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.

Simultaneous determination of 2',3'-dideoxyinosine and the active metabolite, 2',3'-dideoxyadenosine-5'-triphosphate in human peripheral-blood mononuclear cell by HPLC-MS/MS and the application to cell pharmacokinetics.

A specific and reliable HPLC-MS/MS method was developed and validated for the simultaneous determination of 2',3'-dideoxyinosine (ddI) and the active metabolites, 2',3'-dideoxyadenosine-5'-triphosphate (ddA-TP) in human peripheral-blood mononuclear cell for the first time. The analytes were separated on a HILIC column (100mm×2.1mm, 1.7µm) and a triple-quadrupole mass spectrometry equipped with an electrospray ionization (ESI) source was used for detection. The cell homogenates sample was prepared by the solid phase extraction. The calibration curves were linear over a concentration range of 0.5-200.0ng/mL for ddI and 0.25-100.0ng/mL for ddA-TP. The intra-day and inter-day precision was less than 15% and the relative error (RE) were all within ±15%. The validated method was successfully applied to assess the disposition characteristics of ddI and support cell pharmacokinetics after the patients with AIDS were orally administrated with ddI and tenofovir disoproxyl fumarate (TDF).

Establishment of a highly metastatic tongue squamous cell carcinoma cell line from New Zealand White rabbit.

OBJECTIVE: Prior to this study, the widely used tongue squamous cell carcinoma cell lines could only initiate tumours in immunodeficient mice, which greatly delayed studies on immune function during carcinogenesis. This study established a new tongue squamous cell carcinoma cell line named 'RSCC-1', which can initiate tumours in both immunocompetent rabbits and immunodeficient nude mice and has high metastatic ability. DESIGN: Primary tongue cancer was induced by DMBA and local mechanical stimulation in New Zealand White rabbits. The induced cancer was serially transplanted into homogeneous rabbits to establish transplanted models. At the same time, cancer samples were collected, cultured and passaged in vitro. Finally, a cell line named 'RSCC-1' was established. Its growth behaviour, cell cycle distribution and tumourigenicity in rabbits and nude mice were investigated. RESULTS: RSCC-1 cells were cultured continuously in vitro for 19 months (165 passages). They contain between 54 and 196 chromosomes, with a modal number of 75. Tumourigenicity rates were 100% in both homogeneous rabbits and nude mice, with 20% lung metastasis and 50% cervical lymph node metastasis in homogeneous rabbits. CONCLUSION: RSCC-1 is a poorly differentiated, highly malignant rabbit tongue squamous cell carcinoma cell line. Its behaviour in the inoculated animal model closely resembles human tongue cancer, and could metastasize to local lymph nodes and remote organs.

A clinical analysis of multidisciplinary treatment effectiveness in patients with breast cancer / 重庆医科大学学报

Objective:To investigate the multidisciplinary treatment outcome in 166 patients with breast cancer,and explore the relationship between treatment method and prognosis.Methods:The anlysis was performed with the clinical and pathologic materials of 166 breast cancer cases.The treatment outcome of operation,chemotherapy,radiotherapy and endocrine therapy was retrospectively evaluated.Results:The 3-year and 5-year overall survival rate were 87.0% and 77.0% respectively.And the multidisciplinary treatment improved patients' quality of life(QOL).Conclusion:The multidisciplinary treatment mainly including operation,chemotherapy,radiotherapy and endocrine therapy,reduce local recurrence rate and improve survival rate and patients' QOL.

Clinicopathological features and their relationship with prognosis in 166 cases of breast cancer / 重庆医科大学学报

Objective:To study the relationship between clinicopathological and biological characteristics and prognosis in 166 patients with breast cancer.Methods:The clinicopathological data of 166 patients with primary breast cancer were analyzed retrospectively.The histological specimens were reviewed.The expression of ER and PR was assessed by immunohistochemistry.Results:The 3-year overall survival rate and 5-year survival rate were 87.0% and 77.0%,respectively.The 3-year local recurrence rate was 7.1%,and the 3-year metastasis rate was 21.0%.The univariate analysis showed that the survival rate was related to the tumor size,lymph node involvement,ER,PR,menopause status,clinical stage and pathologic grade.The COX multivariate analysis identified that only menopause status,PR,lymph node involvement and pathologic grade were significant independent prognostic factors.Conclusion:Our analysis demonstrates that menopause status,PR,lymph node involvement and pathologic grade are significant independent prognostic factors.