Background:The Venus-P valve was the first self-expanding valve used world-wide for transcatheter pulmonary valve replacement(TPVR)in patients with severe pulmonary regurgitation(PR).We intended to report the extended...Background:The Venus-P valve was the first self-expanding valve used world-wide for transcatheter pulmonary valve replacement(TPVR)in patients with severe pulmonary regurgitation(PR).We intended to report the extended follow-up results from the prospective trial(No.NCT02590679).Methods:A total of 38 patients with severe PR(mean age 24.2±13.2)were included.Follow-up data were obtained after implanted at 1,6,and 12 months and yearly after.The frame geometry was assessed on post-implant computer tomography(CT)scanning by calculating the non-circularity[circularity ratio(minimum diameter/maximum diameter)<0.9]and under-expansion[expansion ratio(derived external valve area/nominal external valve area)<0.9).Adverse events(all-cause mortality,reintervention,valve dysfunction,stent fracture and endocarditis)were recorded.Results:All valves were implanted successfully with normal function at discharge.Geometric CT analysis showed underexpanded valve was detected in 22 patients(63%)and non-circular valve was seen in 16 patients(46%).During a median follow-up of 4.8 years(range 0.3-8.1),there were 1 death and 1 surgical explant,both resulting from endocarditis.Five-year freedom from valve dysfunction and stent fracture were 84.8%(95%CI 74.8-94.7)and 83.5%(95%CI 73.8-93.2).Endocarditis occurred in 3 patients at a median time of 7 months.Stent fracture was more common in patients with non-circularity stents.Conclusion:TPVR using Venus-P valve is associated with favorable outcomes at 5 years.Non-circular shapes in the valve level may have a higher risk of stent fracture.展开更多
Compared with traditional nickel-titanium alloy patent foramen ovale occluders,which are widely used in clinical practice,biodegradable patent foramen ovale occluders have obvious differences in material characteristi...Compared with traditional nickel-titanium alloy patent foramen ovale occluders,which are widely used in clinical practice,biodegradable patent foramen ovale occluders have obvious differences in material characteristics,interventional operation mode and postoperative management strategy.This article gives expert consensus on the selection of clinical indications and standardized operating procedures,so as to standardize the clinical application of biodegradable patent foramen ovale occluders.展开更多
Background In an effort to avoid x-ray and contrast agents for patients of atrial fibrillation(AF)with chronic kidney disease,we developed a method for transcatheter closure of left atrial appendage(LAA)under the guid...Background In an effort to avoid x-ray and contrast agents for patients of atrial fibrillation(AF)with chronic kidney disease,we developed a method for transcatheter closure of left atrial appendage(LAA)under the guidance of transesophageal echocardiography(TEE)without fluoroscopy.展开更多
Problem:Chest radiography is a crucial tool for diagnosing thoracic disorders,but interpretation errors and a lack of qualified practitioners can cause delays in treatment.Aim:This study aimed to develop a reliable mu...Problem:Chest radiography is a crucial tool for diagnosing thoracic disorders,but interpretation errors and a lack of qualified practitioners can cause delays in treatment.Aim:This study aimed to develop a reliable multi-classification artificial intelligence(AI)tool to improve the accuracy and efficiency of chest radiograph diagnosis.Methods:We developed a convolutional neural network(CNN)capable of distinguishing among 26 thoracic diagnoses.The model was trained and externally validated using 795,055 chest radiographs from 13 datasets across 4 countries.Results:The CNN model achieved an average area under the curve(AUC)of 0.961 across all 26 diagnoses in the testing set.COVID-19 detection achieved perfect accuracy(AUC 1.000,[95%confidence interval{CI},1.000 to 1.000]),while effusion or pleural effusion detection showed the lowest accuracy(AUC 0.8453,[95%CI,0.8417 to 0.8489]).In external validation,the model demonstrated strong reproducibility and generalizability within the local dataset,achieving an AUC of 0.9634 for lung opacity detection(95%CI,0.9423 to 0.9702).The CNN outperformed both radiologists and nonradiological physicians,particularly in trans-device image recognition.Even for diseases not specifically trained on,such as aortic dissection,the AI model showed considerable scalability and enhanced diagnostic accuracy for physicians of varying experience levels(all P<0.05).Additionally,our model exhibited no gender bias(P>0.05).Conclusion:The developed AI algorithm,now available as professional web-based software,substantively improves chest radiograph interpretation.This research advances medical imaging and offers substantial diagnostic support in clinical settings.展开更多
The advancement of catheter-based interventional techniques represents a significant evolution in cardiovascular medicine.However,traditional methods that rely on fluoroscopic guidance present considerable limitations...The advancement of catheter-based interventional techniques represents a significant evolution in cardiovascular medicine.However,traditional methods that rely on fluoroscopic guidance present considerable limitations including radiation exposure and contrast agentrelated risks and the heavy load-caused lead suits.In response,zero or low X-ray emerge,including percutaneous and non-fluoroscopical(PAN)procedure coming as a transformative solution,particularly in treating congenital heart disease,valvular disease,and arrhythmias.These methods minimize the risk of iatrogenic injuries associated with radiative procedures.Innovative PAN procedures and methodologies have been developed to enhance imaging,transcatheter interventions,safety,and accuracy,overcoming previous limitations.By eliminating radiation and expanding accessibility,PAN procedures offer a safe,effective,and economically viable alternative to traditional methods,ushering in a new era of minimally invasive cardiovascular treatment.展开更多
The ribosome is a multi-unit complex that translates mRNA into protein.Ribosome biogenesis is the process that generates ribosomes and plays an essential role in cell proliferation,differentiation,apoptosis,developmen...The ribosome is a multi-unit complex that translates mRNA into protein.Ribosome biogenesis is the process that generates ribosomes and plays an essential role in cell proliferation,differentiation,apoptosis,development,and transformation.The mTORC1,Myc,and noncoding RNA signaling pathways are the primary mediators that work jointly with RNA polymerases and ribosome proteins to control ribosome biogenesis and protein synthesis.Activation of mTORC1 is required for normal fetal growth and development and tissue regeneration after birth.Myc is implicated in cancer development by enhancing RNA Pol II activity,leading to uncontrolled cancer cell growth.The deregulation of noncoding RNAs such as microRNAs,long noncoding RNAs,and circular RNAs is involved in developing blood,neurodegenerative diseases,and atherosclerosis.We review the similarities and differences between eukaryotic and bacterial ribosomes and the molecular mechanism of ribosome-targeting antibiotics and bacterial resistance.We also review the most recent findings of ribosome dysfunction in COVID-19 and other conditions and discuss the consequences of ribosome frameshifting,ribosome-stalling,and ribosome-collision.We summarize the role of ribosome biogenesis in the development of various diseases.Furthermore,we review the current clinical trials,prospective vaccines for COVID-19,and therapies targeting ribosome biogenesis in cancer,cardiovascular disease,aging,and neurodegenerative disease.展开更多
Inflammasomes are protein complexes of the innate immune system that initiate inflammation in response to either exogenous pathogens or endogenous danger signals.Inflammasome multiprotein complexes are composed of thr...Inflammasomes are protein complexes of the innate immune system that initiate inflammation in response to either exogenous pathogens or endogenous danger signals.Inflammasome multiprotein complexes are composed of three parts:a sensor protein,an adaptor,and pro-caspase-1.Activation of the inflammasome leads to the activation of caspase-1,which cleaves pro-inflammatory cytokines such as IL-ip and IL-18,leading to pyroptosis.Effectors of the inflammasome not only provide protection against infectious pathogens,but also mediate control over sterile insults.Aberrant inflammasome signaling has been implicated in the development of cardiovascular and metabolic diseases,cancer,and neurodegenerative disorders.Here,we review the role of the inflammasome as a double-edged sword in various diseases,and the outcomes can be either good or bad depending on the disease,as well as the genetic background.We highlight inflammasome memory and the two-shot activation process.We also propose the M-and N-type inflammation model,and discuss how the inflammasome pathway may be targeted for the development of novel therapy.展开更多
Ventricular septal defect(VSD)is one of the commonest congenital heart diseases(CHDs).Current occluders for VSD treatment are mainly made of nitinol,which has the risk of nickel allergy,persistent myocardial abrasion ...Ventricular septal defect(VSD)is one of the commonest congenital heart diseases(CHDs).Current occluders for VSD treatment are mainly made of nitinol,which has the risk of nickel allergy,persistent myocardial abrasion and fatal arrythmia.Herein,a fully biodegradable polydioxanone(PDO)occluder equipped with a shape line and poly-L-lactic acid PLLA membranes is developed for VSD closure without the addition of metal marker.PDO occluder showed great mechanical strength,fatigue resistance,geometry fitness,biocompatibility and degradability.In a rat subcutaneous implantation model,PDO filaments significantly alleviated inflammation response,mitigated fibrosis and promoted endothelialization compared with nitinol.The safety and efficacy of PDO occluder were confirmed in a canine VSD model with 3-year follow-up,demonstrating the biodegradable PDO occluder could not only effectively repair VSD,induce cardiac remodeling but also address the complications associated with metal occluders.Furthermore,a pilot clinical trial with five VSD patients indicated that all the occluders were successfully implanted under the guidance of echocardiography and no adverse events occurred during the 3-month follow-up.Collectively,the fully bioresorbable PDO occluder is safe and effective for clinical VSD closure and holds great promise for the treatment of structural CHDs.展开更多
Dear Editor,Lower-limb ischemia is a serious clinical condition affecting many patients world-wide and there is no effective therapy.Ischemia activates the NLRP3 inflammasome,which triggers tissue damage by releasing ...Dear Editor,Lower-limb ischemia is a serious clinical condition affecting many patients world-wide and there is no effective therapy.Ischemia activates the NLRP3 inflammasome,which triggers tissue damage by releasing inflammatory cytokines including IL-1β and IL-18.1 However,the molecular mechanisms underlying activation of the NLRP3 inflammasome remain largely unknown.展开更多
Objectives:The aim of this multicenter,prospective,single-arm pilot study(ClinicalTrials.gov number:NCT05040074)was to observe the procedural and 30-day results of the novel transcatheter mitral valve repair system,SQ...Objectives:The aim of this multicenter,prospective,single-arm pilot study(ClinicalTrials.gov number:NCT05040074)was to observe the procedural and 30-day results of the novel transcatheter mitral valve repair system,SQ-Kyrin■-M Clip(Shenqi Medical,Shanghai,China),in patients with severe mitral regurgitation(MR).Methods:The heart team considered patients from 5 centers in China with clinically significant functional mitral regurgitation≥3+despite optimal medical therapy or degenerative mitral regurgitation≥3+with high surgical risk as candidates for transcatheter repair.All patients received transcatheter edge-to-edge mitral valve repair under general anesthesia.The primary outcome was technical success,which included all of the following measured at the exit from the catheterization laboratory:(1)absence of procedural mortality;(2)successful access,delivery,and retrieval of the device delivery system;(3)successful deployment and correct positioning of the frst intended device;and(4)no emergency surgery or reintervention related to the device or access procedure.The secondary outcomes included all-cause mortality,serious adverse events,device success,and procedural success 30 d after the intervention.Results:From June 2021 to December 2021,18 patients were enrolled in this study with age(75.7±7.4)years.Fifteen patients had MR 4+,while 3 had MR 3+.Technical success was achieved in all patients,including 6 degenerative mitral regurgitation and 12 functional mitral regurgitation patients.There was no all-cause mortality at 30 d.One patient had single leaflet device attachment within 30 d,which was regarded as a serious adverse event,and the patient was successfully treated with reintervention by implanting another clip.Another patient's transmitral gradient was 6 mmHg(>5 mmHg),with an effective orifice area of 2.57 cm^(2) after the procedure.Sixteen patients had device success and procedural success at 30 d postoperation.Fourteen patients had MR 1+,3 had MR 2+,and only 1 patient had MR 3+30 d after the procedure.Conclusions:The results of this feasibility study showed the efficacy and safety of the SQ-Kyrin■-M device in the Chinese population with severe MR,laying a solid foundation for a subsequent large-scale confirmatory study.展开更多
Mitral valve regurgitation(MR)is a common heart valve disease that affects>10%of the elderly population.Epidemiological data estimate that the number of MR patients has reached more than2.5 million in the USA,with ...Mitral valve regurgitation(MR)is a common heart valve disease that affects>10%of the elderly population.Epidemiological data estimate that the number of MR patients has reached more than2.5 million in the USA,with an extremely low surgical intervention rate(<5%)[1].展开更多
Background:Due to the wide variety of morphology,size,and dynamics,selecting an optimal valve size and location poses great difficulty in percutaneous pulmonary valve implantation(PPVI).This study aimed to report our ...Background:Due to the wide variety of morphology,size,and dynamics,selecting an optimal valve size and location poses great difficulty in percutaneous pulmonary valve implantation(PPVI).This study aimed to report our experience with in vitro bench testing using patient-specific three-dimensional(3D)-printed models for planning PPVI with the Venus P-valve.Methods:Patient-specific 3D soft models were generated using PolyJet printing with a compliant synthetic material in 15 patients scheduled to undergo PPVI between July 2018 and July 2020 in Central China Fuwai Hospital of Zhengzhou University.Results:3D model bench testing altered treatment strategy in all patients(100%).One patient was referred for surgery because testing revealed that even the largest Venus P-valve would not anchor properly.In the remaining 14 patients,valve size and/or implantation location was altered to avoid valve migration and/or compression coronary artery.In four patients,it was decided to change the point anchoring because of inverted cone-shaped right ventricular outflow tract(RVOT)(n=2)or risk of compression coronary artery(n=2).Concerning sizing,we found that an oversize of 2-5 mm suffices.Anchoring of the valve was dictated by the flaring of the in-and outflow portion in the pulmonary artery.PPVI was successful in all 14 patients(absence of valve migration,no coronary compression,and none-to-mild residual pulmonary regurgitation[PR]).The diameter of the Venus P-valve in the 3D simulation group was significantly smaller than that of the conventional planning group(36[2]vs.32[4],Z=-3.77,P<0.001).Conclusions:In vitro testing indicated no need to oversize the Venus P-valve to the degree recommended by the balloon-sizing technique,as 2-5 mm sufficed.展开更多
Once considered unconventional cellular structures,membraneless organelles(MLOs),cellular substructures involved in biological processes or pathways under physiological conditions,have emerged as central players in ce...Once considered unconventional cellular structures,membraneless organelles(MLOs),cellular substructures involved in biological processes or pathways under physiological conditions,have emerged as central players in cellular dynamics and function.MLOs can be formed through liquid-liquid phase separation(LLPS),resulting in the creation of condensates.From neurodegenerative disorders,cardiovascular diseases,aging,and metabolism to cancer,the influence of MLOs on human health and disease extends widely.This review discusses the underlying mechanisms of LLPS,the biophysical properties that drive MLO formation,and their implications for cellular function.We highlight recent advances in understanding how the physicochemical environment,molecular interactions,and post-translational modifications regulate LLPS and MLO dynamics.This review offers an overview of the discovery and current understanding of MLOs and biomolecular condensate in physiological conditions and diseases.This article aims to deliver the latest insights on MLOs and LLPS by analyzing current research,highlighting their critical role in cellular organization.The discussion also covers the role of membrane-associated condensates in cell signaling,including those involving T-cell receptors,stress granules linked to lysosomes,and biomolecular condensates within the Golgi apparatus.Additionally,the potential of targeting LLPS in clinical settings is explored,highlighting promising avenues for future research and therapeutic interventions.展开更多
objective:Severe tricuspid regurgitation frequently leads to increased mortality and a poor prognosis.Transcatheter edge-to-edge repair(TEER)for tricuspid valve regurgitation has been reported as a safe alternative to...objective:Severe tricuspid regurgitation frequently leads to increased mortality and a poor prognosis.Transcatheter edge-to-edge repair(TEER)for tricuspid valve regurgitation has been reported as a safe alternative to traditional open-heart surgery.This study endeavors to assess the efficacy and safety of a newly designed Neoblazar TEER system in this high-risk population.Methods:This investigation was structured as a prospective,single-arm,first-in-man trial in China(ClinicalTrials.gov number:NCT05497141).From August 2022 to October 2022,patients with severe tricuspid regurgitation were enrolled from 3 centers(Xiamen Cardiovascular Hospital,Fuwai Yunnan Cardiovascular Hospital,and Wuhan Union Hospital).The primary endpoint was achieving a minimum 1-grade reduction in tricuspid regurgitation at the 6-month post-TEER intervention,in addition to the pertinent New York Heart Association class.Scheduled echocardiographic evaluations were conducted at the following distinct intervals:baseline,discharge,1 month,and 6 months post-TEER intervention.Results:A total of 10 patients were enrolled in the study.Immediately after the TEER procedure with the Neoblazar system,massive tricuspid regurgitation(grade 5+)at baseline decreased to moderate-severe tricuspid regurgitation(grade 3+)in 2 patients and the optimal tricuspid regurgitation reduction(severe tricuspid regurgitation(grade 4+)to mild tricuspid regurgitation(grade 1+)were achieved in 6 patients.After 6 months of follow-up,tricuspid regurgitation reduction was found to be durable in all enrolled patients,among whom at least 1 grade of tricuspid regurgitation reduction was sustained,even without reintervention.Consistently,the New York Heart Association class among these subjects significantly improved,with the percentage of patients categorized as class I-ll increasing from 0/10 at baseline to 5/10 after 1 month(P=0.015)and 8/10 after 6 months(P<0.001).Conclusion:Tricuspid TEER with the newly designed Neoblazar system appears to be a feasible and safe alternative in treating patients with severe tricuspid regurgitation.However,the implementation of larger and more robust randomized trials is still necessary for further verification of the potential benefits.展开更多
Transcatheter edge-to-edge repair(TEER)of the mitral valve has emerged as a standard treatment for patients with severe degenerative mitral regurgitation at high or prohibitive surgical risk.The devices approved by th...Transcatheter edge-to-edge repair(TEER)of the mitral valve has emerged as a standard treatment for patients with severe degenerative mitral regurgitation at high or prohibitive surgical risk.The devices approved by the Food and Drug Administration including MitraClip(Abbott Vascular,California,USA)and PASCAL(Edwards Lifesciences,California,USA)cost over$33,000 in western countries.[1]This pricing presents a significant economic burden especially in developing countries,where TEER devices are typically not covered by health insurance.展开更多
The surgical treatment of isolated tricuspid regurgitation presents a notable mortality risk,particularly in patients who are referred late.Tricuspid transcatheter edge-to-edge repair(TEER)has become a safe and effect...The surgical treatment of isolated tricuspid regurgitation presents a notable mortality risk,particularly in patients who are referred late.Tricuspid transcatheter edge-to-edge repair(TEER)has become a safe and effective therapeutic option for patients with tricuspid regurgitation.^([1])The Kyrin^(TM)Tricuspid TEER system(Shenqi Medical,Shanghai,China)consists of a 24-French delivery catheter that is used to place one or more clips devices on the tricuspid-valve leaflets.Four clip sizes are available with a 12-or 9-mm arm length and 6-or 4-mm arm width.Herein,we report the initial result of using this tricuspid TEER system in Chinese patients with severe tricuspid regurgitation.展开更多
On October 23,2025,the Journal of the American Medical Association(JAMA)published online a multicenter,randomized study led by Chinese scientists,demonstrating that a novel fully bioresorbable occluder for atrial sept...On October 23,2025,the Journal of the American Medical Association(JAMA)published online a multicenter,randomized study led by Chinese scientists,demonstrating that a novel fully bioresorbable occluder for atrial septal defect(ASD)closure exhibits non-inferior efficacy and safety compared to conventional metal occluders,with near-complete degradation achieved within 2 years.1 This landmark achievement,based on China’s independently developed bioresorbable occluder.展开更多
文摘Background:The Venus-P valve was the first self-expanding valve used world-wide for transcatheter pulmonary valve replacement(TPVR)in patients with severe pulmonary regurgitation(PR).We intended to report the extended follow-up results from the prospective trial(No.NCT02590679).Methods:A total of 38 patients with severe PR(mean age 24.2±13.2)were included.Follow-up data were obtained after implanted at 1,6,and 12 months and yearly after.The frame geometry was assessed on post-implant computer tomography(CT)scanning by calculating the non-circularity[circularity ratio(minimum diameter/maximum diameter)<0.9]and under-expansion[expansion ratio(derived external valve area/nominal external valve area)<0.9).Adverse events(all-cause mortality,reintervention,valve dysfunction,stent fracture and endocarditis)were recorded.Results:All valves were implanted successfully with normal function at discharge.Geometric CT analysis showed underexpanded valve was detected in 22 patients(63%)and non-circular valve was seen in 16 patients(46%).During a median follow-up of 4.8 years(range 0.3-8.1),there were 1 death and 1 surgical explant,both resulting from endocarditis.Five-year freedom from valve dysfunction and stent fracture were 84.8%(95%CI 74.8-94.7)and 83.5%(95%CI 73.8-93.2).Endocarditis occurred in 3 patients at a median time of 7 months.Stent fracture was more common in patients with non-circularity stents.Conclusion:TPVR using Venus-P valve is associated with favorable outcomes at 5 years.Non-circular shapes in the valve level may have a higher risk of stent fracture.
基金Chinese Academy of Medical Sciences Fuwai Hospital High Level Hospital clinical research fund(2022-GSPGG-18).
文摘Compared with traditional nickel-titanium alloy patent foramen ovale occluders,which are widely used in clinical practice,biodegradable patent foramen ovale occluders have obvious differences in material characteristics,interventional operation mode and postoperative management strategy.This article gives expert consensus on the selection of clinical indications and standardized operating procedures,so as to standardize the clinical application of biodegradable patent foramen ovale occluders.
文摘Background In an effort to avoid x-ray and contrast agents for patients of atrial fibrillation(AF)with chronic kidney disease,we developed a method for transcatheter closure of left atrial appendage(LAA)under the guidance of transesophageal echocardiography(TEE)without fluoroscopy.
基金supported by the Fundamental Research Funds for the Central Universities(2019PT350005)National Natural Science Foundation of China(nos.81970444 and 82300345)+6 种基金Beijing Municipal Science and Technology Project(Z201100005420030)National high level talents special supportplan(2020-RSW02)CAMS Innovation Fund for MedicalSciences(2021-I2M-1-065)Sanming Project of Medicine in Shenzhen(SZSM202011013)the project for the distinguishing academic discipline of Fuwai Hospital(2022-FWQN16)the National High Level Hospital Clinical Research Funding(2023-GSP-QN-23)the National High Level Hospital Clinical Research Funding(2023-GSP-RC-04).
文摘Problem:Chest radiography is a crucial tool for diagnosing thoracic disorders,but interpretation errors and a lack of qualified practitioners can cause delays in treatment.Aim:This study aimed to develop a reliable multi-classification artificial intelligence(AI)tool to improve the accuracy and efficiency of chest radiograph diagnosis.Methods:We developed a convolutional neural network(CNN)capable of distinguishing among 26 thoracic diagnoses.The model was trained and externally validated using 795,055 chest radiographs from 13 datasets across 4 countries.Results:The CNN model achieved an average area under the curve(AUC)of 0.961 across all 26 diagnoses in the testing set.COVID-19 detection achieved perfect accuracy(AUC 1.000,[95%confidence interval{CI},1.000 to 1.000]),while effusion or pleural effusion detection showed the lowest accuracy(AUC 0.8453,[95%CI,0.8417 to 0.8489]).In external validation,the model demonstrated strong reproducibility and generalizability within the local dataset,achieving an AUC of 0.9634 for lung opacity detection(95%CI,0.9423 to 0.9702).The CNN outperformed both radiologists and nonradiological physicians,particularly in trans-device image recognition.Even for diseases not specifically trained on,such as aortic dissection,the AI model showed considerable scalability and enhanced diagnostic accuracy for physicians of varying experience levels(all P<0.05).Additionally,our model exhibited no gender bias(P>0.05).Conclusion:The developed AI algorithm,now available as professional web-based software,substantively improves chest radiograph interpretation.This research advances medical imaging and offers substantial diagnostic support in clinical settings.
基金National High Level Hospital Clinical Research Funding(2022-GSP-GG-18)National Key Research and Development Program of China(2022YFC2503400,2023YFC2412705)+1 种基金Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences[2021-I2M-1-065]Sanming Project of Medicine in Shenzhen[SZSM202011013].
文摘The advancement of catheter-based interventional techniques represents a significant evolution in cardiovascular medicine.However,traditional methods that rely on fluoroscopic guidance present considerable limitations including radiation exposure and contrast agentrelated risks and the heavy load-caused lead suits.In response,zero or low X-ray emerge,including percutaneous and non-fluoroscopical(PAN)procedure coming as a transformative solution,particularly in treating congenital heart disease,valvular disease,and arrhythmias.These methods minimize the risk of iatrogenic injuries associated with radiative procedures.Innovative PAN procedures and methodologies have been developed to enhance imaging,transcatheter interventions,safety,and accuracy,overcoming previous limitations.By eliminating radiation and expanding accessibility,PAN procedures offer a safe,effective,and economically viable alternative to traditional methods,ushering in a new era of minimally invasive cardiovascular treatment.
基金This work was supported by the National Natural Science Foundation of China(NSFC,No.81870194 to Y.Li,No.91849122 to Y.Li,NSFC,Nos.81873528,81670358 to Y.-H.S.,No.U1601227 to X.-Y.Y.)Jiangsu Province Peak of Talent in Six Industries(BU24600117 to Y.Li.)+6 种基金the project for the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD),and Translational Research Grant of NCRCH(2020WSB07)The Introduction Project of Clinical Medicine Expert Team for Suzhou(No.SZYJTD201704)The Fundamental Research Funds for the Central Universities(2019PT350005 to X.P.)National Natural Science Foundation of China(81970444 to X.P.)Beijing Municipal Science and Technology Project(Z201100005420030 to X.P.)National high-level talents special support plan(2020-RSW02 to X.P.)CAMS Innovation Fund for Medical Sciences(2021-I2M-1-065 to X.P.).We apologize in advance to colleagues whose work was not directly cited in this Review because of space limitations.
文摘The ribosome is a multi-unit complex that translates mRNA into protein.Ribosome biogenesis is the process that generates ribosomes and plays an essential role in cell proliferation,differentiation,apoptosis,development,and transformation.The mTORC1,Myc,and noncoding RNA signaling pathways are the primary mediators that work jointly with RNA polymerases and ribosome proteins to control ribosome biogenesis and protein synthesis.Activation of mTORC1 is required for normal fetal growth and development and tissue regeneration after birth.Myc is implicated in cancer development by enhancing RNA Pol II activity,leading to uncontrolled cancer cell growth.The deregulation of noncoding RNAs such as microRNAs,long noncoding RNAs,and circular RNAs is involved in developing blood,neurodegenerative diseases,and atherosclerosis.We review the similarities and differences between eukaryotic and bacterial ribosomes and the molecular mechanism of ribosome-targeting antibiotics and bacterial resistance.We also review the most recent findings of ribosome dysfunction in COVID-19 and other conditions and discuss the consequences of ribosome frameshifting,ribosome-stalling,and ribosome-collision.We summarize the role of ribosome biogenesis in the development of various diseases.Furthermore,we review the current clinical trials,prospective vaccines for COVID-19,and therapies targeting ribosome biogenesis in cancer,cardiovascular disease,aging,and neurodegenerative disease.
基金This work was supported by the National Natural Science Foundation of China(81870194 and 91849122 to Y.L.,81873528 and 81670358 to Y.-H.S.,91839101 to Z.S.,and U1601227 to X.-Y.Y.)Jiangsu Province Peak of Talent in Six Industries(BU24600117 to Y.L.)Introduction Project of Clinical Medicine Expert Team for Suzhou(No.SZYJTD201704).
文摘Inflammasomes are protein complexes of the innate immune system that initiate inflammation in response to either exogenous pathogens or endogenous danger signals.Inflammasome multiprotein complexes are composed of three parts:a sensor protein,an adaptor,and pro-caspase-1.Activation of the inflammasome leads to the activation of caspase-1,which cleaves pro-inflammatory cytokines such as IL-ip and IL-18,leading to pyroptosis.Effectors of the inflammasome not only provide protection against infectious pathogens,but also mediate control over sterile insults.Aberrant inflammasome signaling has been implicated in the development of cardiovascular and metabolic diseases,cancer,and neurodegenerative disorders.Here,we review the role of the inflammasome as a double-edged sword in various diseases,and the outcomes can be either good or bad depending on the disease,as well as the genetic background.We highlight inflammasome memory and the two-shot activation process.We also propose the M-and N-type inflammation model,and discuss how the inflammasome pathway may be targeted for the development of novel therapy.
基金supported by National Natural Science Foundation of China[81970444]The Fundamental Research Funds for the Central Universities[2019PT350005]+4 种基金Beijing Municipal Science and Technology Project[Z201100005420030]National high level talents special support plan[2020-RSW02]CAMS Innovation Fund for Medical Sciences[2021-I2M-1-065,2021-I2M-1-058]Sanming Project of Medicine in Shenzhen[SZSM202011013]Natural Science Fund for Distinguished Young Scholars of Tianjin[21JCJQJC00020].
文摘Ventricular septal defect(VSD)is one of the commonest congenital heart diseases(CHDs).Current occluders for VSD treatment are mainly made of nitinol,which has the risk of nickel allergy,persistent myocardial abrasion and fatal arrythmia.Herein,a fully biodegradable polydioxanone(PDO)occluder equipped with a shape line and poly-L-lactic acid PLLA membranes is developed for VSD closure without the addition of metal marker.PDO occluder showed great mechanical strength,fatigue resistance,geometry fitness,biocompatibility and degradability.In a rat subcutaneous implantation model,PDO filaments significantly alleviated inflammation response,mitigated fibrosis and promoted endothelialization compared with nitinol.The safety and efficacy of PDO occluder were confirmed in a canine VSD model with 3-year follow-up,demonstrating the biodegradable PDO occluder could not only effectively repair VSD,induce cardiac remodeling but also address the complications associated with metal occluders.Furthermore,a pilot clinical trial with five VSD patients indicated that all the occluders were successfully implanted under the guidance of echocardiography and no adverse events occurred during the 3-month follow-up.Collectively,the fully bioresorbable PDO occluder is safe and effective for clinical VSD closure and holds great promise for the treatment of structural CHDs.
基金This work was supported by the National Natural Science Foundation of China(NSFC,No.91849122 to Y.L,No.81870194 to Y.L)Jiangsu Province Peak of Talent in Six Industries(BU24600117 to Y.L.)+1 种基金National Natural Science Foundation of China(No.91839101 to Z.S.,No.U1601227 to X.Y.)Introduction Project of Clinical Medicine Expert Team for Suzhou(No.SZYJTD201704).
文摘Dear Editor,Lower-limb ischemia is a serious clinical condition affecting many patients world-wide and there is no effective therapy.Ischemia activates the NLRP3 inflammasome,which triggers tissue damage by releasing inflammatory cytokines including IL-1β and IL-18.1 However,the molecular mechanisms underlying activation of the NLRP3 inflammasome remain largely unknown.
基金supported by the National Key Project of Research and Development Plan during the fourteenth Five-year Plan Period(2022YFC2503400).
文摘Objectives:The aim of this multicenter,prospective,single-arm pilot study(ClinicalTrials.gov number:NCT05040074)was to observe the procedural and 30-day results of the novel transcatheter mitral valve repair system,SQ-Kyrin■-M Clip(Shenqi Medical,Shanghai,China),in patients with severe mitral regurgitation(MR).Methods:The heart team considered patients from 5 centers in China with clinically significant functional mitral regurgitation≥3+despite optimal medical therapy or degenerative mitral regurgitation≥3+with high surgical risk as candidates for transcatheter repair.All patients received transcatheter edge-to-edge mitral valve repair under general anesthesia.The primary outcome was technical success,which included all of the following measured at the exit from the catheterization laboratory:(1)absence of procedural mortality;(2)successful access,delivery,and retrieval of the device delivery system;(3)successful deployment and correct positioning of the frst intended device;and(4)no emergency surgery or reintervention related to the device or access procedure.The secondary outcomes included all-cause mortality,serious adverse events,device success,and procedural success 30 d after the intervention.Results:From June 2021 to December 2021,18 patients were enrolled in this study with age(75.7±7.4)years.Fifteen patients had MR 4+,while 3 had MR 3+.Technical success was achieved in all patients,including 6 degenerative mitral regurgitation and 12 functional mitral regurgitation patients.There was no all-cause mortality at 30 d.One patient had single leaflet device attachment within 30 d,which was regarded as a serious adverse event,and the patient was successfully treated with reintervention by implanting another clip.Another patient's transmitral gradient was 6 mmHg(>5 mmHg),with an effective orifice area of 2.57 cm^(2) after the procedure.Sixteen patients had device success and procedural success at 30 d postoperation.Fourteen patients had MR 1+,3 had MR 2+,and only 1 patient had MR 3+30 d after the procedure.Conclusions:The results of this feasibility study showed the efficacy and safety of the SQ-Kyrin■-M device in the Chinese population with severe MR,laying a solid foundation for a subsequent large-scale confirmatory study.
基金supported by a grant from Yunnan Provincial Cardiovascular Disease Clinical Medical Center Project(FZX201906-01)。
文摘Mitral valve regurgitation(MR)is a common heart valve disease that affects>10%of the elderly population.Epidemiological data estimate that the number of MR patients has reached more than2.5 million in the USA,with an extremely low surgical intervention rate(<5%)[1].
基金Henan Province health science and technology innovation talents training project(No.YXKC 2020047)
文摘Background:Due to the wide variety of morphology,size,and dynamics,selecting an optimal valve size and location poses great difficulty in percutaneous pulmonary valve implantation(PPVI).This study aimed to report our experience with in vitro bench testing using patient-specific three-dimensional(3D)-printed models for planning PPVI with the Venus P-valve.Methods:Patient-specific 3D soft models were generated using PolyJet printing with a compliant synthetic material in 15 patients scheduled to undergo PPVI between July 2018 and July 2020 in Central China Fuwai Hospital of Zhengzhou University.Results:3D model bench testing altered treatment strategy in all patients(100%).One patient was referred for surgery because testing revealed that even the largest Venus P-valve would not anchor properly.In the remaining 14 patients,valve size and/or implantation location was altered to avoid valve migration and/or compression coronary artery.In four patients,it was decided to change the point anchoring because of inverted cone-shaped right ventricular outflow tract(RVOT)(n=2)or risk of compression coronary artery(n=2).Concerning sizing,we found that an oversize of 2-5 mm suffices.Anchoring of the valve was dictated by the flaring of the in-and outflow portion in the pulmonary artery.PPVI was successful in all 14 patients(absence of valve migration,no coronary compression,and none-to-mild residual pulmonary regurgitation[PR]).The diameter of the Venus P-valve in the 3D simulation group was significantly smaller than that of the conventional planning group(36[2]vs.32[4],Z=-3.77,P<0.001).Conclusions:In vitro testing indicated no need to oversize the Venus P-valve to the degree recommended by the balloon-sizing technique,as 2-5 mm sufficed.
基金supported by the National Natural Science Foundation of China(82370264 to Y.Li,82370501 to Y.H.S.,81870194 and 91849122 to Y.Li,92168203 to Z.S.)Project of State Key Laboratory of Radiation Medicine and Protection,Soochow University(No.GZK12023023 to Y.Li)+4 种基金Jiangsu Cardiovascular Medicine Innovation Center(CXZX202210)China Postdoctoral Science Foundation(No.2021M702394 to Y.W.)Jiangsu Funding Program for Excellent Postdoctoral Talent(No.2022ZB578 to Y.W.)The project for the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)The National Key Research and Development Program of China(2022YFE0209700)to X.Y.Translational Research Grant of NCRCH(2020WSB07).
文摘Once considered unconventional cellular structures,membraneless organelles(MLOs),cellular substructures involved in biological processes or pathways under physiological conditions,have emerged as central players in cellular dynamics and function.MLOs can be formed through liquid-liquid phase separation(LLPS),resulting in the creation of condensates.From neurodegenerative disorders,cardiovascular diseases,aging,and metabolism to cancer,the influence of MLOs on human health and disease extends widely.This review discusses the underlying mechanisms of LLPS,the biophysical properties that drive MLO formation,and their implications for cellular function.We highlight recent advances in understanding how the physicochemical environment,molecular interactions,and post-translational modifications regulate LLPS and MLO dynamics.This review offers an overview of the discovery and current understanding of MLOs and biomolecular condensate in physiological conditions and diseases.This article aims to deliver the latest insights on MLOs and LLPS by analyzing current research,highlighting their critical role in cellular organization.The discussion also covers the role of membrane-associated condensates in cell signaling,including those involving T-cell receptors,stress granules linked to lysosomes,and biomolecular condensates within the Golgi apparatus.Additionally,the potential of targeting LLPS in clinical settings is explored,highlighting promising avenues for future research and therapeutic interventions.
基金National Key Researchand Development Program(2022YFC2503400)Yunnan Provincial Clinical Research Center for Cardiovascular Diseases(202302AA310045).
文摘objective:Severe tricuspid regurgitation frequently leads to increased mortality and a poor prognosis.Transcatheter edge-to-edge repair(TEER)for tricuspid valve regurgitation has been reported as a safe alternative to traditional open-heart surgery.This study endeavors to assess the efficacy and safety of a newly designed Neoblazar TEER system in this high-risk population.Methods:This investigation was structured as a prospective,single-arm,first-in-man trial in China(ClinicalTrials.gov number:NCT05497141).From August 2022 to October 2022,patients with severe tricuspid regurgitation were enrolled from 3 centers(Xiamen Cardiovascular Hospital,Fuwai Yunnan Cardiovascular Hospital,and Wuhan Union Hospital).The primary endpoint was achieving a minimum 1-grade reduction in tricuspid regurgitation at the 6-month post-TEER intervention,in addition to the pertinent New York Heart Association class.Scheduled echocardiographic evaluations were conducted at the following distinct intervals:baseline,discharge,1 month,and 6 months post-TEER intervention.Results:A total of 10 patients were enrolled in the study.Immediately after the TEER procedure with the Neoblazar system,massive tricuspid regurgitation(grade 5+)at baseline decreased to moderate-severe tricuspid regurgitation(grade 3+)in 2 patients and the optimal tricuspid regurgitation reduction(severe tricuspid regurgitation(grade 4+)to mild tricuspid regurgitation(grade 1+)were achieved in 6 patients.After 6 months of follow-up,tricuspid regurgitation reduction was found to be durable in all enrolled patients,among whom at least 1 grade of tricuspid regurgitation reduction was sustained,even without reintervention.Consistently,the New York Heart Association class among these subjects significantly improved,with the percentage of patients categorized as class I-ll increasing from 0/10 at baseline to 5/10 after 1 month(P=0.015)and 8/10 after 6 months(P<0.001).Conclusion:Tricuspid TEER with the newly designed Neoblazar system appears to be a feasible and safe alternative in treating patients with severe tricuspid regurgitation.However,the implementation of larger and more robust randomized trials is still necessary for further verification of the potential benefits.
基金supported by the National Key R&D Program of China(2022YFC2503400)Major science and technology special plan project of Yunnan Province(202302AA310045)Yunnan Provincial Clinical Research Center for Cardiovascular Diseases(202102AA310002).
文摘Transcatheter edge-to-edge repair(TEER)of the mitral valve has emerged as a standard treatment for patients with severe degenerative mitral regurgitation at high or prohibitive surgical risk.The devices approved by the Food and Drug Administration including MitraClip(Abbott Vascular,California,USA)and PASCAL(Edwards Lifesciences,California,USA)cost over$33,000 in western countries.[1]This pricing presents a significant economic burden especially in developing countries,where TEER devices are typically not covered by health insurance.
基金supported by the National Key R&D Program of China(2022YFC2503400)the Major Science and Technology Special Plan Project of Yunnan Province(202302AA310045).
文摘The surgical treatment of isolated tricuspid regurgitation presents a notable mortality risk,particularly in patients who are referred late.Tricuspid transcatheter edge-to-edge repair(TEER)has become a safe and effective therapeutic option for patients with tricuspid regurgitation.^([1])The Kyrin^(TM)Tricuspid TEER system(Shenqi Medical,Shanghai,China)consists of a 24-French delivery catheter that is used to place one or more clips devices on the tricuspid-valve leaflets.Four clip sizes are available with a 12-or 9-mm arm length and 6-or 4-mm arm width.Herein,we report the initial result of using this tricuspid TEER system in Chinese patients with severe tricuspid regurgitation.
基金supported by the Beijing Research Ward Excellence Program(BRWEP2024W014030101)National Major Research Instruments and Facilities of the National Natural Science Foundation of China(82327801)+6 种基金the Chinese Academy of Medical Sciences(CAMS)Innovation Fund for Medical Sciences(2024-I2M-ZH-003)the Clinical and Translational Medicine Research Program of the Chinese Academy of Medical Sci-ences(2024-I2M-C&T-C-006)National High Level Hospital Clinical Research Funding(2022-GSP-GG-18)the National Clinical Research Center for Cardiovascular Diseases,Fu-wai Hospital,CAMS(NCRC2020009)the Yunnan Pan Xiangbin Expert Workstation under the Yunnan Provincial Project for Scientific and Technological Talents and Platforms(proj-ect no.202305AF150069)the National Natural Science Foundation of China(82300345)the Fundamental Research Funds for the Central Universities,Peking Union Medical College(no.3332025033).
文摘On October 23,2025,the Journal of the American Medical Association(JAMA)published online a multicenter,randomized study led by Chinese scientists,demonstrating that a novel fully bioresorbable occluder for atrial septal defect(ASD)closure exhibits non-inferior efficacy and safety compared to conventional metal occluders,with near-complete degradation achieved within 2 years.1 This landmark achievement,based on China’s independently developed bioresorbable occluder.
