Establishment and evaluation of a new fluorescent probe method based on loop-mediated isothermal amplification for the detection of Mycobacterium tuberculosis complex.

We aimed to develop a novel diagnostic method called multiplex fluorescence of loop primer upon self-dequenching loop-mediated isothermal amplification (mFLOS-LAMP) for the rapid detection of Mycobacterium tuberculosis complex (MTBC). A set of specific primers was designed to target the detection of IS1081 and IS6110 genes, which are insertion sequences within the MTBC. The 110 sputum specimens collected were assessed using the established mFLOS-LAMP method, multiplex polymerase chain reaction, Xpert MTB/RIF, and smear microscopy. The optimal reaction temperature and duration for mFLOS-LAMP were determined to be 65°C and 30 min, respectively, by optimizing the entire system. The detection sensitivity of mFLOS-LAMP was 6.0 × 101 CFU/mL, by Bacillus Calmette-Guerin, and the mFLOS-LAMP sensitivity of M. tuberculosis H37Rv genomic DNA was 500 fg, and the specificity was 100%. The sensitivity of mFLOS-LAMP was 94.2% and the specificity was 96.6%, when Xpert MTB/RIF was used as the reference method. There was no statistically significant difference in their detection rate (χ2 = 0, P = 1.000), and the consistency was good (kappa = 0.909, P < 0.001). The receiver operating characteristic analysis yielded the maximum area under the curve of 0.954. The mFLOS-LAMP method demonstrated high sensitivity and specificity, allowing for swift and accurate detection of MTBC.

Plasma Methylated SEPT9 as a Novel Biomarker for Predicting Liver Metastasis in Colorectal Cancer.

This study aimed to explore the role of plasma methylated SEPT9 (mSEPT9) in predicting liver metastasis (LM) in colorectal cancer (CRC) patients. The clinicopathological information of 115 consecutive CRC patients were collected. The differences of clinical characteristics and several biomarkers between CRC patients with LM and those with non-liver metastasis (NM) were analyzed. Multivariate logistic regression analysis was used to identify the risk factors for predicting LM in CRC patients. Receiver operating characteristic curve (ROC) analysis was applied to investigate the sensitivity and specificity of potential biomarkers in indicating the presence of LM in CRC. Compared with the CRC without LM, the levels of plasma mSEPT9 and carcinoembryonic antigen (CEA) were significantly increased in CRC with LM. Multivariate logistic regression analysis showed that plasma mSEPT9 was an independent risk factor for predicting LM in CRC. ROC curves showed that mSEPT9 and CEA could efficiently distinguish LM from NM in CRC. The area under the curve (AUC) of mSEPT9 was 0.850, which was slightly higher than that of CEA (0.842). The optimal cut-off value of mSEPT9 was 35.09 with a sensitivity of 81.82% and a specificity of 73.33%, both similar with that of CEA (sensitivity 87.27% and specificity 75.00%). In addition, the combination of mSEPT9 and CEA had a higher specificity than CEA alone (81.70% Vs 75.00%). Our findings suggest, for the first time, that plasma mSEPT9 might serve as a potential biomarker to predict LM in CRC, which deserves further in-depth study.

Immune and inflammation-related gene polymorphisms and susceptibility to tuberculosis in Southern Xinjiang population: A case-control analysis.

Genetic and immune factors play an important role in tuberculosis. Under different ethnicities and genetic backgrounds, different immune and inflammation-related gene polymorphisms may confer different susceptibility to tuberculosis. This study investigated the relationship between immune and inflammation-related gene polymorphism and susceptibility to tuberculosis in Xinjiang Uyghur population, China. In this case-control study, we enrolled 507 pulmonary tuberculosis patients and 454 healthy controls from Southern Xinjiang. single nucleotide polymorphism (SNP) genotyping was performed. The 12 SNPs of nine immune and inflammation-related genes (including TNF rs361525, IL6 rs2066992 and rs1524107, IL17A rs3748067, IL17F rs763780, VDR rs731236, rs2228570 and rs1544410, IFNGR1 rs1327474, P2RX7 rs3751143, CTAGE1 rs4331426 and Toll-like receptor 4 (TLR4) rs4986790) and their relationship with tuberculosis were evaluated. The T allele and TT genotype of IL-6 rs2066992 and rs1524107 increased the risk of active tuberculosis. The C allele of IFNGR1 rs1327474 was related to the reduced risk of tuberculosis in the Xinjiang Uyghur population. The G allele and AG/GG genotypes of TLR4 rs4986790 were associated with an increased risk of tuberculosis (p < .05). Furthermore, haplotype analysis found that the haplotype TT of interleukin (IL)-6 was a risk factor, whereas the CG type was a protective factor for active tuberculosis in the Xinjiang Uyghur population. There were three immune and inflammation-related genes (IL-6, IFNGR1 and TLR4) and a total of four SNPs (rs2066992, rs1524107, rs1327474 and rs4986790) related to the susceptibility of the Uyghur population to tuberculosis. Our findings may provide evidence for further understanding the mechanism of tuberculosis susceptibility in the Xinjiang Uyghur population.

Novel mesoporous silica nanocarriers containing gold; a rapid diagnostic tool for tuberculosis.

Tuberculosis (TB) is major health concern and reason of deaths from decades to current date. Even though with a lot of advancements, diagnostic techniques, and discovery of standard antibiotics TB remains crucial challenge and can create worst scenario for human health in near future. Nanoparticles play emerging role in diagnosis and treatment of TB. In this study, we developed mesoporous silica nanoparticles containing gold (MSNs@GNPs) for rapid diagnosis and treatment of TB. The physicochemical characterization revealed effective surface morphology and particles diameter, that is applicable for in vitro applications. The in vitro antimicrobial analysis revealed that the designed MSNs@GNPs has retained significantly lower minimal inhibitory concentration (MIC) values and can effectively demolish mycobacterium tuberculosis (Mtb). Furthermore, the diagnosis efficiency of the MSNs@GNPs was evaluated by calorimetric analysis. Which demonstrates that MSNs@GNPs can be used for rapid diagnosis of the tuberculosis when applied on in vitro culture of the Mtb. The current study needs further verification on human's clinical samples from tuberculosis patients. However, MSNs@GNPs can be a versatile clinical approach for the rapid diagnosis and clinical treatment of the tuberculosis.

Serum Tumor Marker Carbohydrate Antigen 125 Levels and Carotid Atherosclerosis in Patients with Coronary Artery Disease.

OBJECTIVE: We assessed the correlation between serum carbohydrate antigen 125 (CA125) and carotid intima-media thickness (cIMT) in patients with coronary artery disease (CAD). METHODS: We collected 518 CAD patients from the cardiovascular disease center in our hospital, and all cIMT values were measured in patients with CAD. RESULTS: The serum CA125 concentrations were found to be increased in CAD patients with early carotid atherosclerosis compared with patients without early carotid atherosclerosis (20.1±7.72 vs. 17.7±6.41 U/mL, p<0.001). The cIMT values were increased in patients with higher serum CA-125 levels than those with lower serum CA-125 concentrations (1.16±0.32 vs. 0.98±0.29 mm, p<0.001). There was a positive correlation between serum CA125 and cIMT in CAD patients (r=0.262, p<0.001). Moreover, the serum CA125 concentrations also were positively correlated with cIMT in subjects with early carotid atherosclerosis and without early carotid atherosclerosis (r=0.255, p<0.001; r=0.189, p=0.002). We found that serum CA-125 concentrations were independently correlated with cIMT (beta = 0.293, p<0.001) in multiple linear regression analysis. CONCLUSIONS: We found that serum CA125 concentrations were positively correlated with cIMT in CAD patients, serum CA125 might be a potential biochemical marker for the estimation of atherosclerosis in patients with CAD.

Monocyte chemoattractant protein-1 (MCP-1)-2518 A/G polymorphism and lupus nephritis risk: A PRISMA-compliant meta-analysis.

BACKGROUND: Monocyte chemoattractant protein-1 (MCP-1) plays an important role in the development of allergic inflammatory reactions by recruiting various immune cells, which is associated with many autoimmune diseases, but the association with the MCP-1-2518A/G gene polymorphism and lupus nephritis (LN) was still controversial in previous studies. Thus, we performed a meta-analysis to derive a more precise evaluation of the association between MCP-1 -2518A/G polymorphism and LN risk and evaluated influence of ethnicity and source of controls. METHODS: A systematic review and meta-analysis that will be performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Relevant literatures dated to September 2016 were acquired from the PubMed, EMBASE, Cochran Library databases. A total of 961 LN cases and 1867 controls were extracted from 10 published case-control studies. We used odds ratios (OR) with 95% confidence intervals (CI) to assess the risk of LN with MCP-1-2518A/G. RESULTS: Our meta-analysis suggested that MCP-1-2518A/G polymorphism was associated with the risk of LN (GG vs AG+AA: P < .01, OR = 1.42, 95% CI: 1.13-1.79 and A vs G P = .02, OR = 0.74, 95% CI: 0.58-0.95). Then the subgroup analysis showed MCP-1 -2518 A/G gene has a certain correlation with LN susceptibility in the American population (GG vs AA: P < .01, OR = 5.70, 95% CI: 2.09-15.50, GG vs AG+AA: P < .01, OR = 3.31, 95% CI: 1.97-5.54, GG+AG vs AA: P < .01, OR = 2.86, 95% CI: 1.14-7.18, and A vs G: P < .01, OR = 0.43, 95% CI: 0.24-0.79), while no significant risk in Europeans and Asians. CONCLUSION: The current meta-analysis suggests that the MCP-1-2518A/G polymorphism is associated with an increased risk of LN, especially in the American population. However, better-designed studies with larger sample sizes are needed to validate the results.

The association between red blood cell distribution width and acute pancreatitis associated lung injury in patients with acute pancreatitis.

BACKGROUND: Red blood cell distribution width (RDW) that describes red blood cell volume heterogeneity is a common laboratory test. Our aim was to focus on the association between RDW and acute pancreatitis associated lung injury (APALI). METHODOLOGY: A total of 152 acute pancreatitis (AP) patients who conformed to the criteria were included in this study. The demographic data, medical histories and laboratory measures was obtained from each patient on admission, further, the medical histories and biological data were analyzed, retrospectively. RESULTS: Increased RDW at admission was observed in patients with APALI compared with the non-APALI groups. Our results exhibited that RDW was an independent risk factor for APALI after adjusting leukocyte, neutrophil percentage, random blood glucose (RBG), total bilirubin (TB) and total bile acid (TBA) (Crude model) (OR=2.671;CI 95% 1.145-6.230; P=0.023), further adjustment based on Crude model for sex and age did not attenuate the significantly high risk of APALI in patients with AP, RWD still remained a roles as an independent risk factor for APALI (OR=2.653;CI95 % 1.123-6.138; P=0.026). CONCLUSIONS: Our study demonstrate that RDW at admission is associated with APALI and should be considered as an underlying risk factor of APALI.