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Neural Regeneration Research 2024年第11期19卷 2335-2336页

作者： Ibrahim Olabayode Saliu Guoyan Zhao department of Genetics Washington University School of MedicineSt.LouisMOUSA department of Neurology Department of Pathology and ImmunologyWashington University School of MedicineSt.LouisMOUSA

Astrocytes are a major glial cell type in the central nervous system,and they provide trophic and metabolic support to *** addition to these roles,they play crucial roles in modulating synaptic functions,development,and pruning(Brandebura et al.,2023).Astrocytes become reactive(activated)by undergoing morphological,molecular,and functional alterations in response to neuropathology such as in injuries and neurodegenerative diseases(NDs)(Escartin et al.,2021).

关键词： degenerative injuries

Evaluation of sodium borocaptate(BSH)and boronophenylalanine(BPA)as boron delivery agents for neutron capture therapy(NCT)of cancer:an update and a guide for the future clinical evaluation of new boron delivery agents for NCT

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Cancer Communications 2024年第8期44卷 893-909页

作者： Rolf F.Barth Nilendu Gupta Shinji Kawabata department of pathology The Ohio State UniversityColumbusOhioUSA department of Radiation Oncology The Ohio State UniversityColumbusOhioUSA department of Neurosurgery Osaka Medical and Pharmaceutical UniversityTakatsukiOsakaJapan

Boron neutron capture therapy(BNCT)is a cancer treatment modality based on the nuclear capture and fission reactions that occur when boron-10,a stable isotope,is irradiated with neutrons of the appropriate energy to produce boron-11 in an unstable form,which undergoes instantaneous nuclear fission to produce high-energy,tumoricidal alpha *** primary purpose of this review is to provide an update on the first drug used clinically,sodium borocaptate(BSH),by the Japanese neurosurgeon Hiroshi Hatanaka to treat patients with brain tumors and the second drug,boronophenylalanine(BPA),which first was used clinically by the Japanese dermatologist Yutaka Mishima to treat patients with cutaneous ***,BPA has become the primary drug used as a boron delivery agent to treat patients with several types of cancers,specifically brain tumors and recurrent tumors of the head and neck *** focus of this review will be on the initial studies that were carried out to define the pharmacokinetics and pharmacodynamics of BSH and BPA and their biodistribution in tumor and normal tissues following administration to patients with high-grade gliomas and their subsequent clinical use to treat patients with highgrade ***,wewill summarize the studies thatwere carried out in Japan with BSH and subsequently at our own institution,The Ohio State university,and those of several other ***,we will describe studies carried out in Japan with BPA and then in the United States that have led to its use as the primary drug that is being used clinically for ***,although there have been intense efforts to develop new and better boron delivery agents for BNCT,none of these have yet been evaluated *** present reportwill provide a guide to the future clinical evaluation of new boron delivery agents prior to their clinical use for BNCT.

关键词： Boron neutron capture therapy(BNCT) boronophenylalanine(BPA) brain tumors head and neck cancer sodium borocaptate(BSH)

Pathologic assessment of hepatocellular carcinoma in the era of immunotherapy:a narrative review

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Hepatobiliary Surgery and Nutrition 2024年第3期13卷 472-493页

作者： Han Wang You-Wen Qian Hui Dong Wen-Ming Cong department of pathology Shanghai Eastern Hepatobiliary Surgery HospitalNaval Medical UniversityShanghaiChina

Background and Objective:Immune checkpoint inhibitor(ICI)-based therapy has achieved impressive success in various cancer *** ICIs have been unprecedentedly approved as the treatment regimens for advanced hepatocellular carcinoma(HCC)in recent ***,numerous clinical trials are being performed to exploit more ICIs into initially unresectable HCC and postoperative HCC to expectantly induce adequate tumor downstaging for further resection or implement adjuvant treatment for relapse-free survival,*** this review,we aim to summarize some pragmatic histomorphologic,immunohistochemical,and molecular pathologic parameters which promisingly indicate the response of neoadjuvant/conversion ICI-related therapy and predict the efficacy of adjuvant/therapeutic ICI-related therapy for ***:We searched PubMed using the terms hepatocellular carcinoma,immunotherapy,immune checkpoint inhibitor,immune checkpoint blockade,conversion therapy,neoadjuvant therapy,adjuvant therapy,biomarker,pathologic evaluation,pathologic assessment till February *** Content and Findings:Although there is no consensus regarding the pathologic evaluation of relevant HCC specimens,it is encouraging that a few of studies have concentrated on this field,and moreover,the methods and parameters noted on other cancer types are also worthy of *** the pathologic assessment of HCC specimens underwent immunotherapy,a suitable sampling scheme,identifying immunotherapy-related pathologic response,and quantification of pathologic response rate should be *** the patients of HCC who are scheduled to receive immunotherapy,tumor-infiltrating lymphocyte,intratumoral tertiary lymphoid structure,programmed cell death ligand 1,Wnt/β-catenin,microsatellite instability and mismatch repair,tumor mutational burden and tumor neoantigen,as well as some other signaling pathways are the potential predictive biomarkers of treatment response of ***:The managem

关键词： Hepatocellular carcinoma(HCC) immune checkpoint blockade pathologic evaluation neoadjuvant therapy conversion therapy adjuvant therapy

COmbination of Targeted temperature management and Thrombectomy after acute Ischemic Stroke(COTTIS):a pilot study

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Stroke & Vascular Neurology 2024年第3期9卷 258-267页

作者： Jürgen Bardutzky Rainer Kollmar Forat Al-Rawi Johann Lambeck Mohammad Fazel Christian Taschner Wolf-Dirk Niesen department of Neurology and Neurophysiology Medical Center-University of FreiburgFaculty of MedicineUniversity of FreiburgFreiburgGermany Neurology and Neurointensive Care Darmstadt HospitalDarmstadtGermany BrainCool AB LundSweden department of Neuroradiology Medical Center-University of FreiburgFaculty of MedicineUniversity of FreiburgFreiburgGermany

Background To evaluate the feasibility and safety of a fast initiation of cooling to a target temperature of 35℃by means of transnasal cooling in patients with anterior circulation large vessel occlusion(LVO)undergoing endovascular thrombectomy(EVT).Methods Patients with an LVO onset of<24hour who had an indication for EVT were included in the *** cooling(RhinoChill)was initiated immediately after the patient was intubated for EVT and continued until an oesophageal target temperature of 35℃was *** was maintained with surface cooling for 6-hour postrecanalisation,followed by active rewarming(+0.2℃/hour).The primary outcome was defined as the time required to reach 35℃,while secondary outcomes comprised clinical,radiological and safety *** Twenty-two patients(median age,77 years)were included in the study(14 received additional thrombolysis,4 additional stenting of the proximal internal carotid artery).The median time intervals were 309min for last-seen-normal-to-groin,58min for door-to-cooling-initiation,65min for door-to-groin and 123min for *** target temperature of 35℃was reached within 30min(range 13–78min),corresponding to a cooling rate of 2.6℃/*** recanalisation,86%of the patients had a body temperature of≤35℃.The median National Institutes of Health Stroke Scale at admission was 15 and improved to 2 by day 7,and 68%of patients had a good outcome(modified Rankin Scale 0–2)at 3 *** complications included asymptomatic bradycardia(32%),pneumonia(18%)and asymptomatic haemorrhagic transformation(18%).Conclusion The combined application of hypothermia and thrombectomy was found to be feasible in sedated and ventilated *** events were comparable to those previously described for EVT in the absence of *** effect of this procedure will next be evaluated in the randomised COmbination of Targeted temperature management and Thrombectomy after acute Ischemic Stro

关键词： maintained continued initiated

Exosome-Transmitted miR-224-5p Promotes Colorectal Cancer Cell Proliferation via Targeting ULK2 in p53-Dependent Manner

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Biomedical and Environmental Sciences 2024年第1期37卷 71-84页

作者： YANG Le Mei ZHENG Qi LIU Xiao Jia LI Xian Xian Veronica Lim CHEN Qi ZHAO Zhong Hua WANG Shu Yang department of pathology School of Basic MedicineFudan UniversityShanghai 200032China department of pathology Dunedin School of MedicineUniversity of OtagoDunedin 9054New Zealand department of pathology Huashan HospitalFudan UniversityShanghai 200040China Shanghai Cancer Institute Renji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200127China Teladoc Health Inc Shanghai 200335China Shanghai Medical College Fudan UniversityShanghai 200032China Shanghai Key Laboratory of Medical Imaging Computing and Computer Assisted Intervention Shanghai 200032China

Objective To investigate the role and molecular mechanism of exosomal miR-224-5p in colorectal cancer(CRC).Methods The miR-224-5p expression in CRC patient tissues and cell-derived exosomes was measured by laser capture microdissection and qRT-PCR,***-luciferase reporter gene assay was used to determine the target gene of *** protein expressions of p53 and unc-51 like kinase 2(ULK2)in CRC cells were detected by western *** cytometry was used to detect cell cycle and *** proliferation was measured by CCK8 and EdU *** The miR-224-5p expression was upregulated in CRC tissues and increased progressively with the rise of CRC *** cells secreted extracellular miR-224-5p mainly in an exosome-dependent manner,and then miR-224-5p could be transferred to surrounding tumor cells to regulate cell proliferation in the form of autocrine or ***,ULK2 was characterized as a direct target of miR-224-5p and was downregulated in CRC ***,ULK2 inhibited CRC cell proliferation in a p53-dependent ***,exosome-derived miR-224-5p partially reversed the proliferation regulation of ULK2 on CRC *** Our findings demonstrate that exosome-transmitted miR-224-5p promotes p53-dependent cell proliferation by targeting ULK2 in CRC,which may offer promising targets for CRC prevention and therapy.

关键词： miR-224-5p Exosome ULK2 p53 Cell proliferation Colorectal cancer

NLRP3/1-mediated pyroptosis:beneficial clues for the development of novel therapies for Alzheimer’s disease

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Neural Regeneration Research 2024年第11期19卷 2400-2410页

作者： Bo Hu Jiaping Zhang Jie Huang Bairu Luo Xiansi Zeng Jinjing Jia department of pathology and Municipal Key-Innovative Discipline of Molecular Diagnostics Jiaxing Hospital of Traditional Chinese MedicineJiaxing UniversityJiaxingZhejiang ProvinceChina Research Center of Neuroscience Jiaxing University Medical CollegeJiaxingZhejiang ProvinceChina department of Clinical pathology Jiaxing University Master Degree Cultivation BaseZhejiang Chinese Medical UniversityJiaxingZhejiang ProvinceChina

The inflammasome is a multiprotein complex involved in innate immunity that mediates the inflammatory response leading to pyroptosis,which is a lytic,inflammatory form of cell *** is accumulating evidence that nucleotide-binding domain and leucine-rich repeat pyrin domain containing 3(NLRP3)inflammasome-mediated microglial pyroptosis and NLRP1 inflammasome-mediated neuronal pyroptosis in the brain are closely associated with the pathogenesis of Alzheimer’s *** this review,we summarize the possible pathogenic mechanisms of Alzheimer’s disease,focusing on *** also describe the structures of NLRP3 and NLRP1 and the role their activation plays in Alzheimer’s ***,we examine the neuroprotective activity of small-molecule inhibitors,endogenous inhibitor proteins,microRNAs,and natural bioactive molecules that target NLRP3 and NLRP1,based on the rationale that inhibiting NLRP3 and NLRP1 inflammasome-mediated pyroptosis can be an effective therapeutic strategy for Alzheimer’s disease.

关键词： Alzheimer’s disease caspase-1 GSDMD inflammasome neuroinflammation NLRP1 NLRP3 pyroptosis therapeutic strategies

ATM Activation is Key in Vasculogenic Mimicry Formation by Glioma Stem-like Cells

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Biomedical and Environmental Sciences 2024年第8期37卷 834-849页

作者： Jing Xie Jiaxin Tang Yuan Li Xue Kong Wei Wang Haibo Wu department of pathology the First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei 230036AnhuiChina Intelligent pathology Institute Division of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei 230036AnhuiChina

Objective Vasculogenic mimicry(VM)is a novel vasculogenic process integral to glioma stem cells(GSCs)in glioblastoma(GBM).However,the relationship between VM and ataxia-telangiectasia mutated(ATM)serine/threonine kinase activation,which confers chemoradiotherapy resistance,remains *** We investigated VM formation and phosphorylated ATM(pATM)levels by CD31/GFAPperiodic acid-Schiff dual staining and immunohistochemical staining in 145 GBM *** stem-like cells(GSLCs)derived from the formatted spheres of U87 and U251 cell lines and their pATM level and VM formation ability were examined using western blot and three-dimensional *** the examination of the function of pATM in VM formation by GSLCs,ATM knockdown by shRNAs and deactivated via ATM phosphorylation inhibitor KU55933 were *** VM and high pATM expression occurred in 38.5% and 41.8% of tumors,respectively,and were significantly associated with reduced progression-free and overall *** with VM-positive GBMs exhibited higher pATM levels(r_(s)=0.425,P=0.01).The multivariate analysis established VM as an independent negative prognostic factor(P=0.002).Furthermore,GSLCs expressed high levels of pATM and formed vascular-like networks in *** inactivation or knockdown hindered VM-like network formation concomitant with the downregulation of pVEGFR-2,VE-cadherin,and laminin *** VM may predict a poor GBM prognosis and is associated with pATM *** propose that pATM promotes VM through extracellular matrix modulation and VE-Cadherin/pVEGFR-2 activation,thereby highlighting ATM activation as a potential target for enhancing anti-angiogenesis therapies for GBM.

关键词： Glioblastoma Vasculogenic mimicry Ataxia-telangiectasia mutated(ATM) Glioma stem-like cell

Primary Ewing sarcoma of the kidney mimicking cystic papillary renal cell carcinoma in an older patient:A case repor

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World Journal of Clinical Cases 2024年第15期12卷 2606-2613页

作者： Suhong Kim Jongsoo Park Young Hwii Ko Hee Jung Kwon department of Radiology Yeungnam UniversityDaegu 42415South Korea department of Urology Yeungnam UniversityDaegu 42415South Korea department of pathology Yeungnam UniversityDaegu 42415South Korea

BACKGROUND Ewing’s sarcoma(ES)is a neuroectodermal tumor that typically occurs in the bones and soft tissues of children and young *** renal ES is rare;only a few cases and a small case series have been documented,and only four cases involved primary renal ES in older people(>65 years old).CASE SUMMARY Herein,we describe the radiological and pathological features of primary renal ES in an older person.A 76-year-old man complained of poor oral intake and was found to have a large cystic renal mass with indistinct margins on computed ***-guided biopsy revealed that the tumor contained small round blue *** patient underwent a right radical *** tumor cells showed diffuse membranous CD99,and nuclear friend leukemia integration 1 transcription factor and NK2 Homeobox *** in situ hybridization revealed EWSR1 ***,18F-fluorodeoxyglucose positron emission tomography revealed no evidence of *** patient was diagnosed with primary renal *** months following the surgery,local recurrence and distant metastasis were *** renal ES is rare and often lethal in older *** specific imaging findings are unknown,and treatment protocols have not been *** This case report describes the radiological and pathological features of primary renal ES in an older person.

关键词： Ewing sarcoma Elder Renal Kidney Neuroectodermal Case report

Role of Vickers Ligament in the Pathogenesis of Madelung Deformity

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Current Medical Science 2024年第4期44卷 735-740页

作者： Ge XIONG Wei ZHENG Li-hua GONG department of Hand Surgery Beijing Jishuitan HospitalCapital Medical UniversityBeijing 100035China department of pathology Beijing Jishuitan HospitalCapital Medical UniversityBeijing 100035China

Objective The Vickers ligament is thought to hinder the growth of palmar ulnar radius by tethering the lunate to the radius,leading to Madelung *** purpose of this study was to clarify the nature of the Vickers ligament and investigate its pathogenesis in Madelung deformities based on our observation of the Vickers *** All 22 patients(33 wrists)with Madelung deformities treated surgically between 2018 and 2022 were *** diagnosis was confirmed radiographically in all *** three-dimensional computed tomography(3D-CT)data of 16 patients(19 wrists)were *** resonance imaging(MRI)data were available for 9 patients(14 wrists).Wrist arthroscopy was used in 4 *** Vickers ligament was resected and submitted for histopathological examination in 8 *** outcomes,3D-CT,MRI,arthroscopy,surgical findings,and histopathology of the Vickers ligament were *** The 3D-CT revealed that the Vickers ligament originated in the metaphysis and formed a metaphyseal defect at the palmar ulnar *** the sequential MR coronal images,the Vickers ligament could be divided into 3 branches,extending to the lunate,triquetrum and ulnar *** and surgical findings revealed that the nature of the Vickers ligament was the stretched palmar ligament of the *** histopathology results revealed ligamentous tissue and fibrocartilaginous metaplasia with a structure similar to that of the triangular fibrocartilage complex(TFCC).Conclusions The Vickers ligament is not a separate aberrant *** nature of the Vickers ligament is a combination of the stretched TFCC ligament(palmar radioulnar ligament,ulnotriquetral ligament and ulnolunate ligament)and radiolunate *** possible pathogenesis of Madelung deformity might be focal early epiphyseal closure at the middle part of the sigmoid notch,which leads to focal growth retardation of the radius and pulls palmar ligaments proximally to for

关键词： Vickers ligament Madelung deformity pathogenesis computed tomography magnetic resonance imaging

Myocardial metastasis from ZEB1-and TWIST-positive spindle cell carcinoma of the esophagus:A case report

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World Journal of Gastroenterology 2024年第11期30卷 1636-1643页

作者： Yoshihiro Shibata Hirofumi Ohmura Kazuki Komatsu Kosuke Sagara Atsuji Matsuyama Ryuji Nakano Eishi Baba department of Medical Oncology Fukuoka Wajiro HospitalFukuoka 811-0213Japan department of Oncology and Social Medicine Kyushu University Graduate School of Medical SciencesFukuoka 812-8582Japan department of pathology and Oncology University of Occupational and Environmental HealthKitakyushu 807-8555Japan department of Diagnostic pathology Fukuoka Wajiro HospitalFukuoka 811-0213Japan

BACKGROUND Metastatic cardiac tumors are known to occur more frequently than primary cardiac tumors,however,they often remain asymptomatic and are commonly dis-covered on *** tumors with a relatively high frequency of cardiac metastasis include mesothelioma,melanoma,lung cancer,and breast cancer,whereas reports of esophageal cancer with cardiac metastasis are *** SUMMARY The case of a 60-year-old man who complained of dysphagia is *** gastrointestinal endoscopy showed a submucosal tumor-like elevated lesion in the esophagus causing ***-enhanced computed tomography showed left atrial compression due to the esophageal tumor,multiple liver and lung metastases,and a left pleural *** examination of a biopsy speci-men from the esophageal tumor showed spindle-shaped cells,raising suspicion of esophageal *** disease progressed rapidly,and systemic chemotherapy was deemed necessary,however,due to his poor general condition,adminis-tration of cytotoxic agents was considered *** his high Combined Positive Score,nivolumab was administered,however,the patient soon died from the *** autopsy confirmed spindle cell carcinoma(SCC)of the esophagus and cardiac metastasis with similar histological *** stem cell markers,ZEB1 and TWIST,were positive in both the primary tumor and the cardiac *** To the best of our knowledge,there have been no prior reports of cardiac metastasis of esophageal *** case highlights our experience with a patient with esophageal SCC who progressed rapidly and died from the disease,with the autopsy examination showing cardiac metastasis.

关键词： Spindle cell carcinoma Esophagus Myocardial metastasis Epithelial-mesenchymal transition Case report