Objective To summarize the clinical efficacy of modified Morrow surgery in the treatment of hypertrophic obstructive cardiomyopathy. Methods A retrospective analysis was conducted on the clinical data of patients with hypertrophic obstructive cardiomyopathy treated with modified Morrow surgery at Zhongshan Hospital Affiliated to Fudan University from 2020 to 2023. Results A total of 318 patients were enrolled, including 156 males and 162 females, with an average age of (55.6±13.1) years. Preoperative echocardiography showed a mean interventricular septal thickness of (18.1±3.8) mm, peak left ventricular outflow tract pressure difference of (86.4±24.9) mm Hg. The surgery time was (162.3±51.0) min, extracorporeal circulation time was (80.9±31.0) min, and aortic occlusion time was (44.8±20.8) min. After the surgery, transesophageal echocardiography showed that the interventricular septal thickness was (11.0±1.8) mm and left ventricular outflow tract peak pressure difference was (9.4±5.1) mm Hg. The incidence rate of postoperative complete left bundle branch block was 45.3%, Ⅲ° atrioventricular block was 3.8%, and postoperative newly developed atrial fibrillation was 3.1%. The postoperative hospital stay was (6.6±4.9) days, and one perioperative death occurred, with a mortality rate of 0.3%. The follow-up time was (10.3±9.4) months, during which the transthoracic echocardiography revealed a ventricular septal thickness of (12.9±2.9) mm and a peak left ventricular outflow tract pressure difference of (13.9±10.0) mm Hg. Conclusion The modified Morrow procedure for the treatment of hypertrophic obstructive cardiomyopathy is safe and effective, with good results in the short and medium term.

Background::The ratio of high-density lipoprotein cholesterol (HDL-C) to low-density lipoprotein cholesterol (LDL-C) predicts cardiovascular disease (CVD) endpoints, yet its prognostic validity in high-risk populations and for type 2 diabetes mellitus (T2DM)-related adverse events remains unestablished.Methods::This study included 32,609 people aged 35-75 years in Fujian Province, China, who were at high risk for CVD. The primary endpoint was all-cause mortality during follow-up. Cox proportional hazard models and restricted cubic spline (RCS) analysis were used to evaluate the correlation between the HDL-C/LDL-C ratio and the endpoints.Result::On the basis of the restricted RCS curve, the participants were classified as having a low (< 0.3), middle (0.3-0.5), or high (> 0.5) HDL-C/LDL-C ratio. Multivariate Cox regression analyses revealed that the risk of all-cause mortality (HR = 1.48, 95% CI 1.14-1.93, p < 0.01 for low; HR = 1.30, 95% CI 1.06-1.58, p < 0.05 for high) was increased in the low and high groups. Participants without T2DM who were at high risk for CVD had similar prognoses (HR = 1.65, 95% CI 1.19-2.28, p < 0.01 for low; HR = 1.35, 95% CI 1.05-1.74, p < 0.01 for high). However, this association was not found in participants with T2DM who were at high risk for CVD. Conclusion::HDL-C/LDL-C can be used to predict the prognosis of individuals at high risk for CVD, and maintaining HDL-C/LDL-C ratios between 0.3 and 0.5 may be the most helpful range for this population. Furthermore, maintaining this ratio range holds clinical significance for cohorts without T2DM, although further exploration is needed in this T2DM cohort.

Distinct from the complementary inhibition mechanism through binding to the target with three-dimensional conformation of small molecule inhibitors, targeted protein degradation technology takes tremendous advantage of endogenous protein degradation pathway inside cells to degrade plenty of “undruggable” target proteins, which provides a novel route for the treatment of many serious diseases, mainly including proteolysis-targeting chimeras, lysosome-targeting chimeras, autophagy-targeting chimeras, antibody-based proteolysis-targeting chimeras, etc. Unlike proteolysis-targeting chimeras first found in 2001, which rely on ubiquitin-proteasome system to mainly degrade intracellular proteins of interest, lysosome-targeting chimeras identified in 2020, which was act as the fastly developing technology, utilize cellular lysosomal pathway through endocytosis mediated by lysosome-targeting receptor to degrade both extracellular and membrane proteins. As an emerging biomedical technology, nucleic acid-driven lysosome-targeting chimeras utilize nucleic acids as certain components of chimera molecule to replace with ligand to lysosome-targeting receptor or protein of interest, exhibiting broad application prospects and potential clinical value in disease treatment and drug development. This review mainly introduced present progress of nucleic acid-driven lysosome-targeting chimeras technology, including its basic composition, its advantages compared with antibody or glycopeptide-based lysosome-targeting chimeras, and focused on its chief application, in terms of the type of lysosome-targeting receptors. Most research about the development of nucleic acid-driven lysosome-targeting chimeras focused on those which utilized cation-independent mannose-6-phosphonate receptor as the lysosome-targeting receptor. Both mannose-6-phosphonate-modified glycopeptide and nucleic aptamer targeting cation-independent mannose-6-phosphonate receptor, even double-stranded DNA molecule moiety can be taken advantage as the ligand to lysosome-targeting receptor. The same as classical lysosome-targeting chimeras, asialoglycoprotein receptor can also be used for advance of nucleic acid-driven lysosome-targeting chimeras. Another new-found lysosome-targeting receptor, scavenger receptor, can bind dendritic DNA molecules to mediate cellular internalization of complex and lysosomal degradation of target protein, suggesting the successful application of scavenger receptor-mediated nucleic acid-driven lysosome-targeting chimeras. In addition, this review briefly overviewed the history of lysosome-targeting chimeras, including first-generation and second-generation lysosome-targeting chimeras through cation-independent mannose-6-phosphonate receptor-mediated and asialoglycoprotein receptor-mediated endocytosis respectively, so that a clear timeline can be presented for the advance of chimera technique. Meantime, current deficiency and challenge of lysosome-targeting chimeras was also mentioned to give some direction for deep progress of lysosome-targeting chimeras. Finally, according to faulty lysosomal degradation efficiency, more cellular mechanism where lysosome-targeting chimeras perform degradation of protein of interest need to be deeply explored. In view of current progress and direction of nucleic acid-driven lysosome-targeting chimeras, we discussed its current challenges and development direction in the future. Stability of natural nucleic acid molecule and optimized chimera construction have a great influence on the biological function of lysosome-targeting chimeras. Discovery of novel lysosome-targeting receptors and nucleic aptamer with higher affinity to the target will greatly facilitate profound advance of chimera technique. In summary, nucleic acid-driven lysosome-targeting chimeras have many superiorities, such as lower immunogenicity, expedient synthesis of chimera molecules and so on, in contrast to classical lysosome-targeting chimeras, making it more valuable. Also, the chimera technology provides new ideas and methods for biomedical research, drug development and clinical treatment, and can be used more widely through further research and optimization.

All four patients were female, with an average age of 28.8 days and an average weight of 3.64 kg. Only case 4 was born prematurely at 34 W+5 and was treated conservatively until 71 days to complete operation. All the others completed primary corrective surgery in the neonatal period, and all survived after operation. Two different surgical techniques were used to repair the aortic-pulmonary window and the aortic origin of the right pulmonary artery, including 1 case using the aortic internal baffle technique and another 3 cases underwent replantation of the right pulmonary artery (1 case was reconstructed in situ, and the other 2 cases were reconstructed by moving the right pulmonary artery in the anterior of aorta). Case 2 who received aortic internal baffle technique underwent two reoperation because of right pulmonary artery stenosis. While, right pulmonary artery of cases 3 and 4 developed well after being reconstructed the right pulmonary artery anterior translocation. After the diagnosis of Berry syndrome through cardiac color ultrasound and CT angiography, a primary surgical radical treatment should be performed as soon as possible at an experienced pediatric cardiac center. Although the surgery is high-risk and complex, it is safe and effective.

Objective:To determine the safety and efficacy of the modified off-pump biatrial mini-maze procedure to treat isolated atrial fibrillation.Methods:This study retrospectively included isolated atrial fibrillation patients who underwent the modified off-pump biatrial mini-maze procedure at the Department of Cardiothoracic Surgery, Zhongshan Hospital, Fudan University from January 2021 to December 2023. These patients underwent a mini-maze procedure using the Dallas lesion set protocol. A purse-string suture was then performed on the right atrium, and 4 ablation lesions were made to the superior vena cava, the inferior vena cava, the appendix of the right atrium and the tricuspid valve annulus from the purse-string suture point using the bipolar radiofrequency clamp. After the operation, the patients were followed up at 3, 6 and 12months and every year thereafter.Results:A total of 301 patients were followed up. There were no deaths or strokes. A follow-up at intervals of 3, 6, 12, 24 and 36 months showed that the cumulative success rate free from isolated atrial fibrillation was 96.0%、91.0%、85.9%、79.5% and 72.7%.Conclusion:The modified off-pump biatrial mini-maze procedure is safe and effective and can be considered as an off-pump ablation option for patients and cardiac surgeons.

Objective:Coarctation of the aorta is a genetically related diffuse aortic disease. Even after successful repair and with normal blood pressure, patients have a significant increase of risk in long-term cardiovascular events. Coarctation of the aorta accounts for 6%-8% of congenital heart diseases. Although the results of surgery and interventional treatment are satisfactory, the long-term survival rate of patients is still lower than that of health people, and there is a high proportion of re-intervention. Factors affecting prognosis include concomitant diseases, genetic characteristics, restenosis, hypertension, heart failure, neurodevelopmental disorders, obesity, psychology, etc. Therefore, people with coarctation of the aorta need cardiovascular monitoring throughout their life cycle. Currently, there are relevant guidelines of follow-up management for adult patients, but there is still no clear cardiovascular monitoring strategy for child and adolescent patients in transition. Based on a large number of domestic and foreign literature and clinical experience, this article summarizes the follow-up management strategies for full-life cardiovascular monitoring immediately after the repair of coarctation of the aorta in infancy and childhood from the perspective of concomitant diseases, genetic characteristics and long-term complications.

Background::The ratio of high-density lipoprotein cholesterol (HDL-C) to low-density lipoprotein cholesterol (LDL-C) predicts cardiovascular disease (CVD) endpoints, yet its prognostic validity in high-risk populations and for type 2 diabetes mellitus (T2DM)-related adverse events remains unestablished.Methods::This study included 32,609 people aged 35-75 years in Fujian Province, China, who were at high risk for CVD. The primary endpoint was all-cause mortality during follow-up. Cox proportional hazard models and restricted cubic spline (RCS) analysis were used to evaluate the correlation between the HDL-C/LDL-C ratio and the endpoints.Result::On the basis of the restricted RCS curve, the participants were classified as having a low (< 0.3), middle (0.3-0.5), or high (> 0.5) HDL-C/LDL-C ratio. Multivariate Cox regression analyses revealed that the risk of all-cause mortality (HR = 1.48, 95% CI 1.14-1.93, p < 0.01 for low; HR = 1.30, 95% CI 1.06-1.58, p < 0.05 for high) was increased in the low and high groups. Participants without T2DM who were at high risk for CVD had similar prognoses (HR = 1.65, 95% CI 1.19-2.28, p < 0.01 for low; HR = 1.35, 95% CI 1.05-1.74, p < 0.01 for high). However, this association was not found in participants with T2DM who were at high risk for CVD. Conclusion::HDL-C/LDL-C can be used to predict the prognosis of individuals at high risk for CVD, and maintaining HDL-C/LDL-C ratios between 0.3 and 0.5 may be the most helpful range for this population. Furthermore, maintaining this ratio range holds clinical significance for cohorts without T2DM, although further exploration is needed in this T2DM cohort.

Objective:To establish venetoclax-resistant acute myeloid leukemia(AML)cell lines,assess the sensitivity of venetoclax-resistant cell lines to the BCL-2 protein family,and investigate their resistance mechanisms.Methods:CCK-8 method was used to screen AML cell lines(MV4-11,MOLM13,OCI-AML2)that were relatively sensitive to venetoclax.Low concentrations of venetoclax continuously induced drug-resistance development in the cell lines.Changes in cell viability and apoptosis rate before and after resistance development were measured using the CCK-8 method and flow cytometry.BH3 profiling assay was performed to anayze the transform of mitochondrion-dependent apoptosis pathway as well as the sensitivity of resistant cell lines to BCL-2 family proteins and small molecule inhibitors.Real-time fluorescence quantitative PCR(RT-qPCR)was utilized to examine changes in the expression levels of BCL-2 protein family members in both venetoclax-resistant cell lines and multidrug-resistant patients.Results:Venetoclax-resistant cell lines of MV4-11,MOLM13,and OCI-AML2 were successfully established,with IC50 values exceeding 10-fold.Under the same concentration of venetoclax,the apoptosis rate of resistant cells decreased significantly(P＜0.05).BH3 profiling assay revealed that the drug-resistant cell lines showed increased sensitivity to many pro-apoptotic proteins(such as BIM,BID and NOXA).RT-qPCR showed significantly upregulated MCL1 and downregulated NOXA1 were detected in drug-resistant cell lines.Expression changes in MCL1 and NOXA1 in venetoclax-resistant patients were consistent with our established drug-resistant cell line results.Conclusion:The venetoclax-resistant AML cell lines were successfully established through continuous induction with low concentrations of venetoclax.The venetoclax resistance resulted in alterations in the mitochondrial apoptosis pathway of the cells and an increased sensitivity of cells to pro-apoptotic proteins BIM,BID,and NOXA,which may be associated with the upregulation of MCL1 expression and downregulation of NOXA1 expression in the drug-resistant cells.

Objective:To determine the safety and efficacy of the modified off-pump biatrial mini-maze procedure to treat isolated atrial fibrillation.Methods:This study retrospectively included isolated atrial fibrillation patients who underwent the modified off-pump biatrial mini-maze procedure at the Department of Cardiothoracic Surgery, Zhongshan Hospital, Fudan University from January 2021 to December 2023. These patients underwent a mini-maze procedure using the Dallas lesion set protocol. A purse-string suture was then performed on the right atrium, and 4 ablation lesions were made to the superior vena cava, the inferior vena cava, the appendix of the right atrium and the tricuspid valve annulus from the purse-string suture point using the bipolar radiofrequency clamp. After the operation, the patients were followed up at 3, 6 and 12months and every year thereafter.Results:A total of 301 patients were followed up. There were no deaths or strokes. A follow-up at intervals of 3, 6, 12, 24 and 36 months showed that the cumulative success rate free from isolated atrial fibrillation was 96.0%、91.0%、85.9%、79.5% and 72.7%.Conclusion:The modified off-pump biatrial mini-maze procedure is safe and effective and can be considered as an off-pump ablation option for patients and cardiac surgeons.

Objective:Coarctation of the aorta is a genetically related diffuse aortic disease. Even after successful repair and with normal blood pressure, patients have a significant increase of risk in long-term cardiovascular events. Coarctation of the aorta accounts for 6%-8% of congenital heart diseases. Although the results of surgery and interventional treatment are satisfactory, the long-term survival rate of patients is still lower than that of health people, and there is a high proportion of re-intervention. Factors affecting prognosis include concomitant diseases, genetic characteristics, restenosis, hypertension, heart failure, neurodevelopmental disorders, obesity, psychology, etc. Therefore, people with coarctation of the aorta need cardiovascular monitoring throughout their life cycle. Currently, there are relevant guidelines of follow-up management for adult patients, but there is still no clear cardiovascular monitoring strategy for child and adolescent patients in transition. Based on a large number of domestic and foreign literature and clinical experience, this article summarizes the follow-up management strategies for full-life cardiovascular monitoring immediately after the repair of coarctation of the aorta in infancy and childhood from the perspective of concomitant diseases, genetic characteristics and long-term complications.