To the Editor: Depression is a common psychiatric disorder, affecting over 260 million people of all ages globally.[1] Prior studies investigating the association between antidepressant use and stroke risk have yielded inconsistent results.[2,3] Consequently, it remains unclear which of the various antidepressant categories may affect stroke. Thus, the rational use of antidepressants is important for reducing stroke risk and recurrence, while offering candidate therapeutic targets. Drug-target Mendelian randomization (MR) analysis, which uses genetic variants located in or near the region of drug target genes as proxies for drug effects, is a promising tool for identifying causal links between drug targets and diseases. This study aimed to evaluate the causal associations between antidepressant target genes and stroke and its various subtypes (including any stroke [AS], ischemic stroke [IS], large artery atherosclerosis stroke [LAA], cardioembolic stroke [CES], and small vessel stroke [SVS]) using drug-target MR analysis. Various antidepressants were identified from the World Health Organization Collaborating Centre for Drug Statistics Methodology, and were classified by the Anatomical Therapeutic Chemical classification system. The DrugBank (https://go.drugbank.com/) and ChEMBL (https://www.ebi.ac.uk/chembl/) databases were used to determine the genes encoding the targets of antidepressants. To identify genetic variants as proxies for the effect of drug target genes, blood cis-expression quantitative trait loci (eQTL) data from the eQTLGen Consortium (n = 31,684) were used. The cis-eQTL located within 1 Mb downstream or upstream of the region of the drug target genes with a false discovery rate (FDR) <0.05 and F-statistic (calculated by the formula: F-statistic = beta2/se2) >10 were screened. Independent genetic variants without linkage disequilibrium (r2 <0.1) were used as the instrumental variables (IVs). Genome-wide association studies (GWAS) summary data for stroke and its subtypes were from GIGASTROKE consortium. Our study included only individuals of European ancestry, comprising AS (73,652 cases and 1,234,808 controls), IS (62,100 cases), LAA (6399 cases), CES (10,804 cases), and SVS (6811 cases). All participants enrolled in this study were of European ancestry, with no sample overlap with the exposure dataset in the main analysis. Detailed information of the different data sources is provided in Supplementary Table 1, https://links.lww.com/CM9/C261. All MR analyses were performed using TwoSampleMR R package in R software (v.4.0.3, R Development Core Team, Vienna, Austria), while the inverse variance weighted method was used to estimate the causal effects. The FDR method was applied for multiple testing, with an FDR <0.05 indicating statistical significance. Sensitivity analyses, including heterogeneity and pleiotropy tests, were performed using Cochrane's Q test, Rucker's Q test, MR-Egger intercept test, MR pleiotropy residual sum and outlier global test, and leave-one-out analysis. Colocalization analysis was conducted between the significant drug target genes identified in the primary MR analysis and stroke outcomes. A posterior probability of hypothesis 4 (PPH4) >0.8 was used to characterize significant evidence for colocalization. Further, we assessed the causal relationship between the candidate target genes and cerebrovascular risk factors. For drug target genes causally linked to both stroke and risk factors, a two-step mediation MR analysis was conducted to evaluate the effects of drug target genes (exposure) on stroke (outcomes) via the cerebrovascular risk factors (mediators). To determine whether the observed associations between antidepressant target gene expression and stroke risk are likely mediated by major depressive disorder (MDD) or independent of MDD, MR analysis was also conducted to evaluate the associations between MDD and stroke. Further details of this analysis are provided in the Supplementary Methods, https://links.lww.com/CM9/C261. A flow diagram of the study is presented in Supplementary Figure 1, https://links.lww.com/CM9/C261. A total of 111 drug targets encoding proteins have previously been experimentally shown to be modified by one or more antidepressants. After selecting the IVs for the antidepressant target genes, 29 of the 111 genes were identified in the outcome datasets [Supplementary Tables 2–4, https://links.lww.com/CM9/C261]. The associations between genetically predicted antidepressant target genes and stroke are presented in Figure 1, Supplementary Figures 2 and 3, and Supplementary Tables 5–11, https://links.lww.com/CM9/C261. Following FDR adjustment, we identified five drug target genes significantly associated with AS risk: KCNH2 (odds ratio [OR] = 1.057, 95% confidence interval [CI] 1.017–1.098, FDR = 0.027), MPO (OR = 1.071, 95% CI = 1.050–1.093, FDR = 7.81E−10), SIGMAR1 (OR = 0.952, 95% CI = 0.934–0.971, FDR = 1.12E−05), WARS (OR = 0.982, 95% CI = 0.973–0.992, FDR = 0.003), WARS2 (OR = 0.981, 95% CI = 0.970–0.993, FDR = 0.010). Moreover, four genetically predicted drug target genes were found to be significantly associated with IS risk: MPO (OR = 1.078, 95% CI = 1.052–1.105, FDR = 5.55E−08), SIGMAR1 (OR = 0.946, 95% CI = 0.927–0.965, FDR = 1.05E−06), SLC18A2 (OR = 0.942, 95% CI = 0.902–0.983, FDR = 0.043), WARS (OR = 0.980, 95% CI = 0.970–0.991, FDR = 0.002). Genetically predicted GRIN2D (LAA: OR = 0.465, 95% CI = 0.293–0.739, FDR = 0.034), KCNH2 (CES: OR = 1.222, 95% CI = 1.128–1.325, FDR = 2.95E−05), and WARS2 (SVS: OR = 0.938, 95% CI = 0.905–0.972, FDR = 0.011) levels were also found to be significantly associated with LAA, CES and SVS, respectively. Colocalization analysis indicated that MPO and IS, as well as GRIN2D and LAA, probably shared a causal single nucleotide polymorphism in the gene locus (MPO: PPH4 = 0.884; GRIN2D: PPH4 = 0.824; Supplementary Figure 4 and Supplementary Table 12, https://links.lww.com/CM9/C261).Figure 1: MR analysis of significant drug target genes with stroke risk. Five antidepressant targets (KCNH2, MPO, SIGMAR1, WARS, and WARS2) were significantly associated with AS risk after FDR adjustment. Additionally, four targets (MPO, SIGMAR1, SLC18A2, and WARS) showed significant associations with IS risk. Genetically predicted GRIN2D, KCNH2, and WARS2 were significantly linked to LAA, CES, and SVS, respectively. AS: Any stroke; CES: Cardioembolic stroke; CI: Confidence interval; FDR: False discovery rate; IS: Ischemic stroke; LAA: Large artery atherosclerosis stroke; MR: Mendelian randomization; OR: Odds ratio; SVS: Small-vessel stroke.The associations between MPO and GRIN2D with 14 cerebrovascular risk factors were also investigated [Supplementary Figure 5 and Supplementary Tables 13–15, https://links.lww.com/CM9/C261]. Genetically predicted MPO levels were significantly associated with atrial fibrillation (AF; OR = 1.043, 95% CI = 1.018–1.068, FDR = 0.003), heart failure (HF; OR = 1.048, 95% CI = 1.023–1.075, FDR = 0.002), and systolic blood pressure (SBP; OR = 1.256, 95% CI = 1.104–1.428, FDR = 0.003). MR analysis further revealed the causal effects of genetically predicted GRIN2D on AF (OR = 0.819, 95% CI = 0.732–0.917, FDR = 0.008) and triglyceride levels (OR = 0.829, 95% CI = 0.724–0.948, FDR = 0.045). A two-step mediation MR analysis was applied to evaluate the effects of MPO on stroke outcomes (AS and IS) via risk factors (AF, HF, and SBP). The proportions of the mediation effect of MPO on AS and IS via AF were 9.7% and 9.4%, respectively, while the corresponding values via SBP were 8.5% and 8.0%, respectively. The indirect effect of MPO on the risk of AS and IS via HF accounted for 29.7% and 30.2% of the total effect, respectively [Supplementary Figure 6 and Supplementary Table 16, https://links.lww.com/CM9/C261]. We found no evidence to support an association between genetically estimated MDD and AS, IS, LAA, CES, or SVS (all P values >0.05; stroke GWAS from GIGASTROKE or MEGASTROKE; Supplementary Figure 7 and Supplementary Tables 17 and 18, https://links.lww.com/CM9/C261). This indicates that the observed association of target genes with stroke is unlikely to be solely caused by MDD, and indicates that this association is likely independent of the association with MDD. The present study identified associations between antidepressant targets and stroke and its subtypes through drug-target MR analysis. In addition, we identified two candidate antidepressant target genes for IS and LAA (MPO and GRIN2D, respectively). Myeloperoxidase (MPO), a key inflammatory factor in the myeloid system, is highly expressed in activated human neutrophils, and plays an important role in inflammation and oxidative stress responses. Prior studies have shown that inhibition of MPO activity can reduce inflammation and enhance cellular protection against IS.[4]GRIN2D encodes the glutamate ionotropic receptor N-Methyl-D-Aspartate (NMDA) type subunit 2D (GluN2D), which is a subunit of the NMDA Receptor (NMDAR) and is involved in learning, memory, and synaptic functioning.[5] There is currently limited evidence linking GRIN2D with LAA or atherosclerosis, highlighting the need for further investigation. This study has several strengths. First, this MR study integrated the latest and largest GWAS and eQTL datasets to investigate causality and reduce confounding factors and reverse causation. Second, we systematically examined various antidepressant targets and stroke subtypes, and performed several sensitivity analyses to support our findings. Third, MR analysis of multiple cerebrovascular risk factors was performed to identify potential side effects and alternative indications crucial for future clinical applications. However, this study has several limitations, as follows. First, all participants included in the GWAS used in the present study were of European ancestry; therefore, our findings require validation in other races. Although our MR analysis indicated potential causal relationships, these associations should not be interpreted as direct evidence to indicate that antidepressants targeting these proteins would have causal effects on stroke risk. Inferring the actual pharmacological effects from genetic analyses is associated with complexities owing to variations in drug mechanisms, timing, magnitude, and duration of exposure. Although our colocalization analysis provided strong evidence to support the existence of shared causal variants in MPO and GRIN2D, the lack of colocalization evidence for other genes with MR evidence indicates that these relationships may require further investigation using larger datasets or complementary methods. Further studies are thus required to determine the effects of antidepressants on the risk of stroke. Our findings also require validation using independent datasets to ensure their robustness and broader applicability. Future research should thus explore downstream biomarkers to gain a more comprehensive understanding of the effects of antidepressant targets on stroke risk. As larger protein quantitative trait locus datasets become available, the investigation of drug-target relationships should be enhanced. Moreover, there is the potential for survivor bias because the GWAS primarily recruited survivors, possibly missing the genetic risk profiles of those who did not survive severe strokes. Finally, we identified a robust causal relationship between MPO and HF, with HF mediating the association between MPO and IS risk. Further research in non-HF patients is required to minimize potential pleiotropic effects. In conclusion, our drug target MR analysis provides insights into the associations between antidepressant targets and stroke, guiding the selection of antidepressants for individuals at risk of stroke, and identifying MPO and GRIN2D as promising stroke drug targets. However, further research is required to verify the long-term effects of antidepressants on stroke risk.

1 病例资料 65岁男性,因突发左侧肢体乏力伴言语不清20h于2021年5月24日急诊入院.既往有高血压病6年,未规律监测血压及用药;有糖尿病6年,长期服用二甲双胍+格列齐特,未规律监测血糖.入院体格检查:GCS评分15分,NIHSS评分4分.急诊头颈部CTA显示基底动脉局部未见显影.入院后予以双抗、降脂、改善循环等药物治疗.

BACKGROUND:The main treatment for a ruptured sinus of Valsalva aneurysm (SVA) is surgical repair. Postoperative progression of aortic regurgitation (AR) following SVA repair increases the risk of reoperation, which decreases the long-term survival. Thus, identifying the risk factors for postoperative AR progression is of great significance.METHODS:Adult patients who were diagnosed with ruptured SVA and underwent surgical repair at the current centre were reviewed. Necessary data in the institutional database were extracted. The perioperative and follow-up assessments of the aortic valve by transthoracic echocardiography were also obtained. The aortic regurgitation progression was grouped into three categories: newly developing, recurrence, and worsening. Sixteen (16) variables were screened to identify potential risk factors by univariate logistic regression analysis or Chi-squared test. Variables with p-values <0.1 were further analysed by multivariate logistic regression models to find independent risk factors.RESULTS:A total of 198 consecutive patients from June 2006 to January 2018 were included. The overall incidence of postoperative AR progression was 19.2% (38 of 198). After the univariate analysis, SVA originating from the right coronary sinus, coexisting with ventricular septal defect, larger diameter of aortic annulus, and larger cardiothoracic ratio were screened as potential risk factors. Multivariate analysis indicated that coexisting with a ventricular septal defect (VSD) (OR, 2.82; 95% CI, 1.217-6.532; p=0.016) and larger cardiothoracic ratio (OR, 1.061; 95% CI, 1.001-1.124; p=0.047) were independent risk factors for postoperative AR progression.CONCLUSIONS:To prevent postoperative AR progression after surgical repair, more careful inspection and appropriate surgical techniques are necessary for patients coexisting with VSD or with a larger cardiothoracic ratio.

Objective:To explore the value of quantitative parameters of dynamic CT myocardial perfusion imaging (CT-MPI) in evaluating coronary microcirculation dysfunction (CMD) in a porcine model.Methods:Ten Chinese miniature pig age of 5 to 8 months were randomly selected in this experimental study. After anesthesia, a micro guide wire was introduced via a percutaneous direct puncture through superficial femoral artery. Then 1 ml of microsphere mixture, which contained 0.5×10 5/0.5 ml of microsphere, was slowly injected into the distal of anterior descending artery to establish a CMD animal model. Resting and stress CT-MPI were performed 60 min before and 10 min after CMD. The quantitative parameters of dynamic CT-MPI including myocardial blood flow (MBF) and myocardial blood volume (MBV) were measured. Using the changes of MBF and MBV before and after CMD as self-references, a paired-sample t test was used to compare the differences of MBF and MBV of resting and stress CT-MPI before and after CMD. The animals were sacrificed for myocardial histopathological examination after the imaging examination. Results:Of the 10 experimental animals, two pigs died, and CMD model was successfully established in the other 8 pigs. The MBF and MBV of CMD myocardial segments in resting CT-MPI were (98.6±20.9) ml·100 ml -1·min -1 and (9.0±2.8) ml/100 ml, respectively. The MBF and MBV of CMD myocardial segments in stress CT-MPI were (87.6±14.6) ml·100 ml -1·min -1 and (8.0±1.8) ml/100 ml, respectively. Both of the MBF and MBV of CMD myocardial segments in resting CT-MPI were significantly reduced, compared with those of the normal myocardial segments ( P<0.001). HE staining showed myocardial infarcts interspersed with normal myocardial foci at low magnification. Pathological alterations, including myocardial cytoplasm cohesion, eosinophil level variations, stripe disappearance, nuclear relocation, and cardiomyocyte interstitial edema, were displayed at high-magnification by microscopy. Conclusions:In this experimental study of CMD animal models, MBF and MBV of dynamic CT-MPI were significantly decreased in CMD myocardial segments compared with those before CMD. The changes of MBF or/and MBV can be used as dynamic CT-MPI quantitative parameters for evaluation of CMD.

SIRT1 (silent information regulator 1) is a histone deacetylase. It can sense the energy level in cells and delay cell senescence, leading to resistance to external stress and improving metabolism. Mitral regurgitation (MR) is a common disease in cardiac surgery. However, there are no previous studies on SIRT1 and left atrial fibrosis caused by MR. In this study, we aimed to explore the regulatory effect of SIRT1 on left atrial fibrosis induced by MR. We used Guizhou miniature pigs to establish an MR model and a sham operation model after anaesthesia induction and respiratory intubation, and these model animals were followed for 30 months after the surgery. The differential distribution and expression of SIRT1 and collagen I in the left atrium was determined by immunofluorescence and Western blotting. Furthermore, we treated NIH3T3 fibroblasts (CFs) with resveratrol and Angiotensin II (Ang II) to analyse the specific mechanism involved in the development of myocardial fibrosis. The results showed that the MR model was successfully constructed. There were 8 pigs in the MR group and 6 pigs in the control group. In both the animal experiments and the cell experiments, the expression of collagen I in the MR group was increased significantly compared to that in the control group, while the expression of SIRT1 was decreased.

Background: Cardiopulmonary bypass is the basis of open heart surgery. Through simulation-based learning, residents may receive structured training of cardiopulmonary bypass techniques. Therefore, we built a high-fidelity, tissue-based simulation model for cardiopulmonary bypass cannulation/decannulation training. Methods: The core of the model is a whole block of cadaveric animal heart and lung. The discarded membrane oxygenators are used as blood reservoirs. The tubing and suckers recycled from animal experiments are washed and reused. To set up the model, the cadaveric heart and lung are placed into a container of appropriate size. The “arterial” tubing is connected with a pressure gauge, the distal aorta, the superior vena cava, and arterial cannula, respectively. The “venous” tubing is composed of three independent catheters, respectively, for the practice of venous cannulation, for the connection of sucker and for the practice of placing left atrial/ventricular vent. All tubes are installed on the roller pumps to maintain the correct flow direction. A technician should be responsible for operating the heart–lung machine, clamping and releasing the specific segments of tubing, adjusting the pressure, and cooperating with the trainees to practice. Results: Using the simulation model, 18 residents underwent cardiopulmonary bypass techniques training, with an average satisfaction of 8.94 points. The mean score on the overall fidelity of the simulation model assessed by nine experienced cardiothoracic surgeons was 8.67 points. Conclusion: The tissue-based simulation model has a certain degree of realism. Cardiac surgery residents can practice necessary cardiopulmonary bypass cannulation/decannulation techniques by this model.

Objectives This study was conducted to investigate whether percutaneous closure of ruptured sinus of Valsalva aneurysm (SVA) is as safe and effective as surgery repair. Background Percutaneous closure of ruptured SVA has been becoming an alternative to the traditional surgical repair recently. The reports regarding direct comparison of these two treatment options are scarce. Methods The medical records from the institutional database were retrospectively analyzed. A total of 134 patients were reviewed, including 26 patients undergoing percutaneous closure and 108 patients being treated surgically. To reduce the potential bias, 32 patients from Surgical Repair group were selected by propensity score matching. Results All the ruptured SVAs were successfully closed in each group. No severe procedure-related complications were found in the perioperative period. After matching, there were no significant differences in the baseline clinical characteristics. The median postoperative hospital stays of Matched group were significantly longer than that of Percutaneous Closure group (7 days vs. 1 day,p < .001). Aortic regurgitation, residual shunt and recurrence of SVAs were common complications in both Percutaneous Closure group and Surgical Repair group. Conclusions The appropriately selected patients with ruptured SVA could be treated by percutaneous closure with an acceptable risk of short-term complications. Though surgical repair remains the main treatment option for ruptured SVAs, percutaneous closure could be considered in patients with a small-size rupture and no associated cardiac abnormalities.

目的 观察腺苷对心肌灌注的影响,对比腺苷负荷前后心肌灌注变化,并得出定量指标.方法 对10只中华小型猪依次行静息态及负荷态动态CT心肌灌注成像(CT-MPI),测量左心室心肌17个节段、右冠状动脉(RCA)、左前降支(LAD)及回旋支(LCx)3支血管支配心肌,基底部、中间部、心尖部(包括心尖)3个区域及心肌各壁所属节段心肌血流量(MBF)、心肌血容量(MBV)、达峰时间(TTP)及组织通过时间(TTT).将心肌节段分为静息组和负荷组,比较组间MBF、MBV、TTP及TTT差异.通过腺苷负荷后心肌血流灌注量化指标改变,观察腺苷对冠状动脉微循环的负荷效能.结果 静息组MBF、MBV、TTP及TTT分别为(199.82±66.24)ml/(100 ml·min)、(15.71±5.58)ml/100 ml、(6.38士2.03)s及(13.39±4.91)s;负荷组分别为(278.87±123.24)ml/(100 ml·min)、(20.91±7.66)ml/100 ml、(5.83±1.68)s及(12.53±4.49)s.相比静态组,负荷组MBF、MBV显著升高、TTP缩短(t=8.757、7.738、3.367,P均＜0.05),2组TTT差异无统计学意义(t=1.743,P＞0.05).结论 腺苷可增加心肌小型猪血流灌注、缩短灌注TTP;结合动态CT-MPI,可定量分析负荷前后心肌灌注变化及程度.正常心肌组织灌注储备不受腺苷影响.

通过动物实验,对一种新型国产二尖瓣夹合器系统的可行性和安全性进行评价.14只正常三元杂交系猪分为实验组10只和对照组4只,实验组植入新型二尖瓣夹合器系统,对照组行传统二尖瓣修复术.分别于术前、术后不同时间点行超声心动图检查、血液检查,术后140 d对动物安乐死取材,进行心脏及主要脏器大体、病理检查,观察植入后的情况.实验组共8只动物、对照组共4只动物达到实验终点,所有动物术中未出现夹合器脱落、心脏破裂、瓣膜损伤、顽固性心律失常、脏器栓塞、心力衰竭、死亡等严重并发症.超声显示,所有夹合器均固定在二尖瓣处,不同时间点二尖瓣平均跨瓣压差、左心室射血分数等两组间均未见具有统计学意义的差异.血液学检查,未见植入器械对肝肾功能产生明显影响.病理检查提示,夹合器周围瓣叶呈现慢性炎症、黏液样变性、少量出血,未引起二尖瓣及心脏组织损伤,未出现心脏血栓、感染,各脏器也未见血栓栓塞.动物实验结果表明,新型国产二尖瓣夹合器系统生物相容性好,能够有效固定在二尖瓣处而不引起严重的相关并发症.

Purpose: To investigate the hemodynamics characteristics of the "no-touch" saphenous vein graft (SVG) conduits by nicardipine intraluminal administration in vivo experiment. Methods: A total of 59 consecutive patients were enrolled and underwent a sequential SVG to three non-left anterior descending (LAD) targets with the average runoff >= 2 mm, 30 with "no-touch" harvest technique (group A) and 29 with conventional preparation (group B). The patients were subject to nicardipine intraluminal injection during offpump coronary artery bypass grafting (CABG) procedure. The intraoperative flow was measured with the ultrasonic transit time flow meter (TTFM), and the graft patency testified by multi-detector computed tomography (MDCT) angiography, respectively. Results: The baseline blood flow was higher in group A than that in group B (p <0.05). However, the increases in blood flow of SVG conduits in group A were lower than those in group B with 19.7 +/- 5.9 vs. 35.4 +/- 9.2 mL/min, 14.8 +/- 5.6 vs. 23.1 +/- 6.8 mL/min, 6.6 +/- 2.1 vs. 11.2 +/- 4.3 mL/min before the first, second, and third anastomose after nicardipine intraluminal administration, respectively (all p <0.01). Conclusions: No-touch SVGs were associated with higher baseline blood flow and less rises after nicardipine intraluminal administration during off-pump CABG procedure compared with conventional preparation. The no-touch SVGs seemed to be less spastic and well-tolerated on flow dilatation.

Objective: Many countries are facing a shortage of cardiac surgeons, who are crucial in meeting the demands of growing number of patients in need of coronary artery bypass grafting. This situation poses a serious challenge, especially in China. The purpose of this study is to determine whether cardiac surgeons are suitable for training in coronary artery anastomosis at an earlier stage in their career. Methods: We divided 12 cardiac surgeons with no prior experience in coronary artery anastomosis into senior and junior groups for training and assessment. All trainees received training in coronary artery anastomosis for a defined period. We performed in vivo and in vitro examinations before and after training, respectively. Additionally, we assessed individual surgical performance of surgeons by using performance rating scores, including different aspects of surgical skills rated on a five-point scale. Results: The post-training scores (overall, junior, senior) were significantly higher than the pre-training scores (overall, junior, and senior). We observed no differences in pre-training and post-training scores between the junior and senior groups. Conclusion: Senior surgeons did not had any significant advantages over junior surgeons with respect to coronary artery anastomosis in the absence of training. Junior surgeons achieved the same results as the senior surgeons after training.

OBJECTIVESSurgical intervention is the main treatment for a ruptured congenital sinus of Valsalva aneurysm (SVA). However, reports on the surgical experience are scarce. We retrospectively analysed the cases of our centre to summarize our 10-year experience.METHODSA total of 286 patients who were diagnosed with a congenital ruptured SVA and underwent surgical repair between 2007 and 2016 were identified for the analysis. Follow-up data (mean ± standard deviation: 49.6 ± 34.9 months) were obtained from outpatient department records and telephone calls.RESULTSThe SVAs originated from the right coronary sinus (79.7%), the non-coronary sinus (19.6%) and the left coronary sinus (0.7%) but ruptured into the right ventricle (58.4%) and the right atrium (41.3%). The most commonly associated deformities were a ventricular septal defect (46.3%), aortic valve regurgitation (33.2%) and tricuspid regurgitation (20.3%). The SVA defect was closed by direct suturing (9.1%) or patching (90.9%) through an incision in the cardiac chamber involved or a transaortic approach. The mean postoperative hospital stay duration was 7.2 days, and 98.6% of the patients were discharged in New York Heart Association functional class I or II. The incidence rate of short-term complications was 5.7%. There were 4 late deaths, and 9 patients required rehospitalization due to surgery-related events. The estimated 10-year survival rate was greater than 90% according to the Kaplan-Meier survival curve.CONCLUSIONSSurgical repair is an effective and safe treatment for a ruptured SVA. The majority of patients who undergo surgical repair can survive for a long time.

The present study was performed to evaluate the feasibility and safety of the ValveClamp system for transcatheter edge‐to‐edge mitral valve repair in a porcine model.

There is still no satisfactory large-animal model of ischemic heart failure (IHF) with ideal survival rate and model time. The aim of this study is to explore a novel chronic IHF model in swine. 23 healthy Ba-Ma miniature pigs were included. Pigs in the experimental group underwent multiple strategic ligations on side branches of the left anterior descending (LAD) and circumflex coronary arteries. One week later, sequential intervention occlusion of the distal end of the LAD trunk was performed. In the experimental groups, LV end-diastolic (LVEDV) and end-systolic volume (LVESV) gradually increased starting at 4 weeks post operation. At 12 WPO, LVEDV increased from 45.0 ± 2.9 ml at baseline to 110.0 ± 9.8 ml and LVESV increased from 17.0 ± 1.4 ml at baseline to 42.0 ± 3.6 ml. Meanwhile, left ventricular ejection fraction significantly decreased from 73.8 ± 4.2 % at baseline to 31.0 ± 2.5%. According to histomorphometric assessment, viable cells were observed in infarction lesions, indicating the model has replicated the structural and functional features of chronic IHF.

OBJECTIVES The aim of this study was to investigate the operability, 6-month efficacy, and safety of the novel sirolimus-eluting iron bioresorbable coronary scaffold (IBS) system compared with a cobalt-chromium everolimus-eluting stent (EES) (XIENCE Prime stent) in porcine coronary arteries. BACKGROUND Bioresorbable scaffolds have been considered the fourth revolution in percutaneous coronary intervention. However, the first-generation bioresorbable scaffold showed suboptimal results. METHODS Forty-eight IBS and 48 EES were randomly implanted into nonatherosclerotic swine. The operability, efficacy, and safety of the IBS and EES were evaluated using coronary angiography, optical coherence tomography, micro-computed tomography, scanning electron microscopy, and histopathologic evaluation at 7, 14, 28, 90, and 180 days after implantation. RESULTS The operability of the ultrathin IBS (similar to 70 mu m) was comparable with that of the EES, except for its visibility. There was no statistically significant difference in area stenosis between the IBS and EES from 28 to 180 days. The IBS maintained its integrity up to 90 days without corrosion, while corrosion was observed in a few struts in 2 of 10 IBS at 180 days. The percentage of endothelialization of IBS was higher than that of XIENCE Prime stents within 14 days after implantation. The fibrin score was higher in the IBS group at 28 days but comparable with the EES group at 90 and 180 days. No scaffold or stent thrombosis was seen in either group. No abnormal histopathologic changes in scaffolded or stented vessel segments and 5 main remote organs were observed in either group. CONCLUSIONS Preclinical results suggest that the novel IBS has comparable operability, mid-term efficacy, and safety with the EES, and its corrosion profile in porcine coronary arteries is reasonable, which could support initial clinical study of the IBS. (c) 2019 by the American College of Cardiology Foundation.

目的 探讨丝裂原活化蛋白激酶p38(p38 MAPK)抑制剂对高糖诱导神经母细胞瘤细胞SH-SY5Y凋亡的保护作用及机制.方法 将培养好的SH-SY5Y细胞随机分为6组,A、B、C组分别加入45、90、135 mmol/L高糖进行处理;D、E组分别加入10、25 μmol/L的p38 MAPK抑制剂PD169316预处理30 min,之后加入135 mmol/L高糖溶液进行培养;对照组常规培养不做干预;另随机选部分细胞用135 mmol/L高糖处理3h作为高糖对照组.采用Western blotting法检测细胞内磷酸化p38 MAPK及凋亡相关蛋白,用Annexin V-PI染色法检测细胞凋亡.结果 高糖处理1.5、3h,与对照组比较,A、B、C组磷酸化p38 MAPK蛋白相对表达量呈浓度依赖性升高、抗凋亡蛋白BCL-2相对表达量低、促凋亡蛋白BAX、BID、BAD相对表达量高(P均＜0.05).高糖处理6h,A组BCL-2蛋白相对表达量低,BAX、BID、BAD蛋白相对表达量高(P均＜0.05),而B、C组促凋亡蛋白未见明显变化(P均＞0.05).与高糖对照组比较,D、E组磷酸化p38 MAPK蛋白相对表达量低(P均＜0.05),BCL-2蛋白蛋白相对表达量高(P均＜0.05),BAD蛋白及BID蛋白相对表达量低(P均＜0.05),E组以上指标变化最明显(P均＜0.05).与对照组比较,C组细胞凋亡重;与C组比较,E组细胞凋亡轻.结论 p38 MAPK抑制剂可抑制高糖诱导的SH-SY5Y细胞凋亡,其作用机制可能与调控抗凋亡蛋白及促凋亡蛋白表达有关.

Background A “boot camp” program is commonly adopted in surgical skills training. Due to a shortage of cardiac surgeons, establishment of a well-designed training curriculum for cardiac surgery residents is needed in developing countries. Methods We established a comprehensive 3-module training curriculum, including: (1) the cardiopulmonary bypass establishment technique, (2) coronary artery anastomosis and (3) basic surgical skills of thoracoscopy. Each module was designed for one technique, with a training time of 1 week. Each module included theoretical knowledge learning, demonstration by senior surgeons, and practice through simulators and in vivo animal experiment. A series of questionnaires were used to assess the training effect. Results We organized 50 person-times of training. The overall satisfaction of residents participating in the entire 3-module training was 7.88 points (from a full score of 10 points). The satisfaction of each module was 8.94, 8.13, and 7.63, respectively. The survey suggested the training could increase trainees’ confidence in the operation (P < 0.05). Some trainees also proposed some suggestions for the further improvement of the curriculum. Conclusions It is feasible to develop a multimodule comprehensive surgical skill training curriculum for cardiac surgery residents in China, whose confidence can be effectively enhanced.

目的:构建小型猪二尖瓣反流致心力衰竭模型,探究慢性心力衰竭过程中硫化氢(H2S)体系的变化.方法:12只8月龄中华小型猪随机分为对照组(n=6)与二尖瓣反流组(n=6),采用小切口非体外循环下二尖瓣腱索拉伤造成二尖瓣反流建立慢性心力衰竭模型.6个月后采用超声心动图、在体血流动力学和病理学方法评价动物左心室结构和功能的变化,采用分子生物学方法检测心脏重构分子Ⅰ型胶原(CollagenⅠ)、Ⅲ型胶原(CollagenⅢ)和H2S合成酶体系中胱硫醚-β-合成酶(CBS)、胱硫醚-γ-裂解酶(CSE)蛋白和mRNA表达.结果:术后6个月二尖瓣反流组动物与对照组相比,左心室收缩末期容积(LVESV)和左心室舒张末期容积(LVEDV)明显增加[(18.50±2.88)ml vs(10.50±0.99)ml,P<0.05;(87.50±12.12)ml vs(42.33±2.04)ml,P<0.01],左心室收缩末期压力明显降低[(86.66±5.60)mmHg vs(117.70±5.49)mmHg,1 mmHg=0.133 kPa,P<0.01],但左心室射血分数(LVEF)无明显变化[(78.67±1.87)％vs(75.33±1.87)％,P>0.05].病理学可见二尖瓣反流组动物二尖瓣后瓣腱索断裂,瓣叶卷曲增厚,边缘不规则增生,石蜡切片染色可见左心室心肌细胞损伤、心肌间胶原纤维明显增多.二尖瓣反流组与对照组比较,血浆H2S水平明显降低[(27.48±2.78)μmol/L vs(37.87±3.55)μmol/L,P=0.044],血清N末端B型利钠肽原(NT-proBNP)水平明显升高[(2132.00±212.30)μg/L vs(456.70±40.79)μg/L,P<0.001].分子生物学手段检测二尖瓣反流组心肌组织与心脏重构相关的CollagenⅠ、CollagenⅢ水平明显上调,H2S合成相关的酶CSE、CBS明显下调.结论:H2S合成体系下调可能参与二尖瓣反流所致心肌重构和心力衰竭的发展过程.

目的 有毒醛的堆积可产生心血管毒性,乙醛脱氢酶2(ALDH2)可有效清除醛类物质,本研究旨在兔心肺转流(CPB)模型中探索ALDH2活化的心肌保护作用.方法 21只新西兰白兔随机分为三组:CPB不停跳组(C组)、停跳组(CA组)、停跳+Alda-1组(CAA组),Alda-1为ALDH2特异性激动剂,另随机选取21只作为供血兔.右腋动脉插管及右房插管建立CPB模型,主动脉阻断120 min后开放,生命体征平稳后停机,恢复心肌灌注120 min测定心功能并取左室心肌组织,测定ALDH2的含量及活性、4-羟基壬烯醛(4-HNE)含量、丙二醛(MDA)含量、氧化型与还原型谷胱甘肽比值(GSH/GSSG)、蛋白羰基含量,检测不同时点血气及血清肌酸磷酸激酶同工酶(CKMB)值.结果 各组间ALDH2含量无明显差异,CAA组与CA组相比ALDH2活性明显增加(P<0.001),4-HNE、MDA含量在CA组较C组增加(4-HNE:P<0.001,MDA:P=0.001),CAA组较CA组明显下降(4-HNE:P=0.013,MDA:P<0.001).CAA组较CA组心肌蛋白羰基水平、血清CKMB明显降低,GSH/GSSH生成增加(P<0.05),CAA组左室压力形成最大速率较CA组明显升高(P=0.040),但三组间左室舒张末压、左室收缩末压、左室压力形成最小速率无统计学差异.结论 CPB期间ALDH2活化可加强有毒醛清除,增强心肌抗氧化损伤能力,减轻心肌的氧化应激,改善心肌收缩功能.