Peptide-Based Therapeutic HPV Cancer Vaccine Synthesized via Bacterial Outer Membrane Vesicles.

Background: Peptide-based vaccines have broad application prospects because of their safety, simple preparation, and effectiveness, especially in the development of personalized cancer vaccines, which have shown great advantages. However, the current peptide-based vaccines often require artificial synthesis and intricate delivery technology, which increases the cost and complexity of preparation.

Methods: Here, we developed a simple technique for combining a peptide and a delivery system using the natural secretion system of bacteria.

Recommendations for Dose Selection for Adolescent Patients in Relevant Adult Oncology Clinical Trials.

Our research supported the dose selection recommendations for adolescents in the US Food and Drug Administration (FDA) Guidance on Inclusion of Adolescent Patients in Adult Oncology Clinical Trials. The FDA Guidance states that for drugs administered as a flat dose in adults and data showing no clinically meaningful effect of body size on drug exposure and toxicity in adults, a minimum body weight threshold may need to be defined to prevent adolescents who have a lower body weight from exceeding adult exposures. Our review of adult population pharmacokinetic analyses of new molecular entities approved for oncology between January 2015 and March 2021 suggested that 40 kg (the approximate median body weight of a 12-year-old) is generally the lower end of the body weight range that has no clinically relevant effect on drug pharmacokinetics or safety.

Role of Model-Informed Drug Development in Pediatric Drug Development, Regulatory Evaluation, and Labeling.

The unique challenges in pediatric drug development require efficient and innovative tools. Model-informed drug development (MIDD) offers many powerful tools that have been frequently applied in pediatric drug development. MIDD refers to the application of quantitative models to integrate and leverage existing knowledge to bridge knowledge gaps and facilitate development and decision-making processes.

Factors Contributing to Fentanyl Pharmacokinetic Variability Among Diagnostically Diverse Critically Ill Children.

Objective: The objective of this study was to characterize the population pharmacokinetics of fentanyl and identify factors that contribute to exposure variability in critically ill pediatric patients.

Methods: We conducted a single-center, retrospective cohort study using electronic record data and remnant blood samples in the setting of a mixed medical/surgical intensive care unit (ICU) at a quaternary children's hospital. Children with a predicted ICU length of stay of at least 3 days and presence of an indwelling central venous or arterial line were included.

Cerebral microcirculatory alterations and the no-reflow phenomenon in vivo after experimental pediatric cardiac arrest.

Decreased cerebral blood flow (CBF) after cardiac arrest (CA) contributes to secondary ischemic injury in infants and children. We previously reported cortical hypoperfusion with tissue hypoxia early in a pediatric rat model of asphyxial CA. In order to identify specific alterations as potential therapeutic targets to improve cortical hypoperfusion post-CA, we characterize the CBF alterations at the cortical microvascular level in vivo using multiphoton microscopy.

Alterations in Cerebral Blood Flow after Resuscitation from Cardiac Arrest.

Greater than 50% of patients successfully resuscitated from cardiac arrest have evidence of neurological disability. Numerous studies in children and adults, as well as in animal models have demonstrated that cerebral blood flow (CBF) is impaired after cardiac arrest. Stages of cerebral perfusion post-resuscitation include early hyperemia, followed by hypoperfusion, and finally either resolution of normal blood flow or protracted hyperemia.

ABCB1 genotype is associated with fentanyl requirements in critically ill children.

BackgroundThe gene ABCB1 encodes p-glycoprotein, a xenobiotic efflux pump capable of transporting certain opioids, including fentanyl. ABCB1 genotype has been previously associated with patient opioid requirements and may influence fentanyl dosing requirements in critically ill children.MethodsA diagnostically diverse cohort of 61 children who received a fentanyl infusion while admitted to the pediatric intensive care unit (PICU) were included in this study.

[Effect of long-term treatment of Wuzhi tablet on the expression and activity of cytochrome P450 3A in rats].

The study aims to evaluate the effect of long-term pretreatment of the rat with Wuzhi tablet（WZ） on hepatic and intestinal CYP3A mRNA and protein expression and activity. Male Sprague-Dawley rats were orally administered of midazolam (2 mg·kg-1) with or without 14 days of pretreatment of WZ (0.25 g·kg-1) to determine CYP3A activity.

Effect of long-term co-administration of Wuzhi tablet (Schisandra sphenanthera extract) and prednisone on the pharmacokinetics of tacrolimus.

Tacrolimus (TAC) is an immunosuppressant that has been widely used alone or in combination with prednisone (PRED) to prevent acute rejection after organ transplantation. Wuzhi tablet (WZ, Schisandra sphenanthera extract) is often prescribed with TAC to prevent drug-induced hepatitis. We recently reported that WZ could significantly increase TAC blood exposure by inhibiting P-gp-mediated efflux and CYP3A-mediated metabolism of TAC.