Impact of telomere length and mitochondrial DNA copy number variants on survival of newborn cloned calves.

An established technology to create cloned animals is through the use of somatic cell nuclear transfer (SCNT), in which reprogramming the somatic cell nucleus to a totipotent state by enucleated oocyte cytoplasm is a necessary process, including telomere length reprogramming. The limitation of this technology; however, is that the live birth rate of offspring produced through SCNT is significantly lower than that of IVF. Whether and how telomere length play a role in the development of cloned animals is not well understood. Only a few studies have evaluated this association in cloned mice, and fewer still in cloned cows. In this study, we investigated the difference in telomere length as well as the abundance of some selected molecules between newborn deceased cloned calves and normal cows of different ages either produced by SCNT or via natural conception, in order to evaluate the association between telomere length and abnormal development of cloned cows. The absolute telomere length and relative mitochondrial DNA (mtDNA) copy number were determined by real-time quantitative PCR (qPCR), telomere related gene abundance by reverse-transcription quantitative PCR (RT-qPCR), and senescence-associated ß-galactosidase (SA-ß-gal) expression by SA-ß-gal staining. The results demonstrate that the newborn deceased SCNT calves had significantly shortened telomere lengths compared to newborn naturally conceived calves and newborn normal SCNT calves. Significantly lower mtDNA copy number, and significantly lower relative abundance of LMNB1 and TERT, higher relative abundance of CDKN1A, and aberrant SA-ß-gal expression were observed in the newborn deceased SCNT calves, consistent with the change in telomere length. These results demonstrate that abnormal telomere shortening, lower mtDNA copy number and abnormal abundance of related genes were specific to newborn deceased SCNT calves, suggesting that abnormally short telomere length may be associated with abnormal development in the cloned calves.

Left atrial morpho-functional remodeling in atrial fibrillation assessed by three dimensional speckle tracking echocardiography and its value in atrial fibrillation screening.

BACKGROUND: Three dimensional speckle tracking echocardiography (3D STE) is a novel technique combining 3D echocardiography and speckle tracking analysis. 3D STE software dedicated to the left atrium (LA) was recently available. Our study aimed to assess (1) atrial fibrillation (AF) related LA morpho-functional remodeling using 3D STE and (2) value of LA function parameters in identifying paroxysmal AF (PAF). METHODS: One hundred thirty-nine PAF, 109 persistent AF (Per-AF) and 59 non-AF subjects underwent 3D STE. LA phasic volumes and total LA emptying fraction (LAEF) were obtained and used to calculate passive (pLAEF) and active LA emptying fraction (aLAEF) based on atrial contraction. LA longitudinal and circumferential strain representing reservoir (LASr/LASrc), conduit (LAScd/LAScdc) and pump (LASct/LASctc) function were also assessed. RESULTS: 3D STE was found to have good reproducibility. Increase of LA volumes and decrease of parameters representing LA reservoir and pump function were independently associated with AF as well as AF burden. The correlations between LA emptying fraction and LA circumferential strain representing the same function were always stronger than those with LA longitudinal strain (p < 0.001). Minimal LA volume, LAEF, aLAEF, LASrc and LASctc can be used to accurately differentiate PAF from non-AF subjects (AUC > 0.8) with great sensitivity and specificity. CONCLUSIONS: Assessing LA remodeling in AF using 3D STE was feasible. AF and AF burden were independently associated with LA enlargement and impairment of reservoir and pump function but not conduit function. LA function parameters can indicate underlying PAF and thus can guide AF screening strategy.

Is There a Diabetes-Kidney-Heart Continuum? Perspectives From the Results of the Cardiovascular and Renal Outcome Clinical Trials With SGLT2 Inhibitors.

Heart failure is associated with a substantial risk of mortality and morbidity. Findings from recent cardiovascular outcome trials have shown promise for sodium-glucose cotransporter-2 (SGLT2) inhibitors in preventing heart failure in patients with type 2 diabetes mellitus (T2DM). Notably, the benefits of SGLT2 inhibitors were consistent despite the presence of risk factors like atherosclerosis. Increasing evidence suggests that SGLT2 inhibitors may confer their cardioprotective effects through multiple mechanisms, ranging from improving cardiac and vascular performance to metabolism. The reduction of heart failure risk by SGLT2 inhibitors may also be attributed to the preservation of renal function. Indeed, renal insufficiency is a frequent comorbidity of patients with heart failure and T2DM; hence, the natriuretic and kidney protective effects offered by SGLT2 inhibitors may contribute to limiting adverse cardiac outcomes. In this article, we discuss the latest findings from the cardiovascular and renal outcome trials, paying special attention to the interlink between heart and kidney function, and how effective treatment of heart failure-irrespective of T2DM diagnosis-may require agents that offer both cardiac and renal protection.

The different risk factors for isolated diastolic hypertension and isolated systolic hypertension: a national survey.

BACKGROUND: Hypertension is highly prevalent and is one of the modifiable risk factors for cardiovascular outcomes. Isolated diastolic hypertension (IDH), however, tends to be ignored due to insufficient recognition. We sought to depict the clinical manifestation of IDH and isolated systolic hypertension (ISH) to find a more efficient way to improve the management. METHODS: Patients with primary hypertension aged over 18 years were investigated from all over the country using convenience sampling during 2017-2019. IDH was defined as systolic blood pressure (SBP) < 140 mmHg and diastolic blood pressure (DBP) ≥90 mmHg. ISH was defined as SBP ≥ 140 mmHg and DBP < 90 mmHg. RESULTS: A total of 8548 patients were screened, and 8475 participants were included. The average age was 63.67 ± 12.78 years, and males accounted for 54.4%. Among them, 361 (4.3%) had IDH, and 2096 had ISH (24.7%). Patients with IDH (54.84 ± 13.21 years) were much younger. Aging turned out to be negatively associated with IDH but positively associated with ISH. Multivariate logistic regression analysis showed BMI was a significant risk factor for IDH (OR 1.30, 95%CI 1.05-1.61, p = 0.018), but not for ISH (OR 1.05, 95%CI 0.95-1.16, p = 0.358). Moreover, smoking was significantly associated with IDH (OR 1.36, 95%CI 1.04-1.78, p = 0.026) but not with ISH (OR 1.04, 95%CI 0.90-1.21, p = 0.653). CONCLUSIONS: Patients with IDH were much younger, and the prevalence decreased with aging. BMI and smoking were remarkably associated with IDH rather than ISH. Keeping fit and giving up smoking might be particularly efficient in the management of young patients with IDH. TRIAL REGISTRATION: NCT03862183 , retrospectively registered on March 5, 2019.

Protective effect of exosomes derived from bone marrow mesenchymal stem cells on rats with diabetic nephropathy and its possible mechanism.

OBJECTIVE: To investigate the effect of exosomes derived from bone marrow mesenchymal stem cells (BMMSC-Exos) on diabetic nephropathy (DN) rats and its possible mechanism. METHODS: Thirty rats were divided into the following three groups of 10 rats each: the NC group (normal rats), the DN group (rats with DN), and the BM group (DN rats injected with BMMSC-Exo). Blood glucose level, renal function, blood lipid level, and plasma viscosity of the rats were detected. Renal tissue morphology was observed using hematoxylin-eosin staining. Expression levels of JAK2 and STAT3 in rats' kidneys were measured by RT-PCR and western blot. RESULTS: The rats in the DN group had higher levels of blood glucose, blood lipids, and blood viscosity, worse renal function, and lower body weight than those in the NC group (all P<0.05). After treatment with BMMSC-Exos, rats in the BM group had markedly decreased levels of blood glucose, blood lipids, and blood viscosity, improved renal function, and higher body weight compared to those in the DN group (all P<0.05). The renal tissues in the NC group had intact structure, and no hyperplastic or hypertrophic cells were observed. In the DN group, the renal glomerulus and mesangial matrix were abnormal, and the capillary lumen and renal tubule lumen were depressed and blocked, accompanied by interstitial edema. Pathologic changes in the renal glomerulus and tubule in the BM group were less severe than those in the DN group. The DN rats had higher expression levels of JAK2 and STAT3 than normal rats, and the rats treated with BMMSC-Exos had lower levels of JAK2 and STAT3 compared to the DN rats (all P<0.05). CONCLUSION: BMMSC-Exo can achieve a good therapeutic effect in DN, which may be due to its ability to lower the blood glucose level, improve renal function, and inhibit JAK2/STAT3 expression.

The Integrated Management of Hypertension in General Hospitals and Community Hospitals.

PURPOSE: We sought to investigate and improve the integrated management of hypertension in general and community hospitals in China. PATIENTS AND METHODS: We carried out a cross-sectional study in 90 centers from 15 cities in China from 2017 to 2018. Patients with primary hypertension were included. RESULTS: Of the total 4286 patients included, 43.2% of them controlled blood pressure (BP) below 140/90 mmHg while only 11.5% controlled BP below 130/80 mmHg. The control rate of low-density lipoprotein-C (LDL-C) in patients with concomitant coronary artery disease (CAD), diabetes (DM), and chronic kidney disease (CKD) was 24.7%, 49.4%, and 40.6%, respectively. Thirty-one percent of the DM patients had HbA1c levels greater than 8% while 21.7% of the non-DM patients had HbA1c≥6.5%. The control rate of body mass index (BMI) was 54.4% in men and 59.8% in women. As compared to patients from community hospitals, patients from general hospitals had poorer control of BP<140/90 mmHg (OR 0.63, 95% CI 0.55-0.73, p<0.001), comparatively better attainment of LDL-C, particularly <1.8 mmol/L in CAD (OR 3.25, 95% CI 2.02-5.24, p<0.001), similar control of HbA1c < 8.0% in diabetes (OR 0.64, 95% CI 0.41-1.00, p=0.052) and comparatively worse achievement of BMI<25 kg/m2 (OR 0.72, 95% CI 0.63-0.83, p<0.001). CONCLUSION: The integrated management of hypertension needs to be improved. Besides LDL-C, the management of BP, blood glucose (BG), and BMI need to be strengthened in not only community hospitals but also general hospitals.

A stricter control of low-density lipoprotein is necessary for thrombosis reduction in "lower thrombosis risk" patients with atrial fibrillation: a multicenter retrospective cohort study.

Patients with atrial fibrillation (AF) are associated with increased thrombotic events. Our previous case-control study showed low-density lipoprotein cholesterol (LDL-C) was an independent predictor of ischemic stroke in AF patients. To investigate the risks of thrombosis in relation to LDL-C among AF patients at different stroke risks by long-time follow-up. Atrial fibrillation patients without history of thrombosis enrolled from five hospitals were classified into low-risk (LR) and high-risk (HR) group according to CHA2DS2VASc score and followed up with a median period of 26 months. Univariate and multivariate logistic regression analysis were performed in each group. The best cut-off value calculated by receiver operating characteristic (ROC) analysis was used to divide patients into low LDL-C (L-LDL) and high LDL-C (H-LDL) subgroups. Propensity score matching (PSM) and inverse probability of treatment weighted (IPTW) were utilized in both subgroups, after which Kaplan-Meier curves for thrombosis were performed. Univariate and multivariate analysis showed LDL-C was significantly related to thrombosis in LR, but less significantly in HR group. The best cut-off value was 2.155 mmol/L in LR and 2.795 mmol/L in HR group. Lower LDL-C was associated with decreased thrombosis in both groups by PSM and IPTW. Kaplan-Meier curves displayed that H-LDL subgroup was at higher thrombosis risk with significant difference at 24th month in LR patients. LDL-C independently predicts thrombosis with different cut-off values in AF patients at different risks. A stricter control of LDL-C level is necessary for thrombosis reduction in patients with lower score.

The association of metabolic syndrome components and chronic kidney disease in patients with hypertension.

BACKGROUND: Hypertension is a highly prevalent disease and the leading cause of chronic kidney disease (CKD). Metabolic syndrome could also be the risk factor for CKD. We sought to study the association between metabolic syndrome components and the prevalence of CKD in patients with hypertension. METHODS: We carried out a multi-center cross-sectional study from Apr. 2017- Apr. 2018 in 15 cities in China. RESULTS: A total of 2484 patients with hypertension were enrolled. Among them, 56% were male and the average age was 65.12 ± 12.71 years. The systolic BP/diastolic BP was 142 ± 18/83 ± 12 mmHg. Metabolic syndrome components turned out to be highly prevalent in patients with hypertension, ranging from 40 to 58%. The prevalence of chronic kidney disease reached 22.0%. Multi-variate logistic analysis revealed that elevated triglyceride (TG) (OR = 1.81, 95% CI 1.28-2.57, p < 0.01), elevated fasting blood glucose (FBG) (OR = 1.43, 95% CI 1.00-2.07, p = 0.05) and hypertension grades (OR = 1.20, 95% CI 1.00-1.44, p = 0.05) were associated with the prevalence of CKD. In sub-group analysis, elevated TG remained strongly associated with CKD in both diabetes (OR = 2.10, 95%CI 1.22-3.61, p < 0.01) and non-diabetes (OR = 1.53, 95% CI 1.09-2.16, p = 0.01). In sub-group analysis of hypertension grades, there was also a graded trend between elevated TG and CKD from controlled blood pressure (BP) to hypertension grade 2 (OR = 1.81, 95%CI 1.06-3.11, p = 0.03; OR = 1.85, 95%CI 1.00-3.43, p = 0.05; OR = 2.81, 95% CI 1.09-7.28, p = 0.03, respectively). CONCLUSION: Elevated TG, elevated FBG and hypertension grades were significantly associated with the prevalence of CKD in patients with hypertension. Particularly, elevated TG was strongly associated with CKD, independent of diabetes and hypertension grades.

Correlation between CTLA-4 and CD40 gene polymorphisms and their interaction in graves' disease in a Chinese Han population.

BACKGROUND: Single-nucleotide polymorphism (SNP) haplotype and SNP-SNP interactions of CTLA-4 and CD40 genes, with susceptibility to Graves' disease (GD), were explored in a Chinese Han population. METHODS: SNP were genotyped by high resolution melting (HRM). Use the method of Pearson χ2 test and Logistic regression for the association between single SNP and Graves' disease. Using the method of χ2 test and Multifactor Dimensionality Reduction (MDR) to analysis the haplotype frequency distribution, the interaction of SNPs respectively. RESULTS: Genotypic and allelic frequencies of SNP rs231775, rs3087243 and rs1883832 were statistically different between controls and GD (p < 0.05). Mutant allelic frequency of G rs231775 was higher, and A and T allelic frequencies of rs3087243 and rs1883832 were lower in GD than in controls (P < 0.05). In CTLA-4 rs1024161, rs5742909, rs231775, rs231777, rs231779, rs3087243 and rs11571319 showed D' < 50% and r2 < 0.3 among each SNP. We identified six commonly found haplotypes; TCGCTGC was associated with the highest GD risk (OR = 2.565) and TCACTAC the lowest (OR = 0.096). MDR analysis indicated interactions among the rs231775 GG, rs231779 TT and rs3087243 GG genotypes in CTLA-4 might increase GD risk by 2.53-fold (OR = 2.53). CONCLUSION: CTLA-4 and CD40 were associated with GD incidence in a Chinese Han population. The TCGCTGC and TCACTAC haplotypes in the CTLA-4 gene, were risk and protective factors for Graves'disease respectively. Interactions among the SNPs of rs231775, rs231779 and rs3087243 significantly increase the susceptibility to GD.

Echocardiography with Elevated Central Venous Pressure Diagnosing Constrictive Pericarditis More Accurately Than Chest CT Scan: A Retrospective Study in 36 Cases.

BACKGROUND: Constrictive pericarditis (CP) is defined as impaired diastolic cardiac function caused by a calcified and thickened pericardium. We assessed the clinical characteristics and time to diagnosis, as well as patient prognosis after pericardiectomy. Methods: We analyzed the records of 36 CP patients who underwent pericardiectomy at Huashan Hospital, China, between 2012 and 2015. Clinical manifestations, length of time to diagnosis, laboratory parameters, and diagnostic imaging results were examined. All patients underwent pericardiectomy, and were assessed post-operatively for quality of life and improvement of cardiac function using the Minnesota Living with Heart Failure Questionnaire (MLHFQ). Results: All patients displayed shortness of breath and polyserous effusion, as well as elevated pro B-type natriuretic peptide and thickened pericardium. Mean time between onset of symptoms and a definitive diagnosis of CP was 9.5 ± 2.1 months. Pericardiectomy was performed within one week of diagnosis. Mean central venous pressure decreased from a pre-operative 19.92 ± 6.6 mmHg to a post-operative 8.5 ± 2.7 mmHg. Within 1.5 ± 0.7 years of surgery, all patients maintained good quality of life and cardiac function, which resulted in a mean score of 0.9 ± 0.6 on the MLHFQ. Conclusion: A definitive diagnosis of CP is usually made long after the onset of symptoms. Early detection and diagnosis by echocardiography with elevated central venous pressure and early treatment by surgery are key to an improved prognosis and resumption of good cardiac function.

Cardiac arrhythmias as the initial manifestation of adult primary Sjögren's syndrome: a case report and literature review.

Two middle-aged female patients presenting with heart palpitation and electrocardiogram revealed complex cardiac arrhythmias. A review of systems was positive for dry mouth and transient arthralgia, while laboratory and instrumental tests enabled us to make the diagnosis of primary Sjögren's syndrome (pSS). Cardiac electrophysiology revealed atrioventricular node dysfunction and impaired intraventricular conduction. Prednisone therapy induced a significant improvement in symptoms and electrocardiographic readings. The diagnosis of pSS should be considered in a patient presenting with complex cardiac arrhythmias.

Synergistic combined effect between CD40-1C>T and CTLA-4+6230G>A polymorphisms in Graves' disease.

The aim of this study was to investigate whether a genetic combined effect exists between CD40-1C>T and CTLA-4+6230G>A (CT60) polymorphisms and whether the combined effect renders susceptibility to Graves' disease (GD). We recruited 260 patients with GD and 248 healthy controls. Single nucleotide polymorphisms were genotyped by polymerase chain reaction-high resolution melting. Genetic polymorphisms related to GD were identified, levels of thyroid stimulating hormone receptor antibodies (TRAb) were measured, and genetic interactions were assessed by logistic regression analysis. Significant difference in allele and genotype frequency of CD40-1C>T polymorphism was observed between the patients and control subjects (P<0.001, 0.002 respectively). As for CTLA-4+6230G>A polymorphism, significant difference was observed only in allele frequencies between the patient and control groups (P=0.014). Moreover, a significant combined effect was presented in CD40-1C>T and CTLA-4+6230G>A polymorphism (P=0.020), and all, but one, combination CC-genotype of CD40-1C>T and GG-genotype of CTLA-4+6230G>A polymorphism has 54% lower risk of GD development than subjects with the CC and GG genotypes (OR=0.46, 95% CI=0.25-0.84). In newly onset GD group, neither single SNP (CD40-1C>T or CTLA-4+6230G>A polymorphism) nor their combined effect was showed a significant association with TRAb concentration (all P>0.05). Our findings suggest a possible additive combined effect between CD40-1C>T and CTLA4+6230G>A polymorphisms in the development of GD.