Background: The goal of this study was to delineate the patterns of distant metastasis from colon adenocarcinoma (CAC) and evaluate the survival differences by metastatic patterns.Methods: Using the Surveillance, Epidemiology, and End Results (SEER) database, we extracted patients diagnosed with stage IV CAC between 2010 and 2016. Kaplan‐Meier survival curves were plotted with log‐rank tests to compare overall survival (OS) of patients with different metastatic patterns. Univariate and multivariate Cox proportional hazards regression models were used to evaluate the effects of different metastatic patterns on survival outcomes in terms of OS and disease‐specific survival (DSS).Results: A total of 26 170 patients were analyzed. The 3‐ and 5‐year OS were 20.7% and 10.5%, respectively, for patients with stage IV CAC. The most common distant metastatic site was the liver, followed by the lung, bone, and brain, but the frequency differed greatly by histology subtypes. The site of metastasis was a significant prognostic factor for OS and DSS in patients with stage IV CAC, independent of the number of metastatic sites and other clinical and demographic prognostic factors. Using liver‐only metastasis as reference, lung‐only metastasis was associated with better OS (hazard ratio [HR] = 0.82, 95% confidence interval [CI], 0.71‐0.94) and DSS (HR = 0.75, 95% CI, 0.64‐0.88). Older age, black race, unmarried status, grade III/IV tumors, advanced tumor‐node‐metastasis (TNM) stage, proximal colon, elevated preoperative carcinoembryonic antigen (CEA), no surgery of the primary site, and no chemotherapy were independent predictors of poor OS.Conclusions: The site of distant metastasis and number of metastasis site were independent prognostic factors for survival of patients with stage IV CAC. This study highlights the need for diverse treatment strategies for patients with different metastatic patterns.

The mechanisms underlying pathophysiological regulation of tissue macrophage (Mφ) subsets remain poorly understood. From the expression of 207 Mφ genes comprising 31 markers for 10 subsets, 45 transcription factors (TFs), 56 immunometabolism enzymes, 23 trained immunity (innate immune memory) enzymes, and 52 other genes in microarray data, we made the following findings. (1) When 34 inflammation diseases and tumor types were grouped into eight categories, there was differential expression of the 31 Mφ markers and 45 Mφ TFs, highlighted by 12 shared and 20 group-specific disease pathways. (2) Mφ in lung, liver, spleen, and intestine (LLSI-Mφ) express higher M1 Mφ markers than lean adipose tissue Mφ (ATMφ) physiologically. (3) Pro-adipogenic TFs C/EBPα and PPARγ and proinflammatory adipokine leptin upregulate the expression of M1 Mφ markers. (4) Among 10 immune checkpoint receptors (ICRs), LLSI-Mφ and bone marrow (BM) Mφ express higher levels of CD274 (PDL-1) than ATMφ, presumably to counteract the M1 dominant status via its reverse signaling behavior. (5) Among 24 intercellular communication exosome mediators, LLSI- and BM- Mφ prefer to use RAB27A and STX3 than RAB31 and YKT6, suggesting new inflammatory exosome mediators for propagating inflammation. (6) Mφ in peritoneal tissue and LLSI-Mφ upregulate higher levels of immunometabolism enzymes than does ATMφ. (7) Mφ from peritoneum and LLSI-Mφ upregulate more trained immunity enzyme genes than does ATMφ. Our results suggest that multiple new mechanisms including the cell surface, intracellular immunometabolism, trained immunity, and TFs may be responsible for disease group-specific and shared pathways. Our findings have provided novel insights on the pathophysiological regulation of tissue Mφ, the disease group-specific and shared pathways of Mφ, and novel therapeutic targets for cancers and inflammations.

Background: The mechanisms underlying low intensity ultrasound (LIUS) mediated suppression of inflammation and tumorigenesis remain poorly determined. Methods: We used microarray datasets from NCBI GEO Dataset databases and conducted a comprehensive data mining analyses, where we studied the gene expression of 299 cell death regulators that regulate 13 different cell death types (cell death regulatome) in cells treated with LIUS. Results: We made the following findings: (1) LIUS exerts a profound effect on the expression of cell death regulatome in cancer cells and non-cancer cells. Of note, LIUS has the tendency to downregulate the gene expression of cell death regulators in non-cancer cells. Most of the cell death regulator genes downregulated by LIUS in non-cancer cells are responsible for mediating inflammatory signaling pathways; (2) LIUS activates different cell death transcription factors in cancer and non-cancer cells. Transcription factors TP-53 and SRF- were induced by LIUS exposure in cancer cells and non-cancer cells, respectively; (3) As two well-accepted mechanisms of LIUS, mild hyperthermia and oscillatory shear stress induce changes in the expression of cell death regulators, therefore, may be responsible for inducing LIUS mediated changes in gene expression patterns of cell death regulators in cells; (4) LIUS exposure may change the redox status of the cells. LIUS may induce more of antioxidant effects in non-cancer cells compared to cancer cells; and (5) The genes modulated by LIUS in cancer cells have distinct chromatin long range interaction (CLRI) patterns to that of non-cancer cells. Conclusions: Our analysis suggests novel molecular mechanisms that may be utilized by LIUS to induce tumor suppression and inflammation inhibition. Our findings may lead to development of new treatment protocols for cancers and chronic inflammation.

Background. The immune mechanisms underlying low-intensity ultrasound- (LIUS-) mediated suppression of inflammation and tumorigenesis remain poorly determined. Methods. We used microarray datasets from the NCBI GEO DataSet repository and conducted comprehensive data-mining analyses, where we examined the gene expression of 1376 innate immune regulators (innatome genes (IGs) in cells treated with LIUS. Results. We made the following findings: (1) LIUS upregulates proinflammatory IGs and downregulates metastasis genes in cancer cells, and LIUS upregulates adaptive immunity pathways but inhibits danger-sensing and inflammation pathways and promote tolerogenic differentiation in bone marrow (BM) cells. (2) LIUS upregulates IGs encoded for proteins localized in the cytoplasm, extracellular space, and others, but downregulates IG proteins localized in nuclear and plasma membranes, and LIUS downregulates phosphatases. (3) LIUS-modulated IGs act partially via several important pathways of reactive oxygen species (ROS), reverse signaling of immune checkpoint receptors B7-H4 and BTNL2, inflammatory cytokines, and static or oscillatory shear stress and heat generation, among which ROS is a dominant mechanism. (4) LIUS upregulates trained immunity enzymes in lymphoma cells and downregulates trained immunity enzymes and presumably establishes trained tolerance in BM cells. (5) LIUS modulates chromatin long-range interactions to differentially regulate IGs expression in cancer cells and noncancer cells. Conclusions. Our analysis suggests novel molecular mechanisms that are utilized by LIUS to induce tumor suppression and inflammation inhibition. Our findings may lead to development of new treatment protocols for cancers and chronic inflammation.

Background: Although ultrasound (US) guided axillary vein (AV) catheterization has been well described, evidence for its efficacy and safety compared with conventional infraclavicular landmark guided subclavian vein (SCV) cannulation have not been comprehensively appraised. Thus, we conducted a systematic review and meta-analysis to determine whether US guided AV catheterization reduces catheterization failures and adverse events compared to SCV puncture based on landmark technique. Methods: We searched the PubMed, Embase, Cochrane Library, CINAHL, Web of Science, SCOPUS, China Biology Medicine, China National Knowledge Infrastructure, Wan Fang, and Wei Pu databases for randomized controlled trials (RCTs) studies published from inception to May 2021. Two investigators reviewed and extracted data on study design, number and type of inclusion criteria. Study quality was assessed using the Jadad scale. Outcomes included the puncture success rates and the incidence of adverse events. Results: Data of 1852 patients from five RCTs were included in this meta-analysis. The analysis showed that US guided AV catheterization increased the first (risk ratio (RR), confidence interval (CI)) (RR = 1.17, 95% CI = 1.13~1.22, P < .01) and overall (RR = 1.09, 95% CI = 1.04~1.15, P < .01) puncture success rate, and reduce the occurrence of adverse events, including the risk of arterial puncture (RR = 0.18, 95% CI = 0.06~0.55, P < .01), pneumo-and hemothorax (RR = 0.12, 95% CI = 0.02~0.64, P = .01). Conclusion: This meta-analysis indicates that US guided AV catheterization reduces catheterization failures and mechanical complications compared with conventional landmark guided SCV puncture.