Heterozygous CARD9 mutation favors the development of allergic bronchopulmonary aspergillosis / 中华医学杂志(英文版)

BACKGROUND@#Previous research demonstrated that a homozygous mutation of g.136372044G>A (S12N) in caspase recruitment domain family member 9 ( CARD9 ) is critical for producing Aspergillus fumigatus -induced ( Af -induced) T helper 2 (T H 2)-mediated responses in allergic bronchopulmonary aspergillosis (ABPA). However, it remains unclear whether the CARD9S12N mutation, especially the heterozygous occurrence, predisposes the host to ABPA.@*METHODS@#A total of 61 ABPA patients and 264 controls (including 156 healthy controls and 108 asthma patients) were recruited for sequencing the CARD9 locus to clarify whether patients with this heterozygous single-nucleotide polymorphisms are predisposed to the development of ABPA. A series of in vivo and in vitro experiments, such as quantitative real-time polymerase chain reaction, flow cytometry, and RNA isolation and quantification, were used to illuminate the involved mechanism of the disease.@*RESULTS@#The presence of the p.S12N mutation was associated with a significant risk of ABPA in ABPA patients when compared with healthy controls and asthma patients, regardless of Aspergillus sensitivity. Relative to healthy controls without relevant allergies, the mutation of p.S12N was associated with a significant risk of ABPA (OR: 2.69 and 4.17 for GA and AA genotypes, P = 0.003 and 0.029, respectively). Compared with patients with asthma, ABPA patients had a significantly higher heterozygous mutation (GA genotype), indicating that p.S12N might be a significant ABPA-susceptibility locus ( aspergillus sensitized asthma: OR: 3.02, P = 0.009; aspergillus unsensitized asthma: OR: 2.94, P = 0.005). The mutant allele was preferentially expressed in ABPA patients with heterozygous CARD9S12N , which contributes to its functional alterations to facilitate Af -induced T H 2-mediated ABPA development. In terms of mechanism, Card9 wild-type ( Card9WT ) expression levels decreased significantly due to Af -induced decay of its messenger RNA compared to the heterozygous Card9S12N . In addition, ABPA patients with heterozygous CARD9S12N had increased Af -induced interleukin-5 production.@*CONCLUSION@#Our study provides the genetic evidence showing that the heterozygous mutation of CARD9S12N , followed by allele expression imbalance of CARD9S12N , facilitates the development of ABPA.

The experimental study of saline and diluted hydrochloric acid enhanced radiofrequency ablation in ex vivo porcine liver / 中华放射学杂志

Objective To compare the size of ablation lesions created by normal saline enhanced radiofrequency ablation (NS-RFA) and dilute hydrochloric acid enhanced radiofrequency ablation (HCl-RFA), explore their affecting factors, and observe the morphological manifestations of the ablated lesions.Methods NS-RFA and HCl-RFA were performed on 30 excised porcine livers with 9 different combinations of durations (5, 10, 15, and 20 minutes), temperatures (83, 93, 103, and 113 ℃ ) and powers (20, 30,and 40W). For each ablated lesion, the longitudinal and transverse diameters were measured, and volumes calculated. Multifactor analysis of variance was used to analyze the affecting factors of the size of ablated lesions. Macroscopic and microscopic morphological characteristics of lesions were observed. Results ( 1 )NS-RFA lesion volumes under 9 combinations were ( 3.53 ± 0. 34 ), (6. 41 ± 0. 42 ), ( 10. 69 ± 0. 37 ),(11.40±0.51), (3.20±0.23), (6.59 ±0.50), (12.11 ±0.70), (11.12 ±0.52), (11.81 ±0. 64) cm3, respectively. HCl-RFA lesion volumes under 9 combinations were ( 11.97 ± 1. 00), (28.72 ±0.99), (59.45 ±1.33), (105.65 ±2.40), (13.64±0.60), (29.70±0.58), (59.22±1.32),( 57. 22 ± 3.99 ), ( 59. 74 ± 2. 18 )cm3, respectively. The size differences of ablation zones caused by different types of ablation ( F = 948.9 ) ( main factor), durations ( F = 269. 3 ) and temperatures ( F =214. 6) (covariates) were statistically significant (P ＜ 0. 01 ), whereas which caused by power ( F = 0. 2 )(covariate) was not statistically significant (P ＞ 0. 05 ). (2)At gross examination, all ablation lesions were elliptical in cross section and there were three zones in NS-RFA induced lesions and five zones in HCl-RFA induced lesions. At microscopic examination of NS-RFA induced lesions, a small amount of liver cell debris were found at the edge of zone Ⅰ , a few of deformed and ruptured liver cells in zone Ⅱ. The shape of the most of the liver cells in zone Ⅲ was normal. At microscopic examination of HCl-RFA induced lesions, a small amount of liver cell debris were found at the edge of zone Ⅰ , classical coagulation necrosis in zone Ⅱ and Ⅲ, widened hepatic sinusoids lossened junction of hepatocytes and some hepatocytes detached into sinusoids in zones Ⅳ. The liver cells in zone V were normalexcept a small amount of hepatoeytes with pyknosis, karyorrhexis and karyolysis. Condusion Compared with NS-RFA, HCl-RFA can produce lager ablation zones. The duration and temperature were the factors that affected the size of ablation zone. HCl-RFA lesions typically showed coagulation necrosis at microscopical examination.