Lineage-mosaic and mutation-patched spike proteins for broad-spectrum COVID-19 vaccine

The widespread SARS-CoV-2 in humans results in the continuous emergence of new variants. Recently emerged Omicron variant with multiple spike mutations sharply increases the risk of breakthrough infection or reinfection, highlighting the urgent need for new vaccines with broad-spectrum antigenic coverage. Using inter-lineage chimera and mutation patch strategies, we engineered a recombinant monomeric spike variant (STFK1628x), which showed high immunogenicity and mutually complementary antigenicity to its prototypic form (STFK). In hamsters, a bivalent vaccine comprised of STFK and STFK1628x elicited high titers of broad-spectrum antibodies to neutralize all 14 circulating SARS-CoV-2 variants, including Omicron; and fully protected vaccinees from intranasal SARS-CoV-2 challenges of either the ancestral strain or immune-evasive Beta variant. Strikingly, the vaccination of hamsters with the bivalent vaccine completely blocked the within-cage virus transmission to unvaccinated sentinels, for either the ancestral SARS-CoV-2 or Beta variant. Thus, our study provides new insights and antigen candidates for developing next-generation COVID-19 vaccines.

Contemporary Update of Retinoblastoma in China: Three-Decade Changes in Epidemiology, Clinical Features, Treatments, and Outcomes.

PURPOSE: To report three-decade changes of clinical characteristics, progress of treatments, and risk factors associated with mortality and enucleation in patients with retinoblastoma in China. DESIGN: Retrospective cohort study. METHODS: This multicenter study included 2552 patients diagnosed with retinoblastoma in 38 medical centers in 31 provinces in China from 1989 to 2017, with follow-up data. Kendall's tau-b value was used to describe correlation coefficients between the three eras (between 1989 and 2008, between 2009 and 2013, and between 2014 and 2017) and clinical or demographic features. Hazard ratios and odds ratios were applied to measure risk factors. RESULTS: A total of 324 (13%) patients died and 1414 (42%) eyes were removed. The 1-year, 3-year, and 5-year overall survival rates were 95%, 86%, and 83%, respectively. Patients were diagnosed at a better stage by International Classification for Retinoblastoma over time (Kendall's tau-b value = -0.084, P < .001). Pathological risk factors were also observed less in recent eras. New conservative therapies were adopted and used in more patients. The eye removal rate gradually decreased (Kendall's tau-b value = -0.167, P < .001). The overall survival rates were 81%, 83%, and 91% in the three eras. By multivariate Cox regression, bilateral tumors and extraocular extension were identified as risk factors for death. Among intraocular disease, Group E indicated higher risk of mortality. By multivariate logistics regression, unilateral tumors, earlier era of diagnosis, and extraocular extension were risk factors for eye salvage failure. Among intraocular retinoblastoma, Groups D and E had higher risk of eye salvage failure. CONCLUSIONS: Patients were diagnosed at an earlier stage in recent eras. Conservative therapies, including intra-arterial chemotherapy, were increasingly being used. The above changes may contribute to the decreasing enucleation rate. Although no significant impact was identified on the mortality by the three eras, a decreasing trend was shown.

A bibliometric analysis of China's liver neoplasms literature from 2005 to 2010 through CMCI / 中华肝胆外科杂志

Objective To reveal the research trends and hotspots of China's liver neoplasms literature from 2005 to 2010. Methods A bibliometric analysis was made based on the results of retrieving from the Chinese Medical Citation Index (CMCI). Results The number of China' s liver neoplasms literature increased regularly in the last 5 years. The fund articles accounted for 30% of total articles. This paper reports the highly cited articles, authors, institutions and journals. The top 5 provinces of publishing articles are Guangdong, Shanghai, Jiangsu, Shandong and Beijing. There are some major aspects of liver neoplasms research, such as treatment modalities, analysis of causes of disease, evaluation after radiation therapy, and experimental research. 3-dimensional conformal radiotherapy, radiofrequency ablation and chemoembolization have been becoming research hotspots. Conclusions The researches on liver neoplasms have been widely and deeply developing in China. A lot of research progresses were made. As the higher mortality of liver neoplasms, the research of comprehensive treatment is to be the further trend.

Clinical observation of amniotic membrane transplantation loaded with autologons marrow mesenchymal stem cells in treatment of pterygium patients / 中国基层医药

Objective To study the clinical effects of human amniotic membrane transplantation loaded with autologons marrow mesenchymal stem cells(MSCs) in treatment of pterygium patient. Methods Totally 10 patient (10 eyes) with primary giant pterygium aged 42 ～60 years(7 males and 3 females) were enrolled. All patients were informed consents. Bone marrow was sterilely collected by bone marrow aspiration. MSCs were harvested, purified and cultured. At the third passage,MSCs were incubated in amniotic membrane. After pterygium resection,amniotic membrane patch with cells surface upward was covered on surface of exposed sclera. Another simple amniotic membrane was sutured to protect transplanted cells. Results 1 ～ 3 days after dissection of corneal epithelial area was repaired,a week around later,migration of conjunctival epithelial gradually grew,about 10 ～ 14 days, absorption and fusion of amniotic membrane began. Follow-up of 6 months to 3 years, there was no recurrence. Conclusion After amniotic membrane loaded with MSCs were transplanted to the ocular surface ,corneal epithelium repaired rapidly ,transplanted amniotic membrane and conjunctival integrated, conjunctival irritation was few, ocular surface scar was light, the pterygium was no recurrence.

DETECTION OF THE LEVELS OF THE IFN-γ AND TNF-α IN SERUM OF THE PATIENES WITH THE DENGUE VIRUS INFECTION AND ITS CLINICAL SIGNIFICANCE / 中国人兽共患病学报

AimTo study the effect of interferon gamma( IFN-γ) and tumor necrosis factor alpha(TNF-α) in the immune pathogenesis of dengue virus infection. Method The serum levels of IFN-γ and TNF-α were measured with emzyme linked immunosorbent assay (ELISA) method in 30 cases of the patients with the dengue virus infection in Guangzhou district. The results were treated with t-test of two sample mean. ResultsThe serum levels of IFN-γ and TNF-α in patients with the dengue virus infection were much higher than healthy controls( P ＜ 0.05、 P ＜ 0.01 ). IFN-γ was detectable on the first day of postinfection. Level of IFN-γ reached their peaks on the second day, then declined . The level of TNF-α had an obvious rise from the second day and reached their peaks on the third day, then declined. ConclusionThe data suggest that the IFN-γ and TNF-α may play an important role in the dengue virus pathogenicity and immunity.

Clone and mutagenesis analysis of nhaA gene in Vibrio cholerae O1 and O139 / 中华传染病杂志

Objective Clone and mutagenesis analysis of nhaA gene in Vibrio cholerae O1 and O139. Methods 40 strains of Vibrio cholerae O1 and O139 were collected. A full length nhaA gene fragment was amplified with PCR and cloned into plasmid vector pcDNA3. Homology and mutagenesis of nhaA gene in Vibrio cholerae O1 and O139 were analyzed after sequencing the nhaA gene. Results nhaA gene of Vibrio cholerae O1 and O139 were successfully amplified and cloned. Sequence analysis manifested that nhaA gene of Vibrio cholerae O1 and O139 in China share a high homology with reference sequence of wide-type Vibrio cholerae O1 in GENEBANK(99% and 96% respectively). The amino acid mutagenesis rates of nhaA gene in Vibrio cholerae O1 and O139 were 2% and 11% respectively. The important residues(Asp133,Asp163,Asp164,His225,Leu73 and Gly338 )had no mutation. But in residues 203 and 221 of nhaA gene Vibrio cholerae O1 and O139 had common mutation. Conclusions Mutagenesis of nhaA gene and NhaA protein may be the result of Vibrio cholerae adaptation to survival environment.

CONSTRUCTION AND IDENTIFICATION OF RECOMBINANT RETROVIRAL VECTOR CARRYING RAT GDNF GENE / 神经解剖学杂志

Through genetic recombination technique, the rat glial cell line-derived neurotrophic factor (rGDNF) cDNA was in-serted into polylinker site of retroviral vector pLXSN, to generate a recombinant plasmid pLXSN-GDNF as transfer vector. Therecombinant plasmid was verified with restriction analysis, PCR, dot blot hybridization and Southern blot hybridization. The re-sults showed that GDNF cDNA was cloned correctly into retroviral vector pLXSN, recombinant retroviral vector was construct-ed. It is concluded that the eukaryotic cell expression vector was constructed successfully for gene therapy of Parkinson's,Alzheimer's and other central nervous system diseases.

Immunogenicity of dengue virus E antigen gene in BALB/c mice / 中国免疫学杂志

Objective:To study the possibility of dengue virus E gene vaccine.Methods:The recombinant eukaryotic expression plasmid pcDNA3 E was first transfected into NIH3T3 cells by lipofectin SDS PAGE and Western blotting analyzed the expression of E gene Then the recombinant plasmid was intramuscularly injected to BALB/c mice,and the specific humoral and cellular immunity were tested Results:The recombinant plasmid DNA could induce specific immune reactions and the immune response could last a long time Conclusion:The dengue virus E gene vaccine could induce specific immune reaction,which might have provided some material and new experimential data for the further study of dengue vaccines