Search

ABSTRACTObjectives:To access the trends and focuses of publications on public health emergency preparedness in the timeframe 1997-2019.Methods:Publications related to public health emergency preparedness (PHEP) were retrieved from the Web of Science Core Collection database. Bibliometric analyses including output statistics, co-authorship analysis, citation analysis, co-citation analysis, and co-occurrence analysis were performed and mapped using VOSviewer.Results:A total of 1058 publications on PHEP were included in this study. There was an increasing trend of publication output and citations since 2002. A total of 4605 authors from 1587 institutes and 92 countries contributed to the publications, and the United States lead the field. Disaster Medicine and Public Health Preparednesswas the most active and co-cited journal among 243 journals. The knowledge foundation mainly focused on the professionals’ capacity, education, and conceptions of PHEP. Epidemics, natural disasters, terrorism, education, and communication were the principle topics; while “vulnerable populations,” “disaster medicine,” and “hurricane” were the recent hotspots in this field.Conclusions:Significant progresses had been achieved worldwide in the past 2 decades, however, improvement of research activity and international collaboration is still a need for most countries.

Phenotypic plasticity is a rising cancer hallmark, and lung adeno-to-squamous transition (AST) triggered by LKB1 inactivation is significantly associated with drug resistance. Mechanistic insights into AST are urgently needed to identify therapeutic vulnerability in LKB1-deficient lung cancer. Here, we find that ten-eleven translocation (TET)–mediated DNA demethylation is elevated during AST in KrasLSL-G12D/+; Lkb1L/L (KL) mice, and knockout of individual Tet genes reveals that Tet2 is required for squamous transition. TET2 promotes neutrophil infiltration through STAT3-mediated CXCL5 expression. Targeting the STAT3–CXCL5 nexus effectively inhibits squamous transition through reducing neutrophil infiltration. Interestingly, tumor-infiltrating neutrophils are laden with triglycerides and can transfer the lipid to tumor cells to promote cell proliferation and squamous transition. Pharmacological inhibition of macropinocytosis dramatically inhibits neutrophil-to–cancer cell lipid transfer and blocks squamous transition. These data uncover an epigenetic mechanism orchestrating phenotypic plasticity through regulating immune microenvironment and metabolic communication, and identify therapeutic strategies to inhibit AST.

To explore the role of cyclophilin A (CyPA) in sensitization of lung adenocarcinoma to radiotherapy using CRISPR/Cas9 technology.

DNA vaccines are simple to produce and can generate strong cellular and humoral immune response, making them attractive vaccine candidates. However, a major shortcoming of DNA vaccines is their poor immunogenicity when administered intramuscularly. Transcutaneous immunization (TCI) via microneedles is a promising alternative delivery route to enhance the vaccination efficacy. A novel dissolving microneedle array (DMA)-based TCI system loaded with cationic liposomes encapsulated with hepatitis B DNA vaccine and adjuvant CpG ODN was developed and characterized. The pGFP expression in mouse skin using DMA was imaged over time. In vivo immunity tests in mice were performed to observe the capability of DMA to induce immune response after delivery of DNA. The results showed that pGFP could be delivered into skin by DMA and expressed in skin. Further, the amount of expressed GFP was likely to peak at day 4. The immunity tests showed that the DMA-based DNA vaccination could induce effective immune response. CpG ODN significantly improved the immune response. The cationic liposomes could further improve the immunogenicity of DNA vaccine. In conclusion, the novel DMA-based TCI system can effectively deliver hepatitis B DNA vaccine into skin, and induce effective immune response.

Transdermal administration is a promising non-invasive and convenient method of drug delivery in clinic and avoid serious gastrointestinal adverse reactions. In this study, a hybrid nanocarrier was developed to facilitate transdermal delivery of drugs. The low water-soluble ketoprofen (KP) was ultrasonically loaded on functionalized multi-walled carbon nanotubes (f-MWCNTs), and the preparation process was optimized using Box-Behnken design. Then, KP-loaded f-MWCNTs composite ethosomes (f-MWCNTs-KP-ES) were prepared by a single-step injection technology. Over the study period, the preparation was verified by a series of characterizations, and ex vivo release characteristics, ex vivo permeation of rat skin and in vivo pharmacokinetics were studied. The characterization results consistently showed that f-MWCNTs-KP-ES were successfully prepared. The preparation can obviously improve the solubility of KP. Ex vivo permeation experiments showed that had a sustained release effect and the skin penetration rate of f-MWCNTs-KP-ES gel is the fastest, with a cumulative permeation amount of 602.35 ± 41.06 μg/cm2. In addition, both ethosomes and f-MWCNTs could increase the retention of drugs and form drug reservoirs. Fluorescence microscope images of rat skin clearly illustrated the faster and deeper penetration of f-MWCNTs composite ethosomes formulation loaded with rhodamine B (RB) (f-MWCNT-RB-ES). In vivo pharmacokinetic experiments showed the area under the drug time curve (AUC0-t) and elimination half-life (T1/2β) of f-MWCNTs-KP-ES gel group were significantly increased and prolonged compared with KP commercial gel group, respectively. The overall data indicate that the f-MWCNTs composite ethosomes formulation is a promising transdermal drug delivery system.

Gout is a disease that affects quality of life and has economic implications. However, most patients with gout are not adequately managed due to the adverse effects of current medical treatments. This study was performed to investigate the transdermal delivery of polydatin via the combination of inclusion complexes and dissolving microneedles and the therapeutic effect of polydatin on the treatment of acute gout arthritis. In vitro cytotoxicity of polydatin on HaCaT cells was measured by a CCK-8 assay. The results showed that polydatin exerted less cytotoxicity compared to indomethacin and colchicine. The aqueous solubility of polydatin increased considerably to 124.47 mg/mL via the formation of polydatin/Hydroxypropyl-β-cyclodextrin inclusion complexes. The complexes loaded dissolving microneedles showed significant improvement for in vitro polydatin permeation compared to the absence of complexes. Pharmacodynamic studies indicated that the polydatin complexes-loaded dissolving microneedles had significant inhibitory effects on swelling of the ankle in the arthritic mice. Furthermore, compared to the oral colchicine treatment, the body weights of the polydatin-treated mice increased significantly during the treatment, which implied a lower toxicity of polydatin microneedles delivery. The overall results indicate that the combination of inclusion complexes with dissolving microneedles provides a potential route for treatment of acute gout arthritis by enhanced transdermal delivery of polydatin.