N6-methyladenosine levels in peripheral blood RNA: a potential diagnostic biomarker for colorectal cancer.

BACKGROUND: N6-methyladenosine (m6A) is dysregulated in various cancers, including colorectal cancer (CRC). Herein, we assess the diagnostic potential of peripheral blood (PB) m6A levels in CRC. METHODS: We collected PB from healthy controls (HCs) and patients with CRC, analyzed PB RNA m6A levels and the expression of m6A-related demethylase genes FTO and ALKBH5, cocultured CRC cells with PB mononuclear cells (PBMCs), and constructed an MC38 cancer model. RESULTS: PB RNA m6A levels were higher in the CRC than that in HCs. The area under the curve (AUC) of m6A levels (0.886) in the CRC was significantly larger compared with carbohydrate antigen 199 (CA199; 0.666) and carcinoembryonic antigen (CEA; 0.834). The combination of CEA and CA199 with PB RNA m6A led to an increase in the AUC (0.935). Compared with HCs, the expression of FTO and ALKBH5 was decreased in the CRC. After coculturing with CRC cells, the PBMCs RNA m6A were significantly increased, whereas the expression of FTO and ALKBH5 decreased. Furthermore, m6A RNA levels in the PB of MC38 cancer models were upregulated, whereas the expression of FTO and ALKBH5 decreased. CONCLUSIONS: PB RNA m6A levels are a potential diagnostic biomarker for patients with CRC.

Molecular Epidemiological Characteristics of Carbapenem Resistant Aeromonas from Hospital Wastewater.

Background: Hospital wastewater (HWW) promotes the spread of carbapenem resistance genes (CRGs). Aeromonas carry a large number of CRGs in HWW, they may play a role as a suitable reservoir for CRGs, while resistomes in HWW are still poorly characterized regarding carbapenem resistant Aeromonas. Thus, the aim of the study was to evaluate the molecular epidemiological characteristics of carbapenem resistant Aeromonas in HWW. Methods: A total of 33 carbapenem resistant Aeromonas were isolated from HWW. Antimicrobial susceptibility testing and polymerase chain reaction (PCR) were used to assess the antimicrobial resistance profiles. Molecular typing was performed using enterobacterial repetitive intergenic consensus PCR (ERIC-PCR) and multilocus sequence typing (MLST). The horizontal transmission mode of bla KPC was explored through conjugation and transformation experiments. The stability of bla KPC-IncP-6 plasmids was assessed through plasmid stability and in vitro competition test. The PCR mapping method was used to investigate the structural diversity of bla KPC. Results: The detection rates of bla KPC and cphA in Aeromonas were 97.0% and 39.4% respectively. Aeromonas caviae were grouped into 13 clusters by ERIC-PCR and 12 STs by MLST. Aeromonas veronii were grouped into 11 clusters by ERIC-PCR and 4 STs by MLST. 56.3% bla KPC were located on mobilizable IncP-6 plasmids. bla KPC-IncP-6 plasmid showed high stability and low cost fitness. Conclusion: Carbapenem resistant Aeromonas from HWW mainly carried bla KPC, which exhibited great structural diversity. Aeromonas might serve as reservoirs for bla KPC and bla KPC might spread mainly through transformation in HWW.

Clinical and genomic characterization of carbapenem-resistant Enterobacterales bloodstream infections in patients with hematologic malignancies.

Background: Carbapenem-resistant Enterobacterales (CRE) bloodstream infections (BSIs) pose a significant risk to patients with hematologic malignancies, yet the distinct features and outcomes of these infections are not thoroughly understood. Methods: This retrospective study examined the characteristics and clinical outcomes of patients with Enterobacterales BSIs at the Hematology Department of Fujian Medical University Union Hospital from 2018 to 2022. Whole-genome sequencing was conducted on 45 consecutive CRE BSI isolates during this period. Results: A total of 301 patients with Enterobacterales BSIs were included, with 65 (21.6%) cases of CRE and 236 (78.4%) cases of carbapenem-susceptible Enterobacterales (CSE). CRE infections accounted for 16.9% to 26.9% of all Enterobacterales BSIs, and carbapenem-resistant Klebsiella pneumoniae (CRKP) was the predominant strain. The most frequent sequence type (ST) and carbapenemase among CRKP were ST11 (68.6%) and blaKPC-2 (80.0%), respectively. Perianal infections, multiple infection foci, and a history of multiple hospitalizations, ICU stays, and prior CRE infections were identified as risk factors for CRE BSIs. Patients in the CRE group experienced significantly higher proportions of infection-related septic shock (43.1% vs. 19.9%, P < 0.0003) and 30-day all-cause mortality (56.9% vs. 24.6%, P < 0.0001) compared to those in the CSE group. Patient's age and disease subtypes, strain subtypes, and antimicrobial treatment regimens significantly influenced survival in patients with CRE BSIs. Conclusions: CRE BSIs are a frequent complication in patients with hematological malignancies undergoing treatment and are associated with poor survival rates. A comprehensive understanding of risk factors and ongoing surveillance of prevalent strains are essential for the effective management of these infections.

[Rapid identification of 14 bile acids contained in Qingkailing injection by HPLC-ESI-MS/MS].

OBJECTIVE: To investigate ESI-MS/MS fragmentation pattern of bile acids contained in Qingkailing injection, and the rapid identification method. METHOD: HPLC-ESI-MS/MS technology was adopted to investigate ESI-MS/MS fragmentation pattern of five bile acids contained in Qingkailing injection, and rapidly identify bile acids contained in Qingkailing injection from eight different manufacturers. RESULT: 5 bile acids showed similar ESI-MS/MS fragmentation patterns, based on which 14 bile acids were rapidly separated from Qingkailing injection. Among them, 11 were found in injections of all of the manufacturers, and the rest three were found in individual manufacturers. CONCLUSION: HPLC-ESI-MS/MS is used to rapidly identify bile acids from complex material systems, which provides an effective method for interpreting the complex material base of compound traditional Chinese medicine preparations and enhance the quality standards.

Identification of the metabolites of Ixerin Z from Ixeris sonchifolia Hance in rats by HPLC-LTQ-Orbitrap mass spectrometry.

Ixerin Z, one of major sesquiterpene lactones from Ixeris sonchifolia Hance, was considered to be a major active compound because of their special structure and activity. However, studies on Ixerin Z metabolism have rarely been reported. This study is the first to investigate the in vivo metabolism of Ixerin Z following intravenously administered of Ixerin Z by HPLC-LTQ-Orbitrap mass spectrometry and multiple mass defect filters (MMDF) technique. A total of 41 metabolites as well as parent drug after using two MMDF filter templates were unambiguously or tentatively identified based on accurate mass measurements, fragmentation patterns, and chromatographic retention times. The metabolic pathways of Ixerin Z were also proposed for the first time. The results demonstrated that Ixerin Z underwent extensive metabolic reaction including hydrogenation, hydroxylation, hydrolysis, methylation, cysteine conjugation, glutathione (GSH) conjugation, sulfate conjugation, N-acetylcysteine conjugation, and glucuronidation. In conclusion, our study provided an insight into the metabolism of Ixerin Z.