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Recombinant chitinase-3-like protein 1 alleviates learning and memory impairments via M2 microglia polarization in postoperative cognitive dysfunction mice

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Neural Regeneration Research 2025年第9期20卷 2727-2736页

作者： Yujia Liu Xue Han Yan Su Yiming Zhou Minhui Xu Jiyan Xu Zhengliang Ma Xiaoping Gu Tianjiao Xia Department of Anesthesiology Nanjing Drum Tower HospitalAffiliated Hospital of Medical SchoolNanjing UniversityNanjingJiangsu ProvinceChina Medical School Nanjing UniversityNanjingJiangsu ProvinceChina Jiangsu Key Laboratory of Molecular Medicine Nanjing UniversityNanjingJiangsu ProvinceChina State Key Laboratory of Pharmaceutical Biotechnology Nanjing UniversityNanjingJiangsu ProvinceChina Department of Anesthesiology Zhongshan HospitalFudan UniversityShanghaiChina

Postoperative cognitive dysfunction is a seve re complication of the central nervous system that occurs after anesthesia and surgery,and has received attention for its high incidence and effect on the quality of life of *** date,there are no viable treatment options for postoperative cognitive *** identification of postoperative cognitive dysfunction hub genes could provide new research directions and therapeutic targets for future *** identify the signaling mechanisms contributing to postoperative cognitive dysfunction,we first conducted Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses of the Gene Expression Omnibus GSE95426 dataset,which consists of mRNAs and long non-coding RNAs differentially expressed in mouse hippocampus3 days after tibial *** dataset was enriched in genes associated with the biological process"regulation of immune cells,"of which Chill was identified as a hub ***,we investigated the contribution of chitinase-3-like protein 1 protein expression changes to postoperative cognitive dysfunction in the mouse model of tibial fractu re *** were intraperitoneally injected with vehicle or recombinant chitinase-3-like protein 124 hours post-surgery,and the injection groups were compared with untreated control mice for learning and memory capacities using the Y-maze and fear conditioning *** addition,protein expression levels of proinflammatory factors(interleukin-1βand inducible nitric oxide synthase),M2-type macrophage markers(CD206 and arginase-1),and cognition-related proteins(brain-derived neurotropic factor and phosphorylated NMDA receptor subunit NR2B)were measured in hippocampus by western *** with recombinant chitinase-3-like protein 1 prevented surgery-induced cognitive impairment,downregulated interleukin-1βand nducible nitric oxide synthase expression,and upregulated CD206,arginase-1,pNR2B,and brain-derived neurotropic factor expr

关键词： Chil1 hippocampus learning and memory M2 microglia neuroinflammation postoperative cognitive dysfunction(POCD) recombinant CHI3L1

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Exploring the potential of extrachromosomal DNA as a novel oncogenic driver

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Science China Life Sciences 2025年第1期 144-157页

作者： Huanbo Zhu Longtao Huangfu Junbing Chen Jiafu Ji Xiaofang Xing Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing) Division of Gastrointestinal Cancer Translational Research LaboratoryPeking University Cancer Hospital & Institute Department of Gastrointestinal Cancer Center Peking University Cancer Hospital & Institute Department of Liver Surgery & Transplantation Liver Cancer InstituteZhongshan HospitalFudan University Key Laboratory of Carcinogenesis and Cancer Invasion Ministry of Education State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers Beijing Key Laboratory of Carcinogenesis and Translational ResearchDivision of Gastrointestinal Cancer Translational Research LaboratoryPeking University Cancer Hospital & Institute

Extrachromosomal DNA(ecDNA) is a form of circular DNA mostly found in tumor cells. Unlike the typical chromosomal DNA, ecDNA is circular, self-replicating, and carries complete or partial gene fragments. Although ecDNA occurrence remains a rare event in cancer, recent studies have shown that oncogene amplification on ecDNA is widespread throughout many types of cancer, implying that ecDNA plays a central role in accelerating tumor evolution. ecDNA has also been associated with increased tumor mutation burden, chromosomal instability, and even tumor microenvironment remodeling. ecDNA may be crucial in influencing tumor heterogeneity, drug sensitivity,oncogenic senescence, and tumor immunogenicity, leading to a worsening prognosis for tumor patients. In this way, several clinical trials have been conducted to investigate the importance of ecDNA in clinical treatment. In this review, we summarize the biogenesis, characteristics, and current research methods of ecDNA, discuss the vital role of ecDNA-caused tumor heterogeneity in cancers, and highlight the potential role of ecDNA in cancer therapy.

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MST4 kinase regulates immune thrombocytopenia by phosphorylating STAT1-mediated M1 polarization of macrophages

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Cellular & Molecular Immunology 2023年第12期20卷 1413-1427页

作者： Jingjing Cao Lili Ji Yanxia Zhan Xia Shao Pengcheng Xu Boting Wu Pu Chen Luya Cheng Xibing Zhuang Yang Ou Fanli Hua Lihua Sun Feng Li Hao Chen Zhaocai Zhou Yunfeng Cheng Department of Hematology Zhongshan HospitalFudan UniversityShanghai200032China Center for Tumor Diagnosis&Therapy Jinshan HospitalFudan UniversityShanghai201508China Department of Transfusion Medicine Zhongshan HospitalFudan UniversityShanghai200032China Department of Laboratory Medicine Zhongshan HospitalFudan UniversityShanghai200032China Department of Hematology Zhongshan Hospital Qingpu BranchFudan UniversityShanghai201700China Department of Thoracic Surgery Zhongshan-Xuhui HospitalFudan UniversityShanghai200031China State Key Laboratory of Genetic Engineering Zhongshan HospitalSchool of Life SciencesFudan UniversityShanghai200438China Institute of Clinical Science Zhongshan HospitalFudan UniversityShanghai200032China

Primary immune thrombocytopenia(ITP)is an autoimmune hemorrhagic disorder in which macrophages play a critical *** sterile-20-like kinase 4(MST4),a member of the germinal-center kinase STE20 family,has been demonstrated to be a regulator of *** MST4 participates in the macrophage-dependent inflammation of ITP remains *** expression and function of MST4 in macrophages of ITP patients and THP-1 cells,and of a macrophage-specific Mst4−/−(Mst4ΔM/ΔM)ITP mouse model were *** phagocytic assays,RNA sequencing(RNA-seq)analysis,immunofluorescence analysis,coimmunoprecipitation(co-IP),mass spectrometry(MS),bioinformatics analysis,and phosphoproteomics analysis were performed to reveal the underlying *** expression levels of the MST4 gene were elevated in the expanded M1-like macrophages of ITP patients,and this elevated expression of MST4 was restored to basal levels in patients with remission after high-dose dexamethasone *** expression of the MST4 gene was significantly elevated in THP-1-derived M1 *** of MST4 decreased the expression of M1 macrophage markers and cytokines,and impaired phagocytosis,which could be increased by overexpression of *** a passive ITP mouse model,macrophage-specific depletion of Mst4 reduced the numbers of M1 macrophages in the spleen and peritoneal lavage fluid,attenuated the expression of M1 cytokines,and promoted the predominance of FcγRIIb in splenic macrophages,which resulted in amelioration of *** of MST4 directly inhibited STAT1 phosphorylation,which is essential for M1 polarization of *** study elucidates a critical role for MST4 kinase in the pathology of ITP and identifies MST4 kinase as a potential therapeutic target for refractory ITP.

关键词： Primary immune thrombocytopenia Mammalian sterile-20-like kinase 4(MST4) Macrophages M1 polarization Signal transducer and activator of transcription-1(STAT1)

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Yes-associated protein promotes endothelial-tomesenchymal transition of endothelial cells in choroidal neovascularization fibrosis

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International Journal of Ophthalmology(English edition) 2022年第5期15卷 701-710页

作者： Rong Zou Yi-Fan Feng Ya-Hui Xu Min-Qian Shen Xi Zhang Yuan-Zhi Yuan Department of Ophthalmology Zhongshan HospitalFudan UniversityShanghaiChina Department of Ophthalmology Xiamen BranchZhongshan HospitalFudan UniversityXiamenFujian ProvinceChina

AIM:To reveal whether and how Yes-associated protein(YAP)promotes the occurrence of subretinal fibrosis in agerelated macular degeneration(AMD).METHODS:Cobalt chloride(Co Cl2)was used in primary human umbilical vein endothelial cells(HUVECs)to induce hypoxia in ***-week-old male C57 BL/6 J mice weighing 19-25 g were used for a choroidal neovascularization(CNV)model induced by laser photocoagulation in *** levels of YAP,phosphorylated YAP,mesenchymal markers[αsmooth muscle actin(α-SMA),vimentin,and Snail],and endothelial cell markers(CD31 and zonula occludens 1)were measured by Western blotting,quantitative real-time PCR,and immunofluorescence *** molecules YC-1(Lificiguat,a specific inhibitor of hypoxia-inducible factor 1α),CA3(CIL56,an inhibitor of YAP),and XMU-MP-1(an inhibitor of Hippo kinase MST1/2,which activates YAP)were used to explore the underlying ***:Co Cl2 increased expression of mesenchymal markers,decreased expression of endothelial cell markers,and enhanced the ability of primary HUVECs to proliferate and ***-1 suppressed hypoxia-induced endothelialto-mesenchymal transition(End MT).Moreover,hypoxia promoted total expression,inhibited phosphorylation,and enhanced the transcriptional activity of ***-MP-1 enhanced hypoxia-induced End MT,whereas CA3 elicited the opposite *** of YAP,α-SMA,and vimentin were upregulated in the laser-induced CNV ***,silencing of YAP by vitreous injection of small interfering RNA targeting YAP could reverse these ***:The findings reveal a critical role of the hypoxia-inducible factor-1α(HIF-1α)/YAP signaling axis in End MT and provide a new therapeutic target for treatment of subretinal fibrosis in AMD.

关键词： endothelial-to-mesenchymal transition Yes-associated protein hypoxia-inducible factor-1α choroidal neovascularization age-related macular degeneration

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Burden of mental disorders and risk factors in the Western Pacific region from 1990 to 2021

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World Journal of Psychiatry 2025年第1期15卷 93-105页

作者： Ya-Xin Xu Xiao-Xuan Niu Wen-Chang Jia Jing Wen Xue-Lin Cheng Yan Han Ming-Hui Peng Jing Zhou Yao Liu Sun-Fang Jiang Xiao-Pan Li Department of Health Management Centre Zhongshan HospitalFudan UniversityShanghai 200030China Department of General Practice Zhongshan HospitalFudan UniversityShanghai 200030China Department of Nutrition Zhongshan HospitalFudan UniversityShanghai 200032China School of Public Health Fudan UniversityShanghai 200032China

BACKGROUND The burden of mental disorders(MD)in the Western Pacific Region(WPR)re-mains a critical public health concern,with substantial variations across demogra-phics and *** To analyze the burden of MD in the WPR from 1990 to 2021,along with associated risk factors,to reveal changing trends and emerging *** We used data from the Global Burden of Disease 2021,analyzing prevalence,incidence,and disability-adjusted life years(DALYs)of MD from 1990 to *** methods included age-standardisation and uncertainty analysis to address variations in population structure and data *** Between 1990 and 2021,the prevalence of MD rose from 174.40 million cases[95%uncertainty interval(UI):160.17-189.84]to 234.90 million cases(95%UI:219.04-252.50),with corresponding DALYs increasing from 22.8 million(95%UI:17.22-28.79)to 32.07 million(95%UI:24.50-40.68).During this period,the burden of MD shifted towards older age *** and anxiety disorders were predominant,with females showing higher DALYs for depressive and anxiety disorders,and males more affected by conduct disorders,attention-deficit hyperactivity disorder,and autism spectrum ***,New Zealand,and Malaysia reported the highest burdens,whereas Vietnam,China,and Brunei Darussalam reported the ***,childhood sexual abuse and bullying,and intimate partner violence emerged as significant risk *** This study highlights the significant burden of MD in the WPR,with variations by age,gender,and *** coronavirus disease 2019 pandemic has exacerbated the situation,emphasizing the need for a coordinated response.

关键词： Mental disorders Western pacific region Global Burden of Disease Risk factors Disability-adjusted life years

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World Journal of Clinical Cases 2022年第24期10卷 8490-8505页

作者： Shi-Hao Guan Xin-Yu Wang Ping Shang Qian-Cheng Du Ming-Zhi Li Xiao Xing Bin Yan Department of General Surgery The Qingpu Branch of Zhongshan Hospital Affiliated to Fudan UniversityShanghai 201700China Department of General Surgery Shanghai Fourth People’s Hospital Affiliated to Tongji University School of MedicineShanghai 200434China Department of General Surgery Zhongshan-xuhui HospitalFudan UniversityShanghai 200030China

BACKGROUND Pyroptosis is an inflammatory form of programmed cell death,which has been shown to be related to the prognosis of many ***,its role in gastric cancer(GC)is not fully *** To evaluate the expression of pyroptosis-related genes in GC and its correlation with *** We constructed prognostic multigene markers of differentially expressed genes associated with pyroptosis by least absolute contraction and selection operator Cox *** risk model was analyzed by Kaplan-Meier curve,two-sided log-rank test and functional enrichment *** Sixty-three pyroptosis-related genes were differentially expressed in tumor tissues and adjacent nontumor *** on these differentially expressed genes,5 gene signature were constructed and all GC patients were classified into two risk ***-Meier survival curve showed that the overall survival(OS)of patients in the high-risk group was significantly lower than that of the low-risk *** Cox regression analyses showed that the risk score was an independent risk factor for *** operating characteristic curve analysis confirmed the predictive ability of the *** validation indicated increased OS in the low-risk *** immune function and immune cell scores of the high-risk group were generally higher than those of the low-risk *** Pyroptosis-related genes play a significant role in tumor immune *** novel model,which contains 5 pyroptosis-related genes,is an independent predicting factor for OS in GC patients,and may help to evaluate the prognosis of GC.

关键词： Gastric cancer Pyroptosis Gene signature Overall survival

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Robot-assisted one-stage resection of rectal cancer with liver and lung metastases

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World Journal of Gastroenterology 2015年第9期21卷 2848-2853页

作者： Jian-Min Xu Ye Wei Xiao-Ying Wang Hong Fan Wen-Ju Chang Li Ren Wei Jiang Jia Fan Xin-Yu Qin zhongshan hospital Fudan University

The Da Vinci Surgical System may help to overcome some of the difficulties of laparoscopy for complicated abdominal *** authors of this article present a case of robot-assisted, one-stage radical resection of three tumors, including robotic anterior resection for rectal cancer, segmental hepatectomy for liver metastasis, and wedge-shaped excision for lung metastasis.A 59-year-old man with primary rectal cancer and liver and lung metastases was operated upon with a one-stage radical resection approach using the Da Vinci Surgical *** and anastomosis of rectal cancer were performed extracorporeally afterundocking the *** procedure was successfully completed in 500 *** surgical complications occurred during the intervention and postoperative period, and no conversion to laparotomy or additional trocars were *** the best of our knowledge, this is the first case of simultaneous resection for rectal cancer with liver and lung metastases using the Da Vinci Surgery System to be *** procedure is feasible and safe and its main advantages for patient are avoiding repeated operation, reducing surgical trauma, shortening recovery time, and early implementation of postoperative adjuvant therapy.

关键词： Robotic surgery Minimally invasive colorectal surg

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Senegenin suppresses hepatocellular carcinoma by regulating O-GlcNAcylation

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World Journal of Gastrointestinal Oncology 2024年第9期16卷 3994-4005页

作者： Xiang Zhang Li-Qiong Wang Zhi-Yong Liu Department of Traditional Chinese Medicine Qingpu Branch of Zhongshan Hospital Affiliated to Fudan UniversityShanghai 201700China Department of Hepatology Longhua Hospital Affiliated to Shanghai University of Traditional Chinese MedicineShanghai 200032China

BACKGROUND Based on current knowledge,hepatocellular carcinoma(HCC)is a condition with numerous etiologies and risk ***,the pathogenesis of HCC remains *** To investigate the roles of senegenin and O-GlcNAcylation in the growth and metastasis of *** The levels of O-linked N-acetylglucosamine transferase(OGT)and O-GlcNAcylation in HCC cells and tissues were detected using western blot *** effects of senegenin and O-GlcNAcylation on the proliferation of HCC cells were investigated in vitro using cell counting kit-8 and clonogenic *** potential effects of senegenin and O-GlcNAcylation on HCC metastasis were examined using the transwell migration assay.O-GlcNAcylation levels were altered via drug treatment and lentiviral infection,and western blot analysis was used to detect proteins involved in various *** Western blot analysis revealed that OGT and O-GlcNAcylation levels were significantly elevated in HCC tissues and cells.O-GlcNAcylation levels in HCC cells were significantly altered by drug treatment and lentiviral *** increase in the glycosylation level was linked to enhanced proliferation,invasiveness,clonogenicity,and metastatic potential of cancer cells.O-GlcNAcylation induced by senegenin was found to slow the proliferation and migration of HCC *** levels of proteins involved in nuclear factor-kappa B(NF-κB)and c-Jun N-terminal kinase(JNK)pathways,which are associated with endoplasmic reticulum stress,were *** Senegenin lowers O-GlcNAcylation levels,decreases OGT expression,and inhibits cancer cell growth and metastasis by regulating proteins involved in NF-κB and JNK pathways.

关键词： Senegenin O-GlcNAcylation Liver cancer Pathogenesis Metastasis

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Membrane Aging as the Real Culprit of Alzheimer's Disease:Modification of a Hypothesis

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Neuroscience Bulletin 2018年第2期34卷 369-381页

作者： Qiujian Yu Chunjiu Zhong Department of Neurology Zhongshan Hospital Fudan University

Our previous studies proposed that Alzheimer’s disease(AD) is a metabolic disorder and hypothesized that abnormal brain glucose metabolism inducing multiple pathophysiological cascades contributes to AD pathogenesis. Aging is one of the great significant risk factors for AD. Membrane aging is first prone to affect the function and structure of the brain by impairing glucose *** presume that risk factors of AD, including genetic factors(e.g., the apolipoprotein E ε4 allele and genetic mutations) and non-genetic factors(such as fat, diabetes,and cardiac failure) accelerate biomembrane aging and lead to the onset and development of the disease. In this review,we further modify our previous hypothesis to demonstrate‘‘membrane aging’’ as an initial pathogenic factor that results in functional and structural alterations of membranes and, consequently, glucose hypometabolism and multiple pathophysiological cascades.

关键词： Alzheimer’s disease Membrane aging Amyloid-β Thiamine

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Contrast-enhanced ultrasound in diagnosis of gallbladder adenoma

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Hepatobiliary & Pancreatic Diseases International 2015年第2期14卷 201-207页

作者： Hai-Xia Yuan Jia-Ying Cao Wen-Tao Kong Han-Sheng Xia Xi Wang Wen-Ping Wang Department of Ultrasound Zhongshan Hospital Fudan University

BACKGROUND：Gallbladder adenoma is a pre-cancerous neoplasm and needs surgical *** is difficult to differentiate adenoma from other gallbladder polyps using imaging *** study aimed to illustrate characteristics of contrast-enhanced ultrasound（CEUS）and its diagnostic value in gallbladder ***： Thirty-seven patients with 39 gallbladder adenoma- toid lesions （maximal diameter _〉10 mm and without metastasis） were enrolled in this study. Lesion appearances in conventional ultrasound and CEUS were documented. The imaging features were compared individuaUy among gallbladder cholesterol polyp, gallbladder adenoma and malignant lesion. RESULTS： Adenoma lesions showed iso-echogenicity in ul- trasound, and an eccentric enhancement pattern, ＂fast-in and synchronous-out＂ contrast enhancement pattern and homo- geneous at peak-time enhancement in CEUS. The homogenic- ity at peak-time enhancement showed the highest diagnostic ability in differentiating gallbladder adenoma from cholesterol polyps. The sensitivity, specificity, positive predictive value, negative predictive value, accuracy and Youden index were 100%, 90.9%, 92.9%, 100%, 95.8% and 0.91, respectively. The characteristic of continuous gallbladder wall shown by CEUS had the highest diagnostic ability in differentiating adenoma from malignant lesion （100%, 86.7%, 86.7%, 100%, 92.9% and 0.87, respectively）. The characteristic of the eccentric enhance- ment pattern had the highest diagnostic ability in differenti- ating adenoma from cholesterol polyp and malignant lesion, with corresponding indices of 69.2%, 88.5%, 75.0%, 85.2%, 82.1% and 0.58, ***： CEUS is valuable in differentiating gallbladder adenoma from other gallbladder polyps （〉_10 mm in diameter）. Homogeneous echogenicity on peak-time enhancement, a continuous gallbladder wall, and the eccentric enhancement pattern are important indicators of gallbladder adenoma on CEUS.

关键词： contrast-enhanced ultrasound discontinuity gallbladder wall eccentric enhancement gallbladder adenoma homogeneous echogenicity

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