Tumor-induced, myeloid-derived suppressor cells (MDSCs)-mediated immune dysfunction is an important mechanism that leads to tumor immune escape and the inefficacy of cancer immunotherapy. Importantly, tumor-infiltrating MDSCs have much stronger ability compared to MDSCs in the periphery. However, the mechanisms that tumor microenvironment induces the accumulation and function of MDSCs are poorly understood. Here, we report that Interleukin-33 (IL-33) - a cytokine which can be abundantly released in tumor tissues both in 4T1-bearing mice and breast cancer patients, is crucial for facilitating the expansion of MDSCs. IL-33 in tumor microenvironment reduces the apoptosis and sustains the survival of MDSCs through induction of autocrine secretion of GM-CSF, which forms a positive amplifying loop for MDSC accumulation. This is in conjunction with IL-33-driven induction of arginase-1 expression and activation of NF-κB and MAPK signaling in MDSCs which augments their immunosuppressive ability, and histone modifications were involved in IL-33 signaling in MDSCs. In ST2 mice, the defect of IL-33 signaling in MDSCs attenuates the immunosuppressive and pro-tumoral capacity of MDSCs. Our results identify IL-33 as a critical mediator that contributes to the abnormal expansion and enhanced immunosuppressive function of MDSCs within tumor microenvironment, which can be potentially targeted to reverse MDSC-mediated tumor immune evasion.

MDR1 is highly expressed in MDR A2780DX5 ovarian cancer cells, MDR SGC7901R gastric cancer cells and recurrent tumours. It pumps cytoplasmic agents out of cells, leading to decreased drug accumulation in cells and making cancer cells susceptible to multidrug resistance. Here, we identified that miR‐495 was predicted to target ABCB1, which encodes protein MDR1. To reduce the drug efflux and reverse MDR in cancer cells, we overexpressed a miR‐495 mimic in SGC7901R and A2780DX cells and in transplanted MDR ovarian tumours in vivo. The results indicated that the expression of MDR1 in the above cells or tumours was suppressed and that subsequently the drug accumulation in the MDR cells was decreased, cell death was increased, and tumour growth was inhibited after treatment with taxol‐doxorubicin, demonstrating increased drug sensitivity. This study suggests that pre‐treatment with miR‐495 before chemotherapy could improve the curative effect on MDR1‐based MDR cancer.

WHAT THIS PAPER ADDS Endovascular treatment (EVT) has favourable short-term outcomes for spontaneous isolated dissection of the superior mesenteric artery (SIDSMA). However, evidence for this comes mainly from case reports and cohort studies with small patient numbers. This study, including 128 patients with up to five year follow up, showed that EVT was associated with a satisfactory superior mesenteric artery remodelling rate and stent patency. The cumulative event free survival rate in patients with stents was also superior to that in patents without stents, indicating that EVT could be an effective approach for SIDSMA.Objectives: Endovascular treatment (EVT) is an alternative method to treat spontaneous isolated dissection of the superior mesenteric artery (SIDSMA). Although its short-term results are promising, few mid-term results have been reported. This study reports the five year follow up of EVT for SIDSMA. Methods: A total of 128 consecutive patients with SIDSMA admitted to the study hospital between 2011 and 2016 were enrolled in this retrospective study. Their demographic information, clinical findings, EVT outcomes, and follow up results were analysed. Results: Conservative treatment and pre-operative preparation were given immediately after admission, then digital subtraction angiography was performed. Stents were deployed in 112 out of 128 patients. The 16 patients who did not receive stents then continued conservative treatment. Peri-procedural complications occurred in three patients, including one death and two pseudoaneurysms at puncture sites. Mean follow up was 29.7 months (range 6e60 months) in patients with stents and 31.4 months (range 14e45 months) in patients without stents. During follow up, the overall complete remodelling rate in the stent group was 88.3%. Most took place within three months of stenting. The cumulative primary stent patency rate was 99.1%, and the cumulative event free survival rate was 99.0%, 95.8%, and 95.8% at one, three, and five years in patients with stents, compared with 62.5% at both one and three years in patents without stents (p < .001). Conclusions: EVT for SIDSMA is clinically successful. The event free survival rate, primary patency, and complete remodelling are satisfactory during mid-term follow up. Endovascular treatment is an effective approach for SIDSMA.

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Background: Spontaneous isolated superior mesenteric artery dissection (SISMAD) is a rare vascular disorder, and the treatment strategies remain controversial. This study aimed to compare outcomes of conservative and endovascular treatments in symptomatic patients with SISMAD. Methods: Forty-two consecutive SISMAD patients who were admitted to a single center between October 2009 and May 2018 were enrolled in this study. Based on their symptoms, 15 had conservative treatment, and 27 had endovascular treatment. The baseline characteristics, treatments, and follow-up results of the conservative group and endovascular group were analysed. Results: The rates of symptom relief were 93.3% in the conservative group and 96.3% in the endovascular group. The procedure-related complications in the endovascular group included one case of pseudoaneurysm formation in the left brachial artery. During the follow-up period (median 28.5 months), a higher proportion of patients in the conservative group had symptom recurrence (42.9% in the conservative group versus 4.8% in the endovascular group, p < 0.001). Four patients in the conservative group and one patient in the endovascular group had additional endovascular intervention during follow-up. Compared with the conservative group, patients in the endovascular group had statistically significantly longer symptom-free survival (p = 0.014) and a higher rate of superior mesenteric artery (SMA) remodeling (p < 0.001).

Background: This study aimed to synthesize data from recently published literature to evaluate the safety and efficacy of endovascular treatment (EVT) for infrarenal aortic occlusion (IAO). Methods: The PubMed and Embase were searched to identify all studies reporting EVT for IAO from January 1st, 2000 to December 31st, 2017. Information about patients' characteristics, comorbidities, technical success, mortality, complications, and patency was collected and analyzed. Results: 9 articles consisting of 220 patients were included in this meta-analysis. Patients often had severe symptoms and many comorbidities. The overall technical success and periprocedural mortality was 95.64% (95% confidence interval [CI], 88.60%e99.42%) and 0.35% (95% CI, 0.00% to 2.33%). In successful cases, ankle-brachial index was raised from 0.42 to 0.91. The complication described in one article is of the whole samples and that of the technical success cases was not represented separately. We made the meta-analysis on the other 8 articles. Periprocedural complications included vascular complications (11.35% [95% CI: 3.50%e19.20%]) mainly pseudoaneurysm, thromboses, hematoma, and dissections; limb complications 8.28% (95% CI: 4.86%e13.77%); and renal complications 1.25% (95% CI: 0.00%e3.65%). In an article, vascular complications of whole samples were 12.24%, limb complication 6.12%, and renal complication 10.20%. Overall primary patency was 93.53% (95% CI: 89.37%e97.68%) at 1 year, 78.96% (95% CI: 72.26%e84.96%) at 3 years, and 75.31% (95% CI: 66.42%e84.20%) at 5 years. Overall secondary patency was 98.25% (95% CI: 95.50%e99.73%) at 1 year, 95.92% (95% CI: 89.25%e99.47%) at 3 years, and 94.02% (95% CI: 88.10%e98.00%) at 5 years. Conclusions: EVT for IAO is acceptable with relatively high technical success rate, low mortality, and satisfying short-term patency. Although primary patency was lower than after surgery, secondary patency was roughly similar to that of surgical repair. However, this conclusion is based on retrospective observational studies, and the results could be imprecise due to the limited sample sizes, especially in midterm and long-term patency. More studies with longer follow-up and bigger sample size are needed to further elucidate this. L.F. and Z.L. are contributed equally to this study. Conflict of interest: All authors have no relevant financial relationships to disclose.

Purpose: To report the findings of an in vitro experiment to evaluate the quality of needle fenestrations dilated by different size balloons in various stent-grafts and to investigate the differences between gradual and rapid dilation. Materials and Methods: Fenestrations were made using an 18-G needle in 5 different polyester or expanded polytetrafluoroethylene (ePTFE) stent-grafts: Relay, Valiant, Hercules, TAG, and Ankura. Each stent-graft received 2 groups of fenestrations: one was followed by gradual sequential dilation (4-, 6-, 8-, and 10-mm balloons) and the other by rapid dilation (4- and 10-mm balloons). The pressure was increased to 10 atmospheres or until the balloon was fully inflated with no waist. Quantitative and qualitative evaluations, including fenestration diameter, area, shape, and margins were conducted using light microscopy and scanning electron microscopy. Results: Relay had the strongest resistance to dilation and Ankura the slightest. The maximum length and area of holes expanded as the balloon diameter increased. The fenestrations in polyester devices were mostly elliptical or slit-like, with limited tears but extensive fibers visible in the margin, while ePTFE stent-grafts showed larger fenestration areas with clearer margins. Ankura showed the best quality of fenestrations, which were always circular or square without fabric tears, while the holes in the TAG were square or elliptical but sometimes had a slit after large balloon dilation (≥6 mm). The Relay, Valiant, Hercules, and Ankura devices showed no difference in maximum diameter, fenestration area, or scores of shape and margin (p>0.05). Rapid dilation in the TAG increased the rate of uncontrolled fabric tear, resulting in a larger final diameter (12.90 vs 10.82 mm, p=0.047), smaller area (30.46 vs 41.09 mm2, p=0.028), worse shape (0.75 vs 1.20, p=0.268), and worse margin (0.40 vs 1.00, p=0.174). Though the decreased fenestration shape and margin scores did not reach statistical significance, the trend for decline was more obvious than with the other devices. Conclusion: Materials and structures of the stent-grafts determine the quality of fenestrations dilated by different size balloons. The use of sequential vs rapid balloon dilation is also crucial for fashioning high-quality fenestrations and should be selected judiciously.

Objective: The majority of patients with COVID-19 showed mild symptoms. However, approximately 5% of them were critically ill and require intensive care unit admission for advanced life supports. Patients in the intensive care unit were high risk for venous thromboembolism and hemorrhage due to the immobility and anticoagulants used during advanced life supports. The aim of the study was to report the incidence and treatments of the two complications in such patients. Method: Patients with COVID-19 (Group 1) and patients with community-acquired pneumonia (Group 2) that required intensive care unit admission were enrolled in this retrospective study. Their demographics, laboratory results, ultrasound findings and complications such as venous thromboembolism and hemorrhage were collected and compared. Results: Thirty-four patients with COVID-19 and 51 patients with community-acquired pneumonia were included. The mean ages were 66 and 63 years in Groups 1 and 2, respectively. Venous thromboembolism was detected in 6 (18%) patients with COVID-19 and 18 (35%) patients with community-acquired pneumonia (P = 0.09). The major type was distal deep venous thrombosis. Twenty-one bleeding events occurred in 12 (35%) patients with COVID-19 and 5 bleeding events occurred in 5 (10%) patients with community-acquired pneumonia, respectively (P = 0.01). Gastrointestinal system was the most common source of bleeding. With the exception of one death due to intracranial bleeding, blood transfusion with or without surgical/endoscopic treatments was able to manage the bleeding in the remaining patients. Multivariable logistic regression showed increasing odds of hemorrhage with extracorporeal membrane oxygenation (odds ratio: 13.9, 95% confidence interval: 4.0–48.1) and COVID-19 (odds ratio: 4.7, 95% confidence interval: 1.2–17.9). Conclusion: Venous thromboembolism and hemorrhage were common in both groups. The predominant type of venous thromboembolism was distal deep venous thrombosis, which presented a low risk of progression. COVID-19 and extracorporeal membrane oxygenation were risk factors for hemorrhage. Blood transfusion with or without surgical/endoscopic treatments was able to manage it in most cases.