1.Tetrahydrocurcumin protects against thoracic aortic aneurysm and dissection in mice by activating the SIRT3 signaling pathway
Xiangyan PENG ; Bin ZHANG ; Xinan QIAO ; He SUN ; Liqing JIANG ; Hanzhao ZHU ; Zhenxiao JIN ; Jincheng LIU ; Weixun DUAN
Acta Laboratorium Animalis Scientia Sinica 2025;33(3):311-323
Objective To investigate the protective effects and potential mechanisms of tetrahydrocurcumin(THC)on thoracic aortic aneurysm and dissection(TAAD)in mice.Methods TAAD was induced in 3-week-old C57BL/6J mice by oral administration of β-aminopropionitrile(BAPN)(diluted in drinking water,1 g/(kg·d)).Eighty mice were divided randomly into Con,BAPN,BAPN+THC,and BAPN+THC+3-TYP(SIRT3 inhibitor)groups(n=20 mice per group).The survival rate of mice in each group was recorded after 4 weeks.The maximum diameter of the aorta was measured and the histomorphology and aortic wall elastin integrity were evaluated by hematoxylin and eosin and elastin van Gieson staining.Macrophage infiltration was detected by immunohistochemical staining and α-smooth muscle actin(α-SMA)and osteopontin(OPN)expression were detected by immunofluorescence staining.The production of reactive oxygen species(ROS)was measured by dihydroethidium staining and superoxide dismutase(SOD)activity and malondialdehyde(MDA)levels were determined using kits.Protein expression levels of matrix metalloproteinase(MMP)2,MMP9,interleukin(IL)-6,tumor necrosis factor(TNF)-α,nuclear factor erythroid 2-related factor 2(NRF2),NADPH oxidase 2(NOX2),α-SMA,OPN,sirtuin 3(SIRT3),Ac-SOD2,and SOD2 were measured by Western Blot.Results Mice in the BAPN+THC group showed significantly higher survival and a lower incidence of TAAD compared with the BAPN group and the degree of aortic dilatation and morphology and structure were improved(P<0.05).Infiltration of CD68-positive macrophages and MMP2,MMP9,IL-6,and TNF-α expression levels were lower(P<0.05),ROS generation,MDA content,and NOX2 expression in aortic tissue were also significantly decreased,while SOD activity and NRF2 expression were increased(P<0.05).α-SMA expression was also increased,while OPN expression was reduced(P<0.05).SIRT3 expression was increased while the Ac-SOD2/SOD2 ratio was decreased(P<0.01).Treatment with the SIRT3-specific inhibitor and silencing of SIRT3 counteracted the ability of THC to resist TAAD via the SIRT3 signaling pathway(all P<0.05).Conclusions THC alleviated inflammation and oxidative stress in aortic tissues by activating the SIRT3 signaling pathway,thus inhibiting the phenotypic transformation of vascular smooth muscle cells and resisting the formation of TAAD in mice.
2.Tetrahydrocurcumin protects against thoracic aortic aneurysm and dissection in mice by activating the SIRT3 signaling pathway
Xiangyan PENG ; Bin ZHANG ; Xinan QIAO ; He SUN ; Liqing JIANG ; Hanzhao ZHU ; Zhenxiao JIN ; Jincheng LIU ; Weixun DUAN
Acta Laboratorium Animalis Scientia Sinica 2025;33(3):311-323
Objective To investigate the protective effects and potential mechanisms of tetrahydrocurcumin(THC)on thoracic aortic aneurysm and dissection(TAAD)in mice.Methods TAAD was induced in 3-week-old C57BL/6J mice by oral administration of β-aminopropionitrile(BAPN)(diluted in drinking water,1 g/(kg·d)).Eighty mice were divided randomly into Con,BAPN,BAPN+THC,and BAPN+THC+3-TYP(SIRT3 inhibitor)groups(n=20 mice per group).The survival rate of mice in each group was recorded after 4 weeks.The maximum diameter of the aorta was measured and the histomorphology and aortic wall elastin integrity were evaluated by hematoxylin and eosin and elastin van Gieson staining.Macrophage infiltration was detected by immunohistochemical staining and α-smooth muscle actin(α-SMA)and osteopontin(OPN)expression were detected by immunofluorescence staining.The production of reactive oxygen species(ROS)was measured by dihydroethidium staining and superoxide dismutase(SOD)activity and malondialdehyde(MDA)levels were determined using kits.Protein expression levels of matrix metalloproteinase(MMP)2,MMP9,interleukin(IL)-6,tumor necrosis factor(TNF)-α,nuclear factor erythroid 2-related factor 2(NRF2),NADPH oxidase 2(NOX2),α-SMA,OPN,sirtuin 3(SIRT3),Ac-SOD2,and SOD2 were measured by Western Blot.Results Mice in the BAPN+THC group showed significantly higher survival and a lower incidence of TAAD compared with the BAPN group and the degree of aortic dilatation and morphology and structure were improved(P<0.05).Infiltration of CD68-positive macrophages and MMP2,MMP9,IL-6,and TNF-α expression levels were lower(P<0.05),ROS generation,MDA content,and NOX2 expression in aortic tissue were also significantly decreased,while SOD activity and NRF2 expression were increased(P<0.05).α-SMA expression was also increased,while OPN expression was reduced(P<0.05).SIRT3 expression was increased while the Ac-SOD2/SOD2 ratio was decreased(P<0.01).Treatment with the SIRT3-specific inhibitor and silencing of SIRT3 counteracted the ability of THC to resist TAAD via the SIRT3 signaling pathway(all P<0.05).Conclusions THC alleviated inflammation and oxidative stress in aortic tissues by activating the SIRT3 signaling pathway,thus inhibiting the phenotypic transformation of vascular smooth muscle cells and resisting the formation of TAAD in mice.
3.Establishment of a mouse model of thoracic aortic dissection with acute lung injury by BAPN
Zhiyan MAI ; Liqing JIANG ; Hanzhao ZHU ; Liyun ZHANG ; Yun WANG ; Weixun DUAN
Acta Laboratorium Animalis Scientia Sinica 2024;32(1):9-16
Objective A feasible and stable mouse model of thoracic aortic dissection(TAD)combined with acute lung injury(ALI)was established using β-aminopropionitrile monofumarate(BAPN)1 g/(kg·d)administered in drinking water.The mouse model of TAD combined with acute lung injury(ALI)was established to provide a rational animal model to study TAD combined with ALI.Methods Forty-five SPF-grade 3-week-old C57BL/6J male mice were selected and randomly allocated to a CON group(normal dietary water;15 mice)or BAPN group(administration in sterile water at 1 g/(kg·d);30 mice)for 4 weeks.During the experimental period,the general condition and modeling rate of mice were observed.TAD model mice were validated,and the BAPN group was divided into TAD and non-TAD groups by measuring the maximum diameter of the thoracic aorta and HE staining of aortic tissues.HE pathological staining,the wet/dry weight(W/D)ratio,total protein level in bronchioalveolar lavage fluid(BALF),and interleukin(IL)-1 β,IL-6,and tumor necrosis factor-α(TNF-α)in BALF)were used to validate the TAD combined ALI model in mice.Results BAPN treatment significantly delayed the increase in body mass and water intake of mice.Compared with CON and non-TAD groups,the maximum diameter of the thoracic aorta of mice in the TAD group was significantly thickened(P<0.05).HE staining of the aorta showed significant thickening of the middle aortic layer,and the structure of the aortic wall was damaged and disordered.HE staining of lung tissues showed significant interstitial edema and inflammatory exudation accompanied by enlargement of alveolar lumen,alveolar wall epithelial exfoliation and hyaline membrane formation,and a significant increase in the pathological scores of lung injury(P<0.05).Total protein levels and expression of IL-1β,IL-6,and TNF-α in lung tissue,W/D ratio,and BALF were also significantly increased(P<0.05),whereas no significant difference was observed in the above indexes between the other two groups.Conclusions A mouse model of thoracic aortic dissection combined with acute lung injury can be established by BAPN administration in drinking water.
4.A meta-analysis of aortic root remodeling and replantation in acute Stanford type A aortic dissection
Jingwei SUN ; Jincheng LIU ; Weixun DUAN
Chinese Journal of Thoracic and Cardiovascular Surgery 2023;39(12):712-719
Objective:To systematically compare the safety and reliability of remodeling and reimplantation in aortic root valve preservation surgery for acute Stanford type A aortic dissection.Methods:We searched the databases of CNKI, VIP, Wanfang, CBM, Pubmed, EMBASE, Cochrane Central Register of Controlled Trials ( CENTRAL ) to find the clinical controlled research literature on acute type A aortic dissection remodeling and replantation. The relevant outcome indicators were analyzed by Review Manager 5.3 combined with Stata15.0 statistical software.Results:Seven studies involving 356 patients were included. Remodeling surgery versus replantation surgery. There was a higher incidence of postoperative grade Ⅱ or Ⅲ aortic regurgitation( OR=5.56, 95% CI: 1.89-16.41, P<0.05 ), higher 5-year reoperation rate ( OR=7.50, 95% CI: 2.11-26.65, P<0.05 ), shorter cardiopulmonary bypass time ( MD=-20.81, 95% CI: -35.08-6.54, P< 0.05 ), and longer aortic occlusion time ( MD=35.23, 95% CI: 21.21-49.26, P<0.05 ). The 30-day/in-hospital mortality( OR=1.09, 95% CI: 0.56-2.13, P>0.05) , postoperateive secondary thoracotomy for hemostasis( OR=2.91, 95% CI: 0.34-24.99, P>0.05), the rate of reoperation 1 year after surgery( OR=1.22, 95% CI: 0.20-7.56, P> 0.05) and 5-year mortality( OR=7.50, 95% CI: 2.11-26.65, P>0.05), were no significant difference between remodeling surgery group and replantation surgery group. Conclusion:Compared with replantation surgery, remodeling surgery in patients with acute type A aortic dissection has a higher incidence of grade Ⅱ or Ⅲ aortic insufficiency, a higher rate of reoperation 5 years after surgery, a shorter duration of cardiopulmonary bypass, and a longer duration of aortic occlusion. There were no statistically significant differences in postoperative hospitalization/30-day mortality, postoperative secondary thoracotomy, reoperation rate 1 year after surgery, and late mortality using remodeling and replantation techniques, which could be selected according to the actual situation of the aortic root and the experience of the surgeon.
5.Analysis of risk factors of death after cardiopulmonary bypass in children with congenital heart disease less than 5 kg
Jingjuan YANG ; Weixun DUAN ; Yanyan LI
Clinical Medicine of China 2022;38(1):73-78
Objective:To investigate the risk factors for surgical death in children with congenital heart disease (CHD) less than 5 kg undergoing cardiopulmonary bypass.Methods:The clinical data of 225 children with CHD who underwent open cardiopulmonary bypass in the First Affiliated Hospital of Air Force Military Medical University from February 2017 to February 2020 were collected for a retrospective case-control study. The independent sample T test was used for inter-group comparison of measurement data, Chi square test or chi squre correction test was used for the comparision between count data. Mann-Whitney rank-sum test was used for rank distribution data and multiple Logistic regression analysis was performed for factors affecting surgical death of children with CHD.Results:Among the 225 cases, 204 (90.67%, 204/225) survived surgery and 21 (9.33%, 21/225) died. Univariate analysis showed that age (2.48±0.68) months and body weight (2.28±0.56) kg in the death group were significantly lower than that in the survival group (4.92±0.65) months ( t=16.33, P<0.001) and body weight (4.26±0.52) kg ( t=16.38, P<0.001), while the proportion of female (66.67% (14/21)), malnutrition (none: 14.28% (3/21); Mild: 42.86% (9/21). Severity: 42.86%(9/21)), palliative surgery proportion (28.57%(6/21)), emergency surgery proportion (71.43%(15/21)), congenital heart surgery risk assessment (RACHS-1) grading ratio (
6.Retrospective cohort study of early and mid-term results of HCR and MICS-CABG in coronary artery disease patients with low ejection fraction and non diabetes mellitus
Hongliang LIANG ; Diancai ZHAO ; Kaijie WANG ; Pengfei JI ; Weixun DUAN ; Wei YI ; Xiaochao DONG ; Tao CHEN ; Shiqiang YU ; Jincheng LIU
Chinese Journal of Thoracic and Cardiovascular Surgery 2022;38(12):757-761
Objective:To compare the early and mid-term results of hybrid coronary revascularization (HCR) and minimally invasive multivessel coronary artery bypass grafting (MICS-CABG) in coronary artery disease patients with low left ventricular ejection fraction and non diabetes mellitus, and to explore the indication of HCR and MICS-CABG.Methods:A retrospective cohort analysis of HCR and MICS-CABG cases with preoperative left ventricular ejection fraction less than 0.40, and without diabetes mellitus were conducted in Xijing Hospital from January 2015 to December 2019. 36 cases in HCR group and 17 cases in MICS group were included in this study. For HCR procedure, minimally invasive left internal mammary artery(LIMA) to the left anterior descending artery (LAD) bypass surgery were performed, and followed by percutaneous coronary intervention (PCI) to treat non LAD lesion 1 to 4 weeks later. MICS-CABG procedure was performed through left anterior small thoracotomy minimally invasive direct coronary artery bypass grafting for multiple diseased vessels.Results:The preoperative SYNTAX score in MICS group was significantly higher than that in HCR group ( P<0.05). There was no perioperative death in both groups. Troponin I, postoperative drainage volume, blood transfusion volume and ventilator ventilation time in MICS group were significantly higher than those in HCR group ( P<0.05). After 12 months follow-up, no patient died in both groups. Furthermore, all LIMA grafts were patency. The stenosis rate of drug-eluting stents in HCR group was similar to that of great saphenous vein grafts in MICS group. LVEF and left ventricular end diastolic diameter of both groups were significantly improved 12 months after operation ( P<0.05). Conclusion:HCR and MICS-CABG are minimally invasive and safe treatment for multivessel coronary artery disease patients with low ejection fraction and non diabetese mellitus. The early and mid-term therapeutic effects are satisfactory. If coronary artery lesions other than LAD are suitable for PCI, HCR should be the preferred treatment.
7.The therapeutic effect and mid-term follow-up of 154 patients of multiple valvular surgery through right anterolateral intercostal thoracotomy: A retrospective cohort study
Hongliang LIANG ; Tao CHEN ; Weixun DUAN ; Wei YI ; Liang CHENG ; Xiaochao DONG ; Yang LIU ; Diancai ZHAO ; Pengfei JI ; Jincheng LIU
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2021;28(02):164-168
Objective To investigate the therapeutic effect, safety and effectiveness of multiple valvular surgery through right anterolateral intercostal thoracotomy, as well as the mid-term follow-up results and surgeon's learning curve. Methods The clinical data of 154 patients with multiple valvular disease were performed minimally invasive cardiac surgery in the Department of Cardiovascular Surgery, The First Affiliated Hospital of Air Force Medical University, from 2015 to 2019 were retrospectively analyzed. There were 103 males and 51 females, aged 23-68 years. Closed cardiopulmonary bypass was established through femoral artery and femoral vein, and the thoracic cavity was entered through a 6 cm transverse incision in the fourth intercostal space on the right side of sternum. Baseline and perioperative characteristics and postoperative outcomes were reviewed. Results There was no perioperative death. The average cardiopulmonary bypass time was 159.3±39.4 min, and the aortic clamping time was 102.3±20.3 min. One patient underwent thoracotomy during the operation, and two patients underwent second thoracotomy for hemostasis. During the follow-up period of 10-55 months, 1 patient died, 2 patients developed mild perivalvular regurgitation, 6 patients developed moderate tricuspid regurgitation, and no serious cardiovascular events occurred in the rest of the patients. Conclusion Our findings demonstrate that multiple valvular surgery through right anterolateral intercostal thoracotomy is safe, and in an acceptable risk of complication. The early and middle follow-up results are satisfactory. The minimally invasive cardiac surgery can also meet the requirements of cosmetology, and is conducive to the recovery of patients' mental and physical health. This method is worthy of application in medical centers with rich experience in routine cardiac surgery.
8.Study on the association between vasoactive-inotropic score and mortality of total arch replacement in type A aortic dissection patients
Peng HOU ; Zhenxiao JIN ; Xiaochao DONG ; Bo YU ; Kai REN ; Chao XUE ; Shan LYU ; Liqing JIANG ; Weixun DUAN ; Shiqiang YU
Chinese Journal of Thoracic and Cardiovascular Surgery 2020;36(4):213-217
Objective:To study on the association between vasoactive-inotropic score(VIS) and mortality of total arch replacement in Stanford type A aortic dissection(TAAD) patients.Methods:Data of TAAD patients admitted from January 2018 to November 2018 were analyzed retrospectively. According to the inclusion and exclusion criteria, 187 patients were finally included in the analysis. 30-day mortality was calculated and the patients were divided into death group(18 cases) and non-death group(169 cases). The VIS at each time point and perioperative indexes of the two groups were compared. The value of VIS in predicting mortality was analyzed.Results:The 30-day mortality was 9.63%(18/187). The operation time, cardiopulmonary bypass time, ventilator assistance time, the incidence of tracheotomy and major postoperative complications in the death group were significantly higher than those in the non-death group( P<0.05). VIS of death group was significantly higher than that of non-death group( P<0.05). At each time point, the area under ROC curve(AUC) of VIS was greater than 0.500( P<0.05), among which AUC of ICU 48 h VIS was the largest(0.817), and the best cut-off point of ICU 48 h VIS was determined to be 9, sensitivity 61.1%, specificity 92.3%. Logistic regression analysis showed that ICU 48 h VIS was an independent risk factor for predicting the death of total arch replacement in TAAD patients( OR=1.465, 95% CI: 1.194-1.796, P<0.001). Conclusion:When ICU 48 h VIS≥9, the risk of death was increased in patients with total arch replacement of TAAD. VIS may be a useful reference index for predicting the mortality of total arch replacement in TAAD patients in the early postoperative period.
9.Retrospective study of the diagnosis and treatment of culture-negative aortic infective endocarditis
Xiaochao DONG ; Jinbao YANG ; Weixun DUAN ; Dawei LIU ; Yang LIU ; Shiqiang YU
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2020;27(07):749-753
Objective To discuss the diagnosis and treatment of culture-negative aortic infective endocarditis. Methods The clinical data of 73 patients with infective endocarditis of the aortic valve whose results of bacteria culture were negative from January 2013 to January 2018 were retrospectively analyzed, including 59 males and 14 females aged 14-71 (39.2±14.8) years. Results Sixty seven (91.8%) patients received aortic valve replacement, 2 (2.7%) patients received the second operation in hospital, and 12 (16.4%) patients had concomitant mitral valvuloplasty. In-hospital death occurred in 8 (11.0%) patients. Postoperatively, 11 (20.7%) patients had a low cardiac output and 4 (11.0%) patients had heart block, and 1 patient required implantation of a permanent pacemaker. The 1- and 5- year survival rates were 92.3%±2.3% and 84.5%±4.5%, respectively. Conclusion There are difficulties in the diagnosis and treatment of culture-negative infective endocarditis. Most of the affected patients are in a healed status, which could be a cause of negative culture results. In-hospital mortality in the patients is associated with a history of previous cardiac surgery, whereas the long-term survival rate is good for the patients after surgery.
10.Interventional treatment with covered stent graft for retrograde Stanford type A aortic dissection and intramural hematoma: A systematic review and meta-analysis
Hanzhao ZHU ; Peng HOU ; Zhengxi CHEN ; Lin XIA ; Liyun ZHANG ; Shiqiang YU ; Jincheng LIU ; Weixun DUAN
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2020;27(09):1037-1044
Objective To evaluate the prognosis of interventional treatment with covered stent graft for retrograde Stanford type A aortic dissection and intramural hematoma by single-arm meta-analysis. Methods Related studies on treating retrograde Stanford type A aortic dissection and intramural hematoma with covered stent graft were retrieved from the databases by computer, including PubMed, EMbase, The Cochrane Library, Wanfang Data, VIP, CNKI and CBM, from inception to January 2020. Literatures were screened by researchers step by step according to the predefined inclusion and exclusion criteria. Quality of the enrolled literatures was evaluated, and data were extracted from the included studies. Afterwards, single-arm meta-analysis was carried out by the R3.6.3 software. Results A total of 12 English and 5 Chinese studies were included, which were all case series, and the quality of all literatures was moderate evaluated by Newcastle-Ottawa Scale (NOS). After analyzing the clinical prognosis of 260 patients, the 30-day mortality was 6% (95%CI 0.04 to 0.11, P=0.97), the late mortality was 8% (95%CI 0.05 to 0.14, P=0.78), the incidence of endoleak was 21% (95%CI 0.16 to 0.29, P=0.06), the incidence of stroke was 5% (95%CI 0.03 to 0.09, P=0.99), the incidence of new aortic dissection was 7% (95%CI 0.04 to 0.11, P=0.96), the incidence of dissection progression was 10% (95%CI 0.07 to 0.16, P=0.24), and the absorption rate of intramural hematoma was 84% (95%CI 0.37 to 1.00, P<0.01). Conclusion Interventional treatment with covered stent graft for retrograde Stanford type A aortic dissection and intramural hematoma can obtain good early treatment results for some patients, and can be used as a safe and effective treatment for aged patient with high risk who cannot tolerate surgery. Endoleak, stroke and new aortic dissection are the early serious complications of this method.

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