M2 Macrophage Classification of Colorectal Cancer Reveals Intrinsic Connections with Metabolism Reprogramming and Clinical Characteristics.

Introduction: Immune cell interactions and metabolic changes are crucial in determining the tumor microenvironment and affecting various clinical outcomes. However, the clinical significance of metabolism evolution of immune cell evolution in colorectal cancer (CRC) remains unexplored. Methods: Single-cell RNA sequencing (scRNA-seq) and bulk RNA sequencing data were acquired from TCGA and GEO datasets. For the analysis of macrophage differentiation trajectories, we employed the R packages Seurat and Monocle. Consensus clustering was further applied to identify the molecular classification. Immunohistochemical results from AOM and AOM/DSS models were used to validate macrophage expression. Subsequently, GSEA, ESTIMATE scores, prognosis, clinical characteristics, mutational burden, immune cell infiltration, and the variance in gene expression among different clusters were compared. We constructed a prognostic model and nomograms based on metabolic gene signatures identified through the MEGENA framework. Results: We found two heterogeneous groups of M2 macrophages with various clinical outcomes through the evolutionary process. The prognosis of Cluster 2 was poorer. Further investigation showed that Cluster 2 constituted a metabolically active group while Cluster 1 was comparatively metabolically inert. Metabolic variations in M2 macrophages during tumor development are related to tumor prognosis. Additionally, Cluster 2 showed the most pronounced genomic instability and had highly elevated metabolic pathways, notably those associated with the ECM. We identified eight metabolic genes (PRELP, NOTCH3, CNOT6, ASRGL1, SRSF1, PSMD4, RPL31, and CNOT7) to build a predictive model validated in CRC datasets. Then, a nomogram based on the M2 risk score improved predictive performance. Furthermore, our study demonstrated that immune checkpoint inhibitor therapy may benefit patients with low-risk. Discussion: Our research reveals underlying relationships between metabolic phenotypes and immunological profiles and suggests a unique M2 classification technique for CRC. The identified gene signatures may be key factors linking immunity and tumor metabolism, warranting further investigations.

Dynamic regulation of EXO1 promotes the progression from liver fibrosis to HCC through TGF-ß1/Smad signaling feedback loop.

BACKGROUND: HSCs are the main stromal cells in the process of liver fibrosis and accelerate HCC progression. Previous studies determined that highly expressed exonuclease 1 (EXO1) increases the malignant behavior of HCC cells and is closely related to liver cirrhosis. This study aimed to explore the roles and mechanisms of EXO1 in the development of liver cirrhosis and HCC. METHODS: We fully demonstrated that EXO1 expression was positively correlated with liver fibrosis and cirrhotic HCC by combining bioinformatics, hepatic fibrosis mouse models, and human HCC tissues. The role of EXO1 in a murine HCC model induced by activated forms of AKT and Ras oncogenes (AKT/Ras) was investigated by employing an adeno-associated virus-mediated EXO1 knockdown technique. RESULTS: The knockdown of EXO1 promoted a regression of HCC in AKT/Ras mice and reduced the degree of liver fibrosis. Downregulated EXO1 inhibited LX-2 cell activation and inhibited the proliferation and migration of HCC cells. Moreover, conditioned medium of LX-2 cells with EXO1 overexpression increased the proliferation and migration of HCC cells, which was attenuated after EXO1 knockout in LX-2 cells. EXO1 knockdown attenuated the role of LX-2 in promoting HepG2 xenograft growth in vivo. Mechanistically, EXO1 promotes the activation of the downstream TGF-ß-smad2/3 signaling in LX-2 and HCC cells. Interestingly, increased TGF-ß-smad2/3 signaling had a feedback effect on EXO1, which sustains EXO1 expression and continuously stimulates the activation of HSCs. CONCLUSIONS: EXO1 forms a positive feedback circuit with TGF-ß-Smad2/3 signaling and promotes the activation of HSCs, which accelerates HCC progression. Those findings indicate EXO1 may be a promising target for the diagnosis and treatment of cirrhotic HCC.

Effect of "Internet + tertiary hospital-primary hospital-family linkage home care" model on self-care ability and quality of life of discharged stroke patients.

OBJECTIVE: To investigate the intervention effect of an "Internet + tertiary hospital-primary hospital-family linkage home care" model on the quality of life and self-care abilities of discharged stroke patients. METHODS: The clinical data of 90 patients with stroke who were hospitalized and discharged from the Department of Neurology of the Affiliated Hospital of Youjiang Medical College for Nationalities from October 2020 to September 2021 were retrospectively analyzed. They were split into a control group (41 cases) and an intervention group (40 cases) based on different care modes. The intervention group was given the "Internet + tertiary hospital-primary hospital-family connection home care" paradigm, while the control group received normal nursing interventions. The degree of nerve defect, quality of life, anxiety and depression, self-care ability and exercise ability of the patients were evaluated by National Institutes of Health Stroke Scale (NIHSS), Stroke Specific Quality of Life Scale (SS-QOL), General Hospital Anxiety and Depression Scale (HADS), Self-care Ability Scale (ESCA), and Fugl-Meyer Motor Function Assessment (FMA) before discharge and at 3rd, 6th and 12th month after discharge, respectively. The re-hospitalization rate, treatment compliance and exercise ability of the two groups were compared within a year after discharge. RESULTS: The scores of SS-QOL, ESCA and FMA in the intervention group increased with time, and the scores of SS-QOL, ESCA and FMA at 3rd, 6th and 12th month after discharge were higher than those in the control group (all P<0.05). The NIHSS and HADS scores decreased over time, and the NIHSS and HADS scores were lower than the control group at 12th month after discharge (P<0.05). Within a year of discharge, the intervention group had a lower rehospitalization rate than the control group (P<0.05), and the treatment compliance score was higher in the intervention group than that in the control group (P<0.05). CONCLUSION: The "Internet + tertiary hospital-primary hospital-family nursing" model can improve self-care ability and treatment compliance of patients, improve their nerve defects and psychological status as well as quality of life, and reduce rehospitalization rate.