Integrating apaQTL and eQTL analysis identifies a potential causal variant associated with lung adenocarcinoma risk in the Chinese population.

Alternative polyadenylation (APA) plays a crucial role in cancer biology. Here, we used data from the 3'aQTL-atlas, GTEx, and the China Nanjing Lung Cancer GWAS database to explore the association between apaQTL/eQTL-SNPs and the risk of lung adenocarcinoma (LUAD). The variant T allele of rs277646 in NIT2 is associated with an increased risk of LUAD (OR = 1.12, P = 0.015), lower PDUI values, and higher NIT2 expression. The 3'RACE experiment showed multiple poly (A) sites in NIT2, with the rs277646-T allele causing preferential use of the proximal poly (A) site, resulting in a shorter 3'UTR transcript. This leads to the loss of the hsa-miR-650 binding site, thereby affecting LUAD malignant phenotypes by regulating the expression level of NIT2. Our findings may provide new insights into understanding and exploring APA events in LUAD carcinogenesis.

Type 2 diabetes, glycaemic traits and upper gastrointestinal cancer risk: a prospective cohort study.

BACKGROUND: Type 2 diabetes (T2D) has been linked with site-specific upper gastrointestinal (UGI) cancers during the past decades, but associations are still inconclusive. This study aimed to determine the association between T2D, glycaemic traits (random blood glucose and HbA1c) and UGI cancer (oesophageal and gastric cancer). METHODS: In the present study, based on the large-scale prospective cohort of UK Biobank, we included 452 631 eligible participants. T2D was defined according to baseline self-report data, clinical data and biochemistry data. Random blood glucose and HbA1c were measured at baseline. Polygenic risk score was used to classify individuals into different UGI cancer genetic risks. Multivariable Cox regression models were used to estimate HRs and 95% CIs. RESULTS: During a median follow-up of 10.26 years (IQR: 9.47-10.97), 1392 incident UGI cancer cases were identified. T2D was significantly associated with a 44% increment in UGI cancer risk (95% CI 1.22 to 1.70, p<0.001). Moreover, per SD increase in random blood glucose and HbA1c was associated with 7% (95% CI 1.03 to 1.12, p<0.001) and 6% (95% CI 1.04 to 1.09, p<0.001) increased hazards of developing UGI cancer, respectively. Patients with T2D at high genetic risk had a 2.33-fold hazard of UGI cancer (95% CI 1.66 to 3.28, p<0.001), compared with non-T2D individuals at low genetic risk. CONCLUSION: Our results indicate that T2D and elevated levels of glycaemic traits may be risk factors for incident UGI cancer. Individuals with a high genetic risk and T2D have a significantly increased risk of developing UGI cancer.

Identification of novel lncRNAs associated with sensitivity of HIV antiretroviral therapy: A two-stage matched case-control study.

BACKGROUND: To identify long non-coding RNAs (lncRNAs) that may be used as potential biomarkers of sensitivity to antiretroviral therapy (ART) against human immunodeficiency virus (HIV) infection. METHOD: A two-stage matched case-control study was conducted. First, in the screening stage, peripheral blood lymphocytes (PBLs) of six subjects receiving lamivudine-based ART (3 ART-resistant and 3 ART-sensitive subjects with matching durations of ART) were subjected to comprehensive microarray expression profiling in order to screen out lncRNAs associated with ART sensitivity. Secondly, during the validation stage, promising lncRNAs were evaluated via a 1:4 matched case-control study using 50 subjects (10 ART-resistant and 40 ART-sensitive subjects with matching durations of ART). RESULTS: Seven lncRNAs were screened out (P < 1.06 × 10-3) in the first stage. Among these, two lncRNAs (n341598 and n407911) survived validation conducted at the second stage (n341598: P < 0.001; n407911: P = 0.007), while another lncRNA n406445 showed marginally significant (P = 0.049). All three showed higher expression in ART-resistant subjects compared to that in ART-sensitive subjects. The area under the ROC curve (AUC) for n341598 was 0.867 (95 % CI: 0.796-0.966; P < 0.001), which was better than that for n406445 (0.702) and n407911 (0.780). Meanwhile, the AUC for n341598 was better than that of any combination of the three lncRNAs. CONCLUSION: Our study identified three highly expressed lncRNAs in patients with HIV ART-resistant, among which the lncRNA n341598 may be utilized as an optimal biomarker to distinguish ART-resistant and ART-sensitive patients. Further studies aimed at revealing the molecular mechanisms underlying the regulation of ART sensitivity by n341598 are warranted to complement our findings.

Peripheral blood circular RNA hsa_circ_0058493 as a potential novel biomarker for silicosis and idiopathic pulmonary fibrosis.

Existing studies reported that some circular RNAs (circRNAs) play vital roles in the development of pulmonary fibrosis. However, few studies explored the biomarker potential of circRNAs for pulmonary fibrosis based on population data. Therefore, we aimed to identify peripheral blood circRNAs as potential biomarkers for diagnosing silicosis and idiopathic pulmonary fibrosis (IPF). In brief, an RNA-seq screening based on 4 silicosis cases and 4 controls was initially performed. Differentially expressed circRNAs were combined with the human serum circRNA dataset to identify overlapping serum-detectable circRNAs, followed by validation using the GEO dataset (3 IPF cases and 3 controls) and subsequent qRT-PCR, including 84 additional individuals. Following the above steps, 243 differentially expressed circRNAs were identified during the screening stage, with fold changes ≥ 1.5 and P < 0.05. Of note, the human serum circRNA dataset encompassed 28 of 243 circRNAs. GEO (GSE102660) validation revealed two highly expressed circRNAs (P < 0.05) in the IPF case group. Furthermore, at the enlarged sample validation stage, hsa_circ_0058493 was highly expressed in both silicosis and IPF cases (silicosis: P = 1.16 × 10-6; IPF: P = 7.46 × 10-5). Additionally, hsa_circ_0058493 expression was significantly increased in MRC-5 cells upon TGF-ß1 treatment, while hsa_circ_0058493 knockdown inhibited the expression of fibrotic molecules by affecting the epithelial-mesenchymal transition process. These shreds of evidence indicated that hsa_circ_0058493 might serve as a novel biomarker for diagnosing silicosis and IPF.

A novel regQTL-SNP and the risk of lung cancer: a multi-dimensional study.

RegQTL, a novel concept, indicates that different genotypes of some SNPs have differential effects on the expression patterns of miRNAs and their target mRNAs. We aimed to identify the association between regQTL-SNPs and lung cancer risk and to explore the underlying mechanisms. The two-stage case-control study included the first stage in a Chinese population (626 lung cancer cases and 667 healthy controls) and the second stage in a European population (18,082 lung cancer cases and 13,780 healthy controls). Functional annotations were conducted based on the GTEx and the TCGA databases. Functional experiments were performed to explore the underlying biological mechanisms in vitro and vivo. After strict screening, five candidate regQTL-SNPs (rs7110737, rs273957, rs6593210, rs3768617, and rs6836432) were selected. Among them, the variant T allele of rs3768617 in LAMC1 was found to significantly increase the risk of lung cancer (first stage: P = 0.044; second stage: P = 0.007). The eQTL analysis showed that LAMC1 expression level was significantly higher in subjects with the variant T allele of rs3768617 (P = 1.10 × 10-14). In TCGA paired database, the regQTL annotation indicated the different expression patterns between LAMC1 and miRNA-548b-3p for the distinct genotypes of rs3768617. Additionally, LAMC1 knockdown significantly inhibited malignant phenotypes in lung cancer cell lines and suppressed tumor growth. A novel regQTL-SNP, rs3768617, might affect lung cancer risk by modulating the expression patterns of miRNA-548b-3p and LAMC1. RegQTL-SNPs could provide a new perspective for evaluating the regulatory function of SNPs in lung cancer development.

miR-608 rs4919510 Polymorphism May Affect Susceptibility to Colorectal Cancer by Upregulating MRPL43 Expression.

There are many studies on the association between miR-608 rs4919510 polymorphism and susceptibility to colorectal cancer (CRC). However, the role of rs4919510 in CRC development and its underlying mechanism remain unclear. We first evaluated the gene that may be regulated by the variation of rs4919510 through a two-stage expression quantitative trait loci analysis and then compared the expression of that identified gene in CRC tissues and adjacent nontumor tissues. Next, methyl thiazolyl tetrazolium (MTT) assay, transwell assay, and flow cytometry analyses were performed to investigate the in vitro capacity of cell proliferation, migration, invasion, apoptosis, and cell cycle of CRC cells, respectively. Finally, through bioinformatics prediction, we contrasted the regulatory network and identified microRNAs (miRNAs) and long noncoding RNAs (lncRNAs) that could regulate the obtained gene. We found that the variant G allele of rs4919510 located in miR-608 was associated with a potentially increased expression of MRPL43 in colon tissues (p = 0.065). Moreover, the results of functional experiments suggested that knockdown of the MRPL43 gene could inhibit the growth of the CRC HCT-116 cell line and promote apoptosis. Additionally, the cell cycle of CRC HCT-116 cell line was significantly arrested at the G2 phase. Next, we obtained a competing endogenous RNA regulatory network of MRPL43 with 17 pairs of miRNAs-lncRNAs by bioinformatics prediction, out of which, survival analysis indicated that different expression levels of miR-193b-3p (p = 0.0269) and miR-194-3p (p = 0.0113) were associated with overall survival in CRC patients. The rs4919510 variant G allele in miR-608 may increase the proliferation, invasion, and migration ability and decrease the apoptosis of CRC HCT-116 cell line by upregulating the expression of MRPL43, ultimately may affect the risk of CRC. Moreover, miR-193b-3p and miR-194-3p that target MRPL43 may serve as potential predictive biomarkers of CRC survival.

Analysis of hospitalization expenses of 610 HIV/AIDS patients in Nantong, China.

BACKGROUND: The goal of this study was to describe the expenses related to human immunodeficiency virus (HIV) and acquired immune deficiency syndrome (AIDS) management and care in Nantong Infectious Disease Hospital from October 2013 through June 2017. METHODS: The information of 610 HIV/AIDS inpatients were collected from the Electronic Medical Record System of the hospital. Univariate and path analysis were employed to evaluate the association between hospitalization expense and its related factors. RESULTS: The average hospitalization expenses per person was 5454 RMB (Renminbi, the currency of China, about $808 USD) and 23,555 RMB (about $3489 USD), respectively for HIV/AIDS patients. The average length of hospital stay was 10.0 ± 5.5 days for HIV patients and 21.7 ± 12.4 days for AIDS patients. For HIV patients, laboratory test fees constituted 37.46% of total expenses; while drug fees accounted for the largest proportion for AIDS patients. Path analysis indicated that the length of hospital stay was the most important factor affecting total expenses (total path coefficient = 0.563 for HIV patients and 0.649 for AIDS patients). Total expenses for HIV-infected females was higher than that of males (total path coefficient = 0.217), and the more complications led to higher expenses for AIDS patients. CONCLUSIONS: Though antiretroviral therapy (ART) is provided for free in China, associated medical care, particularly hospitalizations and fees, continue to drive up the medical costs of patients living with HIV and AIDS. Understanding the factors influencing these costs are crucial for determining policies and strategies that can reduce the economic burden of HIV/AIDS patients in China.

Effect of perioperative amplitude-integrated electroencephalography on neurodevelopmental outcomes following infant heart surgery.

The purpose of the current study was to determine the effect of perioperative amplitude-integrated electroencephalography (aEEG) on neurodevelopmental outcomes in infants with congenital heart disease (CHD). A total of 93 children with CHD were included in the current study. All patients enrolled in the present study had undergone cardiac surgery prior to 3 months of age and pre- or postoperative aEEG was monitored. Participants were assessed after 1 year using the Bayley Scales of Infant Test. A total of 82.2% of infants exhibited continuous normal voltage preoperatively (CNV) and 93.7% exhibited CNV postoperatively. Seizures were indicated in 2 infants preoperatively and 3 infants postoperatively. Compared with infants with PDI, infants with cyanotic CHD (ß=17.218) exhibited a significantly lower MDI, an increased length of intensive care stay, and lower PDI scores (ß=-0.577). Infants that underwent surgery with CPB exhibited higher PDI scores (ß=11.956). Infants that exhibited behavioral problems also had lower PDI scores (ß=-10.605). An abnormal preoperative background pattern and an absent postoperative SWC independently predicted poorer motor (P=0.014) and cognitive (P=0.049) outcomes at 1 year. The current study demonstrated that infants with CHD who underwent cardiac surgery prior to 3 months of age exhibited delayed neurodevelopmental outcomes, and that an aEEG assessment can aid in predicting these outcomes following surgery.

RNA Sequencing Reveals LINC00167 as a Potential Diagnosis Biomarker for Primary Osteoarthritis: A Multi-Stage Study.

OBJECTIVES: Given the roles played by lncRNA in human diseases and the high incidence of OA, this study investigated the pivotal pathways involved in the disease and identified potential biomarkers for OA diagnosis. METHODS: We first performed an exploration of RNA-sequencing in peripheral blood leukocytes from six subjects (3 OA and 3 healthy controls). Promising candidate lncRNAs were evaluated in first stage validation using a GEO dataset (GSE114007) of 38 subjects (20 OA and 18 healthy controls), followed by a second stage validation using quantitative PCR analysis with 101 subjects (67 OA and 34 controls). The third stage investigated the potential value of validated lncRNA in the early diagnosis of OA in peripheral blood leukocytes from a total of 120 participants (60 cases and 60 controls). RESULTS: The dataset identified a total of 1,380 up-regulated and 719 down-regulated mRNAs and 5,743 up-regulated and 7,384 down-regulated lncRNAs. The up-regulated DEGs were mainly enriched in the extracellular matrix, while the down-regulated DEGs were mainly enriched in the IL-17 and wnt signaling pathways. 18 overlapping candidate lncRNAs survived after first-stage validation. 3 hub lncRNAs were selected for the second validation stage and qualified in an external sample, and lncRNA LINC00167 was further confirmed with a similar result (down-expressed in both stages). Receiver operating characteristic analysis showed that LINC00167 can distinguish OA cases from healthy controls with a high area under the curve of 0.879 (95%CI: 0.819, 0.938; P < 0.001), with a sensitivity of 80.7% and specificity of 83.5%. CONCLUSION: The expression profile of OA was identified and critical pathways were elucidated by an integrated approach to RNA-seq from easily accessible blood. LINC00167 may serve as a potential early diagnosis marker for OA in clinical practice. The detailed mechanism of action of this lncRNA requires further elucidation in future studies.

miRNA sequencing reveals miRNA-4508 from peripheral blood lymphocytes as potential diagnostic biomarker for silica-related pulmonary fibrosis: A multistage study.

BACKGROUND AND OBJECTIVE: This study aimed to identify miRNA as potential diagnostic biomarkers for silica-related pulmonary fibrosis (SPF). METHODS: We first performed a comprehensive miRNA-seq screening in PBL of eight subjects exposed to silica dust (four individuals with SPF and four healthy controls). The promising miRNA were then evaluated in the first-stage validation using an independent GEO data set (GSE80555) of 6 subjects (3 individuals with SPF and 3 healthy controls), followed by a second-stage validation using 120 subjects exposed to silica dust (60 individuals with SPF and 60 healthy controls). RESULTS: Thirty-five miRNA showed strong expression differences in miRNA-seq screening, while miRNA-4508 (P = 9.52 × 10-3 ) was retained as a candidate after the first-stage validation (GSE80555), which was further confirmed in the second-stage validation with similar and strong effect (P = 9.93 × 10-17 ). ROC analysis showed that miRNA-4508 could distinguish SPF cases from healthy controls with high AUC (0.886), with sensitivity of 81.7% and specificity of 86.7%. In addition, the miRNA-4508 upstream rs6576457 mutant A allele exhibited a strong association with susceptibility to SPF (OR = 1.64, 95% CI = 1.20-2.23, P = 0.002), while eQTL analysis revealed a potential association between different genotypes of rs6576457 and miRNA-4508 expression (P = 0.068) in 60 healthy subjects with silica dust exposure. CONCLUSION: miRNA-4508 may be a potential diagnostic marker for SPF, and rs6576457, a functional variant of miRNA-4508, may affect SPF susceptibility. The detailed mechanism of action of this miRNA remains to be elucidated.

Functional Variant in 3'UTR of FAM13A Is Potentially Associated with Susceptibility and Survival of Lung Squamous Carcinoma.

FAM13A is associated with aging lung disease (primarily chronic obstructive pulmonary disorder and pulmonary fibrosis) and shows stable expression throughout lung development. However, a few systematic studies of FAM13A have been conducted to assess the pathogenesis of lung cancer, particularly susceptibility. We predicted that single-nucleotide polymorphisms (SNPs) in FAM13A may be associated with lung cancer development. We systematically selected five functional SNPs (rs2602120, rs3017895, rs9224, rs7657817, and rs3756050) and genotyped them with the Genesky proprietary improved Multiligase Detection Reaction multiplex SNP genotyping system in a case-control study of 626 lung cancer cases and 667 cancer-free controls. The functional effects of FAM13A and specific miRNAs (miRNA-22-5p and miRNA-1301-3p) were evaluated based on The Cancer Genome Atlas database. We found that rs9224 in the 3' untranslated region (UTR) of FAM13A was potentially associated with an increased risk of lung squamous carcinoma (LUSQ) (additive model: odds ratio = 1.47, 95% confidence interval = 1.04-2.07, p = 0.028). In addition, the results of expression quantitative trait loci analysis suggested that the rs9224 polymorphism affects the expression of FAM13A (p = 0.050) and miRNA-22-5p (p = 0.031) in LUSQ. Further, survival analysis indicated decreased overall survival in the presence of the variant alleles of rs9224 (p = 0.048). The present results indicate that variant genotypes of rs9224 in the FAM13A 3'UTR may modify LUSQ susceptibility by affecting the binding of miRNA-22-5p and predict a poor prognosis of patients with LUSQ.

MiR-204 inhibits hepatocellular cancer drug resistance and metastasis through targeting NUAK1.

Liver cancer is a leading cause of cancer-related deaths globally. Tumor response rate of liver cancer patients towards systemic chemotherapy is low and chemoresistance can easily develop. Identifying novel molecules that can repress drug resistance and metastasis of liver cancer will facilitate the development of new therapeutic strategies. The aim of this study is to determine the roles of NUAK1 and miR-204 in the drug resistance and metastasis of liver cancer and to reveal their relationship. We found that NUAK1 was increased in the tumor of primary liver cancer. Knockdown of NUAK1 significantly inhibited cell growth and migration. Moreover, NUAK1 was the direct downstream target of miR-204, and there was clinical relevance between miR-204 down-regulation and NUAK1 up-regulation in liver cancer. Furthermore, we found that miR-204 increased drug sensitivity by down-regulating NUAK1 expression. Based on these results, we identified miR-204 as a tumor suppressor by inhibiting NUAK1 expression in liver cancer, indicating both miR-204 and NUAK1 may act as promising targets for liver cancer therapy.

Functional variant of the carboxypeptidase M (CPM) gene may affect silica-related pneumoconiosis susceptibility by its expression: a multistage case-control study.

OBJECTIVES: In a genome-wide association study, we discovered chromosome 12q15 (defined as rs73329476) as a silica-related pneumoconiosis susceptibility region. However, the causal variants in this region have not yet been reported. METHODS: We systematically screened eight potentially functional single-neucleotide polymorphism (SNPs) in the genes near rs73329476 (carboxypeptidase M (CPM) and cleavage and polyadenylation specific factor 6 (CPSF6)) in a case-control study including 177 cases with silicosis and 204 healthy controls, matched to cases with years of silica dust exposure. We evaluated the associations between these eight SNPs and the development of silicosis. Luciferase reporter gene assays were performed to test the effects of selected SNP on the activity of CPM in the promoter. In addition, a two-stage case-control study was performed to investigate the expression differences of the two genes in peripheral blood leucocytes from a total of 64 cases with silicosis and 64 healthy controls with similar years of silica dust exposure as the cases. RESULTS: We found a strong association between the mutant rs12812500 G allele and the susceptibility of silicosis (OR=1.45, 95% CI 1.03 to 2.04, p=0.034), while luciferase reporter gene assays indicated that the mutant G allele of rs12812500 is strongly associated with increased luciferase levels compared with the wild-type C allele (p<0.01). Moreover, the mRNA (peripheral blood leucocytes) expression of the CPM gene was significantly higher in subjects with silicosis compared with healthy controls. CONCLUSIONS: The rs12812500 variant of the CPM gene may increase silicosis susceptibility by affecting the expression of CPM, which may contribute to silicosis susceptibility with biological plausibility.

Different Types of Family History of Stroke and Stroke Risk: Results Based on 655,552 Individuals.

BACKGROUND: Many studies concentrated on the relationships between different types of family history and stroke, but they have not arrived at an unified conclusion. We conducted a comprehensive systematic review to further evaluate the associations. METHODS: Different databases were searched for related studies published from 1990 to August 2017. The relative risk was considered as the common measure of association across different studies. Heterogeneity of effects across studies was quantified by I2. RESULTS: Sixteen published studies (total participants: 655,552) were eligible in this study. The pooled multifactorial adjusted relative risk (RR) (95% confidence interval [CI]) was 1.40 (1.18, 1.67) for individuals with paternal history, 1.36 (1.20, 1.53) for those with maternal history, and 1.44 (1.17, 1.77) for those with sibling history. Based on cohort studies, the pooled adjusted RRs (95%CIs) for paternal, maternal, and sibling history were 1.33 (1.11-1.59), 1.28 (1.14-1.45), and 1.24 (1.01-1.51), respectively, all of which were smaller than those based on case-control and cross-sectional studies. In studies with large sample size, the respective adjusted RR (95%CI) of stroke for paternal, maternal, and sibling history was 1.30 (1.09, 1.56), 1.30 (1.18, 1.44), and 1.26 (1.02, 1.56), which was lower than that in studies with small sample size. CONCLUSIONS: Each type of family history of stroke was associated with an increased stroke risk. We could not find significant differences among stroke risks relating to different types of family history of stroke. Thus, paternal, maternal, and sibling history require our equal attention in the stroke prevention and control work.

A Novel Variant of Desmoplakin Is Potentially Associated with Silicosis Risk.

Two genome-wide association studies and one sequencing study have coincidently reported significant associations of single nucleotide polymorphisms (SNPs) in the desmoplakin (DSP) gene with the risk of pulmonary fibrosis (mainly idiopathic pulmonary fibrosis). However, these findings have not been well generalized to occupational pulmonary fibrosis (e.g., silica-related silicosis). We systematically genotyped 8 potentially functional SNPs and the previously reported rs2076295 and rs2744371 in DSP gene region and evaluated the associations between these 10 SNPs and silicosis risk in a case-control study that included 177 silicosis cases and 204 controls with similar numbers of silica dust exposure years as the cases from a Chinese population. Genotyping was performed using the improved multiligase detection reaction multiplex SNP genotyping system. The variant A allele of rs2076304 exhibited significant association with the risk of silicosis (odds ratio = 1.53, 95% confidence interval = 1.03-2.29, p = 0.036). Moreover, significant association was observed between different genotypes of rs2076304 and DSP expression (p = 1.1 × 10-7) in 383 normal lung tissues. Further functional annotation indicated that the rs2076304 might influence the binding of RHOXF1. The rs2076304 in DSP gene is associated with a significantly increased risk of silicosis in a Han Chinese population. Further studies are warranted to validate and extend our findings, especially the biological mechanisms of rs2076304 in silicosis susceptibility.

The rs2609255 polymorphism in the FAM13A gene is reproducibly associated with silicosis susceptibility in a Chinese population.

BACKGROUND: Two recent genome-wide association studies (GWASs) reported that the FAM13A gene at the 4q22 locus associated with pulmonary fibrosis (defined by rs2609255) overlapping with COPD (defined by rs6837671). We hypothesized that single-nucleotide polymorphisms (SNPs) related to lung disease (especially pulmonary fibrosis) identified in this region are also associated with the risk of silicosis. METHODS: To test this hypothesis, we genotyped these two SNPs (rs2609255 and rs6837671) in a case-control study including 177 silicosis cases and 204 controls with silica dust exposure years similar to the levels for cases in a Chinese population. RESULTS: We found that rs2609255 was significantly associated with increased silicosis risk (dominant model: OR = 1.71; 95% CI = 1.01-2.92; P = 0.047). Additionally, eQTL analysis based on the GTEx database indicated that the rs2609255 polymorphism may alter the expression level of FAM13A in lung tissues (P = 1.8 × 10-4). Furthermore, interaction analyses showed that rs2609255 interacts multiplicatively with years of silica dust exposure to contribute to silicosis risk (interaction P = 0.040). CONCLUSIONS: These results indicate that rs2609255 may modify silicosis susceptibility in the Chinese population.

Phylogenetic and temporal dynamics of human immunodeficiency virus type 1 CRF01_AE and CRF07_BC among recently infected antiretroviral therapy-naïve men who have sex with men in Jiangsu province, China, 2012 to 2015: A molecular epidemiology-based study.

The prevalence and incidence of human immunodeficiency virus type 1 (HIV-1) among men who have sex with men (MSM) are on the rise throughout China. With a large population of MSM, Jiangsu Province is facing an escalating HIV-1 epidemic.The aim of this study was to explore the phylogenetic and temporal dynamics of HIV-1 CRF01_AE and CRF07_BC among antiretroviral therapy (ART)-naïve MSM recently infected with HIV-1 in Jiangsu Province.We recruited MSM in Jiangsu Province (Suzhou, Wuxi, Nantong, Taizhou and Yancheng) 2012 to 2015. We collected information on demographics and sexual behaviors and a blood sample for HIV genome RNA extraction, RT-PCR amplification, and DNA sequencing. Multiple alignments were made using Gene Cutter, with the selected reference sequences of various subtypes/recombinants from the Los Alamos HIV-1 database. Phylogenetic and Bayesian evolutionary analysis was performed by MEGA version 6.0, Fasttree v2.1.7. and BEAST v1.6.2. Categorical variables were analyzed using χ test (or Fisher exact test where necessary). χ test with trend was used to assess the evolution of HIV-1 subtype distribution over time. All data were analyzed using SPSS20.0 software package (IBM Company, New York, NY).HIV-1 phylogenetic analysis revealed a broad viral diversity including CRF01_AE (60.06%), CRF07_BC (22.29%), subtype B (5.88%), CRF67_01B (5.26%), CRF68_01B (2.79%), CRF55_01B (1.55%), CRF59_01B (0.93%), and CRF08_BC (0.62%). Two unique recombination forms (URFs) (0.62%) were also detected. Four epidemic clusters and 1 major cluster in CRF01_AE and CRF07_BC were identified. The introduction of CRF01_AE strain (2001) was earlier than CRF07_BC strain (2004) into MSM resided in Jiangsu based on the time of the most recent common ancestor.Our study demonstrated HIV-1 subtype diversity among ART-naïve MSM recently infected with HIV-1 in Jiangsu. We first depicted the spatiotemporal dynamics, traced the dates of origin for the HIV-1 CRF01_AE/07_BC strains and made inference for the effective population size among newly infected ART-naïve MSM in Jiangsu from 2012 to 2015. A real-time surveillance of HIV-1 viral diversity and phylodynamics of epidemic cluster would be of great value to the monitoring of the epidemic and control of transmission, improvement of antiretroviral therapy strategies, and design of vaccines.

Identification of pathogenic genes and upstream regulators in age-related macular degeneration.

BACKGROUND: Age-related macular degeneration (AMD) is the leading cause of irreversible blindness in older individuals. Our study aims to identify the key genes and upstream regulators in AMD. METHODS: To screen pathogenic genes of AMD, an integrated analysis was performed by using the microarray datasets in AMD derived from the Gene Expression Omnibus (GEO) database. The functional annotation and potential pathways of differentially expressed genes (DEGs) were further discovered by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. We constructed the AMD-specific transcriptional regulatory network to find the crucial transcriptional factors (TFs) which target the DEGs in AMD. Quantitative real time polymerase chain reaction (qRT-PCR) was performed to verify the DEGs and TFs obtained by integrated analysis. RESULTS: From two GEO datasets obtained, we identified 1280 DEGs (730 up-regulated and 550 down-regulated genes) between AMD and normal control (NC). After KEGG analysis, steroid biosynthesis is a significantly enriched pathway for DEGs. The expression of 8 genes (TNC, GRP, TRAF6, ADAMTS5, GPX3, FAP, DHCR7 and FDFT1) was detected. Except for TNC and GPX3, the other 6 genes in qRT-PCR played the same pattern with that in our integrated analysis. CONCLUSIONS: The dysregulation of these eight genes may involve with the process of AMD. Two crucial transcription factors (c-rel and myogenin) were concluded to play a role in AMD. Especially, myogenin was associated with AMD by regulating TNC, GRP and FAP. Our finding can contribute to developing new potential biomarkers, revealing the underlying pathogenesis, and further raising new therapeutic targets for AMD.

Up-regulation of ECT2 is associated with poor prognosis in gastric cancer patients.

OBJECTIVES: The aim of this study was to investigate the expression of ECT2 in gastric cancer and its clinical significance. METHODS AND RESULTS: We investigated the differentially expressed genes between gastric cancer tissues and normal gastric mucosa by cDNA microarray, and then we found ECT2 was up-regulated in gastric cancer. What is more, we verified ECT2 expression level by quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR) and measured its protein level by immunohistochemistry (IHC). qRT-PCR analysis indicated ECT2 was significantly up-regulated in gastric cancer and Immunohistochemistry confirmed the percentage of ECT2-positive specimens was significantly higher in gastric carcinoma than in non-tumor tissues. Up-regulation of ECT2 is associated with the degree of histological differentiation (P = 0.007), invasion depth (P = 0.047), lymph node metastasis (P = 0.016), distant metastasis (P = 0.021) and TNM stage (P = 0.016), patients with up-regulated ECT2 had a lower overall survival rate (P = 0.000). Cox regression analysis revealed that up-regulation of ECT2 is an independent prognostic factor in gastric cancer patients (P = 0.012). CONCLUSION: Up-regulation of ECT2 might contribute to the progression of gastric carcinogenesis and may be a useful prognostic indicator in gastric cancer.