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Growing evidences have revealed that a histone deacetylase inhibitor (HDACi), suberoylanilide hydroxamic acid (SAHA) has anti-fibrotic effect in different diseases. In this study, we first evaluated whether SAHA could suppress cardiac fibrosis. Mice with MI-induced cardiac fibrosis were treated with SAHA by intraperitoneal injection and their cardiac function was improved after SAHA treatment. Results of western blotting and qRT-PCR in heart tissues suggested that TGFβ1/P38 pathway was activated in MI mice, and this effect was reversed by SAHA. Cell proliferation assay suggested that SAHA could suppress TGF-β1-induced cardiac fibroblasts proliferation. Furthermore, results of western blotting and qRT-PCR in cardiac fibroblasts depicted that SAHA may exert its anti-fibrotic effect through inhibiting TGF-β1-induced P38 phosphorylation by promoting DUSP4 expression. Our findings may substantiate SAHA as a promising treatment for MI-induced cardiac fibrosis., (© 2021. The Author(s).)

Objective: Presently, an effective model to predict long-term cardiac mortality in patients with hypertrophic obstructive cardiomyopathy (HOCM) is lacking. Therefore, the objective of this study was to evaluate the predictive value of the modified Age, Creatinine clearance, and Ejection Fraction (mACEF) score for long-term cardiac mortality in patients with HOCM., Methods: Two hundred and ninety two patients with HOCM treated non-invasively were enrolled in this study, all of whom had intact medical information., Results: Over a median follow-up period of 41.9 months, 28 cardiac deaths occurred. In univariate Cox regression analysis, the mACEF score was associated with long-term cardiac death [hazard ratio (HR)=1.795, 95% confidence interval (CI) 1.518-2.124, p<0.001]. Multiple Cox regression analysis identified the mACEF score as an independent risk factor for long-term cardiac death (adjusted HR=1.372, 95% CI 1.076-1.749, p=0.011). Analysis of the receiver operating characteristic (ROC) for long-term cardiac death showed that the mACEF score had a considerable predictive value (area under ROC 0.844, sensitivity 89.29%, specificity 75.00%) with an optimum cut-off value of 0.96. The study population was divided into high-risk (mACEF score ≥0.96, n=91) and low-risk (mACEF score <0.96, n=201) groups according to the optimum cut-off value. Kaplan-Meier survival analysis was performed and showed a dramatic higher rate of long-term cardiac mortality in the high-risk group than in the low-risk group (27.4% vs. 1.7%, p<0.001 by log-rank test)., Conclusion: The mACEF score has a considerable predictive value for long-term cardiac mortality in patients with HOCM treated non-invasively. A mACEF score ≥0.96 could be considered as a sign of poor prognosis in patients with HOCM.

Purpose: Thyroid dysfunction contributes to adverse events in several types of cardiovascular diseases. The aim of the present study is to determine whether thyroid status is associated with the prognosis of patients with acute myocardial infarction (AMI)., Methods: The present cohort arose from the China PEACE‑Prospective AMI study. Based on the evaluation of thyroid status, participants were divided into euthyroid, hypothyroid, and hyperthyroid groups. A total of 2569 AMI patients met the inclusion criteria of our present study. The primary outcomes were the 12-month composite cardiovascular endpoint (CCVE, a composite of all-cause death, myocardial infarction, revascularization, and heart failure) and the composite cardio-cerebral vascular endpoint (CCCVE, comprising CCVE and stroke)., Results: Of the entire cohort, 431 patients (16.8%) confirmed hypothyroid status and 102 (4.0%) were at hyperthyroid status. There were total 594 CCVEs (23.1%) and 687 CCCVEs (26.7%) in the general population. After adjusting conventional risk factors, AMI patients from the hypothyroid status group were at increased risk of the two composite endpoints, compared with euthyroid individuals (CCVE, HR:1.337, 95%CI: 1.097-1.630; CCCVE, HR:1.336, 95%CI: 1.111-1.607). However, no significant increased trends of the two composite endpoints could be observed in hyperthyroid group. Furthermore, hypothyroid status was also independently associated with a higher risk of revascularization (HR: 1.648, 95%CI: 1.047-2.595) and heart failure (HR: 1.382, 95%CI: 1.066-1.792)., Conclusion: Compared with euthyroid status, hypothyroid status has an independent predicting value for adverse cardiovascular events in AMI patients. Further investigations are required to illustrate whether treatment of thyroid dysfunction could improve the prognosis of AMI patients., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Dorsal raphe (DR) and median raphe (MR) 5-HT neurons are two distinct sub-systems known to be regulated by 5-HT 1A and 5-HT 1B auto-receptors. Whether the auto-receptors in each sub-system are functionally altered in depressive-like state remains unknown. The present study is aimed to study a specific circuit (DR-ventral hippocampus and MR-dorsal hippocampus) within each sub-system to investigate changes in receptor sensitivity in the pathogenesis of depression. A mouse model of depression was developed through the social defeat paradigm, and was then treated with fluoxetine (FLX). 5-HT 1A auto-receptor in the neuronal cell body (DR or MR) and 5-HT 1B auto-receptor in the axonal terminal (ventral or dorsal hippocampus) were directly targeted by local perfusion of antagonists (5-HT 1A : WAY100635; 5-HT 1B : GR127935) through reverse microdialysis. Time courses of dialysate 5-HT measured at the axonal terminal were subsequently determined for each circuit. At baseline, 5-HT 1A and 5-HT 1B antagonists dose-dependently increased dialysate 5-HT, with sub-circuit specificity. In the depressive-like state, greater increases in dialysate 5-HT were observed only in the DR-ventral hippocampus circuit following local delivery of both antagonists, which were then fully restored following the FLX treatment. In contrast, no changes were observed in the MR-dorsal hippocampus circuit. Our results demonstrate differential changes in sensitivities of 5-HT 1A and 5-HT 1B auto-receptors in the DR-ventral hippocampus and MR-dorsal hippocampus circuits. 5-HT 1A and 5-HT 1B auto-receptors in the DR-ventral hippocampus circuit are sensitized in the depressive-like state. Taken together, these results suggest that the DR sub-system maybe the neural substrate mediating depressive phenotypes., Competing Interests: Declaration of Competing Interest The authors have declared that no competing interests exist., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The effect of dual antiplatelet therapy, clopidogrel combined with aspirin, was influenced by CYP2C19 gene mutation and heterogeneity of population. Related studies remained controversial and limited, especially in Chinese. Total 3295 unrelated ACS Chinese patients undergoing percutaneous coronary intervention (PCI) were recruited and followed up to 1 year. Meanwhile, baseline and clinical data were retrieved. CYP2C19*2 and *3 were genotyped by sequencing. Associations of variants and metabolic types with platelet reactivity (PR) were analyzed by a logistic regression model. And, a Cox proportional hazards model was utilized to analyze survival data. Confounders included gender, age, smoking status, dosage of aspirin and clopidogrel, and BMI. It was found that patients with allele A in CYP2C19*2 and *3 were susceptibility to high PR (OR, 95%CI and P values were 1.34, 1.20-1.50, <0.0001 and 1.42, 1.13-1.79, 0.0029, respectively) after taking clopidogrel. The PR increased along with the number of loss of function (LOF) allele increased and did in order of haplotype*1, *2, and *3. This research suggested that LOF alleles and risk haplotypes in CYP2C19 could significantly attenuate the response to clopidogrel, which resulted in platelet aggregation.

The amygdala is a limbic structure that is involved in many brain functions, including emotion, learning and memory. It has been reported that melanopsin-expressing retinal ganglion cells (ipRGCs) innervate the medial amygdala (MeA). However, whether conventional RGCs (cRGCs) project to the MeA remains unknown. The goal of this study was to determine if cRGCs project to the MeA and to determine the morphological properties of MeA-projecting RGCs (MeA-RGCs). Retrogradely labeled RGCs in whole-mount retinas were intracellularly injected to reveal their dendritic morphologies. Immunohistochemical staining was performed to selectively label ipRGCs (MeA-ipRGCs) and cRGCs (MeA-cRGCs). The results showed that 95.7% of the retrogradely labeled cells were cRGCs and that the rest were ipRGCs. Specifically, MeA-cRGCs consist of two morphological types. The majority of them exhibit small but dense dendritic fields and diffuse ramification patterns as previously reported in RG B2 (95%), while the rest exhibit small but sparse dendritic branching patterns resembling those of RG B3 cells (5%). MeA-ipRGCs consist of M1 and M2 subtypes. The MeA-RGCs showed an even retinal distribution patterns. The soma and dendritic field sizes of the MeA-RGCs did not vary with eccentricity. In conclusion, the present results suggest that MeA-RGCs are structurally heterogeneous. These direct RGCs that input to the MeA could be important for regulating amygdala functions.

Background: A variety of risk models have been developed to predict acute myocardial infarction (AMI) in-hospital mortality risk. As a distinct, higher-risk population, women with AMI have different risk profiles from their men counterparts. Published researches have indicated that the interaction between variables in these models for in-hospital mortality and gender are significant. Due to the interaction and gender differences, the predicting value of these risk models for women could be controversial., Methods: Databases from the China Patient-centered Evaluative Assessment of Cardiac Events (China PEACE) Retrospective AMI Study were utilized for model derivation (n=16,100, women were 4896) and databases from the China PEACE Prospective AMI Study for model validation (n=6207, women were 2090). A multivariable backward stepwise logistic regression was used to examine correlates of in-hospital mortality, and the variables were subsequently weighted and integrated into a scoring system., Results: We constructed a novel risk-predicting tool to estimate the baseline risk of in-hospital mortality among women with AMI. The risk score includes 8 variables [age, systolic blood pressure, heart rate, initial glomerular filtration rate (GFR), serum glucose, Killip class, cardiac arrest, ventricular tachycardia/ventricular fibrillation (VT/VF)]. The prognostic discriminatory capacity of the Women Acute Myocardial Infarction in-Hospital Mortality (WAMI) risk score was excellent (c statistic 0.84, 95% confidence interval [CI]: 0.83 to 0.86, p<0.001). External validation of the model showed better prognostic capacity (c statistic 0.87, 95% CI: 0.84 to 0.90, p<0.001) than the GRACE risk score (0.77, 95% CI 0.72-0.82, p<0.001) and TIMI risk score (0.72, 95% CI 0.68-0.77, p<0.001)., Conclusions: The WAMI Score is a simple robust tool for predicting the in-hospital mortality risk of women with AMI., Trial Registration: "China PEACE-Retrospective AMI Study", NCT01624883, retrospectively registered: April 2012. Date of enrolment of the first participant to the trial: June 17, 2012. "China PEACE-Prospective AMI Study", NCT01624909, prospectively registered: December 2012. Date of enrolment of the first participant to the trial: June 17, 2012., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objective: To explore the correlation between incidence of atrial fibrillation (AF) and thyroid dysfunction., Methods: Patients with stable angina pectoris with thyroid function test results hospitalized at Fuwai Hospital from 2011 Jan to 2011 Dec were included in this analysis (n = 2 541). General clinical data and related biochemical parameters were analyzed. We divided patients into 5 subgroups according to TSH levels: <0.55 mIU/L (n = 105), 0.55-2.49 mIU/L (n = 1599), 2.50-4.77 mIU/L (n = 621), 4.78-9.99 mIU/L (n = 180), >10.00 mIU/L (n = 36)., Results: A total of 157 patients were diagnosed with AF (6.8%). (1) Compare to stable angina pectoris patients without AF, stable angina pectoris patients with AF have older age (P < 0.001), higher proportion of female (P = 0.04), uric acid (P < 0.001), NT-proBNP (P = 0.001), larger left atrial diameter (P < 0.001), left ventricular end diastolic diameter (P < 0.001) and lower LVEF (P = 0.038), FT3(P = 0.002), TT3 (P < 0.001). (2) When TSH levels were less than 0.55,0.55-2.49, 2.50-4.77, 4.78-9.99 mIU/L and greater than 10.00 mIU/L, the incidence of AF were 7.6% (8/105) , 5.7% (91/1 599), 7.9% (49/621), 9.4% (17/180) and 22.2% (8/36), respectively. Both a high and a low TSH level were associated with an increased incidence of AF. After adjustment for common risk factor (age, gender and so on) , stepwise multiple logistic regression analysis revealed that TSH levels were significantly related with the incidence of AF. Compared to patients with TSH 0.55-2.49 mIU/L, the adjusted odds ratio of AF for TSH < 0.55, 2.50-4.77, 4.78-9.99, >10.00 mIU/L were 1.37 (95%CI 0.65-2.90, P = 0.415), 1.42 (95CI 0.99-2.04, P = 0.057), 1.73 (95%CI 1.01-2.97, P = 0.048), 4.74 (95%CI 2.10-10.69, P < 0.001), respectively., Conclusion: Our results show that incidence of AF increases in proportion to TSH level in patients with stable angina pectoris.