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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.
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Humans , Aspergillosis, Allergic Bronchopulmonary/complications , Aspergillus fumigatus/genetics , Asthma/genetics , Aspergillus , Mutation/genetics , CARD Signaling Adaptor Proteins/geneticsABSTRACT
Objective:To investigate the clinical characteristics and prognostic factors of 2019 novel coronavirus (2019-nCoV) Omicron variant infected cases.Methods:A total of 987 coronavirus disease 2019 (COVID-19) adult imported cases admitted to Shanghai Public Health Clinical Center, Fudan University from July 1, 2021 to January 6, 2022 were recruited. The cases were divided into Omicron group (193 cases) and non-Omicron group (794 cases) according to the genotype of the virus. The clinical data, imaging examination and laboratory results of two groups were collected and compared. Chi-square test and Mann-Whitney U test were used as statistical methods. Multiple linear regression analysis was used for multiple linear regression analysis. Results:The majority of patients in Omicron group were 18 to 30 years old, accounting for 51.3%(99/193), which was higher than 31.4%(249/794) in non-Omicron group. The difference was statistically significant ( χ2=52.75, P<0.001). The proportion of mild cases in Omicron group was 88.6%(171/193), which was higher than 81.6%(648/794) in non-Omicron group. The difference was statistically significant ( χ2=5.37, P=0.021). Cases with symptoms were more common in Omicron group than those in non-Omicron group (60.1%(116/193) vs 29.1%(231/794)), and the difference was statistically significant ( χ2=65.49, P<0.001), with the main clinical manifestations of sore/itchy throat, fever and cough/expectoration. The proportion of cases with pulmonary computed tomography (CT) imaging manifestations at admission in Omicron group was 13.0%(25/193), which was lower than that in non-Omicron group (215/794, 27.1%). The difference was statistically significant ( χ2=16.83, P<0.001). The proportion of cases with 2019-nCoV IgG positive at admission was 47.7%(92/193) in Omicron group, which was lower than 61.1%(485/794) in non-Omicron group, and the difference was statistically significant ( χ2=11.51, P<0.001). The hospitalization time of Omicron group was 20.0 (16.0, 23.0) d, which was longer than that of non-Omicron group (14.0 (10.0, 22.0) d), and the difference was statistically significant ( Z=-7.42, P<0.001). Multiple linear regression analysis showed that the time of hospitalization of cases with 2019-nCoV IgG positive at admission was shorter, while that of the cases with fever in Omicron group was longer (both P<0.050). Conclusions:The main clinical characteristics of cases with Omicron variant are fever and upper respiratory symptoms. Their pulmonary CT imaging manifestations are less, and the time of hospitalization is slightly longer. The time of hospitalization and the virus clearance time in Omicron variant infected cases with 2019-nCoV IgG positive at admission and not presented with fever are both shorter.
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The detection and molecular characterization of circulating tumor cells(CTCs) is one of the most important tool for liquid biopsy, which has the potential to enable non-invasive diagnostic tests for personalized medicine. Commercial platforms represented by CellSearch, the first FDA approved assay, have been considered to be valid for CTCs detection. However, special equipment and consumptive materials are required in the techniques listed above. Besides, most of them can not differentiate between apoptotic and viable cells, which indicates the portion of active and functional CTCs. Therefore, how to develop novel method for CTCs enrichment with metastatic potential has great significance in clinical routine. Telomerase-specific replication-selective oncolytic viruses expressing green fluorescent protein(GFP), including herpes simplex virus and adenovirus, allow the detection for human CTCs in the peripheral blood. After 24 h of transfection with recombinant virus, the tumor cells stably express GFP, and it could be used for CTCs counting by fluorescent microscopy or flow cytometry. Moreover, downstream analysis would be achieved by combination with PCR or DNA sequencing. Recombinant virus enables early detection of metastatic tumor cells, because the fluorescent signal is amplified only in viable, infected CTCs, by viral replication. This GFP-expressing virus-based method is remarkably sensitive, simple, and feasible, and it offers a new opportunity to detect and characterize CTCs in clinical routine.
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Objective To explore the inflammatory mechanisms of pulmonary embolism ( PTE ) and/or deep venous thrombosis ( DVT ) in elders secondary to chronic obstructive pulmonary disease ( COPD) exacerbation.Methods A total of 26 elders with acute exacerbation of high-risk COPD secondary PTE and/or DVT and 26 patients with low-risk COPD during stable phase diagnosed during the period of January 2008 to December 2012 were enrolled.The relevant parameters of routine blood examination , blood viscosity, D-dimer, fibrinogen ( FIB), arterial blood gas, blood cytokine, erythrocyte sedimentation rate ( ESR ) and C-reactive protein ( CRP ) were retrospectively analyzed.Results The major nonspecific symptoms were cough, sputum and dyspnea.The mean of neutrophile percentage (N%), D-dimer, FIB, interleukin-6 (IL-6), tumor necrosis factor (TNF), C-reactive protein (CRP), low and high shear blood viscosity in blood samples of patients with acute exacerbation of high-risk COPD secondary PTE and ( or ) DVT were higher than those of the control group ( t =3.339, 2.700, 2.207, 2.431, 2.257, 2.143, 2.223, 2.797, all P<0.05).However arterial partial pressure of oxygen ( PaO2 ) was lower than that of lower-risk COPD patients (t=4.312, P<0.05).IL-6 in blood of patients with acute exacerbation of high-risk COPD secondary PTE and ( or) DVT was positively correlated with low-shear blood viscosity , D-dimer and FIB (r=0.437, 0.624, 0.429, all P<0.05).TNF in blood of patients with acute exacerbation of high-risk COPD secondary PTE and ( or ) DVT was positively correlated to FIB , low and high cut blood viscosity ( r =0.624, 0.519, 0.513, all P <0.05 ).Plasma CRP in blood of patients with acute exacerbation of high-risk COPD secondary PTE and/or DVT was positively correlated with D-dimer, FIB, IL-6 and TNF ( r=0.478, 0.541, 0.533, 0.491, all P<0.05).Conclusions Inflammation may exist in elders with acute exacerbation of high-risk COPD secondary thrombotic disease.IL-6 and TNF may promote thrombosis secondary to acute exacerbation of COPD disease.Early screening and/or prophylactic anticoagulation are necessary for prevention.
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OBJECTIVE To observe a time course of keratinocyte growth factor(KGF) and surfactant protein A(SPA) changes in rats with Pseudomonas aeruginosa pneumonia and to find out the significances of them.METHODS Specific pathogen-free male Sprague-Dawley rats were used to study.Standard P.aeruginosa strain ATCC 27853 was instilled into airway by the tracheal route to induce model of pneumonia.Samples of lung tissue and BALF were harvested before infection,and 6 h,9 h and 72 h after infection.Six rats per each point were sacrificed for harvesting samples.Expression of KGF protein in lungs was detected by Western blotting.Western-dot-blot was used to detect SPA expressions in BALF.RESULTS After infected with P.aeruginosa,KGF protein in lungs was markedly increased,reached the peak at 72 h postinfection.KGF protein level at 72 h postinfection was markedly higher than that of before infection(P