This study aimed to address knowledge gaps related to the prevention and management of mental health responses among those with a condition that presents risk of severe COVID-19 infection. A scoping review that mapped English and Chinese-language studies (2019–2020) located in MEDLINE (Ovid), Cumulative Index to Nursing and Allied Health Literature (CINAHL), PsycInfo, Sociological Abstracts, Embase, China National Knowledge Infrastructure (CNKI), Wanfang Data, and Airiti Library was undertaken. Search terms related to COVID-19, mental health, and physical health were used and articles that included all three of these factors were extracted (n = 77). With the exception of one hospital-based pilot study, there were no intervention studies targeting mental health in those at risk of severe COVID-19 infection. Promising practices such as integrated care models that appropriately screen for mental health issues, address health determinants, and include use of digital resources were highlighted. Patient navigator programs, group online medical visits, peer support, and social prescribing may also support those with complex needs. Future policies need to address digital health access inequities and the implementation of multi-integrated health and social care. Furthermore, research is needed to comprehensively assess multi-integrated interventions that are resilient to public health crises.

Background Overexpressed vascular endothelial growth factor A (VEGFA) and phosphorylated signal transducer and activator of transcription 3 (P-STAT3) cause unrestricted tumor growth and angiogenesis of breast cancer (BRCA), especially triple-negative breast cancer (TNBC). Hence, novel treatment strategy is urgently needed. Results We found sphingosine 1 phosphate receptor 1 (S1PR1) can regulate P-STAT3/VEGFA. Database showed S1PR1 is highly expressed in BRCA and causes the poor prognosis of patients. Interrupting the expression of S1PR1 could inhibit the growth of human breast cancer cells (MCF-7 and MDA-MB-231) and suppress the angiogenesis of human umbilical vein endothelial cells (HUVECs) via affecting S1PR1/P-STAT3/VEGFA axis. Siponimod (BAF312) is a selective antagonist of S1PR1, which inhibits tumor growth and angiogenesis in vitro by downregulating the S1PR1/P-STAT3/VEGFA axis. We prepared pH-sensitive and tumor-targeted shell-core structure nanoparticles, in which hydrophilic PEG2000 modified with the cyclic Arg-Gly-Asp (cRGD) formed the shell, hydrophobic DSPE formed the core, and CaP (calcium and phosphate ions) was adsorbed onto the shell; the nanoparticles were used to deliver BAF312 (BAF312@cRGD-CaP-NPs). The size and potential of the nanoparticles were 109.9 ± 1.002 nm and − 10.6 ± 0.056 mV. The incorporation efficacy for BAF312 was 81.4%. Results confirmed BAF312@cRGD-CaP-NP could dramatically inhibit tumor growth and angiogenesis in vitro and in MDA-MB-231 tumor-bearing mice via downregulating the S1PR1/P-STAT3/VEGFA axis. Conclusions Our data suggest a potent role for BAF312@cRGD-CaP-NPs in treating BRCA, especially TNBC by downregulating the S1PR1/P-STAT3/VEGFA axis. Graphic abstract

Introduction: Functional heterogeneity, defined as variations between and within tumours, is the underlying cause for malignant tumour processes such as tumour progression, metastasis and treatment resistance. In particular, cancer stem cells (CSCs) could be important contributors to functional heterogeneity within tumours, as CSCs can differentiate into different tumorous cells. This study aims to identify models for the genesis of functional heterogeneity among cancer cells and strategies for targeting CSCs. Methods: Using an integrated review process, various models for functional heterogeneity genesis in cancer and cancer stem cell treatments were explored. Papers that explicitly focused on either explaining a model for the genesis of functiona l heterogeneity in cancer or on describing targeting strategies for CSCs were included. To conduct our search the following databases were used: PubMed, OVID (Medline), and Web of Science. Results: Several prominent models for genesis of cancer functional heterogeneity were identified, including the hierarchy model, stochastic model, and plasticity model. There is no definitive model as different types of cancer may follow different models of functional heterogeneity. However, multiple models suggest that CSCs, tumor cells with acquired or innate multipotency, are responsible for enhancing tumour progression. Hence, many therapeutic methods have been explored to target CSCs including: interfering with signalling pathways, targeting biomarkers, exerting transcriptional control, damaging quiescence, disrupting the microenvironment and immunotherapy. Discussion: This study identified a gap in current literature to be the lack of clinical studies, with the majority of experiments being conducted on mice models or in vitro. As such the applicability of the findings on a human in vivo level are unclear. Strengths of this paper include the extensive scope of literature reviewed, while limitations include the lack of a quality assessment stage. Conclusion:This study suggests that CSCs are involved in the development of functional heterogeneity in tumours and identifies some preliminary strategies to target them. However, more clinical trials are needed to further validate current proposed treatments. By developing CSC-specific therapies, functional heterogeneity amongst cancer cells can be decreased, which will prevent cancer cells from continuing to progress. As a result, these treatments will be more likely to effectively treat cancer.