Currently available echocardiographic reference values are derived mainly from North American and European population studies, and no echocardiographic reference values are available for the Chinese ...population. The aim of this study was to establish normal values of echocardiographic measurements of the cardiac chambers and great arteries in a nationwide, population-based cohort of healthy Han Chinese adults.
A total of 1,586 healthy Han Chinese volunteers aged 18 to 79 years were screened at 43 collaborating laboratories throughout China. Standard M-mode and two-dimensional echocardiography was performed to obtain measurements of the cardiac chambers and great arteries. The impacts of gender and age on all echocardiographic measurements were analyzed.
A total of 1,394 qualified healthy subjects (mean age, 47.3 ± 16.0 years; 678 men) were ultimately enrolled. Except for left ventricular ejection fraction, values of cardiac chamber and great arterial dimensions were significantly higher in men than in women. Most measurements of the atrial and great arterial dimensions, left ventricular wall thickness, and left ventricular mass increased with age in both men and women.
Normal reference values of cardiac dimensional parameters were established for the first time in a nationwide, population-based cohort of healthy Han Chinese adults. Because most of these parameters were found to vary with gender and age, reference values stratified for gender and age should be used in clinical practice.
Objectives The aim of this study was to test the hypothesis that angiotensin (Ang)-converting enzyme-2 (ACE2) overexpression may inhibit myocardial collagen accumulation and improve left ventricular ...(LV) remodeling and function in diabetic cardiomyopathy. Background Hyperglycemia activates the renin-Ang system, which promotes the accumulation of extracellular matrix and progression of cardiac remodeling and dysfunction. Methods Ninety male Wistar rats were divided randomly into treatment (n = 80) and control (n = 10) groups. Diabetes was induced in the treatment group by a single intraperitoneal injection of streptozotocin. Twelve weeks after streptozotocin injection, rats in the treatment group were further divided into adenovirus-ACE2, adenovirus–enhanced green fluorescent protein, losartan, and mock groups (n = 20 each). LV volume; LV systolic and diastolic function; extent of myocardial fibrosis; protein expression levels of ACE2, Ang-converting enzyme, and Ang-(1-7); and matrix metalloproteinase–2 activity were evaluated. Cardiac myocyte and fibroblast culture was performed to assess Ang-II and collagen protein expression before and after ACE2 gene transfection. Results Four weeks after ACE2 gene transfer, the adenovirus-ACE2 group showed increased ACE2 expression, matrix metalloproteinase–2 activity, and LV ejection fractions and decreased LV volumes, myocardial fibrosis, and ACE, Ang-II, and collagen expression in comparison with the adenovirus–enhanced green fluorescent protein and control groups. ACE2 was superior to losartan in improving LV remodeling and function and reducing collagen expression. The putative mechanisms may involve a shift in balance toward an inhibited fibroblast-myocyte cross-talk for collagen and transforming growth factor–beta production and enhanced collagen degradation by matrix metalloproteinase–2. Conclusions ACE2 inhibits myocardial collagen accumulation and improves LV remodeling and function in a rat model of diabetic cardiomyopathy. Thus, ACE2 provides a promising approach to the treatment of patients with diabetic cardiomyopathy.
Objectives The purpose of this study was to assess the safety and efficacy of recombinant human neuregulin-1 (rhNRG-1) in chronic heart failure (CHF) patients. Background Neuregulin-1 plays important ...roles in maintaining cardiomyocyte structure and cardiac pumping functionality and physiology. Previously, rhNRG-1 was proven to be effective in treating heart failure in animals by reducing end-diastolic volume (EDV) and end-systolic volume (ESV) and increasing left ventricular ejection fraction (LVEF%). Methods A total of 44 CHF patients designated as New York Heart Association functional class II or III were enrolled in a double-blind, randomized manner and treated with a placebo or rhNRG-1 (0.3, 0.6, or 1.2 μg/kg/day) for 10 days, in addition to standard therapies. The follow-up period was 90 days; left ventricular function and structure measured by magnetic resonance imaging were the primary end points. Results Although not statistically different from placebo, the LVEF% was significantly increased by 27.11 ± 31.12% (p = 0.009) at day 30 after rhNRG-1 treatment in the 0.6-μg/kg group, whereas it was only increased 5.83 ± 25.75% in the placebo group (p = 0.49). In addition, there were decreases in ESV (−11.58 ± 12.74%, p = 0.002) and EDV (−5.64 ± 10.03%, p = 0.05) in the 0.6-μg/kg/day group at day 30; more importantly, both ESV and EDV levels continued to decrease at day 90 (−20.79 ± 17.03% and −14.03 ± 13.17%, respectively), accompanied by a sustained increase in LVEF%. This suggests that short-term treatment with rhNRG-1 results in a long-term reversal of remodeling. The effective dose was proven to be tolerable and safe for CHF patients. Conclusions rhNRG-1 improved the cardiac function of CHF patients by increasing the LVEF% and showed the capability of antiremodeling by decreasing ESV and EDV compared with pre-treatment. (A Randomized, Double-Blind, Multi-Center, Placebo Parallel controlled, Standard Therapy Based Phase II Clinical Trial to Evaluate the Efficacy and Safety of Recombinant Human Neuregulin-1 for Injection in Patients with Chronic Heart Failure; ChiCTR-TRC-00000414 )
Objectives The goal of this study was to conduct a direct head-to-head comparison of different stem cell types in vitro for various assays of potency and in vivo for functional myocardial repair in ...the same mouse model of myocardial infarction. Background Adult stem cells of diverse origins (e.g., bone marrow, fat, heart) and antigenic identity have been studied for repair of the damaged heart, but the relative utility of the various cell types remains unclear. Methods Human cardiosphere-derived cells (CDCs), bone marrow–derived mesenchymal stem cells, adipose tissue–derived mesenchymal stem cells, and bone marrow mononuclear cells were compared. Results CDCs revealed a distinctive phenotype with uniform expression of CD105, partial expression of c-kit and CD90, and negligible expression of hematopoietic markers. In vitro, CDCs showed the greatest myogenic differentiation potency, highest angiogenic potential, and relatively high production of various angiogenic and antiapoptotic-secreted factors. In vivo, injection of CDCs into the infarcted mouse hearts resulted in superior improvement of cardiac function, the highest cell engraftment and myogenic differentiation rates, and the least-abnormal heart morphology 3 weeks after treatment. CDC-treated hearts also exhibited the lowest number of apoptotic cells. The c-kit+ subpopulation purified from CDCs produced lower levels of paracrine factors and inferior functional benefit when compared with unsorted CDCs. To validate the comparison of cells from various human donors, selected results were confirmed in cells of different types derived from individual rats. Conclusions CDCs exhibited a balanced profile of paracrine factor production and, among various comparator cell types/subpopulations, provided the greatest functional benefit in experimental myocardial infarction.
Background Previous studies have shown that individuals with schizophrenia have a greater risk for psoriasis than a typical person. This suggests that there might be a shared genetic etiology between ...the 2 conditions. We aimed to characterize the potential shared genetic susceptibility between schizophrenia and psoriasis using genome-wide marker genotype data. Methods We obtained genetic data on individuals with psoriasis, schizophrenia and control individuals. We applied a marker-based coheritability estimation procedure, polygenic score analysis, a gene set enrichment test and a least absolute shrinkage and selection operator regression model to estimate the potential shared genetic etiology between the 2 diseases. We validated the results in independent schizophrenia and psoriasis cohorts from Singapore. Results We included 1139 individuals with psoriasis, 744 with schizophrenia and 1678 controls in our analysis, and we validated the results in independent cohorts, including 441 individuals with psoriasis (and 2420 controls) and 1630 with schizophrenia (and 1860 controls). We estimated that a large fraction of schizophrenia and psoriasis risk could be attributed to common variants ( h2SNP = 29% ± 5.0%, p = 2.00 × 10−8 ), with a coheritability estimate between the traits of 21%. We identified 5 variants within the human leukocyte antigen ( HLA ) gene region, which were most likely to be associated with both diseases and collectively conferred a significant risk effect (odds ratio of highest risk quartile = 6.03, p < 2.00 × 10−16 ). We discovered that variants contributing most to the shared heritable component between psoriasis and schizophrenia were enriched in antigen processing and cell endoplasmic reticulum. Limitations Our sample size was relatively small. The findings of 5 HLA gene variants were complicated by the complex structure in the HLA region. Conclusion We found evidence for a shared genetic etiology between schizophrenia and psoriasis. The mechanism for this shared genetic basis likely involves immune and calcium signalling pathways.
Abstract Background Implantation-associated infections have increased significantly with the recent widespread use of medical implants. Treatments for these infections are not always successful ...because these infections are sometimes caused by multiantibiotic-resistant organisms. It is therefore particularly urgent to provide doctors with more effective antimicrobial agents against these antibiotic-resistant organisms. Human β-defensin 3 (hBD-3) has been shown to have strong broad-spectrum antibacterial activity. However, its effect on methicillin-resistant Staphylococcus epidermidis (MRSE) and methicillin-resistant Staphylococcus aureus (MRSA) in medical implant biofilm formation has not been reported. Methods In this study, we evaluated the effects of hBD-3 on S epidermidis ATCC 35984 (methicillin-resistant strain), MRSE287, and MRSA (ATCC43300) by evaluating bacterial adhesion, biofilm formation, and maturation. In addition, we used the spread plate method, confocal laser scanning microscopy, scanning electron microscopy, and real-time polymerase chain reaction to evaluate the effect of hBD-3. Results After evaluating biofilm adhesion and formation, we found that the number of each strain on the titanium surface was decreased in those groups exposed to 1MIC (minimum inhibitory concentration) of hBD-3 and was significantly lower than the number of colonies of the control. In the initial maturation of the biofilm, the numbers of each strain on the titanium surface from the 2MIC to 6MIC groups were significantly lower than the control. When the concentrations were further increased, hBD-3 was significantly effective against drug-resistant bacteria from the biofilms. Conclusions HBD-3 has the potential to eliminate the biofilm formation of Staphylococcus , especially antibiotic-resistant strains, effectively.
•
SCFAs alleviate the progression of AAA in both Ca
3
(PO
4
)
2
- and elastase-induced mouse AAA models.
•
Propionate expands the pool of Tregs in the cLP and enhances the cell-intrinsic ability of ...cLP-Tregs to recirculate by downregulating CD69 expression on the surface of cLP-Tregs.
•
Propionate facilitates the recirculation of cLP-Tregs from the cLP through colonic dLNs and circulating blood to the inflamed aneurysm to mitigate AAA.
Emerging evidence supports that intestinal microbial metabolite short-chain fatty acids (SCFAs) increase the pool of regulatory T cells (Tregs) in the colonic lamina propria (cLP) and protect against nonintestinal inflammatory diseases, such as atherosclerosis and post-infarction myocardial inflammation. However, whether and how SCFAs protect the inflamed aortas of subjects with abdominal aortic aneurysm (AAA) remains unclear. Here, the authors revealed the protective effect of SCFAs on AAA in mice and the expansion of Tregs in the cLP, and propionate exerted Treg-dependent protection against AAA by promoting the recirculation of cLP-Tregs through colonic draining lymph nodes (dLNs) to the inflamed aorta.
Summary Although epithelial ovarian cancer cells are eliminated by debulking surgery and chemotherapy during initial treatment, it is believed that only a subset of cancer cells, that is, cancer stem ...cells, may be an important source of tumor recurrence and drug resistance. This review highlights our current understanding of high-grade serous carcinoma, ovarian cancer stem cells, common methods for enrichment of ovarian cancer stem cells, mechanisms involved in drug resistance, and potential strategies for overcoming drug resistance, with associated potential controversies and pitfalls. We also review the potential relationship between epithelial-to-mesenchymal transition and cancer stem cells and how we can induce cancer cells to differentiate into benign stromal fibroblasts in response to certain chemotherapy drugs.
Background Saphenous vein grafts continue to be the backbone of daily coronary revascularization practice, but controversy still exists about whether to use them as an individual or sequential graft. ...We undertook a systematic review and meta-analysis of cohort studies to compare the midterm or long-term patency of sequential vein coronary bypass grafts with those of vein grafts. Methods A comprehensive search strategy was run in PubMed, Embase, the Cochrane Library, and the Chinese Biomedical Literature Database. Inclusion criteria were the following: (1) two cohorts of patients received sequential and single saphenous vein coronary bypass grafting, respectively; (2) prospective or retrospective cohort design; and (3) graft patency examined by angiography or ultrafast computed tomography. Two researchers independently performed the literature search, data extraction, and quality assessment. Results We identified 1,385 titles, reviewed 38 articles for inclusion criteria, and included 12 studies in the meta-analysis. The risk of occlusion in sequential grafts was lower (risk ratio RR = 0.67, 95% confidence interval CI 0.60 to 0.74) than that in single grafts. The risk of occlusion in side-to-side anastomoses was lower (RR = 0.52; 95% CI, 0.34 to 0.80) than that of end-to-side anastomoses for sequential vein grafts. There was no difference in occlusion between the distal end-to-side anastomoses of sequential vein grafts and those of single vein grafts (RR = 0.85; 95% CI, 0.68 to 1.06). Conclusions The midterm and long-term patency of sequential vein grafts appears to be better than that of single vein grafts and the patency of side-to-side anastomoses appears to be better than that of end-to-side anastomoses for sequential vein grafts.
To look for previously unrecognized cardiac structural abnormalities and address the genetic cause for sudden unexplained nocturnal death syndrome (SUNDS).
Data for 148 SUNDS victims and 444 controls ...(matched 1:3 on sex, race, and age of death within 1 year) were collected from Sun Yat-sen University from January 1, 1998, to December 31, 2014, to search morphological changes. An additional 17 patients with Brugada syndrome (BrS) collected from January 1, 2006, to December 31, 2014, served as a comparative disease cohort. Target-captured next-generation sequencing for 80 genes associated with arrhythmia/cardiomyopathy was performed in 44 SUNDS victims and 17 patients with BrS to characterize the molecular spectrum.
The SUNDS victims had slight but statistically significant increased heart weight and valve circumference compared with controls. Twelve of 44 SUNDS victims (SCN5A, SCN1B, CACNB2, CACNA1C, AKAP9, KCNQ1, KCNH2, KCNJ5, GATA4, NUP155, ABCC9) and 6 of 17 patients with BrS (SCN5A, CACNA1C; P>.05) carried rare variants in primary arrhythmia-susceptibility genes. Only 2 of 44 SUNDS cases compared with 5 of 17 patients with BrS hosted a rare variant in the most common BrS-causing gene, SCN5A (P=.01). Using the strict American College of Medical Genetics guideline-based definition, it was found that only 2 of 44 (KCNQ1) SUNDS and 3 of 17 (SCN5A) patients with BrS hosted a "(likely) pathogenic" variant. Fourteen of 44 SUNDS cases with cardiomyopathy-related variants had a subtle but significantly decreased circumference of cardiac valves, and tended to die on average 5 to 6 years younger compared with the remaining 30 cases (P=.02).
We present the first comprehensive autopsy evidence that SUNDS victims may have concealed cardiac morphological changes. SUNDS and BrS may result from different molecular pathological underpinnings. The distinct association between cardiomyopathy-related rare variants and SUNDS warrants further investigation.
PDF
