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Immune-tumor interaction dictates spatially directed evolution of esophageal squamous cell carcinoma

National Science Review 2024年第5期11卷 170-185页

作者： Yong Zhou Shanlan Mo Heyang Cui Ruifang Sun Weimin Zhang Xiaofei Zhuang Enwei Xu Hongyi Li Yikun Cheng Yongsheng Meng Meilin Liu Ting Yan Huijuan Liu Ling Zhang Bin Yang Yanfeng Xi Shubin Wang Xiaolong Cheng Shuai Cheng Li Zhihua Liu Qimin Zhan Zheng Hu Yongping Cui cancer Institute Department of Pathology Peking University Shenzhen Hospital Shenzhen Peking University-the Hong Kong University of Science and Technology(PKU-HKUST) Medical Center Institute of Cancer ResearchShenzhen Bay Laboratory Key Laboratory of Cellular Physiology of the Ministry of Education Department of Pathology Shanxi Medical University City University of Hong Kong Shenzhen Research Institute CAS Key Laboratory of Quantitative Engineering Biology Shenzhen Institute of Synthetic BiologyShenzhen Institute of Advanced TechnologyChinese Academy of Sciences Department of Surgery Faculty of Medicine The Chinese University of Hong Kong Department of Tumor Biobank Shanxi Province Cancer HospitalShanxi Hospital Affiliated to Cancer HospitalChinese Academy of Medical SciencesCancer Hospital Affiliated to Shanxi Medical University Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing) Laboratory of Molecular Oncology Peking University Cancer Hospital & Institute Research Unit of Molecular cancer Research Chinese Academy of Medical Sciences Department of Thoracic Surgery Shanxi Province Cancer HospitalShanxi Hospital Affiliated to Cancer HospitalChinese Academy of Medical SciencesCancer Hospital Affiliated to Shanxi Medical University Department of Pathology Shanxi Province Cancer HospitalShanxi Hospital Affiliated to Cancer HospitalChinese Academy of Medical SciencesCancer Hospital Affiliated to Shanxi Medical University College of Letters & Science University of California Berkeley State Key Laboratory of Molecular Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical College

Esophageal squamous cell carcinoma（ESCC） is a poor-prognostic cancer type with extensive intra-and inter-patient heterogeneity in both genomic variations and tumor microenvironment（TME）. However, the patterns and drivers of spatial genomic and microenvironmental heterogeneity of ESCC remain largely unknown. Here, we generated a spatial multi-omic atlas by whole-exome, transcriptome, and methylome sequencing of 507 tumor samples from 103 patients. We identified a novel tumor suppressor PREX2,accounting for 22% of ESCCs with frequent somatic mutations or hyper-methylation, which promoted migration and invasion of ESCC cells in vitro. Analysis of the TME and quantification of subclonal expansion indicated that ESCCs undergo spatially directed evolution, where subclones mostly originated from the tumor center but had a biased clonal expansion to the upper direction of the ***, we found upper regions of ESCCs often underwent stronger immunoediting with increased selective fitness, suggesting more stringent immune selection. In addition, distinct TMEs were associated with variable genomic and clinical outcomes. Among them, hot TME was associated with high immune evasion and subclonal heterogeneity. We also found that immunoediting, instead of CD8+T cell abundance, acts as an independent prognostic factor of ESCCs. Importantly, we found significant heterogeneity in previously considered potential therapeutic targets, as well as BRCAness characteristics in a subset of patients, emphasizing the importance of focusing on heterogeneity in ESCC targeted ***, these findings provide novel insights into the mechanisms of the spatial evolution of ESCC and inform precision therapeutic strategies.

关键词： squamous cell carcinoma heterogeneity multi-omics evolution tumor microenvironment

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Investigation of the quality of life,mental status in patients with gynecological cancer and its influencing factors

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World Journal of Psychiatry 2024年第7期14卷 1053-1061页

作者： Hai-Xia Shang Wen-Ting Ning Jin-Fen Sun Nan Guo Xin Guo Jan-Nan Zhang Hong-Xin Yu Su-Hui Wu Department of Gynaecology and Obstetrics The Third Hospital of Shanxi Medical UniversityShanxi Bethune HospitalShanxi Academy of Medical SciencesTongji Shanxi HospitalTaiyuan 030032Shanxi ProvinceChina

BACKGROUND Having a gynecological tumor or undergoing treatment can be a traumatic experience for women,as it affects their self-image and sexual relationships and can lead to psychological *** adjustment following cancer occurrence remains a key issue among the *** To examine the current status of quality of life(QoL),anxiety,and depression in patients with gynecological cancer and to analyze the factors associated with *** Data for 160 patients with gynecological malignancies treated at shanxi bethune hospital from June 2020 to June 2023 were collected and analyzed ***’QoL was assessed using the European Organization for Research on Treatment of cancer Quality of Life Questionnaire Core 30 and the Functional Assessment of cancer Therapy-General *** emotional status was evaluated using the Self-Rating Anxiety/Depression *** associated factors of anxiety and depression were *** The overall QoL score of the patients 6 months after surgery was 76.39±3.63 *** included low levels of social and emotional function and severe fatigue and *** scores for physiological,functional,emotional,social,and family well-being exhibited an upward trend following surgery compared with those before *** month after surgery,some patients experienced anxiety and depression,with an incidence of 18.75%and 18.13%,*** analysis revealed that good sleep was a protective factor against anxiety and depression in patients with gynecological tumors,whereas physical pain was a risk *** Patients with gynecological malignancies often experience anxiety and *** analyzing the factors that affect patients’QoL,effective nursing measures can be administered.

关键词： Gynecological Tumors Quality of life Anxiety Depression

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Beyond success: unveiling the hidden potential of radiotherapy and immunotherapy in solid tumors

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cancer Communications 2024年第7期44卷 739-760页

作者： Yuze Wu Ming Yi Mengke Niu Binghan Zhou Qi Mei Kongming Wu Department of Oncology Tongji Hospital of Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubeiP.R.China Department of Breast Surgery Zhejiang University School of Medicine First Affiliated HospitalHangzhouZhejiangP.R.China cancer center Shanxi Bethune HospitalShanxi Academy of Medical ScienceTongji Shanxi HospitalThird Hospital of Shanxi Medical UniversityTaiyuanShanxiP.R.China cancer center Tongji Hospital of Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubeiP.R.China

Immunotherapy,particularly with immune checkpoint inhibitors,has significantly transformed cancer *** its success,many patients struggle to respond adequately or sustain long-lasting clinical improvement.A growing consensus has emerged that radiotherapy(RT)enhances the response rate and overall efficacy of *** combining RT and immunotherapy has been extensively investigated in preclinical models and has shown promising results,establishing itself as a dynamic and thriving area of research,clinical evidence for this combination strategy over the past five years has shown both positive and disappointing results,suggesting the need for a more nuanced *** review provides a balanced and updated analysis of the combination of immunotherapy and *** summarized the preclinical mechanisms through which RT boosts antitumor immune responses andmainly focused on the outcomes of recently updated clinical trials,including those that may not have met *** investigated the optimization of the therapeutic potential of this combined strategy,including key challenges,such as fractionation and scheduling,lymph node irradiation,and ***,we offered insights into the prospects and challenges associated with the clinical translation of this combination therapy,providing a realistic perspective on the current state of research and potential future directions.

关键词： immunotherapy radiotherapy immune checkpoint inhibitor abscopal effect tumor microenvironment

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NUDT5 promotes the growth,metastasis,and Warburg effect of IDH wild-type glioblastoma multiforme cells by upregulating TRIM47

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Asian Pacific Journal of Tropical Biomedicine 2024年第2期14卷 82-92页

作者： Zi-Fa Zhang Shu-Ming Liu Neurosurgery Department Shanxi Bethune HospitalTaiyuanShanxi Province030022China shanxi Academy of Medical Sciences TaiyuanShanxi province030022China Emergency Department Taiyuan People’s HospitalTaiyuanShanxi Province030021China

Objective:To explore the regulatory mechanism of NUDT5 in glioblastoma multiforme(GBM).Methods:GEPIA database was used to predict the expressions of NUDT5 and tripartite motif family proteins 47(TRIM47)in GBM ***-qPCR and Western blot analyses were performed to examine NUDT5 expression in GBM ***-229 cell proliferation,migration as well as invasion were estimated by CCK-8,colony formation,wound healing,and Transwell assays following interference with *** assay,L-lactic acid kit,glucose detection kit,and ATP detection kit were applied for the detection of glycolysis-related ***-immunoprecipitation experiment was carried out to verify the relationship between NUDT5 and ***:GEPIA database showed that NUDT5 expression was significantly increased in GBM *** the expression of NUDT5 in GBM cells significantly suppressed the viability,proliferation,invasion,migration,and glycolysis of GBM ***,TRIM47 was highly expressed in GBM cells and interacted with *** of TRIM47 partially reversed the inhibitory effect of NUDT5 downregulation on the proliferation,metastasis,and glycolysis of GBM ***:NUDT5 promotes the growth,metastasis,and Warburg effect of GBM cells by upregulating *** NUDT5 and TRIM47 can be used as targets for GMB treatment.

关键词： Glioblastoma multiforme NUDT5 TRIM47 Growth Metastasis Warburg effect

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Methyl functionalization of trimesic acid in copper-based metal-organic framework for ammonia colorimetric sensing at high relative humidity

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Chinese Chemical Letters 2024年第6期35卷 211-215页

作者： Yuxin Wang Zhengxuan Song Yutao Liu Yang Chen Jinping Li Libo Li Jia Yao College of Chemical Engineering and Technology Shanxi Key Laboratory of Gas Energy Efficient and Clean UtilizationTaiyuan University of TechnologyTaiyuan 030024China Department of Gastroenterology Shanxi Bethune HospitalShanxi Academy of Medical SciencesTongji Shanxi HospitalThird Hospital of Shanxi Medical UniversityTaiyuan 030024China

Exhaled ammonia(NH_(3))can be used as a crucial biomarker of kidney and liver ***,the high humidity in the detection conditions remains a challenge for accurate detection by gas ***,a copper-based metal-organic framework(CH_(3)-Cu-BTC)with methyl(CH_(3)^(-))functionalization of trimesic acid was synthesized for NH_(3) colorimetric *** CH_(3)-Cu-BTC exhibited a strong response for 5 ppm NH_(3) with high selectivity under high relative humidity(75%RH).Density functional theory(DFT)simulations indicated that the NH_(3) molecules interacted more strongly with CH_(3)-Cu-BTC than H_(2)O molecules did,and the corresponding color switching was attributed to the lone-pair electron in NH_(3) changing the coordination environment of Cu^(2+)ions,leading to an obviously visible color switching response from ruby green to *** on the tailor-made pore chemistry,the precise detection of trace amounts of NH_(3) in exhaled air was realized through functionalized MOF *** strategy used in this study not only offers a new pathway for the rapid detection of low concentration NH_(3) under humid conditions,but also shows a method for early respiration diagnosis of kidney and liver diseases.

关键词： Metal-organic framework Ammonia sensing Naked-eye color switching High humidity Respiration diagnosis

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Scutellarein Ameliorated Chondrocyte Inflammation and Osteoarthritis in Rats

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Current Medical Science 2024年第2期44卷 355-368页

作者： Shao-ze JING Shu-han YANG Yun-kun QU Hai-hu HAO Hua WU Department of Orthopedics Third Hospital of Shanxi Medical UniversityShanxi Bethune HospitalShanxi Academy of Medical SciencesTongji Shanxi HospitalTaiyuan 030032China Department of Orthopedics Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China

Objective:Osteoarthritis(OA)is a degenerative joint disorder characterized by the gradual degradation of joint cartilage and local *** study aimed to investigate the anti-OA effect of scutellarein(SCU),a single-unit flavonoid compound obtained from Scutellaria barbata ***,in ***:The extracted rat chondrocytes were treated with SCU and IL-1β.The chondrocytes were divided into control group,IL-1βgroup,IL-1β+SCU 50µmol/L group,and IL-1β+SCU 100µmol/L *** of rat chondrocytes was observed by toluidine blue and safranin O ***-8 method was used to detect the cytotoxicity of ***,qRT-PCR,Western blotting,immunofluorescence,SAβ-gal staining,flow cytometry,and bioinformatics analysis were applied to evaluate the effect of SCU on rat chondrocytes under IL-1β***,anterior cruciate ligament transection(ACL-T)was used to establish a rat OA *** changes were detected by safranin O/fast green,hematoxylin-eosin(HE)staining,and ***:SCU protected cartilage and exhibited anti-inflammatory effects via multiple ***,it could enhance the synthesis of extracellular matrix in cartilage cells and inhibit its *** addition,SCU partially inhibited the nuclear factor kappa-B/mitogen-activated protein kinase(NF-κB/MAPK)pathway,thereby reducing inflammatory cytokine production in the joint ***,SCU significantly reduced IL-1β-induced apoptosis and senescence in rat chondrocytes,further highlighting its potential role in OA *** vivo experiments revealed that SCU(at a dose of 50 mg/kg)administered for 2 months could significantly delay the progression of cartilage damage,which was reflected in a lower Osteoarthritis Research Society International(OARSI)score,and reduced expression of matrix metalloproteinase 13(MMP13)in ***:SCU is effective in the therapeutic management of OA and could serve as a potential candidate f

关键词： scutellarein osteoarthritis apoptosis mitogen-activated protein kinase(MAPK) nuclear factor kappa-B(NF-κB)

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Clinical study of neutrophil-to-lymphocyte ratio and platelet-tolymphocyte ratio in hypertriglyceridemia-induced acute pancreatitis and acute biliary pancreatitis with persistent organ failure

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World Journal of Gastrointestinal Surgery 2024年第6期16卷 1647-1659页

作者： Mu-Sen Xu Jia-Le Xu Xin Gao Shao-Jian Mo Jia-Yu Xing Jia-Hang Liu Yan-Zhang Tian Xi-Feng Fu The Third hospital of shanxi Medical University Shanxi Bethune HospitalShanxi Academy of Medical SciencesTongji Shanxi HospitalTaiyuan 030032Shanxi ProvinceChina Department of Environmental Health School of Public HealthShanxi Medical UniversityTaiyuan 030032Shanxi ProvinceChina

BACKGROUND The neutrophil-to-lymphocyte ratio(NLR)and platelet-to-lymphocyte ratio(PLR)are novel inflammatory indicators that can be used to predict the severity and prognosis of various *** categorize acute pancreatitis by etiology into acute biliary pancreatitis(ABP)and hypertriglyceridemia-induced acute pancreatitis(HTGP).AIM To investigate the clinical significance of NLR and PLR in assessing persistent organ failure(POF)in HTGP and *** A total of 1450 patients diagnosed with acute pancreatitis(AP)for the first time at shanxi bethune hospital between January 2012 and January 2023 were *** patients were categorized into two groups according to the etiology of AP:ABP in 530 patients and HTGP in 241 *** collected and compared the clinical data of the patients,including NLR,PLR,and AP prognostic scoring systems,within 48 h of hospital *** The NLR(9.1 vs 6.9,P<0.001)and PLR(203.1 vs 160.5,P<0.001)were significantly higher in the ABP group than in the HTGP *** the HTGP group,both NLR and PLR were significantly increased in patients with severe AP and those with a SOFA score≥***,in the ABP group,NLR and PLR were significantly elevated in patients with severe AP,modified computed tomography severity index score≥4,Japanese Severity Score≥3,and modified Marshall score≥***,NLR and PLR showed predictive value for the development of POF in both the ABP and HTGP *** NLR and PLR vary between ABP and HTGP,are strongly associated with AP prognostic scoring systems,and have predictive potential for the occurrence of POF in both ABP and HTGP.

关键词： Acute pancreatitis Gallstone Hypertriglyceridemia Neutrophil-to-lymphocyte ratio Platelet-to-lymphocyte ratio Persistent organ failure

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Risk Factors of Depression Screened by Two-Sample Mendelian Randomization Analysis:A Systematic Review

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Biomedical and Environmental Sciences 2024年第1期37卷 85-95页

作者： WANG Han Lin XUE Yan Feng CUI Bao Qiu LIU Hong SHEN Xin Xin Shandong Provincial Research center for Bioinformatic Engineering and Technique School of Life SciencesShandong University of TechnologyZibo 255049ShandongChina shanxi Province cancer hospital/shanxi hospital Affiliated to cancer hospital Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical UniversityTaiyuan 030013ShanxiChina State Key Laboratory of Infectious Disease Prevention and Control National Institute for Viral Disease Control and PreventionChinese Center for Disease Control and PreventionBeijing 102206China

Objective This study explored the potentially modifiable factors for depression and major depressive disorder(MDD)from the MR-Base database and further evaluated the associations between drug targets with *** We analyzed two-sample of Mendelian randomization(2SMR)using genetic variant depression(n=113,154)and MDD(n=208,811)from Genome-Wide Association Studies(GWAS).Separate calculations were performed with modifiable risk factors from MR-Base for 1,001 *** MR analysis was performed by screening drug targets with MDD in the DrugBank database to explore the therapeutic targets for *** variance weighted(IVW),fixed-effect inverse variance weighted(FE-IVW),MR-Egger,weighted median,and weighted mode were used for complementary *** The potential causal relationship between modifiable risk factors and depression contained 459 results for depression and 424 for ***,the associations between drug targets and MDD showed that SLC6A4,GRIN2A,GRIN2C,SCN10A,and IL1B expression are associated with an increased risk of *** contrast,ADRB1,CHRNA3,HTR3A,GSTP1,and GABRG2 genes are candidate protective factors against *** This study identified the risk factors causally associated with depression and MDD,and estimated 10 drug targets with significant impact on MDD,providing essential information for formulating strategies to prevent and treat depression.

关键词： Risk factors Drug targets Depression Major depressive disorder Two-sample Mendelian randomization

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Exercise-induced modulation of miR-149-5p and MMP9 in LPS-triggered diabetic myoblast ER stress: licorice glycoside E as a potential therapeutic target

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Traditional Medicine Research 2024年第8期9卷 23-34页

作者： Yi Du Hong Liu Department of Critica Care Medicine Third Hospital of Shanxi Medical UniversityShanxi Bethune HospitalShanxi Academy of Medical Sciences Tongji Shanxi HospitalTaiyuan 030032China Department of ICU First Hospital of Shanxi Medical UniversityTaiyuan 030001China

Background:This study explores the relationship between endoplasmic reticulum(ER)stress and diabetes,particularly focusing on the impact of physical exercise on ER stress mechanisms and identifying potential therapeutic drugs and targets for diabetes-related *** research also incorporates traditional physical therapy perspectives,emphasizing the genomic insights gained from exercise therapy in disease management and ***:Gene analysis was conducted on the GSE168796 and GSE94717 datasets to identify ER stress-related *** interactions and immune cell correlations were mapped using GeneCard and STRING databases.A screening of 2,456 compounds from the TCMSP database was performed to identify potential therapeutic agents,with a focus on their docking *** such as luciferase reporter gene assay and RNA interference were used to examine the interactions between microRNA-149-5p and ***:The study identified 2,006 differentially expressed genes and 616 *** genes like MMP9,TNF-α,and IL1B were linked to an immunosuppressive *** glycoside E demonstrated high affinity for MMP9,suggesting its potential effectiveness in treating *** constructed miRNA network highlighted the regulatory roles of MMP9,IL1B,IFNG,and TNF-α.Experimental evidence confirmed the binding of microRNA-149-5p to MMP9,impacting apoptosis in diabetic ***:The findings highlight the regulatory role of microRNA-149-5p in managing MMP9,a crucial gene in diabetes *** glycoside E emerges as a promising treatment option for diabetes,especially targeting MMP9 affected by ER *** study also underscores the significance of physical exercise in modulating ER stress pathways in diabetes management,bridging traditional physical therapy and modern scientific *** study has *** focuses on the microRNA-149-5p-MMP9 network in sepsis,using cell-based methods without animal or clinical tria

关键词： ER stress diabetes physical exercise gene expression microRNA-149-5p MMP9 licorice glycoside E traditional physical therapy genomics insights

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Gut microbiota remodeling drived by dietary millet protein prevents the metabolic syndrome

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Food Science and Human Wellness 2024年第4期13卷 1987-2001页

作者： Shuhua Shan Ruopeng Yin Jiangying Shi Lizhen Zhang Jiaqi Zhou Qinqin Qiao Xiushan Dong Wenjing Zhao Zhuoyu Li Institute of Biotechnology Key Laboratory of Chemical Biology and Molecular Engineering of National Ministry of EducationShanxi UniversityTaiyuan 030006China School of Life Science Shanxi UniversityTaiyuan 030006China shanxi bethune hospital Shanxi Academy of Medical SciencesTongji Shanxi HospitalThird Hospital of Shanxi Medical UniversityTaiyuan 030032China Department of Biology Biological Science and Technology CollegeTaiyuan Normal UniversityJinzhong 030619China

Metabolic syndrome(Met S)is a chronic disease associated with the disturbance of gut microbiota *** derived from gut microbes play essential roles in Met S prevention and ***,we focused on the inhibitory effect of the extract of millet bran protein(EMBP)on a high-fat diet(HFD)-induced Met S,aiming to identify gut microbiota and their metabolites that involve in the anti-Met S activity of *** obesity,chronic inflammation,insulin resistance in Met S mouse models were abolished after EMBP *** protective mechanism of EMBP against HFD-induced Met S may depend on improved gut barrier *** microbiome analysis,we found that EMBP supplementation improved gut microbiome dysbiosis in Met S mice,specifically upregulating Bacteroides *** fecal microbiota transplantation(FMT)also demonstrated this *** addition,metabolomic analysis showed that EMBP mediates metabolic profiling reprogramming in Met S ***,a microbiota-derived metabolite,gamma-aminobutyric acid(GABA),is enriched by *** addition,exogenous GABA treatment produced a similar protective effect to EMBP by improving NRF2-dependent gut barrier function to protect HFDinduced Met *** results suggest that EMBP suppress host Met S by remodeling of gut microbiota as an effective candidate for next-generation medicine food dual purpose dietary supplement to intervene in MetS.

关键词： Metabolic syndrome Gut microbiota Extract of millet bran protein Gamma-aminobutyric acid Gut barrier function

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