Objective: To investigate the independent risk factors, outcomes and genotypes associated with carbapenem-non-susceptible K. pneumoniae bloodstream infections (BSIs) in northern China from 2014 to 2016. Methods: Over a three-year period, a total of 289 K. pneumoniae BSI patients were identified. Medical records were extracted to obtain the clinical information. Polymerase chain reactions (PCRs) were performed to analyse the multilocus sequence typing (MLST) types, Klebsiella pneumoniae carbapenemase (KPC) and metallo-β-lactamases (MBL) genes, for replicon typing of the 10 randomly selected carbapenem-non-susceptible K. pneumoniae. Results: A total of 59 carbapenem-non-susceptible K. pneumoniae strains were identified. Resistance rates to imipenem, meropenem, ertapenem and amikacin were low. Multivariate analyses showed that a central venous catheter odds ratio (OR) of 4.021 (CI 1.002–16.134); mechanical ventilation of 7.587 (2.856–20.156); Pitt bacteraemia score of 1.481 (CI 1.218–1.800); hospitalization prior to culture of 1.026 (CI 1.001–1.053); and some antibiotic use 30 days prior to K. pneumoniae bacteremia, including carbapenem of 9.123 (CI 2.995–27.791), aminoglycoside of 34.079 (2.091–555.396), and tigecycline of 5.065 (CI 1.261–20.339) were associated with carbapenem-non-susceptible K. pneumoniae bacteremia. Sequence type 11 (ST11) was the most predominant MLST type, which accounted for 50% of the isolates. Eighty per cent of the isolates harbored the KPC-2 gene. The overall 28-day mortality rates of carbapenem-non-susceptible and carbapenem-susceptible K. pneumoniae were 54.24% and 19.56%, respectively. Conclusion: Central venous catheter, mechanical ventilation, high Pitt bacteraemia score, hospitalization prior to culture, and prior antibiotic use (carbapenem, aminoglycoside and tigecycline) were identified as independent risk factors for carbapenem-non-susceptible K. pneumoniae BSI, which was mostly caused by KPC-2 in northern China.

Background: Ras association domain family 1A gene (RASSFlA) is a candidate suppressor gene, Lack of RASSF1A expression was found in lung cancer. High DNA methylation at the promoter region is the main reason for inactivating RASSF1A transcription. Methods: In this study, we examined RASSF1A’s methylation status and its mRNA expression level between non-small cell lung cancer cell line A549 and anti-Cisplatin cell strain A549DDP, Furthermore, methylation of A549DDP was reversed by treatment of 5-Aza-2′ - deoxycytidine (5-Aza-cdR),a DNA methyltransferase inhibitor. Results: We found that RASSF1A’s methylation status and its mRNA expression were obvious differences between A549 and A549DDP. 5-Aza-CdR treatment remarkablly reduced cell vability of A549DDP. Moreover, 5-Aza-CdR treatment induced A549DDP cell apoptosis in a dose dependent manner with declining cell percentage in S and G2/M stage, and increasing proportion in G0/G1 stage. Cell motility was blocked in G0/G1 stage. All of A549DDP cells showed unmethylated expression, its high methylation status was reversed in a dose-dependent manner within a certain range. Conclusions: The abnormal gene methylation status of RASSF1A is a molecular biomarker in lung cancer diagnosis, treatment and prognosis.

Infectious diseases, especially sepsis from bacterial infections, significantly threaten global health, with antimicrobial resistance (AMR) complicating treatment and increasing clinical burdens. Antibiotic overuse contributes to AMR by creating selective pressure, reducing the efficacy of traditional therapies, and necessitating new approaches. Endogenous hydrogen sulfide (H₂S), a gaseous signaling molecule produced by most bacteria through cystathionine-γ-lyase (CSE), cystathionine-β-synthase (CBS), and 3-mercaptopyruvate sulfurtransferase (3MST), plays a crucial role in bacterial resistance. This review explores the biological functions of bacterial endogenous H₂S and its impact on AMR. H₂S enhances resistance by neutralizing antibiotic-induced reactive oxygen species (ROS), reducing oxidative stress and DNA damage, and promoting biofilm formation, which obstructs antibiotic penetration and facilitates resistance gene exchange. Furthermore, enhancing H₂S-based assays could significantly improve the diagnosis of AMR. Additionally, strategies such as targeting H₂S metabolism—through the use of H₂S synthase inhibitors or disrupting biofilms via H₂S clearance—or the combination of H₂S synthase inhibitors with antibiotics, may reverse resistance. A deeper understanding of the mechanisms by which H₂S mediates resistance is essential for the development of advanced diagnostic tools and innovative therapies to combat AMR. Its clinical translation may reverse AMR passivity, guide antibiotic sensitizer development, and optimize therapies, holding significant clinical and translational value.