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Exploring the potential of extrachromosomal DNA as a novel oncogenic driver

Science China Life Sciences 2025年第1期68卷 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.

关键词： extrachromosomal DNA cancer therapy tumor heterogeneity drug resistance tumor evolution

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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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Clinical Observation on Tuina Treatment for Cervical Intervertebral Disc Herniation

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Journal of Acupuncture and Tuina Science 2010年第6期8卷 371-374页

作者：叶建国 qingpu branch of Shanghai zhongshan hospital Shanghai 201700 P. R. China

Objective： To observe the clinical effect of tuina for cervical intervertebral disc herniation. Methods： Eighty seven cases were randomized into a treatment and a control group. 39 cases in the treatment group were treated with tuina manipulation, while 48 cases in the control group were treated with combined cervical traction and medium-frequency impulse. Cases in both groups were treated 3 times a week, and 10 times constitute a course of treatment. Results： Of 39 cases in the treatment group, 22 obtained recovery, 13 obtained marked effects and 4 obtained improvement, manifesting a marked effect rate of 89.7% and an effective rate of 100.0%. Of 48 cases in the control group, 23 obtained recoveries, 17 obtained marked effects, 7 obtained improvements and 1 saw no improvement, manifesting a marked effect rate of 83.3% and an effective rate of 97.9%. There were no statistical differences in the marked effect rate and total effective rate. Cases in the treatment group were treated 17.8 times on average, while cases in the control group were treated 26.6 times on average. Conclusion： Despite the equivalent effects in the treatment of cervical intervertebral disc herniation, tuina is superior to combined traction and medium-frequency impulse in terms of a faster effect and shorter course of treatment.

关键词： Tuina Massage Traction Intervertebral Disc Displacement Neck Pain

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A controlled study on treatment of acute lumbar sprain by acupuncture at Yaotongdian(EX-UE 7) plus tuina manipulation

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Journal of Acupuncture and Tuina Science 2015年第3期13卷 194-198页

作者：叶建国 qingpu branch of Shanghai zhongshan hospital

Objective：To observe the clinical effects of acupuncture at Yaotongdian （EX-UE 7） plus the oblique Ban-pulling manipulation for acute lumbar sprain. Methods：A total of 180 patients were divided into an observation group and a control group by drawing lots. The 98 cases in the observation group were treated by puncturing Yaotongdian （EX-UE 7） plus the oblique Ban-pulling manipulation. The 82 cases in the control group were only treated by the oblique Ban-pulling manipulation. After the two groups were treated continuously for three sessions, the therapeutic effects were observed. Results：In the observation group, 96 cases were cured and 2 cases were improved; the curative rate was 98.0% and the total effective rate was 100%. In the control group, 76 cases were cured, 4 cases were improved and 2 cases failed; the curative rate was 92.7% and the total effective rate was 97.6%. In comparison of the curative rate and total effective rate, the differences were not statistically significant （P〉0.05）. But, the curative rate after the first treatment was higher in the observation group than that in the control group, with a significant difference between the two groups （P〈0.05）. Conclusion：The therapeutic effects were similar by acupuncture at Yaotongdian （EX-UE 7） plus oblique Ban-pulling manipulation and by single oblique Ban-pulling manipulation for acute lumbar sprain. But, it took effect quickly by puncturing Yaotongdian （EX-UE 7） plus the oblique Ban-pulling manipulation.

关键词： Acupuncture Therapy Tuina Massage Low Back Pain Sprains and Strains

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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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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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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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25-Hydroxyvitamin D Is Associated with Islet Homeostasis in Type-2 Diabetic Patients with Abdominal Obesity

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Current Medical Science 2023年第5期43卷 919-926页

作者： Qing LI Wen ZHANG Bing HAN Yu-ying WANG Heng WAN Min ZHANG Ning-jian WANG Ying-li LU Institute and Department of Endocrinology and Metabolism Shanghai Ninth People's HospitalShanghai Jiaotong University School of MedicineShanghai 200011China Institute and Department of Endocrinology and Metabolism Qingpu Branch of Zhongshan Hospital Affiliated to Fudan UniversityShanghai 201700China

Objective Isletαcells input is essential for insulin secretion fromβ*** present study aims to investigate the association between 25-hydroxyvitamin D[25(OH)D]and islet function homeostasis in type-2 diabetes(T2D)*** A total of 4670 T2D patients from seven communities in Shanghai,China were *** anthropometric indices,biochemical parameters,serum 25(OH)D,and islet function[including C-peptide(C-p)and glucagon]were *** The fasting plasma glucose(FPG),glycated hemoglobin(HbA1c),glucagon,and C-p levels exhibited a significantly decreasing trend in T2D patients as the 25(OH)D levels ***,the population was divided into two groups:abdominal obesity and non-abdominal obesity *** adjustment,the 25(OH)D level was found to be associated with HbA1c,glucagon,and homeostasis model assessment ofβ(HOMA-β)in the non-abdominal obesity *** was a significant relationship between 25(OH)D and HbA1c,glucagon,HOMA-IR,baseline insulin or C-p in the abdominal obesity *** the abdominal obesity group,the ordinary least squares(OLS)regression and quantile regression revealed that 25(OH)D was obviously associated with glucagon and fasting C-p *** the abdominal obesity group,the moderate analysis revealed a significant interaction effect of 25(OH)D and glucagon on C-p(P=0.0124).Furthermore,the conditional indirect effect of 25(OH)D on the glucagon/C-p ratio was significantly lower at 1 standard deviation(SD)below the mean(P=0.0002),and lower at the mean of the course of diabetes(P=0.0007).Conclusion 25(OH)D was found to be negatively correlated to glucagon and C-p in T2D patients with abdominal *** 25(OH)D influenced C-p in part by influencing *** effect of 25(OH)D on the glucagon/C-p ratio in T2D patients with abdominal obesity,in terms of islet homeostasis,is influenced by the course of diabetes.

关键词： 25-hydroxyvitamin D glucagon C-peptide isletαcells isletβcells type-2 diabetes

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Recurrent undifferentiated embryonal sarcoma of the liver in adult patient treated by pembrolizumab: A case report

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World Journal of Clinical Cases 2021年第10期9卷 2281-2288页

作者： Xiao-He Yu Jian Huang Nai-Jian Ge Ye-Fa Yang Jin-Yan Zhao Department of Radioactive Intervention Eastern Hepatobiliary Surgery HospitalThe Second Military Medical UniversityShanghai 200438China zhongshan hospital qingpu branch Fudan UniversityShanghai 200092China Department of Laboratory Medicine Shanghai General HospitalShanghai Jiao Tong University School of MedicineShanghai 200080China

BACKGROUND Undifferentiated embryonal sarcoma of the liver(UESL)is a neoplasm that rarely develops in *** main treatments for UESL are upfront gross total surgical resection and adjuvant multiagent ***,we report a case of recurrent UESL in an adult treated with pembrolizumab and discuss a method to identify proper candidates for antibody of programmed cell death protein 1(anti-PD-1)*** SUMMARY A 69-year-old woman was admitted for abdominal pain that developed for 1 *** tomography showed a 16 cm mass in the right lobe of the *** hemihepatectomy and lymphadenectomy were performed,and histological diagnosis was *** months later,the patient suffered from painless obstructive jaundice,and positron emission tomography-computed tomography revealed multiple ***,percutaneous transhepatic cholangial drainage was applied to reduce jaundice,and radiofrequency ablation was used to control the lesion near the hepatic ***,the patient suffered from a serious fever caused by the *** patient received treatment with pembrolizumab,and the prescribed dosage was 2 mg/kg every 3 *** the seventh dose,positron emission tomography-computed tomography revealed that the multiple metastases had nearly *** exam was used to evaluate the disease state,and no new lesions were ***-generation sequencing and immunohistology were applied to determine the reason why the patient had such a favorable response to *** mutation burden,microsatellite instability,and programmed death ligand 1 expression can be combined to predict the effect of PD-1 antibodies. When every one of thesebiomarkers are detected in a tumor patient, the patient may be a proper candidatefor PD-1 *** Anti-PD-1 treatment for tumors needs further research to identify indications andproper biomarkers.

关键词： Undifferentiated embryonal sarcoma of the liver Pembrolizumab Programmed cell death protein 1 Tumor mutation burden Immunohistology Case report

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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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