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.

Classification and management strategy of spontaneous carotid artery dissection.

OBJECTIVE: Spontaneous carotid artery dissections (sCADs) are the common cause of stroke in middle-aged and young people. There is still a lack of clinical classification to guide the management of sCAD. We reviewed our experience with 179 patients with sCAD and proposed a new classification for sCAD with prognostic and therapeutic significance. METHODS: This is a retrospective review of prospectively collected data from June 2018 to June 2023 of patients with sCAD treated at a large tertiary academic institution in an urban city in China. Based on imaging results, we categorize sCAD into four types: type Ⅰ, intramural hematoma or dissection with <70% luminal narrowing; type Ⅱ, intramural hematoma or dissection with ≥70% luminal narrowing; type Ⅲ, dissecting aneurysm; type ⅣA, extracranial carotid artery occlusion; and type ⅣB, tandem occlusion. We compared the clinical data and prognostic outcomes among various types of sCADs. RESULTS: A total of 179 patients and 197 dissected arteries met the inclusion criteria. The mean age of the 179 patients with sCAD was 49.5 years, 78% were male, and 18 patients (10%) had bilateral sCAD. According to our classification, there were 56 type Ⅰ (28.4%), 50 type Ⅱ (25.4%), 60 type Ⅲ (30.5%), and 31 type Ⅳ (15.7%) dissections. During a mean hospitalization length of 11.4 ± 47.0 days, there were nine recurrent strokes (4.6%) after medical treatment, two type Ⅲ dissections (1.0%), seven type Ⅳ dissections (3.6%), all ipsilateral, and one death. Overall, there were seven (3.6%, 1 type Ⅰ dissection, 3 type Ⅱ dissections, 2 type Ⅲ dissections, and 1 type Ⅳ dissection) recurrent strokes and three (1.5%, all type Ⅲ dissections) recurrent transient ischemic attacks in patients treated with just medical therapy during the follow-up period, all ipsilateral, with a mean follow-up of 26 months (range, 3-59 months). These patients did not undergo further intervention due to the high difficulty associated with endovascular treatment (EVT) or the mild nature of recurrent cerebral ischemic symptoms. Twenty-nine type I dissections (51.8%) were completely recanalized after antithrombotic therapy. A total of 19 type II dissections (38%) and 44 type III dissections (73%) received EVT for persistent flow-limited dissections, enlargement of dissecting aneurysms, or aggravation of neurological symptoms despite antithrombotic therapy. Type Ⅳ dissections are more likely to lead to the occurrence of ischemic stroke and presented with more severe symptoms. Eight type IVB dissections (33%) received acute phase intervention due to distal thromboembolism or aggravation of neurological symptoms after medical treatment. In terms of cerebral ischemic events and mortality, there were no statistically significant differences among the four types of sCAD (all P > .05). Favorable outcome was achieved in 168 patients (93.9%). CONCLUSIONS: This study proposed a novel and more comprehensive classification method and the modern management strategy for sCAD. Antithrombotic therapy is beneficial to reduce the risk of recurrent stroke for stable sCAD. Non-emergent EVT can be an alternative therapeutic approach for patients who meet indications as in type II to IVA dissections. Urgent procedure with neurovascular intervention is necessary for some type IVB dissections. The short-term results of EVT for sCAD are encouraging, and long-term device-related and functional outcomes should undergo further research.

Localized Elevation of Wall Shear Stress Is Linked to Recent Symptoms in Patients with Carotid Stenosis.

BACKGROUND: Estimation of symptomatic and asymptomatic carotid atherosclerosis differences can be the basis for prevention and management of carotid artery stenosis disease. In clinical practice, carotid plaque vulnerability is assessed only on the basis of luminal stenosis. However, the evolution of carotid plaque from an asymptomatic state to a symptomatic one is a complex process and the underlying hemodynamic mechanisms are unknown. We aimed to investigate the differences in hemodynamic parameters between patients with recently symptomatic carotid stenosis and asymptomatic ones. METHODS: Hemodynamic simulations were performed on 26 carotid plaques from 25 patients with carotid artery stenosis ≥50%, 16 of whom had recent cerebrovascular ischemic events. Using human-specific flow parameters and 3D reconstruction of carotid computed tomography angiography images, we assessed hemodynamic characteristics such as wall shear stress (WSS), time-averaged WSS (TAWSS), oscillatory shear index, and relative residence time (RRT) during the cardiac cycle in patients with and without symptoms. RESULTS: We found that symptomatic carotid stenosis patients had greater local TAWSS (99.59 ± 26.29 vs. 60.40 ± 20.46 dyn/cm2, p = 0.0007) and maximal WSS (116.65 ± 39.11 vs. 68.28 ± 23.67 dyn/cm2, p = 0.003), but lower RRT (0.019 ± 0.006 vs. 0.013 ± 0.069 s, p = 0.049), than asymptomatic patients, but this hemodynamic difference was not associated with carotid stenosis severity (p = 0.70). Patients with transient ischemic attack (TIA) or stroke had higher local TAWSS and WSSmax than patients with asymptomatic stenosis (p < 0.05). Subgroup analysis showed that there was no statistical difference in local hemodynamic variables between TIA and stroke patients with carotid artery stenosis. CONCLUSIONS: Patients with carotid artery stenosis are more likely to experience acute ischemic cerebrovascular accidents if they have higher WSS. Simultaneous assessment with hemodynamic parameters like WSS along with stenosis severity may aid risk stratification in patients with asymptomatic carotid artery stenosis.

Early and midterm outcomes of in situ laser fenestration during thoracic endovascular aortic repair for acute and subacute aortic arch diseases and analysis of its complications.

OBJECTIVE: An analysis was conducted of early and midterm outcomes of a large series of patients treated with in situ laser fenestration (ISLF) during thoracic endovascular aortic repair (TEVAR) of acute and subacute complex aortic arch diseases, such as Stanford type A aortic dissection (TAAD), type B aortic dissection (TBAD) requiring proximal sealing at zone 2 or more proximal, thoracic aortic aneurysm or pseudoaneurysm, and penetrating aortic ulcer. We present the perioperative and follow-up outcomes and discuss the rate of complications. METHODS: This is a retrospective review of prospectively collected data from January 2017 to March 2019 of patients treated with TEVAR and ISLF of aortic arch branches at a large tertiary academic institution in an urban city in China. Preoperative, intraoperative, and follow-up clinical and radiographic data are analyzed and discussed. RESULTS: A total of 148 patients presented with symptomatic and acute or subacute TAAD, TBAD, thoracic aortic aneurysm, or penetrating aortic ulcer for a total of 183 arch vessels. There were 105 men and 43 women, 21 to 79 years of age (mean, 54.9 ± 12.9 years). Time from symptom onset to time of surgery was an average of 7 ± 3 days. Survivor follow-up duration ranged from 5 to 24 months (mean, 15 ± 5 months). Single-vessel fenestration was carried out in 124 cases, two-vessel fenestration in 13 cases, and three-vessel fenestration in 11 cases. There were four cases with technical failure to laser fenestration, with a technical success rate of 97.3%. Postoperatively, there were seven cases of endoleak (4.7%; one type IB distal from the left subclavian artery branch stent graft, three type IIIC at the fenestration site, and three type II), three retrograde dissections (2.0%), and five strokes (3.4%); death occurred in three patients with 30-day mortality of 2.9%, and two deaths occurred during follow-up for 3.4% mortality at an average 15 months of follow-up. There was no branch stent graft occlusion or spinal ischemia postoperatively or during follow-up. The distribution of arch diseases varied significantly according to the number of vessels that were laser fenestrated; TAAD was more likely to receive multivessel laser fenestrations, and TBAD was more likely to receive single-vessel fenestration (P < .001). The rate of complications was distributed differently between the three ISLF groups, with more complications occurring in multivessel fenestrations. However, a statistical weakening was observed when frequency of complications between the three groups was stratified by type of arch disease. The complication rate varied significantly between the different arch diseases, higher in TAAD than in TBAD (P = .008). CONCLUSIONS: ISLF during TEVAR for treatment of acute and subacute complex aortic arch diseases in the proximal aortic arch is safe and effective on the basis of these early to midterm follow-up data of a large cohort. However, care should be taken in intervening on TAAD using TEVAR with adjunctive multivessel laser fenestration. Continued investigation of TEVAR and adjunctive ISLF is needed to elucidate the long-term outcomes of this minimally invasive treatment for complex aortic arch disease in an urgent setting.

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.

Long-term safety and outcome of percutaneous transhepatic venous balloon angioplasty for Budd-Chiari syndrome.

BACKGROUND AND AIMS: The restenosis following percutaneous transluminal balloon angioplasty (PTBA) is high for Budd-Chiari syndrome (BCS) patients with hepatic venous obstruction (HVO). We aim to evaluate the safety and long-term outcome of PTBA with a large balloon catheter in a large series of patients with HVO. METHODS: Between January 2005 and December 2013, 93 consecutive BCS patients with HVO were referred for PTBA and subsequently underwent color Doppler ultrasonography or angiography follow-up. Data were retrospectively collected, and follow-up observations were performed at 1-, 2-, 2- to 5-, and 5- to 8-years postoperatively. RESULTS: Percutaneous transluminal balloon angioplasty was technically successful in all patients. Ninety-one patients (97.85%) were treated with PTBA and two with PTBA and stent. Major procedure-related complications occurred in six of the 93 patients (6.45%). The cumulative 1-, 2-, 2- to 5-, and 5- to 8-year primary patency rates were 97.5%, 92.9%, 90%, and 86.5%, respectively. Cumulative 1-, 2-, 2- to 5-, and 5- to 8-year secondary patency rates were 100%, 100%, 98.6%, and 97.3%, respectively. Mean and median primary patency rates were 51.50 ± 3.01 months and 55.0 ± 3.63 months, respectively. Cumulative 1-, 2-, 2- to 5-, and 5- to 8-year survival rates were 98.75%, 98.6%, 100%, and 100%, respectively. Mean and median survival times were 53.10 ± 3.04 months and 55.0 ± 3.64 months, respectively. CONCLUSION: Percutaneous transluminal balloon angioplasty with a large balloon is a safe and effective treatment that could provide excellent rates of long-term patency and survival for the majority of Chinese patients with BCS and HVO.

Identifying vulnerable plaques: A 3D carotid plaque radiomics model based on HRMRI.

Background: Identification of vulnerable carotid plaque is important for the treatment and prevention of stroke. In previous studies, plaque vulnerability was assessed qualitatively. We aimed to develop a 3D carotid plaque radiomics model based on high-resolution magnetic resonance imaging (HRMRI) to quantitatively identify vulnerable plaques. Methods: Ninety patients with carotid atherosclerosis who underwent HRMRI were randomized into training and test cohorts. Using the radiological characteristics of carotid plaques, a traditional model was constructed. A 3D carotid plaque radiomics model was constructed using the radiomics features of 3D T1-SPACE and its contrast-enhanced sequences. A combined model was constructed using radiological and radiomics characteristics. Nomogram was generated based on the combined models, and ROC curves were utilized to assess the performance of each model. Results: 48 patients (53.33%) were symptomatic and 42 (46.67%) were asymptomatic. The traditional model was constructed using intraplaque hemorrhage, plaque enhancement, wall remodeling pattern, and lumen stenosis, and it provided an area under the curve (AUC) of 0.816 vs. 0.778 in the training and testing sets. In the two cohorts, the 3D carotid plaque radiomics model and the combined model had an AUC of 0.915 vs. 0.835 and 0.957 vs. 0.864, respectively. In the training set, both the radiomics model and the combination model outperformed the traditional model, but there was no significant difference between the radiomics model and the combined model. Conclusions: HRMRI-based 3D carotid radiomics models can improve the precision of detecting vulnerable carotid plaques, consequently improving risk classification and clinical decision-making in patients with carotid stenosis.

Comparative outcomes of anticoagulation alone versus anticoagulation plus endovascular intervention in adults with isolated renal vein thrombosis.

BACKGROUND: Limited therapeutic strategies are available for adults with isolated renal vein thrombosis (RVT). In the present study, we explore and compare the efficacy of anticoagulation therapy alone vs anticoagulation plus endovascular intervention in the treatment of this rare disease. METHODS: In the present study, we analyzed the clinical data of RVT patients treated in a tertiary referral center in urban China from April 2012 to April 2022. These patients were classified into anticoagulation therapy (best medical treatment [BMT]) and endovascular intervention (endovascular-based treatment [EBT]) groups. The primary end points, including thrombus clearance and renal function changes, were evaluated by measuring the serum creatinine levels and glomerular filtration rates (GFRs). RESULTS: A total of 40 consecutive patients with RVT (25 men and 15 women) were included in the present study, with a median age of 37 years (range, 18-72 years). Some patients developed symptoms, including 12 with low back pain (30%), 11 with lower extremity edema (28%), and 10 with abdominal pain (30%). Nephrotic syndrome was the underlying etiology for most patients (30 of 40; 75%). Additionally, 28 patients (70%) developed unilateral RVT, including 18 cases of left RVT (45%). Of the 40 patients, 17 had received BMT (42%) and 23 had received EBT (58%). In the acute phase of RVT, defined as <14 days from symptom onset, the EBT group had higher thrombus clearance and better improvement of creatinine and GFR after treatment compared with the BMT group (P < .05). In the subacute phase, defined as 14 to 30 days after symptom onset, thrombus clearance was higher in the EBT group than in the BMT group (P < .05). However, the improvement in creatinine and GFR were insignificantly different between the two groups (P > .05). CONCLUSIONS: The etiologies of RVT can and should be investigated. In the present study, RVT was primarily caused by nephrotic syndrome in young patients and also was attributed to malignancy and lupus nephritis. In addition to anticoagulation therapy, endovascular intervention, including catheter-directed thrombolysis and mechanical thrombectomy, contributed to the improvement of renal function in patients with acute RVT. Endovascular intervention markedly promoted thrombus clearance in patients in the subacute phase but did not improve renal function. Therefore, endovascular intervention should be considered if RVT is diagnosed in the acute phase.

Congenital Abdominal Aortic Aneurysm: A Case Report and Literature Review.

Congenital abdominal aortic aneurysm is a rare disease with unknown etiology, and the common symptoms are abdominal pulsatile mass and pain caused by aneurysm rupture. The disease has a high mortality rate and fewer reports of surgical treatment. Here, we present a case of an idiopathic congenital abdominal aortic aneurysm. A 4-year-old boy had an abdominal pulsatile mass, and computed tomography angiography revealed an isolated infrarenal abdominal aortic aneurysm. To prevent rupture of the aneurysm, we repaired the aneurysm with artificial graft transplantation. No genetic mutation of the known congenital aneurysmal diseases was found in the whole-exome sequencing of the patient and his parents. There was no graft obstruction, and the patient grew well 40 months after surgery. Open surgery is the best treatment for idiopathic congenital abdominal aortic aneurysms. Surgical details such as timing and graft selection need to be further explored.

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.

EGR1 and KLF4 as Diagnostic Markers for Abdominal Aortic Aneurysm and Associated With Immune Infiltration.

BACKGROUND: Formation and rupture of abdominal aortic aneurysm (AAA) is fatal, and the pathological processes and molecular mechanisms underlying its formation and development are unclear. Perivascular adipose tissue (PVAT) has attracted extensive attention as a newly defined secretory organ, and we aim to explore the potential association between PVAT and AAA. METHODS: We analyzed gene expression and clinical data of 30 PVAT around AAA and 30 PVAT around normal abdominal aorta (NAA). The diagnostic markers and immune cell infiltration of PVAT were further investigated by WGCNA, CIBERSORT, PPI, and multiple machine learning algorisms (including LASSO, RF, and SVM). Subsequently, eight-week-old C57BL/6 male mice (n = 10) were used to construct AAA models, and aorta samples were collected for molecular validation. Meanwhile, fifty-five peripheral venous blood samples from patients (AAA vs. normal: 40:15) in our hospital were used as an inhouse cohort to validate the diagnostic markers by qRT-PCR. The diagnostic efficacy of biomarkers was assessed by receiver operating characteristic (ROC) curve, area under the ROC (AUC), and concordance index (C-index). RESULTS: A total of 75 genes in the Grey60 module were identified by WGCNA. To select the genes most associated with PVAT in the grey60 module, three algorithms (including LASSO, RF, and SVM) and PPI were applied. EGR1 and KLF4 were identified as diagnostic markers of PVAT, with high accurate AUCs of 0.916, 0.926, and 0.948 (combined two markers). Additionally, the two biomarkers also displayed accurate diagnostic efficacy in the mice and inhouse cohorts, with AUCs and C-indexes all >0.8. Compared with the NAA group, PVAT around AAA was more abundant in multiple immune cell infiltration. Ultimately, the immune-related analysis revealed that EGR1 and KLF4 were associated with mast cells, T cells, and plasma cells. CONCLUSION: EGR1 and KLF4 were diagnostic markers of PVAT around AAA and associated with multiple immune cells.

Development and Validation of Ischemic Events Related Signature After Carotid Endarterectomy.

Background: Ischemic events after carotid endarterectomy (CEA) in carotid artery stenosis patients are unforeseeable and alarming. Therefore, we aimed to establish a novel model to prevent recurrent ischemic events after CEA. Methods: Ninety-eight peripheral blood mononuclear cell samples were collected from carotid artery stenosis patients. Based on weighted gene co-expression network analysis, we performed whole transcriptome correlation analysis and extracted the key module related to ischemic events. The biological functions of the 292 genes in the key module were annotated via GO and KEGG enrichment analysis, and the protein-protein interaction (PPI) network was constructed via the STRING database and Cytoscape software. The enrolled samples were divided into train (n = 66), validation (n = 28), and total sets (n = 94). In the train set, the random forest algorithm was used to identify critical genes for predicting ischemic events after CEA, and further dimension reduction was performed by LASSO logistic regression. A diagnosis model was established in the train set and verified in the validation and total sets. Furthermore, fifty peripheral venous blood samples from patients with carotid stenosis in our hospital were used as an independent cohort to validation the model by RT-qPCR. Meanwhile, GSEA, ssGSEA, CIBERSORT, and MCP-counter were used to enrichment analysis in high- and low-risk groups, which were divided by the median risk score. Results: We established an eight-gene model consisting of PLSCR1, ECRP, CASP5, SPTSSA, MSRB1, BCL6, FBP1, and LST1. The ROC-AUCs and PR-AUCs of the train, validation, total, and independent cohort were 0.891 and 0.725, 0.826 and 0.364, 0.869 and 0.654, 0.792 and 0.372, respectively. GSEA, ssGSEA, CIBERSORT, and MCP-counter analyses further revealed that high-risk patients presented enhanced immune signatures, which indicated that immunotherapy may improve clinical outcomes in these patients. Conclusion: An eight-gene model with high accuracy for predicting ischemic events after CEA was constructed. This model might be a promising tool to facilitate the clinical management and postoperative surveillance of carotid artery stenosis patients.

Integrated Analysis of Multi-Omics Alteration, Immune Profile, and Pharmacological Landscape of Pyroptosis-Derived lncRNA Pairs in Gastric Cancer.

Background: Recent evidence demonstrates that pyroptosis-derived long non-coding RNAs (lncRNAs) have profound impacts on the initiation, progression, and microenvironment of tumors. However, the roles of pyroptosis-derived lncRNAs (PDLs) in gastric cancer (GC) remain elusive. Methods: We comprehensively analyzed the multi-omics data of 839 GC patients from three independent cohorts. The previous gene set enrichment analysis embedding algorithm was utilized to identify PDLs. A gene pair pipeline was developed to facilitate clinical translation via qualitative relative expression orders. The LASSO algorithm was used to construct and validate a pyroptosis-derived lncRNA pair prognostics signature (PLPPS). The associations between PLPPS and multi-omics alteration, immune profile, and pharmacological landscape were further investigated. Results: A total of 350 PDLs and 61,075 PDL pairs in the training set were generated. Cox regression revealed 15 PDL pairs associated with overall survival, which were utilized to construct the PLPPS model via the LASSO algorithm. The high-risk group demonstrated adverse prognosis relative to the low-risk group. Remarkably, genomic analysis suggested that the lower tumor mutation burden and gene mutation frequency (e.g., TTN, MUC16, and LRP1B) were found in the high-risk group patients. The copy number variants were not significantly different between the two groups. Additionally, the high-risk group possessed lower immune cell infiltration abundance and might be resistant to a few chemotherapeutic drugs (including cisplatin, paclitaxel, and gemcitabine). Conclusion: PDLs were closely implicated in the biological process and prognosis of GC, and our PLPPS model could serve as a promising tool to advance prognostic management and personalized treatment of GC patients.

LncRNA ZEB1-AS1 facilitates ox-LDL-induced damage of HCtAEC cells and the oxidative stress and inflammatory events of THP-1 cells via miR-942/HMGB1 signaling.

AIMS: The role of long noncoding RNA ZEB1 antisense 1 (lncRNA ZEB1-AS1) in carotid artery atherosclerosis remains barely explored. MATERIALS AND METHODS: The viability and apoptosis of HCtAEC cells were measured by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), Caspase-3 activity detection assay and flow cytometry. The oxidative stress status and inflammation of THP-1 cells were detected by oxidative stress indicator detection kit and Enzyme-linked immunosorbent assay (ELISA). The abundance of ZEB1-AS1, miR-942 and high-mobility group box 1 (HMGB1) was measured by quantitative real time polymerase chain reaction (qRT-PCR). The targets of ZEB1-AS1 and miR-942 in HCtAEC and THP-1 cells were predicted by DIANA tool, and the combination was confirmed by dual-luciferase reporter assay, RNA immunoprecipitation (RIP) assay and RNA-pull down assay. Western blot was conducted to examine the protein expression of HMGB1. KEY FINDINGS: ZEB1-AS1 promoted ox-LDL-mediated injury in HCtAEC and THP-1 cells. MiR-942 was a direct target of ZEB1-AS1, and it was negatively modulated by ZEB1-AS1 in HCtAEC and THP-1 cells. HMGB1 could bind to miR-942, and it was regulated by ZEB1-AS1/miR-942 axis in HCtAEC and THP-1 cells. HMGB1 overexpression or miR-942 depletion reversed the inhibitory effects of ZEB1-AS1 intervention on the injury and apoptosis of HCtAEC cells and the oxidative stress and inflammation of THP-1 cells. SIGNIFICANCE: LncRNA ZEB1-AS1 contributed to ox-LDL-mediated injury and apoptosis of HCtAEC cells and the oxidative stress and inflammation of THP-1 cells through up-regulating HMGB1 via sponging miR-942. ZEB1-AS1/miR-942/HMGB1 axis might provide a new direction to treatment carotid artery atherosclerosis.

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.