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Genetic Engineered Ultrasound-Triggered Injectable Hydrogels for Promoting Bone Reconstruction

Research 2024年第2期2023卷 431-447页

作者： Zhenyu Zhao Huitong Ruan Aopan Chen Wei Xiong Mingzhu Zhang Ming Cai Wenguo Cui Department of Orthopaedics Shanghai Tenth People's HospitalSchool of MedicineTongji University No.301 Middle Yanchang RoadShanghai 200072China Department of Orthopaedics Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint DiseasesShanghai Institute of Traumatology and OrthopaedicsRuijin HospitalShanghai Jiao Tong University Schoolof Medicine197 Rujin 2nd RoadShanghai 200025China Department of Foot and Ankle Surgery Beijing Tongren HospitalCapital Medical University1 Dongjiao MinxiangBeijing 100730China

Genetic engineering technology can achieve specific gene therapy for a variety of diseases, but the current strategy still has some flaws, such as a complex system, single treatment, and large implantation trauma. Herein, the genetic engineering injectable hydrogels were constructed by ultrasonic technology for the first time to realize in vivo ultrasound-triggered in situ cross-linking and cell gene transfection, and finally complete in situ gene therapy to promote bone reconstruction. First, ultrasound-triggered calcium release was used to activate transglutaminase and catalyze the transamidation between fibrinogen. Simultaneously, liposome loaded with Zinc-finger E-box-binding homeobox 1 (ZEB1) gene plasmid (Lip-ZEB1) was combined to construct an ultrasound-triggered in situ cross-linked hydrogels that can deliver Lip-ZEB1. Second, ultrasound-triggered injectable hydrogel introduced ZEB1 gene plasmid into endothelial cell genome through Lip-ZEB1 sustained release, and then acted on the ZEB1/Notch signal pathway of cells, promoting angiogenesis and local bone reconstruction of osteoporosis through genetic engineering. Overall, this strategy provides an advanced gene delivery system through genetic engineered ultrasound-triggered injectable hydrogels.

关键词： sustained release linking

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Insights into the history and tendency of glycosylation and digestive system tumor:A bibliometric-based visual analysis

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World Journal of Gastrointestinal Oncology 2024年第3期16卷 1059-1075页

作者： Jie Jiang Zai Luo Ren-Chao Zhang Yue-Ling Wang Jun Zhang Ming-Yu Duan Zheng-Jun Qiu Chen Huang Department of Gastrointestinal Surgery Shanghai General HospitalShanghai Jiao Tong University School of MedicineShanghai 200080China Jiangnan University Wuxi School of medicine Wuxi 214122Jiangsu ProvinceChina Department of education Shanghai General HospitalShanghai Jiao Tong University School of MedicineShanghai 200080China

BACKGROUND Glycosylation,a commonly occurring post-translational modification,is highly expressed in several tumors,specifically in those of the digestive system,and plays a role in various cellular pathophysiological *** the importance and detection methods of glycosylation in digestive system tumors have garnered increasing attention in recent years,bibliometric analysis of this field remains *** present study aims to identify the developmental trends and research hotspots of glycosylation in digestive system *** To find and identify the developmental trends and research hotspots of glycosylation in digestive system *** We obtained relevant literature from the Web of Science Core Collection and employed VOSviewer 1.6.19 and CiteSpace(version 6.1.R6)to perform bibliometric *** A total of 2042 documents spanning from 1978 to the present were analyzed,with the research process divided into three phases:the period of obscurity(1978-1990),continuous development period(1991-2006),and the rapid outbreak period(2007-2023).These documents were authored by researchers from 66 countries or regions,with the United States and China leading in terms of publication *** Celso A had the highest number of publications,while Pinho SS was the most cited ***-occurrence analysis revealed the most popular keywords in this field are glycosylation,expression,cancer,colorectal cancer,and pancreatic ***,the Journal of Proteome Research was the most prolific journal in terms of publications,while the Journal of Biological Chemistry had the most *** The bibliometric analysis shows current research focus is primarily on basic research in this ***,future research should aim to utilize glycosylation as a target for treating tumor patients.

关键词： Glycosylation Cancer Digestive system Bibliometric analysis CiteSpace VOS viewer

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Anti-metabolic agent pegaspargase plus PD-1 antibody sintilimab for first-line treatment in advanced natural killer T cell lymphoma

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Signal Transduction and Targeted Therapy 2024年第4期9卷 1665-1674页

作者： Jie Xiong Shu Cheng Xiao Gao Shan-He Yu Yu-Ting Dai Xin-Yun Huang Hui-Juan Zhong Chao-Fu Wang Hong-Mei Yi Hao Zhang Wei-Guo Cao Rong Li Wei Tang Yan Zhao Peng-Peng Xu Li Wang Wei-Li Zhao shanghai Institute of Hematology State Key Laboratory of Medical GenomicsNational Research Center for Translational Medicine at ShanghaiRuijin Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghaiChina Department of Nuclear medicine Shanghai Ruijin HospitalShanghai Jiao Tong University School of MedicineShanghaiChina Department of Pathology Shanghai Ruijin HospitalShanghai Jiao Tong University School of MedicineShanghaiChina Department of Otolaryngology Shanghai Rujin HospitalShanghai Jiao Tong University School of MedicineShanghaiChina Department of Radiation Shanghai Ruijin HospitalShanghai Jiao Tong University School of MedicineShanghaiChina Department of Hematology Navy Medical Center of PLAShanghaiChina Pole de Recherches Sino-Francais en Science du Vivant et Genomique Laboratory of Molecular PathologyShanghaiChina

Natural killer T cell lymphoma(NKTCL)is highly aggressive,with advanced stage patients poorly responding to intensive *** explore effective and safe treatment for newly diagnosed advanced stage NKTCL,we conducted a phase ll study of anti-metabolic agent pegaspargase plus PD-1 antibody sintilimab(NCT04096690).Twenty-two patients with a median age of 51 years(range,24-74)were enrolled and treated with induction treatment of pegaspargase 2500 IU/m2 intramuscularly on day 1 and sintilimab 200 mg intravenously on day 2 for 6 cycles of 21 days,followed by maintenance treatment of sintilimab 200 mg for 28 cycles of 21 *** complete response and overall response rate after induction treatment were 59%(95%Cl,43-79%)and 68%(95%Cl,47-84%),*** a median follow-up of 30 months,the 2 year progression-free and overall survival rates were 68%(95%Cl,45-83%)and 86%(95%Cl,63-95%),*** most frequently grade 3/4 adverse events were neutropenia(32%,n=7)and hypofibrinogenemia(18%,n=4),which were manageable and led to no discontinuation of *** proportion score of PD-L1,peripheral blood high-density lipoprotein cholesterol,and apolipoprotein A-l correlated with good response,while PD-1 on tumor infiltrating lymphocytes and peripheral Treg cells with poor response to pegaspargase plus sintilimab *** conclusion,the chemo-free regimen pegaspargase plus sintilimab was effective and safe in newly diagnosed,advanced stage *** lipid profle and immunosuppressive signature contributed to treatment resistance,providing an alternative therapeutic approach dual targeting fatty acid metabolism and CTLA-4 in NKTCL.

关键词： killer metabolism lymphoma

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Surface Topological Glycosylation-Mediated Mucoadhesion of Bacteria

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Chinese Journal of Chemistry 2024年第13期42卷 1447-1455页

作者： Xiao Kuang Xiaobing Liu Ju Chen Wenyan Lv Mengmeng Zhang Huan Chen Feng Wu Jinyao Liu School of Life Sciences Shanghai UniversityShanghai 200444China shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine Institute of Molecular MedicineState Key Laboratory of Systems Medicine for CancerRenji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200127China School of Chemistry and Chemical Engineering Frontiers Science Center for Transformative Molecules and National Center for Translational MedicineShanghai Jiao Tong UniversityShanghai 200240China College of Chemistry and Materials Science Shanghai Normal UniversityShanghai 200234China

Sugar moieties present on bacterial surface serve as pivotal regulators of bacterial *** adjusting the abundance and distribution of surface sugar moieties can offer an important approach to manipulating bacterial behavior,but has been proven to be ***,surface topological glycosylation is reported to mediate the interaction of bacteria with mucous *** functionalized by sugar moieties with different branching are synthesized through iterative Michael addition and amide condensation *** a copper-catalyzed azide-alkyne cycloaddition,the resulting compounds with different branching structures can be attached onto bacterial surface that is modified with azido *** a proof-of-concept study,a set of topologically glycosylated probiotics(TGPs)is prepared using linear,two-branched,and tetra-branched compounds,*** interaction between mucin and TGPs was studied and the results demonstrate that,compared to unmodified bacteria,TGPs exhibit an enhanced adhesive capacity to mucin,which increases with the branching *** binding trend is observed in ex vivo colonic mucus adhesion experiments and bacteria glycosylated with tetra-branched compounds display the highest binding *** work proposes a chemical method to tune the abundance and distribution of sugar moieties on bacteria,providing unique significant insights into the manipulation of bacterial behavior through surface modification.

关键词： Topochemistry Bacteria Glycosylation Surface modification Mucoadhesion Click chemistry

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Decitabine induces IRF7-mediated immune responses in p53-mutated triple-negative breast cancer:a clinical and translational study

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Frontiers of medicine 2024年第2期18卷 357-374页

作者： Haoyu Wang Zhengyuan Wang Zheng Wang Xiaoyang Li Yuntong Li Ni Yan Lili Wu Ying Liang Jiale Wu Huaxin Song Qing Qu Jiahui Huang Chunkang Chang Kunwei Shen Xiaosong Chen Min Lu Department of General Surgery Comprehensive Breast Health CenterRuijin Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai200025China shanghai Institute of Hematology State Key Laboratory of Medical GenomicsNational Research Center for Translational Medicine(Shanghai)Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai200025China Department of Hematology Shanghai Institute of HematologyRuijin Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai200025China Department of Hematology Shanghai Jiao Tong University Affiliated Sixth People’s HospitalShanghai200025China

p53 is mutated in half of cancer ***,no p53-targeting drugs have been ***,we reposition decitabine for triple-negative breast cancer(TNBC),a subtype with frequent p53 mutations and extremely poor *** a retrospective study on tissue microarrays with 132 TNBC cases,DNMT1 overexpression was associated with p53 mutations(P=0.037)and poor overall survival(OS)(P=0.010).In a prospective DEciTabinE and Carboplatin in TNBC(DETECT)trial(NCT03295552),decitabine with carboplatin produced an objective response rate(ORR)of 42%in 12 patients with stage IV *** the 9 trialed patients with available TP53 sequencing results,the 6 patients with p53 mutations had higher ORR(3/6 vs.0/3)and better OS(16.0 vs.4.0 months)than the patients with wild-type *** a mechanistic study,isogenic TNBC cell lines harboring DETECT-derived p53 mutations exhibited higher DNMT1 expression and decitabine sensitivity than the cell line with wild-type *** the DETECT trial,decitabine induced strong immune responses featuring the striking upregulation of the innate immune player IRF7 in the p53-mutated TNBC cell line(upregulation by 16-fold)and the most responsive patient with *** integrative studies reveal the potential of repurposing decitabine for the treatment of p53-mutated TNBC and suggest IRF7 as a potential biomarker for decitabine-based treatments.

关键词： p53 mutation triple-negative breast cancer decitabine DNMT1 IRF7 innate immune response

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The real-world study of the clinical characteristics,diagnosis,and treatment of advanced pancreatic cancer in China

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Journal of Pancreatology 2024年第1期7卷 1-9页

作者： Jiujie Cui Qihan Fu Xiaobing Chen Yanling Wang Qi Li Feng Wang Zhihua Li Guanghai Dai Yusheng Wang Hongmei Zhang Houjie Liang Jun Zhou Liu Yang Fenghua Wang Leizhen Zheng Xiaofeng Chen Ping Gong Jiang Liu Ying Yuan Lin Wang Yuejuan Cheng Jun Zhang Yuhong Zhou Weijian Guo Xianbao Zhan Zhengyun Zou Da Li Shan Zeng Enxiao Li Zhiwei Li Zan Teng Dan Cao Jie Kan Jianping Xiong Ming Quan Jiayu Yao Haiyan Yang Liwei Wang Department of Medical Oncology Renji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghaiChina Department of Medical Oncology The First Affiliated HospitalCollege of MedicineZhejiang UniversityHangzhouChina Department of Medical Oncology Affiliated Cancer Hospital of Zhengzhou UniversityHenan Cancer HospitalZhengzhouChina Department of Medical Oncology Shanghai General HospitalShanghai Jiao Tong UniversityShanghaiChina Department of Medical Oncology The First Affiliated Hospital of Zhengzhou UniversityZhengzhouChina Department of Medical Oncology Sun Yat-sen Medical Hospital Sun Yat-sen UniversityGuangzhouChina Medical Oncology Chinese PLA General HospitalBeijingChina Department of Gastrointestinal Oncology Shanxi Provincial Cancer HospitalAffiliated to Shanxi Medical UniversityTaiyuanChina Department of clinical Oncology Xijing HospitalAir Force Medical UniversityXi’anChina Department of Oncology and Southwest Cancer Center Southwest HospitalThird Military Medical University(Army Military Medical University)ChongqingChina Department of Gastrointestinal Oncology Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing)Peking University Cancer Hospital&InstituteBeijingChina Cancer Center Department of Medical OncologyZhejiang Provincial People’s HospitalPeople’s Hospital of Hangzhou Medical CollegeHangzhouChina Department of Medical Oncology Sun Yat-sen University Cancer CenterState Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer MedicineGuangzhouGuangdongChina Oncology Department Xin Hua Hospital Affiliated to Shanghai JiaoTong University School of MedicineShanghaiChina Department of Oncology the First Affiliated Hospital with Nanjing Medical UniversityNanjingChina Department of Oncology The First Affiliated HospitalSchool of MedicineShihezi UniversityShiheziChina Department of Oncology People’s Hospital of Xinjiang Uygur Autonomous RegionXinjiangChina Department of Medical Oncology t

Objective:Real-world diagnostic and treatment data for pancreatic cancer in China are *** such,the present study investigated the clinical characteristics,diagnosis,and treatment of advanced pancreatic cancer(including locally advanced and metastatic disease)in the Hospital-based Advanced Pancreatic Cancer Cohort in China of the China Pancreas Data Center ***:A total of 5349 Chinese patients with advanced pancreatic cancer were identified from a *** entire course of real-world pancreatic cancer management was ***:The proportion of patients with advanced pancreatic cancer was higher among males than females(62.4%vs 37.6%,respectively).Patients typically had a history of hypertension(30.8%),diabetes(21.6%),and cholangitis(20.2%).Abdominal pain(51.6%),abdominal distension(27.1%),jaundice(20.1%),and weight loss(16.3%)were the main symptoms observed in patients with advanced pancreatic cancer in this *** carbohydrate antigen(CA)19-9 is one of the most common tumor *** the present study,2562 patients underwent first-line *** median progression-free survival(PFS)for patients undergoing first-line therapy was 4.1 *** major options for first-line therapy included gemcitabine(GEM)plus S-1(GS/X)(23.4%),nab-paclitaxel plus GEM(AG)(18.1%),oxaliplatin,irinotecan,and leucovorin-modulated fluorouracil(FOLFIRINOX;11.9%),nab-paclitaxel plus S-1(AS)(8.9%),and GEM combined with oxaliplatin/cisplatin(GEMOX/GP)(7.6%).The AS and GS/X regimens were associated with the highest PFS ***:This is the first study to report multicenter,real-world data regarding advanced pancreatic cancer in *** revealed that real-world treatment options differed from guideline recommendations,and PFS was shorter than that in previously reported *** intelligent follow-up systems and standardizing diagnosis and treatment of pancreatic cancer is recommended.

关键词： Advanced pancreatic cancer China Pancreas Data Center Chinese First-line regimens Real-world study

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Approaches to promoting bone marrow mesenchymal stem cell osteogenesis on orthopedic implant surface

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World Journal of Stem Cells 2020年第7期12卷 545-561页

作者： Shi-Cheng Huo Bing Yue Department of Bone and Joint Surgery Renji HospitalShanghai Jiao Tong University School of MedicineShanghai 200011China

Bone marrow-derived mesenchymal stem cells(BMSCs)play a critical role in the osseointegration of bone and orthopedic ***,osseointegration between the Ti-based implants and the surrounding bone tissue must be improved due to titanium’s inherent *** modification stands out as a versatile technique to create instructive biomaterials that can actively direct stem cell ***,we summarize the current approaches to promoting BMSC osteogenesis on the surface of titanium and its *** will highlight the utilization of the unique properties of titanium and its alloys in promoting tissue regeneration,and discuss recent advances in understanding their role in regenerative *** aim to provide a systematic and comprehensive review of approaches to promoting BMSC osteogenesis on the orthopedic implant surface.

关键词： Bone marrow mesenchymal stem cells Osseointegration Orthopedic implant Biofunctionalization

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C30F12.4 influences oogenesis, fat metabolism, and lifespan in C. elegans

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Protein & Cell 2016年第10期7卷 714-721页

作者： Lu Wang Fei Xu Guishuan Wang Xiaorong Wang Ajuan Liang Hefeng Huang Fei Sun International Peace Maternity & Child Health Hospital Shanghai Key laboratory for Reproductive Medicine School of Medicine Institute of Embryo-Fetal Original Adult Disease Shanghai Jiaotong University Shanghai 200030 China School of Life Sciences University of Science and Technology of China Hefei 230026 China

Reproduction, fat metabolism, and longevity are inter- twined regulatory axes; recent studies in C. elegans have provided evidence that these processes are directly coupled. However, the mechanisms by which they are coupled and the reproductive signals modu- lating fat metabolism and lifaspan are poorly under- stood. Here, we find that an oogenesis-enriched gene, c30PI2.4, is specifically expressed and located in germ cells and early embryos; when the gene is knocked out, oogenesis is disrupted and brood size is decreased. In addition to the reproductive phenotype, we find that the loss of c30f12.4 alters fat metabolism, resulting in decreased fat storage and smaller lipid droplets. Mean- while, c30f12.4 mutant worms display a shortened lifaspan. Our results highlight an important role for c30f12.4 in regulating reproduction, fat homeostasis, and aging in C. elegans, which helps us to better understand the relationship between these processes.

关键词： C30F12.4 oogenesis fat metabolism,lifespan

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Low-carbohydrate diets lead to greater weight loss and better glucose homeostasis than exercise: a randomized clinical trial

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Frontiers of medicine 2021年第3期15卷 460-471,F0004页

作者： Lingli Cai Jun Yin Xiaojing Ma Yifei Mo Cheng Li Wei Lu Yuqian Bao Jian Zhou Weiping Jia Department of Endocrinology and Metabolism Shanghai Clinical Center for DiabetesShanghai Diabetes InstituteShanghai Key Laboratory of Diabetes MellitusShanghai Jiao Tong University Affiliated Sixth People’s HospitalShanghai 200233China

Lifestyle interventions,including dietary adjustments and exercise,are important for obesity *** study enrolled adults with overweight or obesity to explore whether either low-carbohydrate diet(LCD)or exercise is more effective in metabolism ***-five eligible subjects were randomly divided into an LCD group(n=22)and an exercise group(EX,n=23).The subjects either adopted LCD(carbohydrate intake<50 g/day)or performed moderate-to-vigorous exercise(≥30 min/day)for 3 *** the interventions,LCD led to a larger weight loss than EX(−3.56±0.37 kg vs.−1.24±0.39 kg,P<0.001),as well as a larger reduction in fat mass(−2.10±0.18 kg vs.−1.25±0.24 kg,P=0.007)and waist circumference(−5.25±0.52 cm vs.−3.45±0.38 cm,P=0.008).Both interventions reduced visceral and subcutaneous fat and improved liver steatosis and insulin *** decreased in both two groups,whereas low-density lipoprotein cholesterol increased in the LCD group but decreased in the EX *** glycemic parameters,including serum glycated albumin,mean sensor glucose,coefficient of variability(CV),and largest amplitude of glycemic excursions,substantially declined in the LCD *** CV slightly decreased after *** pilot study suggested that the effects of LCD and exercise are similar in alleviating liver steatosis and insulin *** with exercise,LCD might be more efficient for weight loss and glucose homeostasis in people with obesity.

关键词： low-carbohydrate diet obesity nonalcoholic fatty liver disease continuous glucose monitoring mean sensor glucose

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Altered intra- and inter-network brain functional connectivity in upper-limb amputees revealed through independent component analysis

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Neural Regeneration Research 2022年第12期17卷 2725-2729页

作者： Bing-Bo Bao Hong-Yi Zhu Hai-Feng Wei Jing Li Zhi-Bin Wang Yue-Hua Li Xu-Yun Hua Mou-Xiong Zheng Xian-You Zheng Department of Orthopedic Surgery Shanghai Jiao Tong University Affiliated Sixth People’s HospitalShanghaiChina Institute of Diagnostic and Interventional Radiology Shanghai Jiao Tong University Affiliated Sixth People’s HospitalShanghaiChina Department of Traumatology and Orthopedics Yueyang HospitalShanghai University of Traditional Chinese MedicineShanghaiChina

Although cerebral neuroplasticity following amputation has been observed, little is understood about how network-level functional reorganization occurs in the brain following upper-limb amputation. The objective of this study was to analyze alterations in brain network functional connectivity(FC) in upper-limb amputees(ULAs). This observational study included 40 ULAs and 40 healthy control subjects;all participants underwent resting-state functional magnetic resonance imaging. Changes in intra-and inter-network FC in ULAs were quantified using independent component analysis and brain network FC analysis. We also analyzed the correlation between FC and clinical manifestations, such as pain. We identified 11 independent components using independent component analysis from all subjects. In ULAs, intra-network FC was decreased in the left precuneus(precuneus gyrus) within the dorsal attention network and left precentral(precentral gyrus) within the auditory network;but increased in the left Parietal_Inf(inferior parietal, but supramarginal and angular gyri) within the ventral sensorimotor network, right Cerebelum_Crus2(crus Ⅱ of cerebellum) and left Temporal_Mid(middle temporal gyrus) within the ventral attention network, and left Rolandic_Oper(rolandic operculum) within the auditory network. ULAs also showed decreased inter-network FCs between the dorsal sensorimotor network and ventral sensorimotor network, the dorsal sensorimotor network and right frontoparietal network, and the dorsal sensorimotor network and dorsal attention network. Correlation analyses revealed negative correlations between inter-network FC changes and residual limb pain and phantom limb pain scores, but positive correlations between inter-network FC changes and daily activity hours of stump limb. These results show that post-amputation plasticity in ULAs is not restricted to local remapping;rather, it also occurs at a network level across several cortical regions. This observation provides addit

关键词： amputation functional connectivity functional magnetic resonance imaging independent component analysis neuroimaging phantom pain phantom sensation resting-state networks

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