Ca²⁺ signaling regulation plays an important role in triggering and/or maintaining atrial fibrillation (AF). Little is known about the relationship of the inositol-1,4,5-triphosphate receptors (InsP₃Rs) and ryanodine receptors (RyRs) in left atrium to chronic AF. In this study, we investigated the expression and function of InsP₃R₁, InsP₃R₂ and RyR₂ in a chronic dog model of AF. AF was induced in 6 dogs by rapid right atrial pacing for 24 weeks, and a sham procedure was performed in 5 dogs (control group). The intact left atrial myocytes were used to examine the expression and function of InsP₃Rs, RyRs by BODIPY^O,R TR-X ryanodine, heparin-fluorescein conjugate, and were stimulated by caffeine, ATP to release Ca²⁺ through RyRs, InsP₃Rs separately. We also assessed the molecular components of left atrial tissue underlying the amount of RyR₂, InsP₃R₁ and InsP₃R₂ determined by RT-PCR, immunohistochemistry and Western blot analysis. In the chronic AF group, the Ca²⁺ released through RyRs is not altered, but the Ca²⁺ released through InsP₃Rs increased significantly. RyR₂ distributed in cytosol of myocytes, cellular membrane; its expression significantly decreased in AF group compared to controls. InsP₃R₁ distributed in cytosol, InsP₃R₂ distributed not only in cytosol, cellular membrane, but also in nuclear envelope and intercalated discs. The InsP₃R₁ and InsP₃R₂ expression significantly increased in chronic AF group compared to controls. These results indicated that in a chronic dog model of AF, the expression and function of RyR₂ down-regulated; on the contrary, the expression and function of InsP₃R₁, InsP₃R₂ up-regulated, and InsP₃R₂ may be the major InsP₃Rs, which regulate intracellular or even intercellular Ca²⁺ signal transmission.

Stromal interaction molecule 1 (STIM1) is the key molecule responsible for store-operated Ca entry (SOCE). Numerous studies have demonstrated that STIM1 levels appeared to be enhanced during cardiac hypertrophy. However, the mechanism underlining this process remains to be clarified. In this study, phenylephrine (PE) was employed to establish a model of hypertrophic neonatal rat cardiomyocytes (HNRCs) in vitro, and low expression of primary and mature miR-223 was detected in PE-induced HNRCs. Our results have revealed that downregulation of miR-223 by PE contributed to the increase of STIM1, which in turn induced cardiac hypertrophy. As expected, overexpression of miR-223 could prevent the increase in cell surface and reduce the mRNA levels of ANF and BNP in cardiomyocytes. To address the mechanism triggering downregulation of miR-223 under PE, we demonstrated that PE-induced inhibition of GSK-3β activity led to the activation of β-catenin, which initiates the transcription of SOX2. Increased expression of SOX2 occupied the promoter region of primary miR-223 and suppressed its transcription. Therefore, miR-223 appears to be a promising candidate for inhibiting cardiomyocyte hypertrophy, and miR-223/STIM1 axis might be one of interesting targets for the clinical treatment of hypertrophy.

SummaryTo investigate the combination of high-sensitivity C-reactive protein (hs-CRP) and Low-density lipoprotein (LDL)-C as the targets for statin treatment in patients with acute coronary syndrome (ACS). This single-center, prospective, randomized study was performed in 400 patients treated with atorvastatin 40 mg/day for 1 month and then with atorvastatin 20 mg/day as maintenance. The patients were randomized to the LDL group (LDL-C target of < 2.07 mmol/L according to the Chinese dyslipidemia guidelines) and to the LDL-CRP group (LDL-C target of < 2.07 mmol/L and hs-CRP target of < 3 mg/L). The patients were followed up for major adverse cardiac events (MACE) at 6, 12, and 18 months. The two groups had similar baseline characteristics and 391 patients completed the follow-up. No differences were found in LDL-C between the two groups, but a difference was found in hs-CRP at 12 and 18 months. There was a significant difference in revascularization (8.7% versus 3.6%, P = 0.04) and MACE (16.8% versus 9.7%; P = 0.04) between the LDL and LDL-CRP groups at 18 months. Compared to LDL-C as the single target, targeting both LDL-C and hs-CRP by statin therapy in patients with ACS could further reduce the incidence of MACE and the residual cardiovascular risk.(Int Heart J Advance Publication)

Based on the comprehensive utilization situation of fly ash in some countries, the contents and characteristics of the existing fly ash comprehensive utilization standard systems of these countries were discussed and compared, so as to provide guidance and suggestions for improving the standard system and the comprehensive utilization of fly ash in China. The average comprehensive utilization rate of fly ash in China is 70%, which is mainly used in building materials, but is relatively low in road, backfill and other scopes. Compared with developed countries, the scope and limit value of indexes involved in the standards of fly ash in China are loose, and the fields involved are mostly traditional building materials and infrastructure construction. The comprehensive utilization of fly ash of China can be improved from the following points: the indexes investigated in standards should reflect and conform to the particularity of China; the comprehensive utilization standard of fly ash should be more suitable for the local region; the power plants should actively explore and improve their own comprehensive utilization.

The SVC is an uncommon site of origin for focal AT (1.7%). There were consistent P-wave morphology and endocardial activation associated with this type of AT. The SVC focal ablation is safe and effective. Long-term success was achieved with focal ablation in all patients.