Study of biodegradable occluder of atrial septal defect in a porcine model.

OBJECTIVE: To evaluate the safety and feasibility of a modified poly(l-lactic acid) (PLLA) atrial septal defect (ASD) occluder. METHODS: Forty-five piglets were divided into two groups: an experimental group (n = 27) and a control group (n = 18). The experimental group underwent percutaneous implantation of a modified PLLA ASD device while the control group underwent percutaneous implantation of a widely used metal ASD device. X-ray imaging, transthoracic echocardiography (TTE), electrocardiogram (ECG), histopathology and electron microscopic examination were performed at 7 days, 1, 3, 6, and 12 months after implantation. RESULTS: Twenty-seven experimental piglets and 18 control piglets were all successfully implanted with modified biodegradable and metal ASD devices, respectively. While both devices exhibited very good occluding effects, the modified PLLA ASD devices were completely endothelialized at 3 months after implantation, and the endothelialization appeared to be more complete compared to the control group. Degradation of the PLLA devices was noted at 12 months follow-up with no loss of integrity at the atrial septum. CONCLUSION: This animal model with implanting of the occluders was effective and not associated with complications. The modified PLLA ASD devices are more controllable and practical than our previous devices. The implanted devices demonstrated good endothelialization and degradability in short and moderate term follow-up. Long-term studies are now underway to further evaluate the biodegradability of this novel device.

Long-term efficacy, safety and biocompatibility of a novel sirolimus eluting iron bioresorbable scaffold in a porcine model.

Iron is considered as an attractive alternative material for bioresorbable scaffolds (BRS). The sirolimus eluting iron bioresorbable scaffold (IBS), developed by Biotyx Medical (Shenzhen, China), is the only iron-based BRS with an ultrathin-wall design. The study aims to investigate the long-term efficacy, safety, biocompatibility, and lumen changes during the biodegradation process of the IBS in a porcine model. A total of 90 IBSs and 70 cobalt-chromium everolimus eluting stents (EES) were randomly implanted into nonatherosclerotic coronary artery of healthy mini swine. The multimodality assessments including coronary angiography, optical coherence tomography, micro-computed tomography, magnetic resonance imaging, real-time polymerase chain reaction (PCR), and histopathological evaluations, were performed at different time points. There was no statistical difference in area stenosis between IBS group and EES group at 6 months, 1year, 2 years and 5 years. Although the scaffolded vessels narrowed at 9 months, expansive remodeling with increased mean lumen area was found at 3 and 5 years. The IBS struts remained intact at 6 months, and the corrosion was detectable at 9 months. At 5 years, the iron struts were completely degraded and absorbed in situ, without in-scaffold restenosis or thrombosis, lumen collapse, aneurysm formation, and chronic inflammation. No local or systemic toxicity and abnormal histopathologic manifestation were found in all experiments. Results from real-time PCR indicated that no sign of iron overload was reported in scaffolded segments. Therefore, the IBS shows comparable efficacy, safety, and biocompatibility with EES, and late lumen enlargement is considered as a unique feature in the IBS-implanted vessels.

One-stage resection of four genotypes of bilateral multiple primary lung adenocarcinoma: A case report.

BACKGROUND: The incidence of multiple primary lung cancer (MPLC) in China is 0.52%-2.45%. Most primary lung cancer cases have reported two lesions or three in rare cases. We report a rare case of bilateral simultaneous multiple primary lung adenocarcinoma of four different genotypes. CASE SUMMARY: A 58-year-old woman was admitted to our hospital on June 29, 2021, and upon physical examination, four multiple pulmonary nodules were identified in both lungs. Further computed tomography (CT) images revealed the presence of ground glass nodules, predicted to be high-risk cancer lesions by artificial intelligence. With the guidance of three-dimensional reconstruction of preoperative CT images, the nodules were resected under thoracoscopy. Postoperative pathological investigation revealed that the nodule types were adenocarcinoma in situ, invasive alveolar adenocarcinoma, and microinvasive adenocarcinoma. The excised nodules were further sequenced using high-throughput sequencing (semiconductor sequencing method) of 26 lung cancer genes to confirm that the four lesions were not homologous. The patient was discharged on postoperative day 8, that is, on July 15, 2021. One month later, she returned to the hospital for follow-up and reexamination. Chest CT examination showed that she had recovered well, and no obvious exudation and effusion were found in both pleural cavities. Evaluation of postoperative pulmonary function showed that her forced vital capacity was 1.40 L (preoperative value, 2.27 L) and forced expiratory volume was 1.24 L (preoperative value, 2.23 L). CONCLUSION: The surgical plan for multiple pulmonary nodules should be carefully considered. For carefully selected patients with concurrently occurring multiple lung nodules in both lungs, sublobectomy is a safe and feasible plan for concurrent bilateral resection of the lesions. Genetic sequencing is necessary for MPLC diagnosis and treatment.

Long-term safety and absorption assessment of a novel bioresorbable nitrided iron scaffold in porcine coronary artery.

This study aimed to investigate the long-term biocompatibility, safety, and degradation of the ultrathin nitrided iron bioresorbable scaffold (BRS) in vivo, encompassing the whole process of bioresorption in porcine coronary arteries. Fifty-two nitrided iron scaffolds (strut thickness of 70 µm) and 28 Vision Co-Cr stents were randomly implanted into coronary arteries of healthy mini-swine. The efficacy and safety of the nitrided iron scaffold were comparable with those of the Vision stentwithin 52 weeks after implantation. In addition, the long-term biocompatibility, safety, and bioresorption of the nitrided iron scaffold were evaluated by coronary angiography, optical coherence tomography, micro-computed tomography, scanning electron microscopy, energy dispersive spectrometry and histopathological evaluations at 4, 12, 26, 52 weeks and even at 7 years after implantation. In particular, a large number of struts were almost completely absorbed in situ at 7 years follow-up, which were first illustrated in this study. The lymphatic drainage pathway might serve as the potential clearance way of iron and its corrosion products.

[Role of Rac1 activation in platelet derived growth factor-BB induced proliferation and migration in rat aortic smooth muscle cells].

OBJECTIVE: To explore the impact of Rac1 activation on the proliferation and migration under the stimulation of PDGF-BB (platelet derived growth factor-BB). METHODS: The inhibitory effects of Rac1 inhibitor (NSC23766) and Rac1siRNA on the proliferation and migration of vascular smooth muscle cell under the stimulation of PDGF-BB were measured by CCK8 assay and Transwell chamber. The time characteristics of Rac1 activity and pi-JNK expression under the stimulation of PDGF-BB was detected by GST pulldown assay and Western blot. And the inhibitory effects of NSC23766 and Rac1siRNA on the Rac1 activation and pi-JNK expression were also measured. RESULTS: Migration and proliferation of vascular smooth muscle cell increased significantly after the stimulation of PDGF-BB (50 µg/L). Migration and proliferation was inhibited significantly after a pretreatment of Rac1siRNA and various concentrations of NSC23766 (25, 50, 100 µg/L). After the stimulation of PDGF-BB, the expression of pi-JNK and Rac1 activity increased over time. Rac1-GTP peaked at 5 minutes and pi-JNK at 15 minute. The expressions of pi-JNK at 15 minutes and Rac1-GTP at 5 minutes were inhibited significantly by Rac1siRNA and NSC23766 in a concentration-dependent manner. CONCLUSION: JNK phosphorylation is controlled by Rac1 activation. And Rac1 activation play a pivotal role in the migration and proliferation of aortic smooth muscle cell under the stimulation of PDGF-BB.

Safety and efficacy of nano lamellar TiN coatings on nitinol atrial septal defect occluders in vivo.

Atrial septal defect (ASD) occlusion devices made of nickel-titanium (NiTi) have a major shortcoming in that they release nickel into the body. We modified NiTi occluders using Arc Ion Plating technology. Nano lamellar titanium-nitrogen (TiN) coatings were formed on the surfaces of the occluders. The safety and efficacy of the modified NiTi occluders were evaluated in animal model. The results showed that 38 out of 39 rams (97%) survived at the end of the experiment. Fibrous capsules formed on the surfaces of the devices. Gradual endothelialization took place through the attachment of endothelial progenitor cells from the blood and the migration of endothelial cells from adjacent endocardium. The neo-endocardium formed more quickly in the coated group than in the uncoated group, as indicated by the evaluation of the six month study group. After TiN coating, there was no significant difference in endothelial cell cycle. TiN coating significantly reduced the release of nickel in both in vivo and in vitro indicating an improved biocompatibility of the nitinol ASD occluders. Superior and modified ASD occluders may provide a good choice for people with nickel allergies after sFDA registration, which is expected in one to two years.