Circular RNA: A promising new star of vaccine.

Circular RNAs (circRNAs) are a class of single-stranded RNAs with covalently closed structures. Owing to their not having 3' or 5' ends, circRNAs are highly durable and insusceptible to exonuclease-mediated degradation. Moreover, some circRNAs with certain structures are translatable, making them novel vaccines. Vaccines are efficient tools for immunotherapy, such as for the prevention of infectious diseases and cancer treatment. The immune system is activated during immunotherapy to fight against abnormal allies or invaders. CircRNA vaccines represent a potential new avenue in the vaccine era. Recently, several circRNA vaccines have been synthesized and tested in vitro and in vivo. Our review briefly introduces the current understanding of the biology and function of translatable circRNAs, molecular biology, synthetic methods, delivery of circRNA, and current circRNA vaccines. We also discussed the challenges and future directions in the field by summarizing the developments in circRNA vaccines in the past few years.

Identification of A novel anoikis-related genes-based signature for non-small cell lung cancer.

The prognostic value of anoikis in NSCLC and its mechanism in tumorigenesis and progress have not been fully elucidated. This study aimed to reveal the correlation between anoikis-related genes (ARGs) and tumor prognosis, to reveal molecular and immune features, and to evaluate the anticancer drug sensitivity and the efficacy of immunotherapy of NSCLC. ARGs were selected from both the GeneCards and Harmonizome databases and then were intersected with the Cancer Genome Atlas (TCGA) database by differential expression analysis, followed by functional analysis of the target ARGs. An ARGs-based prognostic signature was constructed using LASSO (least absolute shrinkage and selection operator) Cox regression analysis; Kaplan-Meier analysis, univariant and multivariant Cox analysis were used to validate the value of this model in NSCLC prognosis. Differential analyses on molecular and immune landscapes were applied in the model. Anticancer drug sensitivity and efficacy in immune-checkpoint inhibitors (ICI) therapy were analyzed. A total of 509 ARGs and 168 differentially expressed ARGs in NSCLC were generated. Functional analysis revealed enrichment in extracolonic apoptotic signaling pathway, collagen-containing ECM, and integrin binding, and indicated an association with the PI3K-Akt signaling pathway. Subsequently, a 14-genes signature was generated. The high-risk group had a worse prognosis, with higherM0 and M2 macrophage infiltration, and fewer CD8 T-cells and T follicular helper (TFH) cells. The high-risk group had higher expression of immune checkpoint genes, HLA-I genes, and higher TIDE scores than the low-risk group, leading to less benefit of ICI therapy. Additionally, an Immunohistochemical staining comparison revealed that FADD was highly expressed in tumor tissue, compared to normal tissue, consistent with the previous results.

Angiosome-directed endovascular intervention and infrapopliteal disease: Intraoperative evaluation of distal hemodynamic changes and foot blood volume of lower extremity.

Objectives: To evaluate foot blood volume and hemodynamics and explore whether quantitative techniques can guide revascularization. Materials and methods: A prospective single-center cohort study included thirty-three patients with infrapopliteal artery occlusion who underwent percutaneous transluminal angioplasty (PTA) between November 2016 and May 2020. The time-to-peak (TTP) from color-coded quantitative digital subtraction angiography (CCQ-DSA) and parenchymal blood volume (PBV) were used to evaluate the blood volume and hemodynamic changes in different regions of the foot before and after the operation. Results: After the intervention procedure, the overall blood volume significantly increased from 25.15 ± 21.1 ml/1,000 ml to 72.33 ± 29.3 ml/1,000 ml (p < 0.001, with an average increase of 47.18 ml/1,000 ml. The overall TTP decrease rate, postoperative blood flow time significantly faster than those preoperatively, from 22.93 ± 7.83 to 14.85 ± 5.9 s (p < 0.001, with an average decrease of 8.08 s). Direct revascularization (DR) resulted in significant blood volume improvement than compared with indirect revascularization (IR) [188% (28, 320) vs.51% (10, 110), p = 0.029]. Patients with DR had a significantly faster blood flow time than those with IR [80% (12, 180) vs. 26% (5, 80), p = 0.032]. The ankle-brachial index (ABI) of the affected extremity also showed an significant change from 0.49 ± 0.3 to 0.63 ± 0.24 (p < 0.001) after the intervention. The relative values of ΔTTP and ΔABI showed a weak correlation (r = -0.330). Conclusions: The quantitative measurement results based on PBV and CCQ-DSA techniques showed that the overall blood volume increased significantly and that the foot distal hemodynamics were significantly improved after endovascular treatment. DR in the ischemic area could r improve foot perfusion.

Infrapopliteal endovascular intervention and the angiosome concept: intraoperative real-time assessment of foot regions' blood volume guides and improves direct revascularization.

OBJECTIVE: There is no consensus for determining which vessel should be revascularized in patients with multiple diseased infrapopliteal arteries. The angiosome concept may guide a more efficient targeted direct revascularization. Therefore, we conducted a study to assess whether the regional evaluation of foot blood volume may guide direct revascularization (DR) and if it will lead to better perfusion improvement than indirect revascularization (IR). METHODS: We performed a prospective single-center observational cohort study in patients treated in the Department of Vascular Surgery of Peking Union Medical College Hospital from November 2016 to April 2019. Twenty-seven patients treated with endovascular intervention were included. The intraoperative parenchymal blood volume of different foot regions was obtained for each patient using C-arm CT before and after intervention. RESULTS: The intervention procedure significantly increased the overall blood volume (48.95 versus 81.97 ml/1000 ml, p = 0.002). Patients with direct revascularization had a 197% blood volume increase while patients with indirect revascularization had a 39% increase (p = 0.028). The preoperative blood volume was higher in patients with mild symptoms than in patients with severe symptoms (58.20 versus 30.45 ml/1000 ml, p = 0.039). However, in regard to postoperative blood volume, no significant difference was discovered between these two groups (75.05 versus 95.01 ml/1000 ml, p = 0.275). CONCLUSION: Based on quantitative measurements, we conclude that overall blood volume can rise significantly after the intervention. Revascularizing the supplying vessel of the ischemic area directly will result in better perfusion improvement than restoring blood supply through the collateral circulation. Preoperative blood volume is associated with preoperative symptoms. KEY POINTS: • Flat panel detector CT can obtain intraoperative perfusion status and guide treatment in endovascular intervention. • Revascularizing the supplying vessel of the ischemic area directly will result in better perfusion improvement than restoring the blood supply through the collateral circulation. • Patients with severer clinical manifestations have lower blood volumes.

Long-term outcomes of conservative treatment and endovascular treatment in patients with symptomatic spontaneous isolated superior mesenteric artery dissection: a single-center experience.

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). CONCLUSIONS: For symptomatic SISMAD, endovascularly treated patients had a lower rate of symptom recurrence and a higher rate of SMA remodeling in the long term. Prospective, multi-center studies are needed to confirm the long-term outcomes of both treatments.

One-year results of drug-coated balloons for long and occlusive Femoropopliteal artery disease: a single-arm trial.

BACKGROUND: The performance of drug-coated balloons (DCBs) in femoropopliteal interventions has been proven through randomized trials in short lesions and lesions with relatively low proportion of occlusions. There is limited evidence of DCBs in long or occlusive lesions. This study is to investigate the efficacy of the paclitaxel-coated balloon for treatment of long and occlusive femoropopliteal arterial lesions. METHODS: A single-arm trial including 44 femoropopliteal lesions (chronic total occlusion (CTO) plus > 10 cm) treated with DCBs was performed to collect data of average 1-year follow-up. Endpoints contain primary patency, target lesion revascularization (TLR), amelioration of the Rutherford classification, change of ankle brachial index (ABI) and major adverse events. RESULTS: Technical success is 97.7% while device success is 100%. Mean lesion length was 186 ± 86.3 cm. Stent implantation was performed in 13.6%. Cumulative probability of primary patency was 78.8% ± 6.8% at 1 year while that of freedom from TLR was 91.4% ± 4.9%. Rutherford classification improved from average 3.3 ± 1.0 to 2.1 ± 1.4 (p < 0.001) at follow-up with a 72.7% amelioration rate. Ankle-branchial index changed from 0.33 ± 0.40 to 0.67 ± 0.37 (p = 0.002). No major adverse event was observed. CONCLUSION: These results suggest that it is safe and effective to treat long and totally occlusive femoropopliteal artery disease with DCBs. Further studies are demanded to confirm these results.