The significance of COVID-19 vaccine has been declared and this study synthesizes the attitudes and determinants in vaccination hesitancy of college students. We searched in PubMed, Web of Science, Cochrane Library and CNKI to enroll the related studies. The modified NOS was used for quality evaluation. Proportion and OR with 95% CI were pooled to estimate the acceptance rates and determinants of COVID-19 vaccination. Data of 34 studies involving 42 countries were pooled. The pooled acceptance rate of COVID-19 vaccination among all the college students was 69% and varies between countries, while medical students have a slightly higher acceptancy rate. Knowledge, trust conception, social behavior, and information sources were important for their decision. Most of the college students intended to COVID-19 vaccination, but the proportion varied among countries. Governments should strengthen credibility, convey trusted information with media influences and improve vaccination services in urging students to be vaccinated.

Fisetin, a natural flavonoid found in a variety of edible and medical plants, has been suggested to inhibit the proliferation of various tumor cells and to induce apoptosis. However, the effects of fisetin on breast cancer have rarely been reported and the underlying mechanism is still undefined. The present study explored the anti-cancer effects of fisetin on mammary carcinoma cells and the underlying mechanisms. Following treatment with fisetin, viability of 4T1, MCF-7 and MDA-MB-231 cells were measured by MTT assay. The inhibitory effects of fisetin on proliferation, migration and invasion were evaluated in 4T1 cells using proliferation array, wound-healing assay, and HUV-EC-C-cell barrier based on electrical cell-substrate impedance sensing platform. Cell apoptosis was analyzed by flow cytometry, and western blotting analysis was performed to identify target molecules. A 4T1 orthotopic mammary tumor model was used to assess the fisetin-inhibition on tumor growth in vivo. Test kits were used to examine the liver and kidney function of tumor-bearing mice. The results suggest that fisetin suppressed the proliferation of breast cancer cells, suppressed the metastasis and invasiveness of 4T1 cells, and induced the apoptosis of 4T1 cells in vitro. The potent anti-cancer effect of fisetin was associated with the regulation of the phosphatidylinositol-3-kinase/protein kinase B/mammalian target of rapamycin pathway. In vivo experiments demonstrated that fisetin suppressed the growth of 4T1 cell-derived orthotopic breast tumors and enhanced tumor cell apoptosis, and the evaluated alanine amino transferase and aspartate amino transferase levels in serum of tumor-bearing mice suggested that fisetin may lead to side effects on liver biochemical function. The present study confirms that fisetin exerted an anti-mammary carcinoma effect. However, in vivo experiments also revealed that fisetin had low solubility and low bioavailability. Further investigation is required to determine the clinical value of fisetin.

A number of murine models are used to mimic the pathology of breast cancer. Tissue inoculation and cell inoculation using orthotopic implantation (OS) and subcutaneous implantation (SQ) are commonly used to generate murine models to investigate cancer. However, limited information is available in regard to the variations of these methods. The present study compared growth, metastasis, survival and histopathology of tumors produced using OS and SQ to characterize features of the tumors produced by the two distinct methods. Additionally, the present study aimed at providing increased options for investigators when designing experiments. 4T1-luc2 cell suspension or 4T1-luc2 tissue suspension was inoculated using either OS or SQ into BALB/c mice. Tumor growth and metastasis were detected using an in vivo imaging system and calipers. Excised tumors and lung were assessed by tissue staining with hematoxylin and eosin, and the vessel marker cluster of differentiation 31. The results of the present study revealed that the cell suspension generated breast tumors of increased size, which was visualized and determined, following inoculation, using calipers at an earlier time point compared with tumors produced by tissue suspension. The increasing bioluminescent trend of OS tumors was more marked compared with that of SQ tumors. The volume of OS tumor was increased with decreased variation, compared with that of SQ tumors. In addition, the OS tumor exhibited increased microvessel density. Bioluminescent signals and histological results in regard to metastasis were consistent: OS implantation produced increased lung metastasis compared with that of SQ implantation, although they exhibited similar survival times. The results of the present study indicated that the inocula from distinct sources (tissue or cell) affected tumor growth. Furthermore, breast tumor progression and histopathological characteristics were distinct between OS and SQ, whereas OS exhibited increased malignant behavior. Understanding the characteristics of murine breast cancer models established by diverse methods may aid investigators to select appropriate animal models, according to the requirements of the study.