Erratum: Estradiol Modulates the Expression Pattern of Myosin Heavy Chain Subtypes via an ERα-Mediated Pathway in Muscle-Derived Tissues and Satellite Cells

<b><i>Background: </i></b>Muscle-derived satellite cells (MDSCs) express MHC molecules intimately related to muscle function, which is supposed to be affected by local estrogen (E₂) levels. However, cellular targets and molecular mechanisms involved are poorly understood. <b><i>Methods: </i></b>Genioglossus (GG) muscle tissues and MDSCs were derived from SHAM, ovariectomized or ovariectomized and 17 β-estradiol injected rats (n=10 ⁄ group). ERα, ERβ, MHC expression and underlying regulatory mechanisms were investigated by RT-PCR, western blot and immunohistochemistry, inter alia upon selective antagonist exposure and Si-RNA transfection. MDSC viability and cell cycle were examined by MTT and flow cytometry. <b><i>Results: </i></b>E₂ upregulated MHC-I and downregulated MHC-IIb expression in MDSCs. E₂ mediated effects on these molecules were inhibited by ERα-selective antagonist MPP and si-ERα, whereas they persisted upon exposure to ERβ-selective antagonist PHTPP. ERα was significantly higher expressed in muscle tissues compared to ERβ. ER positive stainings were fewer in the ovariectomized than in the SHAM group. Injection of E₂ only increased the positive staining of ERα, but not of ERβ. <b><i>Conclusion: </i></b>Results suggest that E₂ regulates MHC expression mainly through an ERα-mediated pathway with opposing effects on MHC-I and MHC-IIb. Thus, different hormonal processes that impact muscular pathophysiology presumably govern the functional properties of these molecules

Supplementary Material for: Drug-Eluting Stent, but Not Bare Metal Stent, Accentuates the Systematic Inflammatory Response in Patients

<b><i>Objective:</i></b> The systematic pro-inflammatory responses after percutaneous coronary intervention with drug-eluting stents (DES) remain poorly defined. Therefore, we compared the systematic pro-inflammatory state of circulating mononuclear cells (MNCs) between DES and bare metal stent (BMS) implantation. <b><i>Methods:</i></b> Patients with indications for treatment with stents were randomized in a 1:1 ratio to placement of DES or BMS. The primary endpoint was a change of pro-inflammatory state at 12 weeks post-procedure. <b><i>Results:</i></b> Thirty-six consecutive patients received DES or BMS. At 12 weeks after stent implantation, the lipid profile and high-sensitivity C-reactive protein (hs-CRP) improved significantly in both groups. The mRNA levels and plasma concentrations of interleukin-6, tumor necrosis factor-a and matrix metalloproteinase-9 were significantly elevated in the DES group, which was not observed in the BMS group. An increase in NF-γB binding activity and a decrease in PPAR-γ expression in MNCs were observed in the DES group, along with increases in IγB phosphorylation and p50 expression. However, similar changes were not observed in the BMS group. <b><i>Conclusions:</i></b> Systematic inflammatory responses were accentuated after the patients were treated percutaneously with DES, despite their improved lipid profile and hs-CRP. These data may provide fundamental information for optimizing therapeutic strategy in the era of DES

Supplementary Material for: General Anesthesia may have Similar Outcomes with Conscious Sedation in Thrombectomy Patients with Acute Ischemic Stroke: A Real-World Registry in China

<b><i>Background and Purpose:</i></b> Clinical trials showed that anesthesia may not influence the functional outcome in stroke patients with endovascular therapy; however, data are lacking in China. Using real-world registry data, our study aims to compare the effects of general anesthesia or conscious sedation on functional outcomes in stroke patients treated with thrombectomy in China. <b><i>Methods:</i></b> Consecutive patients with acute anterior circulation stroke receiving thrombectomy in 21 stroke centers between January 2014 and June 2016 were included in this study. The propensity score analysis with 1: 1 ratio was used to match the baseline variables between patients with general anesthesia and the conscious sedation. The 90-day modified Rankin Scale (mRS), symptomatic intracranial hemorrhage (sICH), and death were compared between groups. <b><i>Results:</i></b> Of the 698 patients undergoing endovascular treatment, 138 were treated with general anesthesia and 560 with conscious sedation. After propensity score matching, 114 general anesthesia and 114 conscious sedation patients were matched. The proportions of patients with 90-day mRS 0–2 were not significantly different between general anesthesia and conscious sedation groups (41.2% [47/114] vs. 46.5% [53/114], <i>p</i> = 0.470), nor were the rates of sICH (21.9% [25/114] vs. 12.3% [14/114], <i>p</i> = 0.072) and 90-day mortality (31.6% [36/114] vs. 21.9% [25/114], <i>p</i> = 0.145). <b><i>Conclusion:</i></b> Anesthesia patterns may have no significant impacts on clinical outcomes in patients with acute anterior circulation occlusion stroke undergoing endovascular treatment in the real-world practice in China

Supplementary Material for: Sex Differences in the Prevalence of and Risk Factors for Nonvascular Cognitive Function in Rural, Low-Income Elderly in Tianjin, China

<b><i>Background:</i></b> At the global level, dementia is the leading cause of dependence and disability among the elderly. Although the preponderant prevalence in women has been identified, the sex differences in risk factors were unclear. We aimed to evaluate the sex differences in the prevalence of nonvascular cognitive impairment and the risk factors among the elderly in rural China screened with the Mini-Mental State Examination (MMSE). <b><i>Methods:</i></b> Between 2014 and 2015, a population-based cross-section study was conducted to collect basic information among the elderly aged 60 years and over. Those participants with the previous history of stroke or heart disease were excluded in this study. Nonvascular cognitive impairment was assessed using the MMSE scores. <b><i>Results:</i></b> The prevalence of cognitive impairment was 32.4% overall, 25.6% in men and 38.1% in women. In the multivariate analysis, older age and lower education were risk factors both in men and in women; older, large waist circumference was a protective factor for cognitive function in men; higher blood pressure was the risk factor in women. <b><i>Conclusion:</i></b> These findings suggest that it is crucial to manage and control hypertension and improve educational attainment in order to reduce the prevalence and burden of nonvascular cognitive impairment among low-income residents, both men and women, in rural China

Supplementary Material for: Rapid Diagnosis of Imprinting Disorders Involving Copy Number Variation and Uniparental Disomy Using Genome-Wide SNP Microarrays

Imprinting disorders, such as Beckwith-Wiedemann syndrome (BWS), Prader-Willi syndrome (PWS) and Angelman syndrome (AS), can be detected via methylation analysis, methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA), or other methods. In this study, we applied single nucleotide polymorphism (SNP)-based chromosomal microarray analysis to detect copy number variations (CNVs) and uniparental disomy (UPD) events in patients with suspected imprinting disorders. Of 4 patients, 2 had a 5.25-Mb microdeletion in the 15q11.2q13.2 region, 1 had a 38.4-Mb mosaic UPD in the 11p15.4 region, and 1 had a 60-Mb detectable UPD between regions 14q13.2 and 14q32.13. Although the 14q32.2 region was classified as normal by SNP array for the 14q13 UPD patient, it turned out to be a heterodisomic UPD by short tandem repeat marker analysis. MS-MLPA analysis was performed to validate the variations. In conclusion, SNP-based microarray is an efficient alternative method for quickly and precisely diagnosing PWS, AS, BWS, and other imprinted gene-associated disorders when considering aberrations due to CNVs and most types of UPD

Supplementary Material for: Interaction of Soluble CXC Ligand 16 and Cardiac Injury Markers in Hemodialysis Patients

<p><b><i>Background:</i></b> Recent data suggest that there is a pathogenic role for CXC ligand 16 (CXCL16) in cardiovascular diseases. Little is known about circulating CXCL16 in patients with kidney dysfunction. We explored the relationships of plasma CXCL16 with cardiac injury markers in a group of dialysis patients. <b><i>Methods:</i></b> Plasma CXCL16 and C-reactive protein (CRP) were measured in 366 patients who were on maintenance hemodialysis. Cardiac injury was evaluated via measurements of the circulating B-type natriuretic peptide (BNP), N-terminal prohormone of brain natriuretic peptide (NT proBNP), Troponin I (TnI), and Troponin T (TnT). Sixty healthy subjects who were frequency matched with the patients on the basis of age and gender were recruited as healthy controls. <b><i>Results:</i></b> The mean age of the patients was 52.5 ± 12.1 years and 56.3% were male. Circulating CXCL16 was significantly higher in the patients than in the controls (patients vs. controls: 477.3 (367.0-647.1) pg/mL vs. 229.5 (203.8-254.5) pg/mL; <i>p</i> < 0.001). The log-transformed (log-) CXCL16 level was correlated with all 4 cardiac markers (log-BNP, log-NTproBNP, log-TnI, and log-TnT) with high levels of significance (all <i>p</i> < 0.001), even after extensive controls for the covariates. In contrast, CRP was correlated only with BNP (marginally) and NT proBNP and was not correlated with troponins. <b><i>Conclusion:</i></b> We showed, for the first time, highly significant relationships of circulating CXCL16 level with cardiac injury markers in dialysis patients. Our data suggest that circulating CXCL16 is possibly involved in the pathological process of cardiovascular damage in dialysis patients and may serve as a therapeutic target for cardiac protection in these patients.</p

Supplementary Material for: Common Genotypes of Long QT Syndrome in China and the Role of ECG Prediction

<br><strong><em>Objectives:</em></strong> Genetic testing, a gold standard for long QT syndrome (LQTS) diagnosis, is time-consuming and costly when all the 15 candidate genes are screened. Since genotype-specific ECG patterns are present in most LQT1-3 mutation carriers, we tested the utility of ECG-guided genotyping in a large cohort of Chinese LQTS patients. <b><i>Methods and Results:</i></b> We enrolled 230 patients (26 ± 17 years, 66% female) with a clinical diagnosis of LQTS. Genotypes were predicted as LQT1-3 based on the presence of ECG patterns typical for each genotype in 200 patients (85 LQT1, 110 LQT2 and 5 LQT3). Family-based genotype prediction was also conducted if gene-specific ECG patterns were found in other affected family members. Mutational screening identified 104 mutations (44% novel), i.e. 46 <i>KCNQ1,</i> 54 <i>KCNH2</i> and 4 <i>SCN5A </i>mutations. The overall predictive accuracy of ECG-guided genotyping was 79% (157/200) and 79% (67/85), 78% (86/110) and 80% (4/5) for LQT1, LQT2 and LQT3, respectively. The predictive accuracy was 98% (42/43) when family-based ECG assessment was performed. <b><i>Conclusions:</i></b> From this large-scale genotyping study, we found that LQT2 is the most common genotype among the Chinese. Family-based ECG-guided genotyping is highly accurate. ECG-guided genotyping is time- and cost-effective. We therefore recommend it as an optimal approach for the genetic diagnosis of LQTS

Supplementray Material for: Clinical Effectiveness and Safety Outcomes of Endovascular Treatment for Acute Anterior Circulation Ischemic Stroke in China

<strong><em>Backgrounds and Purpose:</em></strong> This study was aimed at investigating the outcomes and predictors for the poor functional outcome after endovascular treatment (EVT) in a large, mostly Asian population. <b><i>Methods:</i></b> Between January 2014 and June 2016, acute stroke patients with anterior circulation occlusion and EVT were retrospectively enrolled from 21 stroke centers in China. The main outcomes were modified Rankin Scale (0-2 as functional independence, 3-6 as poor) at 90 days, symptomatic intracranial hemorrhage (sICH) at 72 h, and death at 90 days. Logistic regression was used to identify predictors for poor functional outcome at 90 days. <b><i>Results:</i></b> Of the 698 patients, 304 (43.6%) patients had functional independence at 90 days. The sICH rate was 15.5% (108/698) and mortality rate at 90 days was 25.4% (177/698). Age (OR 1.04, 95% CI 1.02-1.07), National Institutes of Health Stroke Scale score at admission (11-20 vs. ≤10, OR 2.38, 95% CI 1.23-4.59; ≥21 vs. ≤10, OR 3.66, 95% CI 1.72-7.80), baseline<b> </b>glucose level (OR 1.09, 95% CI 1.01-1.18), onset to groin puncture >6 h (OR 1.88, 95% CI 1.06-3.31), sICH (OR 15.49, 95% CI 5.16-46.43), and pneumonia (OR 3.15, 95% CI 1.86-5.32) were independent predictors of poor functional outcomes, while good recanalization (OR 0.26, 95% CI 0.13-0.54), preoperative Alberta Stroke Program Early CT Score 8-10 (OR 0.48, 95% CI 0.28-0.83), and good collateral flow (OR 0.50, 95% CI 0.32-0.79) were protective factors. <b><i>Conclusions:</i></b> This study provides evidence in real world to support the performance of EVT in acute anterior circulation stroke patients in Chinese population. Patients with small infarct core, successful recanalization, good collateral status, and short treatment delay without sICH or pneumonia may benefit from EVT