BACKGROUND: The presence of fibrosis is a criterion for subtype classification in the newly updated hypersensitivity pneumonitis (HP) guidelines. The present study aimed to summarize differences in clinical characteristics and prognosis of non-fibrotic hypersensitivity pneumonitis (NFHP) and fibrotic hypersensitivity pneumonitis (FHP) and explore factors associated with the presence of fibrosis. METHODS: In this prospective cohort study, patients diagnosed with HP through a multidisciplinary discussion were enrolled. Collected data included demographic and clinical characteristics, laboratory findings, and radiologic and histopathological features. Logistic regression analyses were performed to explore factors related to the presence of fibrosis. RESULTS: A total of 202 patients with HP were enrolled, including 87 (43.1%) NFHP patients and 115 (56.9%) FHP patients. Patients with FHP were older and more frequently presented with dyspnea, crackles, and digital clubbing than patients with NFHP. Serum levels of carcinoembryonic antigen, carbohydrate antigen 125, carbohydrate antigen 153, gastrin-releasing peptide precursor, squamous cell carcinoma antigen, and antigen cytokeratin 21-1, and count of bronchoalveolar lavage (BAL) eosinophils were higher in the FHP group than in the NFHP group. BAL lymphocytosis was present in both groups, but less pronounced in the FHP group. Multivariable regression analyses revealed that older age, <20% of lymphocyte in BAL, and ≥1.75% of eosinophil in BAL were risk factors for the development of FHP. Twelve patients developed adverse outcomes, with a median survival time of 12.5 months, all of whom had FHP. CONCLUSIONS Older age, <20% of lymphocyte in BAL, and ≥1.75% of eosinophil in BAL were risk factors associated with the development of FHP. Prognosis of patients with NFHP was better than that of patients with FHP. These results may provide insights into the mechanisms of fibrosis in HP.
Humans ; Bronchoalveolar Lavage Fluid ; Prospective Studies ; Alveolitis, Extrinsic Allergic/diagnosis* ; Fibrosis ; Carbohydrates

OBJECTIVE: To identify pathogenic mutations in 25 Chinese pedigrees affected with congenital adrenal hyperplasia (CAH). METHODS: Mutations of the CYP21A2 gene were detected with locus-specific PCR/restriction endonuclease analysis, multiplex ligation-dependent probe amplification assay, and direct sequencing of the entire CYP21A2 gene. Prenatal diagnosis was offered to fetuses at risk for CAH. RESULTS: All 50 alleles of the CYP21A2 gene carried by the 25 pedigrees were successfully delineated. Large deletions and conversions have accounted for 16 (32%) of the alleles, which included 9 entire CYP21A2 gene deletions, 6 chimeric CYP21A1P/CYP21A2 genes, and 1 partial conversion of the CYP21A2 gene. For the remaining 34 alleles, there were 9 micro-conversions and 4 de novo mutations [including a previously unreported c.62G>A (p.Trp21X) mutation]. Prenatal diagnosis was provided for 28 fetuses with a high risk for CAH, among whom 8 were found to be affected. CONCLUSION The detection of CYP21A2 gene mutations can facilitate appropriate genetic counseling and prenatal diagnosis for the affected pedigrees.
Adrenal Hyperplasia, Congenital ; diagnosis ; genetics ; Asian Continental Ancestry Group ; China ; Female ; Humans ; Mutation ; Pedigree ; Pregnancy ; Prenatal Diagnosis ; Steroid 21-Hydroxylase ; genetics

OBJECTIVETo analyze two fetuses with multiple malformations revealed by ultrasonography using single nucleotide polymorphism array (SNP array), and to explore the strategy for the prenatal diagnosis of 1p36 deletion syndrome.

METHODSAmniocentesis was performed on the two pregnant women. Amnion fluid cells were cultured, and karyotypes of the fetuses were determined through G-banding analysis. Whole genome SNP array was used to detect genomic anomalies of the two fetuses. The karyotypes of their parents were determined through G-banding analysis of peripheral venous blood samples.

RESULTSG-banding analysis showed a 46,XY,add(1p36)? and a 46,XX,add(1p36)? karyotype for fetuses 1 and 2, respectively. SNP array analysis showed that the fetus 1 had arr[19]1p36.33p36.32 (752 566 - 3 393 462)×1 and 7q35q36.3 (144 480 549 - 159 119 486)×3, and fetus 2 had arr[19]1p36.33p36.23 (752 566 - 8 362 754)×1, 6p25.3p22.3 (204 909 - 20 182 185)×3. The mother of fetus 1 had a 46,XX,t(1;7)(p36;q35) karyotype, and the mother of fetus 2 had a 46,XX,t(1;6)(p36;p22) karyotype. The karyotypes of both fathers appeared to be normal.

CONCLUSIONSNP array has the advantages such as high sensitivity and high accuracy for prenatal diagnosis, and can provide more detailed information for genetic counseling of 1p36 deletion syndrome.

Adult ; Amniocentesis ; Chromosome Banding ; Chromosome Deletion ; Chromosome Disorders ; diagnosis ; Chromosomes, Human, Pair 1 ; Female ; Humans ; Karyotyping ; Polymorphism, Single Nucleotide ; Pregnancy ; Prenatal Diagnosis

Objective To statistically summarize the adverse reactions of anti-TB drugs treatment,to analyze the influencing factors of leucopenia and to compare the effect of Qijiao Shengbai Capsule and Leucogen Tablet in the treatment of leucopenia.Methods The adverse reactions in 840 TB patients diagnosed from September 2014 to November 2015 were statistically analyzed.The influencing factors of leucopenia were analyzed.Finally,the effect of Qijiao Shengbai Capsule(n=480) and Leucogen Tablets (n=360) for treating leucopenia.Results Clinicians paid less attention to routine blood monitoring (39.4 ％).Among adverse reactions,the damage of liver function had the highest incidence rate(abnormal liver enzymes 27.0％,increased bile acid 8.2％),followed by leukopenia [25.4％,mainly degree Ⅰ (16.9％)];female patients(P=0.000) and complicating liver damage(P=0.010) might be the risk factors of leukopenia.After treatment by two kinds of drug,white blood cells count was increased,the difference was statistically significant(P=0.000).Conclusion The occurrence rate of leucopenia is higher,females and liver function damage are easier to appear,so more attention should be paid to monitoring the blood routine in return visit.The two kinds of drug for treating leucopenia induced by anti-TB drugs have definite effect and could be used in clinic.

OBJECTIVETo develop and validate a method for mutation screening and prenatal diagnosis of TSC1/TSC2 mutations among patients with tuberous sclerosis complex (TSC) by Ion Torrent semiconductor sequencing.

METHODSPotential mutations of SC1/TSC2 gene was detected in 2 TSC families and 1 sporadic TSC patient using an Ion Torrent PGM sequencer. Candidate variants were validated by Sanger sequencing. The corresponding site of TSC2 in the fetus of family 2 was also detected with Sanger sequencing.

RESULTSIon Torrent semiconductor sequencing has identified a probably pathogenic TSC2 mutation (c.311-312insGCTG) in the patient from family 1, and a probably pathogenic TSC2 mutation (c.1790A>G) in the patient of family 2.

CONCLUSIONTargeted Ion Torrent PGM sequencing is an accurate and efficient method to detect TSC1/TSC2 mutations in TSC.

Adult ; Base Sequence ; DNA Mutational Analysis ; Female ; Humans ; Male ; Molecular Sequence Data ; Mutation ; Pedigree ; Pregnancy ; Prenatal Diagnosis ; Tuberous Sclerosis ; embryology ; genetics ; Tumor Suppressor Proteins ; genetics ; Young Adult

Objective To develop and validate a method for detecting factor 8 gene (F8) mutations in hemophilia A patients by Ion Torrent semiconductor sequencing .Methods Intron 22 and intron 1 inversions of F8 gene were identified by long distance PCR (LD-PCR), other mutations in the F8 gene were identified by Ion Torrent sequencing.Candidate variants were validated by Sanger sequencing .Sanger sequencing was applied to screen HA carriers from 11 female family members in the 8 pedigrees.One pregnant woman was offered prenatal diagnosis via analyzing the fetal DNA obtained through amniocentesis . Results Four missense mutations ( c.1331A >C, 1648C >T, c.6506G >A, c.6544C >T), two frameshift mutations ( c.2393 _2394insT, c.6320delG), one splicing mutation ( IVS5 +5G >A), one nonsense mutation (c.43C >T) and one Inv22 mutation were identified in all nine probands respectively . Among 11 female family members, 10 females were identified to be HA carriers, and one didn′t carry the maternal pathogenic mutation.Prenatal diagnosis result showed that the fetus inherited the wild -type maternal allele and was predicted to be unaffected by HA .Conclusion The targeted Ion Torrent sequencing is a reliable and efficient method to detect F8 mutations in patients with Hemophilia A disease .

OBJECTIVETo explore the value of multiplex ligation-dependent probe amplification (MLPA) for rapid detection of aneuploidies and structural chromosomal abnormalities during prenatal diagnosis.

METHODSTwo hundred and eight six amniotic fluid samples were analyzed with both MLPA and conventional karyotyping. Structural abnormalities were verified with array comparative genomic hybridization.

RESULTSTen cases of trisomy 21, 2 cases of trisomy 18, 1 case of trisomy 13, 1 case of mosaic trisomy 21, 1 case of 45,X, 1 case of large deletion of Xp, 1 case of trisomy 18p and 1 case of large deletion of 18p and 18q were identified. The same results were derived by both MLPA and conventional karyotyping. Structural abnormalities were verified by array comparative genomic hybridization (aCGH) with 100% accuracy.

CONCLUSIONIn addition to aneuploidies, MLPA can rapidly identify large deletions and duplications of chromosomes 21, 18, 13, X and Y. MLPA is supplementary to conventional karyotyping for identification of such chromosomal abnormalities prenatal diagnosis.

Adult ; Aneuploidy ; Female ; Humans ; Multiplex Polymerase Chain Reaction ; methods ; Pregnancy ; Prenatal Diagnosis ; methods ; Young Adult

Objective To investigate activated nano carbon in prophylactic central lymph node dissection of T1 papillary thyroid non-microcarcinoma.Methods Patients with T1 papillary thyroid non-microcarcinoma in Thyroid Surgery Department of Sun Yat-sen Memorial Hospital of Sun Yat-sen University undergoing surgery from Jan.2012 to Jun.2013 were divided into 2 groups:odd numbers were the experimental group,and even numbers were the control group.Activated nano carbon was injected in the affected side of the thyroid in the experimental group.The lymph node metastasis,parathyroid function,and the rate of recurrent laryngeal nerve (RLN) injury were compared between the 2 groups.Results The total number of resected lymph nodes in the experimental group and the control group were 327 and 238 respectively.The positive lymph nodes in the experimental group and the control group were 120 (36.7％)and 56 (23.5 ％)respectively.The difference had statistical significance (P =0.000 85).The number of patients with lymphatic metastasis in the experimental group and the control group was 42 (56％) and 30 (40％) respectively.The difference had statistical significance (P =0.049 9).The average number of positive lymph node for patients in the experimental group and the control group was (2.86 ± 0.13) and(1.87 ± 0.09) respectively.The difference had statistical significance(P =0.009).The rate of transient hypoparathyroidism in the experimental group and the control group was 34.7％ and 60％ respectively.The difference had statistical significance (P =0.002).The incidence of hoarseness caused by RLN injury was 2.7％ and 4％ respectively in the experimental group and the control group.The difference had no statistical significance(P =1.000).Conclusions Activated nano carbon plays an important role in prophylactic central lymph node dissection of T1 papillary thyroid non-microcarcinoma phase.It not only contributes to lymph node dissection,but also protects parathyroid.However,it can't reduce the incidence of RLN injury.

Objective To investigate the causes of thyroid carcinoma reoperation and to explore the tim-ing, surgical pattern of reoperation .Methods The clinicopathologic data of 127 patients undergoing reoperation for differentiated thyroid carcinoma ( DTC) from Sep 2006 to Sep 2011 were retrospectively analyzed .Results The residual rate of first thyroid operation was 54.3%, and the lymphatic metastasis rate was 31.5%.The rate of temporary and permanent recurrent laryngeal nerve injury after reoperation was 3.1%(4/127)and 1.6%(2/127) respectively .The rate of temporary and permanent hypoparathyroidism was 4.7%( 6/127 ) and 0.8%( 1/127 ) respectively .No recurrence of thyroid carcinoma or metastasis of cervical lymph node was reported after reopera -tion during a follow-up of 6 months to 6years.Conclusions Reoperation should be performed according to the initial operative and pathological findings in DTC patients who underwent local resection .The rate of complication in the reoperation , recurrence of thyroid carcinoma and metastasis of cervical lymph node can be effectively re -duced in meticulous and experienced hands .