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Anti-EGFR antibody monotherapy for colorectal cancer with severe hyperbilirubinemia: A case report

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World Journal of Gastrointestinal Oncology 2024年第2期16卷 557-562页

作者： Toshiaki Tsurui Yuya Hirasawa Yutaro Kubota Kiyoshi Yoshimura Takuya Tsunoda department of Medical Oncology Showa UniversityTokyo 1428555Japan department of Clinical Immuno Oncology Clinical Research Institute of Clinical Pharmacology and TherapeuticsShowa UniversityTokyo 1578577Japan

BACKGROUND Hyperbilirubinemia with hepatic metastases is a common complication and a poor prognostic factor for colorectal cancer(CRC).Effective drainage is often im-possible before initiating systemic chemotherapy,owing to the liver’s diffuse metastatic involvement.Moreover,an appropriate chemotherapeutic approach for the treatment of hyperbilirubinemia is currently unavailable.CASE SUMMARY The patient,a man in his 50s,presented with progressive fatigue and severe jaundice.Computed tomography revealed multiple hepatic masses with thick-ened walls in the sigmoid colon,which was pathologically confirmed as a well-differentiated adenocarcinoma.No RAS or BRAF mutations were detected.The Eastern Cooperative Oncology Group(ECOG)performance status(PS)score was 2.Biliary drainage was impossible due to the absence of a dilated bile duct,and panitumumab monotherapy was promptly initiated.Subsequently,the bilirubin level decreased and then normalized,and the patient’s PS improved to zero ECOG score after four cycles of therapy without significant adverse events.CONCLUSION Anti-EGFR antibody monotherapy is a safe and effective treatment for RAS wild-type CRC and hepatic metastases with severe hyperbilirubinemia.

关键词： Colorectal neoplasms Panitumumab Chemotherapy Hyperbilirubinemia Jaundice Case report

Proteomics analysis of coronary atherosclerotic heart disease with different Traditional Chinese Medicine syndrome types before and after percutaneous coronary intervention

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Journal of Traditional Chinese Medicine 2024年第3期44卷 554-563页

作者： WANG Zhibo LI Ying WANG Daoping MA Bo MIAO Lan REN Junguo LIU Jinghua LIU Jianxun Beijing Key Laboratory of pharmacology of Chinese Materia Region Institute of Basic Medical SciencesXiyuan HospitalChina Academy of Chinese Medical SciencesNational Clinical Research Center of Cardiovascular Disease of Traditional Chinese Medicine the National Key Facility for Crop Gene Resources and Genetic Improvement Institute of Crop ScienceChinese Academy of Agricultural Science department of Cardiology Beijing Anzhen HospitalCapital Medical University

OBJECTIVE: To investigate the underlying protein molecular mechanisms of "Qi stagnation and blood stasis syndrome"(QS) and "Qi deficiency and blood stasis syndrome"(QD), as two subtypes of coronary artery disease(CAD) in Traditional Chinese Medicine(TCM),following percutaneous coronary intervention(PCI).METHODS: In this study, a total of 227 CAD patients with QS and 211 CAD patients with QD were enrolled; all participants underwent PCI. Label-free quantification proteomics were employed to analyze the changes in serum in two subtypes of CAD patients before and 6 months after PCI, aiming to elucidate the intervention mechanism of PCI in treating CAD characterized by two different TCM syndromes.RESULTS: Biochemical analysis revealed significant changes in tumor necrosis factor-α, high density lipoprotein cholesterol, blood stasis clinical symptoms observation, and Gensini levels in both patient groups post-PCI; Proteomic analysis identified 79 and 95 differentially expressed proteins in the QS and QD patient groups, respectively, compared to their control groups.complement C8 alpha chain, complement factor H,apolipoprotein H, apolipoprotein B, plasminogen,carbonic anhydrase 2, and complement factor Ⅰ were altered in both comparison groups. Furthermore,enrichment analysis demonstrated that cell adhesion and connectivity-related processes underwent changes in QS patients post-PCI, whereas lipid metabolism-related pathways, including the peroxisome proliferator-activated receptor signaling pathway and extracellular matrix receptor interaction, underwent changes in the QD group.The protein-protein interaction network analysis further enriched 52 node proteins, including apolipoprotein B,lipoprotein(a), complement C5, apolipoprotein A4,complement C8 alpha chain, complement C8 beta chain,complement C8 gamma chain, apolipoprotein H,apolipoprotein A-Ⅱ, albumin, complement C4-B,apolipoprotein C3, among others. The functional network of these proteins is posited to contribute to the pathophysiology of CAD characterized by TC

关键词： Traditional Chinese Medicine syndrome coronary atherosclerotic heart disease peptide mapping percutaneous coronary intervention proteomics

LncR NA CCRR maintains Cahomeostasis against myocardial infarction through the FTO-SERCA2a pathway

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Science China Life Sciences 2024年

作者： Hua Yang Lina Xuan Shengjie Wang Huishan Luo Xiaomeng Duan Jianjun Guo Shijia Cui Jieru Xin Junwei Hao Xiufang Li Jun Chen Feihan Sun Xiaolin Hu Siyun Li Ying Zhang Lei Jiao Baofeng Yang Lihua Sun department of pharmacology Harbin Medical University (State Key Laboratory of Frigid Zone Cardiovascular DiseaseJoint International Research Laboratory of Cardiovascular Medicine Research Ministry of Education China) College of Pharmacy Harbin Medical University department of pharmacology Harbin Medical University (State Key Laboratory of Frigid Zone Cardiovascular Disease Joint International Research Laboratory of Cardiovascular Medicine Research Ministry of Education China) College of Pharmacy Harbin Medical University

Cardiac conduction regulatory RNA(CCRR) has been documented as an antiarrhythmic lncRNA in our earlier investigation. This study aimed to evaluate the effects of CCRR on SERCA2a and the associated Ca2+homeostasis in myocardial infarction(MI). Overexpression of CCRR via AAV9-mediated delivery not only partially reversed ischemia-induced contractile dysfunction but also alleviated abnormal Ca2+homeostasis and reduced the heightened methylation level of SERCA2a following MI. These effects were also observed in CCRR overexpressing transgenic mice. A conserved sequence domain of CCRR mimicked the protective function observed with the full length.Furthermore, silencing CCRR in healthy mice led to intracellular Ca2+overloading of cardiomyocytes. CCRR increased SERCA2a protein stability by upregulating FTO expression. The direct interaction between CCRR and FTO protein was characterized by RNA-binding protein immunoprecipitation(RIP) analysis and RNA pulldown experiments. Activation of NFATc3 was identified as an upstream mechanism responsible for CCRR downregulation in MI. This study demonstrates that CCRR is a protective lncRNA that acts by maintaining the function of FTO, thereby reducing the m6A RNA methylation level of SERCA2a, ultimately preserving calcium homeostasis for myocardial contractile function in MI. Therefore, CCRR may be considered a promising therapeutic strategy with a beneficial role in cardiac pathology.

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Simple procedure for assessing diffuse subarachnoid hemorrhage successfully created using filament perforation method in mice

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Animal Models and Experimental Medicine 2024年第1期7卷 77-81页

作者： Tatsushi Mutoh Ryota Tochinai Hiroaki Aono Masayoshi Kuwahara Yasuyuki Taki Tatsuya Ishikawa department of Surgical Neurology Research Institute for Brain and Blood VesselsAkita Cerebrospinal and Cardiovascular CenterAkitaJapan department of Aging research and Geriatric Medicine Institute of DevelopmentAging and CancerTohoku UniversitySendaiJapan department of Veterinary Pathophysiology and Animal Health Graduate School of Agriculture and Life SciencesThe University of TokyoTokyoJapan

The murine model of subarachnoid hemorrhage(SAH)is a valuable experimental tool for investigating molecular and cellular mechanisms,and the endovascular filament perforation technique can be used to simulate prominent pathophysiological features observed after human SAH;however,current validation methods for assessing an appropriate SAH model are limited.Here,we introduce a simple procedure for se-lecting a mouse model of diffuse SAH.SAH was induced in 24 mice using a standard filament perforation method.After confirming survival at 24 h,SAH was scored 0-1 based on T2*-weighted images on whole-brain magnetic resonance imaging(MRI)and visual surveillance of the cisterna magna(CM)through the dura mater.The CM-based SAH grading correlated well with a reference parameter defined by extracted brain(r^(2)=0.53,p<0.0001).The receiver operating characteristic curve revealed a sensi-tivity of 85%and a specificity of 91%for detecting diffuse SAH,with a similar area under the curve(0.89±0.06[standard error of the mean])as the MRI-based grading(0.72±0.10,p=0.12).Our data suggest that confirming an SAH clot in the CM is a valuable way to select a clinically relevant diffuse SAH model that can be used in future experimental studies.

关键词： cisterna magna clot distribution filament perforation mouse model subarachnoid hemorrhage

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Thiamine-modified metabolic reprogramming of human pluripotent stem cell-derived cardiomyocyte under space microgravity

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Signal Transduction and Targeted Therapy 2024年第5期9卷 2132-2142页

作者： Xinglong Han Lina Qu Miao Yu Lingqun Ye Liujia Shi Guangfu Ye Jingsi Yang Yaning Wang Hao Fan Yong Wang Yingjun Tan Chunyan Wang Qi Li Wei Lei Jianghai Chen Zhaoxia Liu Zhenya Shen Yinghui Li Shijun Hu department of cardiovascular Surgery of the First Affiliated Hospital&institute for cardiovascular Science State Key Laboratory of Radiation Medicine and ProtectionSuzhou Medical CollegeSoochow UniversitySuzhouChina State Key Laboratory of Space Medicine China Astronaut Research and Training CenterBeijingChina department of Hand Surgery Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina

During spaceflight,the cardiovascular system undergoes remarkable adaptation to microgravity and faces the risk of cardiac remodeling.Therefore,the effects and mechanisms of microgravity on cardiac morphology,physiology,metabolism,and cellular biology need to be further investigated.Since China started constructing the China Space Station(CSS)in 2021,we have taken advantage of the Shenzhou-13 capsule to send human pluripotent stem cell-derived cardiomyocytes(hPSC-CMs)to the Tianhe core module of the CSS.In this study,hPSC-CMs subjected to space microgravity showed decreased beating rate and abnormal intracellular calcium cycling.Metabolomic and transcriptomic analyses revealed a battery of metabolic remodeling of hPSC-CMs in spaceflight,especially thiamine metabolism.The microgravity condition blocked the thiamine intake in hPSC-CMs.The decline of thiamine utilization under microgravity or by its antagonistic analog amprolium affected the process of the tricarboxylic acid cycle.It decreased ATP production,which led to cytoskeletal remodeling and calcium homeostasis imbalance in hPSC-CMs.More importantly,in vitro and in vivo studies suggest that thiamine supplementation could reverse the adaptive changes induced by simulated microgravity.This study represents the first astrobiological study on the China Space Station and lays a solid foundation for further aerospace biomedical research.These data indicate that intervention of thiamine-modified metabolic reprogramming in human cardiomyocytes during spaceflight might be a feasible countermeasure against microgravity.

关键词： programming battery modified

LncRNA CCRR maintains Ca2+ homeostasis against myocardial infarction through the FTO-SERCA2a pathway

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Science China Life Sciences 2024年第8期 1601-1619页

作者： Hua Yang Lina Xuan Shengjie Wang Huishan Luo Xiaomeng Duan Jianjun Guo Shijia Cui Jieru Xin Junwei Hao Xiufang Li Jun Chen Feihan Sun Xiaolin Hu Siyun Li Ying Zhang Lei Jiao Baofeng Yang Lihua Sun department of pharmacology Harbin Medical University (State Key Laboratory of Frigid Zone Cardiovascular Diseasethe State-Province Key Laboratories of Biomedicine-Pharmaceutics of ChinaKey Laboratory of Cardiovascular ResearchMinistry of EducationJoint International Research Laboratory of Cardiovascular Medicine ResearchMinistry of EducationChina)College of PharmacyHarbin Medical University

Cardiac conduction regulatory RNA（CCRR） has been documented as an antiarrhythmic lnc RNA in our earlier investigation.This study aimed to evaluate the effects of CCRR on SERCA2a and the associated Ca2+homeostasis in myocardial infarction（MI）.Overexpression of CCRR via AAV9-mediated delivery not only partially reversed ischemia-induced contractile dysfunction but also alleviated abnormal Ca2+homeostasis and reduced the heightened methylation level of SERCA2a following MI.These effects were also observed in CCRR overexpressing transgenic mice.A conserved sequence domain of CCRR mimicked the protective function observed with the full length.Furthermore,silencing CCRR in healthy mice led to intracellular Ca2+overloading of cardiomyocytes.CCRR increased SERCA2a protein stability by upregulating FTO expression.The direct interaction between CCRR and FTO protein was characterized by RNA-binding protein immunoprecipitation（RIP） analysis and RNA pulldown experiments.Activation of NFATc3 was identified as an upstream mechanism responsible for CCRR downregulation in MI.This study demonstrates that CCRR is a protective lnc RNA that acts by maintaining the function of FTO,thereby reducing the m6A RNA methylation level of SERCA2a,ultimately preserving calcium homeostasis for myocardial contractile function in MI.Therefore,CCRR may be considered a promising therapeutic strategy with a beneficial role in cardiac pathology.

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Diagnostic performance of intravascular ultrasound-based fractional flow reserve in evaluating of intermediate left main stenosis

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Journal of Geriatric Cardiology 2024年第1期21卷 34-43页

作者： Yong-Gang SUI Cheng YANG Chang-Dong GUAN Yan-Lu XU Na-Qiong WU Wei-Xian YANG Yong-Jian WU Ke-Fei DOU Yue-Jin YANG Shu-Bin QIAO Wei YU Bo XU Sheng-Xian TU Jie QIAN department of Cardiology Fuwai HospitalNational Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina Catheterization Laboratories Fuwai HospitalNational Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina Biomedical Instrument institute School of Biomedical EngineeringShanghai Jiao Tong UniversityShanghaiChina National Clinical research Center for cardiovascular Diseases BeijingChina

BACKGROUND The recently introduced ultrasonic flow ratio(UFR),is a novel fast computational method to derive fractional flow reserve(FFR)from intravascular ultrasound(IVUS)images.In the present study,we evaluate the diagnostic performance of UFR in patients with intermediate left main(LM)stenosis.METHODS This is a prospective,single center study enrolling consecutive patients with presence of intermediated LM lesions(diameter stenosis of 30%-80%by visual estimation)underwent IVUS and FFR measurement.An independent core laboratory assessed offline UFR and IVUS-derived minimal lumen area(MLA)in a blinded fashion.RESULTS Both UFR and FFR were successfully achieved in 41 LM patients(mean age,62.0±9.9 years,46.3%diabetes).An acceptable correlation between UFR and FFR was identified(r=0.688,P50%(AUC=0.66,P<0.001)and numerically higher than IVUS-derived MLA(AUC=0.82;P=0.09).Patient level diagnostic accuracy,sensitivity and specificity for UFR to identify FFR≤0.80 was 82.9%(95%CI:70.2-95.7),93.1%(95%CI:82.2-100.0),58.3%(95%CI:26.3-90.4),respectively.CONCLUSION In patients with intermediate LM diseases,UFR was proved to be associated with acceptable correlation and high accuracy with pressure wire-based FFR as standard reference.The present study supports the use of UFR for functional evaluation of intermediate LM stenosis.

关键词： stenosis flow fractional

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Surgical Repair of Ventricular Septal Defect in Neonates: Indications and Outcomes

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Congenital Heart Disease 2024年第1期19卷 69-83页

作者： Jae Hong Lee Sungkyu Cho Jae Gun Kwak Hye Won Kwon Woong-Han Kim Mi Kyoung Song Sang-Yun Lee Gi Beom Kim Eun Jung Bae department of Thoracic and cardiovascular Surgery Research Institute for Convergence of Biomedical Science and TechnologyPusan National University Yangsan HospitalYangsanKorea department of Thoracic and cardiovascular Surgery Seoul National University Children’s HospitalSeoulKorea department of Pediatrics Seoul National University Children’s HospitalSeoulKorea

Background:The optimal surgical timing and clinical outcomes of ventricular septal defect(VSD)closure in neo-nates remain unclear.We aimed to evaluate the clinical outcomes of VSD closure in neonates(age≤30 days).Methods:We retrospectively reviewed 50 consecutive neonates who underwent VSD closure for isolated VSDs between August 2003 and June 2021.Indications for the procedure included congestive heart failure/failure to thrive and pulmonary hypertension.Major adverse events(MAEs)were deﬁned as the composite of all-cause mortality,reoperation,persistent atrioventricular block,and signiﬁcant(≥grade 2)valvular dysfunction.Results:The median age and body weight at operation were 26.0 days(interquartile range[IQR],18.8–28.3)and 3.7 kg(IQR,3.3–4.2),respectively.The median follow-up duration was 110.4 months(IQR,56.8–165.0).Seven patients required preoperative respiratory support,andﬁve had signiﬁcant(≥grade 2)preoperative valvular dysfunction.One early mortality occurred due to irreversible cardiogenic shock;no late mortality was observed.One reopera-tion was due to hemodynamically signiﬁcant residual VSD at 103.8 months postoperatively.The overall survival,freedom from reoperation,and freedom from MAE at 15-years were 98.0%,96.3%,and 94.4%,respectively.Pre-operative mechanical ventilation was associated with a longer duration of postoperative mechanical ventilation(p<0.001)and a longer length of intensive care unit stay(p<0.001).Conclusions:VSD closure with favorable outcomes without morbidities is feasible even in neonates.However,neonates requiring preoperative respiratory support may require careful postoperative management considering the long-term postoperative risks.Overall,surgical VSD closure might be indicated earlier in neonates with respiratory compromise.

关键词： Ventricular septal defect neonate early surgery neonatal surgery

Clinical application and management of temporary mechanical circulatory support: A clinical consensus

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中华医学杂志(英文版) 2024年第10期137卷 2023 Dec 26页

作者： Dong Nianguo Chen Liangwan Chen Xin Wang Huishan Xiao Yingbin Wang Xianqiang Huang Jinsong Yan Yang Bonde Pramod Sodha Neel Atluri Pavan Maureira Juan Pablo Vincentelli André Yanase Masanobu Wang Yixuan Zhang Haitao Hou Xiaotong Takami Yoshijuki Leprince Pascal Folliguet Thierry Sellke Frank W Chinese Society for Thoracic and cardiovascular Surgery Chinese Association of cardiovascular Surgeons Cardiac Critical Care Professional Committee of Chinese Medical Association Chinese Society of Extracorporeal Life Support European Society of cardiovascular and Endovascular Surgery French Society of Thoracic and cardiovascular Surgery Japanese Society for cardiovascular Surgery Japanese Society of Artificial Organs department of Cardiothoracic Surgery Alpert Medical School Brown University Rhode Island Hospital Providence RI USA department of cardiovascular Surgery Department of Surgery University of Pennsylvania Philadelphia PA USA department of cardiovascular Surgery and Transplantation University Hospital of Nancy University of Lorraine Vandoeuvre-lès-Nancy France department of cardiovascular Surgery University Hospital of Lille University of Lille Lille France department of Cardiology Fujita Health University School of Medicine Toyoake Aichi-1192 Japan department of Adult Surgical Intensive Care Unit Fuwai Hospital National Center for Cardiovascular Diseases Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China department of Cardiac Intensive Care Beijing Institute of Heart Lung and Blood Vessel Diseases Beijing Anzhen Hospital Capital Medical University Beijing China department of cardiovascular Surgery Fujita Health University School of Medicine Toyoake Aichi-1192 Japan department of cardiovascular Surgery Groupe Hospitalier Pitié-Salpêtrière University Pierre et Marie Curie APHP Paris France department of Cardiac Surgery APHP H?pitaux Universitaires Henri Mondor Créteil F-94010 France department of cardiovascular Surgery Union Hospital of Tongji Medical College Huazhong University of Science and Technology Wuhan Hubei China department of cardiovascular Surgery Fujian Medical University Union Hospital Fuzhou Fujian China department of Thoracic and cardiovascular Surgery Nanjing First Hospital Nanjing Medical University Nanjing Jiangsu China department of cardiovascular Surgery General Hospital of Northern Theater Command Shenyang Liaoning China department of cardiovascular Surgery Xinqiao Hospital Third Military Medical University Chongqing China department of cardiovascular Surgery Fuwai Hospital National Center for Cardiovascular Diseases Chinese Academy of Medical Sciences and Peking Union Medical College Beijing Chi