Myocardial ischemia-reperfusion (MI/R) injury limits the therapeutic effects of revascularization in acute myocardial infarction. In this study, we investigated whether human SIRT3 (hSIRT3) and TIMP3 (hTIMP3) could achieve targeted delivery with the assist of cationic microbubbles (CMBs) and a synergistic protection effect on porcine MI/R myocardium. Firstly, CMBs carrying the hSIRT3 or hTIMP3 plasmids were used individually or synergistically for cardiac-targeted delivery in MI/R pigs. After 7 days of observation, hSIRT3 and hTIMP3 were mainly enriched in myocardium, especially in the infarction center, without additional increase in cTNI and pathological damage to non-cardiac organs. At the same time, hSIRT3 and hTIMP3 exerted a protective role against myocardial injury, as gene therapy significantly inhibited myocardial apoptosis, inflammation and oxidative damage. After 90 days of observation, hSIRT3 and hTIMP3 application exerted an inhibiting effect on development of heart failure, as the strategy significantly increased the density of vascular, and limited the myocardial fibrosis, area scar size, the decline of cardiac function. As expected, collaborative applications of hSIRT3 and hTIMP3 showed a better protective effect than hSIRT3 or hTIMP3 application alone. Collectively, hSIRT3 and hTIMP3 delivered with CMBs in heart could exert positive effect on myocardial protection after MI/R in pigs.

Background:Acute Stanford Type A Aortic Dissection (ATAAD) is a critical medical emergency characterized by significant morbidity and mortality. This study aims to identify specific gene expression patterns and RNA modification associated with ATAAD. Methods:The GSE153434 dataset was obtained from the Gene Expression Omnibus (GEO) database. Differential expression analysis was conducted to identify differential expression genes (DEGs) associated with ATAAD. To validate the involvement of RNA modification in ATAAD, RNA modification-related genes (M6A, M1A, M5C, APA, A-to-I) were acquired from GeneCards, following by Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis. A gene prediction signature consisting of key genes was established, and Real-time PCR was used to validate the gene expression in clinical samples. The patients were then divided into high and low-risk groups, and subsequent enrichment analysis, including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Set Enrichment Analysis (GSEA), Gene Set Variation Analysis (GSVA), and assessments of immune infiltration. A co-expression network analysis (WGCNA) was performed to explore gene-phenotype relationships and identify key genes. Results:A total of 45 RNA modification genes were acquired. Six gene signatures (YTHDC1, WTAP, CFI, ADARB1, ADARB2, TET3) were developed for ATAAD diagnosis and risk stratification. Enrichment analysis suggested the potential involvement of inflammation and extracellular matrix pathways in the progression of ATAAD. The incorporation of pertinent genes from the GSE147026 dataset into the six-gene signature further validated the model's effectiveness. A significant upregulation in WTAP, ADARB2, and TET3 expression, whereas YTHDC1 exhibited a noteworthy downregulation in the ATAAD group. Conclusion:Six-gene signature could serve as an efficient model for predicting the diagnosis of ATAAD.

"微创"是现代心脏外科的重要发展趋势,胸腔镜下的心脏外科手术虽然近年来刚刚起步,但却是心脏外科领域一次非常重要的"微创"技术飞跃,也是微创心脏手术未来发展的重要方向.胸腔镜下的心脏外科手术与传统手术相比较具有损伤小、恢复快、美观等特点,但对心脏外科医师所需要掌握的心脏外科胸腔镜技术要求较高.

Background: Acute Stanford type A aortic dissection (ATAAD) is a potentially fatal outcome of cardiac surgery with a high mortality rate and an unclear pathogenesis. This study aimed to investigate the prospective diagnostic biomarkers and molecular pathways in ATAAD.Methods: We identified autophagy-related differentially expressed genes (DEGs) between control ATAAD groups using three Gene Expression Omnibus (GEO) datasets (GSE153434, GSE98770, and GSE52093). The potential pathways and biomark-ers were then determined through protein-protein interaction (PPI) network and enrichment analysis. The autophagy-related hub genes and their corresponding diagnostic values were determined using receiver operating characteristic analysis and the significant immune-associated pathways were identified using Gene-Set Variation Analysis (GSVA) enrichment.Results: A total of 90 genes were screened as autophagy-related DEGs and 10 hub genes were ultimately identified using a PPI network in patients with ATAAD. Autophagy-related DEGs were enriched in pathways related to autophagy, protein binding, regulation of autophagy, and the relaxin signaling pathway according to Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses. Gene-set enrichment analysis suggested that the regulation of autophagosome assembly, focal adhesion, and calcium-signaling pathways are enriched mainly in ATAAD development. In addition, GSVA showed that DEGs in ATAAD are primarily involved in the metabolic pathways of myocardial diseases and autophagy. Finally, it was found that the immune infiltration between the control and ATAAD groups was significantly different.Conclusions: Through the comprehensive analysis of GEO data, our study provides insights into autophagy-related biomarkers and therapeutic targets to diagnose and treat patients who are susceptible to ATAAD.

Engineered heart tissues (EHTs) are regarded as being the most promising alternative to synthetic materials, and autologous mesenchymal stem cells (MSCs) are widely used as seeding cells. However, few studies have evaluated the feasibility of using MSCs from patients with cyanotic congenital heart disease (C-CHD) as seeding cells for EHTs, in comparison with cells from patients of acyanotic congenital heart disease (A-CHD). In the present study, we cultured MSCs from A-CHD and C-CHD patients in normoxia or hypoxia conditions, and compared their pro-angiogenic, anti-apoptotic and inflammation-modulatory potentials. In vivo, we seeded the cells into collagen patches conjugated with, or without, proangiogenic cytokines, which were used to repair the right ventricular outflow tract (RVOT) of rats. The in vitro results showed that C-CHD MSCs expressed higher levels of VEGFA and VEGFR2, and secreted more pro-angiogenic and anti-inflammatory cytokines under hypoxic conditions. On the other hand, apoptosis-related genes from C-CHD MSCs were modulated adaptably, converting these cells into an anti-apoptotic phenotype. In vivo studies demonstrated that in 4 weeks after RVOT reconstruction, cytokine-immobilized patches seeded with C-CHD MSCs exhibited preserved morphology, prolonged cell survival and enhanced angiogenesis compared to A-CHD MSCs. C-CHD MSCs that undergo “naturally hypoxic precondition” present a better cell source for EHTs, which would provide a promising individualized biomaterial for C-CHD patients.

目的 探讨建立大鼠右室流出道重建术动物模型的可行性.方法 对15只成年雌性Sprague-Dawley (SD)大鼠实施右室流出道重建术.将胶原海绵补片经过碳化二亚胺法处理,并种植人骨髓间充质干细胞(紫绀型先心病患者来源,年龄＜5岁),利用新构建的工程化心肌补片修补大鼠的右心室流出道.3d后,随机取3只大鼠处死,取出心脏,对心脏正面、内面及剖面摄片,以确定透壁切除心肌组织.4周后,将大鼠心脏取出,作抗人线粒体抗体染色确定补片是否仍有种子细胞存活(n=4).此外,在1个月、3个月时,各处死大鼠3只,直视摄影观察并行马洪染色(Masson's trichrome)观察补片降解情况(n=3).结果 2只大鼠于术后24 h内死亡,建模总体死亡率为13.3％(2/15).直视摄片证明右心室流出道为透壁切除,补片完全替代了右室流出道心肌组织.4周后补片上仍有种子细胞存活.结论 大鼠右室流出道重建术模型可作为组织工程心肌补片(EHT)实验研究中一种稳定、可靠且经济的初筛模型.

Background. Engineered heart tissues (EHTs) present a promising alternative to current materials for surgical ventricular restoration (SVR); however, the clinical application remains limited by inadequate vascularization postimplantation. Moreover, a suitable and economic animal model for primary screening is another important issue. Methods. Recently, we used 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride chemistry (EDC) to initiate a strengthened, cytokine-conjugated collagenous platform with a controlled degradation speed. In vitro, the biomaterial exhibited an enhanced mechanical strength maintaining a porous ultrastructure, and the constant release of cytokines promoted the proliferation of seeded human mesenchymal stem cells (hMSCs). In vivo, with the hMSC-seeded, cytokine-immobilized patch (MSCs + GF patch), we performed modified SVR for rats with left ventricular aneurysm postmyocardial infarction (MI). Overall, the rats that underwent modified SVR lost less blood and had lower mortality. After 4 weeks, the rats repaired with this cell-seeded, cytokine-immobilized patch presented preserved cardiac function, beneficial morphology, enhanced cell infiltration, and functional vessel formation compared with the cytokine-free (MSC patch), cell-free (GF patch), or blank controls (EDC patch). Furthermore, the degradable period of the collagen patch in vivo extended up to 3 months after EDC treatment. Conclusions. EDC may substantially modify collagen scaffold and provide a promising and practical biomaterial for SVR.

Allograft rejection is an important issue post cardiac transplantation. In order to investigate the effect of combined treatment with simvastatin and rapamycin on allograft rejection, a cardiac transplantation rat model was employed in the present study. The survival time of rats following cardiac transplantation was recorded, while histopathological alterations were assessed by hematoxylin and eosin staining. The levels of transcription factors were measured by reverse transcription-quantitative polymerase chain reaction. In addition, the levels of CD4+ interleukin (IL)-17+ cells and CD4+ forkhead box P3 (FOXP3)+ cells in the allografts and CD4+ T cells and CD8+ T cells in the spleens were detected by flow cytometry. The results of the current study demonstrated that, following treatment with simvastatin and rapamycin, the survival time of model rats was prolonged, and the histopathological damage was attenuated. Treatment with simvastatin and rapamycin also led to decreased retinoic acid receptor-related orphan receptor γt (RORγt) level, increased FOXP3 level, reduced levels of CD4+IL-17+, CD4+ T and CD8+ T cells, and increased level of CD4+FOXP3+ cells. In conclusion, the current study observed that simvastatin and rapamycin performed a synergistic effect to reduce cardiac transplantation rejection. Thus, combined therapy of simvastatin and rapamycin may be a promising adjuvant therapy to reduce rejection post cardiac transplantation.

目的 对比紫绀型先心病(cyanotic congenital heart disease,C-CHD)和非紫绀型先心病(acyanotic congenital heart disease,A-CHD)患儿来源的骨髓间充质干细胞(human mesenchymal stem cells,hMSCs)在乏氧环境下的抗凋亡能力,并探讨其发生机制.方法 hMSCs取自C-CHD(C组)和A-CHD(A组)患儿(男女不限,0～5岁),于体外乏氧环境下(1％O2,5％ CO2,94％ N2)培养.以Annexin V/PI双染结合流式细胞技术对比两组细胞抵御缺血缺氧诱导细胞凋亡的能力;以Western blot法检测两组细胞中B细胞淋巴瘤-2基因(B-cell lymphoma-2,Bcl-2),Bcl-2相关X蛋白(Bax)以及半胱氨酸天冬氨酸蛋白酶-3(caspase-3)的含量.结果 Annexin V/PI双染结合流式细胞检测结果显示:在缺血缺氧环境下,C组细胞的早期凋亡率(P＜0.01)和总体凋亡率(P＜0.05)低于A组细胞.Western-blot检测结果显示:C组细胞的凋亡抑制基因Bcl-2的含量高于A组细胞(P＜0.05),抗凋亡抑制基因Bax (P＜0.05)以及caspase-3 (P＜0.05)的含量低于A组细胞.结论 C-CHD患者来源的hMSCs具有更好的抗缺血缺氧诱导的总凋亡及早期凋亡能力,这可能与其天然乏氧诱导的Bcl-2表达上调,Bax,caspase-3表达下调有关.

Objective To compare the effect of 4 kinds of biomaterials on rat left ventricular geometry and cardiac function following to surgical ventricular restoration (SVR).Methods Mechanical properties of blank collagen patch (PBSpatch),EDC [1-ethyl-3-(3-dimethylaminopropyl) carbodiimide hydrochloride chemistry]-treated patch (EDC-patch) and cytokine-enhanced patch(GF-patch) were compared with tensile testing machine and the ultra-structure were examined by electrical scan microscopy.Adult SD rats were performed left coronary artery ligation to generate left ventricular aneurysm model following to myocardial infarction(MI).After 4 weeks,surgical ventricular restoration was taken in rats underwent screening with the four kinds of patch.We examined the left ventricular end-systolic volume(LVESV),left ventricular end-diastolic volume (LVEDV) and left ventricular ejection fraction(LVEF) with echocardiography.Examing time was prior to MI,prior to SVR,1 week and 4 weeks after SVR.After harvesting,rat hearts were inflated through intraventricular balloons,and the photo of patch was vertically taken and analyzed with Image J software.After fixation and slicing,Masson' s Trichrome staining and smooth muscle actin(SMA) staining were performed respectively to measure the patch thickness and neo-vessel density.Results In vitro,after EDC treatment,the mechanical properties of collagen patch with or without growth factors were significantly enhanced than that before(P ＜ 0.01),while,no ultra-structure changed significantly.In vivo,the EDC-patch,GF-patch and MSC + GF-patch could be used to repair the transmural defect of left ventricle,while the blank collagen patch failed to fulfill the application.Comparatively,GF-patch and MSC + GF-patch exhibited less area,thicker thickness and enhanced neo-vessel density (P ＜ 0.05).Moreover,rats repaired with GF-patch and MSC + GF-patch illustrated the relative smaller LVEDV(P ＜ 0.05).LVESV was better maintained in MSC + GF-patch (P ＜ 0.05).Also,the heart function was better preserved in MSC + GF-patch (P ＜ 0.05).Conclusion After treated with EDC,the cytokine-immobilized,hMSCs-seeded biomaterials facilitate the maintenance of left ventricular geometry and cardiac function following to SVR in long term.

本文综述目前我国膜式氧合器临床应用,人工膜肺领域的研究成果和发展趋势.通过问卷调查形式显示我国近年CPB(Cardiopulmonary Bypass,体外循环)技术发展迅速,膜式氧合器应用量逐年升高,应用ECMO (extracorporeal membrane oxygenation,体外膜肺氧合)辅助循环的比例显著增加.人工膜肺多方面研究进展包括:为新生儿体外循环设计的婴幼儿膜式氧合器,整合动脉滤过器与超滤设备的小型化氧合器,这些设计可以明显减少体外循环回路整体表面积和预充量,避免CPB中过度血液稀释,降低或不用输入红细胞.同时减轻由于血液与人工材料接触诱发的炎性反应.人工膜肺在人工材料改进和结构设计有很显著发展,通过改进气体交换的人工膜材料,优化结构设计,提高血液抗凝能力和耐受力,设计出如ECMO可以长时间应用于辅助循环来延续和支持病人的生命.对膜式氧合器的试验研究的相关进展和展望也会在本文讨论.

背景：动物实验证明心肌细胞移植可改善心脏功能，但移植细胞效率较低，为减少移植细胞的流失，构建合适的移植载体与细胞共同移植于受体心脏已成为学界的共识。<br>　　目的：观察经碳化二亚胺法处理，共价结合生长因子胶原补片上生长因子的释放情况，以及其对人骨髓干细胞增殖与分化的影响。<br>　　方法：采用碳化二亚胺法将胶原补片激活后，对照组胶原补片直接保存于PBS内，实验组胶原补片继续浸于含有血管内皮生长因子和碱性成纤维细胞生长因子的PBS内，使其与生长因子共价结合，检测共价结合于胶原补片上生长因子的量；保存后1 d、3 d、7 d、2周、3周、4周，采用ELISA法检测上清液内血管内皮生长因子和碱性成纤维细胞生长因子的含量。将0.5×106的人骨髓间充质干细胞均匀接种于两组补片上，采用苏木精-伊红染色计数细胞，MTT法及Brdu增殖实验对比补片上的细胞增殖情况；以RT-PCR法检测两组细胞内Ⅰ、Ⅲ型胶原表达情况，SMA免疫荧光染色对比两组补片上的细胞分化情况。<br>　　结果与结论：胶原补片上血管内皮生长因子和碱性成纤维细胞生长因子的共价结合率分别为42.4%，24.5%。保存4周内，胶原补片上的血管内皮生长因子和碱性成纤维细胞生长因子均呈现持续、缓慢的释放模式。与单纯胶原补片比较，共价结合生长因子的胶原补片可在体外有效促进人骨髓间充质干细胞的增殖并抑制其分化。

目的:观察宫颈癌组织中Th1/Th2类细胞因子的漂移情况.方法:选以IL-2和IFN-γ代表Th1类细胞因子,IL-4和IL-6代表Th2类细胞因子,通过逆转录聚合酶链反应(RT-PCR)检测25例宫颈癌癌组织中Th1/Th2类细胞因子mRNA的表达.结果:ⅢB期宫颈癌组织中,Th1型细胞因子的表达显著低于ⅠB期、ⅡA期、ⅡB期,Th2型细胞因子的表达显著高于ⅠB期、ⅡA期、ⅡB期,差异均有统计学意义(P＜0.05).Ⅰ期和Ⅱ期宫颈癌以Th1型细胞因子表达为主.25例宫颈癌组织中,13例呈典型的Th1类细胞因子的强势表达,7例为Th2型,5例为Th0型,随着宫颈癌分期的增高,由Th1向Th2漂移(P＜0.05).结论:ⅠB期、ⅡA期、ⅡB期宫颈癌患者组织中细胞因子呈Th1状态,ⅢA期呈Th0状态,ⅢB期呈Th2状态,随着宫颈癌分期的增高,由Th1向Th2漂移.

目的 探讨乌司他丁在深低温停循环手术围术期对患者全身炎性因子的影响.方法 选取同期接受深低温停循环大血管手术的患者24例,随机分为两组,乌司他丁组(U组)和对照组(C组),每组12例.U组:预充液中加入乌司他丁2万U/kg.C组:预充液中除不加入乌司他丁外其他成分与U组相同.经腋动脉和/或股动脉、右房二级静脉插管建立体外循环.全部病例分别在体外循环开始前(T1)、主动脉阻断时(T2)、心脏复跳时(T3)和停机器后10 min(T4)4个时间点,抽取静脉血,观察炎性细胞因子:肿瘤坏死因子(TNF-α)、白介素(IL-6、IL-8)浓度的变化.结果 与体外循环开始前比较,U组TNF-α和IL-6在T3和T4点浓度升高,IL-8在T3点浓度升高.与T1比较,C组TNF-α在T3点浓度升高,IL-8在T3和T4点浓度升高.组间比较,U组TNF-α、IL-6和IL-8浓度在T2、T3、T4点均较C组低,C组TNF-α和IL-8在T2和T3点浓度较U组增高更显著(P＜0.05).结论 乌司他丁可抑制TNF-α、IL-6、IL-8等炎性因子的产生和释放,从而降低深低温停循环手术围术期患者的全身炎性反应.

目的 通过观察患者临床资料及手术后精神障碍发生情况,分析研究与心脏手术后精神障碍发生可能的相关因素.方法 统计2005～2006 年期间300例心脏直视手术患者的临床资料,术后通过PTSS-10精神障碍诊断量表对患者进行心脏手术后精神障碍的诊断,回顾分析其中出现精神障碍的24例患者的临床资料和随访资料,对患者的一般资料及围手术期资料中是否存在与心脏手术后精神障碍有关的因素进行统计分析.结果 从全因素的Logistic回归模型上来看,性别、年龄、入院心功、脑梗史、心梗史、手术所用时间、体外循环及患者在ICU中时间可能为术后精神障碍的危险因素,其中又以年龄、在ICU中时间、手术时间、性别与术后精神障碍密切相关.结论 心脏术后精神障碍的发生是包括生理机能、环境、心理因素在内的多种因素共同作用的结果,高龄、ICU中滞留时间长、手术时间长、女性可能更易患术后精神障碍,应对这些患者早期给予关注并采取综合防治措施.

Objective Reviewing the experience of surgical treatment of aortic dissection to approach an effective and safe method to treat this kind of disease.Methods Nineteen patients with AD accepted surgical treatment from January,2000 to August,2005.A graft replacement of ascending aorta and total aortic arch combined with the elephant trunk techniques was performed in 2 patients.Two patients underwent the Bentall procedure and aortic arch graft.Partial thoracic aortic grafting in 1.Partial thoracic and abdominal aortic grafting in 3.David procedure in 1.Aortic arch and descending aorta plasty in 1.Cabrol procedure in 1.Bentall procedure in 8.Concomitant procedures were 1 aortic arch plasty,1 mitral valve plasty and 1 CABG.Four cases of AD with deep hyperthomic circulation arrest,other cases with the assistance of extrocorporeal circulation.Results There were 3 deaths within operation,1 paraplegia and 1 death after operation.The overall mortality is 21.0%.Conclusion Procedures chosen must depend on the location of intimal tear.Appropriate brain and spinal cord protection are essential to the treatment of aortic dissection.

患者女,55岁.阵发性心前区疼痛1年.既往有高血压、高脂血症病史.查体:血压(BP):170/110mmHg, 胸骨左缘第3、4肋间可闻及3/6～4/6级收缩期杂音.

目的总结终末期冠心病患者施行心脏移植的临床经验,探讨术后血管病变的预防策略。方法在体外循环下采用双腔法原位心脏移植。术后采用环孢菌素A、骁悉和泼尼松等药物抗排斥反应,并监测其血药浓度。结果患者术后8h清醒,56h脱离呼吸机。围手术期过程平稳,术后1个月心功能分级(NYHA)恢复至Ⅱ级,10个月后恢复至Ⅰ级。结论心脏移植可作为冠心病患者的终极治疗措施,术后对患者进行系统的药物治疗十分重要。

目前,心脏手术量呈不断上升的趋势,随着外科及麻醉水平的提高,与过去的30年相比,心脏术后神经系统并发症发病率逐年下降,呼吸循环系统并发症的发生率及病死率也持续下降.但体外循环(CPB)心脏手术后精神障碍的发病率却逐年升高,约35%病人在术后1年内出现精神障碍症状[1].并发症不同程度地延长住院时间,增加术后病死率、影响病人生活质量甚至干扰治疗[2].因此,研究心脏术后精神障碍的危险因素、发展趋势及防治方法已成为重要的课题.现就心脏手术后精神障碍的临床研究进展作一综述.