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.
Humans ; Aspergillosis, Allergic Bronchopulmonary/complications* ; Aspergillus fumigatus/genetics* ; Asthma/genetics* ; Aspergillus ; Mutation/genetics* ; CARD Signaling Adaptor Proteins/genetics*

The importance of structural variants(SVs)for human phenotypes and diseases is now recognized.Although a variety of SV detection platforms and strategies that vary in sensitivity and specificity have been developed,few benchmarking procedures are available to confidently assess their performances in biological and clinical research.To facilitate the validation and application of these SV detection approaches,we established an Asian reference material by characterizing the genome of an Epstein-Barr virus(EBV)-immortalized B lymphocyte line along with identified benchmark regions and high-confidence SV calls.We established a high-confidence SV callset with 8938 SVs by integrating four alignment-based SV callers,including 109x Pacific Biosciences(PacBio)continuous long reads(CLRs),22 x PacBio circular consensus sequencing(CCS)reads,104x Oxford Nanopore Technologies(ONT)long reads,and 114×Bionano optical mapping plat-form,and one de novo assembly-based SV caller using CCS reads.A total of 544 randomly selected SVs were validated by PCR amplification and Sanger sequencing,demonstrating the robustness of our SV calls.Combining trio-binning-based haplotype assemblies,we established an SV benchmark for identifying false negatives and false positives by constructing the continuous high-confidence regions(CHCRs),which covered 1.46 gigabase pairs(Gb)and 6882 SVs supported by at least one diploid haplotype assembly.Establishing high-confidence SV calls for a benchmark sample that has been characterized by multiple technologies provides a valuable resource for investigating SVs in human biology,disease,and clinical research.

Objective    To analyze the outcome of fast track surgery after intercostal nerve block (INB) during thoracoscopic resection of lung bullae. Methods    We recuited 76 patients who accepted thoracoscopic resection of lung bullae from February 2013 to March 2015. They were randomly divided into two groups: an intercostal nerve block and intravenous patient-controlled analgesia (INB+IPCA) group, in which 38 patients (30 males, 8 females, with a mean age of 23.63±4.10 years) received INB intraoperatively and IPCA postoperatively, and a postoperative intravenous patient-controlled analgesia (IPCA) group, in which 38 patients (33 males, 5 females, with a mean age of 24.93±6.34 years) only received IPCA postoperatively. Their general clinical data and the postoperative pain visual analogue scale (VAS) were recorded. Analgesia-associated side effects, rate of the pulmonary infection were observed. Expenses associated with analgesia during hospital were calculated. Results    The score of VAS, the incidence of nausea and vomiting, fatigue and other side effects, pulmonary atelectasis and the infection rate in the INB+IPCA group were significantly lower than those in the IPCA group. Postoperative use of analgesic drugs was significantly less than that in the IPCA group. Medical expenses did not significantly increase. Conclusion    INB+IPCA is beneficial for fast track surgery after thoracoscopic resection of lung bullae.

Objective To investigate the effect of gut bacteria under chronic colitis on the progression of hepatoma in mice.Methods 22 hepatitis B virus (HBV) -transgenic mice ( male, 8 weeks) were randomly divided into two groups, one group (n =10) was fed the drinking water containing 2% dextran sodium sulphate(DSS)to induce chronic colitis and the control group(n =12)was fed with normal drinking water.In order to investigate the effect of gut microbes, 7 male HBV-transgenic mice(8 weeks, with no detectable hepatoma under microscopy) were cohoused with 4 mice with hepatoma for 16 weeks.Results No significant liver cell damage was observed in the group of the mice fed with 2% DSS-containing drinking water.By the 22 -week old,9 of the 10 mice(90.0%) fed with 2% DSS-containing drinking water, 2 of the 12 mice(16.7%) fed with normal drinking had hepatoma.Both the hepatoma incidence and the tumor numbers in the group of mice fed with DSS-containing water were significantly higher than that in the controls (P =0.002 and P =0.028respetively).Compared to controls, the bacteria family Prevotella (P =0.022) and Anaeroplasma (P =0.014) reduced significantly in the mice with induced chronic colitis.All the mice (n =7) cohoused with the mice with hepatoma had the liver tumor developed at 24 -week-old.Conclusion Alterations of gut bacteria under chronic colitis may promote the development of liver cancer.