ABSTRACT
Th17 cells are powerful inflammation promoters in the pathogenesis of abdominal aortic aneurysms (AAAs). Myeloid-derived suppressor cells (MDSCs) can promote the differentiation of Th17 cells in chronic inflammatory autoimmune injury. Here, we aim to examine whether MDSCs regulate the differentiation of Th17 cells to participate in the development of AAA. We demonstrated an abnormal accumulation of MDSCs in AAA patients, which was positively associated with Th17 cells. We established angiotensin II-induced apolipoprotein E knockout mice and found the impaired immunosuppressive function of M-MDSCs. After systemic injection of anti-Gr-1 antibody in AAA mice to deplete circulating MDSCs, AAA formation and the differentiation of Th17 cells were abolished, and the overexpression of inducible T-cell costimulator (ICOS) on Th17 cells was reversed accordingly. Regulating the expression of ICOS ligand (ICOSL) on MDSCs affects the differentiation of Th17 cells. The adoptive transfer of ICOSLlowMDSCs in AAA mice inhibited the differentiation of Th17 cells and the development of AAA. Meanwhile, rIL-3 promoted the survival and immunosuppressive dysfunction of MDSCs, upregulated ICOSL expression on MDSCs by inhibiting activation of the PI3K/AKT signaling pathway, and regulated MDSCs to promote the differentiation of Th17 cells via the ICOSL-ICOS axis. An increase in serum IL-3, ICOSL+MDSCs, and ICOS+Th17 cells was detected in AAA patients, and IL-3 levels were positively correlated with the proportion of ICOSL+MDSC cells. In conclusion, we uncovered a pivotal role of MDSCs in promoting the differentiation of Th17 cells through the IL-3-ICOSL-ICOS axis during AAA, providing an important theoretical basis for understanding the pathogenesis of AAA.
ABSTRACT
OBJECTIVES: To evaluate the efficacy and clinical outcomes of accurate embolization of endoleaks after fenestrated thoracic endovascular aortic repair (F-TEVAR) for thoracic aortic dissections. METHODS: Twenty patients with endoleaks (17 type I and 3 type II) after fenestrated thoracic endovascular aortic repair (F-TEVAR) were embolized using detachable and ordinary coils. We assessed the success rate and complications of the operation, and its effects, through clinical and CT follow-up. RESULTS: The mean clinical follow-up duration was 25.68 ± 11.07 months (3-44 months). During follow-up, all endoleaks were completely embolized and aortic remodeling was improved. Secondary endoleaks occurred in four patients who were embolized twice. No other complications or death were reported. CONCLUSION: Embolization using detachable and ordinary coils is effective and safe for the treatment of endoleaks after fenestrated thoracic endovascular aortic repair.
ABSTRACT
Prostate cancer (PCa) is one of the most fatal diseases in male patients with high bone metastatic potential. Bone metastasis severely shortens overall survival and brings skeletal-related events (SREs) which reduces the life quality of patients, and this situation is currently regarded as irreversible and incurable. The progression and metastasis of PCa are found to be closely associated with inflammatory cytokines and chemokines. As pivotal members of inflammatory cytokines, Interleukin-1 (IL-1) family plays a crucial role in this process. Elevated expression of IL-1 family was detected in PCa patients with bone metastasis, and accumulating evidences proved that IL-1 family could exert vital effects on the progression and bone metastasis of many cancers, while some members have dual effects. In this review, we discuss the role of IL-1 family in the bone metastasis of PCa. Furthermore, we demonstrate that many members of IL-1 family could act as pivotal biomarkers to predict the clinical stage and prognosis of PCa patients. More importantly, we have elucidated the role of IL-1 family in the bone metastasis of PCa, which could provide potential targets for the treatment of PCa bone metastasis and probable directions for future research.
ABSTRACT
Accumulating evidence have proved the key role of long non-coding RNA in lung adenocarcinoma (LUAD) progression. Bioinformatics analysis is used to seek the differentially expressed lncRNA LINC01270 from TCGA database. The overexpression of LINC01270 was then verified in LUAD tumor tissues and cell lines by qRT-PCR. LINC01270 knockdown resulted in impaired cell proliferative and invasive ability via CCK-8 assay, EdU assay, colony formation assay, transwell assay, while aberrant upregulation of LINC01270 led to enhanced cell growth and invasion. Moreover, LINC01270 was found inhibiting miR-326 and thereby overexpressing the abundance of LARP1 to promote LUAD development via PI3K/AKT pathway. It was also proved that LINC01270 knockdown could suppress LUAD tumor growth in vivo. All of these findings demonstrate thatLINC01270 is a tumor promotor in LUAD via enhancing LARP1 expressed by sponging miR-326 to facilitate the development of LUAD. LINC01270 play a significant role in LUAD, which could serve as biomarkers for early diagnosis and a novel targeted remedy.
Subject(s)
Adenocarcinoma , Lung Neoplasms , MicroRNAs , RNA, Long Noncoding , Humans , MicroRNAs/genetics , MicroRNAs/metabolism , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , Cell Line, Tumor , Phosphatidylinositol 3-Kinases , Lung Neoplasms/pathology , Cell Proliferation/genetics , Lung/pathology , Adenocarcinoma/geneticsABSTRACT
OBJECTIVE: To evaluate the outcome of thoracic endovascular repair (TEVAR) for aortic arch pathologies with surgeon modified fenestrated stent grafts. METHODS: A multicentre, retrospective study consisting of consecutive patients from seven centres treated with surgeon modified fenestrated stent grafts for aortic arch pathologies was conducted. A technique to align fenestrations and supra-aortic vessels was applied. Rates of technical success, mortality, complications, and re-interventions were evaluated. RESULTS: Between February 2016 and January 2020, 513 consecutive patients with aortic arch pathologies received TEVAR with surgeon modified fenestrated stent grafts. The technical success rate was 98.6% (n = 506). In total, 626 fenestrations were created to revascularise 684 branch arteries of the aortic arch. There were 13 deaths and 15 re-interventions within 30 days of the operation. The estimated clinical success rate at 30 days was 94.4% (95% confidence interval [CI] 92.4 - 96.4), the estimated survival at 30 days was 97.5% (95% CI 96.1 - 98.9), and the estimated freedom from re-intervention at 30 days was 97.1% (95% CI 95.7 - 98.5). The median follow up was 27 (interquartile range 13 - 31) months. During follow up, there were five aortic related deaths, three non-aortic related deaths, and four deaths of unknown cause. Eighteen patients underwent re-intervention. The estimated clinical success rate at 24 months was 88.2% (95% CI 85.5 - 91.0), the estimated survival at 24 months was 94.9% (95% CI 92.7 - 97.1), and the estimated freedom from re-intervention at 24 months was 93.1% (95% CI 91.0 - 95.3). In total, 18 cases of stroke were recorded, including 12 within 30 days and six during follow up; six cases of retrograde type A aortic dissection were recorded, including five within 30 days and one during the follow up. CONCLUSION: TEVAR with surgeon modified fenestrated stent grafts for the treatment of aortic arch pathologies provides acceptable outcomes. Further follow up is required to confirm the benefits of this approach.
Subject(s)
Aorta, Thoracic , Aortic Diseases/surgery , Blood Vessel Prosthesis , Endovascular Procedures , Stents , Aged , Aortic Diseases/diagnosis , Aortic Diseases/mortality , China , Female , Humans , Male , Middle Aged , Prosthesis Design , Retrospective Studies , Survival Rate , Treatment OutcomeABSTRACT
BACKGROUND: A 63-year-old female was diagnosed with acute Stanford type A aortic dissection. The patient had pain in the chest and back for 1 wk. The computed tomography angiography (CTA) showed Stanford type A aortic dissection (Myla type III aortic arch). The intimal tear was located at the top of the aortic arch and retrograded to the ascending aorta. CASE SUMMARY: Preoperatively, a three-dimensional (3D)-printed model of the aortic arch was made according to CTA data. Then, under the guidance of the 3D-printed aortic model, a pre-fenestrated stent-graft was customized, and the diameter of the stent-graft was reduced intraoperatively by surgeons. 3D printing, triple pre-fenestration, and reduced diameter techniques were used during the surgery. The CTA examinations were performed at the 3rd mo and 1st year after the surgery; the results showed that the aortic dissection was repaired without endoleak, and all three branches of the aortic arch remained unobstructed. CONCLUSION: Applying the triple pre-fenestration technique for aortic arch lesions was feasible and minimally invasive in our case. The technique provides a new avenue for thoracic endovascular aortic repair of Stanford type A aortic dissection.
ABSTRACT
Acute aortic dissection (AAD) is one of the most common fatal diseases noted in vascular surgery. Human monocytes circulate in dynamic equilibrium and display a considerable heterogeneity. However, the role of monocytes in AAD remains elusive. In our recent study, we firstly obtained blood samples from 22 patients with Stanford type B AAD and 44 age-, sex-, and comorbidity-matched control subjects. And the monocyte proportions were evaluated by flow cytometry. Results showed that the percentage of total CD14+ monocytes in the blood samples of Stanford AAD patients was increased significantly compared with that of normal volunteers (P < 0.0005), and the absolute numbers of CD14brightCD16+ and CD14brightCD16- monocytes both increased significantly regardless of the percentage of PBMC or CD14+ cells, while CD14dimCD16+ monocytes displayed the opposite tendency. However, the percentage of CD14+ cells and its three subsets demonstrated no correlation with D-dimer (DD) and C-reactive protein (CRP). Then, blood mononuclear cell (PBMC) samples were collected by Ficoll density gradient centrifugation, followed with CD14+ magnetic bead sorting. After the purity of CD14+ cells was validated over 90%, AAD-related genes were concentrated in CD14+ monocytes. There were no significant differences observed with regard to the mRNA expression levels of MMP1 (P = 0.0946), MMP2 (P = 0.3941), MMP9 (P = 0.2919), IL-6 (P = 0.4223), and IL-10 (P = 0.3375) of the CD14+ monocytes in Stanford type B AAD patients compared with those of normal volunteers. The expression levels of IL-17 (P < 0.05) was higher in Stanford type B AAD patients, while the expression levels of TIMP1(P<0.05), TIMP2(P<0.01), TGF-ß1 (P < 0.01), SMAD3 (P < 0.01), ACTA2 (P < 0.001), and ADAMTS-1 (P < 0.001) decreased. The data suggested that monocytes might play an important role in the development of Stanford type B AAD. Understanding of the production, differentiation, and function of monocyte subsets might dictate future therapeutic avenues for Stanford type B AAD treatment and can aid the identification of novel biomarkers or potential therapeutic targets for decreasing inflammation in AAD.
Subject(s)
Aorta/pathology , Aortic Dissection/immunology , Monocytes/pathology , Acute Disease , Adult , Aged , Biomarkers , Female , Flow Cytometry , Humans , Immunomagnetic Separation , Interleukin-17/metabolism , Lipopolysaccharide Receptors/metabolism , Male , Middle AgedABSTRACT
Purpose: To summarize the experience and outcomes of total endovascular repair of thoracoabdominal aortic disease using 3-dimensional (3D) printed models to guide on-site creation of fenestrations in aortic stent-grafts. Materials and Methods: From April 2018 to March 2019, 34 patients (mean age 58±14 years; 24 men) with thoracoabdominal aortic disease were treated in our department. Nineteen patients had thoracoabdominal aortic dissection and 15 had thoracoabdominal aortic aneurysm. Preoperatively, a 3D printed model of the aorta was made according to computed tomography images. In the operating room, the main aortic stent-graft was completely released in the 3D printed model, and the position of each fenestration or branch was marked on the stent-graft. The fenestrations were then made using an electric pen. Wires were sewn to the edge of the fenestrations using nonabsorbable sutures. After customization, the aortic stent-graft was reloaded into the delivery sheath and deployed. Results: The printing process took ~5 hours (1 hour for image reconstruction, 3 hours for printing, and 1 hour for postprocessing). The physician-modified stent-grafts had a total of 107 fenestrations secured by 102 bridging stent-grafts, including 73 covered stents and 29 bare stents. The average procedure time was 5.6±1.2 hours, including a mean 1.3 hours for stent-graft customization. No renal insufficiency or paraplegia occurred. Two branch arteries were lost during the operation. One patient (3%) died 1 week after surgery from a retrograde dissection rupture. One patient developed a minor cerebral infarction postoperatively. The mean follow-up time was 8.5 months. There was 1 endoleak from a fenestration (coil embolized) and 4 distal ruptures of the aortic dissection (3 treated and 1 observed). Conclusion: Three-dimensional printing can be used to guide creation of fenestrated stent-grafts for the treatment of thoracoabdominal aortic diseases involving crucial branches. This technique appears to be more accurate than the traditional measurement method, with short-term follow-up demonstrating the safety and reliability of the method. However, further research and development are needed.
Subject(s)
Aortic Aneurysm, Abdominal/surgery , Aortic Aneurysm, Thoracic/surgery , Aortic Dissection/surgery , Blood Vessel Prosthesis Implantation/instrumentation , Blood Vessel Prosthesis , Computer-Aided Design , Endovascular Procedures/instrumentation , Printing, Three-Dimensional , Prosthesis Design , Stents , Adult , Aged , Aortic Dissection/diagnostic imaging , Aortic Dissection/physiopathology , Aortic Aneurysm, Abdominal/diagnostic imaging , Aortic Aneurysm, Abdominal/physiopathology , Aortic Aneurysm, Thoracic/diagnostic imaging , Aortic Aneurysm, Thoracic/physiopathology , Aortography , Blood Vessel Prosthesis Implantation/adverse effects , Computed Tomography Angiography , Endovascular Procedures/adverse effects , Female , Humans , Male , Middle Aged , Models, Anatomic , Models, Cardiovascular , Patient-Specific Modeling , Retrospective Studies , Time Factors , Treatment Outcome , WorkflowABSTRACT
BACKGROUND: A 46-year-old male underwent ascending aortic replacement, total arch replacement, and descending aortic stent implantation for Stanford type A aortic dissection in 2016. However, an intraoperative stent-graft was deployed in the false lumen inadvertently. This caused severe iatrogenic thoracic and abdominal aortic dissection, and the dissection involved many visceral arteries. CASE SUMMARY: The patient had pain in the chest and back for 1 mo. A computed tomography scan showed that the patient had secondary thoracic and abdominal aortic dissection. The ascending aortic replacement, total arch replacement, and descending aortic stent implantation for Stanford type A aortic dissection were performed 2 years prior. An intraoperative stent-graft was deployed in the false lumen. Endovascular aneurysm repair was performed to address this intractable situation. An occluder was used to occlude the proximal end of the true lumen, and a covered stent was used to direct blood flow back to the true lumen. A three-dimensional printing technique was used in this operation to guide pre-fenestration. The computed tomography scan at the 1stmo after surgery showed that the thoracic and abdominal aortic dissection was repaired, with all visceral arteries remaining patent. The patient did not develop renal failure or neurological complications after surgery. CONCLUSION: The total endovascular repair for false lumen stent-graft implantation was feasible and minimally invasive. Our procedures provided a new solution for stent-graft deployed in the false lumen, and other departments may be inspired by this case when they need to rescue a disastrous stent implantation.
ABSTRACT
BACKGROUND: The aim of this study was to summarize the experience and outcomes of total endovascular repair of aortic arch disease using three-dimensional (3D) printing to guide the application of modified prefenestrated/branched stent grafts. PATIENTS AND METHODS: From April 2018 to March 2019, 17 patients with aortic arch disease were treated in our department. Five patients had an aortic arch aneurysm and 12 had undergone an aortic arch dissection. Thirteen men and 4 were women, with an average age of 57.82 ± 10.47 years. Preoperatively, a 3D-printed model of the aorta was made according to computed tomography data. Then, under the guidance of the 3D-printed aortic model, modified prefenestrated/branched stent grafts were prepared, and the diameter of the stent grafts was reduced intraoperatively by a physician for total endovascular repair. Aortic computed tomography angiography was performed 3 and 6 months after the surgery. RESULTS: All procedures were completed in one stage with no conversions to sternotomy. Among all 17 patients, the operation was successful in 16. One patient was treated with a chimney graft and a stent graft fenestrated in situ because of distortion of the stent. The success rate of the technique was 94.18%. The average operation time was 4.18 ± 1.57 hr, and no patients died. No neurologic complications, such as cerebral infarction or paraplegia, were observed during the follow-up period. CONCLUSIONS: Three-Dimensional printing can be used to help guide the treatment of aortic arch disease using modified prefenestrated/branched stent grafts. This minimally invasive total treatment technique is accurate, allows quick recovery, and has a low complication rate. The short-term follow-up data show the safety and reliability of the method; however, further research and development are needed.