Immunogenicity of quadrivalent influenza virus subunit vaccine combined with RFH01 adjuvant in mice / 中华微生物学和免疫学杂志

Objective:To evaluate the immunogenicity of a quadrivalent subunit vaccine combined with RFH01 adjuvant in a mouse model.Methods:Identification tests were performed on four monovalent influenza virus subunit vaccine stock solutions according to the methods described in Part 3 of the Chinese Pharmacopoeia 2020 Edition. In the study of the quadrivalent subunit vaccine combined with RFH01 adjuvant, 460 female BALB/c mice (6-8 weeks old) were randomly divided into 46 groups including experimental groups, vaccine control group, negative control group and blank group with 10 mice in each group. In the study of the quadrivalent subunit vaccine in old and young mice, 80 female 10-month-old and 80 female 10-week-old BALB/c mice were randomly divided into 16 groups ( n=10) including monovalent influenza virus vaccine group, quadrivalent subunit vaccine group, quadrivalent subunit vaccine+ RFH01 adjuvant group, chicken embryo quadrivalent split vaccine control group and PBS group. All mice were immunized by intramuscular injection. At 21 d after the primary immunization, a booster immunization was conducted using the same strategy. Blood samples were collected at 21 d and 42 d after the primary immunization for serum separation. Haemagglutination inhibition (HI) test was performed to detect the antibody levels in mouse serum samples. Results:After the booster immunization, the positive conversion rates in all vaccine+ RFH01 adjuvant groups reached 100%, and the geometric mean titers (GMTs) of serum antibodies were significantly higher than those of the vaccine groups without RFH01 adjuvant. There were significant differences in serum antibody titers between the monovalent/quadrivalent subunit vaccine groups with and without RFH01 adjuvant. After the booster immunization, the titers of serum antibodies against H1N1, H3N2, B/Victoria and B/Yamagata in the 10-week-old mice were significantly higher than those in the 10-month-old mice.Conclusions:The monovalent and quadrivalent influenza virus vaccines in combination with RFH01 adjuvant could elicit higher antibody titers in young (6-10 weeks old) and old (10 months old) mice, showing good immunogenicity.

Preparation and immunogenicity evaluation of recombinant influenza hemagglutinin trimer vaccine / 中华微生物学和免疫学杂志

Objective:To prepare a recombinant hemagglutinin trimer (HA-Tri) vaccine against influenza viruses and to study its immunogenicity in a mouse model.Methods:A stable CHO cell line that could express HA-Tri was constructed. Western blot, single radial immunodiffusion, protein particle size detection and N-glycosylation site analysis were performed for qualitative and quantitative analysis of the recombinant protein. According to the different treatment conditions such as dosage and adjuvant, BALB/c mice were divided into 11 groups and subjected to consistent immunization procedures. Serum neutralizing antibody titers were measured on 56 d after the first immunization to evaluate the immunogenicity of HA-Tri.Results:The constructed CHO cells could secret and express HA-Tri proteins. The HA-Tri proteins were biologically active and capable of forming precipitation rings in the single radial immunodiffusion. The particle size of HA-Tri was approximately 18.79 nm and 10 N-glycosylation sites were detected, including high mannose, complex glycoforms and heterozygous glycoforms. After prime-boost immunization, there was no statistically significant difference in the titers of neutralizing antibodies induced in mice by 3.75 μg of HA-Tri in combination with RFH01 adjuvant and 15 μg of monovalent vaccine stock solution ( P=0.431 2, U=36). Serum antibody titers in the HA-Tri+ RFH01 groups were higher than those in the corresponding HA-Tri groups without RFH01 adjuvant, and the highest titer was induced in the 15 μg HA-Tri+ RFH01 group, which was 1 280. Conclusions:The recombinant HA-Tri protein was successfully prepared. HA-Tri in combination with RFH01 adjuvant could induce humoral immune responses against influenza viruses in BALB/c mice, which would provide reference for the development of influenza virus recombinant subunit vaccines.

Fibronectin FNDC10 promotes malignant biological behaviors of breast cancer cells by enhancing STAT3 activation / 中国肿瘤生物治疗杂志

@#[Abstract] Objective: To investigate the effects of fibronectin Ⅲ domain containing protein 10 (FNDC10) on the proliferation, migration and invasion of breast cancer cells, and to primarily explore the mechanism. Methods: TCGA database was used to analyze the expression of FNDC10 in breast cancer tissues. The mRNA level of FNDC10 in normal immortalized breast cells (MCF-10A) and breast cancer cells (MCF-7, MDA-MB-231, BT549, MDA-MB-468, HCC1806, HCC1937) was detected by qPCR. MCF-7 and MDA-MB-231 cells were transfected with FNDC10 siRNA or NC-siRNA for functional experiments. CCK-8 assay was used to detect the effect of FNDC10 on the proliferation of breast cancer cells. Colony forming assay was used to detect the colony forming ability of breast cancer cells. Transwell assay was used to detect the effect of FNDC10 on migration and invasion of breast cancer cells. WB was used to detect the changes of metastasis-related molecules and cell signaling pathways at protein level. Results:The expression of FNDC10 in breast cancer tissues was significantly higher than that in normal tissues (P<0.01), and the expression level of FNDC10 in breast cancer MCF-7 and MDA-MB-231 cells was higher than that in normal breast cells (P<0.01 or P<0.05). Knocking down FNDC10 expression inhibited the proliferation, migration and invasion of breast cancer cells (P<0.01 or P<0.05). The mechanism study showed that knockdown of FNDC10 expression inhibited STAT3 activation in breast cancer cells (P<0.01 or P<0.05) and enhanced the expression of EMT maker E-cadherin (P<0.05), leading to the suppression of EMT progression. Conclusion: FNDC10 promotes proliferation and EMT of breast cancer cells through activating STAT3 signaling pathway, thereby promoting the malignant progression of breast cancer.

Is the health workforce distribution in Beijing, China perfectly equitable?

Background: The quantity and distribution of the health workforce is one of the most important aspects of a health care system. Inequality in the distribution of the health workforce is common in China and in many developing countries. This paper aimed to evaluate and discuss inequality in the distribution of the health workforce in Beijing, China, and explain the sources of the inequality. Methods: The study described and measured inequality in the distribution of the health workforce in Beijing using data from the Beijing Regional Statistical Yearbook 2017. The 16 districts of Beijing are divided into four divisions and the paper used methods from the economics literature, including the Lorenz curve, Gini coefficient and Theil L index, to measure inequality in the distribution of the health workforce at sub-provincial level in Beijing for three categories of health workers: doctors, nurses and all health workers. Results: There are inequalities in the densities of health workers at the district and division levels. In terms of the densities of all health workers, doctors and nurses, the Capital Core Functional Division is 3.95 times, 3.82 times and 4.13 times, respectively, higher than the Urban Development New Division. All the Gini coefficients are between than 0.2 to 0.3, which means that the health worker distribution is rather equitable. The Theil L index shows that the inequalities mainly come from the differences between the four divisions, and that nurses are more unequally distributed between divisions (0.28 for Gini coefficient and 0.380 for the Theil L index). Conclusions and recommendations: According to the study findings, the inequalities in health workforce distribution in Beijing could be addressed by increasing investment in the numbers and quality of nurses, as well as by establishing additional policies to attract more health workers to work in remote areas. Chinese governments need to think more carefully about the current distribution of health workers at the sub-provincial level

Progress in research on the novel cancer therapeutic target Cdc20 / 药学学报

The anaphase promoting complex (APC) regulates cell cycle progression by forming two functionally distinct E3 ubiquitin ligase complexes, APCCdc20 activated by cell division cycle protein 20 (Cdc20) and APCCdh1 activated by Cdc20 homologue 1 (Cdh1), respectively. Cdc20 and Cdh1 have different functions in the occurrence and development of the tumor. Cdc20 is a cancer promoter while Cdh1 suppresses tumorigenesis. Emerging evidence has begun to reveal that Cdc20 has positive functions in tumorigenesis, the overexpression of Cdc20 has been observed in many cancers. Currently, Cdc20 inhibitors, mostly non-specific inhibitors except apcin, not only block the combination between Cdc20 and APC, also block the combination between Cdh1 and APC, which leads to a poor selectivity. In this paper, the Cdc20 role in the development and process of cancers and its inhibitors are reviewed.

Pyrrolidine dithiocarbamate alleviated rat cervical intervertebral disc degeneration via reducing tumor necrosis factor α and matrixmetalloproteinase 9 expression and its underlying mechanism / 中国药理学通报

Aim To observe the effect of pyrimidine dithiocarbamate (PDTC) on the variance of disc morphology and the expressions of TNF-α, MMP-9 in the cervical disc in cervical dynamic equilibrium rat models, and to investigate the roles of PDTC in the process of intervertebral disc degeneration and the mechanism involved.Methods Fifty-four SD rats were divided into three groups randomly, then the dynamic equilibrium rat model was established by cutting the nuchal superficial and deep muscle of the rats.The dynamic equilibrium rats with PDTC solution intraperitoneal injection after operations were defined as PDTC group (group A), the models with saline intraperitoneal injection after operations as saline group (group B), the rats of fake operation with saline intraperitoneal injection as blank group (group C), and the animals were sacrificed in batches 10 weeks, 12 weeks, 16 weeks respectively after operation.The C5, C6 vertebrae and C5/6 discs were harvested, and the disc morphology was observed.TNF-α, MMP-9 mRNA expressions were detected by q-PCR and protein expression was observed by Western blot.Results Compared with the saline group, the morphology of disc in PDTC group was destructed slightly and fiber ring arranged orderly.TNF-α, MMP-9 gene and protein expressions had no obvious changes (P>0.05) in blank group (group C) at each time point.The expressions of IL-6, MMP-9 mRNA increased with time in group B, but the amount increased fast firstly, and slow lately, reaching peak in 12 weeks.The expression of TNF-α, MMP-9 protein became steady in group B from 10 weeks compared with other time points(P>0.05).TNF-α, MMP-9 genes and proteins expression decreased obviously in PDTC group (group A) compared with saline group (group B) (P<0.01) at each time point, but higher than blank group C(P<0.01) at each time point.Conclusions TNF-α and MMP-9 are important inflammatory factors involved in rat cervical disc degeneration, PDTC relieves the degeneration of rat cervical disc by reducing the expression of TNF-α and MMP-9 via disturbing the NF-κB signal pathway probably, and PDTC may become potential medicine for disc degeneration.

Comparison of Conbercept with Ranibizumab for the treatment efficiency of macular edema:a meta-analysis / 国际眼科杂志(Guoji Yanke Zazhi)

·AIM: To study the clinical effect of Conbercept and Ranibizumab for macular edema ( ME ) with meta -analysis.·METHODS:We searched Pubmed, EMBASE, Cochrane Library Central Register of Controlled Trials ( CENTRAL) , Google scholar, ClinicalTrials. gov, CNKI, VIP and wanfang database for studies which published between January 12012 and July 12017, on the comparison of conbercept with ranibizumab for the clinical effect of secondary macular edema. The primary endpoints were visual acuity ( VA ) and central macular thickness in this study to assess the efficiency of the drugs. Review Manager 5. 3 and Stata 12. 0 were used for data analysis with the pooled odds ratios (OR), mean difference and 95% confidence interval ( CI) .·RESULTS: Eleven RCTs involving 812 patients met inclusion criteria and included in this meta-analysis, including 414 eyes in conbercept group and 398 eyes in ranibizumab group. Macular edema in this study were secondary to age-related macular degeneration, diabetic retinopathy and retinal vein occlusion. No significant differences in improvement of vision acuity(P=0. 09) or reduction of CMT (P>0. 05) were noted at the end of 3mo between two groups. Compared to ranibizumab, conbercept showed a better effectiveness in macular edema alleviation in the end of 6mo in the present study (OR=-58. 50, 95%CI: -108. 04 to -8. 95;P=0. 02).· CONCLUSION: Despite evidence from the meta -analysis of the RCTs suggesting a strong difference of the effectiveness for macular edema between conbercept and ranibizumab, more clinical trials are still needed to confirm our results because of the heterogeneity in the collected data.