Macrophages play a crucial role in the control and elimination of invading Mycobacterium tuberculosis (Mtb), and also serve as the major residence for Mtb. However, the interaction between macrophages and Mtb remains to be clearly determined. Although long noncoding RNAs (lncRNAs) have emerged as key regulators in many biological processes, their roles in anti-mycobacterial responses of macrophages remain to be elucidated. Here, we applied microarray analysis to examine lncRNA and mRNA expression profiles in human primary macrophages after 72 h of infection with H37Ra or H37Rv. Our results revealed that many lncRNAs were differentially expressed in macrophages after H37Ra or H37Rv infection, indicating a possible role for lncRNAs in immune responses induced by Mtb infection and providing important cues for further functional studies. Furthermore, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) biological pathway analysis of the differentially expressed mRNAs showed the potential functions and pathways related to the pathogenesis of Mtb infection. Finally, two lncRNAs, MIR3945HG V1 and MIR3945HG V2, were identified as novel candidate diagnostic markers for tuberculosis. Our results provide novel insight into the mechanisms of the pivotal Mtb-macrophage interactions, and reveal potential targets for diagnostics and the treatment of tuberculosis.

BackgroundHuman papillomavirus (HPV) DNA testing is an important method in cervical cancer screening. However, the studies on prevalence and genotype distribution of HPV among women in northeastern Guangdong Province of China are very limited.MethodsA total of 28,730 women attending the Department of Gynecology of Meizhou People’s Hospital (Huangtang Hospital), Meizhou Hospital Affiliated to Sun Yat-sen University between January 1st, 2013 and June 1st, 2015 were enrolled in this study. HPV type-specific distribution was tested using flow-through hybridization and gene chip.ResultsThe overall prevalence of HPV infection was 19.81%, among which 79.09% were infected with high-risk HPV subtypes in the subjects. The 5 most predominant genotypes were HPV16, 52, 58, 18 and 81. Most HPV infections were observed in women aged 41–50 and women aged 30–59 accounted for a proportion of over 80%.ConclusionsOur findings suggested a high burden of HPV infection among women in northeastern Guangdong Province of China. We identified the top 5 HPV genotypes as well as the age-specific distribution of HPV infections in this area.

Background The role of apolipoprotein E gene (APOE) in lipid metabolism has been well established, and APOE is associated with the risk of cardiovascular disease (CVD) and diabetes mellitus (DM). However, the relationship between APOE polymorphisms and type 2 diabetes (T2DM) with or without CVD remains unclear. Methods In this cross-sectional study, a total of 924 participants including 211 controls (CVD-T2DM-), 247 T2DM patients with CVD (CVD-T2DM+), 232 CVD patients without T2DM (CVD + T2DM-) and 234 T2DM patients with CVD (CVD + T2DM+), were genotyped using chip platform. The association between APOE polymorphisms and T2DM patients with or without CVD was analyzed by univariable and multivariable logistic analysis. Results The present study showed that the frequency of E3/E4 increased in T2DM patients with CVD (p < 0.01). The ε4 allele was higher in CVD patients without T2DM (p < 0.01) and T2DM patients with CVD (p < 0.01) as compared with the controls. Conclusions The subjects carrying ε4 allele have increased risk of CVD and T2DM, and exhibit higher level of lipid profiles.

BackgroundThe importance of CD4+ and CD8+ T cells in protection against tuberculosis (TB) is well known, however, the association between changes to the T cell repertoire and disease presentation has never been analyzed. Characterization of T-cells in TB patients in previous study only analyzed the TCR β chain and omitted analysis of the Vα family even though α chain also contribute to antigen recognition. Furthermore, limited information is available regarding the heterogeneity compartment and overall function of the T cells in TB patients as well as the common TCR structural features of Mtb antigen specific T cells among the vast numbers of TB patients.Methodology/Principal FindingsCDR3 spectratypes of CD4+ and CD8+ T cells were analyzed from 86 patients with TB exhibiting differing degrees of disease severity, and CDR3 spectratype complexity scoring system was used to characterize TCR repertoire diversity. TB patients with history of other chronic disease and other bacterial or viral infections were excluded for the study to decrease the likely contribution of TCRs specific to non-TB antigens as far as possible. Each patient was age-matched with a healthy donor group to control for age variability. Results showed that healthy controls had a normally diversified TCR repertoire while TB patients represented with restricted TCR repertoire. Patients with mild disease had the highest diversity of TCR repertoire while severely infected patients had the lowest, which suggest TCR repertoire diversity inversely correlates with disease severity. In addition, TB patients showed preferred usage of certain TCR types and have a bias in the usage of variable (V) and joining (J) gene segments and N nucleotide insertions.Conclusions/SignificanceResults from this study promote a better knowledge about the public characteristics of T cells among TB patients and provides new insight into the TCR repertoire associated with clinic presentation in TB patients.

Rabies, caused by rabies virus (RABV), is still the deadliest infectious disease. Mechanism of host immune response upon RABV infection is not yet fully understood. Accumulating evidences suggest that long noncoding RNAs (lncRNAs) plays key roles in host antiviral responses. However, expression profile and function of lncRNAs in RABV infection remain unclear. In the present study, expression profile of lncRNAs and mRNAs profiles were investigated in RABV-infected brain tissues of mice by RNA sequencing. A total of 140 lncRNAs and 3,807 mRNAs were differentially expressed in RABV-infected animals. The functional annotation and enrichment analysis using Gene Oncology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) revealed that differentially expressed transcripts were predominantly involved in signaling pathways related to host immune response. The expression profiles of the selected lncRNAs in brains of mice during RABV infections were verified by quantitative real time polymerase chain reaction (qRT-PCR). To our knowledge, this is the first report to profile the lncRNA expression in RABV infected mice. Our findings provide insights into understanding the role of lncRNAs in host immune response against RABV infection.

OBJECTIVES: Many studies indicate that microRNAs (miRNAs) could be potential biomarkers for various diseases. The purpose of this study was to investigate the clinical value of serum exosomal miRNAs in systemic lupus erythematosus (SLE). METHODS: Serum exosomes were isolated from 38 patients with SLE and 18 healthy controls (HCs). The expression of miR-21, miR-146a and miR-155 within exosomes was examined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Using receiver operating characteristic (ROC) curves, we evaluated the diagnostic value of exosomal miRNAs. RESULTS: Exosomal miR-21 and miR-155 were upregulated ( p <0.01), whereas miR-146a expression ( p <0.05) was downregulated in patients with SLE, compared to that in HCs. The expression of miR-21 ( p <0.01) and miR-155 ( p <0.05) was higher in SLE patients with lupus nephritis (LN) than in those without LN (non-LN). The analysis of ROC curves revealed that the expression of miR-21 and miR-155 showed a potential diagnostic value for LN. Furthermore, miR-21 (R=0.44, p <0.05) and miR-155 (R=0.33, p <0.05) were positively correlated with proteinuria. The expression of miR-21 was negatively associated with anti-SSA/Ro antibodies (R=−0.38, p <0.05), and that of miR-146a was negatively associated with anti-dsDNA antibodies (R=−0.39, p <0.05). CONCLUSIONS: These findings suggested that exosomal miR-21 and miR-155 expression levels may serve as potential biomarkers for the diagnosis of SLE and LN.

BackgroundCytochrome P450 (CYP) 2C19 is an enzyme involved in the bioactivation of various important therapeutic drugs, from pro-drugs to an active inhibitor of platelet action. Variants in the CYP2C19 gene influence the pharmacokinetics and clinical response to antiplatelet drugs such as clopidogrel; however, there is no available data about the genetic variation of CYP2C19 in the Hakka population in China.Material/MethodsA total of 6686 unrelated participants (ages 17–98 years) of self-reported Hakka ancestry admitted at an inpatient department in a hospital in southern China were successfully genotyped by the gene chip platform.ResultsThe identified allele frequencies were CYP2C19*1 (64.33%), *2 (31.06%) and *3 (4.61%). The major prevalent genotype combinations were CYP2C19 *1/*1 (41.73%) and *1/*2 (39.65%). The distribution of CYP2C19 phenotypes was divided into extensive metabolizers (EM) (41.73%), intermediate metabolizers (IM) (45.21%), and poor metabolizers (PM) (13.06%). In the Hakka population, frequencies of the CYP2C19 *2 and *3 variants were observed to be close to those previously identified in Chinese and several other Asian populations.ConclusionsOur study is the first to report on CYP2C19 polymorphisms in the Hakka population, and may help to optimize pharmacotherapy effectiveness by providing personalized medicine to this ethnic group in the near future.

Age- and sex-related differences of lipid profiles were not well understood among ischemic stroke patients in China. Our study aimed to investigate the relationship between lipid abnormalities and ischemic stroke in China. A retrospective analysis was performed involving 2074 patients with ischemic stroke who admitted to Meizhou People's Hospital (Huangtang Hospital), Meizhou Hospital Affiliated to Sun Yat-sen University between January 1, 2014 and March 1, 2017. Our study indicated that there were significant differences in total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), non-high density lipoprotein cholesterol (non-HDL), and Apolipoprotein A (ApoA) between male and female patients. Meanwhile, different lipid levels including TC, TG, and ApoA were observed for patients of various age groups. The nonelderly patients tended to have higher lipid levels than elderly patients. Isolated low HDL (namely, normal LDL + low HDL + normal TG) was the most common lipid abnormalities in patients. In conclusion, there was age- and sex-related difference in lipid profiles among patients with ischemic stroke. Age, sex as well as some other factors should be carefully considered for lipid management in patients with ischemic stroke in China.