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In order to strengthen the supervision of the use of drugs in hospitals，the Sichuan Academy of Medical Sciences· Sichuan Provincial People’s Hospital took the lead in compiling the Principles for the Rational Use of National Key Monitoring Drugs （the Second Batch） with a number of experts from multiple medical units in accordance with the Second Batch of National Key Monitoring Rational Drug Use List （hereinafter referred to as “the List”） issued by the National Health Commission. According to the method of the WHO Guidelines Development Manual， the writing team used the Delphi method to unify expert opinions by reading and summarizing the domestic and foreign literature evidence of related drugs， and applied the evaluation， formulation and evaluation method of recommendation grading （GRADE） to evaluate the quality of evidence formed， focusing on more than 30 drugs in the List about the evaluation of off-label indications of drugs， key points of rational drug use and key points of pharmaceutical monitoring. It aims to promote the scientific standardization and effective management of clinical medication， further improve the quality of medical services， reduce the risk of adverse drug reactions and drug abuse， promote rational drug use， and improve public health.
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Designing and manufacturing safe and effective vaccines is a crucial challenge for human health worldwide. Research on adjuvant-based subunit vaccines is increasingly being explored to meet clinical needs. Nevertheless, the adaptive immune responses of subunit vaccines are still unfavorable, which may partially be attributed to the immune cascade obstacles and unsatisfactory vaccine design. An extended understanding of the crosstalk between vaccine delivery strategies and immunological mechanisms could provide scientific insight to optimize antigen delivery and improve vaccination efficacy. In this review, we summarized the advanced subunit vaccine delivery technologies from the perspective of vaccine cascade obstacles after administration. The engineered subunit vaccines with lymph node and specific cell targeting ability, antigen cross-presentation, T cell activation properties, and tailorable antigen release patterns may achieve effective immune protection with high precision, efficiency, and stability. We hope this review can provide rational design principles and inspire the exploitation of future subunit vaccines.
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The rise of nanotechnology has opened new horizons for cancer immunotherapy. However, most nanovaccines fabricated with nanomaterials suffer from carrier-related concerns, including low drug loading capacity, unpredictable metabolism, and potential systemic toxicity, which bring obstacles for their clinical translation. Herein, we developed an antigen self-assembled nanovaccine, which was resulted from a simple acryloyl modification of the antigen to induce self-assembly. Furthermore, a dendritic cell targeting head mannose monomer and a mevalonate pathway inhibitor zoledronic acid (Zol) were integrated or absorbed onto the nanoparticles (denoted as MEAO-Z) to intensify the immune response. The synthesized nanovaccine with a diameter of around 70 nm showed successful lymph node transportation, high dendritic cell internalization, promoted costimulatory molecule expression, and preferable antigen cross-presentation. In virtue of the above superiorities, MEAO-Z induced remarkably higher titers of serum antibody, stronger cytotoxic T lymphocyte immune responses and IFN-γ secretion than free antigen and adjuvants. In vivo, MEAO-Z significantly suppressed EG7-OVA tumor growth and prolonged the survival time of tumor-bearing mice. These results indicated the translation promise of our self-assembled nanovaccine for immune potentiation and cancer immunotherapy.
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Objective To establish chronic coronary stenosis model for fractional flow reserve derived from coronary CT angiography (FFRcT) in Bama miniature pig,and to evaluate its reliability.Methods Sixteen Bama miniature pigs were used to establish chronic coronary stenosis models through placing Ameroid constrictor into proximal or middle segments of left anterior descending arteries (LAD).In the 2nd week after modeling,the degrees of stenosis were monitored with coronary CTA.Invasive coronary angiography was used to verify stenosis degrees and measure fractional flow reserve (FFR) within 2 days of last coronary CTA examination.Computational fluid dynamics model was constructed and FFRcT was calculated by the specialized laboratory based on coronary CTA data respectively.Simulated FFRcT and FFR values were compared to verify this model.Results Models were successfully established in 10 pigs with a total of 24 coronary CT examinations,of which image quality met the diagnostic requirements.All models were with LAD stenosis＜25 ％ in the 2nd week after operation.LAD stenosis ＞50％ was found in the 3rd week in 9 pigs,and the other one was found with LAD stenosis ＞50％ in the 4th week.The results of coronary CTA corresponded to those of coronary angiography.There was no significant difference between simulated FFRcT and FFR value (t =-1.13,P =0.29).Conclusion Through placing Ameroid constrictor into LAD of Bama miniature pig and monitoring the degree of stenosis with coronary CTA,model of chronic coronary stenosis could be successfully established,which are suitable for noninvasive simulating hemodynamics study based on coronary CTA.