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Purpose A new type of visualized steerable sheath (Vizigo sheath; Biosense Webster Inc., Irvine, CA, USA) has been employed in clinical treatment. This study aimed to compare the effectiveness and safety of the Vizigo sheath to a fixed sheath (Swartz sheath; St. Jude Inc., St. Paul, MN, USA) for catheter ablation of paroxysmal atrial fibrillation (PAF). Methods We analyzed the procedural time, fluoroscopy time, contact force (CF), and initial pulmonary vein isolation (PVI) rate. After 6 months of follow-up, the success rate of ablation between the two groups was compared. Results Compared to the Swartz sheath, using the Vizigo sheath can significantly reduce the total procedural time and fluoroscopy time and increase the overall average CF, especially in the anterior left pulmonary vein (LPV), superior LPV, posterior right pulmonary vein (RPV), and superior RPV. The proportion of CF within a reasonable range in the Vizigo group was significantly higher than that in the Swartz group, especially in the anterior LPV, posterior RPV, and superior RPV. Besides, the left, right, and bilateral initial PVI rates in the Vizigo group were significantly higher. Conclusions The visualized steerable sheath for PAF catheter ablation not only reduced radiation exposure but also significantly improved CF and initial PVI rate, all of which indicated an increased rate of successful ablation.

Purpose: The flow velocity of the left atrial appendage (LAA), which is closely linked to thrombus or spontaneous echo contrast of the LAA, is one of the significant risk factors for stroke. Therefore, a non-invasive and effective method for determining LAA flow velocity that is as accurate as transesophageal echocardiography (TEE) would be of significant therapeutic value. The aim of this study was to construct nomograms for predicting lower LAA flow velocity by using non-invasive methods.Patients and methods: Data were obtained from 1910 non-valvular atrial fibrillation (NVAF) patients who underwent TEE. A nomogram was constructed by using univariate and multivariate logistic regression analysis. We calculated the area under the curve to determine how well the risk scores predicted outcomes. Furthermore, the nomogram's performance was evaluated using calibration.Results: In the training and validation groups, reduced LAA flow velocity was recorded in 344 (27.8%) and 302 (44.9%), respectively. Left atrial diameter, previous stroke or transient ischemic attack, left ventricular ejection fraction, hypertension, estimated glomerular filtration rate, and non-paroxysmal AF was found to be independent factors for decreased LAA flow velocity in multivariate analysis, and a nomogram was created by using these variables. In the training and validation groups, the nomogram had strong concordance scores of 0.760 and 0.791 in predicting decreased LAA flow velocity.Conclusion: In this study, a nomogram was constructed that incorporated five characteristics of AF patients. The nomogram may be of great value to predicting LAA flow velocity and provide a new direction for the evaluation of LAA flow velocity or function

Background New oral anticoagulants (NOACs) are effective and safe in patients with non‐valvular atrial fibrillation (NVAF). Limited evidence is available regarding outcomes for NVAF patients with stable coronary artery disease (CAD). Methods A systematic search of Medline, Embase, and the Cochrane Register was performed. Two reviewers independently performed data extraction and quality assessment using the Cochrane Collaboration risk‐of‐bias assessment tool. We evaluated all primary publications and secondary analyses comparing NOACs with any other oral anticoagulant agent for preventing stroke in patients with both NVAF and stable CAD from phase III clinical randomized control trials. The primary outcomes were stroke, systemic embolism (SE), major bleeding, and intracranial hemorrhage (ICH), and the secondary outcomes were cardiovascular (CV) death, all‐cause death, and myocardial infarction (MI). Results Four articles with a total of 19,266 patients were included in this study. The pooled results showed a relative risk for stroke/SE with NOACs of 0.83 (95% confidence interval (CI): 0.71∼0.97), for major bleeding 0.85 (95% CI: 0.63∼1.14), for ICH 0.36 (95% CI: 0.19∼0.54), for MI 1.00 (95% CI: 0.82∼1.20), for CV death 0.94 (95% CI: 0.83∼1.06), and for all‐cause death 0.95 (95% CI: 0.85∼1.07). Conclusion NOACs were effective in preventing stroke/SE and reducing the risk of ICH in patients with both NVAF and CAD. This article is protected by copyright. All rights reserved

Although outflow tract (OT) ventricular arrhythmias (VAs) are generally regarded as benign, the relationship between circulation pressure and VAs has received considerable attention in recent years. Previous studies have shown that the ratio of main pulmonary artery (MPA) to ascending aorta (AA) diameter is associated with pulmonary pressure. Here, we investigated whether an elevated MPA/AA ratio is associated with right ventricular OT (RVOT) VAs. A total of 67 patients with OT VAs (47 patients with RVOT and 20 patients with LVOT) who underwent cardiac multidetector computed tomography and radiofrequency ablation were enrolled in this study. MPA and AA diameters were measured at the level of the bifurcation of the pulmonary artery. According to the MPA/AA ratio, patients were further divided into two groups: the MPA/AA ratio abnormal group (n = 19), which is defined as MPA/AA ratio ≥ 0.9, and the MPA/AA ratio normal group (n = 48) consisting of patients with an MPA/AA ratio

Multi-electrode mapping (MEM) is increasingly applied in ablation of complex atrial arrhythmias. This study aimed to evaluate MEM for analysis and treatment of complex macroreentry atrial tachycardia (MAT).Patients with MAT related to scarring, history of heart surgery or atrial linear ablation were studied. Patients were mapped with conventional activation mapping (CAM) or MEM. After characterizing the mechanism of atrial tachycardia (AT), the ablation was performed.The study consisted of 114 eligible patients, 74 in the CAM and 40 in MEM. Compared with CAM, MEM had a shorter procedure duration (156.7 ± 59.1 ms vs. 127.3 ± 59.3 ms, P = 0.003) and mapping duration (62.6 ± 35.7 ms vs. 30.5 ± 15.3 ms, P 0.001) and more mapping points (1364.9 ± 828.7 points vs. 148.3 ± 79.6 points, P 0.001). There were no significant differences between CAM and MEM in acute ablation success rate, complication, postoperative AADs, and ablation duration. The mean disease-free survival time in CAM versus MEM was 20.8 (95% CI: 17.6-24.1) months versus 26.6 (95% CI: 22.7-30.4) months. The median disease-free survival time in the CAM versus MEM was 20.0 (95% CI: 13.9-26.1) months versus 30.0 (95% CI: 26.7-36.3) months. The AT recurrence risk of MEM was 0.522 times that of CAM (HR 95% CI: 0.282-0.968; P = 0.039).MEM is strongly recommended in ablation of complex MAT.

Interleukin-38 (IL-38) is strongly associated with chronic inflammatory diseases; however, its role in tumorigenesis is poorly understood. We demonstrated that expression of IL-38, which exhibits high expression in the skin, is downregulated in human cutaneous squamous cell carcinoma and 7,12-dimethylbenzanthracene/12-O-tetradecanoyl phorbol-13-acetate-induced mouse skin tumorigenesis. IL-38 keratinocyte-specific knockout mice displayed suppressed skin tumor formation and malignant progression. Keratinocyte-specific deletion of IL-38 was associated with reduced expression of inflammatory cytokines, leading to reduced myeloid cell infiltration into the local tumor microenvironment. IL-38 is dispensable for epidermal mutagenesis, but IL-38 keratinocyte-specific deletion reduces proliferative gene expression along with epidermal cell proliferation and hyperplasia. Mechanistically, we first demonstrated that IL-38 activates the c-Jun N-terminal kinase (JNK)/activator protein 1 signal transduction pathway to promote the expression of cancer-related inflammatory cytokines and proliferation and migration of tumor cells in an IL-1 receptor-related protein 2 (IL-1Rrp2)-dependent manner. Our findings highlight the role of IL-38 in the regulation of epidermal cell hyperplasia and pro-tumorigenic microenvironment through IL-1Rrp2/JNK and suggest IL-38/IL-1Rrp2 as a preventive and potential therapeutic target in skin cancer.

Psoriasis is a common chronic inflammatory skin disease mediated by innate and adaptive immune systems, characterized by abnormal proliferation and differentiation of epidermal keratinocytes and infiltration of inflammatory cells. Skin-specific keratinocytes are key participants in innate immunity, responding to immune cells and environmental stimulation, thereby serving an important role in the immunopathogenesis of psoriasis. Here, we present a method for inducing psoriasiform keratinocytes inflammation at transcription level with HaCaT cell line using five proinflammatory cytokines combination (M5 combination), including IL-17A, IL-22, IL-1α, TNF-α, and oncostatin M. Results demonstrate that M5 combination induced HaCaT cells showed increased levels of antimicrobial peptides (BD2, S100A7, S100A8, and S100A9), chemokines, and cytokines (CXCL1, CXCL2, CXCL8, CCL20, IL-1β, IL-6 and, IL-18). The mRNA levels of keratinocytes differentiation markers (Keratin1, Keratin10, Filaggrin, and Loricrin) were down regulated, which was consistent with the transcriptome data derived from psoriasis-like keratinocytes. The method described here, therefore, establishes an in vitro psoriasiform cutaneous inflammation at transcription level and contributes to the research for molecular pathogenesis of psoriasis.

Background and objective: Systematically review the current published literature on the impact of exercise training (ET) in chronic heart failure (CHF) patients who were conducted cardiac resynchronization therapy (CRT). Methods: PubMed, EMBASE, and the Cochrane Library of Controlled Trails databases were searched for trials comparing the additional effects of ET in CHF patients after CRT implantation with no exercise or usual care control up until 2020.03.07. We independently screened the literature, extracted data, employed the tool for the assEssment of Study qualiTy and reporting in EXercise (TESTEX) to evaluate study quality and risk of bias, and performed meta-analysis with Revman 5.3 software. Results: Eight trials were identified for qualitative analysis and 7 randomized controlled trails (RCTs) included 235 participants (120 ET; 115 controls) for quantitative analysis. The results showed that the maximal workload (mean difference [MD] 26.32 W, 95% CI 19.41–33.23; P

Adjuvant chemotherapy may cause alterations in serum lipids in postoperative breast cancer (BC) patients, but the specific alterations caused by different chemotherapy regimens remain unclear. The aim of this study was to investigate the status of serum lipids pre- and post-chemotherapy and to compare the side effects of different chemotherapy regimens on serum lipid. We retrospectively analysed the lipid profiles of 1934 consecutive postoperative BC patients who received one of the following chemotherapy regimens: (1) doxorubicin and cyclophosphamide followed by paclitaxel (AC-T); (2) epirubicin and cyclophosphamide followed by paclitaxel (EC-T); (3) cyclophosphamide and paclitaxel (TC); and (4) fluorouracil, cyclophosphamide, and epirubicin (FEC). The levels of triglycerides (TG), total cholesterols (TC), and low-density lipoprotein (LDL-C) were significantly elevated in patients who received chemotherapy regimens above (P 24 was associated with abnormal lipid profiles (TG, TC, HDL-C, LDL-C) post-chemotherapy compared with BMI ≤ 24 (P

Purpose: Endovascular treatment of femoropopliteal arterial diseases remains controversial. We conducted a Bayesian network meta-analysis of randomized controlled trials aiming to investigate the efficacy differences between paclitaxel- or sirolimus-eluting stents, covered stents, drug-coated balloons, bare metal stents, and percutaneous transluminal angioplasty. Method: MEDLINE, Embase, Ovid, and other relevant online material were searched up to October 21, 2020. Primary endpoints were primary patency and target lesion revascularization at 6, 12, and more than 24 months. Results: Thirty-eight eligible trials included 6026 patients. In terms of primary patency, drug eluting stents were ranked as the most effective treatment based on the surface under the cumulative ranking curve values at 6 (80.6), 12 (78.4), and more than 24 months (96.5) of follow-ups. In terms of target lesion revascularization, drug eluting stents were ranked as the most effective treatment based on the surface under the cumulative ranking curve values at 6 (90.3), 12 (71.3), and more than 24 months (82.1) of follow-ups. Covered stents and bare metal stents had higher ranks in target lesion revascularization than those in primary patency. Sirolimus stents had a higher rank than paclitaxel stents. Conclusion: Drug eluting stents showed encouraging results in primary patency rates and freedom from target lesion revascularization at all phases of follow-up for femoropopliteal arterial diseases. Sirolimus stents appear to be more effective in femoropopliteal segment than paclitaxel stent.

BACKGROUND: Although transvenous right ventricular (RV) endocardial lead placement is routine practice in clinical pacing, RV inaccessibility in certain clinical situations mandates the search for other sites. HYPOTHESIS: This study is aimed to verify whether left ventricular lead through coronary sinus is safe and efficient. METHODS: Based on a retrospective analysis of a single‐center series of 4 patients with inaccessibility for RV pacing, we report on the feasibility and reliability of coronary sinus (CS) pacing via left ventricular (LV) lead, which usually is used in cardiac resynchronization therapy. Four patients with valvular heart disease and bradycardias post–mechanical prosthetic tricuspid valve replacement were studied. The LV leads were implanted into the lateral vein or great cardiac vein of the CS, and all parameters were programmed postprocedure. RESULTS: In all cases procedures yielded favorable parameters, with 1 CS dissection. At long‐term follow‐up, there was no threshold increase or lead dislocation. CONCLUSIONS: LV lead implantation through the CS appears safe and efficacious in patients with inaccessibility for RV pacing.

The precise mechanism through which macroautophagy/autophagy affects psoriasis is poorly understood. Here, we found that keratinocyte (KC) autophagy, which was positively correlated with psoriatic severity in patients and mouse models and could be inhibited by mitogen-activated protein kinase (MAPK) family inactivation. The impairment of autophagic flux alleviated psoriasisform inflammation. We also found that an autophagy-based unconventional secretory pathway (autosecretion) dependent on ATG5 (autophagy related 5) and GORASP2 (golgi reassembly stacking protein 2) promoted psoriasiform KC inflammation. Moreover, the alarmin HMGB1 (high mobility group box 1) was more effective than other autosecretory proteins in regulating psoriasiform cutaneous inflammation. HMGB1 neutralization in autophagy-efficient KCs eliminated the differences in psoriasiform inflammation between Krt14(+/+)-Atg5(f/f) KCs and Krt14(Cre/+)-atg5(f/f) KCs, and conversely, recombinant HMGB1 almost completely restored psoriasiform inflammation in Krt14(Cre/+)-atg5(f/f) KCs in vivo. These results suggest that HMGB1-associated autosecretion plays a pivotal role in cutaneous inflammation. Finally, we demonstrated that Krt14(Cre/+)-hmgb1(f/f) mice displayed attenuated psoriatic inflammation due to the essential crosstalk between KC-specific HMGB1-associated autosecretion and γδT cells. Thus, this study uncovered a novel autophagy mechanism in psoriasis pathogenesis, and the findings imply the clinical significance of investigating and treating psoriasis. Abbreviations: 3-MA: 3-methyladenine; ACTB: actin beta; AGER: advanced glycosylation end-product specific receptor; Anti-HMGB1: anti-HMGB1 neutralizing antibody; Anti-IL18: anti-IL18 neutralizing antibody; Anti-IL1B: anti-IL1B neutralizing antibody; ATG5: autophagy related 5; BAF: bafilomycin A(1); BECN1: beclin 1; CASP1: caspase 1; CCL: C-C motif chemokine ligand; CsA: cyclosporine A; ctrl shRNA: lentivirus harboring shRNA against control; CXCL: C-X-C motif chemokine ligand; DCs: dendritic cells; DMEM: dulbecco’s modified Eagle’s medium; ELISA: enzyme-linked immunosorbent assay; EM: electron microscopy; FBS: fetal bovine serum; GORASP2 shRNA: lentivirus harboring shRNA against GORASP2; GORASP2/GRASP55: golgi reassembly stacking protein 2; GR1: a composite epitope between LY6 (lymphocyte antigen 6 complex) locus C1 and LY6 locus G6D antigens; H&E: hematoxylin and eosin; HMGB1: high mobility group box 1; HMGB1 shRNA: lentivirus harboring shRNA against HMGB1; IFNG/IFN-γ: interferon gamma; IL17A: interleukin 17A; IL18: interleukin 18; IL1A/IL-1α: interleukin 1 alpha; IL1B/IL-1β: interleukin 1 beta; IL22/IL-22: interleukin 22; IL23A: interleukin 23 subunit alpha; IL23R: interleukin 23 receptor; IMQ: imiquimod; ITGAM/CD11B: integrin subunit alpha M; ITGAX/CD11C: integrin subunit alpha X; IVL: involucrin; KC: keratinocyte; KD: knockdown; KO: knockout; Krt14(+/+)-Atg5(f/f) mice: mice bearing an Atg5 flox allele, in which exon 3 of the Atg5 gene is flanked by two loxP sites; Krt14(+/+)-Hmgb1(f/f): mice bearing an Hmgb1 flox allele, in which exon 2 to 4 of the Hmgb1 gene is flanked by two loxP sites; Krt14(Cre/+)-atg5(f/f) mice: keratinocyte-specific atg5 knockout mice generated by mating Atg5-floxed mice with mice expressing Cre recombinase under the control of the promoter of Krt4; Krt14(Cre/+)-hmgb1(f/f) mice: keratinocyte-specific hmgb1 knockout mice generated by mating Hmgb1-floxed mice with mice expressing Cre recombinase under the control of the promoter of Krt14; Krt14-Vegfa mice: mice expressing 164-amino acid Vegfa splice variant recombinase under the control of promoter of Krt14; LAMP1: lysosomal associated membrane protein 1; LDH: lactate dehydrogenase; LORICRIN: loricrin cornified envelope precursor protein; M5: TNF, IL1A, IL17A, IL22 and OSM in combination; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MAPK: mitogen-activated protein kinase; MKI67: marker of proliferation Ki-67; MTT: thiazolyl blue tetrazolium bromide; NFKB/NF-κB: nuclear factor kappa B; NHEKs: primary normal human epidermal keratinocytes; NS: not significant; OSM: oncostatin M; PASI: psoriasis area and severity index; PtdIns3K: class III phosphatidylinositol 3-kinase; qRT-PCR: quantitative RT-PCR; RELA/p65: RELA proto-oncogene, NF-kB subunit; rHMGB1: recombinant HMGB1; rIL18: recombinant interleukin 18; rIL1B: recombinant interleukin 1 beta; S100A: S100 calcium binding protein A; SQSTM1/p62: sequestosome 1; T17: IL17A-producing T; TCR: T-cell receptor; tcrd KO mice: tcrd (T cell receptor delta chain) knockout mice, which show deficient receptor expression in all adult lymphoid and epithelial organs; TLR: toll-like receptor; TNF/TNF-α: tumor necrosis factor; WOR: wortmannin; WT: wild-type; γδT17 cells: IL17A-producing γδ T cells.

In radiofrequency ablation near coronary arteries (CA), coronary angiography is traditionally recommended to estimate distance between catheter and CA. This study aimed to investigate the feasibility of an alternative approach for intuitively demonstrating spatial location of catheter and CA during ablation of ventricular arrhythmias (VAs) originating from aortic root (AR) and great cardiac vein (GCV). During mapping and ablation, 3D-reconstructed cardiac CT and electroanatomic mapping were merged, and distance between CA and catheter was monitored. Coronary angiography, for distance verification, was used when the distance was less than 5 mm in image integration model (IIM). Twenty-three patients (52.26 ± 17.89 years, 12 men) with ablation originating in left cusp (LCC, n = 8), right cusp (n = 2), and left-right cusp junction (LCC-RCC, n = 12) and GCV (n = 1) were enrolled. In IIM, the distance between origin and CA was less than 5 mm in 2 VAs originating in LCC and one in GCV (3/23), whereas distance for ablation was always safe (12.3–22.3 mm) for VAs of LCC-RCC origin. IIM avoided angiography use in 20 patients, reducing radiation exposure by 80.6% (650.18 ± 624.31 vs 3356.97 ± 1529.46uGycm2, P = 0.088). VA termination failed in two cases of LCC origin due to proximity to CA, and was achieved in all other patients (91.3%). No CA damage occurred during the procedures. Mapping and ablation under IIM guidance of VAs of AR and GCV origin appears feasible and safe, while avoiding angiography use particularly in VAs of LCC-RCC origin.

Introduction: Hemodynamically-instable ventricular arrhythmias (VAs) are rare in patients with pulmonary hypertension (PH). To the best of our knowledge, only 1 case has been reported so far. Moreover, the pathogenesis of this kind of arrhythmia remains obscured and its treatment is challenging. Here we report another case and presented the substrate for VAs initiation and therapeutic effect of radiofrequency ablation. Patient concerns: This is a 57-year-old man who presented paroxysmal palpitation associated with presyncope at rest. Surface electrocardiogram (ECG) revealed frequent ventricular premature contractions and non-sustained ventricular tachycardia when symptoms occurred. He also had a history of severe PH which was secondary to atrial septal defect and partial anomalous pulmonary venous drainage and suffered from obvious dyspnea when climbing stairs World Health Organization Class III (WHO Class III). Diagnosis: Hemodynamically-instable VAs associated with severe PH. Intervention: Echocardiography revealed enlargement of right ventricle (right ventricle [RV]: 43 mm). Electrophysiological examination showed the origin of VAs is next to a small low-voltage zone of RV. Radiofrequency delivery at the origin successfully terminated VAs without occurrence of complication. Outcome: The patient was free from arrhythmias and got an improvement of exercise tolerance, just with mild dyspnea when climbing stairs World Health Organization Class II (WHO class II), during six-month follow up. Lessons: This case suggests the low-voltage zone of remodeled RV, which may be secondary to increased pulmonary artery pressure, serves as the substrate for VAs initiation in patient with PH. Radiofrequency ablation can successfully terminate VAs and the termination of VAs can significantly improve the patient's impaired exercise tolerance.

Background Interleukin-1β (IL-1β) is a pivotal proinflammatory cytokine that is strongly associated with the inflammation of gout. However, the underlying mechanism through which the production of IL-1β is regulated has not been fully elucidated. Our previous work identified that miR-302b had an important immune regulatory role in bacterial lung infections. This study was conducted to evaluate the function of miR-302b on monosodium urate (MSU) crystal-induced inflammation and its mechanism. Methods The expression pattern and the immune-regulatory role of miR-302b were evaluated both in vitro and in vivo. The functional targets of miR-302b were predicted by bioinformatics, and then validated by genetic approaches. In addition, the clinical feature of miR-302b was analyzed using serum samples of patients with gouty arthritis. Results The extremely high expression of miR-302b was observed in both macrophages and mouse air membranes treated with MSU. Intriguingly, overexpression of miR-302b regulated NF-κB and caspase-1 signaling, leading to significantly attenuate MSU-induced IL-1β. By genetic analysis, miR-302b exhibited inhibitory function on IRAK4 and EphA2 by binding to their 3′-UTR regions. Corporately silencing IRAK4 and EphA2 largely impaired MSU-induced IL-1β protein production. Moreover, it was also found that miR-302b and EphA2 suppressed the migration of macrophages. Finally, it was observed that high expression of miR-302b was a general feature in patients with gouty arthritis. Conclusions These results suggest that miR-302b can regulate IL-1β production in MSU-induced inflammation by targeting NF-κB and caspase-1 signaling, and may be a potential therapeutic target for gouty arthritis. Electronic supplementary material The online version of this article (10.1186/s13075-018-1528-9) contains supplementary material, which is available to authorized users.

presenting patient characteristics, Table S2. presenting primers used in this study, Figure S1. showing function of IRAK4 and EphA2 on level of cleaved caspase-1 p20 and p-NF-κB in THP-1 cells, respectively, Figure S2. showing miR-302b represses MSU-induced IL-1β expression, and Figure S3. showing miR-302b serum levels in gouty arthritis patients and healthy controls. (DOCX 1301 kb)

Background Nonvalvular atrial fibrillation (AF) is a common arrhythmia. The treatment strategy for AF mainly includes controlling symptoms and decreasing the rate of complications. Our study aimed to evaluate the safety and efficacy of combination treatment of catheter ablation and left atrial appendage (LAA) closure (one-stop intervention) in patients with nonvalvular AF. Methods and results Thirty-four patients with symptomatic AF (mean CHA2 DS2 -VASc score 4.1 ± 1.3, mean HAS-BLED score 3.8 ± 1.2) were included. Patients first received radiofrequency-based left atrial ablation, and then the Watchman device (Boston Scientific, Natick, MA, USA) or AMPLATZER Cardiac Plug (ACP) (St. Jude Medical, Inc., St. Paul, MN, USA) was implanted for LAA closure. Follow-up was performed at 45 days and 3 months after LAA closure to assess for recurrence of AF and prevent stroke. Radiofrequency ablation and LAA closure were successful in 100% of patients without evidence of residual flow at the final transesophageal echocardiography evaluation. A Watchman device was implanted in 29 (85.3%) patients, and an ACP was implanted in five (14.7%) patients. No device-related thrombus formation or embolization was identified at the 45-day or 3-month follow-up. Serious complications, including death, transient ischemic attack, ischemic or hemorrhagic stroke, or major bleeding, were also not identified during the follow-ups. Conclusion For symptomatic patients with nonvalvular AF and a high risk of stroke, the one-stop intervention is feasible, safe, and efficacious.

BACKGROUND AND OBJECTIVES This meta-analysis was to investigate the efficacy and safety of new oral anticoagulant (NOAC) in atrial fibrillation (AF) patients with renal function insufficiency, and to explore whether renal decline occurs in AF patients with NOAC and its impact on outcomes. METHODS AND RESULTS In AF patients with mild renal insufficiency, the NOAC was associated with significantly lower rates of stroke (odds ratio [OR], 0.78; 95% confidence interval [CI], 0.67-0.91; P

After myocardial infarction (MI), injured cardiomyocytes recruit neutrophils, leading to extravasated monocytes polarized to inflammatory and reparative macrophages sequentially, which contribute to the healing and regenerative process. As an endogenous leukocyte-endothelial adhesion inhibitor, the role of EDIL3 in MI remains obscure. We found that serum EDIL3 level of MI patients was negatively associated with MI biomarkers, including CK-MB, cTnI and MGB. EDIL3−/− mice showed improved infarct healing with lower mortality, better cardiac function and decreased infarcted size compared with wild type (WT). Enhanced neutrophil infiltration resulted in the increase of Ly6Chi MHClo Mertk− macrophages, which we identified to be pro-inflammatory, protecting EDIL3−/− mice hearts from excessive fibrosis. A neutrophil infiltration antagonist not only eliminated the difference in cardiac function between WT and EDIL3−/− mice, but also reduced Ly6Chi MHClo Mertk− macrophage polarization. These data implied that improved cardiac healing was associated with increased infiltration of neutrophil and it mediated macrophage polarization. Notably, we confirmed that this polarization depended on NETs, which were more abundant in hearts and serum in EDIL3−/− mice than in WT. Indeed, self-DNA released from NETs primed the pro-inflammatory polarization of macrophages. The degradation of NETs by DNase I reduced this polarization and thus affected post-MI outcome, indicating the pivotal role of NETs in MI healing. Meanwhile, the pro-inflammatory macrophages induced apoptosis of neutrophils and restrained excessive inflammation. Our findings reveal a novel neutrophil–macrophage crosstalk essential to cardiac healing after MI.

Basic fibroblast growth factor (bFGF) and platelet-derived growth factor (PDGF) have been shown to be involved in a spectrum of cellular processes. In a previous study, we constructed a novel multigenic vector that contained two separate transcription units, each consisting of a strong promoter and an efficient polyadenylation signal. The two promoters were chosen for their ability to work simultaneously. Dual gene transfer of bFGF and PDGF in a single plasmid resulted in a significant increase in collateral blood vessel formation in a rabbit model of hind limb ischemia. The aim of the present study was to investigate the effect of this dual gene transfer strategy in a rat model of acute myocardial infarction (AMI). AMI was induced in rats by ligation of the left anterior descending coronary artery. The animals were randomly divided into four groups and treated with the following therapeutic strategies: Empty plasmid (control), plasmid encoding bFGF (PL-bFGF), plasmid encoding PDGF (PL-PDGF) or plasmid encoding bFGF and PDGF (PL-F-P). Echocardiography and histological examinations were performed 28 days subsequent to gene transfer. Dual gene therapy with bFGF and PDGF resulted in a significant angiogenic effect accompanied by vessel maturation, along with a significant reduction in infarct size and improvement in cardiac function. In a rat model of AMI, single plasmid-mediated dual gene therapy with bFGF and PDGF decreased infarct size and improved cardiac function due to the formation of functionally and morphologically mature vasculature. These results are relevant to the ongoing clinical trials involving the use of single plasmid-mediated angiogenic factors for the treatment of myocardial ischemic disease.

Epidermal growth factor receptor (EGFR) is overexpressed in a variety of human malignancies, including pancreatic cancer, breast cancer, colon cancer, and non-small cell lung cancer. Overexpression of EGFR is a predictive marker of therapeutic response and several lines of evidence suggest that EGFR is an excellent target for tumor therapy. However, the effective antitumor capacity of EGFR-specific T cells against EGFR-overexpressing tumor cells has not been fully elucidated. In our previous study, we identified an anti-EGFR single-chain variable fragment (scFv) with specific and high affinity after screening by ribosome display. In this study, the anticancer potential of anti-EGFR scFv was investigated on the basis of cell-targeted therapy. A chimeric antigen receptor (CAR) targeting EGFR was constructed and expressed on the cell membrane of T lymphocytes. These CAR-modified T cells demonstrated antitumor efficacy both in vitro and in vivo. In addition, the safety evaluation showed that CAR-modified lymphocytes have no or very minimal acute systemic toxicity. Taken together, our study provided the experimental basis for clinical application of genetically engineered lymphocytes; moreover, we also evaluate a new and interesting cell therapy protocol.

A 32-year-old woman presented with a history of palpitations over the prior 7 days. Twelve-lead ECG indicated an irregular, wide QRS complex tachycardia with a left bundle branch block (LBBB) morphology and …

A 44-year-old man was admitted to our department with chief complaint of palpitations for 1 year which had become more frequent in the preceding month. Paroxysmal atrial fibrillation was recorded by electrocardiogram (ECG) and 24-h Holter monitoring ( Panel A and Supplementary material online, Figure S1 ). Transthoracic and transoesophageal echocardiography revealed a large cystic mass ( Panels B and C , arrows; Supplementary material online, Movies S1 and S2 ) next …

A 37-year-old male patient was referred for atrioventricular nodal reentrant tachycardia ablation. Chest radiography showed enlargement …

Members of the interleukin-1 (IL-1) family play important roles in inflammation and host defense against pathogens. Here, we describe a novel member of the IL-1 family, interleukin-38 (IL-38, IL-1F10, or IL-1HY2), which was discovered in 2001. Although the functional role of IL-38 remains unclear, recent reports show that IL-38 binds to the IL-36 receptor (IL-36R) which is also targeted by the IL-36 receptor antagonist (IL-36Ra). Consequently, these two molecules have similar effects on immune cells. Here, we describe the expression of soluble and active recombinant IL-38 in Escherichia coli (E. coli). The IL-38 gene sequence was optimized for expression in E. coli and then cloned into a pEHISTEV expression vector, which has an N-terminal 6-His affinity tag under control of the T7 lac strong promoter. Optimization of culture conditions allowed induction of the recombinant fusion protein with 0.1 mM isopropyl β-D-1-thio galactoside (IPTG) at 37°C for 4h. The recombinant fusion protein was purified using an Ni affinity column and was further digested with TEV protease; the cleaved protein was purified by molecular-exclusion chromatography. Next, we measured IL-38 binding ability using functional ELISA. The purified proteins were used to immunize a New Zealand white rabbit four times to enable the production of polyclonal antibodies. The specificity of the prepared polyclonal antibodies was determined using Western blot, and the results showed they have high specificity against IL-38. Here, we describe the development of an effective and reliable method to express and purify IL-38 and anti-IL-38 antibodies. This will enable the function and structure of IL-38 to be determined.

IL-37 is a potent inhibitor of innate immunity by shifting the cytokine equilibrium away from excessive inflammation. Psoriasis is thought to be initiated by abnormal interactions between the cutaneous keratinocytes and systemic immune cells, triggering keratinocyte hyperproliferation. In the current study, we assessed IL-37 in two well-known psoriasis models: a human keratinocyte cell line (HaCaT) and the keratin 14 VEGF-A–transgenic mouse model. First, we used the HaCaT cell line, which was transiently transfected with an overexpressing IL-37 vector, and tested the effect of IL-37 on these cells using a mixture of five proinflammatory cytokines. IL-37 was effective in suppressing the production of CXCL8, IL-6, and S100A7, which were highly upregulated by the mixture of five proinflammatory cytokines. Keratin 14 VEGF-A–transgenic mice were treated with plasmid coding human IL-37 sequence–formulated cationic liposomes, and we observed potent immunosuppressive effects over the 18-d period. In this model, we observed reduced systemic IL-10 levels, local IFN-γ gene transcripts, as well as mild mast cell infiltration into the psoriatic lesions of the mice. Immunohistochemical analysis indicated that IL-37 was expressed by effector memory T cells, as well as macrophages, in human psoriatic plaques. In conclusion, our studies strongly indicate that IL-37 plays a potent immunosuppressive role in the pathogenesis of both experimental psoriasis models in vitro and in vivo by downregulating proinflammatory cytokines. Importantly, our findings highlight new therapeutic strategies that can be designed to use this immunosuppressive anti-inflammatory cytokine in psoriasis and other inflammatory cutaneous diseases.