A de novo PKD1 mutation in a Chinese family with autosomal dominant polycystic kidney disease.

BACKGROUND: PKD1, which has a relatively high mutation rate, is highly polymorphic, and the role of PKD1 is incompletely defined. In the current study, in order to determine the molecular etiology of a family with autosomal dominant polycystic kidney disease, the pathogenicity of an frameshift mutation in the PKD1 gene, c.9484delC, was evaluated. METHODS: The family clinical data were collected. Whole exome sequencing analysis determined the level of this mutation in the proband's PKD1, and Sanger sequencing and bioinformatics analysis were performed. SIFT, Polyphen2, and MutationTaster were used to evaluate the conservation of the gene and pathogenicity of the identified mutations. SWISS-MODEL was used to predict and map the protein structure of PKD1 and mutant neonate proteins. RESULTS: A novel c.9484delC (p.Arg3162Alafs*154) mutation of the PKD1 gene was identified by whole exome sequencing in the proband, which was confirmed by Sanger sequencing in his sister (II7). The same mutation was not detected in the healthy pedigree members. Random screening of 100 normal and end-stage renal disease patients did not identify the c.9484delC mutation. Bioinformatics analysis suggested that the mutation caused the 3162 nd amino acid substitution of arginine by alanine and a shift in the termination codon. As a result, the protein sequence was shortened from 4302 amino acids to 3314 amino acids, the protein structure was greatly changed, and the PLAT/LH2 domain was destroyed. Clustal analysis indicated that the altered amino acids were highly conserved in mammals. CONCLUSION: A novel mutation in the PKD1 gene has been identified in an affected Chinese family. The mutation is probably responsible for a range of clinical manifestations for which reliable prenatal diagnosis and genetic counseling may be provided.

The mortality for the implantable cardiac defibrillator in nonischemic cardiomyopathy: An updated systematic review and meta-analysis.

The implantable cardiac defibrillator (ICD) is common for the management of nonischemic cardiomyopathy (NICM). Mortality is a crucial issue for patients with NICM. We can understand the mortality events of ICD versus medicine treatment via a systemic review and meta-analysis of randomized clinical trials. The comparison between ICD treatment and medicine treatment was performed to find if the ICD treatment can be associated with lower relative risk and hazard ratio of mortality than the medicine treatment. In addition, the different kinds of mortality events were analyzed for the ICD treatment. After a restricted selection, 9 studies with a total of 4001 NICM patients were enrolled. The focused outcome was the events of all-cause mortality, sudden cardiac death, and cardiovascular death. The results showed that ICD treatment might be associated with lower relative risk and hazard ratio of all-cause mortality and sudden cardiac death. However, the relative risk and hazard ratio of cardiovascular mortality was not significantly different between ICD treatment and medicine treatment. In the current meta-analysis, the ICD treatment might show a lower relative risk and hazard ratio of all-cause mortality and sudden cardiac death when compared with medicine treatment. However, no significant differences were observed in cardiovascular mortality between ICD and medicine treatment.

Adropin Alleviates Myocardial Fibrosis in Diabetic Cardiomyopathy Rats: A Preliminary Study.

Aim: Adropin (ADR) is a novel regulatory polypeptide and has important effects on energy metabolism in the heart. However, it is still unclear whether ADR can relieve ventricular remodeling in DCM. Therefore, this study was conducted to assess the effect of ADR on myocardial fibrosis in DCM rats. Materials and Methods: Twenty Wistar rats were randomly assigned into four groups: healthy control group (CON), DCM model group (DCM), DCM model treated with ADR group (ADR) and DCM model treated with perindopril group (PER). Collagen volume fraction (CVF) and perivascular collagen area (PVCA) were calculated. Diastolic function was assessed by echocardiography. The mitochondrial membrane potential assay was conducted by Rhodamine 123 staining. The protein expression levels of Col I, Col III, Mitofusin-1, Mitofusin-2 and Drp1 were evaluated using western blot. Results: Compared to CON group, CVF, PVCA and the relative protein expression of Col I, Col III and Drp1 increased in DCM group. And the relative expression of Mitofusin-1 and Mitofusin-2 proteins decreased. During our investigations, CVF, PVCA and the relative protein expression of Col I, Col III and Drp1 decreased in ADR treated rats compared to DCM group. The diastolic function was elevated in ADR group. The fluorescence of Rhodamine 123 and the expression of Mitofusin-1 and Mitofusin-2 also increased in ADR group. Conclusion: Our study demonstrated that ADR could alleviate myocardial fibrosis and improve diastolic function in DCM rats. ADR may be a putative candidate for the treatment of DCM.

Mechanical chest compression with LUCAS device does not improve clinical outcome in out-of-hospital cardiac arrest patients: A systematic review and meta-analysis.

BACKGROUND: Cardiac arrest (CA) is a serious threat to human health. Cardiopulmonary resuscitation (CPR) is an effective treatment for CA. Early and high-quality CPR is closely related to the survival rate of patients with CA. But manual chest compression has a lot of defects. To solve the defects and improve the quality of CPR, mechanical CPR device was invented. However, it has still controversy whether manual chest compression or mechanical chest compression is better. This systematic review was aimed to investigate the difference in clinical outcomes between manual chest compression and Lund University Cardiac Assist System (LUCAS) assisted CPR in patients with out-hospital CA. METHODS: Original research studies, conducted on adult out-of-hospital CA, were included. PubMed/Medline, EMBASE, Scopus, Cochrane Library, CNKI, and Wanfang database were searched from the setting to February 21, 2019. Odds ratio (OR) with 95% confidence interval (CI) was selected as effect scale index for evaluation of the difference in return of spontaneous circulation (ROSC), survival to hospital admission, survival to hospital discharge, and survival to 30 days. Random effects model was used in this study to estimate overall mean effects. RESULTS: A total of 6 articles, including 4 randomized controlled trials and 2 nonrandomized controlled trials, were selected. And 8501 subjects were involved to analyze the clinical outcomes of LUCAS and manual chest compression for patients with out-hospital CA. Comparisons of ROSC (33.3% vs 33.0%, P = .98; OR = 1; 95% CI: [0.89,1.13]), survival to hospital admission (22.7% vs 24.3%, P = .32; OR = 0.86; 95% CI: [0.65,1.15]), survival to hospital discharge (8.6% vs 10.7%, P = .50; OR = 0.92; 95% CI: [0.73,1.17]), and survival to 30 days (7.5% vs 8.5%, P = .50; OR = 0.92; 95% CI: [0.73,1.17]) were made. No significant difference was found. CONCLUSION: The synthesis of available evidence does not support that mechanical chest compression with LUCAS device improves clinical outcome in out-of-hospital CA patients compared with manual chest compression. Large scale studies with improved designs are still needed in the future.

Effect of paeoniflorin on cardiac remodeling in chronic heart failure rats through the transforming growth factor ß1/Smad signaling pathway.

BACKGROUND: Cardiac remodeling is an important mechanism for the occurrence and development of chronic heart failure (CHF). Paeoniflorin (Pae) is the main active ingredient of Chinese herbaceous peony and has novel anti-inflammatory effect. This study was conducted to assess the effects and mechanisms of Pae on cardiac remodeling in CHF rats. METHODS: A cardiac remodeling rat model was induced by isoprenaline (Iso). Pae (20 µg/kg/d) was administrated to CHF rats for six weeks. Cardiac ultrasound was used to assess the structure and function of CHF rats. Collagen volume fraction (CVF) and perivascular collagen volume area of myocardial tissues were calculated. With real-time polymerase chain reaction and Western blot, the protein and mRNA levels of transforming growth factor ß1 (TGF-ß1) and Smad3 were detected. RESULTS: Compared to Iso group, Pae can alleviate cardiac remodeling and improve cardiac function in CHF rats. The levels of CVF and perivascular collagen volume area reduced in Pae group (P<0.05). The expression of TGF-ß1 and Smad3 protein decreased in Pae and Cap group (P<0.05). Further, the expression of TGF-ß1 and Smad3 mRNA also decreased markedly in the Pae group (P<0.05). CONCLUSIONS: Pae could attenuate cardiac remodeling and improve cardiac function in CHF rats. The potential mechanism for the cardioprotective effect of Pae may be highly associated with the down-regulating of TGF-ß1/Smad signaling pathway.