Early-start antiplatelet therapy after operation in patients with spontaneous intracerebral hemorrhage and high risk of ischemic events (E-start):Protocol for a multi-centered, prospective, open-label, blinded endpoint randomized controlled trial

BACKGROUND: For severe spontaneous intracerebral hemorrhage (sSICH) patients with high risk of ischemic events, the incidence of postoperative major cardiovascular/cerebrovascular and peripheral vascular events (MACCPE) is notable. Although antiplatelet therapy is a potential way to benefit these patients, the severe hemorrhagic complications, e.g., intracranial re-hemorrhage, is a barrier for early starting antiplatelet therapy. OBJECTIVES: This randomized controlled trial aims to identify the benefit and safety of early starting antiplatelet therapy after operation for sSICH patients with high risk of ischemic events. METHODS: This study is a multicenter, prospective, randomized, open-label, blinded-endpoint trial. We will enroll 250 sSICH patients with a high risk of ischemic events (including cerebral infarcts, transient ischemic attack, myocardial infarction, pulmonary embolism, and deep venous thrombosis). The participants will be randomized in a 1:1 manner to early-start group (start antiplatelet therapy at 3 days after operation) and normal-start group (start antiplatelet therapy at 30 days after operation). The early-start group will receive aspirin 100 mg daily. The control group will not receive antithrombotic therapy until 30 days after operation. The efficacy endpoint is the incidence of MACCPE, and the safety endpoint is the incidence of intracranial re-hemorrhage. DISCUSSION: The Early-Start antiplatelet therapy after operation in patients with spontaneous intracerebral hemorrhage trial (E-start) is the first randomized trial about early start antiplatelet therapy for operated sSICH patients with a high risk of ischemic events. This study will provide a new strategy and evidence for postoperative management in the future. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, identifier NCT04820972; Available at: https://clinicaltrials.gov/ct2/show/NCT04820972?term=NCT04820972&draw=2&rank=1. Chinese Clinical Trial Registry, identifier ChiCTR2100044560; Available at: http://www.chictr.org.cn/showproj.aspx?proj=123277

Preparation of fluorescent thermoplastic polyurethane microcellular foam films blown by supercritical CO2

Preparation of fluorescent thermoplastic polyurethane microcellular foam films blown by supercritical CO

Improved expansion ratio and heat resistance of microcellular poly(L-lactide) foam via in-situ formation of stereocomplex crystallites

It is critical to broaden the applications of poly(L-lactic acid) foams by improving heat resistance properties. The stereocomplex crystallites that are formed by melt blending of poly(L-lactic acid)/polylactide possess high melting point of about 220? and thus exhibit high heat resistance; therefore, the introduction of stereocomplex crystallites tends to improve the thermal stability of poly(lactic acid) foam. Unfortunately, using the solid-state foaming method, it was found that the expansion ratio of the obtained poly(lactic acid) foams was compromised with the value of 1.7 times once the stereocomplex crystallites were formed during the sample saturation stage. In this study, by applying a high compression molding temperature of 230?, the as-prepared poly(L-lactic acid) and poly(L-lactic acid)/polylactide blends were amorphous. After being CO2 saturated at a mild condition, the specimens were foamed at 90-160?. The wide-angle X-ray diffraction profiles presented that the stereocomplex crystallites and PLA homocrystals were in-situ generated during the foaming process. It is observed that the in-situ formed stereocomplex crystallites could act as the physical cross-linking agent to stabilize the nucleated bubbles and suppress cell coalescence, resulting in the increased expansion ratio (with value of about 23.6-25.6 times) and cell density, especially at high foaming temperatures and extended foaming time. Furthermore, the in-situ formed stereocomplex crystallites during the foaming increased the heat resistance performance of poly(L-lactic acid) foams. This novel crystallization control method helps us to find a balance point in preparing poly(L-lactic acid) foam with high expansion ratio, well-defined cell structure and high heat resistance performance

Efficient Modulation of Exon Skipping via Antisense Circular RNAs

Splice-switching antisense oligonucleotides (ASOs) and engineered U7 small nuclear ribonucleoprotein (U7 Sm OPT) are the most commonly used methods for exon skipping. However, challenges remain, such as limited organ delivery and repeated dosing for ASOs and unknown risks of by-products produced by U7 Sm OPT. Here, we showed that antisense circular RNAs (AS-circRNAs) can effectively mediate exon skipping in both minigene and endogenous transcripts. We also showed a relatively higher exon skipping efficiency at the tested Dmd minigene than U7 Sm OPT. AS-circRNA specifically targets the precursor mRNA splicing without off-target effects. Moreover, AS-circRNAs with adeno-associated virus (AAV) delivery corrected the open reading frame and restored the dystrophin expression in a mouse model of Duchenne muscular dystrophy. In conclusion, we develop an alternative method for regulating RNA splicing, which might be served as a novel tool for genetic disease treatment