Constructed competitive endogenous RNA network and patterns of immune infiltration revealing the prognostic signature for cervical cancer.

Aim: To investigate the relationship between potential abnormal epigenetic modification and immune cell infiltration in patients with cervical carcinoma. Materials & methods: RNA expression profiles from The Cancer Genome Atlas database were used to explore the relationship between key biomarkers and tumor-infiltrating immune cells and for clinical specimen validation. Results: Two nomogram models were developed, one with specific ceRNA and the other based on biological markers of related tumor-infiltrating immune cells. Moreover, a key biomarker (RIPOR2), which was significantly relevant to CD8 T cells. Conclusion: RIPOR2 and CD8 T cells play a crucial role in the development and progression of cervical carcinoma, suggesting their potential as markers for guiding future therapeutic strategies.

Genomic Investigation of Proteus mirabilis Isolates Recovered From Pig Farms in Zhejiang Province, China.

Proteus mirabilis is a common opportunistic zoonotic pathogen, and its ongoing acquisition of antimicrobial resistance genes poses challenges to clinical treatments. Human-sourced whole genomic sequencing of human P. mirabilis isolates has been reported, but pig-sourced isolates have not been thoroughly investigated even though these animals can serve as reservoirs for human infections. In the current study, we report a molecular epidemiological investigation to unravel the antimicrobial and virulence gene risk factors for P. mirabilis contamination in 9 pig farms in 3 different cities in Zhejiang Province, China. We collected 541 swab samples from healthy pigs and 30 were confirmed as P. mirabilis. All 30 isolates were resistant to tetracyclines, macrolides, sulfonamides, ß-lactams and chloramphenicol, and all were multiple drug-resistant and 27 were strong biofilm formers. Phylogenetic analyses indicated these 30 isolates clustered together in 2 major groups. Whole genome sequencing demonstrated that the isolates possessed 91 different antimicrobial resistance genes belonging to 30 antimicrobial classes including rmtB, sul1, qnrS1, AAC(6') - Ib - cr, blaCTX - M - 65 and blaOXA - 1. All isolates contained mobile genetic elements including integrative conjugative elements (ICEs) and integrative and mobilizable elements (IMEs). Minimum inhibitory concentration (MIC) testing indicated direct correlates between cognate genes and antimicrobial resistance. We also identified 95 virulence factors, almost all isolates contained 20 fimbrial and flagellar operons, and this represents the greatest number of these operon types found in a single species among all sequenced bacterial genomes. These genes regulate biofilm formation and represent a confounding variable for treating P. mirabilis infections. Our P. mirabilis isolates were present in healthy animals, and multiple drug resistance in these isolates may serve as a reservoir for other intestinal and environmental Enterobacteriaceae members. This prompts us to more strictly regulate veterinary antibiotic use.

Genomic Sequence and Pathogenicity of the Chicken Anemia Virus Isolated From Chicken in Yunnan Province, China.

Chicken anemia virus (CAV), which has been reported in many countries, causes severe anemia and immunosuppression in chickens. In this study, a CAV strain YN04 belonging to genotype A was first identified from infected chickens in Yunnan province, China. Moreover, the animal infection experiments further confirmed that the strain YN04 is a highly pathogenic strain, which can cause 86.67% mortality in chickens in the infection group. The mean death time of infected chickens was 13.1 days post infection (dpi). CAV infection induced severe anemia with significant decrease in packed cell volume (PCV), and serious atrophy and lesion of thymus and bursa with high viral load at 14 dpi. Besides, CAV infection caused a sharp decrease in chicken body weight and immune organ indices including the ratio of thymus or bursa to body weight at 21 dpi, which displayed the potential immunosuppression state at this stage. These findings enrich the epidemiological data on CAV and may provide information for preventing its further spread in Yunnan province, China.

High expression of eIF4A2 is associated with a poor prognosis in esophageal squamous cell carcinoma.

Eukaryotic initiation factor 4A-II (eIF4A2) is an ATP-dependent RNA helicase involved in mRNA translation. Abnormal expression of eIF4A2 has been reported as a prognostic factor in different types of cancer. However, little is known regarding the function of eIF4A2 in esophageal squamous cell carcinoma (ESCC). In the present study, 253 samples were collected from patients diagnosed with ESCC, and the expression of eIF4A2 was detected by immunohistochemical staining. The clinicopathological and prognostic significance of eIF4A2 expression in ESCC were then statistically analyzed. The results demonstrated that eIF4A2 was specifically localized to the cytoplasm. Kaplan-Meier analysis also revealed that eIF4A2 expression was associated with the clinical prognosis of patients with ESCC. The median disease-free and overall survival times were 40 and 48 months for patients with low eIF4A2 expression, compared with 16 and 25 months in the high eIF4A2 expression group, respectively. In conclusion, high expression levels of eIF4A2 are associated with a poor prognosis and may be used as a potential prognostic indicator in patients with ESCC.

Absence or mislocalization of DNAH5 is a characteristic marker for motile ciliary abnormality in nasal polyps.

OBJECTIVE: Motile cilia impairment is a common condition in patients with chronically inflamed airways, such as is seen in nasal polyps (NPs). The mechanism underlying this pathogenic condition is complex and not fully understood. METHODS: We investigated the presence and localization of dynein axonemal heavy chain 5 (DNAH5) in motile cilia using immunofluorescence staining in paraffin-embedded nasal biopsies from NPs (n = 120) and inferior turbinate mucosa (n = 35) of healthy controls. We also performed single-cell staining on cytospin samples (NP = 5, control = 5). Three patterns of DNAH5 localization are defined, including pattern A (presence throughout the axoneme), pattern B (undetectable in the distal part of the axoneme), and pattern C (completely missing throughout the entire axoneme). We developed a semiquantitative scoring system for which 0 = (pattern A > 70%); 1 = (patterns A + B > 70%); and 2 = (pattern C ≥ 30%) in each high-power field (5 fields per sample). RESULTS: Based on our DNAH5 scoring system, the median (1st and 3rd quartile) score was 0.3 (0.2 and 0.4) for samples from controls, and 1.1 (0.6 and 1.6) for samples from NPs in paraffin specimens (P < 0.001). The DNAH5 score had a significant positive relationship with the Lund-Mackay computed tomography score (r = 0.329, P = 0.005) and was higher in patients with eosinophilic NPs (P = 0.006). For cytospin samples, the mean percentage of patterns A, B, and C were 74%, 14%, and 12% in controls, and 48%, 20%, and 32% in NPs, respectively. CONCLUSION: Our results suggest that the absence or mislocalization of DNAH5 from motile cilia is a common and potentially important pathological phenomenon in chronically inflamed airway epithelium. LEVEL OF EVIDENCE: NA. Laryngoscope, 128:E97-E104, 2018.