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Peficitinib suppresses diffuse-type tenosynovial giant cell tumor by targeting TYK2 and JAK/STAT signaling

Science China Life Sciences 2025年

作者： Shan Lu Chenxi Cao Wenjia Zhang Jiayi Li Jingli Yang Zisheng Huang Zhijun Wu Baitao Liu Hongjie Huang Haijun Wang Yongjian Wang Dingge Liu Zhihua Zhang Kaiping Liu Gang Yang Xi Gong Hui Dai Yingjia Li Erdan Dong Xin Zhang Yan Zhang Haihe laboratory of Cell Ecosystem Institute of Cardiovascular Diseases The First Affiliated Hospital of Dalian Medical University Institute of Cardiovascular Sciences School of Basic Medical Sciences Peking University Health Science Center Department of Cardiology and Institute of Vascular Medicine Peking University Third HospitalState Key Laboratory of Vascular Homeostasis and Remodeling Peking University Department of Sports Medicine Peking University Third Hospital Institute of Sports Medicine of Peking University Beijing key laboratory of Sports Injuries Engineering Research Center of Sports Trauma Treatment Technology and Devices Ministry of Education State key laboratory of Membrane Biology Institute of Molecular Medicine College of Future Technology Peking University Peking University Health Science Centre Peking University Department of Immunology School of Basic Medical Sciences NHC Key Laboratory of Medical Immunology Peking University Research Center for cardiopulmonary Rehabilitation University of Health and Rehabilitation Sciences Qingdao Hospital (Qingdao Municipal Hospital) School of Health and Life Sciences University of Health and Rehabilitation Sciences Research Unit of Medical Science Research Management/Basic and Clinical Research of Metabolic Cardiovascular Diseases Chinese Academy of Medical Sciences

Diffuse-type tenosynovial giant cell tumor(dTGCT) is a destructive but rare benign proliferative synovial neoplasm. Although surgery is currently the main treatment modality for dTGCT, the recurrence risk is up to 50%. Therefore, there is a great need for effective drugs against dTGCT with minor side effects. The Janus kinase(JAK)/signal transducer and activator of transcription(STAT) signaling plays a central role in rheumatoid arthritis(RA), a disease with similar characteristics as dTGCT, but its function in dTGCT remains *** fibroblast-like synoviocytes(FLS) and macrophages were isolated from 10 synovial tissue samples from dTGCT patients for the screening and validation of the five clinically approved JAK inhibitors to treat RA against dTGCT. Cell viability, cell death, inflammation and the activity of the JAK family members of cultured dTGCT FLS(both 2-D and 3-D) and macrophages were investigated for the efficacy of the JAK inhibitors. Here, we found that similar to RA, JAK/STAT signaling was markedly activated in the dTGCT synovium. Of the 5 JAK inhibitors, peficitinib was shown to have the most potency in addressing some of the pathological responses of dTGCT FLS and *** potency of peficitinib was much higher than pexidartinib, which is the only FDA-approved drug for dTGCT. Mechanistically, peficitinib inhibited tyrosine kinase 2(TYK2), a JAK family member necessary for the pathological progression of dTGCT FLS and macrophages. In summary, we not only revealed JAK/STAT(especially TYK2) signaling as the major mechanism underlying dTGCT, but also identified peficitinib as a promising drug against dTGCT.

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Cold-inducible RNA-binding protein as a novel target to alleviate blood-brain barrier damage induced by cardiopulmonary bypass

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中国循环杂志 2018年第S1期 128-129页

作者： Mingyue Liu Yongnan Li Yiwei Liu Shujie Yan Gang Liu Qiaoni Zhang Bingyang Ji Department of cardiopulmonary bypass State Key Laboratory of Cardiovascular Medicine National Center for Cardiovascular DiseaseFuwai HospitalCAMS and PUMC

Background Hypothermia provides neuroprotection and alleviates cerebral injury after cardiopulmonary bypass (CPB). The mechanism of cold-inducible RNA-binding protein (CIRP), which has been reported to be facilitated ...

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Influence of Microcirculatory Dysfunction on Myocardial Injury after cardiopulmonary Resuscitation

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Biomedical and Environmental Sciences 2022年第4期35卷 334-344页

作者： YANG Jun DONG Gui Juan WANG Hong Wei ZHAO Xin WANG Fu Jun ZHANG Jian GUO Shu Bin Emergency Medicine Clinical Research Center of Beijing Chaoyang Hospital Capital Medical UniversityBeijing Key Laboratory of Cardiopulmonary Cerebral ResuscitationBeijing 100020China

Objective This study aimed to examine the effects of microcirculatory dysfunction and 654-1intervention after cardiopulmonary resuscitation on myocardial *** Landrace pigs were divided into a sham operation group(S group,n=6),ventricular fibrillation control group(VF-C group,n=8)and 654-1 intervention group(VF-I group,n=8).Hemodynamics was recorded at baseline,at recovery of spontaneous circulation(ROSC),and 1 h,2 h,4h and 6 h *** dark field(SDF)technology was used to evaluate and monitor the microcirculation flow index,total vessel density,perfusion vessel ratio,De-Backer score,and perfusion vessel density in animal viscera at various time *** After administration of 654-1 at 1.5 h post-ROSC,the hemodynamics in the VF-I group,as compared with the VF-C group,was significantly *** visceral microcirculation detected by SDF was also significantly improved in the VF-I *** observed through electron microscopy,significantly less myocardial tissue injury was present in the VF-I group than the VF-C *** Administration of 654-1 inhibited excessive inflammatory by improving the state of visceral microcirculation.

关键词： cardiopulmonary resuscitation Post-cardiac arrest syndrome Microcirculation dysfunction Myocardial injury Anisodamine hydrobromide(654-1)

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Hypoxia-preconditioned bone marrow-derived mesenchymal stem cells protect neurons from cardiac arrest-induced pyroptosis

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Neural Regeneration Research 2025年第4期20卷 1103-1123页

作者： Xiahong Tang Nan Zheng Qingming Lin Yan You Zheng Gong Yangping Zhuang Jiali Wu Yu Wang Hanlin Huang Jun Ke Feng Chen Shengli Clinical Medical College of Fujian Medical University Fujian Medical UniversityFuzhouFujian ProvinceChina Department of Emergency Fujian Provincial HospitalFuzhouFujian ProvinceChina Fujian Provincial key laboratory of Emergency Medicine FuzhouFujian ProvinceChina The Second Department of Intensive Care Unit Fujian Provincial Hospital South BranchFuzhouFujian ProvinceChina

Cardiac arrest can lead to severe neurological impairment as a result of inflammation,mitochondrial dysfunction,and post-cardiopulmonary resuscitation neurological *** preconditioning has been shown to improve migration and survival of bone marrow–derived mesenchymal stem cells and reduce pyroptosis after cardiac arrest,but the specific mechanisms by which hypoxia-preconditioned bone marrow–derived mesenchymal stem cells protect against brain injury after cardiac arrest are *** this end,we established an in vitro co-culture model of bone marrow–derived mesenchymal stem cells and oxygen–glucose deprived primary neurons and found that hypoxic preconditioning enhanced the protective effect of bone marrow stromal stem cells against neuronal pyroptosis,possibly through inhibition of the MAPK and nuclear factor κB ***,we transplanted hypoxia-preconditioned bone marrow–derived mesenchymal stem cells into the lateral ventricle after the return of spontaneous circulation in an 8-minute cardiac arrest rat model induced by *** results showed that hypoxia-preconditioned bone marrow–derived mesenchymal stem cells significantly reduced cardiac arrest–induced neuronal pyroptosis,oxidative stress,and mitochondrial damage,whereas knockdown of the liver isoform of phosphofructokinase in bone marrow–derived mesenchymal stem cells inhibited these *** conclude,hypoxia-preconditioned bone marrow–derived mesenchymal stem cells offer a promising therapeutic approach for neuronal injury following cardiac arrest,and their beneficial effects are potentially associated with increased expression of the liver isoform of phosphofructokinase following hypoxic preconditioning.

关键词： bone marrow–derived mesenchymal stem cells cardiac arrest cardiac resuscitation hypoxic preconditioning liver isoform of phosphofructokinase mitochondria neuroinflammation oxidative stress pyroptosis reactive oxygen species

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Myocardial protection during heart surgery in China

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Chinese Medical Journal 2007年第1期120卷 62-67页

作者： Bingyang Ji Jinping Liu myocardial protection cardiopulmonary bypass cardiac surgeryDepartment of Pediatric Cardiology Hershey Medical Center PennState College of Medicine USA Department of cardiopulmonary bypass Cardiovascular InstituteFuwai Hospital Peking Union Medical College ＆ ChineseAcademy of Medical Sciences Beijing 100730 China

Myocardial protection （MP） is the key for cardiopulmonary bypass （CPB） heart surgery. MP during cardiac surgery （CS） aims to preserve myocardial function while providing a bloodless and motionless operating field. Strategies on how to attenuate or prevent post-ischemic myocardial dysfunction that occurs intra-operatively during CS have been discussed for more than half a century. In 1950, Bigelow et al, first reported to decrease myocardial oxygen demand by means of hypothermia. Moreover, Melrose and coworkers2 described the use of electromechanical cardiac arrest induced by potassium infusion, permitting CS to be performed on a non-beating flaccid heart and clear surgical field. The combination of both of these techniques has been the golden standard in MP during surgery until now, allowing surgery with excellent clinical outcome. In 1975, Braimbridge et al introduced a crystalloid solution into clinical practice at St. Thomas Hospital. By the 1980s, blood-based potassium solutions were advocated to further improve MP and to reduce myocardial enzymes release based on the theory that blood would be a superior delivery vehicle for its oxygenating and buffering ***, the majority of MP strategies now available do allow patients to undergo conventional and complex CS with an operative mortality rate ranging from less than 2% to 4%.

关键词： myocardial protection cardiopulmonary bypass cardiac surgery

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Epinephrine in Out-of-hospital Cardiac Arrest： Helpful or Harmful？

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Chinese Medical Journal 2017年第17期130卷 2112-2116页

作者： Huan Shao Chun-Sheng Li Beijing key laboratory of cardiopulmonary Cerebral Resuscitation Beijing Chao-Yang Hospital Capital Medical University Beijing 100020 China

Objective：Epinephrine is the primary drug administered during cardiopulmonary resuscitation （CPR） to reverse cardiac *** evidence for the use of adrenaline in out-of-hospital cardiac arrest （OHCA） and in-hospital resuscitation is *** conducted a systematic review on the clinical efficacy of adrenaline in adult OHCA patients to evaluate whether epinephrine provides any overall benefit for *** Sources：The EMBASE and PubMed databases were searched with the key words ＆quot;epinephrine,＆quot; ＆quot;cardiac arrest,＆quot; and variations of these *** Selection：Data from clinical randomized trials,meta-analyses,guidelines,and recent reviews were selected for ***：Sudden cardiac arrest causes 544,000 deaths in China each year,with survival occurring in 〈1% of cases （compared with 12% in the United States）.The American Heart Association recommends the use of epinephrine in patients with cardiac arrest,as part of advanced cardiac life *** is a clear evidence of an association between epinephrine and increased return of spontaneous circulation （ROSC）.However,there are conflicting results regarding long-term survival and functional recovery,particularly neurological outcome,after *** is currently insufficient evidence to support or reject epinephrine administration during *** believe that epinephrine may have a role in resuscitation,as administration of epinephrine during CPR increases the probability of restoring cardiac activity with pulses,which is an essential intermediate step toward long-term ***：The administration of adrenaline was associated with improved short-term survival （ROSC）.However,it appears that the use of adrenaline is associated with no benefit on survival to hospital discharge or survival with favorable neurological outcome after OHCA,and it may have a harmful *** placebo-controlled,double-blind,randomized control trials are required to definitively establis

关键词： Adrenaline Cardiac Arrest cardiopulmonary Resuscitation: Epinephrine Return of Spontaneous Circulation

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Outcome prediction value of National Early Warning Score in septic patients with community-acquired pneumonia in emergency department: A single-center retrospective cohort study

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World Journal of Emergency Medicine 2020年第4期11卷 206-215页

作者： Hai-jiang Zhou Tian-fei Lan Shu-bin Guo Emergency Medicine Clinical Research Center Beijing Chao-yang HospitalCapital Medical University&Beijing Key Laboratory of Cardiopulmonary Cerebral ResuscitationBeijingChina Department of Allergy Beijing Shijitan HospitalCapital Medical UniversityBeijingChina

BACKGROUND:To evaluate the accuracy of National Early Warning Score(NEWS)in predicting clinical outcomes(28-day mortality,intensive care unit[ICU]admission,and mechanical ventilation use)for septic patients with community-acquired pneumonia(CAP)compared with other commonly used severity scores(CURB65,Pneumonia Severity Index[PSI],Sequential Organ Failure Assessment[SOFA],quick SOFA[qSOFA],and Mortality in Emergency Department Sepsis[MEDS])and admission lactate ***:Adult patients diagnosed with CAP admitted between January 2017 and May 2019 with admission SOFA≥2 from baseline were *** characteristics were *** primary outcome was the 28-day mortality after admission,and the secondary outcome included ICU admission and mechanical ventilation *** prediction value of parameters above was compared using receiver operating characteristics(ROC)*** regression analyses were carried out to determine the risk factors for the 28-day ***-Meier survival curves were plotted and compared using optimal cut-off values of qSOFA and ***:Among the 340 enrolled patients,90 patients were dead after a 28-day follow-up,62 patients were admitted to ICU,and 84 patients underwent mechanical *** single predictors,NEWS achieved the largest area under the receiver operating characteristic(AUROC)curve in predicting the 28-day mortality(0.861),ICU admission(0.895),and use of mechanical ventilation(0.873).NEWS+lactate,similar to MEDS+lactate,outperformed other combinations of severity score and admission lactate in predicting the 28-day mortality(AUROC 0.866)and ICU admission(AUROC 0.905),while NEWS+lactate did not outperform other combinations in predicting mechanical ventilation(AUROC 0.886).Admission lactate only improved the predicting performance of CURB65 and qSOFA in predicting the 28-day mortality and ICU ***:NEWS could be a valuable predictor in septic patients with CAP in emergency depa

关键词： Community-acquired pneumonia Sepsis National Early Warning Score(NEWS) Intensive care unit Emergency departments

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CHANGES IN NEUROPEPTIDES AFTER MUSIC EXPOSURE 429Cardioprotective effect of ivabradine via the AMPK/SIRT1/PGC-1αsignaling pathway in myocardial ischemia/reperfusion injuryinduced in H9c2 cell

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BIOCELL 2020年第3期44卷 431-441页

作者： XINGXING ZHU TIANFENG HUA MINGFEI WU JIATIAN WU JIANCHAO HONG MIN YANG The Second Affiliated Hospital of Anhui Medical University HefeiChina The laboratory of cardiopulmonary Resuscitation and Critical Care Medicine The Second Affiliated Hospital of Anhui Medical UniversityHefeiChina School of Pharmacy Anhui Province Key Laboratory of Major Autoimmune DiseasesAnhui Medical UniversityHefeiChina

Post-resuscitation myocardial dysfunction(PRMD)is the most severe myocardial ischemia-reperfusion injury(MIRI)and is characterized by difficult treatment and poor *** has shown the protective effects of the rational use of ivabradine(IVA)against PRMD,however,the molecular mechanisms of IVA remain *** this study,an ischemia-reperfusion injury(IRI)model was established using hypoxic *** results demonstrated that pretreatment with IVA reduced IRI-induced cytotoxicity and *** attenuated mitochondrial damage,eliminated excess reactive oxygen species(ROS),suppressed IRI-induced ATP and NAD+,and increased the AMP/ATP *** further found that IVA increased the mRNA levels of sirtuin 1(SIRT1)and peroxisome proliferator-activated receptor-γcoactivator 1α(PGC-1α)and upregulated the expression levels of phosphorylated AMP-activated protein kinase(p-AMPK)/AMPK,SIRT1,and PGC-1α***,no change in AMPK mRNA levels was *** energy metabolism significantly changed after *** aim of this study was to demonstrate the cardioprotective effect of Ivabradine via the AMPK/SIRT1/PGC-1αsignaling pathway in myocardial ischemia/reperfusion injury-induced in H9c2 cell.

关键词： Ivabradine Myocardial ischemia reperfusion injury Energy metabolism Oxidative stress AMPK/SIRT1/PGC-1α pathway

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Comparable prognosis in different neonatal histidine-tryptophan-ketoglutarate dosage management

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Chinese Medical Journal 2021年第24期134卷 2968-2975页

作者： Li-Ting Bai Yuan-Yuan Tong Jin-Ping Liu Zheng-Yi Feng Ju Zhao Sheng-Wen Guo Yu Jin Pei-Yao Zhang Yi-Xuan Li Department of cardiopulmonary bypass Fuwai HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100037China State key laboratory of Cardiovascular Disease Fuwai HospitalNational Center for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100037China

Background:Histidine-tryptophan-ketoglutarate(HTK)is a solution commonly used for organ ***,there is no certified fixed regimen for on-pump heart surgery in *** aimed to retrospectively evaluate the outcomes related to different HTK dosages and to analyze the safety of high-dosage ***:A total of 146 neonates who underwent on-pump heart surgery with single-shot HTK perfusion were divided into two groups according to HTK dosages:a standard-dose(SD)group(n=63,40 mL/kg60 mL/kg).Propensity score matching(PSM)was performed to control confounding ***:The SD group had a higher weight(3.7±0.4 vs.3.4±0.4 kg,Pcardiopulmonary bypass(CPB)time(123.5[108.0,136.0]vs.132.5[114.8,152.5]min,P=0.034),and a lower aortic x-clamp time(82.9±27.1 vs.95.5±26.0 min,P=0.005).After PSM,44 patients were assigned to each group;baseline characteristics and CPB parameters between the two groups were *** were no significant differences in peri-CPB blood product consumption after PSM(P>0.05).The incidences of post-operative complications were not significantly different between the two *** were no significant differences in ventilation time,intensive care unit stay,and post-operative hospital stay(P>0.05).Follow-up echocardiography outcomes at 1 month,3 to 6 months,and 1 year showed that left ventricular ejection fraction and end-diastolic dimension were comparable between the two ***:In neonatal on-pump cardiac surgery patients,single-shot HD(>60 mL/kg)HTK perfusion had a comparable heart protection effect and short-term post-operative prognosis as standard dosage perfusion of 40 to 60 mL/***,this study provides supporting evidence of the safety of HD HTK perfusion.

关键词： Histidine-tryptophan-ketoglutarate Neonate Perfusion dosage Cardiac recovery Prognosis

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A Novel Porcine Model of Septic Shock Induced by Acute Respiratory Distress Syndrome due to Methicillin-resistant Staphylococcus aureus

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Chinese Medical Journal 2017年第10期130卷 1226-1235页

作者： Shuo Wang Jun-Yu Wang Tao Wang Chen-Chen Hang Rui Shao Chun-Sheng Li Department of Emergency Medicine Beijing Chao-Yang Hospital Capital Medical University Beijing Key Laboratory of Cardiopulmonary Cerebral Resuscitation Beijing 100020 China

Background： Sepsis is one of the main canses of mortality in critically ill patients following progression to septic shock. To investigate the pathophysiologic changes of sepsis, we developed a novel porcine model of septic shock induced by acute respiratory distress syndrome （ARDS） due to methicillin-resistant Staphylococcus aureus （MRSA） pneumonia. Methods： Twenty-six male Landraces （Lvyuanweiye, Beijing, China） weighing 30 - 2 kg were divided into lbur groups： sham gronp （SH： n = 5）; cotton smoke inhalation group （SM; n = 6）; MRSA pneumonia group （MR; n = 6）; and septic shock group with cotton smoke inhalation ＋ MRSA pneumonia （SS; n = 9）. Extensive hemodynamics, oxygen dynamics, and lung function were monitored for 24 11 following the injury or until death. Tissues were collected, and histopathology evaluations were carried out. Results： Blood cultures from 6 of 9 animals in the SS group were positive for MRSA. Two hours following the injury, decreased mean arterial blood pressure （60 70 mmHg） and cardiac index （〈2 L-rain -＇m --） were observed in the animals in the SS group, while systemic vascular resistance index was increased. The hemodynamic characteristics of septic shock were only observed in the SS group but not significant in the other groups, The PO_JFiO2 in the SM and SS groups decreased to 300 and 100, respectively. In the SS group, extravascular lung water index increased to 20 ml/kg, whereas thoracopulmonary compliance decreased to 10 ml/H2O after injury. Deterioration of pulmonary function in the SS group was more serious than the SM and MR groups. Severe lung injury in the SS group was confinaaed by the histopathology evaluations. The lung injury confirmed by high-resolution thin-section computed tomography and histopathology in the SS group was more serious than those of other groups. Conclusions： In the present study, we developed a novel porcine model of septic shock induced by ARDS due to severe MRSA pneumonia with characteristic hyperdynamic

关键词： Acute Respiratory Distress Syndrome: Hemodynamic Methicillin-resistant Staphylococcus aureus: Oxygen Dynamic:Septic Shock

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