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Insulin-like growth factor 2 targets IGF1R signaling transduction to facilitate metastasis and imatinib resistance in gastrointestinal stromal tumors

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World Journal of Gastrointestinal Oncology 2024年第8期16卷 3585-3599页

作者： De-Gang Li Jia-Peng Jiang Fan-Ye Chen Wei Wu Jun Fu Gong-He Wang Yu-Bo Li Department of Gastrointestinal and Anorectal Surgery The First Affiliated Hospital of Guangxi University of Chinese MedicineNanning 530023Guangxi Zhuang Autonomous RegionChina

BACKGROUND Gastrointestinal stromal tumors(GISTs)are typical gastrointestinal tract *** is the first-line therapy for GIST *** resistance limits the long-term effectiveness of *** regulatory effect of insulin-like growth factor 2(IGF2)has been confirmed in various cancers and is related to resistance to chemotherapy and a worse *** To further investigate the mechanism of IGF2 specific to *** IGF2 was screened and analyzed using Gene Expression Omnibus(GEO:GSE225819)*** IGF2 knockdown or overexpression by transfection,the phenotypes(proliferation,migration,invasion,apoptosis)of GIST cells were characterized by cell counting kit 8,Transwell,and flow cytometry *** used western blotting to evaluate pathway-associated and epithelial-mesenchymal transition(EMT)-associated *** injected transfected cells into nude mice to establish a tumor xenograft model and observed the occurrence and metastasis of *** Data from the GEO indicated that IGF2 expression is high in GISTs,associated with liver metastasis,and closely related to drug *** cells with high expression of IGF2 had increased proliferation and migration,invasiveness and *** of IGF2 significantly inhibited those *** addition,OEIGF2 promoted GIST metastasis in vivo in nude ***2 activated IGF1R signaling in GIST cells,and IGF2/IGF1R-mediated glycolysis was required for GIST with liver *** cells with IGF2 knockdown were sensitive to imatinib treatment when IGF2 overexpression significantly raised imatinib ***,2-deoxy-D-glucose(a glycolysis inhibitor)treatment reversed IGF2 overexpressionmediated imatinib resistance in *** IGF2 targeting of IGF1R signaling inhibited metastasis and decreased imatinib resistance by driving glycolysis in GISTs.

关键词： Insulin-like growth factor 2 Gastrointestinal stromal tumors IGF1R Glycolysis Imatinib resistance

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Comprehensive analysis of the protein phosphatase 2A regulatory subunit B56ε in pan-cancer and its role and mechanism in hepatocellular carcinoma

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World Journal of Gastrointestinal Oncology 2024年第2期16卷 475-492页

作者： Hong-Mei Wu Yuan-Yuan Huang Yu-Qiu Xu Wei-Lai Xiang Chang Yang Ru-Yuan Liu Di Li Xue-Feng Guo Zheng-Bao Zhang Chun-Hua Bei Sheng-Kui Tan Xiao-Nian Zhu guangxi Key Laboratory of Environmental Exposomics and Entire Lifecycle Health Guilin Medical UniversityGuilin 541199Guangxi Zhuang Autonomous RegionChina

BACKGROUND B56εis a regulatory subunit of the serine/threonine protein phosphatase 2A,which is abnormally expressed in tumors and regulates various tumor cell *** present,the application of B56εin pan-cancer lacks a comprehensive analysis,and its role and mechanism in hepatocellular carcinoma(HCC)are still *** Cancer Genome Atlas,Genotype-Tissue Expression,Gene Expression Profiling Interactive Analysis,and Tumor Immune Estimation Resource databases were used to analyze B56εexpression,prognostic mutations,somatic copy number alterations,and tumor immune characteristics in 33 *** relationships between B56εexpression levels and drug sensitivity,immuno-therapy,immune checkpoints,and human leukocyte antigen(HLA)-related genes were further *** Set Enrichment Analysis(GSEA)was performed to reveal the role of B56εin *** Cell Counting Kit-8,plate cloning,wound healing,and transwell assays were conducted to assess the effects of B56εinterference on the malignant behavior of HCC *** In most tumors,B56εexpression was upregulated,and high B56εexpression was a risk factor for adrenocortical cancer,HCC,pancreatic adenocarcinoma,and pheochromocytoma and paraganglioma(all P<0.05).B56εexpression levels were correlated with a variety of immune cells,such as T helper 17 cells,B cells,and *** was a positive correlation between B56εexpression levels with immune checkpoint genes and HLA-related genes(all P<0.05).The expression of B56εwas negatively correlated with the sensitivity of most chemotherapy drugs,but a small number showed a positive correlation(all P<0.05).GSEA analysis showed that B56εexpression was related to the cancer pathway,p53 downstream pathway,and interleukin-mediated signaling in *** of B56εexpression in HCC cells inhibited the proliferation,migration,and invasion capacity of tumor *** Tip:The expression of protein phosphatase 2A(PP2A)subunit B56εis up-regulated in most tumors,and its high

关键词： B56ε Prognosis Tumor microenvironment Immune infiltration Immunotherapy Hepatocellular carcinoma

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Overlapping infections of Mycobacterium canariasense and Nocardia farcinica in an immunocompetent patient:A case report

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World Journal of Clinical Cases 2024年第12期12卷 2079-2085页

作者： Hai-Yan Huang Kun-Peng Bu Jin-Wei Liu Jing Wei Department of Comprehensive Internal Medicine The Affiliated Cancer Hospital of Guangxi Medical UniversityNanning 530021Guangxi Zhuang Autonomous RegionChina Department of Doppler Ultrasound The Second Nanning People's HospitalNanning 530021Guangxi Zhuang Autonomous RegionChina

BACKGROUND Infections by non-tuberculous mycobacteria(NTM)have become more common in recent *** canariasense(***)was first reported as an opportunistic pathogen in 2004,but there have been very few case reports since *** is a genus of aerobic and Gram-positive bacilli,and these species are also opportunistic pathogens and in the Mycobacteriales *** methods for diagnosis of NTM are *** next-generation sequencing(mNGS)can rapidly detect many pathogenic microorganisms,even rare *** NTM and Nocardia infections occur in immunocompromised patients with atypical clinical *** are no previous reports of infection by *** and Nocardia farcinica(***),especially in immunocompetent *** case report describes an immunocompetent 52-year-old woman who had overlapping infections of ***,***,and Candida parapsilosis(***)based on *** SUMMARY A 52-year-old woman presented with a productive cough and chest pain for 2 wk,and recurrent episodes of moderate-grade fever for 1 *** received antibiotics for 1 wk at a local hospital,and experienced defervescence,but the productive cough and chest pain *** collected samples of a lung lesion and alveolar lavage fluid for *** lung tissue was positive for ***,***,and ***,and the alveolar lavage fluid was positive for *** diagnosis was pneumonia,and application of appropriate antibiotic therapy cured the *** Etiological diagnosis is critical for patients with infectious *** can identify rare and novel pathogens,and does not require a priori knowledge.

关键词： Overlapping infection Mycobacterium canariasense Nocardia farcinica Metagenomic next-generation sequencing technology Case report

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Deep electrical structures of Qinzhou-Fangcheng Junction Zone in guangxi and seismogenic environment of the 1936 Lingshan M6^(3/4)earthquake

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Science China Earth Sciences 2024年第2期67卷 584-603页

作者： Bin ZHOU Chunheng YAN Yan ZHAN Xiangyu SUN Sha LI Xiang WEN Yajun MO Yongdong YUAN Yuan YUAN Meili HUANG Earthquake Agency of guangxi zhuang autonomous region Nanning530022China state Key Laboratory of Earthquake Dynamics Institute of GeologyChina Earthquake AdministrationBeijing100029China guangxi Geophysical Survey Institute Liuzhou545005China

The tectonic position of the southwest section of the Qinzhou Bay-Hangzhou Bay Tectonic Junction Zone(QHTJZ)can be determined by examining the Qinzhou-Fangcheng Junction Zone(QFJZ)in *** zone is significant because it was the location of the largest earthquake ever recorded in the inland region of South China,specifically the 1936 Lingshan M6^(3/4)earthquake in ***,this region serves as an optimal location for researching the origins of intraplate earthquakes in South *** study presents a display of a broadband magnetotelluric(MT)prospecting profile that traverses the guangxi QFJZ and the Lingshan earthquake zone,extending from the northwest(NW)to the southeast(SE).A resistivity structure model was generated using three-dimensional(3D)inversion technology along the *** main faults in QFJZ were analyzed in terms of their deep extension forms and tectonic *** analysis was performed by integrating the results obtained from geology,gravity,wave velocity ratio,Global Position System(GPS),and geothermal *** results showed that(1)the Dongzhong-Xiaodong fault(DXf),the eastern Fangcheng-Lingshan fault(FLf2),and the eastern Hepu-Beiliu fault(HBf2)were all trans-crustal deep faults,and crust-mantle ductile shear zones developed in the deep *** electrical boundary zones,DXf and HBf2,were *** inclined towards the northwest,while HBf2 inclined towards the *** FangchengLingshan fault(FLf)exhibits a tectonic style resembling a“flower”shape in the upper *** the deeper section,it is characterized by an electrical boundary zone that gradually slopes towards the southeast direction.(2)The Hunan-guangxi Passive Continental Margin(HGPCM)on the NW side of DXf had a stratified resistivity structure and relatively stable Bouguer gravity anomalies,which conformed to the quasi-craton tectonic attribute of the local failure at the southeastern margin of the Yangtze Block(YB).The southeastern side of this bloc

关键词： South China Block Qinzhou-Fangcheng Junction Zone Magnetotelluric 1936 Lingshan M6^(3/4)earthquake Deep seismogenic environment

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Thymic carcinoid with multiple bone metastases:A case report

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World Journal of Clinical Cases 2024年第13期12卷 2275-2280页

作者： Chun-Qiao Chen Ming-Yue Huang Min Pan Qiu-Qiu Chen Fei-Fei Wei Hui Huang Department of Oncology People’s Hospital of GuilinGuilin 541000Guangxi Zhuang Autonomous RegionChina

BACKGROUND Thymic carcinoid(TC)is a rare entity among anterior mediastinal *** are neuroendocrine carcinomas that constitute approximately 2%–5%of all thymic epithelial *** SUMMARY The study reported a rare TC with multiple bone metastases.A 77-year-old man presented with a 2-month history of lower back pain and weight loss of 5 *** resonance imaging scans revealed damage to the lumbar spine,sacrocaudal vertebrae and iliac crest,suggesting bone metastasis;computed tomography(CT)scan of the thorax showed a calcified anterior mediastinal mass;positron emission tomography-CT demonstrated multiple abnormal bone signals;and laboratory work-up showed no endocrine ***-needle aspiration biopsy revealed predominantly single small,round to oval cells with scant cytoplasm and some loose clusters,suggesting endocrine *** pathological diagnosis was atypical carcinoid,which tend to originate from the thymus and was classified as intermediate-highly *** patient underwent anlotinib-targeted ***(12 mg)was administered daily for 2 wk,after which the patient was allowed to rest for 21 ***-up CT after one year demonstrated that the tumor had shrunk by approximately 29%after *** has a long stable disease benefit of more than 2.5 *** These findings demonstrated that anlotinib is a promising treatment regimen for patients with TC and multiple bone metastases.

关键词： Thymic carcinoid Anlotinib Multitargeted tyrosine kinase inhibitor Bone metastasis Case report

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Potential and application of abortive transcripts as a novel molecular marker of cancers

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World Journal of Experimental Medicine 2024年第2期14卷 53-61页

作者： Tian-Miao Zhang Xiao-Nian Zhu Shao-Wei Qin Xue-Feng Guo Xue-Kun Xing Li-Feng Zhao Sheng-Kui Tan guangxi Key Laboratory of Environmental Exposomics and Entire Lifecycle Health Guilin Medical UniversityGuilin 541199Guangxi Zhuang Autonomous RegionChina School of Leisure and Health Guilin Tourism UniversityGuilin 541006Guangxi Zhuang Autonomous RegionChina

Abortive transcript(AT)is a 2-19 nt long non-coding RNA that is produced in the abortive initiation *** initiation was found to be closely related to RNA polymerase through in vitro ***,the distribution of AT length and the scale of abortive initiation are correlated to the promoter,discriminator,and transcription initiation sequence,and can be affected by transcription elongation *** plays an important role in the occurrence and development of various *** we summarize the discovery of AT,the factors responsible for AT formation,the detection methods and biological functions of AT,to provide new clues for finding potential targets in the early diagnosis and treatment of cancers.

关键词： Abortive transcript Abortive initiation RNA polymerase Transcription Tumor marker

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Plasma metabolites and risk of myocardial infarction:a bidirectional Mendelian randomization study

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Journal of Geriatric Cardiology 2024年第2期21卷 219-231页

作者： Dong-Hua LI Qiang WU Jing-Sheng LAN Shuo CHEN You-Yi HUANG Lan-Jin WU Zhi-Qing QIN Ying HUANG Wan-Zhong HUANG Ting ZENG Xin HAO Hua-Bin SU Qiang SU Department of Cardiovascular Medicine Minzu Hospital of Guangxi Zhuang Autonomous RegionGuangxiChina Senior Department of Cardiology the Sixth Medical CenterChinese PLA General HospitalBeijingChina Library of Graduate School Chinese PLA General HospitalBeijingChina Department of Cardiology Jiangbin Hospital of Guangxi Zhuang Autonomous RegionGuangxiChina Health Management Institute the Second Medical CenterChinese PLA General HospitalBeijingChina

BACKGROUND Myocardial infarction(MI)is a critical cardiovascular event with multifaceted etiology,involving several genetic and environmental *** is essential to understand the function of plasma metabolites in the development of MI and unravel its complex *** This study employed a bidirectional Mendelian randomization(MR)approach to investigate the causal relationships between plasma metabolites and MI *** used genetic instruments as proxies for plasma metabolites and MI and conducted MR analyses in both directions to assess the impact of metabolites on MI risk and vice *** addition,the large-scale genome-wide association studies datasets was used to identify genetic variants associated with plasma metabolite(1400 metabolites)and MI(20,917 individuals with MI and 440,906 individuals without MI)*** variance weighted was the primary method for estimating causal *** estimates are expressed as beta coefficients or odds ratio(OR)with 95%*** We identified 14 plasma metabolites associated with the occurrence of MI(P<0.05),among which 8 plasma metabolites[propionylglycine levels(OR=0.922,95%CI:0.881–0.965,P<0.001),gamma-glutamylglycine levels(OR=0.903,95%CI:0.861–0.948,P<0.001),hexadecanedioate(C16-DC)levels(OR=0.941,95%CI:0.911–0.973,P<0.001),pentose acid levels(OR=0.923,95%CI:0.877–0.972,P=0.002),X-24546 levels(OR=0.936,95%CI:0.902–0.971,P<0.001),glycine levels(OR=0.936,95%CI:0.909–0.964,P<0.001),glycine to serine ratio(OR=0.930,95%CI:0.888–0.974,P=0.002),and mannose to trans-4-hydroxyproline ratio(OR=0.912,95%CI:0.869–0.958,P<0.001)]were correlated with a decreased risk of MI,whereas the remaining 6 plasma metabolites[1-palmitoyl-2-arachidonoyl-GPE(16:0/20:4)levels(OR=1.051,95%CI:1.018–1.084,P=0.002),behenoyl dihydrosphingomyelin(d18:0/22:0)levels(OR=1.076,95%CI:1.027–1.128,P=0.002),1-stearoyl-2-docosahexaenoyl-GPE(18:0/22:6)levels(OR=1.067,95%CI:1.027–1.109,P=0.001),alpha-ketobutyrate levels(OR=1.108,95%

关键词： infarction alterations diagnosis

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Glymphatic function and its influencing factors in different glucose metabolism states

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World Journal of Diabetes 2024年第7期15卷 1537-1550页

作者： Bin Tian Chen Zhao Jia-Li Liang Hui-Ting Zhang Yi-Fan Xu Hui-Lei Zheng Jia Zhou Jiang-Nian Gong Shu-Ting Lu Zi-San Zeng Department of Radiology The First Affiliated Hospital of Guangxi Medical UniversityNanning 530021Guangxi Zhuang Autonomous RegionChina Magnetic Resonance Research Collaboration Siemens HealthineersGuangzhou 510620Guangdong ProvinceChina Magnetic Resonance Research Collaboration Siemens Healthineers Ltd.Wuhan 430071Hubei ProvinceChina Department of Health Management The First Affiliated Hospital of Guangxi Medical UniversityNanning 530021Guangxi Zhuang Autonomous RegionChina Department of Endocrinology The First Affiliated Hospital of Guangxi Medical UniversityNanning 530021Guangxi Zhuang Autonomous RegionChina

BACKGROUND Dysfunction of the glymphatic system in the brain in different stages of altered glucose metabolism and its influencing factors are not well *** To investigate the function of the glymphatic system and its clinical correlates in patients with different glucose metabolism states,the present study employed diffusion tensor imaging along the perivascular space(DTI-ALPS)*** Sample size was calculated using the pwr package in R *** crosssectional study enrolled 22 patients with normal glucose metabolism(NGM),20 patients with prediabetes,and 22 patients with type 2 diabetes mellitus(T2DM).A 3.0T magnetic resonance imaging was used to evaluate the function of the glymphatic *** mini-mental state examination(MMSE)was used to assess general cognitive *** DTI-ALPS index of bilateral basal ganglia and the mean DTI-ALPS index was ***,the correlation between DTI-ALPS and clinical features was *** The left-side,right-side,and mean DTI-ALPS index in the T2DM group were significantly lower than that in the NGM *** right-side DTI-ALPS and mean DTI-ALPS index in the T2DM group were significantly lower than those in the prediabetes ***-ALPS index lateralization was not *** MMSE score in the T2DM group was significantly lower than that in the NGM and prediabetes *** controlling for sex,the left-side DTI-ALPS and mean DTI-ALPS index in the prediabetes group were positively correlated with 2-hour postprandial blood glucose level;the left-side DTI-ALPS index was negatively correlated with total cholesterol and low-density lipoprotein *** right-side DTI-ALPS and mean DTI-ALPS index were negatively correlated with the glycosylated hemoglobin level and waist-to-hip ratio in the prediabetes *** left-side,right-side,and mean DTI-ALPS index in the T2DM group were positively correlated with *** left-side and mean DTIALPS index in the T2DM group were negatively

关键词： Glymphatic system Prediabetes Type 2 diabetes mellitus Magnetic resonance imaging Diffusion tensor imaging along the perivascular space

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Complement activation targeted inhibitor C2-FH ameliorates acetaminophen-induced liver injury in mice

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World Journal of Hepatology 2024年第10期16卷 1188-1198页

作者： Chun-Mei Li Tian Sun Mou-Jie Yang Zhi Yang Qing Li Jia-Lin Shi Chong Zhang Jun-Fei Jin guangxi Key Laboratory of Molecular Medicine in Liver Injury and Repair the Affiliated Hospital of Guilin Medical UniversityGuilin 541001Guangxi Zhuang Autonomous RegionChina guangxi Health Commission Key Laboratory of Basic Research in Sphingolipid Metabolism Related Diseases the Affiliated Hospital of Guilin Medical UniversityGuilin 541001Guangxi Zhuang Autonomous RegionChina China-United states Lipids in Health and Disease Research Center Guilin Medical UniversityGuilin 541001Guangxi Zhuang Autonomous RegionChina Laboratory of Hepatobiliary and Pancreatic Surgery the Affiliated Hospital of Guilin Medical UniversityGuilin 541001Guangxi Zhuang Autonomous RegionChina

BACKGROUND Complement activation is recognized as an important factor in the progression of liver damage caused by acetaminophen(APAP).However,the role of the complement inhibitor C2-FH in APAP-induced liver injury remains *** To explore C2-FH in protecting against APAP-induced liver injury by inhibiting complement *** A model of APAP-induced liver injury was used to study the protective effect of C2-FH on liver injury.C2-FH was administered through intraperitoneal injection 30 minutes after APAP *** detected the effects of C2-FH on liver function,inflammatory response and complement ***,RNA-sequencing(RNA-Seq)analysis was conducted to understand the mechanism through which C2-FH provides protection against APAP-induced liver *** C2-FH inhibited the increase in serum alanine aminotransferase activity,aspartate aminotransferase activity and lactate dehydrogenase,and reduced liver tissue necrosis caused by ***,it attenuated the inflammatory response and inhibited complement activation in APAP-induced liver ***-Seq analysis provided additional explanations for the protective role of C2-FH against APAP-induced liver *** C2-FH attenuates APAP-induced liver injury by inhibiting complement activation.

关键词： C2-FH Complement Complement activation Acetaminophen-induced liver injury Inflammation

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Pathological and physiological functional cross-talks ofα-synuclein and tau in the central nervous system

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Neural Regeneration Research 2024年第4期19卷 855-862页

作者： Mingyue Jin Shengming Wang Xiaodie Gao Zhenyou Zou Shinji Hirotsune Liyuan Sun guangxi Key Laboratory of Brain and Cognitive Neuroscience Guilin Medical University Department of Genetic Disease Research Osaka Metropolitan University Graduate School of Medicine Department of Scientific Research Brain Hospital of Guangxi Zhuang Autonomous Region

α-Synuclein and tau are abundant multifunctional brain proteins that are mainly expressed in the presynaptic and axonal compartments of neurons,*** works have revealed that intracellular deposition ofα-synuclein and/or tau causes many neurodegenerative disorders,including Alzheimer’s disease and Parkinson’s *** intense investigation,the normal physiological functions and roles ofα-synuclein and tau are still unclear,owing to the fact that mice with knockout of either of these proteins do not present apparent ***,the co-occurrence ofα-synuclein and tau aggregates was found in post-mortem brains with synucleinopathies and tauopathies,some of which share similarities in clinical ***,the direct interaction ofα-synuclein with tau is considered to promote the fibrillization of each of the proteins in vitro and in *** the other hand,our recent findings have revealed thatα-synuclein and tau are cooperatively involved in brain development in a stage-dependent *** findings indicate strong cross-talk between the two proteins in physiology and *** this review,we provide a summary of the recent findings on the functional roles ofα-synuclein and tau in the physiological conditions and pathogenesis of neurodegenerative diseases.A deep understanding of the interplay betweenα-synuclein and tau in physiological and pathological conditions might provide novel targets for clinical diagnosis and therapeutic strategies to treat neurodegenerative diseases.

关键词： alpha-synuclein microtubule-associated protein neurodegenerative disease tau

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