In the era of digital medicine, a vast number of medical images are produced every day. There is a great demand for intelligent equipment for adjuvant diagnosis to assist medical doctors with different disciplines. With the development of artificial intelligence, the algorithms of convolutional neural network (CNN) progressed rapidly. CNN and its extension algorithms play important roles on medical imaging classification, object detection, and semantic segmentation. While medical imaging classification has been widely reported, the object detection and semantic segmentation of imaging are rarely described. In this review article, we introduce the progression of object detection and semantic segmentation in medical imaging study. We also discuss how to accurately define the location and boundary of diseases.

IDO1 (Indoleamine 2,3-dioxygenase 1) inhibits host anti-tumor immune response by exhausting tryptophan in tumor microenvironment, but the pathogenic mechanisms of IDO1 in gastric cancer (GC) cells need to be further explored. The aim of this study was to use CCLE (Cancer Cell Line Encyclopedia) transcriptomic data of GC cell lines for WGCNA (Weighted Gene Co-expression Network Analysis) analysis, and explore the potential functions and mechanisms of IDO1 in GC progression in vitro and in vivo. The higher expression level of IDO1 was identified in 4 out of 7 GC cell lines. Increased IDO1 expression strongly promoted cell migration via its metabolite kynurenine and was associated with pathways of immune activation according to GSEA (Gene Set Enrichment Analysis). The functions of IDO1 were closely associated with extracellular matrix, collagen metabolic and catabolic process by WGCNA analysis. Among five hub genes (AXL, SGCE, COL12A1, ANTXR1, LOXL2), COL12A1 and LOXL2 were upregulated in GC tissues. IDO1 disclosed positive correlation with six collagen genes by coefficient matrix diagram. Knockdown of IDO1 decreased the expression of LOXL2, COL6A1, COL6A2 and COL12A1 in GC cells in both mRNA and protein levels. Of them, knockdown of COL12A1 inhibited cell migration more apparently than knockdown of others. IDO1 and COL12A1 revealed synergistic efficacy on promoting cell migration via a positive feedback sustained by MAPK pathway. This bioprocess was mediated by IDO1 metabolite kynurenine and integrin β1. A popliteal lymph nodemetastasis model was established for verifying metastatic promotion of IDO1 and COL12A1 in GC. IDO1 and COL12A1 synergistically promoted GC metastasis. The novel findings suggested that both IDO1 and COL12A1 may be promising targets on anti-cancer treatment in GC.

Patient-derived organoids (PDO) are a new biomedical research model that can reconstruct phenotypic and genetic characteristics of the original tissue and are useful for research on pathogenesis and drug screening. To introduce the progression in this field, we review the key factors of constructing organoids derived from epithelial tissues and cancers, covering culture medium and matrix, morphological characteristics, genetic profiles, high-throughput drug screening, and application potential. We also discuss the co-culture system of cancer organoids with tumor microenvironment (TME) associated cells. The co-culture system is widely used in evaluating crosstalk of cancer cells with TME components, such as fibroblasts, endothelial cells, immune cells, and microorganisms. The article provides a prospective for standardized cultivation mode, automatic morphological evaluation, and drug sensitivity screening using high-throughput methods.

T cell exhaustion plays critical roles in tumor immune evasion. Novel strategies to suppress immune evasion are in urgent need. We aimed to identify potential compounds to target T cell exhaustion and increase response to immune checkpoint inhibitors (ICIs). Differentially expressed genes (DEGs) were identified between tumors with different immune evasion potential by comparing the transcriptome data. DEGs were then analyzed in the Connectivity Map (CMap) platform to identify potential compounds to increase response to ICIs. Gene set enrichment analysis, LDH release assay, Chromatin immunoprecipitation (ChIP), and Co-IP were performed to explore the potential mechanisms in vitro. Patients derived organoids and humanized xenograft mouse model were utilized to validate the finding ex vivo and in vivo. We identified 25 potential compounds that may play critical roles in regulating tumor immune evasion. We further pinpointed a specific compound, dexamethasone, which shows potent anti-tumor effect in multiple cancer cell lines when cocultured with T cells. Dexamethasone can suppress T cell exhaustion by decreasing the activity of two immune checkpoints simultaneously, including PD-L1 and IDO1. Functional study shows dexamethasone can increase the sensitivity of ICIs in coculture system, 3D organoid model and humanized mouse model. Mechanism study shows dexamethasone mediated transcriptional suppression of PD-L1 and IDO1 depends on the nuclear translocation of GR/STAT3 complex. These findings demonstrate dexamethasone can suppress immune evasion by inducing GR/STAT3 mediated downregulation of PD-L1 and IDO1 pathways.

The human reference genome is still incomplete, especially for those population-specific or individual-specific regions, which may have important functions. Here, we developed a HUman Pan-genome ANalysis (HUPAN) system to build the human pan-genome. We applied it to 185 deep sequencing and 90 assembled Han Chinese genomes and detected 29.5 Mb novel genomic sequences and at least 188 novel protein-coding genes missing in the human reference genome (GRCh38). It can be an important resource for the human genome-related biomedical studies, such as cancer genome analysis. HUPAN is freely available at http://cgm.sjtu.edu.cn/hupan/ and https://github.com/SJTU-CGM/HUPAN .

COVID-19 is a public health emergency that has rapidly spread to over 200 countries and regions, and no effective treatment has been established to date. Severe and critical cases have been associated with higher mortality due to acute respiratory distress syndrome (ARDS) and cytokine storm. Based on the novelty and recent emergence of COVID-19, no effective treatment regimen has been identified, thus prompting clinicians to engage in drug repurposing to address the immediate therapeutic need. This study focused on the molecular target angiotensin-converting enzyme 2 (ACE2) of SARS-CoV-2 and screened a group of ACE2 agonists by bioinformatics. Glucocorticoids are a type of ACE2 activator. We verified the efficacy of nine chemicals on regulating ACE2 expression in human GES-1, an upper digestive tract epithelial cell line, and THP-1, a human monocyte cell line, and found that several glucocorticoids imparted activating effects on ACE2 in both cell lines. The drugs triciribine and kinetin riboside activate ACE2 expression or inhibit IL-6 production in macrophages to some extent. In addition, we compared the efficacies of several glucocorticoids. Hydrocortisone showed the strongest effect on ACE2 activation, followed by prednisolone, dexamethasone, and methylprednisolone. We retrospectively analyzed the therapeutic efficacy of nine severe or critical patients from a cohort of 90 COVID-19 cases, who received medium to small doses of glucocorticoids from our integrated medical team in Wuhan. Seven out of nine patients revealed significant improvement in clinical parameters and chest CT images. This study provides experimental and clinical evidence that medium-to-low-dose glucocorticoids may play a protective role in the respiratory and digestive systems by activating ACE2 and suppressing cytokine storm.