Aims After myocardial infarction (MI), injured cardiomyocytes recruit neutrophils and monocytes/macrophages to myocardium, which in turn initiates inflammatory and reparative cascades, respectively. Either insufficient or excessive inflammation impairs cardiac healing. As an endogenous inhibitor of neutrophil adhesion, EDIL3 plays a crucial role in inflammatory regulation. However, the role of EDIL3 in MI remains obscure. We aimed to define the role of EDIL3 in cardiac remodeling after MI. Methods and Results Serum EDIL3 levels in MI patients were negatively associated with MI biomarkers. Consistently, WT mice after MI showed low levels of cardiac EDIL3. Compared with WT mice, Edil3-/- mice showed improvement of post-MI adverse remodeling, as they exhibited lower mortality, better cardiac function, shorter scar length and smaller LV cavity. Accordingly, infarcted hearts of Edil3-/- mice contained fewer cellular debris and lower amounts of fibrosis content, with decreased collagen I/III expression and the percentage of α-smooth muscle actin (α-SMA) myofibroblasts. Mechanistically, EDIL3 deficiency did not affect the recruitment of monocytes or T cells, but enhanced neutrophil recruitment and following expansion of pro-inflammatory Mertk-MHC-IIlo-int (myeloid-epithelial-reproductive tyrosine kinase/major histocompatibility complex II) macrophages. The injection of neutrophil-specific C-X-C motif chemokine receptor 2 (CXCR2) antagonist eliminated the differences in macrophage polarization and cardiac function between WT and Edil3-/- mice after MI. Neutrophil extracellular traps (NETs), which were more abundant in the hearts of Edil3-/- mice, contributed to Mertk-MHC-IIlo-int polarization via toll-like receptor 9 pathway. The inhibition of NET formation by treatment of neutrophil elastase inhibitor or DNase I impaired macrophage polarization, increased cellular debris and aggravated cardiac adverse remodeling, thus removed the differences of cardiac function between WT and Edil3-/- mice. Totally, EDIL3 plays an important role in NET-primed macrophage polarization and cardiac remodeling during MI. Conclusion We not only reveal that EDIL3 deficiency ameliorates adverse cardiac healing via NET-mediated pro-inflammatory macrophage polarization but also discover a new crosstalk between neutrophil and macrophage after MI. Translational Perspective We established EDIL3 as a critical regulator of neutrophil recruitment and macrophage polarization during post-MI cardiac remodeling. EDIL3 may be a candidate prognostic biomarker and drug target for cardiovascular diseases. The novel pathways and mechanisms revealed in this study has renewed our understanding of the role of leukocyte adhesion inhibitors in cardiovascular disease. Meanwhile, our study reaffirmed the indispensable role of inflammation in the healing process, thereby prompting the reevaluation of post-MI anti-inflammatory treatments.
BackgroundPatient initiated aggression is common among Chinese health-care workers, reaching over 10,000 incidents annually (Jinyang web. http://6d.dxy.cn/article/55497. 2013), and the tense doctor-patient relationship generates stress among medical students. Because of the paucity of data (few surveys pay attention to the effects of violence perpetrated by patients on medical students), this study aimed to characterize patient initiated aggression against medical students.MethodsIn this cross-sectional survey conducted at a medical school in West China in 2015, 157 medical students completed a self-administered questionnaire and the Short Form-36, which assesses quality of life. The associations between patient initiated aggression exposure and medical students’ career planning or quality of life were assessed using a chi-square test.ResultsOf the 157 medical students, 48 (30.6%) reported having suffered patient initiated aggression at least once during the previous year in the form of mental abuse (20.4%), offensive threat (14.6%), physical violence (8.3%), sexual harassment (verbal: 8.3% or physical: 1.6%), and extreme violence (physical violence leading to surgical treatment or hospitalization) (0.6%). Insufficient communication was the primary reason cited (27.2%). Emotional attack (mental abuse and offensive threat) occurrence differed among age groups (χ2 = 9.786, P = 0.020) and was ubiquitous among those aged >30 years old. Women were more likely than men to suffer physical violence (χ2 = 6.796, P = 0.009). Patient initiated aggression was not significantly associated with medical students’ career planning or quality of life.ConclusionsIn this study, patient initiated aggression, albeit common, as in the rest of China, did not appear to be associated with medical students’ career planning or quality of life. However, the characteristics described can inform policymaking and the design of programs to minimize patient initiated aggression occurrence.
BackgroundThe anticoagulation of atrial fibrillation catheter ablation during the perioperative stage does matter and should be treated with discretion. We aimed to assess impact of three important genes participating in vitamin K cycle (i.e. VKORC1 rs9923231, CYP4F2 rs2108622 and NQO1 rs1800566) on the daily stable warfarin dose requirement in Sichuan Han Chinese patients with catheter ablation of atrial fibrillation.MethodsA total of 222 atrial fibrillation patients taking stable warfarin therapy after catheter ablation operation were enrolled in this study. The study population included had high (≥2) risk according to the CHA2DS2-VASc risk score. Genotypes of VKORC1 rs9923231, CYP4F2 rs2108622 and NQO1 rs1800566 were analyzed by using the polymerase chain reaction restriction fragment length polymorphism method (PCR-RFLP). Multiple linear regression analysis was applied to depict the impact of VKORC1 rs9923231, CYP4F2 rs2108622 and NQO1 rs1800566 on the daily stable warfarin dose requirement.ResultsCarriers of VKORC1 rs9923231 AG/GG genotypes required significantly higher warfarin dose (3.03 ± 0.28 mg/day, 7.19 mg/day, respectively) than AA carriers (2.52 ± 0.07 mg/day; P < 0.001). Carriers of CYP4F2 rs2108622 CT/TT genotypes required significantly higher warfarin dose (3.38 ± 0.22 mg/day, 2.79 ± 0.19 mg/day, respectively) than CC carriers (2.41 ± 0.08 mg/day; P < 0.001). However, the warfarin dose for carriers of NQO1 rs1800566 CT/TT genotypes (2.46 ± 0.24 mg/day, 3.01 ± 0.27 mg/day, respectively) was not significantly higher than that for the CC carriers (2.33 ± 0.1 mg/day). The multiple linear regression model including genotypes and demographic characteristics, could explain 20.1% of individual variations in the daily stable warfarin dose in Sichuan Han Chinese. VKORC1 rs9923231 contributed most (15%) to the individual variations in daily stable warfarin dose, while CYP4F2 rs2108622 contributed least (3%).ConclusionNQO1 rs1800566 is not a significant genetic factor of warfarin dose for Han Chinese, whereas VKORC1 rs9923231 and CYP4F2 rs2108622 are significant genetic factors, which could explain 15% and approximately 3% of individual variations in the daily stable warfarin dose respectively.
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 < .05). Lower rates of bleeding were significantly observed in NOAC group (OR, 0.85; 95% CI, 0.75–0.97; P < .05). In AF patients with moderate renal impairment, similar results were revealed (OR for stroke or systemic embolism, 0.80; 95% CI, 0.67–0.95, P < .05; OR for major bleeding, 0.78; 95% CI, 0.59–1.03; P = .07). During the follow-up, pooled data revealed that NOAC showed a less renal toxicity, but the difference did not reach statistical significance (creatinine clearance decline: −0.12 mL/min [−0.84, 0.61 mL/min]). We have revealed that the NOACs were associated with significantly lower rates of stroke or systemic embolism (hazard ratio [HR], 0.66; 95% CI, 0.42–0.89; P < .05) and lower rates of bleeding (HR, 0.93; 95% CI, 0.70–1.16; P = .153) in AF patients with worsening renal function. Conclusions NOAC may have the potentiality to be at least as effective as warfarin and may equal safety outcomes in AF patients with renal impairment. Renal decline during therapeutics may be less likely happened in NOAC than warfarin dose. NOAC may reveal good efficacy and safety outcomes in these scenarios. Further detailed research is needed to gain more clear profile on this new anticoagulant.
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