Screening of ferroptosis-related genes in sepsis-induced liver failure and analysis of immune correlation.

Purpose: Sepsis-induced liver failure is a kind of liver injury with a high mortality, and ferroptosis plays a key role in this disease. Our research aims to screen ferroptosis-related genes in sepsis-induced liver failure as targeted therapy for patients with liver failure. Methods: Using the limma software, we analyzed the differentially expressed genes (DEGs) in the GSE60088 dataset downloaded from the Gene Expression Omnibus (GEO) database. Clusterprofiler was applied for enrichment analysis of DEGs enrichment function. Then, the ferroptosis-related genes of the mice in the FerrDb database were crossed with DEGs. Sepsis mice model were prepared by cecal ligation and perforation (CLP). ALT and AST in the serum of mice were measured using detection kit. The pathological changes of the liver tissues in mice were observed by hematoxylin-eosin (H & E) staining. We detected the apoptosis of mice liver tissues using TUNEL. The expression of Hmox1, Epas1, Sirt1, Slc3a2, Jun, Plin2 and Zfp36 were detected by qRT-PCR. Results: DEGs analysis showed 136 up-regulated and 45 down-regulated DEGs. Meanwhile, we found that the up-regulated DEGs were enriched in pathways including the cytokine biosynthesis process while the down-regulated DEGs were enriched in pathways such as organic hydroxy compound metabolic process. In this study, seven genes (Hmox1, Epas1, Sirt1, Slc3a2, Jun, Plin2 and Zfp36) were obtained through the intersection of FerrDb database and DEGs. However, immune infiltration analysis revealed that ferroptosis-related genes may promote the development of liver failure through B cells and natural killer (NK) cells. Finally, it was confirmed by the construction of septic liver failure mice model that ferroptosis-related genes of Hmox1, Slc3a2, Jun and Zfp36 were significantly correlated with liver failure and were highly expressed. Conclusion: The identification of ferroptosis-related genes Hmox1, Slc3a2, Jun and Zfp36 in the present study contribute to our understanding of the molecular mechanism of sepsis-induced liver failure, and provide candidate targets for the diagnosis and treatment of the disease.

Molecular Characterization of Carbapenem-Resistant Acinetobacter baumannii Isolates Among Intensive Care Unit Patients and Environment.

Objective: Critical patients in intensive care unit (ICU) are highly susceptible to acquiring carbapenem-resistant Acinetobacter baumannii (CRAB) infection. To investigate the relationship between nosocomial infections and environmental health, we studied the distribution and homology of CRAB isolates from patients and environment and evaluated the effectiveness of infection control measures. Methods: In the 4-month study, we conducted a monthly CRAB screening of the ICU environment prior to disinfection in a Chinese teaching hospital. The ICU underwent routine disinfection procedures twice a day. We collected samples from the environment around the patients before disinfection. Clinical specimens from patients were also screened. The samples obtained were studied for phenotype and homology via antibiotic susceptibility testing, pulsed-field gel electrophoresis (PFGE), and whole-genome sequencing (WGS). Results: Ten specimens were sampled from ICU environments. Five were obtained in May 2020, and sputums from patient a in bed A at this time were cultured for CRAB isolates; in June 2020 another 5 environmental specimens were obtained from the same bed unit for CRAB, and sputums from patient b in bed A at this time were also cultured for CRAB isolates. Following intensive infection control measures, environmental sampling was negative in July and August. These 18 CRAB isolates all carried OXA-66 and OXA-23 genes and showed a similar resistance phenotype. WGS showed a close relationship among specimens from patients' sputum and their surroundings, but no homology between patients. Conclusion: The analysis of cgMLST and SNPs is more accurate for strain homology analysis. Our data confirm that CRAB isolates spread from patient to environment in ICU; however, contact isolation and disinfection measures are effective in avoiding transmission, highlighting the importance of continued education and surveillance of CRAB. WGS could provide rich information on antimicrobial resistance, which is of great value in scientific research and clinical diagnosis.