Enhanced tumor homing of pathogen-mimicking liposomes driven by R848 stimulation: A new platform for synergistic oncology therapy

Although multifarious tumor-targeting modifications of nanoparticulate systems have been attempted in joint efforts by our predecessors, it remains challenging for nanomedicine to traverse physiological barriers involving blood vessels, tissues, and cell barriers to thereafter demonstrate excellent antitumor effects. To further overcome these inherent obstacles, we designed and prepared mycoplasma membrane (MM)-fused liposomes (LPs) with the goal of employing circulating neutrophils with the advantage of inflammatory cytokine-guided autonomous tumor localization to transport nanoparticles. We also utilized in vivo neutrophil activation induced by the liposomal form of the immune activator resiquimod (LPs-R848). Fused LPs preparations retained mycoplasma pathogen characteristics and achieved rapid recognition and endocytosis by activated neutrophils stimulated by LPs-R848. The enhanced neutrophil infiltration in homing of the inflammatory tumor microenvironment allowed more nanoparticles to be delivered into solid tumors. Facilitated by the formation of neutrophil extracellular traps (NETs), podophyllotoxin (POD)-loaded MM-fused LPs (MM-LPs-POD) were concomitantly released from neutrophils and subsequently engulfed by tumor cells during inflammation. MM-LPs-POD displayed superior suppression efficacy of tumor growth and lung metastasis in a 4T1 breast tumor model. Overall, such a strategy of pathogen-mimicking nanoparticles hijacking neutrophils in situ combined with enhanced neutrophil infiltration indeed elevates the potential of chemotherapeutics for tumor targeting therapy.     

PXR activation impairs hepatic glucose metabolism partly via inhibiting the HNF4α–GLUT2 pathway

Drug-induced hyperglycemia/diabetes is a global issue. Some drugs induce hyperglycemia by activating the pregnane X receptor (PXR), but the mechanism is unclear. Here, we report that PXR activation induces hyperglycemia by impairing hepatic glucose metabolism due to inhibition of the hepatocyte nuclear factor 4-alpha (HNF4α)‒glucose transporter 2 (GLUT2) pathway. The PXR agonists atorvastatin and rifampicin significantly downregulated GLUT2 and HNF4α expression, and impaired glucose uptake and utilization in HepG2 cells. Overexpression of PXR downregulated GLUT2 and HNF4α expression, while silencing PXR upregulated HNF4α and GLUT2 expression. Silencing HNF4α decreased GLUT2 expression, while overexpressing HNF4α increased GLUT2 expression and glucose uptake. Silencing PXR or overexpressing HNF4α reversed the atorvastatin-induced decrease in GLUT2 expression and glucose uptake. In human primary hepatocytes, atorvastatin downregulated GLUT2 and HNF4α mRNA expression, which could be attenuated by silencing PXR. Silencing HNF4α downregulated GLUT2 mRNA expression. These findings were reproduced with mouse primary hepatocytes. Hnf4α plasmid increased Slc2a2 promoter activity. Hnf4α silencing or pregnenolone-16α-carbonitrile (PCN) suppressed the Slc2a2 promoter activity by decreasing HNF4α recruitment to the Slc2a2 promoter. Liver-specific Hnf4α deletion and PCN impaired glucose tolerance and hepatic glucose uptake, and decreased the expression of hepatic HNF4α and GLUT2. In conclusion, PXR activation impaired hepatic glucose metabolism partly by inhibiting the HNF4α‒GLUT2 pathway. These results highlight the molecular mechanisms by which PXR activators induce hyperglycemia/diabetes.Key words: Pregnane X receptor, Hepatocyte nuclear factor 4-alpha, Glucose transporter 2, Hepatic glucose uptake, Diabetes, Drug-induced hyperglycemia     

聚维酮在阿霉素诱导膀胱癌EJ细胞凋亡模型中的作用机制

目的:探讨聚维酮(PVP)在体外加阿霉素(ADM)后诱导EJ细胞发生凋亡的情况以及一些相关机制。方法:应用流式细胞仪(FCM)检测ADM诱导EJ细胞的凋亡率、PVP EJ细胞的凋亡率以及PVP ADM对EJ细胞的诱导凋亡率的情况。结果:PVP对ADM诱导膀胱癌EJ细胞凋亡无影响。结论:PVP在整个诱导过程中并没有协同作用,只起到粘附作用,使得药物停留在EJ细胞表面的作用时间延长,从而达到大量杀伤EJ细胞的作用。     

Generation of A Space-Variant Vector Beam with Catenary-Shaped Polarization States

We demonstrate the generation of a space-variant vector beam with catenary-shaped polarization states based on the polarization interferometry. With a spatial light modulator and a common path interferometric configuration, two orthogonally circularly polarized beams with different phase modulation overlap each other, yielding the vector beams. In addition, the polarization states of this vector beam are scalable to the arbitrary spatial distribution because of its great flexibility and universal applicability. It is expected that this vector beam may have many potential and intriguing applications in the micro/nano material processing, liquid crystal elements fabrication and optical micro-manipulation, and so on.     

Impact of National Centralized Drug Procurement Policy on Antiviral Utilization and Expenditure for Hepatitis B in China

Background and AimsThe National Centralized Drug Procurement (NCDP) policy was launched in mainland China in April 2019, with entecavir (ETV) and tenofovir disoproxil fumarate (TDF) being included in the procurement list. We conducted the current study to investigate the impact of the NCDP policy on the utilization and expenditures of antiviral therapy for chronic hepatitis B (CHB) in China.MethodsProcurement records, including monthly purchase volume, expenditure, and price of nucleos(t)ide analogs (NAs), were derived from the National Healthcare Security Administration from April 2018 to March 2021. The changes in volumes and expenditures of the first-line NAs and bid-winning products were calculated. The effects of price, volume, and structure related to drug expenditure were calculated by the Addis and Magrini (AM) Index System Analysis.ResultsThe purchase volume of NAs significantly increased from 134.3 to 318.3 million DDDs, whereas the expenditure sharply decreased from 1,623.41 to 490.43 million renminbi (RMB) or 241.94 to 73.09 million US dollars (USD). The proportions of first-line NAs rose from 72.51% (ETV: 69.00%, TDF: 3.51%) to 94.97% (ETV: 77.42%, TDF: 17.55%). AM analysis showed that the NCDP policy decreased the expenditure of all NAs (S=0.91) but increased that of the first-line NAs in the bid-winning list (S=1.13). Assuming the population size of CHB patients remains stable and a compliance rate of ≥75%, the proportion of CHB patients receiving first-line antiviral therapy would increase from 6.36–8.48% to 11.56–15.41%.ConclusionsThe implementation of the NCDP policy significantly increased the utilization of first-line NAs for CHB patients at a lower expenditure. The findings provided evidence for optimizing antiviral therapy strategy and allocating medical resources in China.     

五年制培训护士医院感染知识认知状况调查分析

目的:探讨五年制培训护士医院感染知识认知状况及防护意识,制定有效的防护措施和继续教育方案.方法:对96例五年制培训的准护士和96例青年护士采取自行设计问卷进行调查.结果:五年制培训的准护士和青年护士对医院感染基本概念的认知情况比较,差异无统计学意义(P＞0.05),医院感染护理干预措施和自身防护的认知情况比较,差异有统计学意义(P＜0.05).结论:对五年制培训的准护士和青年护士分别制定医院感染知识培训计划,加强医院感染的防护意识,可减少患者和自身医院感染的发生,降低医院感染率.     

Fertility regulating agents from traditional Chinese medicines

Chinese scientists have capitalized on the rich flora and the ethnomedical experience in China, in their pursuit of fertility regulating agents from natural products. Discoveries range from anti-implantation agents to abortifacient and pregnancy-terminating compounds, as well as a male contraceptive. Chemistry and bioactivity of these compounds and materials are reviewed in this paper, with the hope that further research and collaboration will take place to help solve the problem of population explosion.     

小檗胺在升高白细胞的同时对乳酸脱氢酶的影响

采用酶细胞化学及平板聚丙烯酰胺凝胶电泳法观察小檗胺(Ber)在升高白细胞的同时,是否对细胞内酶代谢及其同工酶有影响。结果表明:ip Ber的小鼠粒细胞内LDH酶反应明显增强,酶反应的强弱与用药时间长短成正比。LDH同工酶谱分析,所有标本均显示5条区带,LDH_2比例发生变化,对照组及Ber组中出现LDH’_5亚带。提示,Ber在升高白细胞的同时对细胞内酶的代谢有一定影响,同时伴有同工酶谱比例改变。