1.Relationship between plasma proteins and pulmonary arterial hypertension and potential therapeutic targets
Cuicui ZHANG ; Huanyu CHEN ; Qiao YU ; Yuxuan HUANG ; Gengzhen YAO ; Xu ZOU
Chinese Journal of Tissue Engineering Research 2026;30(5):1331-1340
BACKGROUND:Pulmonary arterial hypertension is a destructive cardiopulmonary disease for which there is no cure.An association between plasma proteins and pulmonary arterial hypertension has been suggested,but the causal relationship has not been specifically elucidated.OBJECTIVE:To elucidate the causal relationship between plasma proteome and pulmonary arterial hypertension using a two-sample Mendelian randomization method,thereby searching for potential therapeutic targets for pulmonary arterial hypertension.METHODS:Plasma Protein Gene-Wide Association Analysis Statistics for 4 907 Aptamer Measurements in 35 559 Icelanders from the Icelandic Database;Genome-wide association analysis statistics for pulmonary arterial hypertension were obtained from the Finn Gen database,version R9,including 234 cases and 265 626 controls.Analyses were performed using Mendelian randomization and Bayesian co-localization analysis,the findings were examined using sensitivity analyses,and protein-protein interaction network maps were constructed to explore the causal relationship between plasma proteins and pulmonary arterial hypertension.RESULTS AND CONCLUSION:(1)The results of inverse variance weighting,maximum likelihood and Wald ratio methods showed 19 proteins causally associated with pulmonary arterial hypertension(P<0.05).Among them,10 plasma proteins,including Beta-1,3-N-acetylglucosaminyltransferase manic fringe(odds ratio[OR]=0.12,95%confidence interval[CI]0.02-0.61,P=0.01)and interferon alpha/beta receptor 1(OR=0.45,95%CI 0.24-0.84,P=0.012),might be associated with a reduced risk of pulmonary arterial hypertension.In contrast,nine plasma proteins,such as glucoside xylosyltransferase 1(OR=3.48,95%CI 1.51-8.00,P=0.003)and plasminogen(OR=42.78,95%CI 2.49-734.31,P=0.01),might be associated with an increased risk of pulmonary arterial hypertension.After the false discovery rate was corrected,19 proteins remained significantly associated with pulmonary arterial hypertension.(2)Multiple sensitivity analyses such as the MR-Egger intercept test and leave-one-out method showed no horizontal multiplicity or heterogeneity in the results of the study,indicating the stability of the study's results.(3)Bayesian co-localization analysis showed that six plasma proteins,including plasminogen(PPH4=1.0)and glucoside xylosyltransferase 1(PPH4=0.94),had PPH4>0.8,suggesting that plasma proteins and the genome-wide association study of pulmonary arterial hypertension had similar causal variance in terms of genetic association.(4)By constructing a protein-protein interaction network map,plasminogen,Annexin A1,fibrinogen gamma chain and matrix metalloproteinase 7 were found to be core proteins.(5)The article used Mendelian randomization analysis to reveal a potential causal association between 4 907 plasma proteins and pulmonary arterial hypertension,suggesting that plasma proteins may be potential therapeutic targets for pulmonary arterial hypertension.The core proteins identified in the study also provide a theoretical basis for further in-depth study of the pathophysiological mechanisms of pulmonary arterial hypertension.Secondly,analyses using the large-scale international databases of Iceland and FinnGen provide new research directions and treatment ideas for pulmonary arterial hypertension in specific populations and environments,as well as ideas and methods that can be used to prevent and treat pulmonary arterial hypertension in China.
2.Relationship between plasma proteins and pulmonary arterial hypertension and potential therapeutic targets
Cuicui ZHANG ; Huanyu CHEN ; Qiao YU ; Yuxuan HUANG ; Gengzhen YAO ; Xu ZOU
Chinese Journal of Tissue Engineering Research 2026;30(5):1331-1340
BACKGROUND:Pulmonary arterial hypertension is a destructive cardiopulmonary disease for which there is no cure.An association between plasma proteins and pulmonary arterial hypertension has been suggested,but the causal relationship has not been specifically elucidated.OBJECTIVE:To elucidate the causal relationship between plasma proteome and pulmonary arterial hypertension using a two-sample Mendelian randomization method,thereby searching for potential therapeutic targets for pulmonary arterial hypertension.METHODS:Plasma Protein Gene-Wide Association Analysis Statistics for 4 907 Aptamer Measurements in 35 559 Icelanders from the Icelandic Database;Genome-wide association analysis statistics for pulmonary arterial hypertension were obtained from the Finn Gen database,version R9,including 234 cases and 265 626 controls.Analyses were performed using Mendelian randomization and Bayesian co-localization analysis,the findings were examined using sensitivity analyses,and protein-protein interaction network maps were constructed to explore the causal relationship between plasma proteins and pulmonary arterial hypertension.RESULTS AND CONCLUSION:(1)The results of inverse variance weighting,maximum likelihood and Wald ratio methods showed 19 proteins causally associated with pulmonary arterial hypertension(P<0.05).Among them,10 plasma proteins,including Beta-1,3-N-acetylglucosaminyltransferase manic fringe(odds ratio[OR]=0.12,95%confidence interval[CI]0.02-0.61,P=0.01)and interferon alpha/beta receptor 1(OR=0.45,95%CI 0.24-0.84,P=0.012),might be associated with a reduced risk of pulmonary arterial hypertension.In contrast,nine plasma proteins,such as glucoside xylosyltransferase 1(OR=3.48,95%CI 1.51-8.00,P=0.003)and plasminogen(OR=42.78,95%CI 2.49-734.31,P=0.01),might be associated with an increased risk of pulmonary arterial hypertension.After the false discovery rate was corrected,19 proteins remained significantly associated with pulmonary arterial hypertension.(2)Multiple sensitivity analyses such as the MR-Egger intercept test and leave-one-out method showed no horizontal multiplicity or heterogeneity in the results of the study,indicating the stability of the study's results.(3)Bayesian co-localization analysis showed that six plasma proteins,including plasminogen(PPH4=1.0)and glucoside xylosyltransferase 1(PPH4=0.94),had PPH4>0.8,suggesting that plasma proteins and the genome-wide association study of pulmonary arterial hypertension had similar causal variance in terms of genetic association.(4)By constructing a protein-protein interaction network map,plasminogen,Annexin A1,fibrinogen gamma chain and matrix metalloproteinase 7 were found to be core proteins.(5)The article used Mendelian randomization analysis to reveal a potential causal association between 4 907 plasma proteins and pulmonary arterial hypertension,suggesting that plasma proteins may be potential therapeutic targets for pulmonary arterial hypertension.The core proteins identified in the study also provide a theoretical basis for further in-depth study of the pathophysiological mechanisms of pulmonary arterial hypertension.Secondly,analyses using the large-scale international databases of Iceland and FinnGen provide new research directions and treatment ideas for pulmonary arterial hypertension in specific populations and environments,as well as ideas and methods that can be used to prevent and treat pulmonary arterial hypertension in China.
3.Prediction of major adverse cardiovascular events after acute type A aortic dissection combined with coronary malperfusion by machine learning-based interpretable models
Hao ZHANG ; Bo JIA ; Zuo ZHANG ; Huanyu QIAO ; Bo YANG ; Jing YANG ; Feilong HEI ; Xiaotong HOU ; Junming ZHU ; Yongmin LIU
Chinese Journal of Thoracic and Cardiovascular Surgery 2025;41(3):129-135
Objective:To explore and model risk factors in patients with major adverse cardiovascular events (MACEs) after acute type A aortic dissection (ATAAD), and to develop and validate a personalized machine learning model to assess risk factors and predict MACEs in these patients.Methods:Clinical data of patients who attended Beijing Anzhen Hospital and underwent surgical treatment for ATAAD from January 2018 to October 2022 were retrospectively analyzed. Using MACEs as the endpoint, 70% of these patients were randomly divided into the training set and the remaining 30% into the validation set. LASSO regression was applied to explore key clinical variables in the training set. The optimal predictive model was selected from nine machine learning algorithms based on area under the curve. And Shapley Additive explanations was used to elucidate the predictive model. Results:Of the 481 patients included in this study, 135 (35.6%) patients experienced an endpoint event. By combining the results of the training and validation sets, when assessing the validity of the single model with the highest predictive accuracy for the outcome, it was shown that the logistic model (0.774, 95% CI: 0.717-0.830) was the most effective in the combined effect and had a high model accuracy (0.743, 95% CI: 0.720-0.766). According to the results of the LASSO, the factors most associated with postoperative MACEs were history of cerebrovascular disease, coronary artery involvement, shock status on admission to the operating room, FDP, PLT, CPB, ascending aortic clamping, and age. Conclusion:In this study, nine machine learning models were developed to predict the occurrence of postoperative MACEs in patients with acute type A aortic dissection. The logistic model performed significantly better compared to other algorithms. Our study successfully predicted postoperative MACES and identified the factors most associated with MACEs.
4.Prediction of major adverse cardiovascular events after acute type A aortic dissection combined with coronary malperfusion by machine learning-based interpretable models
Hao ZHANG ; Bo JIA ; Zuo ZHANG ; Huanyu QIAO ; Bo YANG ; Jing YANG ; Feilong HEI ; Xiaotong HOU ; Junming ZHU ; Yongmin LIU
Chinese Journal of Thoracic and Cardiovascular Surgery 2025;41(3):129-135
Objective:To explore and model risk factors in patients with major adverse cardiovascular events (MACEs) after acute type A aortic dissection (ATAAD), and to develop and validate a personalized machine learning model to assess risk factors and predict MACEs in these patients.Methods:Clinical data of patients who attended Beijing Anzhen Hospital and underwent surgical treatment for ATAAD from January 2018 to October 2022 were retrospectively analyzed. Using MACEs as the endpoint, 70% of these patients were randomly divided into the training set and the remaining 30% into the validation set. LASSO regression was applied to explore key clinical variables in the training set. The optimal predictive model was selected from nine machine learning algorithms based on area under the curve. And Shapley Additive explanations was used to elucidate the predictive model. Results:Of the 481 patients included in this study, 135 (35.6%) patients experienced an endpoint event. By combining the results of the training and validation sets, when assessing the validity of the single model with the highest predictive accuracy for the outcome, it was shown that the logistic model (0.774, 95% CI: 0.717-0.830) was the most effective in the combined effect and had a high model accuracy (0.743, 95% CI: 0.720-0.766). According to the results of the LASSO, the factors most associated with postoperative MACEs were history of cerebrovascular disease, coronary artery involvement, shock status on admission to the operating room, FDP, PLT, CPB, ascending aortic clamping, and age. Conclusion:In this study, nine machine learning models were developed to predict the occurrence of postoperative MACEs in patients with acute type A aortic dissection. The logistic model performed significantly better compared to other algorithms. Our study successfully predicted postoperative MACES and identified the factors most associated with MACEs.
5.Observation on early clinical results of one stage whole-course repair of acute aortic dissection
Huanyu QIAO ; Shouming LI ; Chen ZHANG ; Xiaohai MA ; Yongmin LIU
Chinese Journal of Thoracic and Cardiovascular Surgery 2024;40(6):335-338
Objective:To summarize and analyze the early clinical outcomes of aortic endovascular remodeling device (AERD) for single-stage complete repair of acute aortic dissection.Methods:A total of 19 patients with acute aortic dissection who underwent proximal aortic dissection repair combined with distal AERD implantation at the Center for Aortic Surgery of Beijing Anzhen Hospital, Capital Medical University between May 2023 and October 2023, of whom 6 had type A aortic dissection and 13 had type B aortic dissection, were retrospectively analyzed. One-month postoperative follow-up and aortic CTA were completed to compare pre- and postoperative abdominal branch outcomes and aortic wall remodeling.Results:The success rate of AERD implantation in this patient cohort was 100%, and no complications such as paraplegia or visceral ischemia were observed during the perioperative and postoperative follow-up periods. All abdominal branches were patent postoperatively, and 15 branches had preoperative " high-risk" subtype malperfusion, 14 of which improved postoperatively. All patients showed significant increase of the true lumen volume compared with the preoperative one, and 89.5% (17/19) had a postoperative true lumen/overall volume ratio of more than 70%.Conclusion:The single-stage complete repair of proximal aortic dissection repair combined with distal AERD implantation is simple, safe and effective, associated with satisfactory early outcomes.
6.Analysis of anatomical characteristics of residual aortic dissection based on CT imaging and its clinical guidance value
Shouming LI ; Huanyu QIAO ; Chen ZHANG ; Xiaohai MA ; Yongmin LIU
Chinese Journal of Thoracic and Cardiovascular Surgery 2024;40(6):345-350
Objective:This study aims to summarize the pathological anatomy characteristics of residual aortic dissection (RAD) in patients with acute aortic dissection (AAD) during the perioperative period by measuring and analyzing the preoperative and postoperative 60-day computed tomography angiography (CTA) images of the aorta, with the intention of guiding further clinical treatment.Methods:A retrospective cohort study design was adopted. A total of 224 patients hospitalized with acute aortic dissection from December 2021 to October 2022 at a single center were included according to inclusion and exclusion criteria and divided into two groups based on Stanford classification. Computed tomography angiography (CTA) images of the aorta during the perioperative period (preoperative or postoperative 60 days) were collected, and relevant indicators were measured to describe the pathological anatomy characteristics of residual aortic dissection.Results:Among the measured range, there were 4 patients (1.8%) without distal tears, with a total of 648 identified distal tears. The numbers of tears in the A, B, and C segments were 211 (32.6%), 203 (31.3%), and 234 (36.1%), respectively. The average numbers of tears in the A, B, and C segments were 0.9±1.1, 0.9±0.9, and 1.0±1.2 per person, respectively. The corresponding average tear areas were(34.9±46.7)mm 2, (29.0±30.5)mm 2, and(18.6±23.9)mm 2, respectively. The average distances from tears to the upper and lower edges of the celiac trunk were(36.8±33.2)mm and(2.3±3.8)mm, respectively; to the upper and lower edges of the superior mesenteric artery (SMA) were(2.3±4.1 )mm and(1.2±2.6) mm, respectively; to the upper and lower edges of the left renal artery were(0.1±0.6) mm and(38.5±24.4) mm, respectively; and to the upper and lower edges of the right renal artery were(0.7±2.6) mm and(8.1±17.3) mm, respectively. True lumen blood supply for the celiac trunk was observed in 151 cases (67.4%); dual luminal supply in 49 cases (21.9%); and false lumen supply in 24 cases (10.7%). True lumen blood supply for the SMA was observed in 187 cases (83.5%); dual luminal supply in 32 cases (14.3%); and false lumen supply in 5 cases (2.2%). True lumen blood supply for the left renal artery was observed in 150 cases (67.0%); dual luminal supply in 27 cases (12.1%); and false lumen supply in 47 cases (21.0%). True lumen blood supply for the right renal artery was observed in 148 cases (66.1%); dual luminal supply in 30 cases (13.4%); and false lumen supply in 46 cases (20.5%). True lumen blood supply for both renal arteries was observed in 83 cases (37.1%); dual luminal supply in 4 cases (1.8%); and false lumen supply in 1 case (0.5%). Conclusion:The results of this study suggest that the average number of distal tears per person in patients with AAD is 2.9±1.9, with only 1.8% of patients having no distal tears. The average tear areas in the A, B, and C segments are(34.9±46.7) mm 2, (29.0±30.5) mm 2, and (18.6±23.9) mm 2, respectively. 61.2% of patients have tears in the abdominal aortic branch segment, and the tears are located at the same level as the abdominal aortic branches. Among the branches of the abdominal aorta, the renal arteries are most commonly affected by dissection, while the SMA is least affected. This study elucidates the anatomical basis for the limitations of existing repair methods and provides a theoretical basis for the design of subsequent repair techniques.
7.Lifetime changes of the oocyte pool: Contributing factors with a focus on ovulatory inflammation
Chan Jin PARK ; Ji-Eun OH ; Jianan FENG ; Yoon Min CHO ; Huanyu QIAO ; CheMyong KO
Clinical and Experimental Reproductive Medicine 2022;49(1):16-25
In mammalian species, females are born with a number of oocytes exceeding what they release via ovulation. In humans, an average girl is born with over a thousand times more oocytes than she will ovulate in her lifetime. The reason for having such an excessive number of oocytes in a neonatal female ovary is currently unknown. However, it is well established that the oocyte number decreases throughout the entire lifetime until the ovary loses them all. In this review, data published in the past 80 years were used to assess the current knowledge regarding the changing number of oocytes in humans and mice, as well as the reported factors that contribute to the decline of oocyte numbers. Briefly, a collective estimation indicates that an average girl is born with approximately 600,000 oocytes, which is 2,000 times more than the number of oocytes that she will ovulate in her lifetime. The oocyte number begins to decrease immediately after birth and is reduced to half of the initial number by puberty and almost zero by age 50 years. Multiple factors that are either intrinsic or extrinsic to the ovary contribute to the decline of the oocyte number. The inflammation caused by the ovulatory luteinizing hormone surge is discussed as a potential contributing factor to the decline of the oocyte pool during the reproductive lifespan.
8. Retrospective study of right axillary and femoral artery cannulation in Sun’s operation
Kaiyue JIN ; Huanyu QIAO ; Xiaonan LI ; Yifan FENG ; Lin LI ; Yongmin LIU ; Junming ZHU ; Lizhong SUN
Chinese Journal of Thoracic and Cardiovascular Surgery 2019;35(11):680-683
Objective:
Summarize the anatomical features of the aortic dissection of right axillary and femoral artery cannulation in Sun's surgery. Exploring whether right axillary and femoral artery cannulation can reduce the incidence of organ malperfusion and improve patient prognosis.
Methods:
From January 2015 to December 2017, 181 cases with aortic dissection were treated in Beijing Anzhen Hospital affiliated to Capital Medical University, Beijing Great Blood Vessel Research and Treatment Center, 122 patients were enrolled in the right axillary and femoral artery cannulation group, and 59 patients in control group were enrolled. Retrospective analysis the data of two groups, intraoperative, and postoperative univariate were compared between the two groups.
Results:
A total of 17 patients died in the postoperative group, with 9 (7.38%) in the combined perfusion group and 8 (13.56%) in the control group,
9.Medical management of acute aortic dissection
Wenxing PENG ; Honglei ZHAO ; Huanyu QIAO ; Yang LIN ; Xiujin SHI
Chinese Journal of Thoracic and Cardiovascular Surgery 2018;34(4):254-256
Objective Acute aortic dissection occurs when a tear in the inside of the aorta causes blood to flow between the layers of the wall of the aorta,forcing the layers apart.In most cases this is associated with a sudden onset of severe chest or back pain,often described as "tearing" in character.The main management includes medication,endovascular repair and surgery.Medical management plays an very important role in the management of acute aortic dissection.Aortic dissection generally presents as a hypertensive emergency.Individuals can benefit from blood pressure control and anti-impulse therapy in perioperative period.
10.Perioperative outcomes and early closure rate of false lumen of type A aortic dissection patients with different proximal and distal tear size ratio
Xiaonan LI ; Huanyu QIAO ; Bo YANG ; Honglei ZHAO ; Jinrong XUE ; Ningning LIU ; Tao BAI ; Lizhong SUN ; Yongmin LIU
Chinese Journal of Thoracic and Cardiovascular Surgery 2018;34(12):734-738
Objective To retrospectively analyze perioperative and early outcomes after Sun's procedure of type A aortic dissection patients with different tear size ratia.Methods To retrospectively analyze the general information of 120 patients with acute Stanford type A aortic dissectiontreatedin our center from November 2014 to December 2016.Patients were divided into three group according to proximal and distal tear sizeratio(PDTSR):35 patients in Group A(PDTSR≥2),44 patients in Group B (1/2 < PDTSR < 2)and 41 patients in Group C (PDTSR ≤ 1/2).Retrospectively reviewed the data of perioperativeand follow-up period.Results Preoperative mortality was significantly higher in Group A (37.1% vs.2.3% vs.2.4%;P < 0.001).Preoperative morbidity higher in Group A,but there was no significant difference.Ventilator support of duration > 5 days in Group A is significantly higher in Group A (P =0.006).Three-month closure rate of false lumen was higher in Group A (85.0% vs.65.0% vs.72.7 %,P =0.263).Proximal tear significantly larger than distal tear was found associated with preoperative death in logistic regression analysis.Conclusion Acute type A aortic dissection patients with larger proximal tear size need more urgent surgery to fix the dissection.Sun's procedure was an effective way to cure type A aortic dissection,while patients with relatively larger distal tears need more strict postoperative follow-up.

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