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Objective Childhood asthma is closely related to MP infection.This study was to investigate the distribution of ORMDL3 and HLA-DQ gene SNP in children with MP-associated asthma and gene-gene interactions.Methods One hundred and ninety-four patients with MP infection were enrolled.Extraction of whole blood genomic DNA was carried out.The genotype was collected by Flnidigm Juno 96.96 Genotyping integrated fluid pathway system.The patients were divided into MP-asthma group and MP-non-asthma group.Gene-gene interaction was analyzed by generalized multifactor dimensionality reduction.Results MP-asthma group included 63 cases (32.5％),MP-non asthma group included 131 cases (67.5％).ORMDL3 gene rs4794820 had three genotypes of AG,GG,AA.,MP-asthma group GG genotype and G allele frequency was higher than that in MP-non-asthma group.The frequency of AA genotype was the lowest among the two groups,but in the MP-non-asthma group were higher than that in the MP-asthma group.The rs7216389 had three genotypes of TT、TC、CC,the frequency of TT genotype and T allele in MP-asthma group was significantly higher than that in MP-non-asthma group.The frequency of CC genotype was the lowest among the two groups,but CC genotype in MP-non-asthma group was significantly higher than that in MP-asthma group.The rs794820 GG genotype and rs7216389 TT genotype were found to be risk factors.ORMDL3、HLA-DQA1 and HLA-DQA2 have gene-gene interaction.Conclusion MP infection is an important external cause of asthma in children.The genotype of rs7794820 GG genotype and rs7216389 TT genotype are an important internal cause of asthma after childhood MP infection.ORMDL3 rs4794820,rs7216389 and HLA-DQA1 rs9272346,HLADQA2 rs7773955 have gene-gene interaction,synergistically enhance the risk of asthma associated with asthma in children with MP.
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Objective@#To analyze the clinical manifestations, cilia ultrastructure and gene variations of primary ciliary dyskinesia (PCD).@*Methods@#Analysis of three cases diagnosed as PCD by transmission electron microscopy of the endobronchial biopsy material in Division of Pediatric Pulmonology of Shandong Provincial Hospital between 2013 and 2016. Target gene sequence capture and next generation sequencing were used to analyze the gene. Related literatures on gene variation of PCD in Chinese were reviewed from Online Mendelian Inheritance in Man, Human Gene Mutation Database, PubMed and CNKI up to July 2017 by using search terms of "PCD" , "gene" , "Chinese".@*Results@#There were one male and two females aged from 10 to 11 years. The common symptoms included recurrent respiratory infection, sinusitis and bronchiectasis. Two of them had situs inversus. Case 1 had lack of outer and inner dynein arms with compound heterozygous mutation of LRRC6. Case 2 had outer and inner dynein arms defects with heterozygous mutations of DNAH5 and DNAH11. Case 3 had abnormality in microtubule and inner dynein arms with homozygous mutation of CCDC39. All the variations mentioned above have not been reported before. Twelve cases have been reported about gene variations in PCD in Chinese from eight reports. All these patients had recurrent respiratory infection starting soon after birth, rhinosinusitis, and bronchiectasis. Nine of them had dextrocardia. Four cases have taken an effective nasal (or bronchial) mucosal biopsy. 1 case had inner and outer dynein arms defects. One case had inner dynein arms and radial spokes defects. One case had microtubule and central pair defects. And 1 case had normal cilia ultrastructure. Eight kinds of gene variations were found. Three cases had gene variations of DNAH5. 2 cases had gene variations of DYX1C1. 2 cases had gene variations of CCNO. There was 1 case with gene variations of CCDC39, CCDC40, HYDIN, ARMC4 and DNAI1 separately.@*Conclusions@#Recurrent respiratory infection starting soon after birth, rhinosinusitis, and bronchiectasis are the common symptoms of PCD. Eleven of fifteen Chinese PCD patients with positive gene mutations were Kartagener syndrome. Cilia ultrastructure showed defects of inner and outer dynein arms, radial spokes, microtubule and central pair. Ten kinds of gene variations were found: DNAH5, DYX1C1, CCNO, CCDC39, CCDC40, HYDIN, ARMC4, DNAI1, LRRC6、DNAH11.
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Airway epithelial cells,which are the first line of defense against inhaled pathogens and parti-cles,play an important role in initiating airway inflammation,mucous metaplasia and keeping type 2 inflamma-tion in asthma.Mucous metaplasia of airway epithelial cells is one of the important part of airway reconstitution. The mucous overproduction in small airway leads to mucous plug,which is closely related to the high mortality of asthma.Multiple signaling and transcriptional networks influence goblet cell differentiation.These include JAK and the transcription factor STAT6,Notch,EGFR,et al.In this article,the changes of epithelial cells in asthma and its role at the beginning of asthma are described.Furthermore,the progress in airway mucous metaplasia and several related cell signaling pathways were focused on,which may provide some potential target to inhibit the secretion of mucous in asthma.
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Objective To discuss the polymorphisms of asthma susceptibility gene ORMDL3 in infantile wheezing,in order to provide a theoretical basis for early diagnosis of asthma.Methods One hundred and fifty wheezing infants were recruited and divided into 2 groups as asthma predictive index(API) positive group(n =80) and negative group (n =70).Taqman probe was applied to detect the genotypes of 2 single nucleotide polymorphisms (SNPs)in childhood asthma susceptibility gene ORMDL3,which were rs4794820 and rs7216389.The genotype distributions were analyzed and compared between 2 groups,and the correlations among genotype distribution and tidal breath pulmonary function,fractional exhaled nitric oxide (FeNO) concentration,percentage of eosinophils (EOS％),serum immune globulin E (total IgE) levels respectively were also analyzed,respectively.Results (1) The frequencies of rs4794820 AG and rs7216389 TC heterozygotes in the API positive group were the highest,which were significantly higher than those in the negative group(58.75％ vs.31.42％,56.25％ vs.32.86％ respectively,all P ＜0.01).The frequencies of GG and TT homozygotes in the API negative group were the highest,which were significantly higher than those in the positive group (58.57％ vs.30.00％,57.14％ vs.31.25％ respectively,all P ＜0.01).(2)The time to reach the peak expiratory flow in tidal breathing over the total expiratory time (TPTEF/TE) and the volume to reach the peak expiratory flow in tidal breathing over the total expiratory volume (VPEF/VE) of the infants in the API positive group were less than those in the API negative group(16.87 ±5.31 vs.20.12 ± 5.23,20.87 ± 5.92 vs.25.56 ± 6.77,respectively),and the FeNO concentration was higher than that in the API negative group [(22.44 ± 9.77) ppb vs.(13.23 ± 7.90)ppb],and the differences were significant (t =-3.776,-4.490,6.377,respectively;all P ＜ 0.01).(3) In the API positive group,the TPTEF/TE and VPEF/VE of the infants who expressed AG/TC genotype were lower than those who expressed GG/TT genotype (14.55 ± 4.83 vs.19.91 ± 4.17,18.85 ± 4.26 vs.25.20 ± 7.06,respectively,t =-4.727,-3.976,all P ＜ 0.01);while the FeNO concentrations,EOS％ and total IgE levels were higher than those who expressed GG/TT genotype [(25.02 ± 8.77) ppb vs.(18.39 ± 6.56) ppb,7.16 ± 2.62 vs.5.50 ± 1.34,(366 727 ±275 533) IU/L vs.(166 826 ± 62 865) IU/L,respectively] (t =3.484,3.409,4.589 respectively;all P ＜ 0.01).Conclusions Childhood asthma susceptibility gene ORMDL3 SNPs rs4794820 AG and rs7216389 TC heterozygotes are the risk factors for API positive infantile wheezing.The pulmonary function damage and airway inflammation of the infants who expressed AG/TC genotype are more serious than those who expressed GG/TT genotype,and more likely to develop persistent asthma.
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<p><b>OBJECTIVE</b>To analyze the clinical characteristic of Kartagener syndrome in Chinese and foreign children.</p><p><b>METHOD</b>Four cases of Kartagener syndrome diagnosed in our hospital were analyzed with literature review. The differences between Chinese and foreign children in clinical manifestations and diagnosis were compared.</p><p><b>RESULT</b>All of the cases had the following clinical manifestations: recurrent productive cough, nasosinusitis, dextrocardia, total situs inversus and bronchiectasia. Situs inversus of the airway structure was visible under the bronchoscope, and electron microscopy of the respiratory mucosa showed an abnormal ciliary ultrastructure. By using "Kartagener syndrome" and "child" as the key words, reports on 55 Chinese cases and 61 foreign cases in children were retrieved from CNKI and PubMed databases. The average age of diagnosis was 9.16 ± 3.67 years in China, which was significantly later than 7.07 ± 4.92 years in foreign countries (t=2.642, P<0.01). The main clinical manifestations were recurrent productive cough, nasosinusitis or rhinopolyp, recurrent pulmonary infection, recurrent wheezing and otitis media. Sinus imaging showed maxillary sinusitis. Dextrocardia, total situs inversus and bronchiectasia were found on thoracic and abdominal CT. The ciliary ultrastructural analysis showed shorter and missing dynein arm (6/6 cases in China and 25/27 cases in foreign) .</p><p><b>CONCLUSION</b>The clinical manifestations are recurrent upper and lower respiratory tract infection combined with dextrocardia or other situs inversus in both China and other countries. The diagnosis abroad relied more on abnormal ciliary ultrastructure observed under electron microscopy, but in China mainly relied on its typical clinical manifestations.</p>
Subject(s)
Child , Humans , Asian People , China , Cilia , Kartagener Syndrome , Diagnosis , Ethnology , Lung , Pathology , Microscopy, Electron , Respiratory Tract Infections , Diagnosis , Situs Inversus , DiagnosisABSTRACT
The modification of histone is an important mechanism of epigenetics,furthermore histone acetylation and deacetylation is one of the key modifications of histone.There are enhanced expression of histone acetylation and reduced expression and activity of histone deacetylases in asthma,which lead to the unbalance.Glucocoticoids modulate the inflammation of airway in asthma through restoring the balance of the two kinds of enzymes.Theophylline can restore the activity of histone deacetylation in steroid-resistant athma,thereby restoring corticosteroid function.It maybe a new way to find selective histone acetyltransferase inhibitors to therapy asthma.
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AIM: To study the prognositic value of PTEN and Her-2 expression in primary breast cancer.METHODS: 81 breast cancer specimens with 15 years follow-up were obtained from 1989 to 2004.Immunohistochemical methods were used to detect the expression of PTEN and Her-2 in 81 paraffin-embedded specimens.The correlation between expression of PTEN and clinipathological factors was discussed with the Chi-square test.The survival rate analysis results were calculated with Kaplan-meier method.Long-rank test and Cox model by SPSS 10.0 software.RESULTS:(1) PTEN expression significantly affects 5-year and 10-year survival rate of breast cancer(P
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AIM: To explore the relationship between methylation status of promoter region 5′CpG island and the biological phenotype in human colorectal cancer RKO cell lines. METHODS: RKO cells were treated with selective DNA methyltransferase (DNMTs) inhibitor, 5-Aza-2′-deoxycytidine (5-Aza-CdR), for 72 h. Methylation-specific PCR (MSP), T-A clone and DNA sequence analysis were used to detect 5′CpG island methylation status of p16/CDKN2 tumor suppresor gene. Cell growth, cell cycle arrest and apoptosis were analyzed by MTT, flow cytometry (FCM), fluorescent dye staining and transmission electron microscope. RESULTS: DNMTs inhibitor (5-Aza-CdR) effectively reversed the hypermethylation status of 5′CpG island. The effects of 5-Aza-CdR on cell growth inhibition (P