Integrative single-cell transcriptomic analyses reveal the cellular ontological and functional heterogeneities of primary and metastatic liver tumors.

BACKGROUND: The global cellular landscape of the tumor microenvironment (TME) combining primary and metastatic liver tumors has not been comprehensively characterized. METHODS: Based on the scRNA-seq and spatial transcriptomic data of non-tumor liver tissues (NTs), primary liver tumors (PTs) and metastatic liver tumors (MTs), we performed the tissue preference, trajectory reconstruction, transcription factor activity inference, cell-cell interaction and cellular deconvolution analyses to construct a comprehensive cellular landscape of liver tumors. RESULTS: Our analyses depicted the heterogeneous cellular ecosystems in NTs, PTs and MTs. The activated memory B cells and effector T cells were shown to gradually shift to inhibitory B cells, regulatory or exhausted T cells in liver tumors, especially in MTs. Among them, we characterized a unique group of TCF7+ CD8+ memory T cells specifically enriched in MTs that could differentiate into exhausted T cells likely driven by the p38 MAPK signaling. With regard to myeloid cells, the liver-resident macrophages and inflammatory monocyte/macrophages were markedly replaced by tumor-associated macrophages (TAMs), with TREM2+ and UBE2C+ TAMs enriched in PTs, while SPP1+ and WDR45B+ TAMs in MTs. We further showed that the newly identified WDR45B+ TAMs exhibit an M2-like polarization and are associated with adverse prognosis in patients with liver metastases. Additionally, we addressed that endothelial cells display higher immune tolerance and angiogenesis capacity, and provided evidence for the source of the mesenchymal transformation of fibroblasts in tumors. Finally, the malignant hepatocytes and fibroblasts were prioritized as the pivotal cell populations in shaping the microenvironments of PTs and MTs, respectively. Notably, validation analyses by using spatial or bulk transcriptomic data in clinical cohorts concordantly emphasized the clinical significance of these findings. CONCLUSIONS: This study defines the ontological and functional heterogeneities in cellular ecosystems of primary and metastatic liver tumors, providing a foundation for future investigation of the underlying cellular mechanisms.

Thoracic Endovascular Aortic Repair Versus Open Surgery for Stanford Type B Aortic Dissection: A Meta-Analysis and Systematic Review.

BACKGROUND: Thoracic endovascular aortic repair is a relatively new technique relative to open surgery, and our aim was to assess whether there is a difference in the risk of common postoperative complications between thoracic endovascular aortic repair and open surgery. METHODS: The PubMed, Web of Science, and Cochrane library were systematically searched for trials comparing thoracic endovascular aortic repair and open surgical repair from January 2000 to September 2022. Primary outcome was death, other outcomes included common associated complications. Data were combined using risk ratio or standardized mean difference with 95% confidence interval. Funnel plot and egger's test were used for assessing publication bias. The study protocol was registered prospectively with PROSPERO (CRD42022372324). RESULTS: This trial included 11 controlled clinical studies with 3667 patients. Thoracic endovascular aortic repair had lower risk of death (risk ratio [RR], 0.59; 95% CI, 0.49 to 0.73; p < 0.00001; I2 = 0), dialysis (RR, 0.55; 95% CI, 0.47 to 0.65; p < 0.00001; I2 = 37%), stroke (RR, 0.71; 95% CI, 0.51 to 0.98; p = 0.03; I2 = 40%), bleeding (RR, 0.44; 95% CI, 0.23 to 0.83; p = 0.01; I2 = 56%), and respiratory complications (RR, 0.67; 95% CI, 0.60 to 0.76; p < 0.00001; I2 = 37%) compared with open surgical repair. In addition, the length of hospital stay was shorter in the thoracic endovascular aortic repair group (SMD, -0.84; 95% CI, -1.30 to -0.38; p = 0.0003; I2 = 80%). CONCLUSIONS: Thoracic endovascular aortic repair has significant advantages over open surgical repair, in terms of postoperative complications and survival in Stanford type B aortic dissection patients.