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Comparative proteomic analysis of plasma exosomes reveals the functional contribution of N-acetyl-alpha-glucosaminidase to Parkinson’s disease

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Neural Regeneration Research 2025年第10期20卷 2998-3012页

作者： Yuan Zhao Yidan Zhang Xin Liu Jian Zhang Ya Gao Shuyue Li Cui Chang Xiang Liu Guofeng Yang Department of Geriatrics Second Hospital of Hebei Medical UniversityShijiazhuangHebei ProvinceChina Department of Neurosurgery The Second Hospital of Hebei Medical UniversityShijiazhuangHebei ProvinceChina

Parkinson’s disease is the second most common progressive neurodegenerative disorder,and few reliable biomarkers are available to track disease *** proteins,DNA,mRNA,and lipids carried by exosomes reflect intracellular changes,and thus can serve as biomarkers for a variety of *** this study,we investigated alterations in the protein content of plasma exosomes derived from patients with Parkinson’s disease and the potential therapeutic roles of these proteins in Parkinson’s *** a tandem mass tag-based quantitative proteomics approach,we characterized the proteomes of plasma exosomes derived from individual patients,identified exosomal protein signatures specific to patients with Parkinson’s disease,and identified N-acetyl-alpha-glucosaminidase as a differentially expressed protein.N-acetyl-alpha-glucosaminidase expression levels in exosomes from the plasma of patients and healthy controls were validated by enzyme-linked immunosorbent assay and western *** results demonstrated that the exosomal N-acetyl-alpha-glucosaminidase concentration was not only lower in Parkinson’s disease,but also decreased with increasing Hoehn-Yahr stage,suggesting that N-acetyl-alpha-glucosaminidase could be used to rapidly evaluate Parkinson’s disease ***,western blot and immunohistochemistry analysis showed that N-acetyl-alpha-glucosaminidase levels were markedly reduced both in cells treated with 1-methyl-4-phenylpyridinium and cells overexpressingα-synuclein compared with control ***,N-acetyl-alpha-glucosaminidase overexpression significantly increased cell viability and inhibitedα-synuclein expression in 1-methyl-4-phenylpyridinium-treated *** together,our findings demonstrate for the first time that exosomal N-acetyl-alpha-glucosaminidase may serve as a biomarker for Parkinson’s disease diagnosis,and that N-acetyl-alpha-glucosaminidase may reduceα-synuclein expression and 1-methyl-4-phenylpyridinium-induced n

关键词： biomarker diagnosis exosomes N-acetyl-alpha-glucosaminidase Parkinson’s disease proteomic α-synuclein

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Colony-stimulating factor 3 and its receptor promote leukocyte immunoglobulin-like receptor B2 expression and ligands in gastric

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World Journal of Gastrointestinal Oncology 2025年第2期17卷 198-210页

作者： Long Wang Qi Wu Zong-Wen Zhang Hui Zhang Hui Jin Xin-Liang Zhou Jia-Yin Liu Dan Li Yan Liu Zhi-Song Fan Department of Oncology The Fourth Hospital of Hebei Medical UniversityShijiazhuang 050011Hebei ProvinceChina

BACKGROUND Colony-stimulating factor 3(CSF3)and its receptor(CSF3R)are known to promote gastric cancer(GC)growth and ***,their effects on the immune microenvironment remain *** analysis indicated a potential link between CSF3R expression and the immunosuppressive receptor leukocyte immunoglobulin-like receptor B2(LILRB2)in *** hypothesized that CSF3/CSF3R may regulate LILRB2 and its ligands,angiopoietin-like protein 2(ANGPTL2)and human leukocyte antigen-G(HLA-G),contributing to *** To investigate the relationship between CSF3/CSF3R and LILRB2,as well as its ligands ANGPTL2 and HLA-G,in *** Transcriptome sequencing data from The Cancer Genome Atlas were analyzed,stratifying patients by CSF3R *** expressed genes and immune checkpoints were ***(IHC)was performed on GC *** analyses of CSF3R,LILRB2,ANGPTL2,and HLA-G were conducted using The Cancer Genome Atlas data and IHC *** cells were treated with CSF3,and expression levels of LILRB2,ANGPTL2,and HLA-G were measured by quantitative reverse transcriptase-polymerase chain reaction and western *** Among 122 upregulated genes in high CSF3R expression groups,LILRB2 showed the most significant *** results indicated high expression of LILRB2(63.0%),ANGPTL2(56.5%),and HLA-G(73.9%)in GC *** positive correlations existed between CSF3R and LILRB2,ANGPTL2,and HLA-G mRNA levels(P0.05).CSF3 increased LILRB2,ANGPTL2,and HLA-G expression in GC *** nuclear ribonucleoprotein H1 modulation significantly altered their expression,impacting CSF3’s regulatory *** The CSF3/CSF3R pathway may contribute to immunosuppression in GC by upregulating LILRB2 and its ligands,with heterogeneous nuclear ribonucleoprotein H1 playing a regulatory role.

关键词： Gastric cancer Immunosuppressive receptor Colony-stimulating factor 3 Colony-stimulating factor 3 receptor Leukocyte immunoglobulin-like receptor B2 Angiopoietin-like protein 2 Human leukocyte antigen-G Heterogeneous nuclear ribonucleoprotein H1

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Stir-Fried Semen Armeniacae Amarum Suppresses Aristolochic AcidⅠ-Induced Nephrotoxicity and DNA Adducts

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Chinese Journal of Integrative Medicine 2025年第2期31卷 142-152页

作者： LI Cheng-xian XIAO Xiao-he LI Xin-yu XIAO Da-ke WANG Yin-kang WANG Xian-ling ZHANG Ping LI Yu-rong NIU Ming BAI Zhao-fang School of Chinese Materia Medica Beijing University of Chinese MedicineBeijing(100102)China Department of Hepatology Military Institute of Chinese Materiathe Fifth Medical CentreGeneral Hospital of PLABeijing(100039)China National Key Laboratory of Kidney Beijing(100039)China School of Pharmacy Chengdu University of Traditional Chinese MedicineChengdu(610075)China School of Traditional Chinese Medicine Capital Medical UniversityBeijing(100069)China School of Traditional Chinese Medicine Southern Medical UniversityGuangzhou(510515)China Department of Pharmacy Medical Supplies Center of PLA General HospitalBeijing(100039)China Department of Military Patient Management the Fifth Medical Center of PLA General HospitalBeijing(100039)China Department of Hematology the Fifth Medical Center of Chinese PLA General HospitalBeijing(100071)China

Objective:To investigate the protective effects of stir-fried Semen Armeniacae Amarum(SAA)against aristolochic acidⅠ(AAⅠ)-induced nephrotoxicity and DNA adducts and elucidate the underlying mechanism involved for ensuring the safe use of Asari Radix et ***:In vitro,HEK293T cells overexpressing Flag-tagged multidrug resistance-associated protein 3(MRP3)were constructed by Lentiviral transduction,and inhibitory effect of top 10 common pairs of medicinal herbs with Asari Radix et Rhizoma in clinic on MRP3 activity was verified using a self-constructed fluorescence screening *** m RNA,protein expressions,and enzyme activity levels of NAD(P)H quinone dehydrogenase 1(NQO1)and cytochrome P4501A2(CYP1A2)were measured in differentiated Hepa RG *** toxicity after inhibition of AAⅠmetabolite transport was detected using cell counting kit-8 *** vivo,C57BL/6 mice were randomly divided into 5 groups according to a random number table,including:control(1%sodium bicarbonate),AAⅠ(10 mg/kg),stir-fried SAA(1.75 g/kg)and AAⅠ+stir-fried SAA(1.75 and 8.75 g/kg)groups,6 mice in each *** 7 days of continuous gavage administration,liver and kidney damages were assessed,and the protein expressions and enzyme activity of liver metabolic enzymes NQO1 and CYP1A2 were determined ***:In vivo,combination of 1.75 g/kg SAA and 10 mg/kg AAⅠsuppressed AAⅠ-induced nephrotoxicity and reduced d A-ALI formation by 26.7%,and these detoxification effects in a dose-dependent manner(P<0.01).Mechanistically,SAA inhibited MRP3 transport in vitro,downregulated NQO1 expression in vivo,increased CYP1A2 expression and enzymatic activity in vitro and in vivo,respectively(P<0.05 or P<0.01).Notably,SAA also reduced AAⅠ-induced hepatotoxicity throughout the detoxification process,as indicated by a 41.3%reduction in the number of liver adducts(P<0.01).Conclusions:Stirfried SAA is a novel drug candidate for the suppression of AAⅠ-induced liver and kidney dam

关键词： aristolochic acidⅠ stir-fried Semen Armeniacae Amarum detoxification principles of compatibility metabolic enzymes transporters

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Tumor inflammation-specific self-amplifying fluorescent molecular probes induce an anti-tumor immune response

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Science China Chemistry 2025年第1期68卷 273-287页

作者： Shuguang Yang Lijun Hu Hong Xiao Zecong Xiao Xintao Shuai PCFM Lab of Ministry of Education School of Materials Science and EngineeringSun Yat-sen UniversityGuangzhou 510275China Nanomedicine Research Center The Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhou 510630China Department of Medical Ultrasound The Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhou 510630China Department of Ultrasound The Fifth Affiliated HospitalSun Yat-sen UniversityZhuhai 519000China

Enhancing the concentration of exogenous molecular drugs within the tumor microenvironment through enzyme-catalyzed polymerization presents a novel strategy for cancer ***,the optimization of the catalytic efficiency is often impeded by the inefficient expression of ***,we reported a self-amplifying fluorescent molecular probe,Bis-HTPICG,for photodynamic therapy(PDT)and subsequent PDT-induced *** Bis-HTP-ICG probe possesses a noticeable enzyme-catalyzed polymerization facilitated by myeloperoxidase(MPO),a crucial enzyme secreted by neutrophils at inflammation *** exposure to laser irradiation,Bis-HTP-ICG showed a high PDT efficacy,inducing an acute inflammatory response that stimulates further recruitment of neutrophils and then elevated MPO *** heightened level of MPO enhances the accumulation of the Bis-HTP-ICG via self-polymerization or binding with intratumoral proteins following MPO enzyme catalysis,instigating a self-amplifying chain reaction cycle involving Bis-HTP-ICG,neutrophils and ***,PDT efficiently incites immunogenic cell death(ICD)in tumor cells,initiating an anti-tumor immune response including dendritic cells(DCs)maturation,T cell proliferation and reprogramming of tumor-associated neutrophils(TANs).This work portrays a promising strategy for self-amplification of fluorescent molecular probes through adjustable enzyme levels,potentially offering a unique avenue to enhance the tumor accumulation of molecular drugs for improved tumor therapy.

关键词： fluorescent molecular probes self-amplifying myeloperoxidase photodynamic therapy

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Bullous pemphigoid associated with acquired hemophilia A: A case report

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World Journal of Clinical Cases 2025年第4期13卷 28-33页

作者： Su-Ye Hu Meng-Can Li Zi-Jia Hao Xu-Ya Chai Pei-Sai Li Yang Liu Li-Xia Liu Ying Xu Pan-Pan Yang Ling-E Li Department of Dermatology Shijiazhuang Traditional Chinese Medicine HospitalShijiazhuang 050051Hebei ProvinceChina Graduate School Hebei University of Traditional Chinese MedicineShijiazhuang 050051Hebei ProvinceChina Department of Pathology Shijiazhuang Traditional Chinese Medicine HospitalShijiazhuang 050051Hebei ProvinceChina

BACKGROUND Acquired hemophilia A (AHA) is a rare and potentially severe bleeding disordercaused by circulating autoantibodies against factor Ⅷ (FⅧ). In approximately50% of the patients, the condition is associated with autoimmune diseases,cancers, medication use, pregnancy, and the post-partum period. Bullous pemphigoid(BP) is a chronic autoimmune subepidermal blistering disease associatedwith tissue-bound and circulating autoantibodies against BP antigens 180 (BP180)and 230 (BP230). AHA-associated BP has a high mortality rate;hence, the understandingof this disease must *** SUMMARY A 69-year-old man presented with erythema, blisters, blood blisters, and crustsaccompanied by severe pruritus for more than 20 days, and ecchymosis andswelling on his left upper arm for 3 days. Pathological examination revealed asubepidermal blister that contained eosinophils. Laboratory tests showed that theBP180 autoantibody levels had increased, isolated activated partial thromboplastintime was notably prolonged (115.6 s), and coagulation FⅧ activity wasextremely low (hospitalfor effective treatment;however, he died after 2 *** AHA associated BP is rare, dangerous, and has a high mortality rate. Therefore, its timely diagnosis and effectivetreatment are necessary.

关键词： Bullous pemphigoid Acquired hemophilia A Acquired hemophilia A FactorⅧ Case report

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Histopathological diagnosis of microvascular invasion in hepatocellular carcinoma:Is it reliable?

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World Journal of Gastroenterology 2025年第5期31卷 105-116页

作者： Liu-Jun Li Chao-Qun Wu Fei-Le Ye Zhou Xuan Xiao-Li Zhang Jian-Ping Li Jia Zhou Zhong-Zhen Su Department of Ultrasound The First Affiliated HospitalHengyang Medical SchoolUniversity of South ChinaHengyang 421001Hunan ProvinceChina Department of Ultrasound The Fifth Affiliated Hospital of Sun Yat-sen UniversityZhuhai 519000Guangdong ProvinceChina Guangdong Provincial Key Laboratory of Biomedical Imaging and Guangdong Provincial Engineering Research Center of Molecular Imaging The Fifth Affiliated Hospital of Sun Yat-sen UniversityZhuhai 519000Guangdong ProvinceChina Department of Pathology The Fifth Affiliated Hospital of Sun Yat-sen UniversityZhuhai 519000Guangdong ProvinceChina Department of Pathology The First Affiliated HospitalHengyang Medical SchoolUniversity of South ChinaHengyang 421001Hunan ProvinceChina

BACKGROUND Microvascular invasion(MVI)is a critical prognostic factor for postoperative hepatocellular carcinoma recurrence,but the reliability of its current pathological diagnosis remains *** To evaluate the accuracy of current 7-point sampling methods and propose an optimal pathological protocol using whole-mount slide imaging(WSI)for better MVI *** We utilized 40 New Zealand white rabbits to establish VX2 liver tumor *** entire tumor-containing liver lobe was subsequently obtained,following which five different sampling protocols(A-E)were employed to evaluate the detection rate,accuracy,quantity,and distribution of MVI,with the aim of identifying the optimal sampling *** VX2 liver tumor models were successfully established in 37 rabbits,with an incidence of MVI of 81.1%(30/37).The detection rates[27%(10/37),43%(16/37),62%(23/37),68%(25/37),and 93%(14/15)]and quantity(15,36,107,125,and 395)of MVI increased significantly from protocols A to *** distribution of MVI showed fewer MVIs farther away from the tumor,but the percentage of MVI detected quantity gradually increased from 6.7%to 48.3%in the distant nonneoplastic liver tissue from protocols A to *** C was identified as the optimal sampling method by comparing them in *** sampling protocol of three consecutive interval WSIs at the tumor center(WSI3)was further screened to determine the optimal number of *** A(7-point sampling method)exhibited only 46%accuracy and a high false-negative rate of 67%.Notably,the WSI3 protocol improved the accuracy to 78%and decreased the false-negative rate to 27%.CONCLUSION The current 7-point sampling method has a high false-negative rate in MVI *** contrast,the WSI3 protocol provides a practical and effective approach to improve MVI diagnostic accuracy,which is crucial for hepatocellular carcinoma diagnosis and treatment planning.

关键词： Hepatocellular carcinoma Microvascular invasion Histopathological diagnosis Whole-mount slide imaging Sampling protocol

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Relationship between parenting stress and behavioral and emotional problems in preschool children: A mediation effect analysis

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World Journal of Psychiatry 2025年第1期15卷 128-136页

作者： Zhi-Wei Fu Yue-Jing Li Ran Yu Rui-Qing Guo Li-Xia Gao Sheng-Xia Zhao Department of Children's Health Shijiazhuang Maternity and Child Healthcare HospitalShijiazhuang 050000Hebei ProvinceChina

BACKGROUND Emotional reactions,such as anxiety,irritability,and aggressive behavior,have attracted clinical attention as behavioral and emotional problems in preschool-age *** To investigate the current status of family rearing,parental stress,and behavioral and emotional problems of preschool children and to analyze the mediating effect of the current status of family rearing on parental stress and behavioral/emo-tional *** We use convenience sampling to select 258 preschool children in the physical examination center of our hospital from October 2021 to September *** children and their parents were evaluated using a questionnaire ***'s correlation was used to analyze the correlation between child behavioral and emotional problems and parental stress and family rearing,and the structural equation model was constructed to test the mediating *** The score for behavioral/emotional problems of 258 preschool children was(27.54±3.63),the score for parental stress was(87.64±11.34),and the score for parental family rearing was(31.54±5.24).There was a positive correlation between the behavioral and emotional problems of the children and the“hostile/mandatory”parenting style;meanwhile,showed a negative correlation with the“support/participation”parenting style(all P<0.05).The intermediary effect value between the family upbringing of parents in parental stress and children's behavior problems was 29.89%.CONCLUSION Parental family upbringing has a mediating effect between parental stress and behavioral and emotional problems of *** paying attention to the behavioral and emotional problems of preschool-age children,clinical medical staff should provide correct and reasonable parenting advice to their parents to promote the mental health of preschool-age children.

关键词： Preschool children Parenting stress Children's behavioral and emotional problems Family rearing Mediating effect

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Internal transcribed spacer sequencing to explore the intrinsic composition of fungal communities in fungal esophagitis

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World Journal of Gastroenterology 2025年第7期31卷 26-38页

作者： Yi-Kang Song Lin Zheng Ai-Xin Liu Jun-Ji Ma Department of Gastroenterology The Second Hospital of Hebei Medical UniversityHebei Key Laboratory of GastroenterologyHebei Institute of GastroenterologyHebei Clinical Research Center for Digestive DiseasesShijiazhuang050000Hebei ProvinceChina

BACKGROUND Fungal esophagitis(FE)is caused by fungal invasion of the esophageal *** endoscopy,the esophageal mucosa shows edema,congestion,erosion,and ulceration,and bleeds easily when touched,and the surface of the mucosa is covered with small white spots like"bean curd residue".Clinical cases showing typical FE under endoscopic imaging but negative esophageal mucosal brush(referred to as suspected FE)have increased the difficulty and challenge of clinical diagnosis and *** present,the esophageal fungal flora of suspected case has not been thoroughly *** To characterize the fungal flora in FE,suspected FE,and the esophageal normal controls(NCs),and to identify marker species to improve detection of *** This was a case-control study.A total of 19 patients with FE,16 with suspected FE,and 10 NCs were selected by *** esophageal cell brush samples of each group were sequenced by internal transcribed spacer(ITS)1 and analyzed by *** In FE and suspected FE patients,species richness,species diversity and species evenness,as measured by the Chao1 index,Shannon index and Pielou index,were lower than in the NCs,and the comparison between the FE and NCs was the most significant(P<0.05).Compared with the NCs,the relative abundance of Candida in FE and suspected FE patients was significantly increased(P<0.001),while the relative abundance of Yarrowia was significantly decreased(P<0.05).Moreover,Yarrowia abundance in the FE group was significantly lower than in the NCs and suspected FE groups(P<0.001).The area under the curve for Candida in FE and suspected FE patients was 99.5%(P<0.05)and 81.3%(P<0.05),***,compared with FE patients,the relative abundance of Ascomycota and Candida in the esophageal flora of suspected FE patients was decreased,while the relative abundance of Yarrowia,Thermomyces and Pichia was *** ITS showed that composition of the fungal community was similar in the F

关键词： Fungal microbiota Esophagitis Candida Yarrowia Biomarker

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Rare large sigmoid hamartomatous polyp in an elderly patient with atypical Peutz-Jeghers syndrome:A case report

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World Journal of Gastrointestinal Surgery 2025年第3期17卷 406-414页

作者： Zhe-Sen Tian Xiao-Peng Ma Hong-Xun Ruan Yang Yang Ya-Lei Zhao Department of Radiotherapy The Second Hospital of Hebei Medical UniversityShijiazhuang 050000Hebei ProvinceChina Department of Anus and Intestine Surgery The Second Hospital of Hebei Medical UniversityShijiazhuang 050000Hebei ProvinceChina Department of Anus and Intestine Surgery The Third Hospital of Hebei Medical UniversityShijiazhuang 050051Hebei ProvinceChina

BACKGROUND Peutz-Jeghers(PJ)syndrome(PJS)is a rare autosomal dominant genetic disease characterized by the association of intestinal polyposis,mucosal skin pigmen-tation,and cancer *** patients have a significantly increased risk of malignant tumors in the gastrointestinal tract and extra-gastrointestinal tract,including various epithelial malignant tumors(colorectal cancer,gastric cancer,pancreatic cancer,breast cancer,and ovarian cancer,etc.).PJS is commonly seen in children and adolescents with multiple small intestinal polyps,often causing *** SUMMARY A 62-year-old male presented with intermittent left lower abdominal pain after drinking or consuming cold beverages that was accompanied by occasional *** contrast-enhanced computed tomography indicated an isolated sigmoid colon grape-like ***,the patient underwent la-paroscopic surgery,and the pathological diagnosis was PJ hamartomatous *** was not considered at the initial visit,as the patient was older,and the facial pigmentation was not ***,significant pigmentation was observed in the perineum during digital rectal ***,we observed that the patient exhibited nodular shadows in the adrenal glands computed tomo-graphy images that may be related to ***,we performed the determination of adrenal cortical hormones,but the results were not *** with skin and mucosal pigmentation and laboratory examinations,the patient was diagnosed with *** laparoscopic sigmoid colon resection,the patient's symptoms improved,and no discomfort symptoms were reported in the later *** The age of onset and lesion location of this case are different from those of typical or isolated PJS patients.

关键词： Peutz-Jeghers syndrome Sigmoid colon Large isolated colonic polyp Skin pigmentation Case report

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Characteristics and therapeutic strategies for familial gastrointestinal stromal tumors

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World Journal of Gastrointestinal Oncology 2025年第3期17卷 13-18页

作者： Yuan Liu Xiao-Feng Li Department of Gastroenterology The Fifth Affiliated Hospital of Sun Yat-sen UniversityZhuhai 519000Guangdong ProvinceChina

This editorial discusses Wang et al's article on familial gastrointestinal stromal tumors(GISTs).We read with great interest this article concerning the diagnosis,treatment,and post-treatment management of patients with familial *** actual incidence of GISTs may be underestimated due to diagnostic limitations and the long-term low-risk behavior of some *** molecular landscape of GISTs is primarily driven by mutations in the KIT and platelet-derived growth factor receptor alpha(PDGFRA)genes.A subset of GISTs without these mutations known as wild-type GISTs,may harbor other rare mutations,impacting their response to targeted ***,patients with GISTs present with nonspecific symptoms,often leading to delayed *** predispositions in familial GISTs provide insights into the genetic architecture and extragastrointestinal manifestations of *** has evolved from surgical interventions to molecular-based therapies using tyrosine kinase *** management of GISTs,especially in familial cases,requires a multidisciplinary *** of different gene mutations were reported in the same family,suggesting that incorporating genetic testing into routine clinical practice is crucial for the early identification of high-risk individuals and the implementation of tailored surveillance programs.

关键词： Gastrointestinal stromal tumors KIT mutation Platelet-derived growth factor receptor alpha mutation Wild-type gastrointestinal stromal tumor Tyrosine kinase inhibitors Familial gastrointestinal stromal tumor syndromes Molecular characteristics Targeted therapy

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