RAGE is a potential biomarker implicated in immune infiltrates and cellular senescence in lung adenocarcinoma.

BACKGROUND: Receptor for Advanced Glycation End-products (RAGE) is an oncogene abnormally expressed in various cancers. However, the clinical value of RAGE and the biological role of RAGE in lung cancer have not been fully investigated. METHODS: We compared the RAGE expression using several public databases. The relationship between RAGE expression and clinicopathological variables was assessed. The R software package was used to carry out enrichment analyses of RAGE co-expression and gene set enrichment analysis (GSEA). Additionally, we used the TIMER database to assess the association between immune infiltration and RAGE expression. The correlation between RAGE expression and senescence biomarkers in lung adenocarcinoma was analyzed using the TCGA database. RESULTS: Our findings indicated that the expression of RAGE was downregulated in lung adenocarcinoma, and down-regulation of RAGE was related to poor overall survival and disease-free survival. Functional enrichment analysis indicated that RAGE co-expression genes were mainly associated with neutrophil activation involved in immune response, neutrophil degranulation, and regulation of leukocyte-mediated immunity. Correlation analysis revealed that RAGE expression was closely related to the purity of the tumor and immune infiltration. GSEA indicated that the RAGE-related differential genes were mainly enriched in senescence-related pathways. Besides, the RAGE expression was significantly associated with senescence-related genes. CONCLUSION: Down-regulation of RAGE expression was associated with poor prognosis, as well as defective immune infiltration and cellular senescence in lung adenocarcinoma.

Symptom and comorbidity burden in hypertensive patients with obstructive sleep apnea.

Background: Obstructive sleep apnea (OSA) is an important but frequently overlooked risk factor for hypertension (HTN). The prevalence of hypertension is high in patients with OSA, but the differences in clinical symptoms and comorbidities between patients with OSA with hypertension and those with normal blood pressure have not been fully defined. Methods: This study retrospectively analyzed OSA patients diagnosed for the first time in Lihuili Hospital Affiliated to Ningbo University from 2016 to 2020. Patients were divided into an OSA group with hypertension and an OSA group without hypertension. The sociodemographic information, clinical symptoms, comorbidities, and polysomnography results of the two groups were compared. The independent risk factors associated with hypertension in patients with OSA were explored. Results: A total of 1108 patients with OSA initially diagnosed were included in the study, including 387 with hypertension and 721 without. Compared with OSA patients without hypertension, OSA patients with hypertension were older; had a higher body mass index (BMI) and Epworth sleepiness score (ESS); a higher incidence of nocturia; and a higher proportion of diabetes mellitus, coronary heart disease, and cerebrovascular disease. Multivariate analysis showed age (odds ratio [OR]:1.06, 95% confidence interval [CI]:1.04-1.08), BMI (OR:1.17, 95% CI:1.11-1.23), ESS score (OR:0.97, 95%CI: 0.94-1.00) and nocturia symptoms (OR:1.64, 95% CI:1.19-2.27) was independently associated with hypertension in OSA patients, and comorbid diabetes (OR: 3.86, 95% CI: 2.31-6.45), coronary heart disease (OR: 1.90, 95% CI:1.15-3.16), and ischemic stroke (OR: 3.69,95% CI:1.31-10.40) was independently associated with hypertension in OSA patients. Conclusion: Compared to OSA patients with normal blood pressure, OSA patients with hypertension had more significant daytime sleepiness, more frequent nocturnal urination, and a higher risk of diabetes, coronary heart disease, and cerebrovascular disease.

Genome characteristics of a MDR Pseudomonas monteilii carrying a novel VIM-type ß-lactamase, blaVIM-84.

OBJECTIVES: This study aimed to determine the genetic environment and characterize plasmid carrying a novel VIM-type ß-lactamase (VIM-84) in a multidrug-resistant Pseudomonas monteilii isolate obtained from the human gut through whole-genome sequencing. METHODS: DNA extraction of P. monteilii L2757hy was performed using the Genomic DNA Isolation Kit (QIAGEN, Hilden, Germany). Whole-genome sequencing was performed by Illumina NovaSeq 6000 and Oxford Nanopore platforms. The transferability of resistance genes was screened single clonal on MHA plates containing rifampicin and meropenem. Verification was performed using MALDI/TOF-MS and PCR with Pseudomonas aeruginosa PAO1Ri as the recipient strain. RESULTS: L2757hy was identified as P. monteilii through sequencing and ANI analysis. The genome was assigned as ST147 and comprised a 6,130,057 bp chromosome with a GC content of 61.8% and a 49,704 bp plasmid. Several resistance genes, including blaIMP-1, aac(6')-IIa and tmexCD-toprJ, as well as virulence genes such as iroN, and wzaJ, were identified on the chromosome. A novel VIM-type blaVIM-84 was found on the plasmid, which was previously identified in Pseudomonas aeruginosa. Plasmid harboring blaVIM-84 was untypable, and it could be transferred to P. aeruginosa PAO1Ri and was associated with a class I integron with the genetic environment intI1-blaVIM-84-tniR-tniQ-tniB-tniA, likely derived from Tn402. CONCLUSIONS: Our study revealed that the novel blaVIM-84 gene was harbored by P. monteilii rather than P. aeruginosa. We suggested that P. monteilii may serve as a reservoir for resistance genes.

Construction and validation of a prognostic signature based on anoikis-related lncRNAs in lung adenocarcinoma.

Lung adenocarcinoma (LUAD) is the most common type of lung cancer and is characterized by a high death rate and a poor prospect for survival. Anoikis, which is a kind of programmed cell apoptosis, is an important factor in the advancement of tumors. Nonetheless, the function of anoikis-related lncRNAs (ARLRs) in LUAD is still not well understood. The TCGA database was queried for genomic and clinical information. A prognostic signature for ARLRs was established via the use of coexpression analysis and Cox regression. Validation of the model's accuracy was conducted utilizing K-M curves and receiver operating characteristic (ROC) curves, and the signature was utilized to develop a nomogram. LncRNAs were implicated in the progression of tumors, as determined by functional enrichment analysis. There was an improvement in prognosis, increased immune cell infiltration, and higher immune scores among the low-risk patients. Additionally, we found that the two groups had varied anticancer drug sensitivities, which could help guide treatment. The impact of one ARLR, AC026355.2, on migration and invasion was validated by in vitro experiments in LUAD cells. Herein, a new lncRNA signature associated with anoikis was identified and estimated, potentially serving as a prognostic indicator for LUAD patients.

Detection of NDM-1-Positive Aeromonas caviae from Bacteremia by Using Whole-Genome Sequencing.

Purpose: Nosocomial infections caused by New Delhi metallo-ß-lactamase (NDM)-producing bacteria are prevalent worldwide. However, such diseases caused by NDM-producing Aeromonas caviae had never been reported. Our study aimed to elucidate the genomic characteristics of NDM-1-producing A. caviae isolated from hospital patients. Methods: Bacterial genomic features and possible origins were assessed by whole-genome sequencing (WGS) and phylogenetic analysis. Subsequent investigations include antimicrobial susceptibility testing and multilocus sequence typing (MLST). Results: We identified here two NDM-1-producing A. caviae isolates from bacteremia. Susceptibility testing showed that two isolates were multi-drug resistant and shared a similar resistance profile and were only sensitive to amikacin and trimethoprim/sulfamethoxazole. Both A. caviae isolates carry the carbapenem resistance gene bla NDM-1 and also have antibiotic resistance genes such as ß-lactams, AmpC enzymes, macrolides, aminoglycosides, and quinolones. S1-PFGE and Southern blot analysis were negative. Whole-genome sequencing and comparative analysis revealed that these two isolates shared a close relationship. Conclusion: To the best of our knowledge, this work describes the first detection of non-plasmid encoded bla NDM-1 in A. caviae. The A. caviae isolated in this study has a broad drug resistance spectrum. Phenotypic and molecular analysis indicated the two isolates belong to the same clone. Routine genomic surveillance of this species is now necessary to effectively curb the further dissemination of carbapenem-resistant bacteria in the region.

Smoking history and its relationship with comorbidities in patients with obstructive sleep apnea.

INTRODUCTION: Current knowledge on the correlation between smoking and comorbidities associated with obstructive sleep apnea (OSA) is limited. This study evaluated the smoking history of OSA patients and analyzed the association between smoking and OSA comorbidities. METHODS: Retrospective analysis was performed in newly diagnosed OSA patients in our hospital, a tertiary medical center, from January 2016 to December 2019. In all, 1021 patients were enrolled and divided into two groups, non-smokers (n=796) and current/former smokers (n=225), in order to compare their clinical manifestations and polysomnographic results and to analyze the association between smoking and comorbidities. RESULTS: Compared with the non-smokers, the current/former smokers had higher Epworth sleepiness scale (ESS) scores (9.3 ± 4.0 vs 8.5 ± 5.1; p<0.05), longer sleep latency (SL) [20.5 (12.3-39.3) vs 18.5 (10.0-34.0) minutes; p<0.05], and a lower nocturnal mean oxygen saturation (91.8 ± 3.6% vs 92.8 ± 3.4%; p<0.001). There was no significant difference in the apnea-hypopnea index (AHI) between the two groups. OSA patients with a history of smoking had significantly increased risk of hypertension (OR=2.09; 95% CI: 1.46- 3.01), chronic obstructive pulmonary disease (COPD) (OR=9.80; 95% CI: 4.73-20.33), gastroesophageal reflux disease (GERD) (OR=1.97; 95% CI: 1.19-3.27), and chronic pharyngitis (OR=1.83; 95% CI: 1.32-2.54). CONCLUSIONS: No significant association was found between previous smoking history and current OSA severity. OSA patients with a history of smoking had an increased risk of hypertension, COPD, GERD, and chronic pharyngitis.

The effect of helium-oxygen-assisted mechanical ventilation on chronic obstructive pulmonary disease exacerbation: A systemic review and meta-analysis.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is often accompanied by acute exacerbations. Patients of COPD exacerbation suffering from respiratory failure often need the support of mechanical ventilation. Helium-oxygen can be used to reduce airway resistance during mechanical ventilation. The aim of this study is to evaluate the effect of helium-oxygen-assisted mechanical ventilation on COPD exacerbation through a meta-analysis. METHODS: A comprehensive literature search through databases of Pub Med (1966∼2016), Ovid MEDLINE (1965∼2016), Cochrane EBM (1991∼2016), EMBASE (1974∼2016) and Ovid MEDLINE was performed to identify associated studies. Randomized clinical trials met our inclusion criteria that focus on helium-oxygen-assisted mechanical ventilation on COPD exacerbation were included. The quality of the papers was evaluated after inclusion and information was extracted for meta-analysis. RESULTS: Six articles and 392 patients were included in total. Meta-analysis revealed that helium-oxygen-assisted mechanical ventilation reduced Borg dyspnea scale and increased arterial PH compared with air-oxygen. No statistically significant difference was observed between helium-oxygen and air-oxygen as regards to WOB, PaCO2 , OI, tracheal intubation rates and mortality within hospital. CONCLUSIONS: Our study suggests helium-oxygen-assisted mechanical ventilation can help to reduce Borg dyspnea scale. In terms of the tiny change of PH, its clinical benefit is negligible. There is no conclusive evidence indicating the beneficial effect of helium-oxygen-assisted mechanical ventilation on clinical outcomes or prognosis of COPD exacerbation.

Emergence of blaNDM-1 among Klebsiella pneumoniae ST15 and novel ST1031 clinical isolates in China.

The emergence of NDM-1 has become established as a major public health threat and represents a new and major challenge in the treatment of infectious diseases. A total of 39 carbapenem-resistant Enterobacteriaceae isolates collected from patients receiving care at 5 teaching hospitals in Jiangxi province, central China, were analyzed for carriage of resistance genes, including bla(NDM-1). Two carbapenem-resistant Klebsiella pneumoniae isolates (NC12 and NC18) were found to harbor bla(NDM-1). In addition to bla(NDM-1), NC12 also carried bla(SHV-1), while NC18 harbored additional resistance genes, including bla(SHV-12), bla(CTX-M-14), armA and bla(TEM-1). NC12 and NC18 belonged to ST15 and novel ST1031 and were clonally unrelated. Carbapenem resistance for NC12 could be transferred to Escherichia coli recipients through conjugation and chemical transformation, while carbapenem resistance for NC18 was only transferred to E. coli recipients by chemical transformation. The EcoR1-digested DNA pattern of plasmids from the transformants of NC12 was identical to that for NC18. Taken together, this is the first report of bla(NDM-1) carriage by K. pneumoniae clinical isolates in mainland China, indicating that bla(NDM-1) is disseminated among Enterobacteriaceae in China. Systemic surveillance should focus on the dissemination of bla(NDM-1) among Gram-negative clinical isolates, especially some major clones, such as K. pneumoniae ST15 which is a major clone among CTX-M-15-producing isolates.

Virulence gene profiling and molecular characterization of hospital-acquired Staphylococcus aureus isolates associated with bloodstream infection.

A better understanding of virulence gene profiling and molecular characterization of Staphylococcus aureus isolates associated with bloodstream infection (BSI) may provide further insights related to clinical outcomes with these infections. We analyzed 89 S. aureus isolates including 37 MRSA isolates (41.6%) recovered from 89 adult patients with BSI from 4 hospitals in Zhejiang province, eastern China. Thirty-five (94.6%) of MRSA isolates and 4 (7.7%) of methicillin-sensitive S. aureus (MSSA) isolates were resistant to multiple antimicrobials. All isolates harbored at least 2 of 22 possible virulence genes, including sdrC (92.1%), icaA (89.9%), hla (80.9%), clf (69.7%), sea (68.5%), sdrD (67.4%), hlb (67.4%), sdrE (65.2%), sei (51.7%), seg (50.6%), and cna (50.6%). Forty-four (49.4%) of all S. aureus BSI isolates, including 23 (62.2%) of MRSA isolates, harbored ≥10 of the virulence genes evaluated in this study. Sixteen (43.2%) MRSA isolates and 5 (9.6%) MSSA isolates harbored the gene encoding Panton-Valentine leukocidin (PVL). Collective genes for pvl, sdrE, sed, seg, and sei among MRSA isolates were significantly more frequent relative to MSSA isolates (P < 0.05). A total of 22 sequence types (STs), including novel ST2184, ST2199, and ST2200, and 33 spa types, including novel spa types t9530 and t9532, were identified among S. aureus BSI isolates, among which ST188 (15.7%) and ST7 (15.7%), and t091 (12.4%) and t189 (12.4%), seldom noted for Chinese isolates previously, were major STs and spa types, respectively. In contrast to previous reports, no predominant clones were found in the present study. Among the MRSA isolates, although ST239-MRSA-SCCmecIII, predominant clone in China, still represented the most common clone, it only accounted for 18.9%. However, ST188-MRSA- SCCmecIV seldom reported before accounted for 10.8%. Among the MSSA isolates, ST7-MSSA represented the most common clone (23.1%), followed by ST188-MSSA and ST630-MSSA (9.6% each). In conclusion, simultaneous carriage of multiple virulence genes and genetically considerable diversity were common among S. aureus BSI isolates. Furthermore, MRSA isolates exhibited more frequent carriage of superantigen genes and pvl relative to MSSA isolates. Taken together, there are distinctive virulence gene profiling and molecular characteristic among S. aureus isolates associated with bloodstream infection in China.

Molecular characterization and antimicrobial susceptibility of nasal Staphylococcus aureus isolates from a Chinese medical college campus.

Staphylococcus aureus colonization and infection occur more commonly among persons living or working in crowded conditions, but characterization of S. aureus colonization within medical communities in China is lacking. A total of 144 (15.4%, 144/935) S. aureus isolates, including 28 (3.0%, 28/935) MRSA isolates, were recovered from the nares of 935 healthy human volunteers residing on a Chinese medical college campus. All S. aureus isolates were susceptible to vancomycin, quinupristin/dalfopristin and linezolid but the majority were resistant to penicillin (96.5%), ampicillin/sulbactam (83.3%) and trimethoprim/sulfamethoxazole (93.1%). 82%, (23/28) of the MRSA isolates and 66% (77/116) of the MSSA isolates were resistant to multiple antibiotics, and 3 MRSA isolates were resistant to mupirocin--an agent commonly used for nasal decolonization. 16 different sequence types (STs), as well as SCCmec genes II, III, IVd, and V, were represented among MRSA isolates. We also identified, for the first time, two novel STs (ST1778 and ST1779) and 5 novel spa types for MRSA. MRSA isolates were distributed in different sporadic clones, and ST59-MRSA-VId- t437 was found within 3 MRSA isolates. Moreover, one isolate with multidrug resistance belonging to ST398-MRSA-V- t571 associated with animal infections was identified, and 3 isolates distributed in three different clones harbored PVL genes. Collectively, these data indicate a high prevalence of nasal MRSA carriage and molecular heterogeneity of S. aureus isolates among persons residing on a Chinese medical college campus. Identification of epidemic MRSA clones associated with community infection supports the need for more effective infection control measures to reduce nasal carriage and prevent dissemination of MRSA to hospitalized patients and health care workers in this community.