Objective To summarize the experience and effect of applying 3D printing to repair thoraco-abdominal aortic disease with fenestrated stent-graft or branch stent-graft technique.Methods From Oct 2017 to Sep 2018,22 patients with thoracic and abdominal aortic diseases,including aortic arterial dissection (9 patients) and aortic aneurysm (13 patients) were admitted.There were 19 males and 3 females,with mean age of (60 ± 13) years.Before the surgery 3D printing model guide plate was made according to CT,and then the pre-fenestrated stent-graft technique,branch stent-graft technique and other techniques were adopted in the surgery to perform endovascular repair.Resuits All of the operations were completed in one stage without open surgery.The average operation time was (5.67 ± l.23) hours without renal insufficiency and paraplegia,1 branch artery was lost during operation (1.4％) and 1 patient died (4.5％).Conclusion The application of 3D printing in the treatment of thoraco-abdominal aortic disease involving branches is more accurate than traditional measurement and localization.It had a safe and reliable short-term result.

RAS, a member of the small GTPase family, functions as a binary switch by shifting between inactive GDP-loaded and active GTP-loaded state. RAS gain-of-function mutations are one of the leading causes in human oncogenesis, accounting for ∼19% of the global cancer burden. As a well-recognized target in malignancy, RAS has been intensively studied in the past decades. Despite the sustained efforts, many failures occurred in the earlier exploration and resulted in an 'undruggable' feature of RAS proteins. Phosphorylation at several residues has been recently determined as regulators for wild-type and mutated RAS proteins. Therefore, the development of RAS inhibitors directly targeting the RAS mutants or towards upstream regulatory kinases supplies a novel direction for tackling the anti-RAS difficulties. A better understanding of RAS phosphorylation can contribute to future therapeutic strategies. In this review, we comprehensively summarized the current advances in RAS phosphorylation and provided mechanistic insights into the signaling transduction of associated pathways. Importantly, the preclinical and clinical success in developing anti-RAS drugs targeting the upstream kinases and potential directions of harnessing allostery to target RAS phosphorylation sites were also discussed.