The Sixth Hospital of Shaoxing

Shaoxing, China

The Sixth Hospital of Shaoxing

Shaoxing, China
SEARCH FILTERS
Time filter
Source Type

Xu D.-D.,Zhejiang University | Deng D.-F.,Zhejiang University | Li X.,Zhejiang Province Peoples Hospital | Wei L.-L.,The Sixth Hospital of Shaoxing | And 12 more authors.
Proteomics | Year: 2014

Pulmonary tuberculosis (TB) caused by Mycobacterium tuberculosis is a chronic disease. Currently, there are no sufficiently validated biomarkers for early diagnosis of TB infection. In this study, a panel of potential serum biomarkers was identified between patients with pulmonary TB and healthy controls by using iTRAQ-coupled 2D LC-MS/MS technique. Among 100 differentially expressed proteins screened, 45 proteins were upregulated (>1.25-fold at p < 0.05) and 55 proteins were downregulated (<0.8-fold at p < 0.05) in the TB serum. Bioinformatics analysis revealed that the differentially expressed proteins were related to the response to stimulus, the metabolic and immune system processes. The significantly differential expression of apolipoprotein CII (APOCII), CD5 antigen-like (CD5L), hyaluronan-binding protein 2 (HABP2), and retinol-binding protein 4 (RBP4) was further confirmed using immunoblotting and ELISA analysis. By forward stepwise multivariate regression analysis, a panel of serum biomarkers including APOCII, CD5L, and RBP4 was obtained to form the disease diagnostic model. The receiver operation characteristic curve of the diagnostic model was 0.98 (sensitivity = 93.42%, specificity = 92.86%). In conclusion, APOCII, CD5L, HABP2, and RBP4 may be potential protein biomarkers of pulmonary TB. Our research provides useful data for early diagnosis of TB. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


Wang C.,Zhejiang University | Li Y.-Y.,Zhejiang University | Li X.,Zhejiang Province Peoples Hospital | Wei L.-L.,The Sixth Hospital of Shaoxing | And 9 more authors.
BMC Infectious Diseases | Year: 2014

Background: Mycobacterium tuberculosis infection can activate the immune system, leading to characteristic pathological changes such as inflammatory granuloma, caseous necrosis, and cavity formation.Methods: Clinical data of 187 cases of pulmonary tuberculosis (PTB) were analyzed using statistical methods, while serum levels of complement C4b (C4b), fibronectin (FN), and prolidase (PEPD) were detected using the ELISA method among the control, minimal PTB, moderate PTB, and advanced PTB groups.Results: We found significantly higher levels of serum C4b and PEPD (P = 0.018, P = 0.003), and significantly lower levels of serum FN (P < 0.001) in PTB patients. Furthermore, the serum levels of 3 proteins were significantly different among 3 PTB groups. FN level was significantly higher in the moderate PTB group, compared with patients in the minimal and advanced PTB groups (P < 0.05, P < 0.01). PEPD level was significantly higher in the moderate PTB group, compared with the minimal PTB group (P < 0.05). Analysis of clinical data showed that serum albumin, C-reactive protein (CRP), prealbumin, and C4 were significantly higher (P < 0.05), while serum globulin was significantly lower in patients with PTB (P < 0.001). A significant negative correlation was found between C4b and albumin, prealbumin. On the other hand, a significant positive correlation was found between C4b and globulin, CRP, PEPD, as well as between PEPD and CRP (P < 0.05).Conclusions: Our study showed that C4b, FN, and PEPD are associated with tissue damage, granuloma formation, and cavity formation, respectively, in patients with PTB. The present study provides a new experimental basis to understand the pathogenesis and pathological changes of PTB. © 2014 Wang et al.; licensee BioMed Central Ltd.


Zhang X.,Zhejiang University | Jiang F.,Beijing University of Chinese Medicine | Wei L.,The Sixth Hospital of Shaoxing | Li F.,Red Cross | And 9 more authors.
International Journal of Biological Sciences | Year: 2012

Mannose receptor is a member of the C-type lectin receptor family involved in pathogen molecular-pattern recognition and plays a critical role in shaping host immune response. Single nucleotide polymorphisms (SNPs) in the MRC1 gene may affect expression levels and differences in the structure and function of proteins in different individuals thereby affecting individual susceptibility to pulmonary tuberculosis. However to date MRC1 polymorphisms associated with susceptibility to pulmonary tuberculosis have not yet been reported. The present study aimed to investigate potential associations of SNPs in the MRC1 gene with pulmonary tuberculosis in a Chinese population. Six SNPs (G1186A G1195A T1212C C1221G C1303T and C1323T) in exon 7 of the MRC1 gene were genotyped using the PCR and DNA sequencing methods in the pulmonary tuberculosis patients and the healthy controls. Linkage disequilibrium analysis was performed between polymorphic sites. The study found that the allele frequency of G1186A (rs34039386) of the MRC1 gene in a Chinese population was higher in the pulmonary tuberculosis group than the healthy control group. There was a significant difference in frequency distribution between the two groups (P = 0.037; OR = 0.76; 95% CI 0.58-0.98). Genotypic analysis also indicated that the AG genotypes in a Chinese population were significantly correlated with pulmonary tuberculosis (P < 0.01; OR = 0.57; 95% CI 0.37-0.87). After adjustment for age and gender G1186A sites were found to be dominant (P < 0.01; OR = 0.59; 95% CI 0.40-0.87) over-dominant (P = 0.045; OR = 0.69; 95% CI 0.47-0.99) and additive models (P = 0.041; OR = 0.76; 95% CI 0.59-0.99) in association with pulmonary tuberculosis. But no association was found between the other 5 SNPs (G1195A, T1212C, C1221G, C1303T and C1323T) and tuberculosis (P > 0.05). This study is the first to report that genetic variants in the MRC1 gene can be associated with pulmonary tuberculosis in a Chinese population, and may reduce the risk of infecting pulmonary tuberculosis. This also provides a new experimental basis to clarify the pathogenesis of pulmonary tuberculosis. © Ivyspring International Publisher.


Zhang Y.X.,Zhejiang University | Xue Y.,Zhejiang University | Xue Y.,Henan University of Science and Technology | Liu J.Y.,Zhejiang University | And 6 more authors.
Genetics and Molecular Research | Year: 2011

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. © FUNPEC-RP.


Liu J.,Hangzhou Normal University | Jiang T.,Zhejiang University | Jiang F.,Beijing University of Chinese Medicine | Xu D.,Zhejiang University | And 5 more authors.
International Journal of Clinical and Experimental Medicine | Year: 2015

A major challenge in pulmonary tuberculosis (TB) control is early and accurate diagnosis of sputum smear negative pulmonary TB (SSN-PTB). The patients with SSN-PTB have to wait for a longer period of time before receiving proper treatment than sputum smear positive pulmonary TB (SSP-PTB) patients due to delay in diagnosis. The purpose of this study is to discover potential serum protein biomarkers for SSN-PTB. Surface-enhanced laser desorption/ionization-time of flight mass spectrometry (SELDI-TOF MS) combined with weak cation exchange (WCX) magnetic beads was used to screen serum samples from SSN-PTB patients (N = 66), SSP-PTB patients (N = 49), and healthy volunteers (N = 80). The serum protein profiles were analyzed with Biomarker Wizard system. A classification model was established using Biomarker Pattern Software (BPS). Fifty-eight protein peaks were identified to exhibit significant differences between SSN-PTB, SSP-PTB and healthy control groups (P < 0.05), among which 6 peaks were found to be down-regulated, while 10 peaks were up-regulated gradually in the healthy control, SSN-PTB, and SSP-PTB groups. Twenty-three discriminating m/z peaks were detected between SSN-PTB patients and healthy controls (P < 0.01, Fold ≥ 1.5). The classification tree combined with three protein peaks (2747.0, 4480.0, and 9410.1 Da) could distinguish SSN-PTB patients from healthy controls with a sensitivity of 83.33% and a specificity of 82.50%. Early diagnosis of SSN-PTB disease is critical in order to reduce morbidity and mortality associated with TB. The study will help to clarify the role of differential proteins in the pathogenesis of TB. © 2015, Int J Clin Exp Med.All rights reserved.


Wang C.,Zhejiang University | Chen Z.-L.,Zhejiang University | Pan Z.-F.,The First Hospital of Jiaxing | Wei L.-L.,The Sixth Hospital of Shaoxing | And 6 more authors.
International Journal of Biological Sciences | Year: 2014

The association between NOD2 and tuberculosis (TB) risk has been reported widely, but the results of previous studies remained controversial and ambiguous. To assess the association between NOD2 polymorphisms and TB risk, a meta-analysis was performed. A literature search was conducted by using the PubMed, Ovid, ISI Web of Knowledge, Elsevier ScienceDirect, and Chinese National Knowledge Infrastructure (CNKI). We identified the data from all articles estimating the association between NOD2 polymorphisms and TB risk. In total, 2,215 cases and 1,491 controls in 7 case-control studies were included. In meta-analysis, we found significant association between the Arg702Trp polymorphism and TB risk (OR = 0.43, 95% CI = 0.20-0.90, P = 0.02). However, no significant association was found between the Arg587Arg (OR = 1.31, 95% CI = 0.83-2.07, P = 0.25) and Gly908Arg (OR = 0.78, 95% CI = 0.21-2.87, P = 0.71) polymorphisms and TB risk. The present meta-analysis suggested that NOD2 Arg702Trp polymorphism was likely to be a protective factor for TB. However, the Arg587Arg and Gly908Arg polymorphisms might not be the genetic risk factors for TB susceptibility. © Ivyspring International Publisher.


PubMed | Jilin Medical College, Zhejiang University, Shaoxing University, Beijing University of Chinese Medicine and 2 more.
Type: Journal Article | Journal: PloS one | Year: 2015

Ficolin-2 (FCN2) is an innate immune pattern recognition molecule that can activate the complement pathway, opsonophagocytosis, and elimination of the pathogens. The present study aimed to investigate the association of the FCN2 gene single nucleotide polymorphisms (SNPs) with susceptibility to pulmonary tuberculosis (TB). A total of seven SNPs in exon 8 (+6359 C>T and +6424 G>T) and in the promoter region (-986 G>A, -602 G>A, -557 A>G, -64 A>C and -4 A>G) of the FCN2 gene were genotyped using the PCR amplification and DNA sequencing methods in the healthy controls group (n = 254) and the pulmonary TB group (n = 282). The correlation between SNPs and pulmonary TB was analyzed using the logistic regression method. The results showed that there were no significant differences in the distribution of allelic frequencies of seven SNPs between the pulmonary TB group and the healthy controls group. However, the frequency of the variant homozygous genotype (P = 0.037, -557 A>G; P = 0.038, -64 A>C; P = 0.024, +6424 G>T) in the TB group was significantly lower than the control group. After adjustment for age and gender, these variant homozygous genotypes were found to be recessive models in association with pulmonary TB. In addition, -64 A>C (P = 0.047) and +6424 G>T (P = 0.03) were found to be codominant models in association with pulmonary TB. There was strong linkage disequilibrium (r2 > 0.80, P < 0.0001) between 7 SNPs except the -602 G>A site. Therefore, -557 A>G, -64 A>C and +6424 G>T SNPs of the FCN2 gene were correlated with pulmonary TB, and may be protective factors for TB. This study provides a novel idea for the prevention and control of TB transmission from a genetics perspective.


Liu J.,Zhejiang University | Jiang T.,Zhejiang University | Wei L.,The Sixth Hospital of Shaoxing | Yang X.,Tongde Hospital of Zhejiang | And 6 more authors.
BMC Infectious Diseases | Year: 2013

Background: Noninvasive and convenient biomarkers for early diagnosis of tuberculosis (TB) remain an urgent need. The aim of this study was to discover and identify potential biomarkers specific for TB.Methods: The surface-enhanced laser desorption ionization time of flight mass spectrometry (SELDI-TOF MS) combined with weak cation exchange (WCX) magnetic beads was used to screen serum samples from 180 cases of TB and 211 control subjects. A classification model was established by Biomarker Pattern Software (BPS). Candidate protein biomarkers were purified by reverse phase-high performance liquid chromatography (RP-HPLC), identified by MALDI-TOF MS, LC-MS/MS and validated using enzyme-linked immunosorbent assay (ELISA).Results: A total of 35 discriminating m/z peaks were detected that were related to TB (P < 0.01). The model of biomarkers based on the four biomarkers (2554.6, 4824.4, 5325.7, and 8606.8 Da) was established which could distinguish TB from controls with the sensitivity of 83.3% and the specificity of 84.2%. The candidate biomarker with m/z of 2554.6 Da was found to be up-regulated in TB patients, and was identified as a fragment of fibrinogen, alpha polypeptide isoform alpha-E preproprotein. Analysis in 22 patients with TB showed increased fibrinogen degradation product (FDP) (5,005 ± 1,297 vs. 4,010 ± 1,181 ng/mL, P < 0.05) and in 142 patients showed elevated plasma fibrinogen levels.Conclusions: A diagnostic model for TB with high sensitivity and specificity was developed using mass spectrometry combined with magnetic beads. Fibrinogen was identified as a potential biomarker for TB and showed diagnostic values in clinical application. © 2013 Liu et al.; licensee BioMed Central Ltd.


PubMed | Zhejiang Hospital, The Sixth Hospital of Shaoxing, The First Hospital of Jiaxing and Zhejiang University
Type: Journal Article | Journal: International journal of biological sciences | Year: 2016

The epidemic of pulmonary tuberculosis (TB), especially multidrug-resistance tuberculosis (MDR-TB) presented a major challenge for TB treatment today. We performed iTRAQ labeling coupled with two-dimensional liquid chromatography-tandem mass spectrometry (2D LC-MS/MS) and Solexa sequencing among MDR-TB patients, drug-sensitive tuberculosis (DS-TB) patients, and healthy controls. A total of 50 differentially expressed proteins and 43 differentially expressed miRNAs (fold change >1.50 or <0.60, P<0.05) were identified in the MDR-TB patients compared to both DS-TB patients and healthy controls. We found that 22.00% of differentially expressed proteins and 32.56% of differentially expressed miRNAs were related, and could construct a network mainly in complement and coagulation cascades. Significant differences in CD44 antigen (CD44), coagulation factor XI (F11), kininogen-1 (KNG1), miR-4433b-5p, miR-424-5p, and miR-199b-5p were found among MDR-TB patients, DS-TB patients and healthy controls (P<0.05) by enzyme-linked immunosorbent assay (ELISA) and SYBR green qRT-PCR validation. A strong negative correlation, consistent with the target gene prediction, was found between miR-199b-5p and KNG1 (r=-0.232, P=0.017). Moreover, we established the MDR-TB diagnostic model based on five biomarkers (CD44, KNG1, miR-4433b-5p, miR-424-5p, and miR-199b-5p). Our study proposes potential biomarkers for MDR-TB diagnosis, and also provides a new experimental basis to understand the pathogenesis of MDR-TB.


PubMed | Zhejiang Hospital, The Sixth Hospital of Shaoxing, The First Hospital of Jiaxing and Zhejiang University
Type: | Journal: Scientific reports | Year: 2015

Rapid and efficient methods for the determination of cured tuberculosis (TB) are lacking. A total of 85 differentially expressed serum proteins were identified by iTRAQ labeling coupled with two-dimensional liquid chromatography-tandem mass spectrometry (2D LC-MS/MS) analysis (fold change >1.50 or <0.60, P<0.05). We validated albumin (ALB), Rho GDP-dissociation inhibitor 2 (ARHGDIB), complement 3 (C3), ficolin-2 (FCN2), and apolipoprotein (a) (LPA) using the enzyme-linked immunosorbent assay (ELISA) method. Significantly increased ALB and LPA levels (P=0.036 and P=0.012, respectively) and significantly reduced ARHGDIB, C3, and FCN2 levels (P<0.001, P=0.035, and P=0.018, respectively) were observed in cured TB patients compared with untreated TB patients. In addition, changes in ALB and FCN2 levels occurred after 2 months of treatment (P<0.001 and P=0.030, respectively). We established a cured TB model with 87.10% sensitivity, 79.49% specificity, and an area under the curve (AUC) of 0.876. The results indicated that ALB, ARHGDIB, C3, FCN2, and LPA levels might serve as potential biomarkers for cured TB. Our study provides experimental data for establishing objective indicators of cured TB and also proposes potential markers for evaluating the efficacy of anti-TB drugs.

Loading The Sixth Hospital of Shaoxing collaborators
Loading The Sixth Hospital of Shaoxing collaborators