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Microglia lactylation in relation to central nervous system diseases

Neural Regeneration Research 2025年第1期20卷 29-40页

作者： Hui Yang Nan Mo Le Tong Jianhong Dong Ziwei Fan Mengxian Jia Juanqing Yue Ying Wang School of Pharmacy Hangzhou Normal UniversityHangzhouZhejiang ProvinceChina Department of clinical Laboratory The Fourth Clinical Medical College of Zhejiang University of Traditional Chinese Medicine(Hangzhou First People’s Hospital)HangzhouZhejiang ProvinceChina College of Medical Veterinary and Life SciencesUniversity of GlasgowGlasgowUK Department of Orthopedics(Spine Surgery) the First Affiliated Hospital of Wenzhou Medical UniversityWenzhouZhejiang ProvinceChina Department of pathology Affiliated Hangzhou First People’s HospitalWestlake University School of MedicineHangzhouZhejiang ProvinceChina Department of clinical Research Center Affiliated Hangzhou First People’s HospitalWestlake University School of MedicineHangzhouZhejiang ProvinceChina

The development of neurodegenerative diseases is closely related to the disruption of central nervous system homeostasis.Microglia,as innate immune cells,play important roles in the maintenance of central nervous system homeostasis,injury response,and neurodegenerative diseases.Lactate has been considered a metabolic waste product,but recent studies are revealing ever more of the physiological functions of lactate.Lactylation is an important pathway in lactate function and is involved in glycolysis-related functions,macrophage polarization,neuromodulation,and angiogenesis and has also been implicated in the development of various diseases.This review provides an overview of the lactate metabolic and homeostatic regulatory processes involved in microglia lactylation,histone versus non-histone lactylation,and therapeutic approaches targeting lactate.Finally,we summarize the current research on microglia lactylation in central nervous system diseases.A deeper understanding of the metabolic regulatory mechanisms of microglia lactylation will provide more options for the treatment of central nervous system diseases.

关键词： brain central nervous system glycolysis immune response inflammation lactate metabolism lactate lactylation microglia neurodegenerative diseases

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GRK2 inhibits Flt-1^(+)macrophage infiltration and its proangiogenic properties in rheumatoid arthritis

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Acta Pharmaceutica Sinica B 2024年第1期14卷 241-255页

作者： Xuezhi Yang Yingjie Zhao Qi Wei Xuemin Zhu Luping Wang Wankang Zhang Xiaoyi Liu Jiajie Kuai Fengling Wang Wei Wei Institute of clinical Pharmacology Anhui Medical UniversityKey Laboratory of Anti-Inflammatory and Immune MedicineAnhui Collaborative Innovation Center of Anti-Inflammatory and Immune MedicineMinistry of EducationHefei 230032China Department of clinical Pharmacology the Second Affiliated Hospital of Anhui Medical UniversityHefei 230601China

Rheumatoid arthritis(RA)is an autoimmune disease with a complex etiology.Monocyte-derived macrophages(MDMs)infiltration are associated with RA severity.We have reported the deletion of G-protein-coupled receptor kinase 2(GRK2)reprograms macrophages toward an anti-inflammatory phenotype by recovering G-protein-coupled receptor signaling.However,as more GRK2-interacting proteins were discovered,the GRK2 interactome mechanisms in RA have been understudied.Thus,in the collagen-induced arthritis mouse model,we performed genetic GRK2 deletion using GRK2^(f/f)Lyz2-Cre^(+/−)mice.Synovial inflammation and M1 polarization were improved in GRK2^(f/f)Lyz2-Cre^(+/−)mice.Supporting experiments with RNA-seq and dual-luciferase reporter assays identified peroxisome proliferator-activated receptorγ(PPARγ)as a new GRK2-interacting protein.We further confirmed that fms-related tyrosine kinase 1(Flt-1),which promoted macrophage migration to induce angiogenesis,was inhibited by GRK2-PPARγsignaling.Mechanistically,excess GRK2 membrane recruitment in CIA MDMs reduced the activation of PPARγligand-binding domain and enhanced Flt-1 transcription.Furthermore,the treatment of mice with GRK2 activity inhibitor resulted in significantly diminished CIA pathology,Flt-1^(+)macrophages induced-synovial inflammation,and angiogenesis.Altogether,we anticipate to facilitate the elucidation of previously unappreciated details of GRK2-specific intracellular signaling.Targeting GRK2 activity is a viable strategy to inhibit MDMs infiltration,affording a distinct way to control joint inflammation and angiogenesis of RA.

关键词： GRK2 Monocyte-derived macrophages Rheumatoid arthritis PPARg Flt-1

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Pathological diagnosis and immunohistochemical analysis of giant retrosternal goiter in the elderly: A case report

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World Journal of clinical Cases 2024年第3期12卷 643-649页

作者： Yong-Chang Meng Liu-Sheng Wu Ning Li Hong-Wei Li Jing Zhao Jun Yan Xiao-Qiang Li Peng Li Jiang-Qi Wei Department of Cardiothoracic Surgery Xinxiang First People's HospitalXinxiang 453000Henan ProvinceChina School of clinical Medicine Tsinghua UniversityBeijing 100084China Graduate School Qinghai UniversityXining 810016Qinghai ProvinceChina Department of pathology Xinxiang First People's HospitalXinxiang 453000Henan ProvinceChina Department of Thoracic Surgery Peking University Shenzhen HospitalShenzhen 518036Guangdong ProvinceChina

BACKGROUND Elderly giant retrosternal thyroid goiter is a rare yet significant medical condition,often presenting clinical symptoms that can be confused with other diseases,posing diagnostic and therapeutic challenges.This study aims to delve into the characteristics and potential mechanisms of this ailment through pathological diagnosis and immunohistochemical analysis,providing clinicians with more precise diagnostic and treatment strategies.A 77-year-old male,was admitted to hospital with the chief complaint of finding a goiter in the semilunar month during physical examination,accompanied by dyspnea.Locally protruding into the superior mediastinum,the adjacent structure was compressed,the trachea was compressed to the right,and the local lumen was slightly narrowed.The patient was diagnosed with giant retrosternal goiter.Considering dyspnea caused by trachea compression,our department planned to perform giant retrosternal thyroidectomy.Immunohistochemical results:Tg(+),TTF-1(+),Calcitonin(CT)(I),Ki-67(+,about 20%),CD34(-).Retrosternal goiter means that more than 50%of the volume of the thyroid gland is below the upper margin of the sternum.As retrosternal goiter disease is a relatively rare disease,once the disease is diagnosed,it should be timely surgical treatment,and the treatment is more difficult,the need for professional medical team for comprehensive treatment.CONCLUSION The imaging manifestations of giant retrosternal goiter are atypical,histomorphology and immunohistochemistry can assist in its diagnosis.This article reviews the relevant literature of giant retrosternal goiter immunohisto-chemistry and shows that giant retrosternal goiter is positive for Tg,TTF-1,and Ki-67.

关键词： Giant retrosternal goiter pathology Immunohistochemistry Case report

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Liver histological changes in untreated chronic hepatitis B patients in indeterminate phase

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World Journal of Hepatology 2024年第6期16卷 920-931页

作者： De-Liang Huang Qin-Xian Cai Guang-De Zhou Hong Yu Zhi-Bin Zhu Jing-Han Peng Jun Chen Department of Liver Diseases The Third People’s Hospital of ShenzhenShenzhen 510000Guangdong ProvinceChina Department of pathology Beijing Youan HospitalCapital Medical UniversityBeijing 100000China Department of pathology National Clinical Research Centre for Infectious DiseaseThe Third People's Hospital of Shenzhen and the Second Hospital Affiliated with the Southern University of Science and TechnologyShenzhen 518112Guangdong ProvinceChina

BACKGROUND Studies with large size samples on the liver histological changes of indeterminate phase chronic hepatitis B(CHB)patients were not previously conducted.AIM To assess the liver histological changes in the indeterminate phase CHB patients using liver biopsy.METHODS The clinical and laboratory data of 1532 untreated CHB patients were collected,and all patients had least once liver biopsy from January 2015 to December 2021.The significant differences among different phases of CHB infection were compared with t-test,and the risk factors of significant liver histological changes were analyzed by the multivariate logistic regression analysis.RESULTS Among 1532 untreated CHB patients,814(53.13%)patients were in the indeterminate phase.Significant liver histological changes(defined as biopsy score≥G2 and/or≥S2)were found in 488/814(59.95%)CHB patients in the indete-rminate phase.Significant liver histological changes were significant differences among different age,platelets(PLTs),and alanine aminotransferase(ALT)subgroup in indeterminate patient.Multivariate logistic regression analysis indicated that age≥40 years old[adjust odd risk(aOR),1.44;95%confidence interval(CI):1.06-1.97;P=0.02],PLTs≤150×10^(9)/L(aOR,2.99;95%CI:1.85-4.83;P<0.0001),and ALT≥upper limits of normal(aOR,1.48;95%CI:1.08,2.05,P=0.0163)were independent risk factors for significant liver histological changes in CHB patients in the indeterminate phase.CONCLUSION Our results suggested that significant liver histological changes were not rare among the untreated CHB patients in indeterminate phase,and additional strategies are urgently required for the management of these patients.

关键词： Chronic hepatitis B Indeterminate phase Gray-zone Liver biopsy Pathological histology Risk factors

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RIOK1 synergizes with TRIP13 by regulating the E2F-Rb signaling pathway to promote the proliferation of esophageal cancer cells

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Genes & Diseases 2024年第3期11卷 55-58页

作者： Chengyu Li Deyuan Pan Wan Lin Danxia Deng Yingxin Zhou Hui Zhao Feng Pan Liyan Xu Enmin Li Lin Long The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area Department of Biochemistry and Molecular BiologyShantou University Medical CollegeShantouGuangdong 515041China Guangdong Provincial Key Laboratory of Infectious Diseases and Molecular Immunopathology Institute of Oncologic PathologyShantou University Medical CollegeShantouGuangdong 515041China Institute of Basic Medical Science Cancer Research CenterShantou University Medical CollegeShantouGuangdong 515041China clinical Research Center Shantou Central HospitalShantouGuangdong 515041China

Esophageal cancer is one of the leading causes of cancer death in the world,with approximately half of the new cases occurring in China every year.^(1)Esophageal squamous cell carcinoma(ESCC)is the main subtype,accounting for more than 90%,and the five-year survival rate is less than 10%.Using large-scale genome analysis,many driver mutations and key pathways associated with ESCC have been identified.However,these genomic signatures have not improved the clinical management of EscC patients,or established effective targeted therapy.^(2)Esophageal cancer still lacks representative molecular markers.

关键词： cancer esophageal Esophageal

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From text to image:challenges in integrating vision into ChatGPT for medical image interpretation

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Neural Regeneration Research 2025年第2期20卷 487-488页

作者： Shunsuke Koga Wei Du Department of pathology and Laboratory Medicine Hospital of the University of PennsylvaniaPhiladelphiaPAUSA

Large language models(LLMs),such as ChatGPT developed by OpenAI,represent a significant advancement in artificial intelligence(AI),designed to understand,generate,and interpret human language by analyzing extensive text data.Their potential integration into clinical settings offers a promising avenue that could transform clinical diagnosis and decision-making processes in the future(Thirunavukarasu et al.,2023).This article aims to provide an in-depth analysis of LLMs’current and potential impact on clinical practices.Their ability to generate differential diagnosis lists underscores their potential as invaluable tools in medical practice and education(Hirosawa et al.,2023;Koga et al.,2023).

关键词： image diagnosis text

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Establishment of a Multiplex Detection Method for Common Bacteria in Blood Based on Human Mannan-Binding Lectin Protein-Conjugated Magnetic Bead Enrichment Combined with Recombinase-Aided PCR Technology

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Biomedical and Environmental Sciences 2024年第4期37卷 387-398页

作者： ZHAO Zi Jin CHEN Xiao Ping HUA Shao Wei LI Feng Yu ZHAO Meng XING Chen Hao WANG Jie TIAN Feng Yu ZHANG Rui Qing LYU Xiao Na HAN Zhi Qiang WANG Yu Xin LI Hong Yi SHEN Xin Xin MA Xue Jun TIE Yan Qing Graduate School Hebei North UniversityZhangjiakou 075000HebeiChina Department of clinical Laboratory Hebei General HospitalShijiazhuang 050051HebeiChina National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases NHC Key Laboratory of Medical Virology and Viral DiseasesNational Institute for Viral Disease Control and PreventionChinese Center for Disease Control and PreventionBeijing 102206China National Institute for Communicable Disease Control and Prevention Chinese Center for Disease Control and PreventionBeijing 102206China Department of clinical Laboratory pathology Diagnostic Center Shiyan General HospitalShiyan 442000HubeiChina Graduate School Hebei Medical University Shijiazhuang 050031HebeiChina

Objective Recombinase-aided polymerase chain reaction(RAP)is a sensitive,single-tube,two-stage nucleic acid amplification method.This study aimed to develop an assay that can be used for the early diagnosis of three types of bacteremia caused by Staphylococcus aureus(SA),Pseudomonas aeruginosa(PA),and Acinetobacter baumannii(AB)in the bloodstream based on recombinant human mannanbinding lectin protein(M1 protein)-conjugated magnetic bead(M1 bead)enrichment of pathogens combined with RAP.Methods Recombinant plasmids were used to evaluate the assay sensitivity.Common blood influenza bacteria were used for the specific detection.Simulated and clinical plasma samples were enriched with M1 beads and then subjected to multiple recombinase-aided PCR(M-RAP)and quantitative PCR(qPCR)assays.Kappa analysis was used to evaluate the consistency between the two assays.Results The M-RAP method had sensitivity rates of 1,10,and 1 copies/μL for the detection of SA,PA,and AB plasmids,respectively,without cross-reaction to other bacterial species.The M-RAP assay obtained results for<10 CFU/mL pathogens in the blood within 4 h,with higher sensitivity than qPCR.M-RAP and qPCR for SA,PA,and AB yielded Kappa values of 0.839,0.815,and 0.856,respectively(P<0.05).Conclusion An M-RAP assay for SA,PA,and AB in blood samples utilizing M1 bead enrichment has been developed and can be potentially used for the early detection of bacteremia.

关键词： Staphylococcus aureus Pseudomonas aeruginosa Acinetobacter baumannii Human Mannan-binding lectin protein Bloodstream infection Recombinase-aided PCR assay Multiple detection

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Splenic hamartomas in children

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World Journal of clinical Cases 2024年第11期12卷 1909-1917页

作者： Maja Milickovic Petar Rasic Sofija Cvejic Dejana Bozic Djordje Savic Tanja Mijovic Sava Cvetinovic Slavisa M Djuricic Department of Abdominal Surgery Mother and Child Health Care Institute of Serbia"Dr.Vukan Cupic"Belgrade 11000Serbia Faculty of Medicine University of BelgradeBelgrade 11000Serbia Department of Radiology The Children’s University HospitalBelgrade 11000Serbia Department of clinical pathology Mother and Child Health Care Institute of Serbia"Dr.Vukan Cupic"Belgrade 11000Serbia Faculty of Medicine University of Banja LukaBanja Luka 78000Bosnia and Herzegovina

Splenic hamartomas(SHs)are uncommon,benign vascular lesions of unclear etiology and are mostly found incidentally on abdominal images,at surgery,or at autopsy.Since the first case description,in 1861,less than 50 pediatric SH cases have been reported in the literature.In this article,we have performed an analysis of all SH cases in children published in the literature to date and presented our case of an 8-year-old male with SH.These lesions in children were shown to cause symptoms more often than in the adult population.The observed SH sizes in children ranged from a few millimeters to 18 cm,and the symptomatic lesions were mostly larger or multiple.The most common clinical finding was splenomegaly.Signs of hypersplenism were present in children with a single SH larger than 4.5 cm(diameter range:4.5-18.0 cm)and in those with multiple hamartomas,ranging from a few millimeters to 5 cm.Eighty percent of patients with available laboratory findings had hematological abnormalities such as anemia,thrombocytopenia,or pancytopenia.Other symptoms and signs included abdominal pain,recurrent infections,fever,night sweats,lethargy,growth retardation,and weight loss.The use of multiple imaging modalities may suggest the preoperative diagnosis of a splenic mass in children and determine the therapeutic approach.However,the final diagnosis of SH relies on histopathological evaluation.Surgery,including total or partial splenectomy(PS),is the mainstay of SH management.Milickovic M et al.Splenomas in children WJCC https://*** 1910 April 16,2024 Volume 12 Issue 11 Although total splenectomy carries a greater risk of overwhelming post-splenectomy infection than PS it has remained the most performed surgical procedure in children with SH.In the majority of pediatric patients with symptomatic SH,resolution of symptoms and resolution or improvement of cytopenias occurred after surgical treatment.

关键词： Splenic hamartoma Pediatric Splenoma clinical features Radiological features Histopathology Treatment

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Mex-3 RNA binding family member A(MEX3A)/circMPP6 complex promotes colorectal cancer progression by inhibiting autophagy

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Signal Transduction and Targeted Therapy 2024年第5期9卷 2091-2103页

作者： Ri-Xin Chen Shui-Dan Xu Min-Hua Deng Shi-Hui Hao Jie-Wei Chen Xiao-Dan Ma Wei-Tao Zhuang Jing-Hua Cao Yong-Rui Lv Jin-Long Lin Si-Yu Li Gui-Bin Qiao Dan Xie Feng-Wei Wang Department of Thoracic Surgery Guangdong Provincial People’s Hospital(Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhou 510080China State Key Laboratory of Oncology in South China Guangdong Provincial Clinical Research Center for CancerSun Yat-sen University Cancer CenterGuangzhou 510060China Medical Research Institute Guangdong Provincial People’s Hospital(Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhou 510080China Department of pathology Sun Yat-sen University Cancer CenterGuangzhou 510060China

RNA-binding proteins(RBPs)-RNA networks have contributed to cancer development.Circular RNAs(circRNAs)are considered as protein recruiters;nevertheless,the patterns of circRNA-protein interactions in colorectal cancer(CRC)are still lacking.Processing bodies(PBs)formed through liquid-liquid phase separation(LLPS)are membrane-less organelles(MLOs)consisting of RBPs and RNA.Previous evidence suggests a connection between PBs dynamics and cancer progression.Despite the increasingly acknowledged crucial role of RBPs and RNA in the accumulation and maintenance of MLOs,there remains a lack of specific research on the interactions between PBs-related RBPs and circRNAs in CRC.Herein,we identify that MEX-3 RNA binding family member A(MEX3A),frequently upregulated in CRC tissues,predicts poorer patient survival.Elevated MEX3A accelerates malignance and inhibits autophagy of CRC cells.Importantly,MEX3A undergoes intrinsically disordered regions(IDRs)-dependent LLPS in the cytoplasm.Specifically,circMPP6 acts as a scaffold to facilitate the interaction between MEX3A and PBs proteins.The MEX3A/circMPP6 complex modulates PBs dynamic and promotes UPF-mediated phosphodiesterase 5A(PDE5A)mRNA degradation,consequently leading to the aggressive properties of CRC cells.clinically,CRC patients exhibiting high MEX3A expression and low PDE5A expression have the poorest overall survival.Our findings reveal a collaboration between MEX3A and circMPP6 in the regulation of mRNA decay through triggering the PBs aggregation,which provides prognostic markers and/or therapeutic targets for CRC.

关键词： colorectal inhibiting MPP

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Suppression of ITPKB degradation by Trim25 confers TMZ resistance in glioblastoma through ROS homeostasis

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Signal Transduction and Targeted Therapy 2024年第4期9卷 1637-1650页

作者： Yuanliang Yan Shangjun Zhou Xi Chen Qiaoli Yi Songshan Feng Zijin Zhao Yuanhong Liu Qiuju Liang Zhijie Xu Zhi Li Lunquan Sun Department of Pharmacy Xiangya HospitalCentral South UniversityChangsha 410008China Department of Neurosurgery Xiangya HospitalCentral South UniversityChangsha 410008China Department of pathology Xiangya HospitalCentral South UniversityChangsha 410008China Xiangya Cancer Center Xiangya HospitalCentral South UniversityChangsha 410008China Key Laboratory of Molecular Radiation Oncology Hunan Province Changsha 410008China institute of Cancer Research National Clinical Research Center for Geriatric Disorders(Xiangya)Xiangya HospitalCentral South UniversityChangsha 410008China

Temozolomide(TMZ)represents a standard-of-care chemotherapeutic agent in glioblastoma(GBM).However,the development of drug resistance constitutes a significant hurdle in the treatment of malignant glioma.Although specific innovative approaches,such as immunotherapy,have shown favorable clinical outcomes,the inherent invasiveness of most gliomas continues to make them challenging to treat.Consequently,there is an urgent need to identify effective therapeutic targets for gliomas to overcome chemoresistance and facilitate drug development.This investigation used mass spectrometry to examine the proteomic profiles of six pairs of GBM patients who underwent standard-of-care treatment and surgery for both primary and recurrent tumors.A total of 648 proteins exhibiting significant differential expression were identified.Gene Set Enrichment Analysis(GSEA)unveiled notable alterations in pathways related to METABOLISM_OF_LIPIDS and BIOLOGICAL_OXIDATIONS between the primary and recurrent groups.Validation through glioma tissue arrays and the Xiangya cohort confirmed substantial upregulation of inositol 1,4,5-triphosphate(IP3)kinase B(ITPKB)in the recurrence group,correlating with poor survival in glioma patients.In TMZ-resistant cells,the depletion of ITPKB led to an increase in reactive oxygen species(ROS)related to NADPH oxidase(NOX)activity and restored cell sensitivity to TMz.Mechanistically,the decreased phosphorylation of the E3 ligase Trim25 at the S100 position in recurrent GBM samples accounted for the weakened ITPKB ubiquitination.This,in turn,elevated ITPKB stability and impaired ROS production.Furthermore,ITPKB depletion or the ITPKB inhibitor GNF362 effectively overcome TMZ chemoresistance in a glioma xenograft mouse model.These findings reveal a novel mechanism underlying TMZ resistance and propose ITPKB as a promising therapeutic target forTMZ-resistant GBM.

关键词： TMZ homeostasis impaired

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