Preclinical evaluation of RQ3013, a broad-spectrum mRNA vaccine against SARS-CoV-2 variants

The global emergence of SARS-CoV-2 variants has led to increasing breakthrough infections in vaccinated populations, calling for an urgent need to develop more effective and broad-spectrum vaccines to combat COVID-19. Here we report the preclinical development of RQ3013, an mRNA vaccine candidate intended to bring broad protection against SARS-CoV-2 variants of concern (VOCs). RQ3013, which contains pseudouridine-modified mRNAs formulated in lipid nanoparticles, encodes the spike(S) protein harboring a combination of mutations responsible for immune evasion of VOCs. Here we characterized the expressed S immunogen and evaluated the immunogenicity, efficacy, and safety of RQ3013 in various animal models. RQ3013 elicited robust immune responses in mice, hamsters, and nonhuman primates (NHP). It can induce high titers of antibodies with broad cross-neutralizing ability against the Wild-type, B.1.1.7, B.1.351, B.1.617.2, and the omicron B.1.1.529 variants. In mice and NHP, two doses of RQ3013 protected the upper and lower respiratory tract against infection by SARS-CoV-2 and its variants. We also proved the safety of RQ3013 in NHP models. Our results provided key support for the evaluation of RQ3013 in clinical trials.

Regulative effect of pinoresinol diglucoside on gene of ESF-1 cells collagen secretion / 国际中医中药杂志

Objective To study the pinoresinol diglucoside (PDG) on gene regulation role of ESF-1 cells in collagen secretion, to reveal PDG repair mechanisms on scalded skin.Methods The cells cultured in vitro were divided into the control group, the estradiol group and the three different PDG doses groups. The concentration of the high, medium and low dose groups were 100, 10, 1μmol/L, and that of estradiol group were 10-3μmol/L. The activity of proliferation was detected by MTT. Then collagen type I (Col I), collagen typeⅢ (ColⅢ), tissue inhibitors of metalloproteinase 1 (TIMP-1), tissue inhibitors of metalloproteinase 2 (TIMP-2) and matrix metalloproteinase 1 (MMP-1) expression levels of mRNA after administration of cells were detected by RT-PCR.Results Compared with the control group, the proliferation of ESF-1 cells (0.559 ± 0.027, 0.552 ± 0.034vs. 0.489 ± 0.027,P<0.05) in the estradiol and medium-dose PDG was significantly higher. The expression level of mRNA of ColⅠ(0.958 ± 0.021, 0.929 ± 0.031, 0.916 ± 0.015vs. 0.844 ± 0.022), ColⅢ (0.783 ± 0.038, 0.918 ± 0.021, 0.855 ± 0.017vs. 0.678 ± 0.024), TIMP-1 (0.939 ± 0.025, 0.889 ± 0.036, 0.853 ±  0.015 vs. 0.780 ± 0.023), TIMP-2 (0.507 ± 0.024, 0.655 ± 0.037, 0.572 ± 0.025vs. 0.405 ± 0.062) in the estradiol, low-, medium-dose PDG groups were significantly higher than those in the control group (P<0.05 or P<0.01). Besides, the MMP-1 (0.343 ± 0.038, 0.407 ± 0.046, 0.435 ± 0.037vs.0.519 ± 0.041) mRNA expression level in the middle and low dose PDG groups significantly decrease (P<0.05 orP<0.01). Conclusions The PDG could enhance the activity of ESF-1 cell proliferation, increase the expression of related collagen and tissue inhibitor of metalloproteinases and inhibit that of matrix metalloproteinases to repair scalded skin.

Effects of genistein on the mRNA expressions of collagen, matrix metalloproteinase and tissue inhibitor of matrix metalloproteinase in human embryonic skin fibroblasts / 国际中医中药杂志

Objective To investigate the effects of genistein on the mRNA expressions of collagen (Col), matrix metalloproteinase (MMP ) and tissue inhibitor of matrix metalloproteinase (TIMP) in human embryonic skin fibroblasts (CCC-ESF-1).MethodsThe cultured CCC-ESF-1cells were divided into a black control group, an estradiol group and genistein groups of different doses. The mRNA expressions of ColⅠ, ColⅢ , MMP-1, TIMP-1 and TIMP-2 were detected by RT-PCR.Results Compared with the black group, estradiol and medium dose of genistein (0.451 ± 0.037, 0.446 ± 0.047vs.0.385 ± 0.061, allP<0.05) could promote the proliferation of the CCC-ESF-1 cells, estradiol and medium dose of genistein could up-regulate the mRNA expressions of ColⅠ (0.960 ± 0.012, 0.929 ± 0.015vs.0.812 ± 0.014, allP<0.01), ColⅢ (0.892 ± 0.009, 0.824 ± 0.022vs.0.768 ± 0.025, allP<0.01), TIMP-1 (0.841 ± 0.023, 0.838 ± 0.053vs.0.751 ± 0.027, allP<0.01) and TIMP-2 (0.456 ± 0.017, 0.448 ± 0.036vs.0.381 ± 0.029, allP<0.01), and down-regulate MMP-1 mRNAexpression (0.398 ± 0.043, 0.402 ± 0.044vs.0.525 ± 0.006, allP<0.01).Conclusions Genistein could promote the proliferation of the CCC-ESF-1 cells, and that may be related with up-regulating the mRNA expressions of ColⅠ, ColⅢ , MMP-1, TIMP-1and down-regulating MMP-1 mRNA expression.

Analysis and Improvement Suggestions on the Surplus and Deficiency of Public Health Service System / 中国卫生经济

To understand the current situation of public health service system by using diect network report,system report and questionaire surey, so as to provide reasomable suggestion for the existing problems.

The role of Toll like receptor 4 pathway in palmitate-induced interleukin-6 expression in human aortic vascular smooth muscle cells / 中华内分泌代谢杂志

The recombinant adenovirus Toll like receptor 4 (TLR4) shRNA vector (pGSadeno-TLR4) was constructed and transfected into human aortic vascular smooth muscle cells (HA-VSMC).After HA-VSMC were treated with palmitate or different signaling pathway inhibitors,the mRNA and protein levels of interleukin-6 (IL-6)and NF-κB activity were tested with real-time PCR and ELISA,respectively.The results showed that palmitate increased mRNA and protein levels of IL-6 in HA-VSMC in a dose-dependent manner.The expression of IL-6 mRNA reached peak after treatment with 400 μmol/L of palmitate for 6 h,being 10.43 fold of control (P＜0.01).Treatment with 400 pmol/L of palmitate for 24 h maximally upregulated the protein level of IL-6,which was 2.18 fold of control (P＜0.01).NF-κB inhibitor parthenolide markedly inhibited palmitate-stimulated increased in IL-6 mRNA level by 65％ and protein level by 59％ (both P＜0.01).Protein kinase C (PKC) inhibitor chlerythrine suppressed palmitateinduced IL-6 mRNA expression by 24％ and IL-6 protein level by 28％.By contrast,extracellular signal-regulated protein kinase inhibitor PD98059 and phosphatidylinositol 3-kinase inhibitor wortmannin had no effect on the induction of IL-6 by palmitate.Blockade of TLR4 with pGSadeno-TLR4 significantly suppressed palmitate-induced IL-6 mRNA expression by 72％ and IL-6 protein expression by 75％ (both P＜0.01),along with decrease of NF-κB p65 activity decreased by 62％.These results suggest that TLR4/NF-κB and PKC pathways mediate palmitate-induced IL-6 expression in HA-VSMC.

Private Opinion on Economic Benefits of Cancer Prevention Screening / 中国卫生经济

In order to reduce heavy burden of cancer on patients, families and social, it needs to raise special funds, apply regular screening for 45~65 years old group, achieve early detection and treatment of cancer, reduce medical expenses and economic loss of cancer greatly, reduce mental burden, establish the cancer prevention input-output model, calculates the economic benefits up to 1:9.89. It is proposed to establish the organization, improve the mechanism, expand the overall costs, secure the screening and popularize early detection and treatment.

Study on Equivalent Value of Rural Main Cancer Treatment Costs / 中国卫生经济

In order to understand the cost of cancer in rural area, to evaluate the cost burden, the project content and treatment status. Typical sampling and random sampling survey are combined to investigate and account major expenditure and economic loss of cancer treatment and related items, analyzes its rationality and scientific, provide references for improving the level of cancer prevention and treatment.