Patients with multidrug-resistant tuberculosis (MDR-TB) who are resistant to at least both rifampicin and isoniazid, lack effective treatment options in clinic. The gold standard for the diagnosis of MDR-TB is drug sensitivity test, which is time-consuming and has a relatively low positive detection rate. Screening early diagnostic biomarker for MDR-TB is urgent need in clinical practice. A total of 33 patients with MDR-TB, healthy controls and drug-sensitive tuberculosis (DS-TB) were included in this study. Total plasma exosomal RNA was extracted from the subjects, and the MDR-TB plasma-specific exosomal miRNAs were obtained by Illumina sequencing. There were 644 and 647 differentially expressed miRNAs in the plasma exosomes of MDR-TB patients obtained by sequencing and biogenic analysis compared with DS-TB patients and healthy controls, respectively. Differential miRNAs are mainly involved in the biological function of regulation of transcription and protein binding, and enriched in the pathways in cancer and MAPK signaling pathway. Moreover, seven plasma exosomal miRNAs in MDR-TB patients were significantly different from those in DS-TB patients and healthy controls. Among them, three of the miRNAs (hsa-miR-122-5p_R-1, hsa-miR-23b-3p_R + 1, and hsa-miR-15a-5p_R-1) were found to be in target relationship with MDR-TB related genes (NTRK2, KIDINS220, NCKAP1, MAPK9, NFAT5, ATF6 and SLC11A2) by target gene prediction analysis. Further the bioinformatic analysis showed that hsa-miR-122-5p_R-1 targets the protein PGLYRP2, a diagnostic biomarker identified in our previous study. We suggest that hsa-miR-122-5p_R-1, hsa-miR-23b-3p_R + 1, and hsa-miR-15a-5p_R-1 are closely related to MDR-TB.

Background: Pulmonary tuberculosis (TB) is a serious disease burden worldwide, and its effective early diagnosis is still facing challenges. Knowledge, acquired from multi-omics integration analysis about the association between different types of differentially expressed molecules in the plasma of TB patients and the disease traits, is anticipated to improve the accuracy of TB diagnosis through the "integrative pattern". Methods: In this study, the lncRNA-miRNA-mRNA interaction network was constructed based on the competing endogenous RNA (ceRNA) hypothesis by integrating our previous data sets of lncRNA, mRNA, miRNA, and metabolites. Moreover, the key regulatory axis was established by co-expression analysis and verified at the level of metabolites. Results: A ceRNA regulatory network consisting of 23 lncRNAs, 10 miRNAs, and 113 mRNAs was constructed. The analysis results suggested that lncRNA (OSBPL10-AS1), miRNA (has-miR-485-5p), and mRNA (SLC23A2) might be involved in the regulation of vitamin metabolism in patients with TB. Metabolite analysis showed that compared with the normal control group, TB patients had abnormal vitamin metabolism, and the expression levels of pyridoxal phosphate, pyridoxamine phosphate, and folic acid were significantly different between the two groups (p < 0.05). Conclusion: Integrated multi-omics analysis showed that vitamin metabolism disorder may be one of the pathological characteristic of TB. OSBPL10-AS1, hsa-miR-485-5p, SLC23A2, pyridoxal phosphate, pyridoxamine phosphate, and folic acid may collectively constitute the "integrative pattern" of multiple biomarkers, which may provide an accurate diagnosis of TB.

Background: Acute myocardial infarction (AMI) is the most serious type of heart disease. Clinically, there is an urgent need to discover diagnostic biomarkers for the early diagnosis of AMI. Methods: Serum proteomic profiles in AMI patients, healthy controls, and stable angina pectoris (SAP) patients were explored and compared by iTRAQ-2DLC-MS/MS. The clinical data of AMI patients were also analyzed. Differentially expressed proteins were validated by enzyme linked immunosorbent assay (ELISA), and diagnostic models were constructed. Results: A total of 39 differentially expressed proteins were identified in AMI patients. The results showed that the serum levels of apolipoprotein E (APOE) in AMI patients were notably higher than those in the healthy controls (P=0.0172). The serum levels of aspartate aminotransferase (AATC) in AMI patients were markedly higher than those in the healthy controls and SAP patients (P<0.0001 and P<0.0001, respectively). The serum levels of fibronectin (FINC) in SAP patients were significantly higher than those in the healthy controls and AMI patients (P=0.0043 and P=0.0044, respectively). Clinical data analysis showed a considerable difference in blood glucose levels, troponin I (TNI), and creatine kinase (CK) in AMI patients compared with SAP patients and healthy controls. A diagnostic model consisting of AATC and clinical indicators [lactate dehydrogenase (LDH) and CK] was established to distinguish between AMI patients and healthy controls, with an area under the curve (AUC) value of 0.993 sensitivity and specificity of 96.2% and 96.3%, respectively. A diagnostic model consisting of AATC and CK was established to distinguish between AMI patients and SAP patients, with an AUC value of 0.975 and a sensitivity and specificity of 85.2% and 79.30%, respectively. Conclusions: In this study, differentially expressed proteins in AMI patients were combined with clinical indexes, LDH and CK, and two diagnostic models were constructed. This study may provide meaningful data for the early diagnosis of AMI.

Lung cancer is characterized by a high incidence rate and low survival rate. It is important to achieve early diagnosis of the disease. We applied ultra-high performance liquid chromatography tandem mass spectrometry to screen plasma lipid spectrum in non-small cell lung cancer (NSCLC) patients, healthy controls (HC), and community-acquired pneumonia (CAP) patients. Modeling employing orthogonal partial least squares-discriminant analysis combined with t-test was used to screen the differential lipids. Logistic regression analysis was used to establish the diagnostic model, while the accuracy was verified by 10-fold cross-validation. The results showed that the abnormal metabolism of lipid in NSCLC mainly comprised fatty acid metabolism, phospholipid metabolism, and glyceride metabolism. Four potential biomarkers, including LPC (14:0/0:0), LPI (14:1/0:0), DG (14:0/18:2/0:0), and LPC (16:1/0:0), were fitted by the receiver operating characteristic curve model with the area under curve (AUC) value of 0.856, and the specificity and sensitivity were 87.0 and 78.0%, respectively. The results of cross validation showed that the AUC value of the model was 0.812, the sensitivity was 72.9%, and the specificity was 82.6%. The positive rate of four potential lipid biomarkers in this study (>60.0%) was higher than that of existing tumor biomarkers in the clinical application. We investigated the plasma lipid profile of NSCLC patients and identified lipid biomarkers with potential diagnostic values. From the lipidomics perspective, our study may lay a foundation for the biomarker-based early diagnosis of lung cancer.

Yin-deficiency-heat (YDH) syndrome is a very common subhealth status in Traditional Chinese Medicine. However, currently, there is no unified standard for diagnosing YDH syndrome. We applied the iTRAQ-2D LC-MS/MS method to explore the potential of serum protein profiles as biomarker for YDH syndrome. A total of 120 differentially expressed proteins (79 downregulated and 41 upregulated) were identified by the proteomic profiling. The results of KEGG pathway analysis showed that the functions of the differentially expressed proteins were mainly involved in complement and coagulation cascades. The clinical data showed that YDH syndrome was closely related to inflammation and coagulation, compared with the healthy controls. The ELISA validation results indicated that the expression levels of ALB, CFI, and KLKB1 were downregulated in the YDH syndrome group (p < .05). Moreover, we established a decision tree model based on the combination of these three proteins and achieved a sensitivity of 87.5%, a specificity of 84.4%, and AUC of 0.891. The results indicated that the combination of ALB, CFI, and KLKB1 may serve as potential biomarkers for diagnosing YDH syndrome. Our study can provide a new method for YDH syndrome diagnosis, and may also provide an experimental basis to understand the molecular mechanism of YDH syndrome.

Patients with multidrug-resistant tuberculosis (MDR-TB) tend to have a long course of anti-TB treatment and severe side effects. Traditional Chinese Medicine (TCM) has a synergistic effect in attenuation of MDR-TB. However, the lack of objective biological standards to classify and diagnose MDR-TB TCM syndromes could result in less effective TCM treatment. Therefore, in this study, we identified differentially expressed proteins (DEPs) in serum of individuals with MDR-TB TCM syndromes by applying isobaric tags for relative and absolute quantification coupled with two-dimensional liquid chromatography-tandem mass spectrometry (iTRAQ-2DLC-MS/MS) method and bioinformatics analysis. The functional analysis of DEPs was also performed. Additionally, DEPs among three different TCM syndromes of MDR-TB were validated by enzyme-linked immunosorbent assay (ELISA). Finally, a receiver operating characteristic (ROC) curve was performed to estimate the diagnostic ability of DEPs. A total of 71 DEPs were identified in the three different MDR-TB TCM syndrome groups such as the pulmonary Yin deficiency (PYD) syndrome group, the Hyperactivity of Fire due to Yin deficiency (HFYD) syndrome group, and the deficiency of Qi and Yin (DQY) syndrome group. The results showed that the expression level of transforming growth factor-beta-induced protein ig-h3 (TGFBI) was lower in the PYD syndrome group (p = .002), the proprotein convertase subtilisin/kexin type 9 (PCSK9) was overexpressed in the HFYD syndrome group (p < .0001), and the C-C motif chemokine ligand 14 (CCL14) expression level was reduced in the DQY syndrome group (p = .004). Our study demonstrated that serum TGFBI, PCSK9, and CCL14 may serve as potential novel biomarkers for PYD syndrome, HFYD syndrome and DQY syndrome of MDR-TB, respectively. The study provides a biological basis for MDR-TB TCM syndromes classification and can be of great significance for the treatment of different TCM syndromes.

Background: Tuberculosis (TB) treatment takes a long time, and a gold standard test to define TB cure is lacking. This may lead to early discharge of TB patients, resulting in an increased risk of disease transmission and drug resistance. Plasma lncRNAs might act as potential biomarkers to evaluate TB cure in an efficient and precise manner. Methods: A lncRNA microarray assay was used to screen differentially expressed plasma lncRNAs in untreated TB and cured TB subjects. The expression levels of lncRNAs were verified by qPCR. Target genes of lncRNAs were predicted using a coding-non-coding gene co-expression network and mRNA-lncRNA-miRNA interaction network analysis. Results: The expression levels of lncRNAs uc.48+ (p < 0.001) and NR_105053 (p = 0.03) were found to differ significantly between the untreated TB group and the cured TB group. The predicted target genes of uc.48 + were EP300, BAI1 and NR_105053 were TLR9, MYD88, BAI1, respectively. A predictive model for cured TB was established by the combination of uc.48+ and NR_105053 expression, with a sensitivity of 90.00% and specificity of 86.36%, and an area under the curve (AUC) value of 0.945. Conclusions: lncRNAs uc.48+ and NR_105053 may serve as potential biomarkers to distinguish between untreated TB patients and cured TB subjects. This study provides an experimental basis to evaluate the effect of TB treatment and may also provide new clues to the pathological mechanisms of TB. (C) 2020 The Author(s). Published by Elsevier Ltd on behalf of International Society for Infectious Diseases.

The lack of rapid and efficient diagnostics impedes largely the epidemic control of multidrug-resistant tuberculosis, and might misguide the therapeutic strategies as well. This study aimed to identify novel multidrug-resistant tuberculosis biomarkers to improve the early intervention, symptomatic treatment and control of the prevalence of multidrug-resistant tuberculosis. The serum small molecule metabolites in healthy controls, patients with drug-susceptible tuberculosis, and patients with multidrug-resistant tuberculosis were screened using ultra-high-performance liquid chromatography combined with quadrupole-time-of-flight mass spectrometry (UPLC-Q-TOF-MS). The differentially abundant metabolites were filtered out through multidimensional statistical analysis and bioinformatics analysis. Compared with drug-susceptible tuberculosis patients and healthy controls, the levels of 13 metabolites in multidrug-resistant tuberculosis patients altered. Among them, the most significant changes were found in N1-Methyl-2-pyridone-5-carboxamide (N1M2P5C), 1-Myristoyl-sn-glycerol-3-phosphocholine (MG3P), Caprylic acid (CA), and D-Xylulose (DX). And a multidrug-resistant tuberculosis/drug-susceptible tuberculosis differential diagnostic model was built based on these four metabolites, achieved the accuracy, sensitivity, and specificity of 0.928, 86.7%, and 86.7%, respectively. The enrichment analysis of metabolic pathways showed that the phospholipid remodeling of cell membranes was active in multidrug-resistant tuberculosis patients. In addition, in patients with tuberculosis, the metabolites of dipalmitoyl phosphatidylcholine (DPPC), a major component of pulmonary surfactant, were down-regulated. N1M2P5C, MG3P, CA, and DX may have the potential to serve as novel multidrug-resistant tuberculosis biomarkers. This research provides a preliminary experimental basis to further investigate potential multidrug-resistant tuberculosis biomarkers. Impact statement The MDR-TB incidence remains high, making the effective control of TB epidemic yet challenging. Rapid and accurate diagnosis is vitally important for improving the therapeutic efficacy and controlling the prevalence of drug resistance TB. Metabolomics has dramatic potential to distinguish MDR-TB and DS-TB. N1M2P5C, MG3P, CA, and DX that we identified in this study might have potential as novel MDR-TB biomarkers. The phospholipid remodeling of cell membranes was highly active in MDR-TB. The DPPC metabolites in TB were significantly down-regulated. This work aimed to investigate potential MDR-TB biomarkers to enhance the clinical diagnostic efficacy. The metabolic pathway distinctly altered in MDR-TB might provide novel targets to develop new anti-TB drugs.

Multidrug-resistant tuberculosis (MDR-TB), defined as tuberculosis (TB) resistant to at least isoniazid and rifampicin, is a major concern of TB control worldwide. However, the diagnosis of MDR-TB remains a huge challenge to its prevention and control. To identify new diagnostic methods for MDR-TB, a mass spectrometry strategy of data-independent acquisition and parallel reaction monitoring was used to detect and validate differential serum proteins. The bioinformatic analysis showed that the functions of differential serum proteins between the MDR-TB group and the drug-sensitive tuberculosis group were significantly correlated to the complement coagulation cascade, surface adhesion and extracellular matrix receptor interaction, suggesting a disorder of coagulation in TB. Here, we identified three potential candidate biomarkers such as sCD14, PGLYRP2 and FGA, and established a diagnostic model using these three candidate biomarkers with a sensitivity of 81.2%, a specificity of 90% and the area under the curve value of 0.934 in receiver operation characteristics curve to diagnose MDR-TB. Our study has paved the way for a novel method to diagnose MDR-TB and may contribute to elucidate the mechanisms underlying MDR-TB.

Background: The lack of rapid and efficient diagnostic methods has been one of the most frustrating challenges in controlling the pulmonary tuberculosis (TB) epidemic. This study was aimed to identify novel non-invasive biomarkers for pulmonary TB. Methods: The subjects in this study were divided into four groups: the pulmonary TB group, the community-acquired pneumonia (CAP) group, the lung cancer (LC) group, and the normal control (NC) group. Plasma small molecule metabolites were investigated in each group by using ultra-high performance liquid chromatography coupled with Q Exactive mass spectrometry. Multivariate statistical methods and bioinformatics were used to analyze the data. Results: We identified three differential plasma metabolites such as, Xanthine, 4-Pyridoxate and d-glutamic acid in the pulmonary TB group, compared to the other groups (CAP, LC and NC). The pathway enrichment analysis indicated that the energy source in pulmonary TB was multi-center, which might be involved in maintaining the reproductive ability and virulence of Mycobacterium tuberculosis. Conclusion: The results suggested that Xanthine, 4-Pyridoxate, and d-glutamic acid may serve as potential biomarkers for pulmonary TB. The present study provides experimental basis for developing potential biomarkers of pulmonary TB.

Lack of laboratory standards for cured tuberculosis (TB) can lead to early discharge of untreated TB patients from the hospital, resulting in increased risk of TB spread and of developing drug resistant Mycobacterium tuberculosis (Mtb). We used ultra-high performance liquid chromatography coupled with mass spectrometry (LC–MS) to detect heparin anticoagulant in plasma of untreated TB patients, two-month treated TB patients, cured TB subjects, and healthy controls. Screening of differentially expressed metabolites resulted in identification of four differentially expressed metabolites such as, l-Histidine, Arachidonic acid (AA), Biliverdin, and l-Cysteine-glutathione disulfide after 6 months of TB treatment. Among them, l-Cysteine-glutathione disulfide and AA could be identified after 2 months of TB treatment. We established a cured TB model with an area under the curve (AUC) of 0.909 (95% CI, 0.802–0.970), 86.2% sensitivity, and 85.2% specificity. The diagnostic model fitted from the four differential metabolites in combination (l-Histidine, AA, Biliverdin, and l-Cysteine-glutathione disulfide) can be used as potential biomarkers for cured TB. Our study provided laboratory standards for hospital discharge of TB patients, as well as experimental basis for evaluating the efficacy of anti-TB drugs.

Rapid diagnosis of pulmonary tuberculosis is an effective measure to prevent the spread of tuberculosis. However, the grim fact is that the new, rapid, and safe methods for clinical diagnosis are lacking. Moreover, although auto-lysosome is critical in clearing Mycobacterium tuberculosis, the pathological significance of microRNAs, as biomarkers of tuberculosis, in autophagosome maturation is unclear. Here, these microRNAs were investigated by Solexa sequencing and qPCR validation, and a potential diagnostic model was established by logistic regression. Besides that, the mechanism of one of the microRNAs involved in the occurrence of tuberculosis was studied. The results showed that the expression of miR-423-5p, miR-17-5p, and miR-20b-5p were significantly increased in the serum of patients with tuberculosis. The combination of these three microRNAs established a model to diagnose tuberculosis with an accuracy of 78.18%, and an area under the curve value of 0.908. Bioinformatics analysis unveiled miR-423-5p as the most likely candidate in regulating autophagosome maturation. The up-regulation of miR-423-5p could inhibit autophagosome maturation through suppressing autophagosome-lysosome fusion in macrophages. Further investigations showed that VPS33A was the direct target of miR-423-5p, and the two CUGCCCCUC domains in VPS33A 3'-UTR were the direct regulatory sites for miR-423-5p. In addition, an inverse correlation between VPS33A and miR-423-5p was found in peripheral blood mononuclear cells of patients with tuberculosis. Since the inhibition of autolysosome formation plays a critical role in tuberculosis occurrence, our findings suggests that miR-423-5p could suppress autophagosome-lysosome fusion by post-transcriptional regulation of VPS33A, which might be important for the occurrence of active tuberculosis.

This research aimed to discover potential biomarkers for evaluating the therapeutic efficacy of intensive therapy in pulmonary tuberculosis (TB). Protein profiles in 2-months intensively treated TB patients, untreated TB patients, and healthy controls were investigated with iTRAQ-2DLC-MS/MS technique. 71 differential proteins were identified in 2-months intensively treated TB patients. Significant differences in complement component C7 (CO7), apolipoprotein A-IV (APOA4), apolipoprotein C-II (APOC2), and angiotensinogen (ANGT) were found by ELISA validation. CO7 and ANGT were also found significantly different in sputum negative patients, compared with sputum positive patients after intensive treatment. Clinical analysis showed that after 2-months intensive treatment several indicators were significantly changed, and the one-year cure rate of sputum negative patients were significantly higher than sputum positive patients. Diagnostic models consisting of APOC2, CO7 and APOA4 were established to distinguish intensively treated TB patients from untreated TB patients and healthy controls with the AUC value of 0.910 and 0.935. Meanwhile, ANGT and CO7 were combined to identify sputum negative and sputum positive TB patients after intensive treatment with 89.36% sensitivity, 71.43% specificity, and the AUC value of 0.853. The results showed that APOC2, CO7, APOA4, and ANGT may be potential biomarkers for evaluating the efficacy of intensive anti-TB therapy.

[目的]寻找阴虚上火的新型诊断标志物,深化对阴虚上火的认识.[方法]对34例受试者血清样本的临床资料进行统计分析,运用ELISA法检测血清单核细胞分化抗原(monocyte differentiation antigen)CD14、激肽原-1(Kininogen-1,KNG-1)、载脂蛋白B(apolipoprotein B-100,APOB)和载脂蛋白A2(apolipoprotein A2,APOA2)的浓度,并运用ROC曲线对上述蛋白诊断上火的效果进行评估.[结果]阴虚上火患者CD14与KNG-1显著上调,APOB与APOA2显著下调,与健康对照组比较,差异具有统计学意义(P<0.001,P<0.05,P<0.05,P<0.01).将CD14、APOA2、KNG-1进行组合构建诊断模型,ROC曲线显示组合物的曲线下面积(area under curve,AUC)值为0.934,敏感度和特异度分别为100％和71.40％,具有较好的准确性.[结论]阴虚上火与能量代谢、炎症反应密切相关.CD14、APOA2、KNG-1的组合可作为临床诊断阴虚上火的潜在的生物学标志物,有助于中医疾病诊断的客观化.

This study aimed to evaluate the effects and mechanism of action of ASK1 gene on the growth and migration of gastric cancer (GC) cells. Total RNA was extracted from the gastric cell lines and GC tissues. The expression level of ASK1, and the association between ASK1 expression and clinicopathological characteristics was assessed by real-time polymerase chain reaction. The effects of ASK1 on the proliferation of HGC-27 cells were assessed by the CCK-8 assay. In addition, the effects of ASK1 on the migration of HGC-27 cells were analyzed by the migration assay using transwell chambers. The expression levels of signaling proteins related to cell migration were detected by Western blotting. Although no significant differences were observed in the expression levels of ASK1 between the GC tissue samples and the normal tissue samples (P = 0.241), ASK1 expression correlated with tumor lymph node metastasis (P = 0.008). Furthermore, ASK1 inhibited proliferation and migration of HGC-27 cells. The increase in the expression of ASK1 in HGC-27 cells induced the activation of the JNK and p38 signaling pathways. The findings demonstrated that increased ASK1 expression level inhibited migration and proliferation of HGC-27 gastric cancer cells, whereas the possible mechanism of action may be attributed to the activation of the JNK and p38 signaling pathways. Anat Rec, 301:1815-1819, 2018. © 2018 Wiley Periodicals, Inc.

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.

Pulmonary tuberculosis (TB) is among the diseases with the highest morbidity and mortality worldwide. Effective diagnostic methods for TB are lacking. In this study, we investigated long non-coding RNAs (lncRNAs) in plasma using microarray and the potential diagnostic value of lncRNAs for TB. We found a total of 163 up-regulated lncRNAs and 348 down-regulated lncRNAs. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and coding-noncoding co-expression (CNC) analyses showed that functions of differentially expressed lncRNAs were mainly enriched in the regulation of alpha-beta T cell activation and the T cell receptor signalling pathway. Four differentially expressed lncRNAs, NR_038221 (fold change = 3.79, P < 0.01), NR_003142 (fold change = 1.69, P < 0.05), ENST00000570366 (fold change = 3.04, P < 0.05), and ENST00000422183 (fold change = 2.11, P < 0.001), were verified using RT-qPCR. Among those, NR_038221, NR_003142, and ENST00000570366 were found to be up-regulated, while ENST00000422183 was down-regulated. The value of the area under the curve (AUC) for the diagnostic model consisting of the four lncRNAs was 0.845 (sensitivity = 79.2%, specificity = 75%). We further predicted 85 mRNAs and 404 miRNAs that potentially interact with these lncRNAs. Our study revealed the potential value of lncRNAs as biomarkers for early diagnosis of TB and the underlying mechanisms of these abnormally expressed lncRNAs in the pathogenesis of TB.

Pulmonary tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) poses great threat to human health. Delay in the diagnosis of TB may increase the severity and mortality, as well as increase the risk of transmission of the disease. Therefore, early diagnosis and treatment are important for the control of TB spread. The aim of this study was to discover novel biomarkers for TB. Differentially expressed proteins in the serum of patients with TB were screened and identified by iTRAQ‐2DLC‐MS/MS analysis. A total of 47 abnormal proteins were discovered in TB patients, compared with healthy controls, pneumonia and chronic obstructive pulmonary disease (COPD) patients. The levels of serum amyloid A (SAA), vitamin K‐dependent protein Z (PROZ), and C4b‐binding protein β chain (C4BPB) were significantly higher in TB patients (n=136) than healthy controls (n=66) ( P <0.0001, P <0.0001, and P <0.0001, respectively), whereas, significantly lower levels of SAA, PROZ, and C4BPB were observed in TB patients compared with pneumonia patients (n=72) ( P <0.0001, P <0.0001, and P <0.0001, respectively) and COPD patients (n=72) ( P <0.0001, P <0.0001, and P= 0.0016, respectively). After 6 months of treatment, the levels of SAA and PROZ were significantly increased ( P =0.022 and P <0.0001, respectively), while the level of C4BPB was significantly decreased ( P =0.0038) in treated TB cases (n=72). Significantly increased SAA and PROZ levels were observed in TB patients with cavitary lung lesions ( P =0.006 and P =0.03, respectively), compared with TB patients with non‐cavitary lung lesions. Meanwhile, the serum concentrations of SAA were higher in TB patients with double lung lesions than TB patients with single lung lesions ( P =0.003). The serum SAA levels were also found to be increased in smear positive TB patients than smear negative TB patients. Decision trees of TB were constructed, and receiver operating characteristic curve analysis revealed that the area under the curve value (AUC) of the diagnostic model combined by SAA, PROZ, and C4BPB was more accurate than the single serum protein. The AUC was 0.972, 0.928, 0.957, and 0.969, to discriminate the TB group from the healthy controls, pneumonia, COPD, and cured TB groups, respectively. Therefore, the results suggested that SAA, PROZ, and C4BPB may serve as potential biomarkers for TB. Our study could provide experimental data for the differential diagnosis of TB. Support or Funding Information This work was supported by grants from the National Basic Research Program of China (No.2014CB543002), the National Natural Science Foundation of China (No.81573709, No.81273882), and the scientific research fund project of South China University of Technology School of Medicine (NO. yxy2016006).

Objective To investigate serum Ig Gamma-3 Chain C Region (IGHG3) and Haptoglobin (HPT) levels in patients with pulmonary tuberculosis(TB).Methods Serum IGHG3 and HPT levels were tested by enzyme linked immunosorbent assay (ELISA) in 50 TB patients and 36 healthy subjects.Plasma fibrinogen (FIB),prothrombin time (PT),activated partial thromboplastin time (APTT),thromboplastin time (TT),blood glucose,C reaction protein (CRP),triglyceride(TG) were measured.Results Serum IGHG3) and HPT levels in TB patients were significant higher than those in healthy controls (P＜0.0001 and P =0.0037).There were significant differences in plasma FIB,APTT and CRP levels between TB patients and healthy controls (P =0.04,P =0.004,P =0.0001,respectively).Serum IGHG3 level was significantly correlated with serum CRP(r=0.372,P=0.014),and the serum HPT level was significantly correlated with the existence of tuberculosis cavity (r=0.28,P=0.04).A protein model consisting of IGHG3 and HPT was established by logistic regression analysis,and the sensitivity,specificity,and area under curve (AUC) of the model was 90.90％,80.80％,and 0.866,respectively.Conclusion IGHG3 and HPT may be potential biomarkers for TB patients.

Objective To explore the scanning of tuberculosis biomarkers. Methods The enzyme-linked immunosorbent assays aimed on proteins related with the inflammatory state were performed. Result Alpha-1-antichymotrypsin(AACT),clusterin(CLU),and Ig alpha-1 chain C region(IGHA1) showed significantly reduced levels in cured pulmonary tuberculosis(TB) patients than untreated ones. Furthermore,the decision model established by these three proteins reached a sensitivity of 79.59％,and a specificity of 77.36％. Conclusion It is suggested that AACT,CLU, IGHA1 may be served as potential biomarkers for curing TB.