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ObjectiveThis study aims to evaluate the feasibility, efficacy, and safety of a single-branched stent-graft with on-table fenestration for primary retrograde type A aortic dissection (RTAD) during thoracic endovascular aortic repair (TEVAR).Materials and methodsFrom January 2019 to December 2021, 36 patients with primary RTAD from five tertiary hospitals received medical management in the acute phase. They underwent TEVAR with a proximal zone 1 landing for aortic arch reconstruction in the subacute phase, using a fenestration technique on a single-branched stent-graft. Nearly 2 weeks after admission, computed tomography angiography (CTA) was re-examined to evaluate the thrombosis status of retrograde false lumen (FL). The primary outcomes were technical success, patency of the target branch arteries, and absence of type Ia endoleaks. The second outcomes were stent-graft-related complications and all-cause mortality.ResultsThe mean age was 56.2 ± 11.3 years, and 29 (80.6%) were male. After a median interval of 18.0 [interquartile range (IQR), 17.0–20.3] days of medical treatment, the partial and complete thrombosis of proximal FL rates increased to 52.8% and 47.2%, respectively. One patient (2.8%) experienced postoperative type Ia endoleaks, and was successfully re-treated using coli and Onyx glue. The median hospital stay was 20.5 (IQR, 18.0–23.0) days. The overall technical success rate was 100%. The median follow-up time was 31.5 (IQR, 29.8–34.0) months. There was one death (2.8%) due to gastrointestinal bleeding. Distal aortic segmental enlargement (DASE) occurred in two (5.6%) patients. No major complications or recurrent dissections in the proximal landing zone were recorded during follow up.ConclusionThe retrograde FL in primary RTAD could realize partial or complete thrombosis after medical management in the acute phase, and it might be regarded as a valid proximal landing zone for endovascular repair. The single-branched stent graft with on-table fenestration performed in the subacute phase may be feasible strategy in selective primary RTAD patients.

Cystic Fibrosis (CF) is a lethal autosomal recessive disease caused by mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR). The most common mutation is the deletion of phenylalanine residue at position 508 (ΔF508). Here we report the production of CFTR-ΔF508 rabbits by CRISPR/Cas9-mediated gene editing. After microinjection and embryo transfer, 77 kits were born, of which five carried the ΔF508 mutation. To confirm the germline transmission, one male ΔF508 founder was bred with two wild-type females and produced 16 F1 generation kits, of which six are heterozygous ΔF508/WT animals. Our work adds CFTR-ΔF508 rabbits to the toolbox of CF animal models for biomedical research.

The rabbit is a classic animal model for biomedical research, but the production of gene targeted transgenic rabbits had been extremely challenging until the recent advent of gene editing tools. More than fifty gene knockout or knock-in rabbit models have been reported in the past decade. Gene edited (GE) rabbit models, compared to their counterpart mouse models, may offer unique opportunities in translational biomedical research attributed primarily to their relatively large size and long lifespan. More importantly, GE rabbit models have been found to mimic several disease pathologies better than their mouse counterparts particularly in fields focused on genetically inherited diseases, cardiovascular diseases, ocular diseases, and others. In this review we present selected examples of research areas where GE rabbit models are expected to make immediate contributions to the understanding of the pathophysiology of human disease, and support the development of novel therapeutics.

Using the CRISPR/Cas9 gene-editing technology, we recently produced a number of rabbits with mutations in immune function genes, including FOXN1, PRKDC, RAG1, RAG2, and IL2RG. Seven founder knockout rabbits (F0) and three male IL2RG null (−/y) F1 animals demonstrated severe combined immunodeficiency (SCID), characterized by absence or pronounced hypoplasia of the thymus and splenic white pulp, and absence of immature and mature T and B-lymphocytes in peripheral blood. Complete blood count analysis showed severe leukopenia and lymphocytopenia accompanied by severe neutrophilia. Without prophylactic antibiotics, the SCID rabbits universally succumbed to lung infections following weaning. Pathology examination revealed severe heterophilic bronchopneumonia caused by Bordetella bronchiseptica in several animals, but a consistent feature of lung lesions in all animals was a severe interstitial pneumonia caused by Pneumocystis oryctolagi, as confirmed by histological examination and PCR analysis of Pneumocystis genes. The results of this study suggest that these SCID rabbits could serve as a useful model for human SCID to investigate the disease pathogenesis and the development of gene and drug therapies.