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2-APQC,a small-molecule activator of Sirtuin-3(SIRT3),alleviates myocardial hypertrophy and fibrosis by regulating mitochondrial homeostasis

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Signal Transduction and Targeted Therapy 2024年第6期9卷 2748-2764页

作者： Fu Peng Minru Liao Wenke Jin Wei Liu Zixiang Li Zhichao Fan Ling Zou Siwei Chen Lingjuan Zhu Qian Zhao Gu Zhan Liang Ouyang Cheng Peng Bo Han Jin Zhang Leilei Fu West China School of Pharmacy and Department of Biotherapy Cancer Center and State Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengdu 610041China Sichuan Engineering Research center for Biomimetic Synthesis of Natural Drugs School of Life Science and EngineeringSouthwest Jiaotong UniversityChengdu 610031China State Key Laboratory of Southwestern Chinese Medicine Resources Hospital of Chengdu University of Traditional Chinese MedicineSchool of PharmacyChengdu University of Traditional Chinese MedicineChengdu 611137China School of Pharmaceutical Sciences Health Science CenterShenzhen UniversityShenzhen 518060China School of Traditional Chinese Materia Medica Key Laboratory of Structure-Based Drug Design&Discovery of Ministry of EducationShenyang Pharmaceutical UniversityShenyang 110016China

Sirtuin 3(SIRT3)is well known as a conserved nicotinamide adenine dinucleotide^(+)(NAD^(+))-dependent deacetylase located in the mitochondria that may regulate oxidative stress,catabolism and ATP *** evidence has recently revealed that SIRT3 plays its critical roles in cardiac fibrosis,myocardial fibrosis and even heart failure(HF),through its deacetylation ***,discovery of SIRT3 activators and elucidating their underlying mechanisms of HF should be urgently ***,we identified a new small-molecule activator of SIRT3(named 2-APQC)by the structure-based drug designing strategy.2-APQC was shown to alleviate isoproterenol(ISO)-induced cardiac hypertrophy and myocardial fibrosis in vitro and in vivo rat ***,in SIRT3 knockout mice,2-APQC could not relieve HF,suggesting that 2-APQC is dependent on SIRT3 for its protective ***,2-APQC was found to inhibit the mammalian target of rapamycin(mTOR)-p70 ribosomal protein S6 kinase(p70S6K),c-jun N-terminal kinase(JNK)and transforming growth factor-β(TGF-β)/small mother against decapentaplegic 3(Smad3)pathways to improve ISO-induced cardiac hypertrophy and myocardial *** upon RNA-seq analyses,we demonstrated that SIRT3-pyrroline-5-carboxylate reductase 1(PYCR1)axis was closely assoiated with *** activating PYCR1,2-APQC was shown to enhance mitochondrial proline metabolism,inhibited reactive oxygen species(ROS)-p38 mitogen activated protein kinase(p38MAPK)pathway and thereby protecting against ISO-induced mitochondrialoxidative ***,activation of SIRT3 by 2-APQC could facilitate AMP-activated protein kinase(AMPK)-Parkin axis to inhibit ISO-induced ***,our results demonstrate that 2-APQC is a targeted SIRT3 activator that alleviates myocardial hypertrophy and fibrosis by regulating mitochondrial homeostasis,which may provide a new clue on exploiting a promising drug candidate for the future HF therapeutics.

关键词： SIRT3 homeostasis metabolism

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A machine learning model for diagnosing acute pulmonary embolism and comparison with Wells score,revised Geneva score,and Years algorithm

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Chinese Medical Journal 2024年第6期137卷 676-682页

作者： Linfeng Xi Han Kang Mei Deng Wenqing Xu Feiya Xu Qian Gao Wanmu Xie Rongguo Zhang Min Liu Zhenguo Zhai Chen Wang Capital Medical University Beijing 100069China National center for Respiratory Medicine State Key Laboratory of Respiratory Health and MultimorbidityNational Clinical Research Center for Respiratory DiseasesInstitute of Respiratory MedicineChinese Academy of Medical SciencesDepartment of Pulmonary and Critical Care MedicineCenter of Respiratory MedicineChina-Japan Friendship HospitalBeijing 100029China Institute of Advanced Research Infervision Medical Technology Co.Ltd.Beijing 100025China Department of Radiology China-Japan Friendship HospitalBeijing 100029China Chinese Academy of Medical Sciences and Peking Union Medical College Beijing 100730China Department of Radiology Peking University China-Japan Friendship School of Clinical MedicineBeijing 100191China

Background:Acute pulmonary embolism(APE)is a fatal cardiovascular disease,yet missed diagnosis and misdiagnosis often occur due to non-specific symptoms and signs.A simple,objective technique will help clinicians make a quick and precise *** population studies,machine learning(ML)plays a critical role in characterizing cardiovascular risks,predicting outcomes,and identifying *** work sought to develop an ML model for helping APE diagnosis and compare it against current clinical probability assessment ***:This is a single-center retrospective *** with suspected APE were continuously enrolled and randomly divided into two groups including training and testing sets.A total of 8 ML models,including random forest(RF),Naïve Bayes,decision tree,K-nearest neighbors,logistic regression,multi-layer perceptron,support vector machine,and gradient boosting decision tree were developed based on the training set to diagnose ***,the model with the best diagnostic performance was selected and evaluated against the current clinical assessment strategies,including the Wells score,revised Geneva score,and Years ***,the ML model was internally validated to assess the diagnostic performance using receiver operating characteristic(ROC)***:The ML models were constructed using eight clinical features,including D-dimer,cardiac troponin T(cTNT),arterial oxygen saturation,heart rate,chest pain,lower limb pain,hemoptysis,and chronic heart *** eight ML models,the RF model achieved the best performance with the highest area under the curve(AUC)(AUC=0.774).Compared to the current clinical assessment strategies,the RF model outperformed the Wells score(P=0.030)and was not inferior to any other clinical probability assessment *** AUC of the RF model for diagnosing APE onset in internal validation set was ***:Based on RF algorithm,a novel prediction model was finally constructed for AP

关键词： Acute pulmonary embolism Machine learning Wells score Revised Geneva score Years algorithm

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A strategy for mechanically integrating robust hydrogeltissue hybrid to promote the anti-calcification and endothelialization of bioprosthetic heart valve

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Regenerative Biomaterials 2024年第2期3卷 123-136页

作者： Haoshuang Wu Nuoya Chen Tiantian Zheng Li Li Mengyue Hu Yumei Qin Gaoyang Guo Li Yang Yunbing Wang National Engineering Research center for Biomaterials Sichuan UniversityChengdu 610065China Institute of Clinical Pathology West China Hospital of Sichuan UniversityChengdu 610041China College of Polymer Science and Engineering Sichuan UniversityChengdu 610065China

Bioprosthetic heart valve(BHV)replacement has been the predo-minant treatment for severe heart valve diseases over *** clinically available BHVs are crosslinked by glutaraldehyde(GLUT),while the high toxicity of residual GLUT could initiate calcification,severe thrombosis,and delayed ***,we construed a mechanically integrating robust hydrogel-tissue hybrid to improve the performance of *** particular,recombinant humanized coilagen type Ⅲ(rhCOLⅢ),which was precisely customized with anti-coagulant and pro-endothelialization bioactivity,was first incorporated into the polyvinyl alcohol(PVA)-based hydrogel via hydrogen bond ***,tannic acid was introduced to enhance the mechanicalperfo of PVA-based hvdrogel and interfacial bonding between the hydrogel layer and bio-derived tissue due to the strong affinity for a wide range of *** vitro and in vivo experimental results confirmed that the GLUT-crosslinked BHVs modified by the robust PVA-based hydrogel embedded rhCOLII and TA possessed long-term anti-coagulant,accelerated endothelialization,mild inflammatory response and anti-calcification ***,our mechanically integrating robust hydrogel-tissue hybrid strategy showed the potential to enhance the service function and prolong the service life of the BHVs after implantation.

关键词： bioprosthetic heart valves recombinant humanized collagen typeⅢ endothelialization anti-calcification anti-coagulation

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A case report of chylous ascites after cardiac surgery

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Emergency and Critical Care Medicine 2024年第1期4卷 42-45页

作者： Shuaishuai Yuan Pailing Xie Xiantao Liu Peijun Li The University of Hong Kong-Shenzhen Hospital Cardiovascular Medicine center Cardiac Intensive Care Unit ShenzhenGuangdongChina.

Background:Chylous ascites(CA),an emulsion rich in triglycerides,is a rare type of ascites,especially after cardiac ***,there are few reports of the occurrence of CA after mitral valve replacement,aortic valve replacement,tricuspid valvuloplasty,and coronary artery bypass *** presentation:We report the case of a 53-year-old man who underwent surgery for a diagnosis of mitral incompetence,aortic incompetence,tricuspid incompetence,and coronary atherosclerotic heart *** days after surgery,3000 mL of milky-yellow ascites appeared in the abdominal cavity,diagnosed as CA by laboratory *** ascites gradually disappeared after being drained,and the patients *** curative was objective,but the exact cause is not ***:Although CA is rare,it may occur during the surgical intervention in cardiac surgery.

关键词： Cardiac intensive care unit Cardiac valve replacement Case report Chylous ascites Coronary artery bypass graft Department of cardiac surgery

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Homoharringtonine promotes heart allograft acceptance by enhancing regulatory T cells induction in a mouse model

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Chinese Medical Journal 2024年第12期137卷 1453-1464页

作者： Xia Qiu Hedong Zhang Zhouqi Tang Yuxi Fan Wenjia Yuan Chen Feng Chao Chen Pengcheng Cui Yan Cui Zhongquan Qi Tengfang Li Yuexing Zhu Liming Xie Fenghua Peng Tuo Deng Xin Jiang Longkai Peng Helong Dai Medical College Guangxi UniversityNanningGuangxi 530004China Department of Kidney Transplantation Center of Organ TransplantationThe Second Xiangya Hospital of Central South UniversityChangshaHunan 410011China National Clinical Research center for Metabolic Diseases and Department of Metabolism and EndocrinologyThe Second Xiangya Hospital of Central South UniversityChangshaHunan 410011China Department of Organ Transplantation The Fifth Clinical Medical College of Henan University of Chinese Medicine(Zhengzhou People’s Hospital)ZhengzhouHenan 450000China

Background:Homoharringtonine(HHT)is an effective anti-inflammatory,anti-viral,and anti-tumor protein synthesis inhibitor that has been applied ***,we explored the therapeutic effects of HHT in a mouse heart transplant ***:Healthy C57BL/6 mice were used to observe the toxicity of HHT in the liver,kidney,and hematology.A mouse heart transplantation model was constructed,and the potential mechanism of HHT prolonging allograft survival was evaluated using Kaplan-Meier analysis,immunostaining,and bulk RNA sequencing *** HHT-T cell crosstalk was modeled ex vivo to further verify the molecular mechanism of HHT-induced regulatory T cells(Tregs)***:HHT inhibited the activation and proliferation of T cells and promoted their apoptosis ex *** of 0.5 mg/kg HHT for 10 days significantly prolonged the mean graft survival time of the allografts from 7 days to 48 days(Pheart allograft *** findings may have therapeutic implications for organ tr

关键词： heart transplantation Homoharringtonine Immunosuppressive agents T-lymphocytes,Regulatory Graft acceptance

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Juvenile Systemic Sclerosis: About 9 Cases

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Open Journal of Pediatrics 2024年第2期14卷 320-326页

作者： Kaoutar Danaoui Houda Nassih Khadija Oujennane Rabiy El Qadiry Aicha Bourrahouat Said Amal Imane Ait Sab B Pediatric Ward Mohammed VI University Hospital Center Marrakesh Morocco Dermatology Ward Mohammed VI University Hospital Center Marrakesh Morocco

Scleroderma is a rare disease with two primary forms: localized scleroderma (LS) and systemic sclerosis (SSc). Both are chronic conditions that can manifest in various patterns (subtypes) and are linked to extracutaneous involvement in pediatric patients. Juvenile SSc poses a higher risk of morbidity and mortality, with patients facing life-threatening complications such as lung, heart, and visceral organ fibrosis, and vasculopathy. In contrast, mortality is extremely rare in juvenile LS, but patients are susceptible to significant morbidity, leading to severe disfigurement and functional impairment. Treatment for scleroderma aims to control inflammation and address specific issues. An early diagnosis significantly enhances the overall outcome. This study conducts a retrospective descriptive analysis aiming to document the clinical manifestations, management approaches, and outcomes of systemic sclerosis in a cohort of nine children receiving treatment for juvenile systemic sclerosis at Pediatric B department of Mohammed VI University, Hospital center in Marrakech, Morocco.

关键词： Scleroderma Systemic Sclerosis Children Pediatric

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TREM2 as an evolving therapeutic target in Alzheimer's disease

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Neural Regeneration Research 2023年第12期18卷 2680-2681页

作者： Jacob George Cognyxx Pharmaceuticals Tel Aviv Israel and Kaplan Heart CenterRehovotIsrael

Triggering receptor expressed on myeloid cells 2(TREM2) is type I transmembrane protein receptor found in osteoclasts, dendritic cells, macrophages, and microglia(Ulland and Colonna, 2018). In the central nervous system, TREM2 expression is confined exclusively to microglia. TREM2 comprises an extracellular V-type immunoglobulin(Ig) ectodomain, a connecting stalk followed by a transmembrane region and a short C-terminal tail.

关键词： Alzheimer therapeutic Colon

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Challenges in the conduct of randomised controlled trials in cardiogenic shock complicating acute myocardial infarction

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Journal of Geriatric Cardiology 2022年第2期19卷 125-129页

作者： Anne Freund Steffen Desch Holger Thiele Department of Internal Medicine/Cardiology Heart Center Leipzig at the University of LeipzigLeipzigGermany German center for Cardiovascular Research(DZHK) BerlinDeutschland

Cardiogenic shock(CS)following acute myocardial infarction(AMI)is a major challenge in cardiovascular *** remains high with 40%-50%after thirty *** controlled trials(RCTs)play a key role to generate evidence on optimal care in this ***,the number of completed or ongoing RCTs is still relatively low compared to the gaps in *** in the conduct of these trials are in particular the selection of patients and ethical issues in the informed consent *** determining eligibility criteria,special attention should be paid to the severity of CS,to the inclusion of patients with cardiac arrest and to potential age *** age of AMI-CS patients is *** limits are therefore controversial as it is important to include elderly patients in RCTs in order to make the results generalisable and to address the special needs of this *** patients with AMI-CS are in most cases unable to provide informed consent themselves,a step-wise approach with acute consent by a legal representative or independent physicians and later informed consent by the patient if possible might be established depending on regularities of the respective ethical review board and country *** studies should be sought to generate adequate power.

关键词： shock legal consent

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Ductus Arteriosus Stent Compared with Surgical Shunt for Infants with Ductal-Dependent Pulmonary Blood Flow: A Systematic Review and Meta-Analysis

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Congenital heart Disease 2022年第1期17卷 45-60页

作者： Sibao Wang Silin Pan Gang Luo Zhixian Ji Na Liu heart center Qingdao Women and Children’s HospitalQingdao UniversityQingdao266034China

The aim of this study was to perform a systematic review and meta-analysis to evaluate the safety and efficacy of ductus arteriosus stent(DAS)compared with surgical systemic-pulmonary artery shunt(SPS)in patients with ductal-dependent pulmonary blood flow.A literature search was conducted in PubMed,Embase,and the Cochrane Library databases from their inception to December *** reviewers independently screened the articles,evaluated the quality of the articles,and collected the ***-analyses were conducted using fixed and random effects *** used the I-square(I2)test to examine heterogeneity and the funnel plot Egger’s test was used to test for publication *** analyzed nine studies including 842 patients were included in the present study(DAS:n=295;SPS:n=547).There was a benefit in favor of DAS group for medium-term mortality(RR,0.63;95%CI,[0.40,0.99];P=0.91,I^(2)=0%).DAS group demonstrated a reduced risk for complications compared with SPS(RR,0.46;95%CI,[0.29,0.72];P=0.78,I^(2)=0%).There was an increased risk for unplanned reintervention for DAS(RR,1.77;95%CI,[1.42,2.20];P=0.61,I2=0%).DAS demonstrated shorter mean intensive care unit length of stay(MD,–5.12;95%CI,[–7.33,–2.91];P=0.005,I^(2)=76%).There was also demonstrated higher postprocedure oxygen saturation for SPS over DAS(MD,1.78;95% CI,[0.92,2.64];P=0.46,I2=0%).There was no difference between the two groups in terms of mortality within 30 days,Nakata Index,and hospital length of ***:In terms of initial palliative surgical in the ductal-dependent pulmonary blood flow,DAS demonstrated a lower risk of medium-term mortality,lower risk of complications,higher risk of unplanned reintervention,shorter ICU length of stay,and higher postprocedure oxygen saturation compared with SPS.

关键词： Surgical shunt Blalock-Taussig shunt ductus arteriosus stents infants meta-analysis

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Optimized Three-Dimensional Cardiovascular Magnetic Resonance Whole heart Imaging Utilizing Non-Selective Excitation and Compressed Sensing in Children and Adults with Congenital heart Disease

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Congenital heart Disease 2023年第3期18卷 279-294页

作者： Ingo Paetsch Roman Gebauer Christian Paech Frank-Thomas Riede Sabrina Oebel Andreas Bollmann Christian Stehning Jouke Smink Ingo Daehnert Cosima Jahnke Department of Electrophysiology Heart Center Leipzig at University of LeipzigLeipzigGermany Department of Pediatric Cardiology Heart Center Leipzig at University of LeipzigLeipzigGermany Philips Research Laboratories HamburgGermany Philips Medical Systems BestThe Netherlands

Background:In congenital heart disease(CHD)patients,detailed three-dimensional anatomy depiction plays a pivotal role for diagnosis and therapeutical decision ***,the present study investigated the applicability of an advanced cardiovascular magnetic resonance(CMR)whole heart imaging approach utilizing nonselective excitation and compressed sensing for anatomical assessment and interventional guidance of CHD patients in comparison to conventional dynamic CMR ***:86 consecutive pediatric patients and adults with congenital heart disease(age,1 to 74 years;mean,35 years)underwent CMR imaging including a freebreathing,ECG-triggered 3D nonselective SSFP whole heart acquisition using compressed SENSE(nsWHcs).Anatomical assessability and signal intensity ratio(SIR)measurements were compared with conventional dynamic 3D-/4D-MR ***:The most frequent diagnoses were partial anomalous pulmonary venous drainage(17/86,20%),transposition of the great arteries(15/86,17%),tetralogy of Fallot(12/86,14%),and a single ventricle(7/86,8%).Image quality of nsWHcs was rated as excellent/good in 98%of *** resulted in a reliable depiction of all large thoracic vessels(anatomic assessability,99%–100%)and the proximal segments of coronary arteries and coronary sinus(>90%).nsWHcs achieved a homogenously distributed SIR in all cardiac cavities and thoracic vessels without a significant difference between pulmonary and systemic circulation(10.9±3.5 and 10.6±3.4;p=0.15),while 3D angiography showed significantly increased SIR for targeted ***-targeted circulation(PA-angiography,15.2±8.1 vs.5.8±3.6,pheart *** enabled detailed anatomi

关键词： Cardiovascular magnetic resonance imaging congenital heart disease whole heart imaging nonselective SSFP compressed SENSE MR angiography

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