第一部分

“视而不见”技术在急性A型主动脉夹层根部修复中的应用

目的：急性A型主动脉夹层（acute type A aortic dissection, ATAAD）是一种危及生命的主动脉急症，通常累及主动脉根部，可能导致主动脉瓣交界撕脱及冠状动脉开口受累，因此，根部处理成为手术的关键。鉴于生理性主动脉窦结构在维持主动脉瓣功能和心脏血流动力学中的重要作用，本中心提出了“视而不见”主动脉根部修复术，以尽可能地保留主动脉窦。本研究旨在系统阐述该技术的操作要点，并初步评估其在ATAAD治疗中的临床效果。

方法：回顾性分析2017年9月至2019年6月期间在我院应用“视而不见”技术处理ATAAD根部病变的60例患者的临床资料。主要终点事件定义为早期死亡率和随访期累计生存率。次要终点事件定义为随访期累计主动脉再干预豁免率。此外，利用影像学检查对围术期及随访期间的主动脉根部形态学参数进行定量评估，包括主动脉窦管交界直径、主动脉窦直径和主动脉瓣环直径。

结果：本研究队列的平均年龄为（53.5±11.3）岁，术前主动脉窦管交界直径为（40.5±5.3）mm，主动脉窦直径为（39.1±4.0）mm，主动脉瓣环直径为（26.2±1.9）mm。90%的患者接受了升主动脉置换联合全主动脉弓置换及支架象鼻手术。中位手术时间为365.5分钟，中位体外循环时间为168.5分钟，中位主动脉阻断时间为118.0分钟。早期死亡率为1.7%，其中无术中及院内死亡病例，1例为术后30天内院外死亡。中位随访时间为53个月，1年、3年和5年累计生存率分别为96.7%、95.0%和91.2%；相应时间点的累计主动脉再干预豁免率分别为100%、98.3%和98.3%。影像学随访显示，主动脉窦管交界、主动脉窦和主动脉瓣环直径在出院时与随访期间的差异均无统计学意义（P>0.05）。

结论：“视而不见”主动脉根部修复技术具有操作简便、易于掌握的特点，用于ATAAD的根部处理可获得良好的早中期临床效果。影像学随访证实该技术能有效维持主动脉根部结构的稳定性。远期疗效仍需进一步扩大样本量和延长随访时间予以验证。

第二部分

“视而不见”技术与外膜内翻技术治疗急性A型主动脉夹层根部

病变的中远期疗效对比研究

目的：急性A型主动脉夹层（acute type A aortic dissection，ATAAD）是一种起病急、死亡率高的危重疾病，根部修复是决定其手术成败的关键。本研究团队创新性提出了“视而不见”主动脉根部修复技术，并在早期临床应用中取得了良好的效果。然而，尚缺乏该技术与传统根部修复方法（如外膜内翻技术）的系统性对比研究。本研究旨在对比“视而不见”技术与外膜内翻技术在ATAAD根部修复中的中远期应用效果，以进一步评估其可行性与安全性。

方法：回顾性分析2017年9月至2022年10月期间于我院接受主动脉根部修复手术的248例ATAAD患者的临床资料。其中，“视而不见”组和外膜内翻组各124例患者。主要终点事件定义为中晚期死亡率和主动脉再干预率。次要终点事件定义为早期复合不良事件，包括早期死亡率、二次开胸止血、心包填塞、脑卒中、截瘫、肾功能衰竭。采用单因素和多因素logistic回归分析评估根部修复方式对早期复合不良事件的影响，应用单因素和多因素Cox比例风险模型探究根部修复方式与累计死亡率之间的关系。

结果：“视而不见”组患者的1年、3年、5年和7年累计死亡率分别为4.0%、4.9%、7.0%和11.8%，与外膜内翻组（分别为5.6%、7.3%、9.9%和12.6%）相比无显著差异（Log-rank P=0.604）。同样，二者在随访期主动脉再干预率方面未见显著统计学差异，分别为0.8% vs 0.9%（1年）、2.6% vs 3.5%（3年）、3.7% vs 5.4%（5年）和3.7% vs 5.4%（7年）（Log-rank P=0.567）。在早期结局方面，与外膜内翻组相比，“视而不见”组早期复合不良事件的发生率显著降低（22.6% vs 12.1%；P=0.029），住院时间（12.0，IQR 9.0-15.0 vs 13.0，IQR 10.0-18.0，P=0.048）和引流时间（7.0，IQR 5.0-10.0 vs 10.0，IQR 7.0-15.0，P<0.001）均显著降低。同样，单因素和不同模型的多因素logistic回归分析进一步证实了“视而不见”技术是早期复合不良事件发生的显著保护因素（单因素：比值比 [odds ratio, OR] 0.47，95%置信区间 [confidence interval, CI] 0.24-0.94，P=0.031；多因素模型1：OR 0.47，95%CI 0.24-0.93，P=0.031；多因素模型2：OR 0.47，95%CI 0.23-0.95，P=0.036；多因素模型3：OR 0.48，95%CI 0.23-0.99，P=0.050）。

结论：“视而不见”技术在ATAAD根部修复中操作简便、安全有效，在围术期及中远期结局方面均表现出良好的疗效，且不逊色于传统的外膜内翻技术，具有广泛应用的潜力。未来仍需通过前瞻性研究和长期随访，进一步验证其在更大范围临床应用中的安全性和长期效果。

第三部分

基于不同机器学习方法探索急性A型主动脉夹层免疫致病机制及潜在诊疗靶点研究

目的：急性Stanford A型主动脉夹层（acute Stanford type A aortic dissection, ATAAD）是一种具有高发病率和高死亡率的心血管急症，严重威胁患者生命。尽管ATAAD的发生可能与免疫炎症反应相关，但其具体发病机制尚未完全阐明。本研究旨在筛选可用于ATAAD诊断的生物标志物，并探讨其免疫相关的致病机制。

方法：从GEO数据库获取三组人类ATAAD样本及对照样本的基因表达谱数据。首先，识别差异表达基因（differentially expressed genes, DEGs），去除批次效应后合并数据，并随后对其进行GO、DO和KEGG相关通路的富集分析。基于筛选出的DEGs，研究从两个角度进一步挖掘关键基因：一方面，通过相互作用基因/蛋白质检索工具（Search Tool for the Retrieval of Interacting Genes/Proteins, STRING）构建蛋白质-蛋白质相互作用网络，并借助Cytoscape软件识别核心基因模块；另一方面，采用支持向量机-递归特征消除和随机森林算法联合筛选另一组关键基因。将上述两种方法得到的基因集取交集，最终确定潜在的生物标志物。随后，基于受试者工作特征曲线评估其诊断效能，并利用蛋白质印迹实验和额外测序数据集进一步验证。此外，采用CIBERSORT算法分析免疫细胞浸润特征及其与关键生物标志物的关系。

结果：通过整合分析三组训练数据集的基因表达谱数据，共识别出92个DEGs，这些基因显著富集于炎症信号和免疫反应相关通路。MYOCD被确认为ATAAD的关键预测标志物，具有较高的诊断准确性（AUC>0.85），并通过蛋白质印迹实验及验证数据集进行了双重验证。免疫细胞浸润分析显示，MYOCD的表达与幼稚B细胞、静止肥大细胞和滤泡辅助T细胞呈正相关，而与中性粒细胞、单核细胞及M0巨噬细胞呈负相关。

结论：MYOCD可作为ATAAD的诊断标志物，且免疫细胞浸润在ATAAD的发生与进展中起着重要的介导作用。

第四部分

马凡综合征与非马凡综合征患者胸腹主动脉置换术后远期疗效

对比研究

目的：马凡综合征（Marfan syndrome, MFS）是一种遗传性结缔组织病，常伴有广泛的主动脉病变，需进行胸腹主动脉置换术（thoracoabdominal aortic repair, TAAR）。由于MFS患者具有特殊的病理生理特征，其术后预后可能与非MFS患者有所不同。本研究旨在通过对比分析MFS患者与非MFS患者接受TAAR术后的远期疗效，为临床治疗提供数据支持和参考依据。

方法：本研究回顾性纳入2012年10月至2022年10月期间在我院接受TAAR的230例患者，其中69例为MFS组，161例为非MFS组。主要终点事件定义为总体死亡率。次要终点事件定义为早期复合不良事件，包括早期死亡、永久性脑卒中、永久性截瘫、永久性肾功能衰竭和二次开胸止血。采用单因素和多因素logistic回归分析评估MFS对早期复合不良事件的影响，并通过构建单因素和多因素Cox比例风险模型探究MFS与总体死亡率的相关性。

结果：与非MFS组患者相比，MFS组患者更年轻（31.9±8.5岁 vs 44.8±12.3岁；P<0.001），合并冠心病的比例更低（0% vs 8.1%；P=0.034），接受Crawford III型TAAR的比例更高（56.5% vs 34.8%；P=0.002）。两组患者在早期复合不良事件发生率上无显著差异（MFS组 23.2% vs 非MFS组 14.3%；P=0.099），该结果在单因素和不同模型的多因素logistic回归分析中均得到验证。此外，MFS组的总体死亡率显著低于非MFS组（Log-rank P=0.026），其1年、5年和10年的累计死亡率分别为4.4% vs 8.7%、8.1% vs 17.2%和20.9% vs 36.4%。单因素和不同模型的多因素Cox回归分析进一步证实，MFS是远期死亡率的显著保护因素（模型1：风险比 [hazard ratio, HR] 0.31，95%置信区间 [confidence interval, CI] 0.13-0.73，P=0.007；模型2：HR 0.32，95%CI 0.13-0.75，P=0.009；模型3：HR 0.38，95%CI 0.15-0.95，P=0.039）。

结论：尽管MFS患者与非MFS患者在主动脉病理特征和合并症等方面存在差异，但在个性化的手术策略、细致的围术期管理以及密切的随访监督下，MFS患者接受开放TAAR后可获得与非MFS患者相当甚至更优的疗效，尤其是在远期预后方面。

Abstract

Part I

The application of "watching without dealing with" technique in root repair of acute type A aortic dissection

Objective: Acute type A aortic dissection (ATAAD) is a life-threatening aortic emergency, often involving the aortic root, which can lead to aortic valve commissure tear and coronary artery involvement. Therefore, root management is a critical aspect of surgery. Given the crucial role of the physiological aortic sinus structure in maintaining aortic valve function and cardiac hemodynamics, our center has introduced the "watching without dealing with" technique for aortic root repair, aiming to preserve the aortic sinus as much as possible. This study aims to systematically outline the key technical points of this approach and to preliminarily assess its clinical outcomes in the treatment of ATAAD.

Methods: A retrospective analysis was conducted on the clinical data of 60 patients who underwent "watching without dealing with" aortic root repair for ATAAD at our hospital from September 2017 to June 2019. The primary endpoint was early mortality and cumulative survival rate during follow-up. The secondary endpoint was the cumulative rate of freedom from re-intervention on the aorta during follow-up. Additionally, imaging examinations were used to quantitatively evaluate the morphological parameters of the aortic root during the perioperative period and follow-up, including the aortic sinotubular junction diameter, aortic sinus diameter, and aortic valve annulus diameter.

Results: The average age of the study cohort was 53.5±11.3 years. Preoperative measurements were: aortic sinotubular junction diameter 40.5±5.3 mm, aortic sinus diameter 39.1±4.0 mm, and aortic valve annulus diameter 26.2±1.9 mm. Ninety percent of patients underwent replacement of the ascending aorta with total arch replacement and stented elephant trunk surgery. The median surgical time was 365.5 minutes, with a median cardiopulmonary bypass time of 168.5 minutes and a median aortic cross-clamp time of 118.0 minutes. The early mortality rate was 1.7%, with no intraoperative or in-hospital deaths; one patient died within 30 days postoperatively. The median follow-up time was 53 months, with cumulative survival rates at 1, 3, and 5 years of 96.7%, 95.0%, and 91.2%, respectively. The corresponding cumulative freedom from aortic re-intervention rates at these time points were 100%, 98.3%, and 98.3%. Imaging follow-up showed no significant difference (P>0.05) in the aortic sinotubular junction, aortic sinus, and aortic valve annulus diameters between discharge and follow-up.

Conclusion: The "watching without dealing with" technique for aortic root repair is simple, easy to master, and yields favorable early to mid-term clinical outcomes for ATAAD root management. Imaging follow-up confirms its effectiveness in maintaining the stability of the aortic root structure. However, long-term outcomes need further investigation with larger sample sizes and extended follow-up periods for validation.

Part II

A comparative analysis of mid- and long-term outcomes of "watching without dealing with" technique and adventitial inversion technique in the repair of root lesions in acute type A aortic dissection

Objective: Acute type A aortic dissection (ATAAD) is a severe and life-threatening condition, with aortic root repair serving as a critical factor for surgical success. Our center has introduced an innovative "watching without dealing with" technique for aortic root repair, which has demonstrated promising results in preliminary clinical practice. However, systematic comparative studies between this technique and traditional methods, such as adventitial inversion, are lacking. This study aims to compare the mid- and long-term outcomes of the "watching without dealing with" technique and adventitial inversion in treating aortic root lesions in ATAAD, evaluating their feasibility, safety, and long-term efficacy.

Methods: A retrospective analysis was performed on the clinical data of 248 ATAAD patients who underwent aortic root repair surgery at our hospital between September 2017 and October 2022. Of these, 124 patients were assigned to the "watching without dealing with" group, and 124 to the adventitial inversion group. The primary endpoints included mid- and long-term mortality and reintervention rates. Secondary endpoints included early composite adverse events, including 30-day mortality, reoperation for bleeding, cardiac tamponade, stroke, paraplegia, and renal failure. Univariate and multivariate logistic regression analyses were conducted to assess the impact of root repair methods on early composite adverse events, while univariate and multivariate Cox proportional hazards models evaluated the relationship between repair methods and cumulative mortality.

Results: The 1-year, 3-year, 5-year, and 7-year cumulative mortality rates in the "watching without dealing with" group were 4.0%, 4.9%, 7.0%, and 11.8%, respectively, which were similar to those in the adventitial inversion group (5.6%, 7.3%, 9.9%, and 12.6%, respectively; Log-rank P = 0.604). Similarly, no significant statistical differences were observed between the two groups in reintervention rates during follow-up, with 1-year, 3-year, 5-year, and 7-year rates of 0.8% vs. 0.9%, 2.6% vs. 3.5%, 3.7% vs. 5.4%, and 3.7% vs. 5.4%, respectively (Log-rank P = 0.567). Regarding early outcomes, the "watching without dealing with" group had a significantly lower incidence of early composite adverse events compared to the adventitial inversion group (22.6% vs. 12.1%; P = 0.029), along with shorter hospital stays (12.0 days, IQR 9.0-15.0 vs. 13.0 days, IQR 10.0-18.0, P = 0.048) and shorter drainage times (7.0 days, IQR 5.0-10.0 vs. 10.0 days, IQR 7.0-15.0, P < 0.001). Univariate and multivariate logistic regression analyses further confirmed that the "watching without dealing with" technique was a significant protective factor for early composite adverse events (univariate: odds ratio [OR] 0.47, 95% confidence interval [CI] 0.24-0.94, P = 0.031; multivariate model 1: OR 0.47, 95% CI 0.24-0.93, P = 0.031; multivariate model 2: OR 0.47, 95% CI 0.23-0.95, P = 0.036; multivariate model 3: OR 0.48, 95% CI 0.23-0.99, P = 0.050).

Conclusion: The "watching without dealing with" technique is a simple, safe, and effective method for aortic root repair in ATAAD, showing favorable perioperative and mid- to long-term outcomes. Its efficacy is comparable to the adventitial inversion technique and shows potential for broader clinical application. Further prospective studies and long-term follow-up are needed to confirm its safety and long-term effectiveness in larger clinical settings.

Part III

Exploring the immune pathogenesis and potential diagnostic and therapeutic targets of acute type A aortic dissection based on different machine learning methods

Background: Acute Stanford type A aortic dissection (ATAAD) is a life-threatening cardiovascular disease with high morbidity and mortality. Although the incidence of ATAAD may be associated with immune-inflammatory mechanisms, its pathogenesis remains unclear. In this study, we intended to identify critical genetic markers for the diagnosis of ATAAD and explore the molecular mechanisms underlying its pathology.

Methods: Gene expression profiles from three sets of human ATAAD samples and control samples were obtained from the GEO database. Differentially expressed genes (DEGs) were first identified and analyzed after batch effect correction. Functional enrichment analyses of the DEGs were conducted using Gene Ontology (GO), Disease Ontology (DO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. Based on the identified DEGs, we further investigated key genes from two perspectives: (1) a protein-protein interaction network was constructed using the Search Tool for the Retrieval of Interacting Genes/Proteins (Search Tool for the Retrieval of Interacting Genes/Proteins, STRING) database, and key gene modules were identified using Cytoscape software; (2) key genes were further selected using Support Vector Machine-Recursive Feature Elimination and Random Forest algorithms. The intersection of the gene sets identified by both methods was used to determine potential biomarkers. The diagnostic performance of the biomarkers was evaluated using Receiver Operating Characteristic curve analysis, and further validation was performed by Western blot and additional sequencing datasets. Additionally, immune cell infiltration patterns and their correlation with key biomarkers were analyzed using the CIBERSORT algorithm.

Results: By integrating the gene expression data from three training datasets, 92 DEGs were identified, which were significantly enriched in pathways related to inflammation and immune responses. MYOCD was determined as a key predictive biomarker for ATAAD, with high diagnostic accuracy (AUC>0.85), and this was further confirmed through Western blot and validation datasets. Immune cell infiltration analysis revealed that MYOCD expression was positively correlated with naïve B cells, resting mast cells, and follicular helper T cells, while negatively correlated with neutrophils, monocytes, and M0 macrophages.

Conclusions: MYOCD can serve as a diagnostic marker for ATAAD, with immune cell infiltration acting as an important mediator of ATAAD development and progression.

Part IV

Comparative analysis of long-term outcomes in thoracoabdominal aortic aneurysm repair between Marfan syndrome and non-Marfan syndrome patients

Objective: Marfan syndrome (MFS) is a hereditary connective tissue disorder often associated with extensive aortic pathology, which may require thoracoabdominal aortic repair (TAAR). Given the unique pathophysiological characteristics of MFS, the prognosis following TAAR in MFS patients may differ from that in non-MFS patients. Therefore, this study aims to provide clinical data and insights by comparing long-term outcomes of TAAR between MFS and non-MFS patients.

Methods: This retrospective study included 230 patients who underwent TAAR at our hospital between October 2012 and October 2022, consisting of 69 patients in the MFS group and 161 in the non-MFS group. The primary endpoint was overall mortality. The secondary endpoints were early composite adverse events, including early death, permanent stroke, permanent paraplegia, permanent renal failure, and re-exploration for bleeding. Univariate and multivariate logistic regression analyses were performed to assess the impact of MFS on early adverse events, and univariate and multivariate Cox proportional hazard models were used to analyze the relationship between MFS and overall mortality.

Results: Compared with non-MFS patients, MFS patients were younger (31.9±8.5 years vs 44.8±12.3 years; P < 0.001), had a lower incidence of coronary artery disease (0% vs 8.1%; P = 0.034), and a higher proportion of patients undergoing Crawford type III TAAR (56.5% vs 34.8%; P = 0.002). There were no significant differences between the two groups in the incidence of early composite adverse events (23.2% in MFS vs 14.3% in non-MFS; P = 0.099), a result confirmed in both univariate and multivariate logistic regression analyses. Furthermore, the overall mortality rate in the MFS group was significantly lower than that in the non-MFS group (Log-rank P = 0.026), with 1-year, 5-year, and 10-year cumulative mortality rates of 4.4% vs 8.7%, 8.1% vs 17.2%, and 20.9% vs 36.4%, respectively. Univariate and multivariate Cox regression analyses further confirmed that MFS was a significant protective factor for long-term mortality (Model 1: hazard ratio [HR] 0.31, 95% confidence interval [CI] 0.13–0.73, P = 0.007; Model 2: HR 0.32, 95% CI 0.13–0.75, P = 0.009; Model 3: HR 0.38, 95% CI 0.15–0.95, P = 0.039).

Conclusion: Despite differences in aortic pathology and comorbidities between MFS and non-MFS patients, with individualized surgical strategies, meticulous perioperative management, and close follow-up, MFS patients undergoing open TAAR can achieve outcomes comparable to or even better than those of non-MFS patients, particularly in terms of long-term prognosis.