Association of body mass index with disease severity and prognosis in patients with non-cystic fibrosis bronchiectasis.

The objective of this observational, multicenter study was to evaluate the association of body mass index (BMI) with disease severity and prognosis in patients with non-cystic fibrosis bronchiectasis. A total of 339 patients (197 females, 142 males) diagnosed with non-cystic fibrosis bronchiectasis by high-resolution computed tomography were classified into four groups: underweight (BMI<18.5 kg/m2), normal weight (18.5≤BMI<25.0 kg/m2), overweight (25.0≤BMI<30.0 kg/m2), and obese (BMI≥30.0 kg/m2). Clinical variables expressing disease severity were recorded, and acute exacerbations, hospitalizations, and survival rates were estimated during the follow-up period. The mean BMI was 21.90 kg/m2. The underweight group comprised 28.61% of all patients. BMI was negatively correlated with acute exacerbations, C-reactive protein, erythrocyte sedimentation rate, radiographic extent of bronchiectasis, and chronic colonization by P. aeruginosa and positively correlated with pulmonary function indices. BMI was a significant predictor of hospitalization risk independent of relevant covariates. The 1-, 2-, 3-, and 4-year cumulative survival rates were 94%, 86%, 81%, and 73%, respectively. Survival rates decreased with decreasing BMI (χ2=35.16, P<0.001). The arterial carbon dioxide partial pressure, inspiratory capacity, age, BMI, and predicted percentage of forced expiratory volume in 1 s independently predicted survival in the Cox proportional hazard model. In conclusion, an underweight status was highly prevalent among patients with non-cystic fibrosis bronchiectasis. Patients with a lower BMI were prone to developing more acute exacerbations, worse pulmonary function, amplified systemic inflammation, and chronic colonization by P. aeruginosa. BMI was a major determinant of hospitalization and death risks. BMI should be considered in the routine assessment of patients with non-cystic fibrosis bronchiectasis.

Diagnostic value of cytological and microbiological methods in cryptococcal meningitis.

The aim of this study was to investigate diagnostic methods for cryptococcal meningitis (CM). A retrospective analysis was conducted for 31 patients with CM confirmed by etiologic detection of cerebrospinal fluid in our hospital in the past 5 years. Nineteen cases in 31 patients were confirmed with CM in the first diagnosis, with a misdiagnosis rate of 38.7%. The positive rates of cryptococcus detection in cerebrospinal fluid with May-Grünwald-Giemsa (MGG)-, ink-, and Alcian blue-staining methods were 86.9, 70.9, and 80.6%, respectively. The misdiagnosis rate of CM is high during the early stage of disease. The total positive rate of cryptococcus diagnosis using the MGG-staining method was significantly higher than that using the ink-staining method. These results are important for diagnosing CM.

Association of CD14 G(-1145)A and C(-159)T polymorphisms with reduced risk for tuberculosis in a Chinese Han population.

Although the role of CD14 in mediating signals from Toll-like receptors to recognize Mycobacterium tuberculosis is known, how polymorphisms in this gene affect the susceptibility to develop tuberculosis are still not clear. We examined whether single nucleotide polymorphisms at positions -1145 and -159 in the promoter region of the CD14 gene are associated with tuberculosis in a Chinese Han population in a case-control study of 432 Chinese patients with tuberculosis and 404 ethnically matched healthy controls. Genotyping was performed to identify polymorphisms of the CD14 gene by PCR-DNA sequencing. Both the frequency of allele T in the C(-159)T polymorphism (odds ratio (OR) = 1.4; 95% confidence interval (95%CI) = 1.148-1.708) and allele G in the G(-1145)A polymorphism (OR = 1.512; 95%CI = 1.236- 1.849) were significantly more frequent in cases than in controls. The frequencies of genotypes CC and CT in the C(-159)T polymorphism, as well as the frequencies of genotypes AA and AG, were lower in cases than in controls. Based on our results, we conclude that G(-1145)A and C(-159)T polymorphisms of CD14 are associated with decreased risk for the development of tuberculosis in the Chinese Han population.

Genetic instability and CpG methylation in the 5'-flanking region of the PAI-1 gene in Chinese patients with gastric cancer.

We explored a possible correlation of genetic instability and CpG methylation in the 5'-flanking region of the PAI-1 gene with clinicopathologic features of gastric cancer in Chinese patients and looked for molecular markers for diagnosing gastric tumor development. Microsatellite instability and loss of heterozygosity of the PAI-1 gene locus D7S515, D7S471 and pai-1 in 50 specimens of gastric cancer and relevant pericancerous tissues were detected by PCR-single strand conformation polymorphism (PCR-SSCP) with sliver staining. Methylation-specific PCR was used to detect CpG methylation in the 5'-flanking region of the PAI-1 gene. Microsatellite instability was significantly more common in the negative than in the positive serosa infiltration group of gastric cancer (42.86 vs 2.33%). The frequency of microsatellite instability was significantly lower in the cases with lymph node metastasis than in those without metastasis (18.18 vs 2.56%); however, it was significantly higher in the low differentiation group than that in the middle or high differentiation groups (21.05 vs 0.00%). CpG methylation in the 5'-flanking region of the PAI-1 gene did not differ significantly. Microsatellite instability and loss of heterozygosity of the PAI-1 gene apparently regulates the development of gastric cancer through different pathways. Microsatellite instability could be used as a molecular marker for the development of gastric cancer. CpG methylation in the 5'-flanking region of the PAI-1 gene appears not to be involved in the development of gastric cancer.

Association of TIRAP (MAL) gene polymorhisms with susceptibility to tuberculosis in a Chinese population.

Toll-interleukin 1 receptor (TIR) domain containing adaptor protein (TIRAP; also known as MAL) is an essential adaptor molecule in Toll-like receptor signaling, involved in activating the innate immune response during infection. Genetic variations in the TIRAP gene may influence human susceptibility to infectious disease. To date, in the Chinese population, a possible predisposition of TIRAP gene variants to tuberculosis has not been reported. We investigated whether TIRAP gene polymorphisms are associated with the development of tuberculosis in a Chinese population. We investigated all the single-nucleotide polymorphisms (SNPs) within the TIRAP exon 5 in a case-control study of 212 patients with tuberculosis and 215 controls in a Chinese population. Genotyping was performed to identify the polymorphisms of TIRAP gene by PCR-DNA sequencing method. Haplotypes for the TIRAP gene variants were constructed using Haplo view version 4.2. Six polymorphisms of the SNPs listed in the National Center for Biotechnology Information database were detected in these Chinese tuberculosis patients. It was found that both the frequency of the 286A allele (odds ratio (OR) = 13.37; 95% confidence interval (CI) = 0.75-238.3; P < 0.01) and the frequency of 286AG genotype (OR = 13.57; 95%CI = 0.76-242.5; P < 0.01) were significantly higher in patients than in healthy controls. However, two other SNPs, C539T and C558T, reported to be associated with tuberculosis in other populations, were found not to be associated with tuberculosis in this Chinese population. We conclude that TIRAP G286A (D96N) polymorphism is associated with susceptibility to tuberculosis and may be a new risk factor for the development of tuberculosis in China.

Lack of association between MD-2 promoter gene variants and tuberculosis.

Myeloid differentiation-2 (MD-2) is an essential component of the CD14-TLR4/MD-2 receptor complex involved in microbial cell wall component recognition during infection. Genetic variations in the MD-2 gene may influence human susceptibility to infectious diseases. To date, a predisposition of MD-2 gene variants to contract tuberculosis has not been reported. We investigated whether MD-2 gene polymorphisms were associated with the development of tuberculosis in a Chinese population. The six common polymorphisms (rs11465996, rs1809442, rs1809441, rs1809440, rs16938754, and rs7842342) within the MD-2 gene promoter region were all detected in 259 patients with tuberculosis and 276 healthy control subjects by DNA sequencing. None of the allelic frequencies, haplotype patterns or genotype distributions of the assayed polymorphisms was found to be significantly different between patients and controls (P > 0.05). We conclude that these gene variants in the MD-2 gene promoter region are not associated with tuberculosis, and apparently do not play a role in susceptibility to tuberculosis in the Chinese population.