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Pharmacological targeting cGAS/STING/NF-κB axis by tryptanthrin induces microglia polarization toward M2 phenotype and promotes functional recovery in a mouse model of spinal cord injury

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Neural Regeneration Research 2025年第11期20卷 3287-3301页

作者： Ziwei Fan Mengxian Jia Jian Zhou Zhoule Zhu Yumin Wu Xiaowu Lin Yiming Qian Jiashu Lian Xin Hua Jianhong Dong Zheyu Fang Yuqing Liu Sibing Chen Xiumin Xue Juanqing Yue Minyu Zhu Ying Wang Zhihui Huang Honglin Teng department of Orthopedics(Spine Surgery) the First Affiliated Hospital of Wenzhou Medical UniversityWenzhouZhejiang ProvinceChina School of Pharmacy Hangzhou Normal UniversityHangzhouZhejiang ProvinceChina department of Neurology The First Affiliated Hospital of Wenzhou Medical UniversityWenzhouZhejiang ProvinceChina department of pathology Affiliated Hangzhou First People’s HospitalSchool of MedicineWestlake UniversityHangzhouZhejiang ProvinceChina department of Clinical Research Center Affiliated Hangzhou First People’s HospitalSchool of MedicineWestlake UniversityHangzhouZhejiang ProvinceChina

The M1/M2 phenotypic shift of microglia after spinal cord injury plays an important role in the regulation of neuroinflammation during the secondary injury phase of spinal cord *** of shifting microglia polarization from M1(neurotoxic and proinflammatory type)to M2(neuroprotective and anti-inflammatory type)after spinal cord injury appears to be *** possesses an anti-inflammatory biological ***,its roles and the underlying molecular mechanisms in spinal cord injury remain *** this study,we found that tryptanthrin inhibited microglia-derived inflammation by promoting polarization to the M2 phenotype in *** promoted M2 polarization through inactivating the cGAS/STING/NF-κB ***,we found that targeting the cGAS/STING/NF-κB pathway with tryptanthrin shifted microglia from the M1 to M2 phenotype after spinal cord injury,inhibited neuronal loss,and promoted tissue repair and functional recovery in a mouse model of spinal cord ***,using a conditional co-culture system,we found that microglia treated with tryptanthrin suppressed endoplasmic reticulum stress-related neuronal *** together,these results suggest that by targeting the cGAS/STING/NF-κB axis,tryptanthrin attenuates microglia-derived neuroinflammation and promotes functional recovery after spinal cord injury through shifting microglia polarization to the M2 phenotype.

关键词： cGAS/STING functional recovery microglia neuroinflammation neuroprotection nuclear factor-κB polarization spinal cord injury tryptanthrin

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Ubiquitin-specific protease 1 facilitates tumor immune escape from natural killer cells and predicts the prognosis in small cell lung cancer

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Oncology Research 2025年第1期33卷 213-224页

作者： SHIQIN JIANG YICHUN TANG FENG MA YUCHUN NIU LEI SUN department of Clinical Pharmacy Shenzhen Hospital of Integrated Traditional Chinese and Western MedicineShenzhen518104China department of pathology Zhujiang HospitalSouthern Medical UniversityGuangzhou510280China department of Radiation Oncology The First People’s Hospital of FoshanFoshan528000China department of Oncology The First Affiliated Hospital of Jinan UniversityJinan UniversityGuangzhou510630China department of Oncology The First Dongguan Affiliated HospitalGuangdong Medical UniversityDongguan523721China

Objective:Small cell lung cancer(SCLC)is commonly recognized as the most fatal lung cancer *** substantial advances in immune checkpoint blockade therapies for treating solid cancers,their benefits are limited to a minority of patients with *** the present study,novel indicators for predicting the outcomes and molecular targets for SCLC treatment were ***:We conducted bioinformatics analysis to identify the key genes associated with tumor-infiltrating lymphocytes in *** functional role of the key gene identified in SCLC was determined both in vitro and in ***:A significant correlation was observed between patient survival and CD56dim natural killer(NK)cell ***,we noted that the hub gene ubiquitin-specific protease 1(USP1)is closely correlated with both CD56dim NK cells and overall survival in *** analysis revealed that USP1 is upregulated in *** addition,gene set enrichment analysis revealed that USP1 overexpression hinders NK cell-mediated immune *** co-cultivating NK-92 cells with SCLC cells,we demonstrated that NK cell cytotoxicity against SCLC could be improved either via USP1 knock-down or pharmacological ***,using a nude-mice xenograft tumor model,we noted that USP1 inhibition effectively suppressed tumor proliferation and increased the expression of NK cell-associated ***:Our study findings highlight the importance of NK cells in regulating ***1 overexpression can inhibit NK cell-mediated immunity;therefore,USP1 may serve not only as a prognostic biomarker but also as a potential molecular target of SCLC therapy.

关键词： Ubiquitin-specific protease 1(USP1) Natural killer(NK)cell Small cell lung cancer(SCLC) Prognosis Immune escape

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Kinesin family member 14 expression and its clinical implications in colorectal cancer

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World Journal of Gastrointestinal Oncology 2025年第3期17卷 299-321页

作者： Kai Qin Jia-Yuan Luo Da-Tong Zeng Wan-Ying Huang Bin Li Qi Li Yan-Ting Zhan Rong-Quan He Wei-Jian Huang Gang Chen Zu-Yuan Chen Bang-Teng Chi Yu-Xing Tang Rui-Xue Tang Hui Li department of pathology The First Affiliated Hospital of Guangxi Medical UniversityNanning 530021Guangxi Zhuang Autonomous RegionChina department of pathology Redcross Hospital of Yulin CityYulin 537000Guangxi Zhuang Autonomous RegionChina department of Medical Oncology The First Affiliated Hospital of Guangxi Medical UniversityNanning 530021Guangxi Zhuang Autonomous RegionChina department of pathology The First Affiliated Hospital of Shandong First Medical University&Shandong Provincial Qianfoshan HospitalJinan 250000Shandong ProvinceChina department of Colorectal and Anal Surgery The First Affiliated Hospital of Guangxi Medical UniversityNanning 530021Guangxi Zhuang Autonomous RegionChina

BACKGROUND Colorectal cancer(CRC)is the third most common cancer globally,causing over 900000 deaths *** factors include aging,diet,obesity,sedentary lifestyle,tobacco use,genetic predisposition,and inflammatory bowel *** current treatments,survival rates for advanced CRC remain low,highlighting the need for better therapeutic *** To evaluate both the clinical significance and the pathological implications of the Kinesin family member 14(KIF14)expression within CRC ***,this study aims to investigate the interaction between nitidine chloride(NC)and KIF14,considering their potential as therapeutic *** The expression of the KIF14 protein in CRC was analyzed using immunohistochemical *** integration of multicenter high-throughput data facilitated the calculation of the standardized mean difference(SMD)for KIF14 mRNA *** assessment of clinical and pathological impact was enhanced by analyzing combined receiver operating characteristic curves,along with measures of sensitivity,specificity,and likelihood ***,clustered regularly interspaced short palindromic repeats knockout screening for cell growth and single-cell sequencing were employed to validate the significance of KIF14 expression in *** analysis established the prognostic value of KIF14 in *** molecular mechanism of NC against CRC was elucidated through whole-genome sequencing and enrichment analysis,and molecular docking was utilized to explore the targeting affinity between NC and *** KIF14 was highly expressed in 208 CRC *** from 17 platforms involving 2436 CRC samples and 1320 noncancerous colorectal tissue controls indicated that KIF14 expression was significantly higher in CRC samples,with an SMD of 1.92(95%CI:1.49-2.35).The area under the curve was 0.94(95%CI:0.92-0.96),with a sensitivity of 0.85(95%CI:0.78-0.90)and a specificity of 0.90(95%CI:0.85-0.93).The positive and negative l

关键词： Colorectal cancer Kinesin family member 14 Nitidine chloride Molecular docking Standardized mean difference

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Heterochronic gastric adenosquamous carcinoma combined with colonic adenoma:A case report

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World Journal of Gastrointestinal Oncology 2025年第3期17卷 418-423页

作者： Gui-Jiang Liu Xiao-Yi Long Fei Zhang Tao Ren Xun Xia department of Neurosurgery Clinical Medical College and the First Affiliated Hospital of Chengdu Medical CollegeChengdu 610500Sichuan ProvinceChina department of pathology Clinical Medical College and the First Affiliated Hospital of Chengdu Medical CollegeChengdu 610500Sichuan ProvinceChina department of Oncology The First Affiliated Hospital of Chengdu Medical CollegeChengdu 610500Sichuan ProvinceChina

BACKGROUND Metachronous gastric cancer usually refers to a tumor that occurs in the stomach more than half a year after esophageal cancer surgery,and metastasis of primary esophageal cancer should be *** are few reports of metachronous gastric adenosquamous carcinoma with signet ring cell carcinoma combined with early tubular adenoma of the colon after esophageal cancer surgery,which has a high degree of *** is also the reason for the poor treatment *** SUMMARY A 54-year-old male patient was admitted to the hospital with“dysphagia obstruction”.Seven years ago,the patient was diagnosed with well-differentiated squamous cell carcinoma in the middle esophagus(T4N1M0 stage)and left gastric lymph node *** the final resection of the esophageal cancer,no residual cancer tissue was found in the esophageal and gastric *** patient’s medical history 7 years ago(preoperative gastroscopy and other examinations)revealed no gastric *** with the patient’s history,the diagnosis of recurrent esophageal cancer was made on this *** final pathological results were surprising:Metachronous gastric adenosquamous carcinoma with signet ring cell carcinoma combined with early tubular adenoma of the *** the high malignancy of the tumor,the complexity of the second operation,and many complications,the patient received *** He had a history of esophageal cancer *** should be performed simultaneously to avoid missed diagnosis and misdiagnosis.

关键词： Heterochronic tumor Gastric adenosquamous carcinoma Colonic adenoma Esophageal cancer Signet ring cell carcinoma Case report

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Long noncoding RNA LINC01106 promotes lung adenocarcinoma progression via upregulation of autophagy

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Oncology Research 2025年第1期33卷 171-184页

作者： GENGYUN SUN YIPING ZHENG JIANFENG CAI JIE GAO LIE DONG XIANGBIN ZHANG YINGHUI HUANG department of Respiratory and Critical Care Medicine The First Affiliated Hospital of Anhui Medical UniversityHefei230022China department of Respiratory and Critical Care Medicine Nanping First Hospital Affiliated to Fujian Medical UniversityNanping353006China

Background:Long noncoding RNA,LINC01106 exhibits high expression in lung adenocarcinoma(LUAD)tumor tissues,but its functional role and regulatory mechanism in LUAD cells remain ***:LINC01106 expression was analyzed in LUAD tissues and its functional impact on LUAD cells was *** cells were silenced with sh-LINC01106 and injected into nude mice to investigate tumor *** downstream transcription factors and molecular mechanism were determined using the Human transcription factor database(TFDB)database and Gene Expression Profiling Interactive Analysis(GEPIA)***,the impact of linc01106 on autophagy was analyzed by determining the expression of autophagy-related genes(ATGs)in LUAD ***:Our results showed that LINC01106 exhibited upregulation in both LUAD tissues and cell *** silencing of LINC01106 demonstrated a suppressive effect on tumorigenesis in a xenograft mouse model of ***,LINC01106 was found to recruit TATA-binding protein-associated factor 15(TAF15),an RNA-binding protein,thereby enhancing the mRNA stability of TEA domain transcription factor 4(TEAD4).In turn,TEAD4 served as a transcription factor that bound to the LINC01106 promoter and regulated its *** assays indicated that LINC01106 promoted autophagy in LUAD cells by upregulating the expression of autophagy-related genes(ATGs).The silencing of LINC01106 in LUAD cells inhibited autophagy,and cell proliferation,and promoted apoptosis,which all were effectively reversed by ATG5 ***:Overall,LINC01106,transcriptionally activated by TEAD4,interacts with TAF15 to promote the stability of TEAD4 and upregulates the expression of ATGs,promoting malignancy of LUAD cells.

关键词： LINC01106 TAF15 TEAD4 ATG5 Lung adenocarcinoma(LUAD) Non-small cell lung cancer(NSCLC)

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Unveiling expression patterns,mechanisms,and therapeutic opportunities of transmembrane protein 106C:From pan-cancers to hepatocellular carcinoma

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World Journal of Gastrointestinal Oncology 2025年第2期17卷 144-162页

作者： Jian-Di Li Rong-Quan He Yi-Wu Dang Zhi-Guang Huang Dan-Dan Xiong Lu Zhang Xiu-Fang Du Gang Chen department of pathology The First Affiliated Hospital of Guangxi Medical UniversityNanning 530021Guangxi Zhuang Autonomous RegionChina department of Medical Oncology The First Affiliated Hospital of Guangxi Medical UniversityNanning 530021Guangxi Zhuang Autonomous RegionChina

BACKGROUND Although transmembrane protein 106C(TMEM106C)has been elucidated to be overexpressed in cancers,its underlying mechanisms have not yet been fully *** To investigate the expression levels and molecular mechanisms of TMEM106C across 34 different cancer types,including liver hepatocellular carcinoma(LIHC).METHODS We analyzed TMEM106C expression patterns in pan-cancers using microenvironment cell populations counter to evaluate its association with the tumor *** set enrichment analysis was conducted to identify molecular pathways related to *** immunoprecipitation followed by sequencing(ChIP-seq)analysis was conducted to identify upstream transcriptional regulators of *** LIHC,we examined mRNA profiles,performed in-house quantitative polymerase chain reaction,immunohistochemistry,and constructed a co-expression gene *** assays,including cell counting kit-8,cell cycle,apoptosis,migration,and invasion,were *** effect of nitidine chloride(NC)on LIHC xenograft was evaluated through RNA sequencing and molecular ***,potential therapeutic agents targeting TMEM106C were *** TMEM106C was significantly overexpressed in 27 different cancer types and presaged poor prognosis in four of these types,including *** pan-cancers,TMEM106C was inversely correlated to the abundances of immune and stromal ***,TMEM106C was significantly linked to cell cycle and DNA replication pathways in ***-seq analysis predicted CCCTC-binding factor as a pivotal transcriptional factor targeting the TMEM106C gene in *** analysis showed that TMEM106C was upregulated in 4657 LIHC compared with 3652 normal liver tissue[combined standardized mean difference=1.31(1.09,1.52)].Inhouse LIHC samples verified the expression status of *** TMEM106C expression signified worse survival conditions in LIHC patients treated with sorafenib,a tyrosin

关键词： Transmembrane protein 106C Pan-cancers Liver hepatocellular carcinoma Molecular biology Nitidine chloride

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Clinical significance of Ki-67 in patients with lung adenocarcinoma in situ complicated by type 2 diabetes

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World Journal of Diabetes 2025年第2期16卷 114-122页

作者： Ke Chen Ge Wang Jing-Cheng Hu Ying-Yi Zhou Hai-Tao Ma department of Thoracic Surgery The First Affiliated Hospital of Soochow UniversitySuzhou 215000Jiangsu ProvinceChina department of Endocrine The First Affiliated Hospital of Soochow UniversitySuzhou 215000Jiangsu ProvinceChina

BACKGROUND The increasing number of type 2 diabetes mellitus(T2DM)patients leads to higher rates of morbidity and mortality related to lung *** To investigate the utility of the proliferating cell nuclear antigen Ki-67 in patients with lung adenocarcinoma in situ(AIS)complicated by *** One hundred patients with AIS and T2DM(group A),100 patients with AIS alone(group B),and 60 patients with benign lung lesions(group C)admitted to the department of Thoracic Surgery and Endocrinology of the first affiliated hospital of Soochow University from November 2021 to December 2022 were ***-67 expression was compared among the *** Group A had significantly higher levels of fasting plasma glucose(FPG),total cholesterol(TC),total triglyceride,low-density lipoprotein cholesterol,glycosylated hemoglobin(HbA1c),and insulin than groups B and C(P<0.01).Meanwhile,group B had higher insulin levels than group C(P<0.01).Group A exhibited a significantly higher average Ki-67 positivity rate than group B(P<0.01).The Ki-67 positivity rate in group A was 86.87%,while the positivity rate in group B was 77%.Ki-67 was positively correlated with FPG(P<0.01)and HbA1c levels(P<0.01).Ki-67,FBG,insulin,HbA1c,high-density lipoprotein cholesterol and TC were independent factors for patients with AIS complicated by *** K et ***67 in patients with AIS complicated by T2DM WJD https://*** 2 February 15,2025 Volume 16 Issue 2 CONCLUSION Ki-67 expression was higher in patients with AIS complicated by T2DM than in patients with AIS ***,detecting the Ki-67 level might assist in the diagnosis of AIS in patients with T2DM.

关键词： Ki-67 Type 2 diabetes mellitus Lung adenocarcinoma in situ Immunohistochemistry Prognostic marker

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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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HNRNPC as a pan-cancer biomarker and therapeutic target involved in tumor progression and immune regulation

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Oncology Research 2025年第1期33卷 83-102页

作者： YUEZHOU ZHANG ZHAO ZHANG JINXIN DONG CHANGAN LIU department of Hepatobiliary Surgery The Second Affiliated Hospital of Chongqing Medical UniversityChongqing400016China department of Hepatobiliary Surgery The First Affiliated Hospital of Chongqing Medical UniversityChongqing400016China

Background:Aberrant expression of RNA-binding proteins(RBPs)has been linked to a variety of diseases,including hematological disorders,cardiovascular diseases,and multiple types of *** nuclear ribonucleoprotein C(HNRNPC),a member belonging to the heterogeneous nuclear ribonucleoprotein(hnRNP)family,plays a pivotal role in nucleic acid *** studies have underscored the significance of HNRNPC in tumorigenesis;however,its specific role in malignant tumor progression remains inadequately ***:We leveraged publicly available databases,including The Cancer Genome Atlas(TCGA),to explore the potential involvement of HNRNPC across various ***,we performed experimental validation studies focused on liver ***:Our analysis revealed that HNRNPC is overexpressed in a wide range of common malignancies,including liver and lung cancers,and is strongly linked to unfavorable ***,HNRNPC was observed to be closely linked to tumor *** immune checkpoint analysis and immune cell infiltration assessment,HNRNPC emerged as a potential target for modulating tumor ***,silencing of HNRNPC markedly inhibited the proliferation,metastasis,and infiltration of liver cancer ***:In summary,our findings highlight HNRNPC as a prognostic marker in various cancers,including liver cancer,and suggest its involvement in shaping the tumor immune *** insights offer potential avenues for improving clinical outcomes in tumors with elevated HNRNPC expression,particularly through immunotherapeutic strategies.

关键词： Heterogeneous nuclear ribonucleoprotein C(HNRNPC) Pan-cancer analysis Tumor immunity Prognostic biomarker Immunotherapeutic target Hepatocellular carcinoma

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Hemispheric asymmetries and network dysfunctions in adolescent depression:A neuroimaging study using resting-state functional magnetic resonance imaging

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World Journal of Psychiatry 2025年第2期15卷 100-108页

作者： Ying Xiong Ren-Qiang Yu Xing-Yu Wang Shun-Si Liang Jie Ran Xiao Li Yi-Zhi Xu department of Hematology Chongqing General HospitalChongqing UniversityChongqing 401147China department of Radiology The First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China department of Psychiatry The First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China

BACKGROUND Currently,adolescent depression is one of the most significant public health concerns,markedly influencing emotional,cognitive,and social *** advancements in distinguish the neurobiological substrates underlying depression,the intricate patterns of disrupted brain network connectivity in adolescents warrant further *** To elucidate the neural correlates of adolescent depression by examining brain network connectivity using resting-state functional magnetic resonance imaging(rs-fMRI).METHODS The study cohort comprised 74 depressed adolescents and 59 healthy controls aged 12 to 17 *** underwent rs-fMRI to evaluate functional connectivity within and across critical brain networks,including the visual,default mode network(DMN),dorsal attention,salience,somatomotor,and frontoparietal control *** Analyses revealed pronounced functional disparities within key neural circuits among adolescents with *** results demonstrated existence of hemispheric asymmetries characterized by enhanced activity in the left visual network,which contrasted the diminished activity in the right *** DMN facilitated increased activity within the left prefrontal cortex and reduced engagement in the right hemisphere,implicating disrupted self-referential and emotional processing ***,an overactive right dorsal attention network and a hypoactive salience network were identified,underscoring significant abnormalities in attentional and emotional regulation in adolescent *** The findings from this study underscore distinct neural connectivity disruptions in adolescent depression,underscoring the critical role of specific neurobiological markers for precise early diagnosis of adolescent *** observed functional asymmetries and network-specific deviations elucidate the complex neurobiological architecture of adolescent depression,supporting the development of targeted the

关键词： Adolescent depression Brain network connectivity Neuroimaging biomarkers Functional magnetic resonance imaging Default mode network Salience network Hemispheric asymmetry

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