AimsFamilial hypertrophic cardiomyopathy (HCM) is one the most common heart disorders, with gene mutations in the cardiac sarcomere. Studying HCM with patient-specific induced pluripotent stem-cell (iPSC)-derived cardiomyocytes (CMs) would benefit the understanding of HCM mechanism, as well as the development of personalized therapeutic strategies.Methods and resultsTo investigate the molecular mechanism underlying the abnormal CM functions in HCM, we derived iPSCs from an HCM patient with a single missense mutation (Arginine442Glycine) in the MYH7 gene. CMs were next enriched from HCM and healthy iPSCs, followed with whole transcriptome sequencing and pathway enrichment analysis. A widespread increase of genes responsible for ‘Cell Proliferation’ was observed in HCM iPSC-CMs when compared with control iPSC-CMs. Additionally, HCM iPSC-CMs exhibited disorganized sarcomeres and electrophysiological irregularities. Furthermore, disease phenotypes of HCM iPSC-CMs were attenuated with pharmaceutical treatments.ConclusionOverall, this study explored the possible patient-specific and mutation-specific disease mechanism of HCM, and demonstrates the potential of using HCM iPSC-CMs for future development of therapeutic strategies. Additionally, the whole methodology established in this study could be utilized to study mechanisms of other human-inherited heart diseases.
The prevalence of PACG was approximately double that of POAG in adult Chinese. The rate of change of PACG prevalence with age increased more rapidly than that of POAG. The prevalence of POAG in urban was higher than that in rural. PACG was more common in women than in men.
This is the first study demonstrating that hypoglycemia was associated with comparable risk ratios in different study populations and various study endpoints, and a trend of a dose-dependent relationship between hypoglycemia severity and adverse events. The findings of this systematic review support the speculation that hypoglycemia is a risk factor for adverse vascular events and mortality.
In recent years, the role of high mobility group box‐1 (HMGB1) protein and its receptors in autoimmune diseases has received increasing attention. It has been documented that HMGB1 is associated with disease activity in patients with systemic lupus erythematosus (SLE). This study was undertaken to determine the potential role of receptor for advanced glycation end products (RAGE), one receptor for HMGB1, in the pathogenesis of SLE. Plasma levels of soluble RAGE (sRAGE) from 105 patients with clinical diagnosis of SLE and 43 healthy controls were determined by ELISA. Associations between sRAGE levels and clinical, laboratory characteristics were assessed. The data showed that plasma levels of sRAGE in patients with SLE were significantly lower than those in healthy controls (HC) (P = 0.003). Plasma sRAGE in patients receiving short‐period treatment showed an immediate decrease compared with the untreated patients (P = 0.023). In contrast, plasma sRAGE in patients receiving long‐period treatment were significantly increased compared to those with short‐period treatment (P = 0.000) and comparable with those in HC (P = 0.305). The significant decreased levels of sRAGE in patients with SLE suggest the potential association of RAGE signalling and SLE clinical pathology, whereas, long‐period antilupus treatment may counteract the decreased sRAGE levels in patients with SLE.
When lymphovascular invasion is identified in a transurethral bladder tumor resection sample, it will be present in the cystectomy sample in 65% of cases and associated with nodal metastasis in 41%. Lymphovascular invasion is a valuable histological tool in the evaluation of transurethral bladder tumor resection samples, particularly cT2 tumors, because there is significant agreement of lymphovascular invasion status at transurethral bladder tumor resection and at subsequent cystectomy.
Hypertension is the most important risk factor for stroke and stroke recurrence. However, the preferred blood pressure (BP)-lowering drug class for patients who have suffered from a stroke has yet to be determined.To investigate the relative effects of BP-lowering therapies [angiotensin-converting enzyme inhibitor (ACEI), angiotensin receptor blockers (ARB), β blockers, calcium channel blockers (CCBs), diuretics, and combinations of these drugs] in patients with a prior stroke history, we performed a systematic review and meta-analysis using both traditional frequentist and Bayesian random-effects models and meta-regression of randomized controlled trials (RCTs) on the outcomes of recurrent stroke, coronary heart disease (CHD), and any major adverse cardiac and cerebrovascular events (MACCE). Trials were identified from searches of published hypertension guidelines, electronic databases, and previous systematic reviews.Fifteen RCTs composed of 39,329 participants with previous stroke were identified. Compared with the placebo, only ACEI along with diuretics significantly reduced recurrent stroke events [odds ratio (OR) = 0.54, 95% credibility interval (95% CI) 0.33–0.90]. On the basis of the distribution of posterior probabilities, the treatment ranking consistently identified ACEI along with diuretics as the preferred BP-lowering strategy for the reduction of recurrent stroke and CHD (31% and 35%, respectively). For preventing MACCE, diuretics appeared to be the preferred agent for stroke survivors (34%). Moreover, the meta-regression analysis failed to demonstrate a statistical significance between BP reduction and all outcomes (P = 0.1618 for total stroke, 0.4933 for CHD, and 0.2411 for MACCE).Evidence from RCTs supports the use of diuretics-based treatment, especially when combined with ACEI, for the secondary prevention of recurrent stroke and any vascular events in patients who have suffered from stroke.
CD40L can potently induce ICAM-1 expression in OF cells through multiple signal pathways. The p38 MAPKs and NF-kappaB pathways may play an important permissive role in CD40L-induced ICAM-1 expression in OFs.
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