Clinical Impact of Colistin Banning in Food Animal on mcr-1-Positive Enterobacteriaceae in Patients From Beijing, China, 2009-2019: A Long-Term Longitudinal Observational Study.

The colistin resistance gene mcr-1 is emerging as a global public health concern, altering the regulation of colistin usage globally since 2017, especially in China. However, few studies have revealed the impact of policy change on the epidemiology of mcr-positive Enterobacteriaceae (MCRPE) in patients. Here, we describe a molecular epidemiological study to investigate the MCRPE in patients in China from 2009-2019. During the surveillance period, 26,080 non-duplicated Enterobacteriaceae isolates were collected in Beijing. Colistin-resistant isolates were screened by enrichment culture supplemented with colistin, and the presence of the mcr gene was determined by PCR amplification. MCRPE isolates were then analyzed by susceptibility testing, genotyping, and risk factor analysis. Of the 26,080 isolates, mcr-1 was detected in 171 (1.1%) of 15,742 Escherichia coli isolates and 7 (0.1%) of 10,338 Klebsiella pneumoniae isolates. The prevalence of mcr-1-positive E. coli (MCRPEC) showed an increasing trend from 2009 to 2016, while a decreasing trend was observed since 2017. Multi-locus sequence typing analysis showed that MCRPEC isolates had extremely diverse genetic backgrounds, and most of these isolates were non-clonal. The prevalence of MCRPE in China remained at a low level, and even showed a declining trend over the last 3 years after the banning of colistin usage as feed additive in food animal in 2017. However, colistin permission in clinical therapy could still increase the risk of MCRPE transmission and intractable infections, active surveillance and monitoring strategies of MCRPE are recommended to prolong the clinical longevity of colistin.

Prevalence and Molecular Characterization of Fluoroquinolone-Resistant Escherichia coli in Healthy Children.

Faecal E. coli can act as reservoirs for resistance genes. Here, we analyzed prevalence of drug resistance in faecal E. coli isolated from healthy children at a single kindergarten in Beijing, China, then used whole genome sequencing to characterize fluoroquinolone-non-susceptible strains. Our results revealed high resistance to ampicillin (54.0%), trimethoprim/sulphurmethoxazole (47.5%) and tetracycline (58.9%) among 576 faecal E. coli isolates, 49.2% of which exhibited multidrug resistance. A total of 113 E. coli isolates were not susceptible to ciprofloxacin, with four sequence types, namely ST1193 (25.7%), ST773 (13.3%), ST648 (8.8%) and ST131 (7.1%) found to be the most prevalent (54.9%). With regards to resistance to quinolones, we detected chromosomal mutations in gyrA, parC, and parE in 111 (98.2%), 105 (92.9%), and 67 (61.1%) isolates, respectively. blaCTX-M (37.2%) was the major ESBL gene, whereas blaCTX-M-14 (12.4%) and blaCTX-M-27 (11.5%) were the most frequent subtypes. A total of 90 (79.6%) ExPEC and 65 (57.5%) UPEC isolates were classified. Overall, these findings revealed clonal spread of certain prevalent STs, namely ST1193, ST773, ST648 and ST131 E. coli isolates in healthy children within a single kindergarten in Beijing, China, affirming the seriousness of the multidrug resistance problem and potential pathogenicity of E. coli isolates in healthy children. Therefore, there is an urgent need for increased surveillance to enhance control of this problem.

Identification of key genes in calcific aortic valve disease via weighted gene co-expression network analysis.

BACKGROUND: Calcific aortic valve disease (CAVD) is the most common subclass of valve heart disease in the elderly population and a primary cause of aortic valve stenosis. However, the underlying mechanisms remain unclear. METHODS: The gene expression profiles of GSE83453, GSE51472, and GSE12644 were analyzed by 'limma' and 'weighted gene co-expression network analysis (WGCNA)' package in R to identify differentially expressed genes (DEGs) and key modules associated with CAVD, respectively. Then, enrichment analysis was performed based on Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, DisGeNET, and TRRUST database. Protein-protein interaction network was constructed using the overlapped genes of DEGs and key modules, and we identified the top 5 hub genes by mixed character calculation. RESULTS: We identified the blue and yellow modules as the key modules. Enrichment analysis showed that leukocyte migration, extracellular matrix, and extracellular matrix structural constituent were significantly enriched. SPP1, TNC, SCG2, FAM20A, and CD52 were identified as hub genes, and their expression levels in calcified or normal aortic valve samples were illustrated, respectively. CONCLUSIONS: This study suggested that SPP1, TNC, SCG2, FAM20A, and CD52 might be hub genes associated with CAVD. Further studies are required to elucidate the underlying mechanisms and provide potential therapeutic targets.