Potential Genes Related to Levofloxacin Resistance in Mycobacterium tuberculosis Based on Transcriptome and Methylome Overlap Analysis.

Drug-resistant Mycobacterium tuberculosis (M. tuberculosis) has become an increasingly serious public health problem and has complicated tuberculosis (TB) treatment. Levofloxacin (LOF) is an ideal anti-tuberculosis drug in clinical applications. However, the detailed molecular mechanisms of LOF-resistant M. tuberculosis in TB treatment have not been revealed. Our study performed transcriptome and methylome sequencing to investigate the potential biological characteristics of LOF resistance in M. tuberculosis H37Rv. In the transcriptome analysis, 953 differentially expressed genes (DEGs) were identified; 514 and 439 DEGs were significantly downregulated and upregulated in the LOF-resistant group and control group, respectively. The KEGG pathway analysis revealed that 97 pathways were enriched in this study. In the methylome analysis, 239 differentially methylated genes (DMGs) were identified; 150 and 89 DMGs were hypomethylated and hypermethylated in the LOF-resistant group and control group, respectively. The KEGG pathway analysis revealed that 74 pathways were enriched in this study. The overlap study suggested that 25 genes were obtained. It was notable that nine genes expressed downregulated mRNA and upregulated methylated levels, including pgi, fadE4, php, cyp132, pckA, rpmB1, pfkB, acg, and ctpF, especially cyp132, pckA, and pfkB, which were vital in LOF-resistant M. tuberculosis H37Rv. The overlapping genes between transcriptome and methylome could be essential for studying the molecular mechanisms of LOF-resistant M. tuberculosis H37Rv. These results may provide informative evidence for TB treatment with LOF.

A Diagnostic Tool for Identification of Etiologies of Fever of Unknown Origin in Adult Patients.

The diagnosis and treatment of fever of unknown origin (FUO) are huge challenges to clinicians. Separating the etiologies of FUO into infectious and non-infectious disease is conducive to clinical physicians not only on making decisions rapidly concerning the prescription of suitable antibiotics but also on further analysis of the final diagnosis. In order to develop and validate a diagnostic tool to efficiently distinguish the etiologies of adult FUO patients as infectious or non-infectious disease, FUO patients from the departments of infectious disease and internal medicine in three Chinese tertiary hospitals were enrolled retrospectively and prospectively. By using polynomial logistic regression analysis, the diagnostic formula and the associated scoring system were developed. The variables included in this diagnostic formula were from clinical evaluations and common laboratory examinations. The proposed tool could discriminate infectious and non-infectious causes of FUO with an area under receiver operating characteristic curve (AUC) of 0.83, sensitivity of 0.80 and specificity of 0.75. This diagnosis tool could predict the infectious and non-infectious causes of FUO in the validation cohort with an AUC of 0.79, sensitivity of 0.79 and specificity of 0.70. The results suggested that this diagnostic tool could be a reliable tool to discriminate between infectious and non-infectious causes of FUO.

Establishment of a Predictive Model Related to Pathogen Invasion for Infectious Diseases and Its Diagnostic Value in Fever of Unknown Origin.

The present study aimed to establish a list of parameters indicative of pathogen invasion and develop a predictive model to distinguish the etiologies of fever of unknown origin (FUO) into infectious and non-infectious causes. From January 2014 to September 2017, 431 patients with FUO were prospectively enrolled in the study population. This study established a list of 26 variables from the following 4 aspects: host factors, epidemiological factors, behavioral factors, and iatrogenic factors. Predefined predicted variables were included in a multivariate logistic regression analysis to develop a predictive model. The predictive model and the corresponding scoring system were developed using data from the confirmed diagnoses and 9 variables were eventually identified. These factors were incorporated into the predictive model. This model discriminated between infectious and non-infectious causes of FUO with an AUC of 0.72, sensitivity of 0.71, and specificity of 0.63. The predictive model and corresponding scoring system based on factors concerning pathogen invasion appear to be reliable screening tools to discriminate between infectious and non-infectious causes of FUO.

Applied value of monitoring serum hepcidin in differential diagnosis of infection versus tumor fevers.

The applied value of serum hepcidin in differential diagnosis of infection fevers versus tumor fevers was explored. A total of 432 fever patients were selected according to the domestic fever of unknown origin (FUO) diagnostic criteria from our hospital between June 2010 and November 2013. Venous blood samples were taken on the day 1, 5, 10 after admission. The infection group (98 cases) and the tumor group (50 cases) were set up based on the clinical and laboratory findings. ELISA was used to determine the serum hepcidin and IL-6 levels. SPSS 13.0 was used for statistical analysis. Hepcidin showed obvious descending trend on the 10th day in both the bacterial infection group (66 cases) and the virus infection group (32 cases), and the descending trend was similar to that of inflammatory indexes such as procalcitonin (PCT), hypersensitive C-reactive protein (h-CRP), erythrocyte sedimentation rate (ESR), white blood cell (WBC), and ferritin. Serum hepcidin showed no obvious differences in the tumor group on the day 1, 5, 10 after admission. In the infection groups, serum hepcidin was positively correlated with IL-6 (r=0.687, P=0.000) and CRP (r=0.487, P=0.026), but had a poor correlation with blood sedimentation, ferritin, PCT and WBC (P>0.05). Monitoring dynamic changes of hepcidin and related inflammatory factors in patients with fever is expected to be used for clinical identification of infection fever and tumor fever.

Applied Value of Monitoring Serum Hepcidin in Differential Diagnosis of Infection versus Tumor Fevers / 华中科技大学学报（医学）（英德文版）

The applied value of serum hepcidin in differential diagnosis of infection fevers versus tumor fevers was explored.A total of 432 fever patients were selected according to the domestic fever of unknown origin (FUO) diagnostic criteria from our hospital between June 2010 and November 2013.Venous blood samples were taken on the day 1,5,10 after admission.The infection group (98 cases) and the tumor group (50 cases) were set up based on the clinical and laboratory findings.ELISA was used to determine the serum hepcidin and IL-6 levels.SPSS 13.0 was used for statistical analysis.Hepcidin showed obvious descending trend on the 10th day in both the bacterial infection group (66 cases) and the virus infection group (32 cases),and the descending trend was similar to that of inflammatory indexes such as procalcitonin (PCT),hypersensitive C-reactive protein (h-CRP),erythrocyte sedimentation rate (ESR),white blood cell (WBC),and ferritin.Serum hepcidin showed no obvious differences in the tumor group on the day 1,5,10 after admission.In the infection groups,serum hepcidin was positively correlated with IL-6 (r=0.687,P=0.000) and CRP (r=0.487,P=0.026),but had a poor correlation with blood sedimentation,ferritin,PCT and WBC (P＞0.05).Monitoring dynamic changes of hepcidin and related inflammatory factors in patients with fever is expected to be used for clinical identification of infection fever and tumor fever.

Inter-simple sequence repeat data reveals high genetic diversity in wild populations of the narrowly distributed endemic Lilium regale in the Minjiang River Valley of China.

Lilium regale E.H. Wilson is endemic to a narrow geographic area in the Minjiang River valley in southwestern China, and is considered an important germplasm for breeding commercially valuable lily varieties, due to its vigorous growth, resistance to diseases and tolerance for low moisture. We analyzed the genetic diversity of eight populations of L. regale sampled across the entire natural distribution range of the species using Inter-Simple Sequence Repeat markers. The genetic diversity (expected heterozygosity= 0.3356) was higher than those reported for other narrowly distributed endemic plants. The levels of inbreeding (Fst = 0.1897) were low, and most of the genetic variability was found to be within (80.91%) than amongpopulations (19.09%). An indirect estimate of historical levels of gene flow (Nm =1.0678) indicated high levels of gene flow among populations. The eight analyzed populations clustered into three genetically distinct groups. Based on these results, we recommend conservation of large populations representing these three genetically distinct groups.