ET1 acts as a potential plasma biomarker and therapeutic target in deep venous thrombosis rat model.

Deep venous thrombosis (DVT) is the third leading cause of death in cardiovascular disease, following heart attacks and strokes. Early diagnosis and intervention are crucial for effective DVT therapy. We aim to investigate whether endothelin-1 (ET-1) could serve as an early diagnostic marker or a potential therapeutic target in a DVT rat model. CCK8 assay, invasion assay, and flow cytometry were used to detect the proliferation, migration and apoptosis of HUVECs, respectively. Elisa assay was used to detect ET-1 and coagulation factor VII in cell supernatant and rat?s plasma. Western blot was used to detect antioxidant signaling protein. Inferior vena cava stenosis was used to construct the DVT rat model. Lentivirus mediated overexpression of ET-1 in HUVECs impaired the cell proliferation and migration, increased cell apoptosis, inhibited the antioxidant signaling pathway proteins expression (e.g., NQO1, GCLC, Nrf-2), and upregulated coagulation factor VII. Furthermore, overexpression of ET-1 further impaired antioxidant signaling pathway protein in response to H2O2 treatment. However, lentivirus mediated ET-1 knockdown and BQ123 (an ET-1 inhibitor), showed the opposite results with ET-1 overexpression. We then established a DVT rat model by inferior vena cava stenosis. The stenosis induced early expression of ET-1 and coagulation factor VII in plasma at day 1 and restore their level at day 10. BQ123 could downregulate the coagulation factor VII to ameliorate the stenosis effects. Our findings suggest that ET-1 might serve as an early diagnostic marker for DVT rat model and a potential therapeutic target for treating DVT.

Study of cognitive function in patients with severe asymptomatic carotid artery stenosis by a computerized neuropsychological assessment device.

Background: Carotid stenosis can lead to stroke and cognitive impairment. Moreover, the cognitive function was assessed mostly by paper and pencil cognitive tests. This study aimed to evaluate the impact of severe asymptomatic carotid artery stenosis (SACAS) on cognitive function by a computerized neuropsychological assessment device (CNAD). The diagnostic value of screening SACAS of the CNAD was analyzed. Methods: There were 48 patients with ≥70% asymptomatic carotid stenosis and 52 controls without carotid stenosis. Duplex ultrasound defined the degree of stenosis. The differences of cognitive function were analyzed between patients and controls. The relationship of scores of cognitive tests and age were analyzed in the linear regression equation. The diagnostic value of CNAD was evaluated by the receiver operating characteristic (ROC) curve. Results: Stenosis and control subjects had no statistically significant differences in baseline characteristics. Stenosis patients had worse scores for Stroop color-word test (p = 0.002), one back test (p = 0.013), and identification test (p = 0.006) corresponding to attention and executive ability. The analysis of linear regression equation indicated that cognitive scores of stenosis patients declined faster with age, especially for digit span test, Stroop color-word test, one back test and identification test. In analysis of ROC curve, the Stroop color-word test (p = 0.002), one back test (p = 0.013), and identification test (p = 0.006), and comprehensive index of the three tests (p = 0.001) had the diagnostic value. Conclusion: The CNAD has evaluation value and screening value for patients with cognitive impairment and SACAS. But it is necessary to update the CNAD and conduct a study with a bigger sample.

Endovascular Repair Versus Open Surgical Repair for Complex Abdominal Aortic Aneurysms: A Systematic Review and Meta-Analysis.

BACKGROUND: The purpose of this systematic review and meta-analysis was to compare the short and long-term outcomes of endovascular repair (ER) versus open surgical repair (OSR) for complex abdominal aortic aneurysms (CAAAs), using propensity-matched and nonpropensity-matched methods. METHODS: PubMed, OVID, Embase, ELSEVIER and Cochrane library were searched for the studies that compared ER versus OSR for CAAAs from January 1999 to December 2020. CAAAs were defined as short neck, juxtarenal, pararenal and suprarenal abdominal aortic aneurysms. The primary outcomes were 30-day mortality, 30-day reintervention, medium and long-term survival. We pooled outcomes of original studies and also performed subgroup analyses using RevMan. The analysis of statistical heterogeneity was performed with STATA 16.0. RESULTS: A total of 21 studies with 12,049 patients (3847 ERs, 8202 OSRs) were included in this meta-analysis. In general, the patients undergoing ER were significantly older and likely to be man; more common with diabetes mellitus, congestive heart failure, renal failure, but smaller aortic aneurysms. In the nonpropensity-matched subgroup analysis of ER versus OSR, ER was associated with significantly decreased 30-day mortality (odds ratio [OR]: 0.60; 95% confidence interval [CI]: 0.49-0.74; P<0.001; I2 = 4%) and 30-day reintervention (OR: 0.59; 95% CI: 0.40-0.87; P = 0.007; I2 = 56%); lower rate of long-term survival (hazard ratio [HR]: 1.73; 95% CI: 1.21-2.47; P = 0.002; I2 = 0%); less perioperative comorbidities including myocardial infarction, arrhythmia, acute kidney injury, permanent dialysis, wound complications, bowel ischemia; and shorter hospital length of stay. In the propensity-matched subgroup, ER was associated with poorer long-term survival (HR: 1.80; 95% CI: 1.06-3.06; P = 0.03; I2 = 0%), higher incidences of lower extremity ischemia (OR: 12.25; 95% CI: 1.54-97.48; P = 0.02; I2 = 16%) and renal artery restenosis (OR: 7.63; 95% CI: 1.35-43.24; P = 0.02). However, there was no significant difference in 30-day mortality (OR: 1.31; 95% CI: 0.65-2.66; P = 0.45; I2 = 0%), 30-day reintervention (OR: 1.58; 95% CI: 0.62-4.03; P = 0.34; I2 = 26%), mid-term survival (HR: 1.03; 95% CI: 0.30-3.56; P = 0.96; I2 = 0%) between ER and OSR groups. CONCLUSIONS: Our analyses suggest that OSR of CAAAs, compared with ER, is associated with improved long-term survival without increasing of perioperative deaths. ER may be considered in the patients who are high-risk for open repair.

Fenestrated and Branched Stent-Grafts for the Treatment of Thoracoabdominal Aortic Aneurysms: A Systematic Review and Meta-Analysis.

Purpose: To investigate the safety and efficacy of total endovascular repair for thoracoabdominal aortic aneurysms (TAAAs) with fenestrated and branched stent-grafts. Methods: The MEDLINE, EMBASE, and Cochrane databases were searched between January 2001 and December 2021 to identify literature relevant to the use of fenestrated and branched endografts for the treatment of TAAAs. Studies with <4 cases and those on juxtarenal or pararenal aortic aneurysms were excluded. Meta-analyses were conducted to evaluate spinal cord ischemia (SCI), irreversible SCI, renal insufficiency, dialysis, endoleak, reintervention, target vessel patency, 30-day mortality and overall mortality. Fourteen studies comprising 1,114 patients (mean age 72.42 years, 847 men) were selected. The mean TAAA diameter was 67 mm. The Crawford TAAA classification was type I-III in 759 cases, type IV in 344 cases, and type V in 10 cases. Outcomes of the meta-analysis are reported as proportions and 95% confidence intervals (CIs). Results: The pooled rates for 30-day mortality and overall mortality were 6% and 18%, respectively. The pooled rate for technical success was 94% (95% CI, 93-96%), for SCI was 8% (95% CI, 7-10%), for irreversible SCI was 6% (95% CI, 4-7%), for reversible SCI was 5% (95% CI, 4-6%), for reversible SCI was 2% (95% CI, 2-3%), for renal insufficiency was 7% (95% CI, 5-10%), for dialysis was 3% (95% CI, 2-4%), for target vessel patency was 98% (95% CI, 97-99%), and for reintervention was 15% (95% CI, 9-24%). Conclusion: Fenestrated and branched endografts for the treatment of TAAAs are safe and effective with acceptable early results. Lifelong regular follow-up and additional prospective studies are necessary to substantiate whether this technique is valid.

Identification of proteins related with pemetrexed resistance by iTRAQ and PRM-based comparative proteomic analysis and exploration of IGF2BP2 and FOLR1 functions in non-small cell lung cancer cells.

Pemetrexed (PEM), a multi-target folate antagonist, has been extensively used for the treatment of non-small cell lung cancer (NSCLC). However, the therapeutic efficacy of PEM is limited by tumor resistance. In this project, iTRAQ and parallel reaction monitoring (PRM)-based LC-MS/MS comparative proteomic analysis was performed to identify protein determinants of PEM resistance in A549/PEM cells versus A549 parental cells. A total of 567 differentially expressed proteins (DEPs) were identified by iTRAQ analysis. The function and classification of DEPs were analyzed through GO and KEGG Pathway databases. Moreover, PRM analysis further validated the expression changes of 14 DEPs identified by iTRAQ analysis. Moreover, insulin-like growth factor (IGF) 2 mRNA-binding protein 2 (IGF2BP2) or folate receptor alpha (FOLR1) knockdown weakened PEM resistance, reduced cell viability and promoted cell apoptosis in A549/PEM cells. IGF2BP2 depletion inhibited cell migration, invasion and epithelial-mesenchymal transition (EMT), while FOLR1 loss had no much effect on cell migration, invasion and EMT in A549/PEM cells. Our study can provide a deep insight into molecular mechanisms of PEM resistance in NSCLC and contribute to the development of more effective therapeutic schedules. SIGNIFICANCE: Our study can provide deeper insight into molecular mechanisms of PEM resistance in NSCLC and contribute to the development of more effective therapeutic schedules.

The PVT1/miR-216b/Beclin-1 regulates cisplatin sensitivity of NSCLC cells via modulating autophagy and apoptosis.

PURPOSE: The efficacy of cisplatin-based chemotherapy remains an open question for chemo-resistance in non-small cell lung cancer (NSCLC). This study aimed to explore the role and mechanism of long noncoding RNA plasmacytoma variant translocation 1 (PVT1) in cisplatin sensitivity of NSCLC. METHODS: Paired tumor and adjacent tissues were collected from forty patients with NSCLC. The clinical value of PVT1 was investigated according to clinicopathological parameters of patients. Cisplatin-sensitive or -resistant cells (A549 or A549/DDP) were used for in vitro experiments. Cell viability, apoptosis, autophagy and animal experiments were conducted to investigate cisplatin sensitivity. The expressions of PVT1, microRNA-216b (miR-216b) and apoptosis- or autophagy-related proteins were measured by quantitative reverse transcription polymerase chain reaction (qRT-PCR) or western blot assay, respectively. Luciferase reporter assay and RNA immunoprecipitation (RIP) assay were conducted to probe the interaction between miR-216b and PVT1 or Beclin-1. RESULTS: PVT1 was highly expressed and associated with poor prognosis of NSCLC patients (*P < 0.05). PVT1 knockdown enhanced cisplatin-induced viability inhibition and apoptosis induction in A549/DDP cells, but addition of PVT1 caused an opposite effect in A549 cells (*P < 0.05, #P < 0.05). Moreover, accumulation of PVT1 facilitated autophagy of NSCLC cells and tumor growth in vivo (*P < 0.05, #P < 0.05). In addition, miR-216b interacted with PVT1 or Beclin-1. Beclin-1 reversed miR-216b-mediated effect on autophagy and apoptosis of NSCLC cells (*P < 0.05,#P < 0.05). Besides, Beclin-1 protein expression was regulated by PVT1 and miR-216b (*P < 0.05, #P < 0.05). CONCLUSIONS: PVT1 may function as a competing endogenous RNA for miR-216b to inhibit cisplatin sensitivity of NSCLC through regulating apoptosis and autophagy via miR-216b/Beclin-1 pathway, providing a novel target for improving chemo-therapy efficacy of NSCLC.

Iliac Aneurysms Treated with Endovascular Iliac Branch Device: A Systematic Review and Meta-analysis.

BACKGROUND: Iliac branch devices (IBDs) have been increasingly reported for treating aortoiliac aneurysms. However, there are still concerns regarding this device. The aim of this study was to evaluate the safety and outcomes of IBDs in treating aortoiliac aneurysms by performing a systematic review and meta-analysis. METHODS: The Medline, EMBASE, and Cochrane databases were systematically searched to identify studies on the management of aortoiliac aneurysms using IBDs. Studies were reviewed and selected using defined criteria by 2 independent investigators who abstracted data on the study characteristics, study quality, and outcomes. The extracted data were presented as a rate and converted through arcsine transformations. Individual studies were evaluated and analyzed for 7 outcomes, including technical success rate, 30-day mortality, 30-day patency, follow-up patency, endoleak rate, buttock claudication, and IBD-associated reintervention. The heterogeneity of the studies was determined using the chi-squared distribution-based Q test and quantified by I2 statistics. Meta-analyses were performed using both a random effects model and fixed effects model. RESULTS: Twenty-two studies with a total of 1064 patients met the inclusion criteria and were selected for analysis. The pooled technical success rate of IBD was 93% (95% confidence interval [CI]: 91-95%). After patients were treated with the IBD, the 30-day mortality rate was 2% (95% CI, 1-4%), 30-day patency rate was 93% (95% CI, 91-94%), follow-up patency was 86% (95% CI, 84-88%), endoleak rate was 12% (95% CI, 8-17%), buttock claudication rate was 6% (95% CI, 5-8%), and IBD-associated reintervention rate was 11% (95% CI, 8-14%). CONCLUSIONS: Our study demonstrates that treating aortoiliac aneurysm with IBD produces satisfactory outcomes in midterm follow-up.

Endovascular Chimney Technique for Aortic Arch Pathologies Treatment: A Systematic Review and Meta-Analysis.

BACKGROUND: Endovascular chimney technique has been increasingly reported in treating aortic arch pathologies. However, there are still concerns about this technique. The aim of this study is to evaluate the safety and outcome of this technique by performing a systematic review and meta-analysis. METHODS: Medline, EMBASE, and Cochrane databases were systematically searched to identify studies on the management of aortic arch pathologies using chimney technique. Studies were reviewed and selected using a priori defined criteria by 2 independent observers who abstracted data on study characteristics, study quality, and outcomes. The extracted data were presented as rate and were converted through arcsine transformations. Individual studies were evaluated and analyzed for 5 ending factors such as technical success, 30-day mortality, patency, perioperative endoleak, and stroke. Heterogeneity of the studies was determined using the chi-square distribution-based Q test and quantified by I2 statistics. The meta-analyses were performed using both random effects model and fixed-effect model. RESULTS: Twelve studies with a total of 379 patients met the inclusion criteria. The pooled technical success rate of chimney technique was 91% (95% confidence interval [CI]: 87-94%). After patients were treated with chimney technique, the rate of 30-day mortality was 4% (95% CI: 2-7%), the rate of patency was 93% (95% CI: 89-96%), the rate of perioperative endoleak was 21% (95% CI: 17-26%), and the rate of stroke was 5% (95% CI: 3-8%). CONCLUSIONS: This study indicates that using chimney technique for treating aortic arch pathologies produced satisfied midterm outcomes in both elective and emergent situations.

Successful use of retrograde branched extension limb assembling technique in endovascular repair of pararenal abdominal aortic aneurysm.

Surgeon-modified retrograde branched extension limb assembling technique and bridged endografts were successfully used to exclude an asymptomatic pararenal abdominal aortic aneurysm and to reconstruct the superior mesenteric artery and bilateral renal arteries in a case with high-grade celiac artery stenosis, nondilated aorta above the superior mesenteric artery, and large lumen below the renal arteries. In patient-specific models for hemodynamics analysis, enhanced flow diversion to visceral arteries up to 6-month follow-up confirmed treatment feasibility; however, endograft configurations could be improved to avoid sharp corners at bifurcations, thereby ensuring smooth flow transport and possibly reducing risk for endograft narrowing or the development of thrombosis.

Multibranched Stent-Grafts for the Treatment of Thoracoabdominal Aortic Aneurysms: A Systematic Review and Meta-analysis.

PURPOSE: To evaluate the available literature on endovascular repair of thoracoabdominal (TAAA) and pararenal aortic aneurysms (PRAA) using multibranched stent-grafts. METHODS: MEDLINE, EMBASE, and Cochrane databases were searched between January 2001 and June 2015 to identify articles related to the use of multibranched stent-grafts for the treatment of TAAA and PRAA. Articles with <4 cases and those on juxtarenal aortic aneurysms were excluded. Meta-analyses were conducted to evaluate 30-day mortality, all-cause mortality, spinal cord ischemia, renal insufficiency, endoleak, target vessel patency, and reintervention. Of 370 articles screened, only 4 articles encompassing 185 patients (mean age 71.1 years; 137 men) were aligned with the inclusion criteria. There were 23 PRAAs; the mean aneurysm diameter was 64.5 mm. The Crawford TAAA classification was 10 type I, 47 type II, 37 type III, 58 type IV, and 9 type V; there was 1 Stanford type B dissection in association with a large TAAA. Results of the meta-analyses are reported as proportions and 95% confidence interval (CI). RESULTS: Pooled analysis indicated a technical success rate of 98.9%. As study heterogeneity was significant, random effects models were used for meta-analysis. The rate for 30-day mortality was 9% (95% CI 3% to 19%), for all-cause mortality 27% (95% CI 17% to 38%), endoleaks 10% (95% CI 1% to 25%), target vessel patency 98% (95% CI 95% to 99%), SCI 17% (95% CI 1% to 26%), irreversible SCI 6% (95% CI 3% to 10%), renal insufficiency 15% (95% CI 0.8% to 41%), and reinterventions 21% (95% CI 4% to 47%). CONCLUSION: Use of multibranched stent-grafts in the treatment of TAAAs and PRAAs appears to be feasible and safe based on satisfactory early outcomes in the limited literature available to date. Long-term surveillance and further studies are essential to determine the durability of this technique.

Experience With Fenestrated Endovascular Repair of Juxtarenal Abdominal Aortic Aneurysms at a Single Center.

UNLABELLED: To present the early and mid-term results of fenestrated endovascular aneurysm repair (FEVAR) using the Zenith fenestrated device for juxtarenal abdominal aortic aneurysms (JAAAs) at our center in China. DESIGN: Retrospective study.The study included 15 male patients with JAAAs, who underwent FEVAR using the Zenith fenestrated device at our center between February 2011 and June 2015.All custom-made Zenith fenestrated devices were designed according to computed tomography angiography (CTA) images obtained preoperatively. The patients with renal insufficiency underwent duplex ultrasonography, while the patients with normal renal function underwent 3 CT data acquisitions including nonenhanced CT, arterial phase, and venous phase. These examinations and blood examinations were completed at 3, 6, and 12 months after discharge, and annually thereafter.The mean age of the patients was 73.13 ±â€Š9.06 years (range, 57-86 years), and the median follow-up period was 30 months (8-52 months). Small fenestrations were used in 27 renal arteries, scallops were used in 7 superior mesenteric arteries (SMAs) and 2 renal arteries, and large fenestrations were used in 2 SMAs. Conversion to an open procedure was not required in any of the patients, and the technical success rate was 100%. The mean length of hospital stay was 11.33 ±â€Š2.02 days (7-15 days). No patient died within the 1st 30 days after the operation. One patient had a type Ia endoleak, which disappeared at 6 months after the operation, 1 patient had a type Ib endoleak, which was detected at 17 months after the operation, and 2 patients had type II endoleaks. One patient died at 17 months and another patient died at 30 months after the operation. Therefore, the all-cause mortality rate was 13.33% (2/15). The target vessel patency rate was 100% without occlusion.The early and mid-term results of FEVAR using the Zenith fenestrated device were good, demonstrating that this procedure is effective for the treatment of JAAAs.

Fenestrated and Chimney Technique for Juxtarenal Aortic Aneurysm: A Systematic Review and Pooled Data Analysis.

Juxtarenal aortic aneurysms (JAA) account for approximately 15% of abdominal aortic aneurysms. Fenestrated endovascular aneurysm repair (FEVAR) and chimney endovascular aneurysm repair (CH-EVAR) are both effective methods to treat JAAs, but the comparative effectiveness of these treatment modalities is unclear. We searched the PubMed, Medline, Embase, and Cochrane databases to identify English language articles published between January 2005 and September 2013 on management of JAA with fenestrated and chimney techniques to conduct a systematic review to compare outcomes of patients with juxtarenal aortic aneurysm (JAA) treated with the two techniques. We compared nine F-EVAR cohort studies including 542 JAA patients and 8 CH-EVAR cohorts with 158 JAA patients regarding techniques success rates, 30-day mortality, late mortality, endoleak events and secondary intervention rates. The results of this systematic review indicate that both fenestrated and chimney techniques are attractive options for JAAs treatment with encouraging early and mid-term outcomes.

[Research progress of peripheral applications of drug-eluting stent].

In-stent restenosis severely reduces the long-term patency rate after stent implantation, but drug-eluting stent may be possible to solve this problem. This paper mainly from two aspects of the mechanism of in-stent restenosis and clinical trials to state progress in research of drug-eluting stent in the applications of peripheral artery disease.