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Chinese Medical Journal 2024年第2期137卷 140-151页

作者： Minghao Lin Xiaosu Zhao Yingjun Chang Xiangyu Zhao Peking University People’s Hospital Peking University Institute of HematologyNational Clinical Research Center for Hematologic DiseaseBeijing Key Laboratory of Hematopoietic Stem Cell TransplantationBeijing 100044China

Chimeric antigen receptor(CAR)-modified T-cell therapy has achieved remarkable success in the treatment of acute lymphoblastic leukemia(ALL).Measurable/minimal residual disease(MRD)monitoring plays a significant role in the prognostication and management of patients undergoing CAR-T-cell *** MRD detection methods include flow cytometry(FCM),polymerase chain reaction(PCR),and next-generation sequencing(NGS),and each method has advantages and *** has been well documented that MRD positivity predicts a poor prognosis and even disease ***,how to perform prognostic evaluations,stratify risk based on MRD status,and apply MRD monitoring to guide individual therapeutic decisions have important implications in clinical *** review assesses the common and novel MRD assessment *** addition,we emphasize the critical role of MRD as a prognostic biomarker and summarize the latest studies regarding MRD-directed combination therapy with CAR-T-cell therapy and allogeneic hematopoietic stem cell transplantation(allo-HSCT),as well as other therapeutic strategies to improve treatment ***,this review discusses current challenges and strategies for MRD detection in the setting of disease relapse after targeted therapy.

关键词： Measurable/minimal residual disease Acute lymphoblastic leukemia Chimeric antigen receptor-modified T-cell therapy Allogeneic hematopoietic stem cell transplantation Relapse

Trogocytosis of CAR molecule regulates CAR-T cell dysfunction and tumor antigen escape

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Signal Transduction and Targeted Therapy 2024年第1期9卷 326-337页

作者： You Zhai Yicong Du Guanzhang Li Mingchen Yu Huimin Hu Changqing Pan Di Wang Zhongfang Shi Xu Yan Xuesong Li Tao Jiang Wei Zhang Department of Molecular Neuropathology Beijing Neurosurgical InstituteCapital Medical UniversityBeijingPR China Department of Neurosurgery Beijing Tiantan HospitalCapital Medical UniversityBeijingPR China Department of Urology Peking University First HospitalInstitute of UrologyPeking UniversityNational Urological Cancer CenterBeijingPR China Department of Pathophysiology Beijing Neurosurgical InstituteCapital Medical UniversityBeijingPR China China national clinical Research Center for Neurological Diseases BeijingPR China Center of Brain Tumor Beijing Institute for Brain DisordersBeijingPR China Research Unit of Accurate Diagnosis Treatmentand Translational Medicine of Brain TumorsChinese Academy of Medical SciencesBeijingPR China Chinese Glioma Genome Atlas Network(CGGA)and Asian Glioma Genome Atlas Network(AGGA) BeijingPR China

Chimeric antigen receptor(CAR)T-cell therapy has demonstrated clinical response in treating both hematologic malignancies and solid *** instances of rapid tumor remissions have been observed in animal models and clinical trials,tumor relapses occur with multiple therapeutic resistance ***,while the mechanisms underlying the long-term therapeutic resistance are well-known,short-term adaptation remains less ***,more views shed light on short-term adaptation and hold that it provides an opportunity window for long-term *** this study,we explore a previously unreported mechanism in which tumor cells employ trogocytosis to acquire CAR molecules from CAR-T cells,a reversal of previously documented *** mechanism results in the depletion of CAR molecules and subsequent CAR-T cell dysfunction,also leading to short-term antigen loss and antigen *** type of intercellular communication is independent of CAR downstream signaling,CAR-T cell condition,target antigen,and tumor cell ***,it is mainly dependent on antigen density and CAR sensitivity,and is associated with tumor cell cholesterol *** mitigation of this trogocytosis-induced CAR molecule transfer can be achieved by adaptively administering CAR-T cells with antigen density-individualized CAR ***,our study reveals a dynamic process of CAR molecule transfer and refining the framework of clinical CAR-T therapy for solid tumors.

关键词： Together instance depletion

Microdeletion on Xq27.1 in a Chinese VACTERL-Like Family with Kidney and Anal Anomalies

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Biomedical and Environmental Sciences 2024年第5期37卷 503-510页

作者： LI Min ZHANG Yu Lan ZHANG Kai Li LI Ping Ping LYU Yu Han LIANG Ya Xin YU Yue Department of Gynecology and Obstetrics Beijing HospitalNational Center of GerontologyInstitute of Geriatric MedicineChinese Academy of Medical SciencesBeijing 100730China Chinese Academy of Medical Sciences and Peking Union Medical College Beijing HospitalBeijing 100730China The Key Laboratory of Geriatrics Beijing Institute of GeriatricsBeijing HospitalNational Center of GerontologyInstitute of Geriatric MedicineChinese Academy of Medical SciencesBeijing 100730China

Objective VATER/VACTERL-like association is associated with adverse pregnancy *** evidence of this disorder is *** this study,we aimed to provide genetic insights to improve the diagnosis of *** We have described a Chinese family in which four members were affected by renal defects or agenesis,anal atresia,and anovaginal fistula,which is consistent with the diagnosis of a VACTERL-like *** and genetic analyses were conducted using genome and exome *** Segregation analysis revealed the presence of a recessive X-linked microdeletion in two living affected individuals,harboring a 196–380 kb microdeletion on Xq27.1,which was identified by familial exome *** sequencing was performed on the affected male,confirming a-196 kb microdeletion in Xq27.1,which included a 28%loss of the CDR-1 *** family members were included in the co-segregation analysis,and only VACTERL-like cases with microdeletions were reported in *** These results suggest that the 196–380 kb microdeletion in Xq27.1 could be a possible cause of the VATER/VACTERL-like ***,further genetic and functional analyses are required to confirm or rule out genetic background as the definitive cause of the VACTERL association.

关键词： Prenatal diagnosis VACTERL whole-genome sequencing whole-exome sequencing X-linked

Single-cell RNA-seq reveals the transcriptional program underlying tumor progression and metastasis in neuroblastoma

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Frontiers of Medicine 2024年第4期18卷 690-707页

作者： Zhe Nian Dan Wang Hao Wang Wenxu Liu Zhenyi Ma Jie Yan Yanna Cao Jie Li Qiang Zhao Zhe Liu Department of Immunology School of Basic Medical SciencesTianjin Medical UniversityTianjin300070China Zhejiang Key Laboratory of Medical Epigenetics Department of Cell BiologySchool of Basic Medical SciencesHangzhou Normal UniversityHangzhou311121China Department of Pediatric Oncology Tianjin Medical University Cancer Institute and HospitalNational Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjin’s Clinical Research Center for CancerTianjin300060China Collaborative Innovation Center for Cancer Personalized Medicine Nanjing Medical UniversityNanjing211166China

Neuroblastoma(NB)is one of the most common childhood *** percent of patients present with widely disseminated clinical signs at diagnosis and exhibit poor ***,the molecular mechanisms triggering NB metastasis remain largely *** this study,we generated a transcriptomic atlas of 15447 NB cells from eight NB samples,including paired samples of primary tumors and bone marrow *** used time-resolved analysis to chart the evolutionary trajectory of NB cells from the primary tumor to the metastases in the same patient and identified a common‘starter’subpopulation that initiates tumor development and ***‘starter’population exhibited high expression levels of multiple cell cycle-related genes,indicating the important role of cell cycle upregulation in NB tumor *** addition,our evolutionary trajectory analysis demonstrated the involvement of partial epithelial-to-mesenchymal transition(p-EMT)along the metastatic route from the primary site to the bone *** study provides insights into the program driving NB metastasis and presents a signature of metastasis-initiating cells as an independent prognostic indicator and potential therapeutic target to inhibit the initiation of NB metastasis.

关键词： single-cell RNA sequencing metastasis neuroblastoma epithelial-to-mesenchymal transition

Severe aconite poisoning successfully treated with veno-arterial extracorporeal membrane oxygenation:A case report

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World Journal of clinical Cases 2024年第2期12卷 399-404页

作者： Saeko Kohara Yoshito Kamijo Ryoko Kyan Ichiro Okada Eiju Hasegawa Soichiro Yamada Koichi Imai Asuka Kaizaki-Mitsumoto Satoshi Numazawa Department of Critical Care Medicine and Trauma National Hospital Organization Disaster Medical CenterTokyo 1900014Japan Department of clinical Toxicology Saitama Medical UniversitySaitama 3500495Japan Saitama Prefectural institute of Public Health Saitama Prefectural Institute of Public HealthSaitama 3550133Japan Division of Toxicology Department of PharmacologyToxicology and TherapeuticsShowa University School of PharmacyTokyo 1428555Japan

BACKGROUND Most species of aconite contain highly toxic aconitines,the oral ingestion of which can be fatal,primarily because they cause ventricular *** describe a case of severe aconite poisoning that was successfully treated through venoarterial extracorporeal membrane oxygenation(VA-ECMO)and in which detailed toxicological analyses of the aconite roots and biological samples were performed using liquid chromatography-tandem mass spectrometry(LC-MS/MS).CASE SUMMARY A 23-year-old male presented to the emergency room with circulatory collapse and ventricular arrhythmia after ingesting approximately half of a root labeled,“Aconitum japonicum Thunb”.Two hours after arrival,VA-ECMO was initiated as circulatory collapse became refractory to antiarrhythmics and *** hours after arrival,an electrocardiogram revealed a return to sinus *** patient was weaned off VA-ECMO and the ventilator on hospital days 3 and 5,*** hospital day 15,he was transferred to a psychiatric *** other half of the root and his biological samples were toxicologically analyzed using LC-MS/MS,revealing 244.3 mg/kg of aconitine and 24.7 mg/kg of mesaconitine in the *** on admission contained 1.50 ng/mL of *** hospital day 2,neither were *** on admission showed 149.09 ng/mL of aconitine and 3.59 ng/mL of mesaconitine,but these rapidly decreased after hospital day *** The key to saving the life of a patient with severe aconite poisoning is to introduce VA-ECMO as soon as possible.

关键词： Aconite poisoning Fatal arrhythmia Veno-arterial extracorporeal membrane oxygenation Aconitine Mesaconitine Case report

Prediction of the short-term efficacy of anti-VEGF therapy for neovascular age-related macular degeneration using optical coherence tomography angiography

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Eye and Vision 2024年第3期10卷 21-30页

作者： Huixun Jia Bing Lu Zhi Zhao Yang Yu Fenghua Wang Minwen Zhou Xiaodong Sun Department of Ophthalmology Shanghai General Hospital(Shanghai First People’s Hospital)Shanghai Jiao Tong University School of Medicine100 Hai Ning RoadShanghai200080People’s Republic of China Shanghai Key Laboratory of Ocular Fundus Diseases ShanghaiChina national clinical Research Center for Eye Diseases ShanghaiChina Shanghai Engineering Center for Visual Science and Photomedicine ShanghaiChina Shanghai Engineering Center for Precise Diagnosis and Treatment of Eye Diseases ShanghaiChina clinical Research institute Shanghai Jiao Tong University School of MedicineShanghaiChina

Background To evaluate whether the specific choroidal neovascularization(CNV)characteristics measured using optical coherence tomography angiography(OCTA)can predict the 6-month prognosis of neovascular age-related macular degeneration(nAMD)after anti-vascular endothelial growth factor(anti-VEGF)*** Patients with type 1,type 2,or mixed-type neovascularization(NV)were prospectively *** underwent an initial loading phase of three consecutive monthly intravitreal injections of Conbercept(0.5 mg)and were switched to a pro re nata(PRN)treatment *** images were evaluated for eyes that underwent follow-up assessments for more than 6 *** lesions were manually segmented,and the CNV area,vessel area,greatest vascular caliber(GVC),and greatest linear dimension(GLD)were compared between responders and *** masked graders independently measured the above-mentioned parameters using OCTA,and consistency was assessed using the intraclass correlation coefficient(ICC)*** logistic regression analysis was performed to evaluate the effect of a 3-month change in the CNV area,GLD,and GVC on the 6-month response to anti-VEGF *** Among the 60 eyes of 60 patients with nAMD,39 were responders and 21 were *** proportion of CNV types was significantly different between responders and non-responders(P=0.009).Patients with type 2 or mixed NV seemed more likely to respond to the treatment(28.2%vs.0.0%,and 30.8%vs.23.8%,respectively).The change in GVC showed a significant difference between responders(−4.98±17.17μm)and non-responders(11.01±14.10μm)after three monthly intravitreal anti-VEGF *** logistic regression analysis showed that only the change in GVC remained significant after controlling for baseline GVC,injection number,and CNV type(adjusted OR=1.083;P=0.008).Conclusions Type 2 and mixed-type NV were significantly associated with a better response to anti-VEGF *** i

关键词： Age-related macular degeneration Choroidal neovascularization Optical coherence tomography angiography Anti-VEGF

Targeting epigenetic and posttranslational modifications regulating ferroptosis for the treatment of diseases

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Signal Transduction and Targeted Therapy 2024年第1期9卷 105-149页

作者： Yumin Wang Jing Hu Shuang Wu Joshua S.Fleishman Yulin Li Yinshi Xu Wailong Zou Jinhua Wang Yukuan Feng Jichao Chen Hongquan Wang Department of Respiratory and Critical Care Medicine Aerospace Center HospitalPeking University Aerospace School of Clinical MedicineBeijing 100049PR China Department of Pathogen Biology School of Basic Medical SciencesTianjin Medical UniversityTianjin 300060PR China Department of Neurology Zhongnan Hospital of Wuhan UniversityWuhan 430000PR China Department of Pharmaceutical Sciences College of Pharmacy and Health SciencesSt.John’s UniversityQueensNY 11439USA Department of Outpatient Aerospace Center HospitalPeking University Aerospace School of Clinical MedicineBeijing 100049PR China Beijing Key Laboratory of Drug Target and Screening Research Institute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100050PR China Department of Pancreatic Cancer Tianjin Medical University Cancer Institute and HospitalNational Clinical Research Center for CancerTianjin’s Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjin 300060PR China

Ferroptosis,a unique modality of cell death with mechanistic and morphological differences from other cell death modes,plays a pivotal role in regulating tumorigenesis and offers a new opportunity for modulating anticancer drug *** epigenetic modifications and posttranslational modifications(PTMs)promote anticancer drug resistance,cancer progression,and *** studies indicate that epigenetic modifications can transcriptionally and translationally determine cancer cell vulnerability to ferroptosis and that ferroptosis functions as a driver in nervous system diseases(NSDs),cardiovascular diseases(CVDs),liver diseases,lung diseases,and kidney *** this review,we first summarize the core molecular mechanisms of ***,the roles of epigenetic processes,including histone PTMs,DNA methylation,and noncoding RNA regulation and PTMs,such as phosphorylation,ubiquitination,SUMOylation,acetylation,methylation,and ADP-ribosylation,are concisely *** roles of epigenetic modifications and PTMs in ferroptosis regulation in the genesis of diseases,including cancers,NSD,CVDs,liver diseases,lung diseases,and kidney diseases,as well as the application of epigenetic and PTM modulators in the therapy of these diseases,are then discussed in *** the mechanisms of ferroptosis regulation mediated by epigenetic modifications and PTMs in cancer and other diseases will facilitate the development of promising combination therapeutic regimens containing epigenetic or PTM-targeting agents and ferroptosis inducers that can be used to overcome chemotherapeutic resistance in cancer and could be used to prevent other *** addition,these mechanisms highlight potential therapeutic approaches to overcome chemoresistance in cancer or halt the genesis of other diseases.

关键词： diseases epigenetic overcome

Neutrophil peptide 1 accelerates the clearance of degenerative axons during Wallerian degeneration by activating macrophages after peripheral nerve crush injury

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Neural Regeneration Research 2024年第8期19卷 1822-1827页

作者： Yuhui Kou Yusong Yuan Qicheng Li Wenyong Xie Hailin Xu Na Han Department of Trauma and Orthopedics Peking University People’s HospitalBeijingChina national Center for Trauma Medicine BeijingChina Key Laboratory of Trauma and Neural Regeneration(Peking University) Ministry of EducationBeijingChina Department of Orthopedics China-Japan Friendship HospitalBeijingChina Department of Central Laboratory and institute of clinical Molecular Biology Peking University People’s HospitalBeijingChina

Macrophages play an important role in peripheral nerve regeneration,but the specific mechanism of regeneration is still *** preliminary findings indicated that neutrophil peptide 1 is an innate immune peptide closely involved in peripheral nerve ***,the mechanism by which neutrophil peptide 1 enhances nerve regeneration remains *** study was designed to investigate the relationship between neutrophil peptide 1 and macrophages in vivo and in vitro in peripheral nerve crush *** functions of RAW 264.7 cells we re elucidated by Cell Counting Kit-8 assay,flow cytometry,migration assays,phagocytosis assays,immunohistochemistry and enzyme-linked immunosorbent *** debris phagocytosis was observed using the CUBIC(Clear,Unobstructed Brain/Body Imaging Cocktails and Computational analysis)optical clearing technique during Wallerian *** inflammatory factor expression in different polarization states was detected using a protein *** results showed that neutrophil peptide 1 promoted the prolife ration,migration and phagocytosis of macrophages,and CD206 expression on the surfa ce of macrophages,indicating M2 *** axonal debris clearance rate during Wallerian degeneration was enhanced after neutrophil peptide 1 *** peptide 1 also downregulated inflammatory factors interleukin-1α,-6,-12,and tumor necrosis factor-αin invo and in ***,the results suggest that neutrophil peptide 1 activates macrophages and accelerates Wallerian degeneration,which may be one mechanism by which neutrophil peptide 1 enhances peripheral nerve regeneration.

关键词： axonal debris inflammatory factors macrophages neutrophil peptide 1 peripheral nerve injury peripheral nerve regeneration RAW 264.7 cells sciatic nerve Wallerian degeneration

Interconnections between diabetic corneal neuropathy and diabetic retinopathy:diagnostic and therapeutic implications

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Neural Regeneration Research 2025年第8期20卷 2169-2180页

作者： Mingyi Yu Faith Teo En Ning Chang Liu Yu-Chi Liu Tissue Engineering and Stem Cell Group Singapore Eye Research InstituteSingapore Yong Loo Lin School of Medicine National University of SingaporeSingapore Department of Cornea and External Eye Disease Singapore National Eye CenterSingapore Ophthalmology and Visual Sciences Academic clinical Program Duke-NUS Medical SchoolSingapore

Diabetic corneal neuropathy and diabetic retinopathy are ocular complications occurring in the context of diabetes *** corneal neuropathy refers to the progressive damage of corneal *** retinopathy has traditionally been considered as damage to the retinal ***,growing evidence suggests that diabetic retinopathy is a complex neurovascular disorder resulting from dysfunction of the neurovascular unit,which includes both the retinal vascular structures and neural *** retinopathy is one of the leading causes of blindness and is frequently screened for as part of diabetic ocular ***,diabetic corneal neuropathy is commonly overlooked and underdiagnosed,leading to severe ocular surface *** studies have found that these two conditions tend to occur together,and they share similarities in their pathogenesis pathways,being triggered by a status of chronic *** review aims to discuss the interconnection between diabetic corneal neuropathy and diabetic retinopathy,whether diabetic corneal neuropathy precedes diabetic retinopathy,as well as the relation between the stage of diabetic retinopathy and the severity of corneal *** also endeavor to explore the relevance of a corneal screening in diabetic eyes and the possibility of using corneal nerve measurements to monitor the progression of diabetic retinopathy.

关键词： cornea corneal nerves diabetes diabetic corneal neuropathy diabetic retinopathy retina

Congestive ischemic colitis successfully treated with antiinflammatory therapy: A case report

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World Journal of clinical Cases 2024年第1期12卷 142-147页

作者： Geon Woo Lee Su Bum Park Department of Internal Medicine Pusan National University School of Medicine and Research Institute for Convergence of Biomedical Science and TechnologyPusan National University Yangsan HospitalYangsan 50612South Korea

BACKGROUND Congestive ischemic colitis is a rare subtype of ischemic colitis with an unknown *** conservative management,such as fasting,no established treatment exists;therefore,surgical intervention should be considered in some cases if symptoms *** literature suggests that anti-inflam-matory agents may effectively treat congestive ischemic *** SUMMARY We present the case of a 68-year-old female patient who underwent laparoscopic left hemicolectomy for transverse colon cancer 3 years ***,follow-up included an annual colonoscopy and abdominal computed tomography(CT)at a local ***,progressive erythema and edema of the sigmoid colon were observed 1 year *** admission to our hospital,she complained of abdominal pain and *** CT showed thickening of the sigmoid colon walls,and colonoscopy revealed erythema,edema,and multiple ulcers with exudate in the sigmoid *** angiography showed engorgement of the sigmoid vasa recta without any vascular *** diagnosis was congestive ischemic colitis,and we treated the patient with anti-inflammatory *** 2 mo of glucocorticoid therapy(20 mg once daily)and 7 mo of 5-aminosalicylate therapy(1 g twice daily),the ulcers completely *** has not experienced any recurrence for 2 *** Anti-inflammatory therapy,specifically glucocorticoids and 5-aminosalicylate,has demonstrated promising efficacy and introduces potential novel treatment options for congestive ischemic colitis.

关键词： Ischemic colitis Glucocorticoids 5-aminosalicylate Colon cancer