Pathogenic spectrum and drug resistance of bloodstream infection in patients with acute myeloid leukaemia: a single centre retrospective study.

Background: Bloodstream infection (BSI) represent a prevalent complication in haematological malignancies (HMs). Typically, Patients with BSI usually undergo empirical treatment pending pathogen identification. The timely and effective management of BSIs significantly influences patient prognosis. However, pathogen distribution in BSIs exhibits regional variation. In this study, we investigated the clinical characteristics, pathogen spectrum, drug resistance, risk factors of short-term prognosis and long-term prognostic factors of acute myeloid leukemia (AML) patients with BSI at Zhejiang Provincal People's Hospital. Methods: From 2019 to 2021, a total of 56 AML patients with BSI were treated in the Department of Haematology at Zhejiang Province People's Hospital. Data regarding pathogen spectrum and drug resistance were collected for analysis. The patients were stratified into non-survivor cohort and survivor cohort within 30 days after BSI, and the predictors of 30-days mortality were identified through both univariate and multivariate Logistic regression analyses. Furthermore, Kaplan-Meier survival analysis and Cox regression analysis were employed to ascertain the risk factors associated with poor prognosis in AML patients complicated by BSI. Results: A total of 70 strains of pathogenic bacteria were isolated from 56 AML patients with BSI. Gram-negative bacteria constituted the predominant pathogens (71.4%), with Klebsiella pneumoniae being the most prevalent (22.9%). Gram-positive bacteria and fungi accounted for 22.9% and 5.7%, respectively. Univariate and multivariate analyses revealed significant differences in total protein, albumin levels, and the presence of septic shock between the non-survivor cohort and the survior cohort 30 days post-BSI. COX regression analysis showed that agranulocytosis duration exceeding 20 days (HR:3.854; 95% CI: 1.451-10.242) and septic shock (HR:3.788; 95% CI: 1.729-8.299) were independent risk factors for poor prognosis in AML patients complicated by BSI. Notably, the mortality rate within 30 days after Stenotrophomonas maltophilia infection was up to 71.4%. Conclusions: In this study, Gram-negative bacteria, predominantly Klebsiella pneumoniae, constituted the primary pathogens among AML patients with BSIs. Serum albumin levels and the presence of septic shock emerged as independent risk factors for mortality within 30 days among AML patients with BSI. In terms of long-term prognosis, extended agranulocytosis duration exceeding 20 days and septic shock were associated with elevated mortality rates in AML patients with BSI. Additionally, in our centre, Stenotrophomonas maltophilia infection was found to be associated with a poor prognosis. Early intervention for Stenotrophomonas maltophilia infection in our centre could potentially improve patient outcomes.

Synthesis of poly (L-cysteine)/g-C3N4 modified glassy carbon electrodes for electrochemical detection of methotrexate as a medicine for treatment of breast cancer in pharmaceutical fluid samples.

Analyzing the levels of anticancer medications in biological samples and body fluids reveals important details on the course and effects of chemotherapy. p (L-Cys)/graphitic-carbon nitride (g-C3N4)/GCE, a modified glassy carbon electrode, was created for the current study's electrochemical detection of methotrexate (MTX), a drug used to treat breast cancer, in pharmaceutical fluid samples. l-Cysteine was electro-polymerized on the surface of the g-C3N4/GCE after the g-C3N4 was first modified to prepare the p (L-Cys)/g-C3N4/GCE. Analyses of morphology and structure showed that well-crystalline p (L-Cys) on g-C3N4/GCE was successfully electropolymerized. Studying the electrochemical characteristics of p (L-Cys)/g-C3N4/GCE using CV and DPV techniques revealed a synergistic impact between g-C3N4 and l-cysteine that improved the stability and selectivity of the electrochemical oxidation of MTX while enhancing the electrochemical signal. Results showed that 7.5-780 µM was the linear range, and that 0.11841 µA/µM and 6 nM, respectively, were the sensitivity and limit of detection. The applicability of the suggested sensors was assessed using real pharmaceutical preparations, and the results showed that p (L-Cys)/g-C3N4/GCE had a high degree of precision. Five breast cancer patients who volunteered and provided prepared blood serum samples between the ages of 35 and 50 were used to examine the validity and accuracy of the proposed sensor in the current work for the determination of MTX. The results showed good recovery values (greater than 97.20%), appropriate accuracy (RSD less than 5.11%), and good agreement between the ELISA and DPV analysis results. These findings showed that p (L-Cys)/g-C3N4/GCE can be applied as a trustworthy MTX sensor for MTX level monitoring in blood samples and pharmaceutical samples.

A Detailed Study to Discover the Trade between Left Atrial Blood Flow, Expression of Calcium-Activated Potassium Channels and Valvular Atrial Fibrillation.

Background: The present study aimed to explore the correlation between calcium-activated potassium channels, left atrial flow field mechanics, valvular atrial fibrillation (VAF), and thrombosis. The process of transforming mechanical signals into biological signals has been revealed, which offers new insights into the study of VAF. Methods: Computational fluid dynamics simulations use numeric analysis and algorithms to compute flow parameters, including turbulent shear stress (TSS) and wall pressure in the left atrium (LA). Real-time PCR and western blotting were used to detect the mRNA and protein expression of IKCa2.3/3.1, ATK1, and P300 in the left atrial tissue of 90 patients. Results: In the valvular disease group, the TSS and wall ressure in the LA increased, the wall pressure increased in turn in all disease groups, mainly near the mitral valve and the posterior portion of the LA, the increase in TSS was the most significant in each group near the mitral valve, and the middle and lower part of the back of the LA and the mRNA expression and protein expression levels of IKCa2.3/3.1, AKT1, and P300 increased (p < 0.05) (n = 15). The present study was preliminarily conducted to elucidate whether there might be a certain correlation between IKCa2.3 and LA hemodynamic changes. Conclusions: The TSS and wall pressure changes in the LA are correlated with the upregulation of mRNA and protein expression of IKCa2.3/3.1, AKT1, and P300.

Arsenic trioxide induces proteasome dependent TBLR1-RARα degradation to improve leukemia eradication through cell differentiation enhancement.

BACKGROUND: Acute promyelocytic leukemia (APL) mainly harbors PML-RARα fusion gene, which is sensitive to all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) treatment. However, APL harboring other RARα fusion genes exhibit different drug sensitivity. Here, we investigated the role and mechanism of TBLR1-RARα, a rare RARα fusion gene, on ATO treatment in leukemia cells. METHODS: By constructing two cell models of leukemia cell line HL-60 and U937 with overexpressed TBLR1-RARα, we detected the cell differentiation in the two cell models after ATO treatment by flow cytometry and Wright staining. Meanwhile, cell viability, colony formation and apoptosis were also determined after ATO treatment. RESULTS: We found that TBLR1-RARα enhanced ATO-induced apoptosis and cell proliferation inhibition. Besides, TBLR1-RARα also promoted ATO-induced cell differentiation. Furthermore, we found that the mitochondrial caspase pathway was involved in the apoptosis induced by ATO treatment in TBLR1-RARα positive leukemia cells. Moreover, ATO mediated TBLR1-RARα protein degradation via proteasome pathway, which accounts for the transcriptional activation of RARα target gene and is further involved in cell differentiation of TBLR1-RARα positive leukemia cells. CONCLUSIONS: Our study provides evidence that TBLR1-RARα positive APL patients may benefit from ATO treatment, thereby improving the appropriate management in TBLR1-RARα positive APL.

Synthesis and evaluation of novel neamine derivatives effectively targeting to RNA.

Three new derivatives of neamine, 3 (NE), 6 (NEA) and 9 (NEL), were synthesized by connecting arginine or lysine to 5-hydroxyl group of neamine using ethylenediamine as a linker. The binding affinities of these derivatives to A site of 16S RNA and TAR RNA indicate that the modification on 5-hydroxyl of neamine by amino acid can enhance the binding affinity of neamine. Compound 9 (NEL) shows some antibacterial activities. These results demonstrate that modification on 5-hydroxyl group of neamine may provide a promising way for the development of potential candidates effectively targeting to RNAs.

Pharmacokinetics of multiple intravenous instillation of levofloxacin in Chinese healthy subjects.

AIM: To study the pharmacokinetics of multiple doses intravenous infusion of levofloxacin instillation in Chinese healthy volunteers. METHODS: Intravenous infusion of levofloxacin instillation 200 mg within 60 min was given to 10 male healthy volunteers for 7 d, on d 1 and d 7, once-daily, from 2-6 d twice-daily dosing. The concentrations of levofloxacin in serum and urine were assayed by HPLC. RESULTS: The main pharmacokinetic parameters af ter the first dosing were as follows: Cmax was (2.4+/-0.4) mg/L; AUC0- was (16.1 +/- 1.4) mg . h . L-1; T1/2beta was (6.3 +/- 0.3) h. The concentration in serum reached steady state within 72 h. The main parameters after the last dosing were as follows: Cssmax was (2.9 +/- 0.4) mg/L; Cssmin was (0.71 +/- 0.19) mg/L; Cav was (1.40 +/- 0.29) mg/L; AUCss0-12 was (17 +/- 3) mg . h . L-1; T1/2beta was (6.2 +/- 0.8) h. The 24-h cumulative urinary excretion rate was (88 +/- 5) %. From the calculation, the cumulative rate was 1.20; the fluctuation index was 1.30. The difference of T1/2beta and AUC between the first dosing and the last dosing was not significant, and the elimination rate of levofloxacin was not changed after multiple dosing. No clear adverse events were noted during this study. CONCLUSION: There was no accumulation of drug after the repeated intravenous infusion with 200 mg levofloxacin instillation for 7 d.