (ECV) in the differentiation of reversible from irreversible myocardial injury and the prediction value of left ventricular adverse remodeling in patients with STEMI after reperfusion. STUDY TYPE Prospective. POPULATION Twenty-four STEMI patients after reperfusion were included FIELD STRENGTH/SEQUENCE: 3.0 T, T1 mapping, ECV, T2 -STIR, and late gadolinium enhancement (LGE). ASSESSMENT All the patients underwent cardiac MRI at four timepoints (days 1, 3, and 7, and at 6 months). The regions of interest (ROIs) were selected at the infarcted myocardium (with/without intramyocardial hemorrhage [IMH] and microvascular obstruction [MVO]). STATISTICAL TESTS One-way analysis of variance and the Kruskal-Wallis test were used for the statistical analysis. RESULTS Native T1 of MI (without MVO/IMH) gradually decreased after reperfusion (P

BOLD imaging is a quantitative MRI technique allowing the evaluation of the balance between supply/demand in myocardial oxygenation and myocardial haemorrhage. We sought to investigate the ability of BOLD imaging to differentiate reversible from irreversible myocardial injury as well as the chronological progression of myocardial oxygenation after reperfusion in patients with ST segment elevation myocardial infarction (STEMI). Twenty-two patients (age, 60 ± 11 years; 77.3% male) with STEMI underwent cardiac MRIs on four occasions: on days 1, 3, 7 and 30 after reperfusion. BOLD MRI was obtained with a multi-echo turbo field echo (TFE) sequence on a 3-T scanner to assess myocardial oxygenation in MI. T2* value in MI with intramyocardial haemorrhage (IMH) was the lowest (9.77 ± 3.29 ms), while that of the salvaged zone was the highest (33.97 ± 3.42 ms). T2* values in salvaged myocardium demonstrated a unimodal temporal pattern from days 1 (37.91 ± 2.23 ms) to 30 (30.68 ± 1.59 ms). T2* values in the MI regions were significantly lower than those in remote myocardium, although the trends in both were constant overall. There was a slightly positive correlation between T2* in MI regions and EF (Rho = 0.27, p < 0.05) or SV (Rho = 0.22, p = 0.04) and a slightly negative correlation between T2* in salvaged myocardium and LVEDV (Rho = – 0.23, p < 0.05). BOLD MRI performed in post-STEMI patients allows accurate evaluation of myocardial damage severity and could differentiate reversible from irreversible myocardial injury. The increased T2* values may imply the pathophysiological mechanism of salvaged myocardium. BOLD MRI could represent a more accurate alternative to the other currently available options. • Myocardial oxygenation and haemorrhage after myocardial infarction affect BOLD MRI values • BOLD MRI could be used to differentiate irreversible from reversible myocardial damage • Changed oxygenation implies the pathophysiological mechanism of salvaged myocardium

This study aimed to examine the mediating role of rumination on the relationship between neuroticism and anxiety–depression among a sample of 405 elderly adults from China. The participants completed a questionnaire packet containing neuroticism, ruminative response, and depression and anxiety scales. Path analysis was adopted to test the mediating effects, and bootstrap methods were applied to assess the magnitude of indirect effects. Results showed that anxiety and depression were positively correlated with neuroticism and rumination. Neuroticism positively influenced the symptoms of anxiety and depression, and this relationship was partially mediated by rumination. This study expounded the mediating role of rumination underlying the positive association between neuroticism and anxiety–depression in older adults.

Psychological stress has recently been described as a risk factor in the development of pancreatic cancer. Here, we reported that increased neurotransmitter adrenaline was associated with the poor survival in pancreatic cancer patients. Moreover, in the cell model study, we found adrenaline promoted pancreatic cell PANC-1 migration in a dose dependent manner. Block of the β2-adrenoreceptor with ICI118,551, significantly reduced cell migration. Further study found that adrenaline induced a cytoplasmic translocation of RNA binding protein HuR, which in turn activated TGFβ, as shown by the SBE luciferase assay and phosphorylation of Smad2/3. Either HuR knockdown or TGFβ inhibition reduced cell migration induced by adrenaline. Taken together, our study here revealed that adrenaline-HuR-TGFβ regulatory axis at least partially contributes to the psychological stress induced metastasis in PANC-1 cells, shedding light on therapeutic targeting psychological stress in improving the prognosis of pancreatic cancer.

Background: Timely primary percutaneous coronary intervention (PPCI) cannot be offered to all patients with ST-segment–elevation myocardial infarction (STEMI). Pharmaco-invasive (PhI) strategy has been proposed as a valuable alternative for eligible patients with STEMI. We conducted a randomized study to compare the efficacy and safety of a PhI strategy with half-dose fibrinolytic regimen versus PPCI in patients with STEMI. Methods: The EARLY-MYO trial (Early Routine Catheterization After Alteplase Fibrinolysis Versus Primary PCI in Acute ST-Segment–Elevation Myocardial Infarction) was an investigator-initiated, prospective, multicenter, randomized, noninferiority trial comparing a PhI strategy with half-dose alteplase versus PPCI in patients with STEMI 18 to 75 years of age presenting ≤6 hours after symptom onset but with an expected PCI-related delay. The primary end point of the study was complete epicardial and myocardial reperfusion after PCI, defined as thrombolysis in myocardial infarction flow grade 3, thrombolysis in myocardial infarction myocardial perfusion grade 3, and ST-segment resolution ≥70%. We also measured infarct size and left ventricular ejection fraction with cardiac magnetic resonance and recorded 30-day clinical and safety outcomes. Results: A total of 344 patients from 7 centers were randomized to PhI (n=171) or PPCI (n=173). PhI was noninferior (and even superior) to PPCI for the primary end point (34.2% versus 22.8%, P noninferiority P superiority =0.022), with no significant differences in the frequency of the individual components of the combined end point: thrombolysis in myocardial infarction flow 3 (91.3% versus 89.2%, P =0.580), thrombolysis in myocardial infarction myocardial perfusion grade 3 (65.8% versus 62.9%, P =0.730), and ST-segment resolution ≥70% (50.9% versus 45.5%, P =0.377). Infarct size (23.3%±11.3% versus 25.8%±13.7%, P =0.101) and left ventricular ejection fraction (52.2%±11.0% versus 51.4%±12.0%, P =0.562) were similar in both groups. No significant differences occurred in 30-day rates of total death (0.6% versus 1.2%, P =1.0), reinfarction (0.6% versus 0.6%, P =1.0), heart failure (13.5% versus 16.2%, P =0.545), major bleeding events (0.6% versus 0%, P =0.497), or intracranial hemorrhage (0% versus 0%), but minor bleeding (26.9% versus 11.0%, P Conclusions: For patients with STEMI presenting ≤6 hours after symptom onset and with an expected PCI-related delay, a PhI strategy with half-dose alteplase and timely PCI offers more complete epicardial and myocardial reperfusion when compared with PPCI. Adequately powered trials with this reperfusion strategy to assess clinical and safety outcomes are warranted. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01930682.

Background Elevated homocysteine (Hcy) levels showed increasing significance as the predisposing factor for the pathogenesis of atherosclerotic sequelae, including cardiovascular mortality, coronary artery disease, and stroke. There is increasing evidence linking plasma Hcy levels and heart failure (HF). The association between the elevated level of plasma Hcy and HF was examined by meta-analysis and systematic review in this study. Methods The PubMed and ScienceDirect databases until April 2020 were utilized to collect previous literature on plasma Hcy levels and the potential relation to HF. The pooled effects were evaluated depending on standardized mean differences (SMDs) with 95% confidence intervals (CIs), and the calculation was performed using Stata 12 software. Potential sources of heterogeneity were assessed with subgroup analysis and sensitivity analysis. Results A total of 12 research projects including 5506 subjects were selected. For pooled effect, the results confirmed that patients with HF had higher Hcy levels than the control subjects (SMD,1.148 and 95%CI, [0.715, 1.581]). Based on the classification of New York Heart Association (NYHA), the Hcy levels for the group of NYHA I or II (SMD, 1.484 and 95% CI, [0.442, 2.527]) and the group of NYHA III or IV (SMD, 3.361 and 95% CI, [1.902, 4.820]) were significantly increased compared to controls, while the increase was more intensive for the group of NYHA III or IV. Subgroup analyses revealed similar results. Conclusion Our meta-analysis identified that plasma Hcy levels were significantly elevated in HF patients compared to control subjects, which is positively related to the advancement of NYHA class.

The aim of this study is to investigate the effect of 5-aminosalicylic acid (5-ASA) on monocrotaline (MCT)-induced pulmonary arterial hypertension (PAH) in rats and its molecular mechanism. Sixty male Sprague–Dawley rats (250–300 g) were evenly randomized into six groups: control group; PAH group induced by MCT intraperitoneal injection (50 mg/kg) on day 1; and four PAH groups treated for 30 days from day 2 with 5-ASA at 50 (5-ASA-50 group), 100 (5-ASA-100 group), 150 (5-ASA-150 group), and 200 mg/kg/day (5-ASA-200 group), respectively. Body mass, weight increment, survival rates, pulmonary artery pressure (PAP), right ventricular hypertrophy index (RVHI), and the signal pathway regulated by 5-ASA were assessed. (1) Compared with the control group, the PAH group had lower body mass and weight increment, and relative to the latter, 5-ASA-treated groups had larger body mass and weight increment except for groups 5-ASA-150 and 5-ASA-200 and greater overall survival rates; (2) SPAP, DPAP, MPAP, and RVHI in 5-ASA-treated groups, except for MPAP and RVHI in 5-ASA-200 group, were lower than those in the PAH group; (3) compared with the PAH group, Nur77 expression in the pulmonary arteries of 5-ASA-treated groups was increased; and (4) expression of inflammatory mediators (NF-κB p65) was lower, while that of IκBα was higher in the pulmonary arteries of 5-ASA-treated groups and control group than that in the PAH group (all P

The effect of glucagon-like peptide-1 (GLP-1) treatment in patients with type 2 diabetes mellitus (T2DM) remains controversial. The purpose of this study was to compare the effect of GLP-1 and placebo/conventional antidiabetic agents on cardiovascular risk in T2DM patients. PubMed, EmBase and the Cochrane Library were searched to identify its eligible studies as well as manual searches for the reliability of this study. All eligible trials were performed in T2DM patients who received GLP-1 therapy or placebo/conventional antidiabetic agents. The reported outcomes included major cardiovascular events (MACE), and total mortality. Of 490 identified studies, we included 13 trials reporting data on 11,943 T2DM patients. Overall, the pooled results suggested that GLP-1 therapy has no or little effect on MACE (RR: 0.99; 95% CI: 0.88-1.12; P=0.872) and total mortality (RR: 0.90; 95% CI: 0.70-1.15; P=0.399). Furthermore, sensitivity analysis indicated that GLP-1 was associated with lower incidence of total mortality (RR: 0.28; 95% CI: 0.08-0.93; P=0.037). We concluded that GLP-1 therapy was not associated with MACE and total mortality compared with placebo or antidiabetic agents.

Purpose The following study evaluated the diagnostic value of myocardial perfusion in patients with acute myocardial infarction (AMI) and “infarct-like myocarditis” using Intravoxel Incoherent Motion-Diffusion Weighted Imaging (IVIM-DWI imaging). Method CMR data from 20 patients with suspected AMI, 20 patients with “infarct-like myocarditis” and 20 volunteers were retrospectively analyzed. IVIM-DWI data were acquired using multi-b value single-shot spin-echo echo-planar imaging sequence. IVIM-DWI data were generated according to the 16-segments AHA-model. Cine sequences covering left and right ventricle in short axis and three long axis were analyzed using a dedicated tissue-tracking algorithm. Results Overall, the AMI T2+ segments exhibited decreased apparent diffusion coefficient (ADC), ADCslow, ADC fast and f values (1.39 ± 0.23 μm2/ms, 1.36 ± 0.23 μm2/ms, 70.77 ± 7.04 μm2/ms, and 0.1243 ± 0.01, respectively) compared to infarct-like myocarditis T2+ (1.48 ± 0.11 μm2/ms, 1.44 ± 0.11 μm2/ms, 87.66 ± 12.50 μm2/ms, and 0.1411 ± 0.02, respectively) and normal controls (1.55 ± 0.07 μm2/ms, 1.52 ± 0.06 μm2/ms, 108.84 ± 4.06 μm2/ms, and 0.1599 ± 0.01, respectively) (all p Conclusion These findings prove that IVIM-DWI may be used as a reliable sequence for evaluation of different myocardial perfusion patterns in AMI and infarct-like myocarditis. AMI may exhibit lower myocardial perfusion status compared to infarct-like myocarditis due to different pathophysiological process.

IntroductionThe detection rate of somatic symptom disorder (SSD) in general hospitals is unsatisfactory. Self-report questionnaires that assess both somatic symptoms and psychological characteristics will improve the process of screening for SSD. The Somatic Symptom Scale-China (SSS-CN) questionnaire has been developed to meet this urgent clinical demand. The aim of this research is to validate the self-reported SSS-CN as a timely and practical instrument that can be used to identify SSD and to assess the severity of this disorder.Methods and analysisAt least 852 patients without organic disease but presenting physical discomfort will be recruited at a general hospital. Each patient will undergo aDiagnostic and Statistical Manual of Mental Disorders, 5th Edition(DSM-5)-guided physician diagnosis, including disease identification and severity assessment, as the reference standard. This research will compare the diagnostic performance of the SSS-CN for SSD, the Patient Health Questionnaire-15 (PHQ-15) and other SSD-related questionnaires. Statistical tests to measure the area under the curve (AUC) and volume under the surface of the receiver operating curve will be used to assess the accuracy of the SSD identification and the severity assessment, respectively. In addition to this standard diagnostic study, we will conduct follow-up investigations to explore the effectiveness of the SSS-CN in monitoring treatment effects.Ethics and disseminationEthical approval was obtained from the Renji Hospital Human Research Ethics Committee, approval number 2 015 016. The findings of this study will be disseminated via peer-reviewed journals and presented at international conferences.Trial registration numberNCT03513185.

Purpose To investigate the feasibility and diagnostic value of intravoxel incoherent motion (IVIM) in the assessment of myocardial fibrosis in hypertrophic cardiomyopathy (HCM) patients. Methods Fifty-five HCM patients underwent IVIM diffusion-weighted cardiovascular resonance imaging; Cine, T1 mapping, IVIM and late gadolinium enhancement (LGE) were performed. The relationship of strain, pre T1, extracellular volume (ECV), IVIM-derived parameters (D, D* and f) and LGE were analyzed based on 16 American Heart Association segments. Abnormal segments of myocardial fibrosis were defined as: the presence of LGE (LGE+) or ECV ≥ 29.6 %. Results D parameter was significantly increased in LGE + vs LGE- (1.89 ± 0.14 μm2/ms vs. 1.63 ± 0.12 μm2/ms, p Conclusions : IVIM DW-CMR has proven to be ingenious in the investigation of myocardial fibrosis; D* and f parameters may have potential value to assess the perfusion status of fibrotic regions in HCM patients.

Pulmonary arterial hypertension (PAH) is a severe complication of systemic lupus erythematosus (SLE), with unclear etiopathogenesis. We evaluated the role of macrophage migration inhibitory factor (MIF), which has been implicated in idiopathic pulmonary hypertension (PH), in SLE-associated PAH. Circulating MIF was measured in SLE patients, SLE-PAH patients, and healthy donors. In situ pulmonary artery MIF protein expression was determined in spontaneous SLE mice (MRL/lpr) and hypoxia-induced C57BL/6J mice. Daily MIF098 was administered to C57BL/6J mice, and these mice were maintained in a hypoxic chamber for 4 weeks. The right ventricular systolic pressure (RVSP) and pathological characteristics of the pulmonary artery (PA), such as hyperproliferation, muscularization, and fibrosis were then measured in each group of mice. Data were also obtained in vitro using pulmonary smooth muscle cells (PASMC) challenged with platelet-derived growth factor (PDGF)-BB or 1% O2 hypoxia. As a result, circulating MIF was elevated in SLE-PAH patients compared with SLE patients or healthy donors. Higher RVSP SLE mice produced more MIF protein than lower RVSP SLE mice in the pulmonary artery. MIF098 decreased RVSP and inhibited distal pulmonary artery hyperproliferation, muscularization, and collagen deposition in hypoxia challenged mice. In addition, MIF098 inhibited PASMC proliferation and migration by regulating mitogen-activated protein kinase/extracellular signal-regulated kinase 1/2 (MAPK/ERK1/2) signal- and cell-cycle-related proteins. MIF098 also reduced collagen synthesis by inhibiting the TGFβ1/Smad2/Smad3 pathway in cell-based experiments. In conclusion, MIF may serve as a biomarker and a therapeutic target of SLE-associated PAH. Pharmacologic MIF antagonism may be an effective means to ameliorate SLE-PAH.

Background The association between mean platelet volume (MPV) and coronary plaque vulnerability in patients with non-ST-elevation ACS (NSTE-ACS) has not been investigated. We performed a retrospective study to evaluate the association between MPV and plaque vulnerability using optical coherence tomography (OCT). Methods Consecutive NSTE-ACS patients who underwent pre-intervention OCT examination in our center were included in this study. Features of coronary plaques in the culprit arteries were classified as rupture, nonrupture with thin-cap fibroatheroma (TCFA), and nonrupture and non-TCFA. ROC analyses were used to determine the predictive efficacy of MPV for plaque rupture, and multivariate logistic regression analysis was performed to evaluate the potential independent predictors of plaque vulnerability. Results Overall, 94 patients were included in this study. We identified 17 patients with plaque rupture, 10 with nonrupture with TCFA, and 67 with nonrupture and non-TCFA. ROC analyses showed that MPV ≥ 10.5 fL was predictive of plaque rupture in NSTE-ACS patients. Univariate analyses indicated that patients with higher MPV (≥ 10.5 fL) had higher body mass index and poorer lipid profiles compared to those with lower MPV. Moreover, those with higher MPV had higher incidences of plaque rupture and thrombosis (both P