Gasdermin D Inhibitor Necrosulfonamide Alleviates Angiotensin II-Induced Abdominal Aortic Aneurysms in Apolipoprotein E-Deficient Mice.

Abdominal aortic aneurysm (AAA) is a chronic aortic disease that lacks effective pharmacological therapies. This study was performed to determine the influence of treatment with the gasdermin D inhibitor necrosulfonamide on experimental AAAs. AAAs were induced in male apolipoprotein E-deficient mice by subcutaneous angiotensin II infusion (1000 ng/kg body weight/min), with daily administration of necrosulfonamide (5 mg/kg body weight) or vehicle starting 3 days prior to angiotensin II infusion for 30 days. Necrosulfonamide treatment remarkably suppressed AAA enlargement, as indicated by reduced suprarenal maximal external diameter and surface area, and lowered the incidence and reduced the severity of experimental AAAs. Histologically, necrosulfonamide treatment attenuated medial elastin breaks, smooth muscle cell depletion, and aortic wall collagen deposition. Macrophages, CD4+ T cells, CD8+ T cells, and neovessels were reduced in the aneurysmal aortas of necrosulfonamide- as compared to vehicle-treated angiotensin II-infused mice. Atherosclerosis and intimal macrophages were also substantially reduced in suprarenal aortas from angiotensin II-infused mice following necrosulfonamide treatment. Additionally, the levels of serum interleukin-1ß and interleukin-18 were significantly lower in necrosulfonamide- than in vehicle-treated mice without affecting body weight gain, lipid levels, or blood pressure. Our findings indicate that necrosulfonamide reduced experimental AAAs by preserving aortic structural integrity as well as reducing mural leukocyte accumulation, neovessel formation, and systemic levels of interleukin-1ß and interleukin-18. Thus, pharmacologically inhibiting gasdermin D activity may lead to the establishment of nonsurgical therapies for clinical AAA disease.

Inflammatory markers and risk factors of RA patients with depression and application of different scales in judging depression.

To evaluate the association of inflammatory markers and depression in RA patients and the risk factors in RA with depression, a cross-sectional study was conducted in a cohort of RA patients from southern China.Two hundred-fifteen RA patients were enrolled. The demographic and disease-related characteristics were recorded and inflammatory markers in sera were measured. RA patients were guided to fill out PHQ-9 scale by themselves, the psychological state was evaluated by psychiatry experts and graded according to the HAMD-17 scale. The consistency of the two scales in judging depression was evaluated. RA with depression group had HAMD-17 scores greater than 7. The levels of CRP, ESR, fibrinogen, SAA, IL-2, IL-6, TNF-α, IFN-γ, IL-4, and IL-10 were measured and compared. Logistic regression analysis was performed to find the risk factors of RA with different depression levels. One hundred-five (48.84%) RA patients had HAMD-17 scores greater than 7. High consistency was found between HAMD-17 and PHQ-9 in predicting depression. RA patients with depression were more likely to have tender joints, lower income, no employment, higher disease activity, joint deformities and glucocorticoid treatment. The depressed RA patients had higher serum levels of IL-6, CRP, fibrinogen, and SAA. IL-6, CRP, fibrinogen, and SAA were positive correlated with depression in RA patients. PHQ-9 can replace HAMD-17 in clinical application to judge depression.

A Case of Bilateral Aortoiliac Aneurysm with Persistent Aneurysmal Sciatic Artery Treated by Endovascular Aneurysm Repair.

The femoral artery is the conventional access for endovascular abdominal aortic aneurysm repair (EVAR). Patients with an anomalous persistent sciatic artery (PSA) is usually at the expense of an atrophied femoral artery. Therefore, EVAR for patients with PSA anomalies is exceptionally challenging. We report the case of a 69-year-old man with an aortoiliac aneurysm and right PSA. Preoperative computed tomography angiography (CTA) revealed a tortuous infrarenal abdominal aortic aneurysm, bilateral common-internal iliac aneurysms, and a right aneurysmal PSA with an ipsilateral atrophic femoral and superficial femoral artery. The aortoiliac aneurysm was successfully repaired through an endovascular approach with access through the right persistent sciatic artery, bilateral femoral artery, and left brachial artery. One-month postoperation, CTA revealed a type 1 endoleak originating from the proximal end of the aorta graft. The second and third operations were performed to close the endoleak through extended proximal cuff with chimney bilateral renal stents and sac embolization with coils and fibrin glue at 1 and 14 months, respectively, after the first operation. CTA performed three months after the third operation did not show any endoleaks. A persistent sciatic artery can be used as an access for endovascular repair of a complicated infrarenal aortoiliac aneurysm combined with an anomalous persistent sciatic artery and an atrophied femoral artery.

Systematic review and meta-analysis of association of prophylactic cerebrospinal fluid drainage in preventing spinal cord ischemia after thoracic endovascular aortic repair.

OBJECTIVE: We conducted a systemic review and meta-analysis to compare the association between prophylactic cerebrospinal fluid drainage (CSFD) vs non-CSFD in preventing spinal cord ischemia (SCI) after thoracic endovascular aortic repair (TEVAR) for aneurysm and dissection. METHODS: The MEDLINE, Embase, and Cochrane databases were systematically searched to identify all relevant studies reported before April 1, 2020. A systematic review and meta-analysis were performed. We assessed the association between CSFD strategies, including routine CSFD vs selective CSFD or no CSFD, and the SCI rates after TEVAR for patients with aortic dissection (AD), solitary thoracic aortic aneurysm (TAA), or thoracoabdominal aortic aneurysm (TAAA). Subgroup analyses were conducted to assess the association between different aortic pathologies, including AD and thoracic aneurysms, and SCI rates after TEVAR with and without prophylactic CSFD. The data are presented as the pooled event rates (ERs) and 95% confidence intervals (CIs). RESULTS: A total of 34 studies of 3561 patients (2671 with TAA or TAAA and 890 with type B AD) were included in the present analysis. The data are presented as the pooled ERs and 95% CIs. The overall SCI rate for patients who had undergone TEVAR with prophylactic CSFD for AD (ER, 1.80%; 95% CI, 0.88%-2.72%) was significantly lower than that for the aortic aneurysm group (ER, 5.73%; 95% CI, 4.20%-7.27%; P < .0001). The SCI rate after TEVAR with prophylactic CSFD was not significantly different from that without CSFD for AD (P = .51). No association was found between the rates of SCI after TEVAR with routine prophylactic CSFD vs selective prophylactic CSFD for aortic aneurysms (P = .76) and AD (P = .70). The SCI rate after TEVAR without CSFD for aortic aneurysms, including isolated TAA and TAAA (ER, 3.49%; 95% CI, 0.23%-6.76%) was not significantly different from that for AD (ER, 3.20%; 95% CI, 0.00%-7.20%; P = .91). For the patients with TAAAs, the rate of SCI after TEVAR with routine prophylactic CSFD was significantly lower than that with selective prophylactic CSFD (P = .04). CONCLUSIONS: Our systematic review and meta-analysis has shown that SCI occurs more often after TEVAR for aortic aneurysms than for AD. Routine prophylactic CSFD, compared with selective CSFD, was associated with a lower rate of postoperative SCI after TEVAR for TAAAs. No significant association was found between the SCI rate and routine prophylactic CSFD for patients undergoing TEVAR for isolated TAA or AD.

Managing Emergent Surgery for Ruptured Abdominal Aortic Aneurysm during the COVID-19 Pandemic.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has become a global pandemic which may compromise the management of vascular emergencies. An uncompromised treatment for ruptured abdominal aortic aneurysm (rAAA) during such a health crisis represents a challenge. This study aimed to demonstrate the treatment outcomes of rAAA and the perioperative prevention of cross-infection under the COVID-19 pandemic. METHODS: In cases of rAAA during the pandemic, a perioperative workflow was applied to expedite coronavirus testing and avoid pre-operative delay, combined with a strategy for preventing cross-infection. Data of rAAA treated in 11 vascular centers between January-March 2020 collected retrospectively were compared to the corresponding period in 2018 and 2019. RESULTS: Eight, 12, and 14 rAAA patients were treated in 11 centers in January-March 2018, 2019, and 2020, respectively. An increased portion were treated at local hospitals with a comparable outcome compared with large centers in Guangzhou. With EVAR-first strategy, 85.7% patients with rAAA in 2020 underwent endovascular repair, similar to that in 2018 and 2019. The surgical outcomes during the pandemic were not inferior to that in 2018 and 2019. The average length of ICU stay was 1.8 ± 3.4 days in 2020, tending to be shorter than that in 2018 and 2019, whereas the length of hospital stay was similar among 3 years. The in-hospital mortality of 2018, 2019, and 2020 was 37.5%, 25.0%, and 14.3%, respectively. Three patients undergoing emergent surgeries were suspected of COVID-19, though turned out to be negative after surgery. CONCLUSIONS: Our experience for emergency management of rAAA and infection prevention for healthcare providers is effective in optimizing emergent surgical outcomes during the COVID-19 pandemic.

Comparative Effectiveness of Endovascular Treatment Modalities for De Novo Femoropopliteal Lesions: A Network Meta-analysis of Randomized Controlled Trials.

Purpose: To report the results of a network meta-analysis of randomized controlled trials (RCTs) comparing multiple endovascular treatments for de novo femoropopliteal lesions. Materials and Methods: The MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials databases were systematically searched on June 1, 2019, for prospective RCTs comparing 14 treatments [ie, atherectomy, brachytherapy, cryoplasty, cutting balloons, drug-coated balloons, bare nitinol stents, drug-eluting stents (DES), covered stents (CS), and combinations] in the treatment of de novo femoropopliteal lesions. Outcomes were technical success; binary restenosis and target lesion revascularization (TLR) at 6, 12, and/or 24 months; and all-cause mortality at 12 months. Ultimately, 53 articles reporting on 45 studies (91 study arms; 5565 patients) were selected. For the technical success outcome, all types of stents, all balloons, and all atherectomy devices were aggregated in stent, balloon, and atherectomy technology groups, respectively. Results: In terms of technical success for aggregated treatment types, stent technology was the most effective treatment and was better than balloon and atherectomy technologies. In terms of binary restenosis, DES was the most effective single treatment at the 6- and 12-month follow-up and CS at the 24-month follow-up. Both DES and CS were better than the majority of other single treatments, including balloon angioplasty, cutting balloon, cryoplasty, directional atherectomy, and bare nitinol stent during all follow-up periods. In terms of TLR, DES was the second most effective single treatment and the most effective single treatment at the 6- and 12-month follow-up intervals; CS was the most effective single treatment at the 24-month follow-up. Both DES and CS were better than the majority of other single treatments. The 12-month all-cause mortality of both DES and CS were similar to other treatments, whereas cryoplasty seemed to be the least effective treatment with regard to binary restenosis and TLR. Conclusion: Both DES and CS had substantial advantages in terms of restenosis and TLR in femoropopliteal lesions and were similar to aggregate stent technology in terms of technical success. DES performed better within 12 months after operation and CS at ~24 months, but neither had much advantage in terms of mortality. In contrast, cryoplasty seemed to be a less effective treatment.

Comparative Efficacy and Safety of Endovascular Treatment Modalities for Femoropopliteal Artery Lesions: A Network Meta-analysis of Randomized Controlled Trials.

PURPOSE: We conducted a network meta-analysis of randomized controlled trials comparing the efficacy and safety of multiple endovascular treatments for femoropopliteal lesions. METHODS: Nine treatments for femoropopliteal lesions were identified. We compared major amputation and all-cause mortality at 12-month follow-ups and primary patency at 6-, 12- and 24-month follow-ups of the treatments. RESULTS: Altogether, 26 studies (52 study arms; 4102 patients) were considered eligible. In terms of primary patency, drug-eluting stent (DES) placement was the most effective treatment at 6- and 12-month follow-ups and covered stent (CS) placement at 24-month follow-ups, whereas directional atherectomy (DA) was the least effective treatment during all follow-up periods; both DES and CS placements were better than the majority of other single treatments, including balloon angioplasty, DA, nitinol stent (NS) placement and drug-coated balloon use, during all follow-up periods. In terms of 12-month major amputation and all-cause mortality, DA was the most safe treatment, whereas NS placement was the least safe single treatment. CONCLUSIONS: DES and CS placements have shown encouraging results in terms of primary patency for femoropopliteal lesions, DES placement performs better within 12 months after operation and CS placement at approximately 24 months, while DA seems to be less effective. DA may be better than other treatments in terms of major amputation and all-cause mortality, while NS seems to be less safe.

A Network Meta-analysis of Randomized Controlled Trials Comparing Treatment Modalities for Infrapopliteal Lesions in Critical Limb Ischemia.

BACKGROUND: We aimed to conduct a network meta-analysis of randomized controlled trials comparing treatment modalities for infrapopliteal lesions in critical limb ischemia. METHODS: Five treatments for infrapopliteal lesions in critical limb ischemia were recognized. We compared primary patency, target lesion revascularization (TLR), major amputation at the 12-month follow-up, and technical success rate of the treatment modalities. RESULTS: Altogether, 11 studies (22 study arms; 1,330 patients) were considered eligible. The drug-eluting balloon (DEB) significantly increased primary patency compared with balloon angioplasty (BA; odds ratio [OR] 9.02, 95% confidence interval [CI] 3.18-25.55), the bare metal stent (BMS; OR 14.39, 95% CI 4.33-47.87), and the drug-eluting stent (DES; OR 3.70, 95% CI 1.20-11.11). The DES significantly increased primary patency compared with BA (OR 2.42, 95% CI 1.57-3.74) and BMS (OR 3.86, 95% CI 2.24-6.65). DES significantly increased the technical success rate compared with BA (OR 11.78, 95% CI 1.42-97.59). According to the value of the surface under the cumulative ranking curve (SUCRA), DEB was considered the best treatment in terms of primary patency (SUCRA = 99.7) and TLR (SUCRA = 70.7), and DES was considered the best treatment in terms of technical success rate (SUCRA = 90.6) and major amputation (SUCRA = 85.9). CONCLUSIONS: DEB has shown encouraging results in terms of primary patency for infrapopliteal lesions in critical limb ischemia; furthermore, DEB may be better than other treatments in terms of TLR. DES may be better than other treatments in terms of technical success and major amputation. In contrast, BA and BMS seem to be less effective treatment options.

HES1 Promotes Colorectal Cancer Cell Resistance To 5-Fu by Inducing Of EMT and ABC Transporter Proteins.

Background and Aim: Hairy enhancer of split-1 (HES1) is a downstream transcriptional factor of Notch signaling pathway, which was found to be related to chemoresistance. This study was aimed to investigate the role of HES1 in chemoresistance of colorectal cancer (CRC). Methods: Tissue microarray was used to analyze the clinical significance of HES1 in radical resected (R0) stage II/III CRC patients that received adjuvant chemotherapy. 5-fluorouracil (5-Fu) chemoresistance was examined in CRC cell lines (RKO and HCT8, LOVO) with stable over-expression and inhibition of HES1 gene by cytotoxicity test. Gene expression microarray was used to investigate the enriched pathways and different expressed of genes in cells with over-expressed HES1. Expression changes of the chemoresistance related genes were confirmed by qPCR and western blot analysis. Results: Stage II CRC patients with higher HES1 expression showed higher recurrence rate after chemotherapy. Colon cancer cell lines which over-expressed HES1 were more resistant to 5-Fu treatment in vitro. Gene expression microarray revealed that HES1 was related to the signaling pathways of epithelial-mesenchymal transition (EMT) and drug metabolism. Immunofluorescence assay showed HES1 over-expression lead to depressed E-cadherin and elevated N-cadherin. QPCR and western blot analysis confirmed that ABCC1, ABCC2 and P-gp1 were induced after HES1 over-expression. Conclusions: HES1 promotes chemoresistance to 5-Fu by prompting EMT and inducing of several ABC transporter genes. HES1 might be a novel therapeutic target in CRC treatment.

Protein/Polysaccharide Electrostatic Complexes and Their Applications in Stabilizing Oil-in-Water Emulsions.

Consumers are becoming increasingly fastidious in demanding food products with improved quality and functionality. This largely relies on rational design of food structures. As the two key food ingredients, protein and polysaccharides play important roles in food structuring. The combination of protein and polysaccharide provides rich opportunities for food structure and function designs through molecular interaction and assembly. This paper provides a brief review on the formation and characterization of protein/polysaccharide electrostatic complexes and their applications in stabilizing oil-in-water emulsions, particularly those containing polyunsaturated fatty acids.

R-Smad signaling-mediated VEGF expression coordinately regulates endothelial cell differentiation of rat mesenchymal stem cells.

A low-efficiency yield hinders the use of stem cells as a source of endothelial cells (ECs) for therapeutic vascularization, and the diversity of the transforming growth factor-ß (TGF-ß) superfamily has undermined understanding the effects of its potent vascularization-inducing. Herein, we studied the role of the TGF-ß superfamily in EC differentiation of rat bone marrow mesenchymal stem cells (MSCs) induced by Smad2/3 and Smad1/5/8 signaling. MSCs that had been sorted by flow cytometry as CD31-negative were cultured for 14 days in medium supplemented with vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) as the control. The Smad2/3 pathway was activated by TGF-ß1 and Smad1/5/8 by bone morphogenetic proteins (BMPs). In the early phase in the Smad2/3-activated group, there were 10% CD31-positive cells, which was significantly higher than in the control group. A low Smad1/5/8 phosphorylation level after BMP4 activation doubled the number of CD31-positive cells, while a higher phosphorylation level after BMP9 activation showed no effect. A Smad2/3 inhibitor initially blocked differentiation but later promoted it, while a Smad1/5/8 inhibitor reversed the induction observed with BMPs. Moreover, the positive effects of R-Smad on differentiation were weakened by the VEGF neutralizing antibody, and a Smad3 inhibitor decreased VEGF expression and blocked differentiation in both the early and late phases. In conclusion, differentiation of ECs from MSCs via Smad2/3 signaling is stage dependent. Activation, particularly by Smad3, significantly promotes differentiation at an early phase but later is suppressive. A low Smad1/5/8 phosphorylation level has a positive effect, and R-Smad effects are partly mediated by VEGF.