Single-cell transcriptome analysis reveals tumoral microenvironment heterogenicity and hypervascularization in human carotid body tumor.

Carotid body tumor (CBT) is a rare neck tumor located at the adventitia of the common carotid artery bifurcation. The prominent pathological features of CBT are high vascularization and abnormal proliferation. However, single-cell transcriptome analysis of the microenvironment composition and molecular complexity in CBT has yet to be performed. In this study, we performed single-cell RNA sequencing (scRNA-seq) analysis on human CBT to define the cells that contribute to hypervascularization and chronic hyperplasia. Unbiased clustering analysis of transcriptional profiles identified 16 distinct cell populations including endothelial cells (ECs), smooth muscle cells (SMCs), neuron cells, macrophage cells, neutrophil cells, and T cells. Within the ECs population, we defined subsets with angiogenic capacity plus clear signs of later endothelial progenitor cells (EPCs) to normal ECs. Two populations of macrophages were detectable in CBT, macrophage1 showed enrichment in hypoxia-inducible factor-1 (HIF-1) and as well as an early EPCs cell-like population expressing CD14 and vascular endothelial growth factor. In addition to HIF-1-related transcriptional protein expression, macrophages1 also display a neovasculogenesis-promoting phenotype. SMCs included three populations showing platelet-derived growth factor receptor beta and vimentin expression, indicative of a cancer-associated fibroblast phenotype. Finally, we identified three types of neuronal cells, including chief cells and sustentacular cells, and elucidated their distinct roles in the pathogenesis of CBT and abnormal proliferation of tumors. Overall, our study provided the first comprehensive characterization of the transcriptional landscape of CBT at scRNA-seq profiles, providing novel insights into the mechanisms underlying its formation.

TP53 /KRAS Co-Mutations Create Divergent Prognosis Signatures in Intrahepatic Cholangiocarcinoma.

Background: Due to high invasiveness and heterogeneity, the morbidity and mortality of intrahepatic cholangiocarcinoma (ICC) remain unsatisfied. Recently, the exploration of genomic variants has decoded the underlying mechanisms of initiation and progression for multiple tumors, while has not been fully investigated in ICC. Methods: We comprehensively analyzed 899 clinical and somatic mutation data of ICC patients from three large-scale cohorts. Based on the mutation landscape, we identified the common high-frequency mutation genes (FMGs). Subsequently, the clinical features, prognosis, tumor mutation burden (TMB), and pharmacological landscape from patients with different mutation carriers were further analyzed. Results: We found TP53 and KRAS were the common FMGs in the three cohorts. Kaplan-Meier survival curves and univariate and multivariate analysis displayed that TP53 and KRAS mutations were associated with poor prognosis. Considering the co-mutation phenomenon of TP53 and KRAS, we stratified patients into "Double-WT," "Single-Hit," and "Double-Hit" phenotypes by mutation status. Patients with the three phenotypes showed significant differences in the mutation landscape. Additionally, compared with "Double-WT" and "Single-Hit" phenotypes, patients with "Double-Hit" presented a dismal prognosis and significantly high TMB. Through chemotherapy sensitivity analysis, we identified a total of 30 sensitive drugs for ICC patients, of which 22 were drugs sensitive to "Double-WT," 7 were drugs sensitive to "Double-Hit," and only one was a drug sensitive to "Single-Hit." Conclusion: Our study defined a novel mutation classification based on the common FMGs, which may contribute to the individualized treatment and management of ICC patients.

Plasma Metabolomics Analysis Identifies Abnormal Energy, Lipid, and Amino Acid Metabolism in Abdominal Aortic Aneurysms.

BACKGROUND Abdominal aortic aneurysm (AAA) is a complicated aortic dilatation disease. Metabolomics is an emerging system biology method. This aim of this study was to identify abnormal metabolites and metabolic pathways associated with AAA and to discover potential biomarkers that could affect the size of AAAs. MATERIAL AND METHODS An untargeted metabolomic method was used to analyze the plasma metabolic profiles of 39 patients with AAAs and 30 controls. Multivariate analysis methods were used to perform differential metabolite screening and metabolic pathway analysis. Cluster analysis and univariate analysis were performed to identify potential metabolites that could affect the size of an AAA. RESULTS Forty-five different metabolites were identified with an orthogonal projection to latent squares-discriminant analysis model and the differences between them in the patients with AAAs and the control group were compared. A variable importance in the projection score >1 and P<0.05 were considered statistically significant. In patients with AAAs, the pathways involving metabolism of alanine, aspartate, glutamate, D-glutamine, D-glutamic acid, arginine, and proline; tricarboxylic acid cycling; and biosynthesis of arginine are abnormal. The progression of an AAA may be related to 13 metabolites: citric acid, 2-oxoglutarate, succinic acid, coenzyme Q1, pyruvic acid, sphingosine-1-phosphate, platelet-activating factor, LysoPC (16: 00), lysophosphatidylcholine (18: 2(9Z,12Z)/0: 0), arginine, D-aspartic acid, and L- and D-glutamine. CONCLUSIONS An untargeted metabolomic analysis using ultraperformance liquid chromatography-tandem mass spectrometry identified metabolites that indicate disordered metabolism of energy, lipids, and amino acids in AAAs.

AngioJet Aspiration Thrombectomy Combined with Transcatheter Thrombolysis in Treatment of Acute Portal Venous Systemic Thrombosis.

BACKGROUND: This study set out to assess the feasibility, effectiveness, and safety of percutaneous AngioJet aspiration thrombectomy combined with transcatheter thrombolysis for treating acute portal venous systemic thrombosis (APVST). METHODS: Clinical data of 13 patients with APVST who were treated by AngioJet aspiration thrombectomy combined with transcatheter thrombolysis from March 2017 to July 2018 were analyzed retrospectively. The effect of portal venous recanalization was evaluated by intraoperative angiography and postoperative surveillance of clinical findings, portal venous ultrasound, or computed tomography. RESULTS: Successful puncture of the portal vein (PV) was performed in all patients. The PV was punctured successfully in 7 patients via the transjugular intrahepatic route, 2 patients failed to be punctured and then had successful percutaneous transhepatic puncture, and 4 patients underwent percutaneous transhepatic PV puncture directly. The duration of thrombus aspiration was 238.46 ± 89.89 sec (range, 120-360), and the amount of urokinase in thrombus aspiration was 353,000 ± 87,700 IU (range, 200,000-400,000). Portal venous thrombosis was dissolved by the AngioJet thrombectomy device (Boston Scientific, Marlborough, MA) in all patients. After aspiration, angiography showed that grade III lysis was achieved in 8 patients, grade II lysis in 1 patient, and grade I lysis in 4 patients. The length of transcatheter thrombolysis was 3.07 ± 1.75 days (range, 1-7), and the total urokinase dose via an indwelling catheter was 1,230,000 ± 706,000 IU (range, 200,000-2,800,000). Four patients had a transjugular intrahepatic portosystemic shunt, 1 patient with stenosis of the superior mesenteric vein (SMV) achieved balloon angioplasty, and 1 patient with stenosis of the SMV was stented. Operative complications were transient hematuria (4 patients), palpitation (1 patient), and bowel resection (1 patient). No patients died within 30 days. Patients were discharged at 12.00 ± 5.83 days (range, 6-27) after admission. All patients survived, and no recurrence developed during the follow-up of 9.15 ± 3.18 months (range, 4-15). CONCLUSIONS: Percutaneous AngioJet aspiration thrombectomy combined with thrombolytic therapy is feasible and effective for APVST. This treatment is beneficial for APVST in dissolving thrombus, improving SMV flow, and relieving symptoms of PV hypertension.

Endovascular treatment for left innominate vein aneurysm: Case report and literature review.

Innominate vein aneurysms originating from the mediastinum are very rare. Previous treatments for this condition often required thoracotomy. We report a case of a 43-year-old male who presented a mediastinal mass by chest radiography. Contrast-enhanced CT and venography confirmed the diagnosis of left innominate vein aneurysm. The patient underwent endovascular treatment with stent placement and coil embolization of the left innominate vein. The patient remains well 18 months after surgery. The objective of this report is to discuss the diagnosis and endovascular treatment results of innominate vein aneurysm and to review the relevant literature to enhance and expand the pool of knowledge for this abnormality.