Circular RNA hsa_circ_0049657 as a Potential Biomarker in Non-Small Cell Lung Cancer.

Non-small cell lung cancer (NSCLC) is a common lung disorder. In this study, we applied bioinformatics methods to analyze and investigate the role of the NFIX gene in NSCLC. Hsa_circ_0049657 is derived from the NFIX gene, this research aimed to verify the potential role of hsa_circ_0049657 in the development of NSCLC. The results suggested that NFIX was downregulated in most cancers. In addition, the NFIX expression in lung adenocarcinoma (LUAD) was associated with the clinicopathological stage. In LUAD, NFIX expression was associated with the degree of infiltration of most immune cells. The expression levels of hsa_circ_0049657 were significantly lower in cancerous tissues than in paracancerous tissues. Moreover, the results showed that hsa_circ_0049657 expression was downregulated in NSCLC cells. After overexpression of hsa_circ_0049657, the proliferation and migration ability of NSCLC cells were significantly inhibited and the level of apoptosis was increased. We could suppress the proliferation and invasion abilities and promote apoptosis of NSCLC cells by up-regulating hsa_circ_0049657, which might be a potential biomarker for NSCLC.

Large-scale genomic survey and characterization of mcr genes carried by foodborne Cronobacter isolates.

IMPORTANCE: Cronobacter is an emerging foodborne opportunistic pathogen, which can cause neonatal meningitis, bacteremia, and NEC by contaminating food. However, the entire picture of foodborne Cronobacter carriage of the mcr genes is not known. Here, we investigated the mcr genes of Cronobacter isolates by whole-genome sequencing and found 133 previously undescribed Cronobacter isolates carrying mcr genes. Further genomic analysis revealed that these mcr genes mainly belonged to the mcr-9 and mcr-10. Genomic analysis of the flanking structures of mcr genes revealed that two core flanking structures were prevalent in foodborne Cronobacter isolates, and the flanking structure carrying IS1R was found for the first time in this study.

Lack of geographical and ethnic distribution of Hepatitis B virus genotypes in Hainan Island, China.

Recent studies showed that the distribution of hepatitis B virus (HBV) genotype exhibited geographical and ethnic characteristics. Haikou city is the largest city on Hainan Island that geographically isolated from mainland of China, and is the home of multiple ethnic groups. The aim of the study was to investigate the characteristics of the HBV genotype/subgenotype distribution in Haikou city. HBV DNA was isolated from180 serum samples derived from the Han and Li groups. The HBV genotype was detected by polymerase chain reaction using genotype-specific primers and was further determined by full-length genome sequences. The results revealed that the genotype B (37.2%) and C (62.8%) were the predominant HBV genotypes in Haikou, regardless of ethnic background., Additionally, the genotype distribution was not significantly different regarding ethnicity, sex or level of serum HBV DNA. Moreover, there were multiple subgenotypes circulating in the region. In conclusion, our study revealed the diverse HBV genotypes/subgenotypes in Haikou. These findings provide a preliminary study of the distribution of HBV genotypes circulating on Hainan Island.

IDENTIFICATION OF SUBPHENOTYPES OF SEPSIS-ASSOCIATED LIVER DYSFUNCTION USING CLUSTER ANALYSIS.

ABSTRACT: Objectives: We attempted to identify and validate the subphenotypes of sepsis-associated liver dysfunction (SALD) using routine clinical information. Design: This article is a retrospective observational cohort study. Setting: We used the Medical Information Mart for Intensive Care IV database and the eICU Collaborative Research Database. Patients: We included adult patients (age ≥18 years) who developed SALD within the first 48 hours of intensive care unit (ICU) admission. We excluded patients who died or were discharged from the ICU within the first 48 hours of admission. Patients with abnormal liver function before ICU admission were also excluded. Measurements and Main Results: Patients in the MIMIC-IV 1.0 database served as a derivation cohort. Patients in the eICU database were used as validation cohort. We identified four subphenotypes of SALD (subphenotype α, ß, γ, δ) using K-means cluster analysis in 5234 patients in derivation cohort. The baseline characteristics and clinical outcomes were compared between the phenotypes using one-way analysis of variance/Kruskal-Wallis test and the χ 2 test. Moreover, we used line charts to illustrate the trend of liver function parameters over 14 days after ICU admission. Subphenotype α (n = 1,055) was the most severe cluster, characterized by shock with multiple organ dysfunction (MODS) group. Subphenotype ß (n = 1,179) had the highest median bilirubin level and the highest proportion of patients with underlying liver disease and coexisting coagulopathy (increased bilirubin group). Subphenotype γ (n = 1,661) was the cluster with the highest mean age and had the highest proportion of patients with chronic kidney disease (aged group). Subphenotype δ (n = 1,683) had the lowest 28-day and in-hospital mortality (mild group). The characteristics of clusters in the validation cohort were similar to those in the derivation cohort. In addition, we were surprised to find that GGT levels in subphenotype δ were significantly higher than in other subphenotypes, showing a different pattern from bilirubin. Conclusions: We identified four subphenotypes of SALD that presented with different clinical features and outcomes. These results can provide a valuable reference for understanding the clinical characteristics and associated outcomes to improve the management of patients with SALD in the ICU.

MALAT1 Polymorphisms and Lung Cancer Susceptibility in a Chinese Northeast Han Population.

Background: LncRNA MALAT1 (metastasis-associated lung adenocarcinoma transcript 1) was competitive endogenous RNA (ceRNA) involved in various molecular processes for metastasis development in lung cancer. Single nucleotide polymorphisms (SNPs) in MALAT1 gene might be predictive markers for lung cancer. In our study, we selected rs619586 and rs3200401 in MALAT1 gene to explore their effects on lung cancer susceptibility. Methods: The case-control study included 444 lung cancer cases and 460 healthy controls. Genotyping was performed by Taqman allelic discrimination method. Logistic regression, Student t-test, and Chi-square test (χ2 ) were used to analyze the data. Results: The findings of the study showed that rs3200401 was significantly associated with the risk of non-small cell lung cancer (NSCLC) and lung squamous cell carcinoma (LUSC). Compared with homozygous CC genotype, CT heterozygous genotype decreased risk of NSCLC (Pa = 0.034) and LUSC (Pa = 0.025). In addition, no statistical association was detected between rs619586 and lung cancer susceptibility. The interactions between genes and cigarette smoking were discovered via crossover analysis. However, there were no remarkable gene-environment interactions in additive and multiplicative model. Conclusion: Rs3200401 in lncRNA MALAT1 was associated with the susceptibility of non-small-cell lung cancer and lung squamous cell carcinoma. The gene-environmental (cigarette smoking) interactions were not notable.

Cyclocytidine hydrochloride inhibits the synthesis of relaxed circular DNA of hepatitis B virus.

Background: Cyclocytidine hydrochloride (HCl) has been reported to inhibit DNA synthesis by affecting DNA polymerase. Here, we tested the antiviral effect of cyclocytidine on hepatitis B virus (HBV) DNA synthesis, which is reliant on DNA polymerase activity. Materials and Methods: Cyclocytidine HCl was treated to HBV-producing HepAD38 cells or added to an endogenous polymerase reaction, and HBV DNA was detected by Southern blot. Results: Treatment of 20 µM cyclocytidine HCl significantly decreased the production of relaxed circular (rc) DNA in HepAD38 cells and block rcDNA synthesis in endogenous polymerase reaction (EPR), a cell free assay, possibly by inhibiting the HBV DNA polymerase activity. Conclusion: Cyclocytidine HCl could inhibit the synthesis of HBV rcDNA, the precursor of covalently closed circular DNA, and this result provides a case for the usage of "old" drugs for "new" applications.

Discrepant results of hepatitis B virus genotype determination by PCR and DNA sequencing.

Currently, multiplex-PCR with genotype-specific primers is widely used for preliminary screening of hepatitis B virus (HBV) genotypes, despite its relatively lower accuracy compared with whole genome sequencing. Here, we present the discrepant results of HBV genotyping by PCR and full-length sequencing. HBV DNA was isolated from chronic hepatitis B serum and the HBV genotype was detected by PCR using genotype-specific primers and full-length genome sequencing. As a result, the determination of genotype B by the PCR method was consistent with the DNA sequencing results; however, PCR revealed that genotype C showed a mix of B and C genotypes in the current study. In conclusion, the PCR-based genotyping may not provide accurate information of the HBV genotype and whole genome sequencing remains the "gold standard" for HBV genotyping.

Survival Outcome and Clinicopathologicl analysis of Homeobox gene cluster-embedded LncRNAs in Human Cancers: A Systematic Review and Meta-analysis.

OBJECTIVE: The ectopic expression of Homeobox (HOX) gene cluster-embedded long non-coding RNAs (LncRNAs) have been involved several carcinogenic development and progressions. This meta-analysis aimed to summarize the LncRNAs to validate the functions and the prognostic values in several kinds of cancer. METHODS: The retrospective study was conducted to analyze the association between HOX gene-related LncRNAs and the survival outcomes. Cochran's Q and I2 test were used for calculated heterogeneity, and I2 > 50%, P < 0.05 was conformed to the random effect model. Publication bias was indicated by Begg's and Egger's test. RESULTS: Total 15,315 patients extracting from 121 studies focused on assessing the association between LncRNAs and the survival outcomes and 12,110 participants were enrolled to address the clinicopathological features. The results demonstrated that the overexpression of HOX gene cluster-embedded LncRNAs revealed notable association among tumor size (pooled OR = 1.80), lymph node metastasis (LNM) stage (pooled OR = 3.00), tumor node metastasis (TNM) stage (pooled OR = 2.86), histological differentiation (pooled OR = 1.59) and distant metastasis (pooled OR = 2.49). Additionally, the up-regulated LncRNAs predicted a poor prognosis in overall survival (pooled HR = 1.95, 95%CI = 1.86-2.04), and also disclosed worse prognosis among the stratified analysis included HOX clusters, LncRNAs, ethnicity, and tumor classification (pooled HRs >1). CONCLUSION: In summary, the findings proved that HOX gene cluster-embedded LncRNAs acted as potential biomarkers for clinical treatment of several tumors and the overexpression might be a candidate hallmark for prognosis outcome.

Differential efficacy of mycophenolate mofetil in adults with relapsing myelin oligodendrocyte glycoprotein antibody-associated disorders.

BACKGROUND: Myelin oligodendrocyte glycoprotein-immunoglobulin (MOG-IgG) associated disorder (MOGAD) has been recognized as a distinct disease entity with recurrent attacks. But the standard therapeutic approach to reduce relapses is unknown. Different doses of mycophenolate mofetil (MMF) are frequently used in MOGAD. We aimed to investigate the response to stratified doses of MMF in adult patients with MOGAD. METHODS: We determined the frequency of relapses in patients receiving various doses of MMF treatment for MOGAD. Patients were reviewed for relapses before and during long-term treatment. Cox proportional hazards models were used to analyze the correlation between the MMF dosage and the annualized relapse rate (ARR) as well as clinical features. RESULTS: 22 patients receiving low-dose MMF (< 1000 mg/day), 19 patients receiving moderate-dose MMF (1000 mg/day ≤ MMF dose < 2000 mg/day) and 21 patients receiving high-dose MMF (≥ 2000 mg/day) were collected in our cohort. Cox regression analysis showed that high-dose MMF treatment significantly reduced the risk of relapses (HR 0.501 [95% CI 0.268-0.934], p = 0.030) compared with low-dose and moderate-dose of MMF treatment, after adjusted by age, gender, disease duration and prednisone therapy. Patients (13/62) concomitant with autoimmune diseases, had a higher proportion of relapses (76.92%) compared with those without autoimmune diseases (18.37%) (HR = 5.96, 95% CI 1.73-20.48, p < 0.001). The overall median ARR reduced from 1.13 to 0.32 under high-dose MMF treatment (p = 0.004). However, there was no significant reduction in ARR either in patients with low-dose or those with moderate-dose of MMF. CONCLUSION: This study suggests that high-dose of MMF treatment may reduce recurrent demyelinating attacks, with the lowest ARR. Randomized controlled studies are required to validate the effective therapeutic regimen.

The relationship between LncRNAs and lung adenocarcinoma as well as their ceRNA network.

BACKGROUND: More and more studies have shown that long non-coding RNA (LncRNA) as a competing endogenous RNA (ceRNA) plays an important role in lung cancer. Therefore, we analyzed the RNA expression profiles of 82 lung cancer patients which were all from Gene Expression Omnibus (GEO). METHODS: Firstly, we used BLASTN (evalue = 1e-10) to annotate the gene sets, performed in-group correction and batched normalization of the three data sets with R. Secondly, we used the limma and sva packages to compare tumor tissues with normal tissues. Then through WGCNA, we obtained the 4 gene modules most related to the trait. RESULTS: We intersected the genes of above 4 modules with the differential expression genes: 28 LncRNAs (up: 5, down: 23) and 265 mRNAs (up:11, down: 254). Based on these genes, we picked up 6 LncRNAs (CCDC39, FAM182A, SRGAP3-AS2, ADAMTS9-AS2, AC020907.2, SFTA1P), then set and visualized the LncRNA-miRNA-mRNA ceRNA network with 12 miRNAs related to 12 mRNAs. Finally, we performed downstream analysis of 265 mRNAs by Gene Ontology (GO) enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis and Protein-Protein Interaction (PPI) network. CONCLUSION: After analyzing, we think this study provides a new direction for basic and clinical research related to LAD, and is expected to provide new targets for early diagnosis, prognostic evaluation and clinical treatment of lung cancer.

Genetic Polymorphisms of PRNCR1 and Lung Cancer Risk in Chinese Northeast Population: A Case-Control Study and Meta-Analysis.

Long noncoding RNAs (lncRNAs) play vital roles in development and progression of various cancers. To investigate the relationship between three tag single-nucleotide polymorphisms (SNPs) (rs13252298, rs1016343, and rs1456315) in lncRNA prostate cancer-associated noncoding RNA 1 (PRNCR1) and lung cancer (LC) risk, we conducted this study. First, we performed a case-control study, including 576 LC patients and 612 cancer-free controls. Second, a meta-analysis was used to evaluate the association of selected SNPs with risk of overall cancer. We found that rs13252298 and rs1456315 were strongly correlated with risk of LC, nonsmall cell lung cancer (NSCLC), and lung adenocarcinoma. For rs13252298, individuals carrying GG genotype had increased risks of LC compared with those carrying AA genotype (adjusted odds ratio [OR] = 1.565, 95% CI = 1.091-2.245, p = 0.015). A significant result was also found in recessive model with adjusted OR of 1.719. Individuals with GG genotype of rs1456315 were at increased risks of LC compared with those carrying AA genotype. Similar results were found in NSCLC patients. Meta-analysis showed that rs1016343 and rs13252298 were associated with overall cancer. But for rs1016343, no significant association was observed in Asians. In conclusion, rs13252298 and rs1456315 in PRNCR1 may be genetic susceptibility factors for LC in Chinese population. These results need to be confirmed by further studies.

Long Non-coding RNA HOTAIR Function as a Competing Endogenous RNA for miR-149-5p to Promote the Cell Growth, Migration, and Invasion in Non-small Cell Lung Cancer.

Lung cancer is a leading cause of cancer death all around the world. Long non-coding RNAs (lncRNAs) have been confirmed to be involved in carcinogenesis of malignancies. However, the molecular mechanism of most lncRNAs in various kinds of cancers remains unclear. LncRNA HOTAIR and HNRNPA1 are reported to play an oncogenic role in non-small cell lung cancer, and the overexpression of HNRNPA1 is shown to promote the proliferation of lung adenocarcinoma cells. In our study, we find that the overexpression of HOTAIR could promote the proliferation and overexpression of miR-149-5p could inhibit the proliferation of lung cancer cells. Flow cytometric analysis determines that overexpression of miR-149-5p induces cell cycle arrest in the G0/G1 phases, whereas overexpression of HOTAIR decreases the proportion of G0/G1phase cells. Also, overexpression of HOTAIR promotes the migration and invasion ability of lung cancer cells, confirmed by the wound-healing and transwell assays, which are suppressed by overexpression of miR-149-5p. Furthermore, the dual-luciferase reporter assay indicates that miR-149-5p could bind both HOTAIR and the 3'UTR of HNRNPA1. In summary, we find that HOTAIR can regulate HNRNPA1 expression through a ceRNA mechanism by sequester miR-149-5p, which post-transcriptionally targets HNRNPA1, thus promoting lung cancer progression.

Association of LINC00673 rs11655237 polymorphism with cancer susceptibility: A meta-analysis based on 23,478 subjects.

BACKGROUND: Some studies on the relationship between LINC00673 polymorphism and cancer susceptibility have been inconsistent. To perform a more comprehensively quantitative assessment of LINC00673 rs11655237 and risk of overall cancer, we operated this meta-analysis for the first time. METHODS: A comprehensive search was conducted to obtain relevant literature up to November 20, 2019. Pooled odds ratios and 95% confidence intervals were utilized to assess rs11655237 and cancer susceptibility under five different genetic models. RESULTS: Eventually, 11 case-control studies from 9 articles were included. We found that LINC00673 rs11655237 polymorphism increased the susceptibility to overall cancer under all genetic models in the overall population. By dividing ethnicity and cancer type into subgroups, we also obtained similar positive results in subgroups of Chinese population, pancreatic cancer, cervical cancer, neuroblastoma, hepatoblastoma and gastric cancer. CONCLUSION: Overall, this meta-analysis has demonstrated for the first time that LINC00673 rs11655237 could increase susceptibility to cancer.

Investigation of an imported cholera case in China with whole genome sequencing.

Determining the source and genetic characteristics of the imported pathogen is critical in the control of infectious diseases. Here, we reported the investigation of an imported cholera case in China in 2018 with a recent travel history in Nepal and India. Stool culture from the patient was identified as Vibrio cholerae serogroup O1, biotype El Tor, serotype Ogawa. The strain 2018HL24 possessed intact Vibrio seventh pandemic island I (VSP-I), Vibrio pathogenicity Island 1 and 2 (VPI-1, VPI-2). A VSP-II variant with a 13 kb deletion was also detected, which was identical to those observed in V. cholerae in cluster "Nepal-4". Phylogenetic analysis based on the core genome SNPs showed that the isolate was most closely related to the V. cholerae isolated in northern India not far from the border of Nepal in 2012 (16 SNPs). Combining the epidemiological data with phylogenetic analysis results, we speculate that the patient may got infected in Nepal-India region.

The Association Between Two Common Polymorphisms and Cancer Susceptibility: A Meta-Analysis.

BACKGROUND: Most studies revealed that microRNAs could play important roles in the development of various types of cancers. However, the findings remain inconsistent and controversial. To get more accurate results about the association of miR-26a-1 rs7372209 and miR-423 rs6505162 polymorphisms with risk of cancer, we conduct this meta-analysis. MATERIALS AND METHODS: We have searched relevant articles from the PubMed, Web of Science, Wanfang, and Chinese National Knowledge Infrastructure databases up to May 3, 2019. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were analyzed to assess the relationship between these two genetic polymorphisms and susceptibility to cancer. All statistical analyses were performed with Stata 12.0 software. RESULTS: Thirty-five articles were eligible in this meta-analysis, including 17,746 cases and 21,808 controls. Our results suggested that the miR-26a-1 rs7372209 polymorphism was associated with the susceptibility to overall cancer significantly in homozygote comparison and recessive model (TT versus CC: OR = 1.167, 95% CI: 1.025-1.329, P = 0.020; TT versus CT + CC: OR = 1.162, 95% CI: 1.025-1.318, P = 0.019). For miR-423 rs6505162, this study showed that the relationship between it and overall cancer susceptibility was statistically significant among five genetic models (CA versus CC: OR = 0.884, 95% CI: 0.806-0.969, P = 0.009; AA + CA versus CC: OR = 0.870, 95% CI: 0.789-0.959, P = 0.005; AA versus CA + CC: OR = 0.904, 95% CI: 0.827-0.988, P = 0.026; A versus C: OR = 0.899, 95% CI: 0.834-0.970, P = 0.006) rather than homozygote model. CONCLUSIONS: Rs7372209 in miR-26a-1 and rs6505162 in miR-423 are associated with overall cancer susceptibility.

Genomic Epidemiology of an Outbreak of Klebsiella pneumoniae ST471 Producing Extended-Spectrum ß-Lactamases in a Neonatal Intensive Care Unit.

PURPOSE: Klebsiella pneumoniae producing extended-spectrum ß-lactamases (ESBLs) causes nosocomial infections worldwide. The present study aimed to determine the molecular subtyping characteristics and antibiotic resistance mechanisms of ESBL-producing K. pneumoniae strains collected during an outbreak. Moreover, we attempted to reveal the fine transmission route of the strains within this outbreak using whole-genome sequencing (WGS). METHODS: Collecting cases and strain information were carried out. Outbreak-related strains were identified using pulsed-field gel electrophoresis (PFGE). The antibiotic susceptibility, drug-resistant genes, and molecular subtype characteristics of ESBL-producing K. pneumoniae were analyzed. The fine transmission route of the strains within this outbreak was revealed using WGS and minimum core genome (MCG) sequence typing. RESULTS: In mid-January, 2015, five cases of neonatal pneumonia caused by ESBL-producing K. pneumoniae were observed in the neonatal intensive care unit (NICU) of the Affiliated Hospital of Chifeng University, China. Eight ESBL-producing K. pneumoniae were isolated from these five cases, and two additional strains from another two cases were identified using PFGE. All ten isolates harbored bla CTX-M-15, bla TEM-1, bla SHV-108, and bla OXA-1 genes, and belonged to the sequence type 471 (ST471) clone. A putative transmission map was constructed via comprehensive consideration of genomic and epidemiological information. WGS identified the initial case and the "superspreader". The genomic epidemiological investigation revealed that the outbreak was caused by the introduction of the bacteria one month before the first case appeared. CONCLUSION: As far as we know, this is the first report to describe the characteristics of an ST471 ESBL-producing K. pneumoniae outbreak. The data showed that epidemiological inferences could be greatly improved by interpretation in the context of WGS and that K. pneumoniae strains isolated from the same outbreak contain sufficient genomic differences to refine epidemiological linkages on the basis of genetic lineage. These findings suggested that integration of genomic and epidemiological data can help us to have a clearer understanding of when and how outbreaks occur, so as to better control nosocomial transmission.

Candidate lncRNA-microRNA-mRNA networks in predicting non-small cell lung cancer and related prognosis analysis.

PURPOSE: The role of non-coding RNA, once thought to be dark matter, is increasingly prominent in cancer. Our article explores the effect of non-coding RNA in lung adenocarcinoma and lung squamous cell carcinoma by mining TCGA public database. METHODS: Download the data by applying the official TCGA software. The data were analyzed by R data analysis packages, 'edgeR', 'gplots' and 'survival'. We better illustrate the potential networks of lung cancer genes by constructing ceRNAs, using Cytoscape software. RESULTS: We obtained genes which were differentially expressed in lung adenocarcinoma and lung squamous cell carcinoma analysis. Within these differentially expressed genes, we also conducted a survival analysis to find differentially expressed genes associated with prognosis in both lung adenocarcinoma and lung squamous cell carcinoma. Based on genes differentially expressed of both lung adenocarcinoma and lung squamous cell carcinoma, we constructed a ceRNA network to illustrate the mechanism of lung adenocarcinoma and lung squamous cell carcinoma. Our study analyzed genes which were differentially expressed in lung adenocarcinoma and lung squamous cell carcinoma using the TCGA database. CONCLUSION: Based on this, the prognosis in both lung squamous cell carcinoma and lung adenocarcinoma was analyzed. We have also constructed a ceRNA network to provide a basis for the study of ceRNA in lung adenocarcinoma and lung squamous cell carcinoma.