Prognostic implications of immune-related eight-gene signature in pediatric brain tumors

Genomic studies have provided insights into molecular subgroups and oncogenic drivers of pediatric brain tumors (PBT) that may lead to novel therapeutic strategies. Participants of the cohort Pediatric Brain Tumor Atlas: CBTTC (CBTTC cohort), were randomly divided into training and validation cohorts. In the training cohort, Kaplan-Meier analysis and univariate Cox regression model were applied to preliminary screening of prognostic genes. The LASSO Cox regression model was implemented to build a multi-gene signature, which was then validated in the validation and CBTTC cohorts through Kaplan-Meier, Cox, and receiver operating characteristic curve (ROC) analyses. Also, gene set enrichment analysis (GSEA) and immune infiltrating analyses were conducted to understand function annotation and the role of the signature in the tumor microenvironment. An eight-gene signature was built, which was examined by Kaplan-Meier analysis, revealing that a significant overall survival difference was seen, either in the training or validation cohorts. The eight-gene signature was further proven to be independent of other clinic-pathologic parameters via the Cox regression analyses. Moreover, ROC analysis demonstrated that this signature owned a better predictive power of PBT prognosis. Furthermore, GSEA and immune infiltrating analyses showed that the signature had close interactions with immune-related pathways and was closely related to CD8 T cells and monocytes in the tumor environment. Identifying the eight-gene signature (CBX7, JADE2, IGF2BP3, OR2W6P, PRAME, TICRR, KIF4A, and PIMREG) could accurately identify patients' prognosis and the signature had close interactions with the immunodominant tumor environment, which may provide insight into personalized prognosis prediction and new therapies for PBT patients.

Heart failure with preserved ejection fraction: an update on pathophysiology, diagnosis, treatment, and prognosis

Heart failure (HF) with preserved ejection fraction (HFpEF) is a clinical syndrome in which patients have symptoms and signs of HF with normal or near-normal left ventricular ejection fraction (LVEF ≥50%). Roughly half of all patients with HF worldwide have an LVEF ≥50% and nearly half have an LVEF <50%. Thanks to the increased scientific attention about the condition and improved characterization and diagnostic tools, the incidence of HF with reduced ejection fraction (HFrEF) dropped while that of HFpEF has increased by 45%. HFpEF has no single guideline for diagnosis or treatment, the patient population is heterogeneously and inconsistently described, and longitudinal studies are lacking. To better understand and overcome the disease, in this review, we updated the latest knowledge of HFpEF pathophysiology, introduced the existing promising diagnostic methods and treatments, and summarized its prognosis by reviewing the most recent cohort studies.

Preparation of cefquinome sulfate proliposome and its pharmacokinetics in rabbit

Cefquinome Sulfate [CS] is a fourth-generation cephalosporin, which has been developed solely for veterinary use. It shows potent antibacterial activity against a broad spectrum of bacterial species. However, Cefquinome is susceptible to hydrolysis, which limiting its clinical employment efficacies to some extent. So, in this study, to increase Cefquinome Sulfate biological half-life, a novel Cefquinome Sulfate proliposome was prepared by solid dispersion and effervescent techniques and characterized for morphology, particle size, entrapment efficiency and in vitro release. A Reversed Phase-High Performance Liquid Chromatography [RP-HPLC] method was first chosen and established to determine the drug concentration in plasma after intra muscular [IM] administrating Cefquinome Sulfate solution and liposome at a single dosage of 18 mg/kg in rabbit. Then their pharmacokinetics in vivo was compared. Results showed that the received liposome was milky white suspension, spherical or ellipsoidal in shape. The mean particle size was 203 +/- 5 nm and the entrapment efficiency was 53.5 +/- 0.16%. The cefaquinom sulfate solution and liposome both followed a two compartment model, in vivo. The pharmacokinetic parameters for the solution and liposomal formulations were measured as follows: t[1/a alpha] were [1.214 +/- 0.135] h and [1.395 +/- 0.113] h, t[1/2beta] were [8.752 +/- 0.846] h and [16.503 +/- 1.275] h, AUC[0-24] were [49.582 +/- 9.173] [mg-h]/L and [138.727 +/- 11.034] [mg-h]/L, CL/F were [0.357 +/- 0.015] L/[h-kg] and [0.127 +/- 0.012] L/[h-kg], MRT[0-24] were [2.68 +/- 0.229] h and [5.945 +/- 0.479] h, respectively. It could be clearly seen that t[1/2beta] of liposome prolonged [p < 0.05], AUC and MRT both increased remarkably [p < 0.01], CL/F decreased. Results indicated that this preparation has more residence time and exhibits some, sustained-release tendency