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The activity and immune dynamics of PD-1 inhibition on high-risk pulmonary ground glass opacity lesions:insights from a single-arm,phase II trial

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Signal Transduction and Targeted Therapy 2024年第5期9卷 2202-2214页

作者： Bo Cheng Caichen Li Jianfu Li Longlong Gong Peng Liang Ying Chen Shuting Zhan Shan Xiong Ran Zhong Hengrui Liang Yi Feng Runchen Wang Haixuan Wang Hongbo Zheng Jun Liu Chengzhi Zhou Wenlong Shao Yuan Qiu Jiancong Sun Zhanhong Xie Zhu Liang Chenglin Yang Xiuyu Cai Chunxia Su Wei Wang Jianxing He Wenhua Liang Department of Thoracic surgery and Oncology the First Affiliated Hospital of Guangzhou Medical UniversityGuangzhou Institute of Respiratory HealthState Key Laboratory of Respiratory DiseaseNational Clinical Research Center for Respiratory DiseaseGuangzhouChina Medical Department Genecast Biotechnology Co.LtdWuxiChina Department of Radiation Oncology the First Affiliated Hospital of Guangzhou Medical UniversityGuangzhouChina Department of Respiratory Medicine the First Affiliated Hospital of Guangzhou Medical UniversityGuangzhou Institute of Respiratory HealthState Key Laboratory of Respiratory DiseaseNational Clinical Research Center for Respiratory DiseaseGuangzhouChina Department of cardiothoracic surgery Affiliated Hospital of Guangdong Medical UniversityZhanjiangChina Department of Thoracic surgery National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital&Shenzhen HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeShenzhenChina Department of VIP Inpatient Sun Yat-sen University Cancer CenterState Key Laboratory of Oncology in South ChinaSun Yat-sen UniversityGuangzhouChina Department of Medical Oncology Shanghai Pulmonary HospitalSchool of MedicineTongji UniversityShanghaiChina

Immune checkpoint inhibitors targeting the programmed cell death-1(PD-1)protein significantly improve survival in patients with advanced non-small-cell lung cancer(NSCLC),but its impact on early-stage ground-glass opacity(GGO)lesions remains *** is a single-arm,phase II trial(NCT04026841)using Simon’s optimal two-stage design,of which 4 doses of sintilimab(200 mg per 3 weeks)were administrated in 36 enrolled multiple primary lung cancer(MPLC)patients with persistent high-risk(Lung-RADS category 4 or had progressed within 6 months)*** primary endpoint was objective response rate(ORR).T/B/NK-cell subpopulations,TCR-seq,cytokines,exosomal RNA,and multiplexed immunohistochemistry(mIHC)were monitored and compared between responders and ***,two intent-to-treat(ITT)lesions(pure-GGO or GGO-predominant)showed responses(ORR:5.6%,2/36),and no patients had progressive disease(PD).No grade 3-5 TRAEs *** total response rate considering two ITT lesions and three non-intent-to-treat(NITT)lesions(pure-solid or solid-predominant)was 13.9%(5/36).The proportion of CD8^(+)T cells,the ratio of CD8^(+)/CD4^(+),and the TCR clonality value were significantly higher in the peripheral blood of responders before treatment and decreased over ***,the mIHC analysis showed more CD8^(+)T cells infiltrated in ***,responders’cytokine concentrations of EGF and CTLA-4 increased during *** exosomal expression of fatty acid metabolism and oxidative phosphorylation gene signatures were down-regulated among ***,PD-1 inhibitor showed certain activity on high-risk pulmonary GGO lesions without safety *** effects were associated with specific T-cell re-distribution,EGF/CTLA-4 cytokine compensation,and regulation of metabolism pathways.

关键词： lesions metabolism doses

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Extracellular Vesicles from Mesenchymal Stromal Cells (imEVs) Improve Cold Preservation of Isolated Mitochondria

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Journal of Biosciences and Medicines 2024年第1期12卷 52-63页

作者： Xianpeng Jiang Sergey Rodin Ken Braesch-Andersen Catherine C. Baucom Karl-Henrik Grinnemo Brent Segal Elliott Mitochondrial Center Sallie Astor Burdine Breast Foundation Baton Rouge Louisiana USA Mitosense Inc. Boston Massachusetts USA Department of Surgical Sciences Division of Cardiothoracic Surgery Cardio-Thoracic Translational Medicine (CTTM) Laboratory Uppsala University Uppsala University Hospital Uppsala Sweden

Mitochondrial organelle transplantation (MOT) is an innovative strategy for the treatment of mitochondrial dysfunction such as cardiac ischemic reperfusion injuries, Parkinson’s diseases, brain and spinal cord injuries, and amyotrophic lateral sclerosis (ALS). However, one of the major challenges for widespread usage is a methodology for preservation of isolated mitochondria. Extracellular vesicles (EVs) are phospholipid bilayer-enclosed vesicles released from cells. EVs carry a cargo of proteins, nucleic acids, lipids, metabolites, and even organelles such as mitochondria. Purpose: To test if EVs enhance the stability of isolated mitochondria. Methods: We mixed isolated mitochondria of fibroblasts with EVs of mesenchymal stromal cells (imEVs) (9:1 in volume) and stored the mixture at 2°C - 6°C for different time periods. We measured morphology, mitochondrial membrane potential (MMP) and mitochondrial ATP content at 0, 2, 5 days. Key findings: After 2 days of storage, the mito-chondria without imEVs lost approximate 70% MMP (RFU: 1822 ± 68), compared to the fresh mitochondria (RFU: 5458 ± 52) (p 0.05). In agreement with MMP, mitochondria without imEVs lost significant mitochondrial ATP content (p 0.05), after 2 days of cold storage, compared to fresh mitochondria. Microscopy showed that imEVs promoted aggregation of isolated mitochondria. Summary: The preliminary data showed that imEVs enhanced the stability of isolated mitochondria in cold storage.

关键词： Mitochondria Extracellular Vesicles Mitochondrial Preservation MOT imEVs

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Recent advances in the diagnostic methods and therapeutic strategies of transthyretin cardiac amyloidosis

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World Journal of Cardiology 2024年第7期16卷 370-379页

作者： Christos Kourek Alexandros Briasoulis Dimitrios E Magouliotis Panagiotis Georgoulias Grigorios Giamouzis Filippos Triposkiadis John Skoularigis Andrew Xanthopoulos Clinical Ergospirometry Exercise and Rehabilitation Laboratory1^(st)Critical Care Medicine DepartmentEvangelismos HospitalNational and Kapodistrian University of AthensAthens 10676Greece Department of Clinical Therapeutics Alexandra HospitalFaculty of MedicineNational and Kapodistrian University of AthensAthens 11528Greece Department of cardiothoracic surgery University of ThessalyLarissa BiopolisLarissa 41110Greece Department of Nuclear Medicine University Hospital of LarissaLarissa 41110Greece Department of Cardiology School of MedicineUniversity Hospital of LarissaLarissa 41110Greece

Cardiac amyloidosis is a progressive disease characterized by the buildup of amyloid fibrils in the extracellular space of the *** is divided in 2 main types,immunoglobulin light chain amyloidosis and transthyretin amyloidosis(ATTR),and ATTR amyloidosis is further divided in 2 subtypes,non-hereditary wild type ATTR and hereditary mutant variant *** and prevalence of ATTR cardiac amyloidosis is increasing over the last years due to the improvements in diagnostic *** rates are improving due to the development of novel therapeutic *** is the only disease-modifying approved therapy in ATTR amyloidosis so ***,the most recent advances in medical therapies have added more options with the potential to become part of the therapeutic armamentarium of the *** including acoramidis,eplontersen,vutrisiran,patisiran and anti-monoclonal antibody NI006 are being investigated on cardiac function in large,multicenter controlled trials which are expected to be completed within the next 2-3 years,providing promising results in patients with ATTR cardiac ***,further and ongoing research is required in order to improve diagnostic methods that could provide an early diagnosis,as well as survival and quality of life of these patients.

关键词： Transthyretin cardiac amyloidosis Tafamidis Acoramidis Eplontersen Vutrisiran Patisiran

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The Impact of a Prior Norwood Procedure on Cardiac Transplantation in Failed Fontan Physiology

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Congenital Heart Disease 2024年第3期19卷 257-266页

作者： Ryan G.McQueen Nikki M.Singh Ronald K.Woods Medical College of Wisconsin Herma Heart Institute at Children’s WisconsinMilwaukeeUSA Division of Pediatric Cardiology Medical College of WisconsinHerma Heart Institute at Children’s WisconsinMilwaukeeUSA Division of Pediatric cardiothoracic surgery Medical College of WisconsinHerma Heart Institute at Children’s WisconsinMilwaukeeUSA

Objective:The objective of this study was to compare cardiac transplant operative and postoperative courses of patients with failed Fontan physiology who were initially palliated with a Norwood(FFN)to those without a prior Norwood(FF).Methods:A single-institution retrospective review of all patients with Fontan failure who under-went cardiac transplantation from 2003–2021 was completed-22 underwent prior Norwood(FFN)and 11 did not(FF).Descriptive and inferential statistics were calculated for operative course and patient ***:The operative course of the FFN cohort appeared to be more complex(not statistically signiﬁcant,but clinically relevant)-this group exclusively experienced sternal re-entry events(3 of 22 patients)and concomitant neo-aor-tic reconstruction(6 patients),had a longer duration of surgery(median of 682 min vs.575.5 min),more time on circulatory arrest(median of 25.5 min vs.12.5 min),and more frequent use of open sternal management[50%of patients(11/22)vs.27.3%of patients(3/11)].Postoperatively,these patients underwent more mediastinal explora-tions[other than sternal closure;40.9%of patients(9/22)vs.18.2%of patients(2/11)],spent more time on mechanical ventilation(median of 5 days vs.2 days),had a longer length of stay(median of 30 days vs.19 days),and required more catheter-based re-interventions[22.7%of patients(5/22)vs.9.1%of patients(1/11)].Conclu-sion:Although underpowered,our results suggest that the operative course of FFN patients is more challenging,based mostly on neo-aortic arch *** turn,this likely leads to a more complex postoperative *** are currently collaborating with other institutions to increase the cohort size and power of the study.

关键词： Fontan Fontan failure Norwood cardiac transplantation

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Physical exercise reverses immuno-cold tumor microenvironment via inhibiting SQLE in non-small cell lung cancer

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Military Medical Research 2024年第4期 616-619页

作者： Zhi-Wen Luo Ya-Ying Sun Wei Xia Jun-Ying Xu Dong-Jing Xie Chun-Meng Jiao Ji-Ze Dong Hui Chen Ren-Wen Wan Shi-Yi Chen Jie Mei Wen-Jun Mao Department of Sports Medicine Huashan Hospital Affiliated to Fudan University Department of Sports Medicine Shanghai General Hospital Department of Critical Care Medicine the Affiliated Wuxi People's Hospital of Nanjing Medical University Department of Oncology the Affiliated Wuxi People's Hospital of Nanjing Medical University Guangdong Pharmaceutical University Institute of Acupuncture Research Institutes of Integrative MedicineFudan University Department of cardiothoracic surgery the Affiliated Wuxi People's Hospital of Nanjing Medical University

Dear Editor,Physical exercise has been shown to be associated with reduced cancer incidence and cancer-associated mortality[1,2],but the underlying mechanisms are *** regulation has emerged as one of the most prominent mechanisms explaining the effects of exercise on cancer[1,2].Physical exercise primarily lowers blood cholesterol and triglycerides,and protects against cardiovascular diseases[3].

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Management of a patient with an unusual trajectory of a temporary trans-venous pacing lead

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World Journal of Cardiology 2024年第6期16卷 314-317页

作者： Metesh Acharya Ethan Kavanagh Sheena Garg Davorin Sef Fabio De Robertis Department of Cardiac surgery University Hospitals of Leicester NHS TrustLeicester LE39QPUnited Kingdom Department of Cardiac surgery King’s College LondonLondon WC2R 2LSUnited Kingdom Department of Cardiac surgery Royal Brompton and Harefield HospitalsLondon UB96JHUnited Kingdom

Perforation of the right ventricle during placement of pacing wires is a welldocumented complication and can be potentially *** of temporary pacemaker,helical screw leads and steroids use prior to implant are recognised as risk factors for development of post-permanent pacemaker *** reported an unusual case of pacing wire perforating interventricular septum into the left ventricle that occurred during the implant procedure performed in another *** the preoperative work-up and transfer to our tertiary cardiothoracic centre,the patient underwent successful surgical *** conclusion,early recognition and timely diagnosis using advanced multimodality imaging can guide surgical intervention and prevent unfavourable consequences of device-related complications.

关键词： Ventricular perforation Lead perforation Pacing

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Antitumor efficacy and potential mechanism of FAP-targeted radioligand therapy combined with immune checkpoint blockade

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Signal Transduction and Targeted Therapy 2024年第7期9卷 2936-2952页

作者： Liang Zhao Yizhen Pang Yangfan Zhou Jianhao Chen Hao Fu Wei Guo Weizhi Xu Xin Xue Guoqiang Su Long Sun Hua Wu Jingjing Zhang Zhanxiang Wang Qin Lin Xiaoyuan Chen Haojun Chen Department of Nuclear Medicine and Minnan PET Center Xiamen Key Laboratory of RadiopharmaceuticalsThe First Affiliated Hospital of Xiamen UniversitySchool of MedicineXiamen UniversityXiamenChina Departments of Diagnostic Radiology SurgeryChemical and Biomolecular Engineeringand Biomedical EngineeringYong Loo Lin School of Medicine and College of Design and EngineeringNational University of SingaporeSingaporeSingapore Clinical Imaging Research Centre Centre for Translational MedicineYong Loo Lin School of MedicineNational University of SingaporeSingaporeSingapore Department of Radiation Oncology Xiamen Cancer CenterXiamen Key Laboratory of Radiation OncologyThe First Affiliated Hospital of Xiamen UniversitySchool of MedicineXiamen UniversityXiamenChina Department of Colorectal Tumor surgery Xiamen Cancer CenterXiamen Key Laboratory of Radiation OncologyThe First Affiliated Hospital of Xiamen UniversitySchool of MedicineXiamen UniversityXiamenChina Department of cardiothoracic surgery Zhongda HospitalSchool of MedicineSoutheast UniversityNanjingChina Nanomedicine Translational Research Program NUS Center for NanomedicineYong Loo Lin School of MedicineNational University of SingaporeSingaporeSingapore Department of Neurosurgery and Department of Neuroscience Fujian Key Laboratory of Brain Tumors Diagnosis and Precision TreatmentXiamen Key Laboratory of Brain Centerthe First Affiliated Hospital of Xiamen UniversitySchool of MedicineXiamen UniversityXiamenChina Institute of Molecular and Cell Biology Agency for ScienceTechnology and Research(A*STAR)SingaporeSingapore Xiamen Key Laboratory of Rare Earth Photoelectric Functional Materials Xiamen Institute of Rare Earth MaterialsHaixi InstituteChinese Academy of SciencesXiamenChina

Radiotherapy combined with immune checkpoint blockade holds great promise for synergistic antitumor *** radionuclide therapy delivers radiation directly to tumor ***1004 is a fibroblast activation protein(FAP)-targeting radiopharmaceutical,conjugated with the albumin binder Evans Blue,which has demonstrated enhanced tumor uptake and retention in previous preclinical and clinical ***,we demonstrate that^(68)Ga/^(177)Lu-labeled LNC1004 exhibits increased uptake and prolonged retention in MC38/NIH3T3-FAP and CT26/NIH3T3-FAP tumor *** therapy with^(177)Lu-LNC1004 induced a transient upregulation of PD-L1 expression in tumor *** combination of^(177)Lu-LNC1004 and anti-PD-L1 immunotherapy led to complete eradication of all tumors in MC38/NIH3T3-FAP tumor-bearing mice,with mice showing 100%tumor rejection upon ***,single-cell RNA sequencing(scRNA-seq),and TCR sequencing revealed that combination therapy reprogrammed the tumor microenvironment in mice to foster antitumor immunity by suppressing malignant progression and increasing cell-to-cell communication,CD8^(+)T-cell activation and expansion,M1 macrophage counts,antitumor activity of neutrophils,and T-cell receptor diversity.A preliminary clinical study demonstrated that^(177)Lu-LNC1004 was well-tolerated and effective in patients with refractory ***,scRNA-seq of peripheral blood mononuclear cells underscored the importance of addressing immune evasion through immune checkpoint blockade *** was emphasized by the observed increase in antigen processing and presentation juxtaposed with T cell *** conclusion,our data supported the efficacy of immunotherapy combined with^(177)Lu-LNC1004 for cancer patients with FAP-positive tumors.

关键词： immunity retention holds

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Short-(30-90 days)and mid-term(1-3 years)outcomes and prognostic factors of patients with esophageal cancer undergoing surgical treatments

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World Journal of Clinical Cases 2022年第22期10卷 7708-7719页

作者： Meng-Kun Shi Yun-Qing Mei Jia-Lun Shi Department of cardiothoracic surgery Tongji HospitalSchool of MedicineTongji UniversityShanghai 200092China Department of cardiothoracic surgery Heping Hospital Affiliated to Changzhi Medical CollegeChangzhi 046000Shanxi ProvinceChina

BACKGROUND The factors influencing the prognosis of patients with esophageal cancer vary among studies and are still poorly *** To determine the factors associated with survival in patients with esophageal *** This retrospective study included patients with esophageal cancer admitted between January 2017 and March 2020 at Heping Hospital Affiliated to Changzhi Medical College. All patients were treated according to the available guidelines. Follow-up was censored in October 2020. Univariable and multivariable Cox regression analyses were used to determine the independent risk factors for overall survival(OS).RESULTS In total, 307 patients were included. Their median age was 64(range, 44-79) years, 63.5% were male, and the median disease course was 2(0.1-36) months. The median tumor size was 3(0-10) cm. Most patients were T3(29.6%), N0(70.0%). Most tumors were grade 2(48.2%), and 87.3% were squamous cell carcinoma. The in-hospital mortality was 16.9%, the 30-day mortality was 19.9%, and the 90-day mortality was 25.4%. The cumulative OS rates at the last follow-up were 82.1%(95%CI: 67.7%-96.5%) for stage 0/Ⅰ/Ⅱ and 47.4%(95%CI: 16.5-78.6%) for stage Ⅲ/ⅣA(P < 0.001). The multivariable analysis showed that creatinine levels(HR = 1.02, 95%CI: 1.00-1.03, P = 0.050), pTNM Ⅲ/ⅣA(HR = 4.19, 95%CI: 2.19-8.01, P < 0.001), adjuvant radiotherapy and/or chemotherapy(HR = 0.23, 95%CI: 0.11-0.49), and the Comprehensive Complication Index(CCI)(HR = 1.02, 95%CI: 1.004-1.03, P = 0.011) were independently associated with *** The survival of patients with esophageal cancer is poor, especially those with pTNM Ⅲ/ⅣA. pTNM stage Ⅲ/ⅣA, CCI, and adjuvant therapy(radiotherapy and/or chemotherapy) are independently associated with OS.

关键词： Esophageal cancer Survival Prognosis Factors Multivariable analysis

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The Promoting Role of TCM Nursing in the Rehabilitation of Stroke Hemiplegia Patients

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Open Journal of Nursing 2024年第7期14卷 321-328页

作者： Nong Yan Lihua Qin Buqing Su Xiaoye Su Yanfang Wei Department of Internal Medicine Pingguo Hospital of Traditional Chinese Medicine Baise China Department of Neurology Peoples Hospital of Guangxi-ASEAN Economic and Technological Development Zone (10th Peoples Hospital of Nanning City) Nanning China The Clinical Nursing Program at Liaoning Medical Vocational College Shenyang China Department of Internal Medicine Batou Township Central Health Center of Debao County Baise China Department of cardiothoracic surgery Nanning Third Peoples Hospital Nanning China

Objective: To explore the promoting function of TCM nursing in the rehabilitation of hemiplegia patients with stroke. Methods: 78 stroke hemiplegic patients admitted from April 2022 to April 2024 were randomly divided into a control group of 38 cases who received routine care, and an experimental group of 40 cases who received routine nursing basis plus traditional Chinese medicine nursing;the nursing effects of the two groups of patients were compared. Results: After 12 days of nursing care, the experimental group showed better psychological status [SAS score (21.71 ± 3.21), SDS score (22.18 ± 2.31)], limb motor function, daily living ability, and neurological function [NIHSS score (12.23 ± 2.21)] than the control group, with significant differences in data (P Conclusion: Traditional Chinese medicine nursing for stroke hemiplegia patients is more conducive to promoting rehabilitation than routine nursing.

关键词： Traditional Chinese Medicine Nursing Routine Nursing Stroke Hemiplegia Rehabilitation Effect

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One-year survival in recipients older than 50 bridged to heart transplant with Impella 5.5 via axillary approach

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Journal of Geriatric Cardiology 2023年第5期20卷 319-329页

作者： Smit Paghdar Smruti Desai Ji-Min Jang Jose Ruiz Sharan Malkani Parag Patel Daniel S Yip Juan C Leoni Jose Nativi Basar Sareyyupoglu Kevin Landolfo Si Pham Rohan M Goswami Division of Heart Failure and Transplant Mayo Clinic in FloridaUSA Department of cardiothoracic surgery Mayo Clinic in FloridaUSA

BACKGROUND Optimizing patients with advanced heart failure before orthotopic heart transplantation(OHT), especially in patients greater than 50 years old, is imperative to achieving successful post-transplant outcomes. Complications are well-described for patients bridged to transplant(BTT) with durable left ventricular assist device(LVAD) support. Given the lack of data available in older recipients after the recent increase in mechanical support use, we felt it crucial to report our center’s one-year outcomes in older recipients after heart transplantation with percutaneously placed Impella 5.5 as a *** Forty-nine OHT patients were supported with the Impella 5.5 intended as a bridge between December 2019 and October 2022 at Mayo Clinic in Florida. Data were extracted from the electronic health record at baseline and during their transplant episode of care after Institutional Review Boards approval as exempt for retrospective data *** Thirty-eight patients aged 50 or older were supported with Impella 5.5 as BTT. Ten patients underwent heart and kidney transplantation within this cohort. The median age at OHT was 63(58–68) years, with 32 male(84%) and six female patients(16%). Etiology was divided into ischemic(63%) and non-ischemic cardiomyopathy(37%). The baseline median ejection fraction was 19%(15–24). Most patients were in blood group O(60%), and 50% were diabetic. The average duration of support was 27 days(range 6–94). The median duration of follow-up is 488 days(185–693). For patients that have reached the 1-year follow-up timeframe(22 of 38, 58%), the 1-year post-transplant survival is 95%.CONCLUSION Our single-center data provides awareness for using the Impella 5.5 percutaneously placed axillary support device in older heart failure patients in cardiogenic shock as a bridge to transplantation. One-year survival outcomes after heart transplantation are excellent despite the older recipient’s age and prolonged pre-transplant support.

关键词： One approval transplant

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