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Glucose metabolic reprogramming-related parameters for the prediction of 28-day neurological prognosis and all-cause mortality in patients after cardiac arrest:a prospective single-center observational study

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World Journal of Emergency Medicine 2024年第3期15卷 197-205页

作者： Subi Abudurexiti Shihai Xu Zhangping Sun Yi Jiang Ping Gong Department of Emergency Medicine Ruijin Hospital Affi liated to Shanghai Jiaotong University School of MedicineShanghai 200025China Department of Emergency Medicine Shenzhen People's Hospital(the Second Clinical Medical CollegeJinan Universitythe First Affi liated HospitalSouthern University of Science and Technology)Shenzhen 518020China Department of Emergency Medicine the First Affi liated Hospital of Dalian Medical UniversityDalian 116011China Department of Emergency Medicine General Hospital of Tianjin Medical UniversityTianjin 300052China

BACKGROUND:We aimed to observe the dynamic changes in glucose metabolic reprogrammingrelated parameters and their ability to predict neurological prognosis and all-cause mortality in cardiac arrest patients after the restoration of spontaneous circulation(ROSC).METHODS:Adult cardiac arrest patients after ROSC who were admitted to the emergency or cardiac intensive care unit of the First Aflliated hospital of Dalian Medical university from August 1,2017,to May 30,2021,were *** to 28-day survival,the patients were divided into a non-survival group(n=82) and a survival group(n=38).Healthy adult volunteers(n=40) of similar ages and sexes were selected as *** serum levels of glucose metabolic reprogrammingrelated parameters(lactate dehydrogenase [LDH],lactate and pyruvate),neuron-specific enolase(NSE) and interleukin 6(IL-6) were measured on days 1,3,and 7 after *** Acute Physiology and Chronic Health Evaluation II(APACHE II) score and Sequential Organ Failure Assessment(SOFA) score were *** Cerebral Performance Category(CPC) score was recorded on day 28 after ***:Following ROSC,the serum LDH(607.0 U/L vs.286.5 U/L),lactate(5.0 mmol/L vs.2.0 mmol/L),pyruvate(178.0 μmol/L vs.70.9 μmol/L),and lactate/pyruvate ratio(34.1 vs.22.1) significantly increased and were higher in the non-survivors than in the survivors on admission(all P<0.05).Moreover,the serum LDH,pyruvate,IL-6,APACHE II score,and SOFA score on days 1,3 and 7 after ROSC were significantly associated with 28-day poor neurological prognosis and 28-day all-cause mortality(all P<0.05).The serum LDH concentration on day 1 after ROSC had an area under the receiver operating characteristic curve(AUC) of 0.904 [95% confidence interval [95% CI]:0.851–0.957]) with 96.8% specificity for predicting 28-day neurological prognosis and an AUC of 0.950(95% CI:0.911–0.989) with 94.7% specificity for predicting 28-day all-cause mortality,which was the highest among the glucose metabo

关键词： Glucose metabolic reprogramming Lactate dehydrogenase Cardiac arrest Prognosis

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Exploiting the potential of the ubiquitin-proteasome system in overcoming tyrosine kinase inhibitor resistance in chronic myeloid leukemia

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Genes & Diseases 2024年第5期11卷 140-162页

作者： Xudong Li Wei Li Yanli Zhang Linping Xu Yongping Song Department of Hematology Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer HospitalZhengzhouHenan 450008China Academy of Medical Sciences Zhengzhou UniversityZhengzhouHenan 450052China Department of Hematology The First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenan 450052China

The advent of tyrosine kinase inhibitors(TKI)targeting BCR-ABL has drastically changed the treatment approach of chronic myeloid leukemia(CML),greatly prolonged the life of CML patients,and improved their ***,TKI resistance is still a major problem with CML patients,reducing the efficacy of treatment and their quality of *** resistance is mainly divided into BCR-ABL-dependent and BCR-ABL-independent ***,the main clinical strategy addressing TKI resistance is to switch to newly developed ***,data have shown that these new drugs may cause serious adverse reactions and intolerance and cannot address all resistance ***,finding new therapeutic targets to overcome TKI resistance is crucial and the ubiquitin-proteasome system(UPS)has emerged as a *** UPS mediates the degradation of most proteins in organisms and controls a wide range of physiological *** recent years,the study of UPS in hematological malignant tumors has resulted in effective treatments,such as bortezomib in the treatment of multiple myeloma and mantle cell *** CML,the components of UPS cooperate or antagonize the efficacy of TKI by directly or indirectly affecting the ubiquitination of BCR-ABL,interfering with CML-related signaling pathways,and negatively or positively affecting leukemia stem *** of these molecules may help overcome TKI resistance and treat *** this review,the mechanism of TKI resistance is briefly described,the components of UPS are introduced,existing studies on UPS participating in TKI resistance are listed,and UPS as the therapeutic target and strategies are discussed.

关键词： Chronic myeloid leukemia Deubiquitinases E3 ligase PROTAC TKI resistance Ubiquitin-proteasome system

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Associations of sleeping patterns and isotemporal substitution of other behavior with the prevalence of CKD in Chinese adults

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Frontiers of Medicine 2024年第2期18卷 303-314页

作者： Yi Ding Xiaoli Xu Zhuojun Xin Qiuyu Cao Jiaojiao Huang Xianglin Wu Yanan Huo Qin Wan Yingfen Qin Ruying Hu Lixin Shi Qing Su Xuefeng Yu Li Yan Guijun Qin Xulei Tang Gang Chen Min Xu Tiange Wang Zhiyun Zhao Zhengnan Gao Guixia Wang Feixia Shen Zuojie Luo Li Chen Qiang Li Zhen Ye Yinfei Zhang Chao Liu Youmin Wang Tao Yang Huacong Deng Lulu Chen Tianshu Zeng Jiajun Zhao Yiming Mu Shengli Wu Yuhong Chen Jieli Lu Weiqing Wang Guang Ning Yu Xu Yufang Bi Mian Li Department of Endocrine and Metabolic Diseases Shanghai Institute of Endocrine and Metabolic DiseasesRuijin HospitalShanghai Jiao Tong University School of MedicineShanghai200025China Shanghai National Clinical Research Center for Metabolic Diseases Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of ChinaShanghai Key Laboratory for Endocrine TumorState Key Laboratory of Medical GenomicsRuijin HospitalShanghai Jiao Tong University School of MedicineShanghai200025China Jiangxi Provincial People’s hospital Affiliated to Nanchang UniversityNanchang330000China Department of Endocrinology The Affiliated Hospital of Southwest Medical UniversityLuzhou646000China Department of Endocrinology The First Affiliated Hospital of Guangxi Medical UniversityNanning530000China Zhejiang Provincial Center for Disease Control and Prevention Hangzhou310000China Department of Endocrinology Affiliated Hospital of Guiyang Medical UniversityGuiyang550000China Xinhua hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai200000China Tongji hospital Tongji Medical CollegeHuazhong University of Science and TechnologyWuhan430000China Sun Yat-sen Memorial hospital Sun Yat-sen UniversityGuangzhou510000China Department of Endocrinology The First Affiliated Hospital of Zhengzhou UniversityZhengzhou450000China Department of Endocrinology The First Hospital of Lanzhou UniversityLanzhou730000China Fujian Provincial hospital Fujian Medical UniversityFuzhou350000China Dalian Municipal Central hospital Affiliated of Dalian Medical UniversityDalian116000China Department of Endocrinology The First Hospital of Jilin UniversityChangchun130000China Department of Endocrinology The First Affiliated Hospital of Wenzhou Medical UniversityWenzhou325000China Qilu hospital of Shandong university Jinan250000China Department of Endocrinology The Second Affiliated Hospital of Harbin Medical UniversityHarbin150000China Department of Endocrinology Cen

Studies have found a U-shaped relationship between sleep duration and chronic kidney disease(CKD)risk,but limited research evaluated the association of reallocating excessive sleep to other behavior with *** included 104538 participants from the nationwide cohort of the Risk Evaluation of Cancers in Chinese Diabetic Individuals:A Longitudinal Study,with self-reported time of daily-life *** isotemporal substitution models,we found that substituting 1 h of sleeping with sitting,walking,or moderate-to-vigorous physical activity was associated with a lower CKD ***-time physical activity displacement was associated with a greater prevalence reduction than occupational physical activity in working *** stratified analysis,a lower CKD prevalence related to substitution toward physical activity was found in long *** pronounced correlations were observed in long sleepers with diabetes than in those with prediabetes,and they benefited from other behavior substitutions toward a more active *** U-shaped association between sleep duration and CKD prevalence implied the potential effects of insufficient and excessive sleep on the kidneys,in which the pernicious link with oversleep could be reversed by time reallocation to physical *** divergence in the predicted effect on CKD following time reallocation to behavior of different domains and intensities and in subpopulations with diverse metabolic statuses underlined the importance of optimizing sleeping patterns and adjusting integral behavioral composition.

关键词： sleep physical activity chronic kidney disease isotemporal substitution behavioral pattern

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Severe pediatric COVID‑19:a review from the clinical and immunopathophysiological perspectives

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World Journal of Pediatrics 2024年第4期20卷 307-324页

作者： Yi‑Kan Sun Can Wang Pei‑Quan Lin Lei Hu Jing Ye Zhi‑Gang Gao Ru Lin Hao‑Min Li Qiang Shu Li‑Su Huang Lin‑Hua Tan Children's hospital Zhejiang University School of MedicineHangzhou 310052China The Second Affiliated hospital Zhejiang University School of MedicineHangzhou 310030China Surgical Intensive Care Unit Children’s HospitalZhejiang University School of MedicineHangzhou 310052China Department of General Surgery Children’s HospitalZhejiang University School of MedicineHangzhou 310052China Department of Cardiopulmonary and Extracorporeal Life Support Children’s HospitalZhejiang University School of MedicineHangzhou 310052China Clinical Data Center Children’s HospitalZhejiang University School of MedicineHangzhou 310052China Department of Cardiac Surgery Children’s HospitalZhejiang University School of MedicineHangzhou 310052China National Clinical Research Center for Child Health Children’s HospitalZhejiang University School of MedicineHangzhou 310052China Department of Infectious Diseases Children’s HospitalZhejiang University School of MedicineHangzhou 310052China

Background Coronavirus disease 2019(COVID-19)tends to have mild presentations in ***,severe and critical cases do arise in the pediatric population with debilitating systemic impacts and can be fatal at times,meriting further attention from ***,the intricate interactions between the pathogen virulence factors and host defense mechanisms are believed to play indispensable roles in severe COVID-19 pathophysiology but remain incompletely *** sources A comprehensive literature review was conducted for pertinent publications by reviewers independently using the PubMed,Embase,and Wanfang *** keywords included“COVID-19 in children”,“severe pediatric COVID-19”,and“critical illness in children with COVID-19”.Results Risks of developing severe COVID-19 in children escalate with increasing numbers of co-morbidities and an unvaccinated *** respiratory distress stress and necrotizing pneumonia are prominent pulmonary manifestations,while various forms of cardiovascular and neurological involvement may also be *** immunological processes are implicated in the host response to COVID-19 including the type I interferon and inflammasome pathways,whose dysregulation in severe and critical diseases translates into adverse clinical *** inflammatory syndrome in children(MIS-C),a potentially life-threatening immune-mediated condition chronologically associated with COVID-19 exposure,denotes another scientific and clinical conundrum that exemplifies the complexity of pediatric *** the considerable dissimilarities between the pediatric and adult immune systems,clinical trials dedicated to children are lacking and current management recommendations are largely adapted from adult *** Severe pediatric COVID-19 can affect multiple organ *** dysregulated immune pathways in severe COVID-19 shape the disease course,epitomize the vast functional diversity of the

关键词： Immunopathophysiology MIS-C Pediatric critical care Severe pediatric COVID-19

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Therapeutic cancer vaccines:advancements,challenges,and prospects

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Signal Transduction and Targeted Therapy 2024年第1期9卷 150-172页

作者： Ting Fan Mingna Zhang Jingxian Yang Zhounan Zhu Wanlu Cao Chunyan Dong Department of Oncology East Hospital Affiliated to Tongji UniversityTongji University School of MedicineShanghaiChina Postgraduate Training Base Shanghai East HospitalJinzhou Medical UniversityShanghai 200120China

With the development and regulatory approval of immune checkpoint inhibitors and adoptive cell therapies,cancer immunotherapy has undergone a profound transformation over the past ***,therapeutic cancer vaccines have shown promise by eliciting de novo T cell responses targeting tumor antigens,including tumor-associated antigens and tumor-specific *** objective was to amplify and diversify the intrinsic repertoire of tumor-specific T ***,the complete realization of these capabilities remains an ongoing ***,we provide an overview of the current landscape of cancer vaccines in this *** range of antigen selection,antigen delivery systems development the strategic nuances underlying effective antigen presentation have pioneered cancer vaccine ***,this review addresses the current status of clinical trials and discusses their strategies,focusing on tumor-specific immunogenicity and anti-tumor efficacy ***,current clinical attempts toward developing cancer vaccines have not yielded breakthrough clinical outcomes due to significant challenges,including tumor immune microenvironment suppression,optimal candidate identification,immune response evaluation,and vaccine manufacturing ***,the field is poised to overcome hurdles and improve patient outcomes in the future by acknowledging these clinical complexities and persistently striving to surmount inherent constraints.

关键词： breakthrough approval overcome

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Mitochondrial Regulation of Macrophages in Innate Immunity and Diverse Roles of Macrophages During Cochlear Inflammation

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Neuroscience Bulletin 2024年第2期40卷 255-267页

作者： Yuan Zhang Fanglei Ye Xiaolong Fu Shen Li Le Wang Yutian Chen Hongmin Li Shaojuan Hao Kun Zhao Qi Feng Peipei Li Department of Otology The First Afliated Hospital of Zhengzhou UniversityZhengzhou 450052China Shandong Provincial hospital Shandong First Medical UniversityJinan 250000China Department of Neurology The First Afliated Hospital of Zhengzhou UniversityZhengzhou 450052China The Department of Endovascular Surgery The First Afliated Hospital of Zhengzhou UniversityZhengzhou 450052China Department of Integrated Traditional and Western Nephrology The First Afliated Hospital of Zhengzhou UniversityZhengzhou 450052China Henan Province Research Center of Kidney Disease Zhengzhou 450052China

Macrophages are essential components of the innate immune system and constitute a non-specific first line of host defense against pathogens and *** regulate macrophage activation and innate immune responses in various inflammatory diseases,including cochlear *** distribution,number,and morphological characteristics of cochlear macrophages change significantly across different inner ear regions under various pathological conditions,including noise exposure,ototoxicity,and age-related ***,the exact mechanism underlying the role of mitochondria in macrophages in auditory function remains ***,we summarize the major factors and mitochondrial signaling pathways(e.g.,metabolism,mitochondrial reactive oxygen species,mitochondrial DNA,and the inflammasome)that influence macrophage activation in the innate immune *** particular,we focus on the properties of cochlear macrophages,activated signaling pathways,and the secretion of inflammatory cytokines after acoustic *** hope this review will provide new perspectives and a basis for future research on cochlear inflammation.

关键词： Macrophage Mitochondria Innate immunity Cochlea Infammation

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Associated Factors to Poor Blood Pressure Control in Hypertensives Followed Up at the Campus university hospital of Lome (Togo)

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World Journal of Cardiovascular Diseases 2024年第6期14卷 374-380页

作者： Soulemane Pessinaba Yaovi Mignazonzon Afassinou Wiyao Dieudonné Kaziga Komlavi Yayehd Kolani Lamboni Sélim Bolarinwa Mohamed Kpélafia Ekpe Togbossi Akpe Adzodo Machihude Pio Soodougoua Baragou Findibé Damorou Cardiology Department University Hospital of Campus Lome Togo Cardiology Department Sylvanus Olympio University Hospital Lome Togo Cardiology Department Kara University Hospital Kara Togo

Introduction: Hypertension is a real public health issue and its control is very difficult. We aim to determine the frequency of uncontrolled hypertension in hypertensive patients followed up as an outpatient at the campus university hospital of Lome (Togo) and to search for the associated factors. Methodology: The study was cross-sectional, descriptive and analytical, carried out from February (2022) to August 2022 in 260 hypertensive patients aged 22 years old, followed up (on an) as an outpatient for at least 3 months at the Lome university hospital campus. A univariate then multivariate analysis were conducted in order to highlight the most common factors significantly linked to uncontrolled. Results: The mean age of hypertensives was 56.4 ± 12.7 years, the sex ratio (M/F) was 0.59. Prevalence of uncontrolled blood pressure was 42%. Associated Factors to poor blood pressure control in our study were age > 60 years (OR = 1.6 CI [1.17 - 2.50]), low socio-economic level (OR = 2.2 CI [1.96 - 4.33]), high cardiovascular risk level (OR = 3.1 CI [2.18 - 4.52]), non-adherence to regular blood pressure monitoring (OR = 3.3 CI [2.21 - 5.55]), low compliance to treatment (OR = 4.1 CI [2.33 - 6.76]) and a chronic renal failure (OR = 2.1 CI [1.21 - 3.10]). Conclusion: Nearly half of the hypertensives in our study had poorly controlled blood pressure by antihypertensive treatment medication. The factors of this poor control were age > 60 years, low socio-economic level, high or very high level of cardiovascular risk, low compliance to treatment, and renal failure.

关键词： Hypertension Poor Control Associated factors Togo

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Prediction of peritoneal free cancer cells in gastric cancer patients by golden-angle radial sampling dynamic contrast-enhanced magnetic resonance imaging

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Journal of Zhejiang university-Science B(Biomedicine & Biotechnology) 2024年第7期25卷 617-627页

作者： Xueqing YIN Xinzhong RUAN Yongmeng ZHU Yongfang YIN Rui HUANG Chao LIANG The First Affiliated hospital of Ningbo university Ningbo 315000China Ningbo Medical Center Lihuili hospital Ningbo 315000China

Objectiveperitoneal free cancer cells can negatively impact disease progression and patient outcomes in gastric cancer. This study aimed to investigate the feasibility of using golden-angle radial sampling dynamic contrast-enhanced magnetic resonance imaging (GRASP DCE-MRI) to predict the presence of peritoneal free cancer cells in gastric cancer *** enrolled patients were consecutively divided into analysis and validation groups. Preoperative magnetic resonance imaging (MRI) scans and perfusion were performed in patients with gastric cancer undergoing surgery, and peritoneal lavage specimens were collected for examination. Based on the peritoneal lavage cytology (PLC) results, patients were divided into negative and positive lavage fluid groups. The data collected included clinical and MR information. A nomogram prediction model was constructed to predict the positive rate of peritoneal lavage fluid, and the validity of the model was verified based on data from the verification *** was no statistical difference between the proportion of PLC-positive cases predicted by GRASP DCE-MR and the actual PLC test. MR tumor stage, tumor thickness, and perfusion parameter Tofts-Ketty model volume transfer constant (Ktrans) were independent predictors of positive peritoneal lavage fluid. The nomogram model featured a concordance index (C-index) of 0.785 and 0.742 for the modeling and validation groups, *** DCE-MR could effectively predict peritoneal free cancer cells in gastric cancer patients. The nomogram model constructed using these predictors may help clinicians to better predict the risk of peritoneal free cancer cells being present in gastric cancer patients.

关键词： Gastric cancer Magnetic resonance Golden-angle radial sampling Nomogram model Peritoneal free cancer cells

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Ruxolitinib improves the inflammatory microenvironment,restores glutamate homeostasis,and promotes functional recovery after spinal cord injury

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Neural Regeneration Research 2024年第11期19卷 2499-2512页

作者： Jiang Cao Xiao Yu Jingcheng Liu Jiaju Fu Binyu Wang Chaoqin Wu Sheng Zhang Hongtao Chen Zi Wang Yinyang Xu Tao Sui Jie Chang Xiaojian Cao Department of Orthopedics The First Affiliated Hospital of Nanjing Medical UniversityNanjingJiangsu ProvinceChina Department of Trauma Surgery Subei People’s Hospital of JiangsuClinical Medical College of Yangzhou UniversityYangzhouJiangsu ProvinceChina Department of Orthopedics Zhongda HospitalSoutheast UniversityNanjingJiangsu ProvinceChina Department of Orthopedic Surgery Nanjing Drum Tower HospitalThe Affiliated Hospital of Medical School of Nanjing UniversityNanjingJiangsu ProvinceChina

The inflammatory microenvironment and neurotoxicity can hinder neuronal regeneration and functional recovery after spinal cord ***,a JAK-STAT inhibitor,exhibits effectiveness in autoimmune diseases,arthritis,and managing inflammatory cytokine *** studies have shown the neuroprotective potential of ruxolitinib in neurological trauma,the exact mechanism by which it enhances functional recovery after spinal cord injury,particularly its effect on astrocytes,remains *** address this gap,we established a mouse model of T10 spinal cord contusion and found that ruxolitinib effectively improved hindlimb motor function and reduced the area of spinal cord *** sequencing analysis showed that ruxolitinib alleviated inflammation and immune response after spinal cord injury,restored EAAT2 expression,reduced glutamate levels,and alleviated excitatory ***,ruxolitinib inhibited the phosphorylation of JAK2 and STAT3 in the injured spinal cord and decreased the phosphorylation level of nuclear factor kappa-B and the expression of inflammatory factors interleukin-1β,interleukin-6,and tumor necrosis factor-α.Additionally,in glutamate-induced excitotoxicity astrocytes,ruxolitinib restored EAAT2 expression and increased glutamate uptake by inhibiting the activation of STAT3,thereby reducing glutamate-induced neurotoxicity,calcium influx,oxidative stress,and cell apoptosis,and increasing the complexity of dendritic ***,these results indicate that ruxolitinib restores glutamate homeostasis by rescuing the expression of EAAT2 in astrocytes,reduces neurotoxicity,and effectively alleviates inflammatory and immune responses after spinal cord injury,thereby promoting functional recovery after spinal cord injury.

关键词： astrocytes EAAT2 excitotoxicity glutamate homeostasis JAK-STAT pathway locomotor function neurotoxicity ruxolitinib spinal cord injury transcriptome analysis

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Multi-cohort comprehensive analysis unveiling the clinical value and therapeutic effect of GNAL in glioma

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Oncology Research 2024年第5期32卷 965-981页

作者： ZHEN LIU LIANGWANG YANG ZHENGXING XIE HUI YU TIANYI GU DAOMING SHI NING CAI SHENGHUA ZHUO Department of Neurosurgery Affiliated Hospital of Jiangsu UniversityZhenjiang212000China Department of Neurosurgery First Affiliated Hospital of Hainan Medical UniversityHaikou570100China Department of Cardiothoracic Surgery Affiliated Hospital of Jiangsu UniversityZhenjiang212000China Department of General Surgery Affiliated Hospital of Jiangsu UniversityZhenjiang212000China

Clinical data indicates that glioma patients have poor treatment outcomes and clinical *** role of olfactory signaling pathway-related genes(OSPRGs)in glioma has not been fully *** this study,we aimed to investigate the role and relationship between OSPRGs and *** and multivariate Cox regression analyses were performed to assess the relationship between OSPRGs and the overall survival of glioma based on public cohorts,and the target gene(G Protein Subunit Alpha L,GNAL)was *** association of GNAL expression with clinicopathological characteristics,gene mutation landscape,tumor immune microenvironment(TIME),deoxyribonucleic acid(DNA)methylation,and naris-occlusion controlled genes(NOCGs)was *** was used to evaluate GNAL level in *** analysis was conducted to evaluate the drug sensitivity,immunotherapy response,and functional enrichment of *** was an independent prognostic factor,and patients with low GNAL expression have a poor *** of GNAL was closely associated with clinicopathological characteristics,DNA methylation,and several immune-related *** infiltration analysis indicated that GNAL levels were negatively correlated with immune *** low-expression group showed efficacy with anti-PD-1 *** compounds with significantly different half-maximal inhibitory concentration(IC50)values between the GNAL high and low-expression groups were ***,its expression was associated with several immune cells,immune-related genes,and *** expression of GNAL is closely associated with clinicopathological characteristics,TIME,and the response to therapeutic interventions,highlighting its potential as a prognostic biomarker for glioma.

关键词： Glioma Olfaction GNAL Tumor immune microenvironment Immunotherapy/chemotherapy response

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