Association between use of amiodarone for non-valvular atrial fibrillation and patient survival: from the prospective China Atrial Fibrillation Registry / 中华医学杂志(英文版)

BACKGROUND@#Post hoc analysis of the landmark atrial fibrillation follow-up investigation of rhythm management trial revealed that amiodarone was associated with higher risks of mortality, intensive care unit admission, and non-cardiovascular death. We aim to evaluate the association between amiodarone use and patient survival under updated medical mode and level using data from the China Atrial Fibrillation (China-AF) Registry study.@*METHODS@#Clinical data of 8161 non-valvular atrial fibrillation (NVAF) patients who were antiarrhythmic drug (AAD)-naive before enrollment into the China-AF Registry, recruited between August 2011 and February 2017, were collected. The primary outcome was all-cause mortality. A Cox proportional hazard regression model was used to evaluate the association between amiodarone use and the outcome. We also calculated the rate of sinus rhythm maintenance at the penultimate follow-up.@*RESULTS@#Compared with 6167 patients of non-AAD group, 689 patients of the amiodarone group were younger (mean age 65.6 vs. 68.6 years), more frequently completed high school education, had fewer comorbidities such as chronic heart failure, prior bleeding, and stroke, and were more likely to be treated in tertiary hospitals while less hospitalization. The proportion of persistent AF was much lower among users of amiodarone, who were also less likely to be taking oral anticoagulants. The patients in the amiodarone group had a statistically insignificant lower incidence of all-cause mortality (2.44 vs. 3.91 per 100 person-years) over a mean follow-up duration of 300.6 ± 77.5 days. After adjusting for potential confounders, amiodarone use was not significantly associated with a lower risk of all-cause mortality (adjusted hazard ratio, 0.79; 95% confidence interval, 0.42-1.49). Sub-group analysis revealed the consistent results. The rate of sinus rhythm maintenance at the penultimate follow-up in the amiodarone group was significantly higher than in the non-AAD group.@*CONCLUSIONS@#Our study indicated that amiodarone use was not significantly associated with a lower risk of 1-year all-cause mortality compared with a non-AAD strategy in "real-world" patients with NVAF.

Purinergic 2X7 Receptor is Involved in the Podocyte Damage of Obesity-Related Glomerulopathy via Activating Nucleotide-Binding and Oligomerization Domain-Like Receptor Protein 3 Inflammasome / 中华医学杂志(英文版)

Background@#The nucleotide-binding and oligomerization domain-like receptor protein 3 (NLRP3) inflammasome composed of NLRP3, apoptosis-associated speck-like protein containing CARD (ASC), and caspase-1 is engaged in the inflammatory response of many kidney diseases and can be activated by purinergic 2X7 receptor (P2X7R). This study was conducted to explore whether P2X7R plays a pathogenic role in the podocyte damage of obesity-related glomerulopathy (ORG) and whether this role is mediated by the activation of NLRP3 inflammasome.@*Methods@#A mouse model of ORG was established by high-fat diet feeding. The conditionally immortalized mouse podocytes were cultured with leptin or with leptin and P2X7R antagonist (KN-62 or A438079). The mRNA and protein expression of the P2X7R and NLRP3 inflammasome components including NLRP3, ASC, and caspase-1, as well as the podocyte-associated molecules including nephrin, podocin, and desmin in mouse renal cortex or cultured mouse podocytes were tested by real-time-polymerase chain reaction and Western blot analysis, respectively.@*Results@#The significantly upregulated expression of P2X7R and NLRP3 inflammasome components and the NLRP3 inflammasome activation were observed in the renal cortex (in fact their location in podocytes was proved by confocal microscopy) of ORG mice in vivo, which were accompanied with the morphological changes of podocyte damage and the expression changes of podocyte-associated molecules. Similar changes in the expression of P2X7R and NLRP3 inflammasome components as well as in the expression of podocyte-associated molecules were also observed in the cultured podocyte studies treated by leptin in vitro, and all of the above changes were significantly attenuated by the P2X7R antagonist KN-62 or A438079.@*Conclusions@#P2X7R could trigger the activation of NLRP3 inflammasome, and the activated P2X7R/NLRP3 inflammasome in podocytes might be involved in the podocyte damage of ORG.

CD14 genomic polymorphism influences CD14 expression in whole blood culture / 中华外科杂志

<p><b>OBJECTIVE</b>To investigate whether -159C/T promoter polymorphism of the CD14 gene influences the CD14 expression as well as release in whole blood culture.</p><p><b>METHODS</b>One hundred and eighteen healthy human blood donors were included in the present study. CD14 mRNA expression and soluble CD14 levels were measured using a whole blood cell culture model with or without lipopolysaccharide (LPS) stimulation. The CD14 gene polymorphism was determined by polymerase chain reaction and subsequent HaeIII restriction enzyme digestion of the polymerase chain reaction products. TNF-alpha production in the whole blood culture was also measured.</p><p><b>RESULTS</b>Among the 118 individuals, there were 40 subjects homozygous for the T allele (TT), 62 were heterozygous (CT), and 16 had the genotype CC. The CD14 mRNA expression in leukocytes and soluble CD14 levels in supernatant were higher in TT homozygotes and carriers of the genotype TC compared with individuals homozygous for the C allele (P < 0.05 or 0.01). In addition, the highest values of TNF-alpha production were found in TT homozygote [(352 +/- 215) pg/ml] compared with both genotype TC and CC [(261 +/- 163) pg/ml, (198 +/- 122) pg/ml, both P < 0.05].</p><p><b>CONCLUSION</b>The -159C/T promoter polymorphism of the LPS receptor CD14 may influence the CD14 expression as well as release in whole blood culture, and it might be associated with TNF-alpha response to LPS stimulation.</p>