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4-Nitrophenol at environmentally relevant concentrations mediates reproductive toxicity in Caenorhabditis elegans via metabolic disorders-induced estrogen signaling pathway

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Journal of Environmental Sciences 2025年第1期147卷 244-258页

作者： Jia Wang Jiechen Yin Danhong Peng Xiaoqian Zhang Zhouhong Shi Weixi Li Yingchi Shi Mingjun Sun Nan Jiang Beijing Cheng Xingchen Meng Ran Liu Key Laboratory of Environmental medicine Engineering Ministry of EducationSchool of Public HealthSoutheast UniversityNanjing 210009China Department of Obstetrics and Gynecology Zhongda HospitalSchool of MedicineSoutheast UniversityNanjing 210009China Department of Obstetrics and Gynecology The Affiliated Suzhou Hospital of Nanjing Medical UniversitySuzhou Municipal HospitalGusu SchoolNanjing Medical UniversitySuzhouJiangsu 215002China

4-Nitrophenol(4-NP),as a toxic and refractory pollutant,has generated significant concern due to its adverse ***,the potential toxic effects andmechanism remained *** this study,the reproduction,development,locomotion and reactive oxygen species(ROS)production of Caenorhabditis elegans were investigated to evaluate the 4-NP *** used metabolomics to assess the potential damage *** role of metabolites in mediating the relationship between 4-NP and phenotypes was examined by correlation and mediation analysis.4-NP(8 ng/L and 8μg/L)caused significant reduction of brood size,ovulation rate,total germ cells numbers,head thrashes and body bends,and an increase in ***,the oosperm numbers in uterus,body length and body width were decreased in 8μg/***,36 differential metabolites were enriched in the significant metabolic pathways,including lysine biosynthesis,β-alanine metabolism,tryptophan metabolism,pentose phosphate pathway,pentose and glucuronate interconversions,amino sugar and nucleotide sugar metabolism,starch and sucrose metabolism,galactose metabolism,propanoate metabolism,glycerolipid metabolism,and estrogen signaling *** mechanism of 4-NP toxicity was that oxidative stress caused by the perturbation of amino acid,which had effects on energy metabolism through disturbing carbohydrate and lipid metabolism,and finally affected the estrogen signaling pathway to exert toxic ***,correlation and mediation analysis showed glycerol-3P,glucosamine-6P,glucosamine-1P,UDP-galactose,L-aspartic acid,and uracilwere potential markers for the reproduction and glucose-1,6P2 for developmental *** results provided insight into the pathways involved in the toxic effects caused by 4-NP and developed potential biomarkers to evaluate 4-NP toxicity.

关键词： 4-Nitrophenol Caenorhabditis elegans Metabolomics Pathway analysis

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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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Impacts of Nutlin-3a and exercise on murine double minute 2-enriched glioma treatment

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Neural Regeneration Research 2025年第4期20卷 1135-1152页

作者： Yisheng Chen Zhongcheng Fan Zhiwen Luo Xueran Kang Renwen Wan Fangqi Li Weiwei Lin Zhihua Han Beijie Qi Jinrong Lin Yaying Sun Jiebin Huang Yuzhen Xu Shiyi Chen Department of Sport medicine Huashan HospitalFudan UniversityShanghaiChina Department of Orthopedic Surgery Hainan Province Clinical Medical CenterHaikou Affiliated Hospital of Central South University Xiangya School of MedicineHaikouHainan ProvinceChina Department of Basic medicine Shanghai Jiao Tong University School of MedicineShanghai Jiao Tong UniversityShanghaiChina Department of Neurosurgery Second Affiliated Hospital of Zhejiang University School of MedicineZhejiang UniversityHangzhouZhejiang ProvinceChina Department of Orthopedics Shanghai General HospitalSchool of Medicine Shanghai Jiao Tong UniversityShanghaiChina Department of Infectious Diseases Children’s Hospital of Fudan UniversityNational Children’s Medical CenterShanghaiChina Department of Rehabilitation The Second Affiliated Hospital of Shandong First Medical UniversityTaianShandong ProvinceChina

Recent research has demonstrated the impact of physical activity on the prognosis of glioma patients,with evidence suggesting exercise may reduce mortality risks and aid neural *** role of the small ubiquitin-like modifier(SUMO)protein,especially post-exercise,in cancer progression,is gaining attention,as are the potential anti-cancer effects of *** used machine learning to create the exercise and SUMO-related gene signature(ESLRS).This signature shows how physical activity might help improve the outlook for low-grade glioma and other *** demonstrated the prognostic and immunotherapeutic significance of ESLRS markers,specifically highlighting how murine double minute 2(MDM2),a component of the ESLRS,can be targeted by *** underscores the intricate relationship between natural compounds such as nutlin-3 and immune *** comprehensive CRISPR screening,we validated the effects of specific ESLRS genes on low-grade glioma *** also revealed insights into the effectiveness of Nutlin-3a as a potent MDM2 inhibitor through molecular docking and dynamic ***-3a inhibited glioma cell proliferation and activated the p53 *** efficacy decreased with MDM2 overexpression,and this was reversed by Nutlin-3a or *** using a low-grade glioma mouse model highlighted the effect of physical activity on oxidative stress and molecular pathway ***,both physical exercise and Nutlin-3a administration improved physical function in mice bearing tumors derived from MDM2-overexpressing *** results suggest the potential for Nutlin-3a,an MDM2 inhibitor,with physical exercise as a therapeutic approach for glioma *** research also supports the use of natural products for therapy and sheds light on the interaction of exercise,natural products,and immune regulation in cancer treatment.

关键词： exercise and SUMO-related gene signatures(ESLRS) glioblastoma management low-grade glioma natural bioactives neural regeneration physical exercise

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Multi-omics analysis and experimental verification reveal testicular fatty acid metabolism disorder in non-obstructive azoospermia

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Zoological Research 2025年第01期 177-192页

作者： Zhou Li Yi-Jian Xiang Zhi-Chuan Zou Yu-Ming Feng Hui Wang Wei-Qing Chen Xie Ge Jin-Zhao Ma Jun Jing Bing Yao Department of Reproductive medicine Jinling Hospital Affiliated Hospital of Medical School Nanjing University State Key Laboratory of Reproductive medicine and Offspring Health Nanjing Medicine University

Increasing evidence implicates disruptions in testicular fatty acid metabolism as a contributing factor in nonobstructive azoospermia(NOA), a severe form of male infertility. However, the precise mechanisms linking fatty acid metabolism to NOA pathogenesis have not yet been fully elucidated. Multi-omics analyses, including microarray analysis, single-cell RNA sequencing(scRNA-seq), and metabolomics, were utilized to investigate disruptions in fatty acid metabolism associated with NOA using data from public databases. Results identified ACSL6, ACSBG2, and OLAH as key genes linked to fatty acid metabolism dysregulation, suggesting their potential causative roles in NOA. A marked reduction in omega-3 polyunsaturated fatty acids, especially docosahexaenoic acid(DHA), was observed, potentially contributing to the pathological process of NOA. Sertoli cells in NOA patients exhibited apparent fatty acid metabolic dysfunction, with PPARG identified as a key transcription factor(TF) regulating this process. Functional analyses demonstrated that PPARG is crucial for maintaining blood-testis barrier(BTB) integrity and promoting spermatogenesis via regulation of fatty acid metabolism. These findings reveal the pivotal role of fatty acid metabolism in NOA and identify PPARG as a potential therapeutic target.

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Endothelial dysfunction in the kidney transplant population:Current evidence and management strategies

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World Journal of Transplantation 2025年第1期15卷 24-43页

作者： Arun Prabhahar Akshey Batta Juniali Hatwal Vivek Kumar Raja Ramachandran Akash Batta Department of Telemedicine(internal medicine and Nephrology) Post Graduate Institute of Medical Education and ResearchChandigarh 160012India Department of Urology and Renal Transplant Neelam HospitalRajpura 140401PunjabIndia Department of internal medicine Post Graduate Institute of Medical Education and ResearchChandigarh 160012India Department of Nephrology Post Graduate Institute of Medical Education and ResearchChandigarh 160012India Department of Cardiology Dayanand Medical College and HospitalLudhiana 141001PunjabIndia

The endothelium modulates vascular homeostasis owing to a variety of vasoconstrictors and *** dysfunction(ED),characterized by impaired vasodilation,inflammation,and thrombosis,triggers future cardiovascular(CV)*** kidney disease,a state of chronic inflammation caused by oxidative stress,metabolic abnormalities,infection,and uremic toxins damages the *** is also associated with a decline in estimated glomerular filtration *** kidney transplantation,endothelial functions undergo immediate but partial restoration,promising graft longevity and enhanced CV ***,the anticipated CV outcomes do not happen due to various transplant-related and unrelated risk factors for ED,culminating in poor CV health and graft *** in kidney transplant recipients is an underrecognized and poorly studied *** diseases are the leading cause of death among kidney transplant candidates with functioning *** contributes to the pathogenesis of many of the CV *** biomarkers and vasoreactivity tests are available to study endothelial *** an increasing number of transplants happening every year,and improved graft rejection rates due to the availability of effective immunosuppressants,the focus has now shifted to endothelial protection for the prevention,early recognition,and treatment of CV diseases.

关键词： Endothelial dysfunction Endothelium Cardiovascular disease Kidney transplantation Chronic kidney disease Nitric oxide Flow-mediated dilatation Nitro-glycerine-mediated dilatation Biomarkers

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Nerve root magnetic stimulation regulates the synaptic plasticity of injured spinal cord by ascending sensory pathway

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Neural Regeneration Research 2025年第12期20卷 3564-3573页

作者： Ya Zheng Lingyun Cao Dan Zhao Qi Yang Chunya Gu Yeran Mao Guangyue Zhu Yulian Zhu Jing Zhao Dongsheng Xu Department of Rehabilitation medicine Huashan HospitalFudan UniversityShanghaiChina School of Rehabilitation Science Shanghai University of Traditional Chinese MedicineShanghaiChina Department of Rehabilitation medicine Ruijin HospitalShanghai Jiaotong UniversityShanghaiChina Rehabilitation Medical Center Tongji Hospital Affiliated to Tongji University School of MedicineShanghaiChina Department of Rehabilitation Baoshan BranchShuguang Hospital Affiliated to Shanghai University of Traditional Chinese MedicineShanghaiChina National Center for Neurological Disorders ShanghaiChina Department of Neurology Minhang Hospital Affiliated to Fudan UniversityShanghaiChina Engineering Research Center of Traditional Chinese medicine Intelligent Rehabilitation Ministry of EducationShanghaiChina Institute of Rehabilitation medicine Shanghai Academy of Traditional Chinese MedicineShanghaiChina

Promoting synaptic plasticity and inducing functional reorganization of residual nerve fibers hold clinical significance for restoring motor function following spinal cord *** stimulation targeting the nerve roots has been shown to improve motor function by enhancing nerve conduction in the injured spinal cord and restoring the synaptic ultrastructure of both the sensory and motor ***,our understanding of the neurophysiological mechanisms by which nerve root magnetic stimulation facilitates motor function recovery in the spinal cord is limited,and its role in neuroplasticity remains *** this study,we established a model of spinal cord injury in adult male Sprague–Dawley rats by applying moderate compression at the T10 *** then performed magnetic stimulation on the L5 nerve root for 3 weeks,beginning on day 3 *** day 22 post-injury,we observed that nerve root magnetic stimulation downregulated the level of interleukin-6 in the injured spinal cord tissue of ***,this treatment reduced neuronal damage and glial scar formation,and increased the number of neurons in the injured spinal ***,nerve root magnetic stimulation decreased the levels of acetylcholine,norepinephrine,and dopamine,and increased the expression of synaptic plasticity-related m RNA and proteins PSD95,GAP43,and Synapsin *** together,these results showed that nerve root magnetic stimulation alleviated neuronal damage in the injured spinal cord,regulated synaptic plasticity,and suppressed inflammatory *** findings provide laboratory evidence for the clinical application of nerve root magnetic stimulation in the treatment of spinal cord injury.

关键词： dendrite inflammation magnetic stimulation nerve root neurological function neuronal damage neurotransmitter spinal cord injury synaptic plasticity synaptic transmission

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Real-world evidence on the efficacy and safety of vonoprazanamoxicillin dual therapy for Helicobacter pylori treatment in elderly patients

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World Journal of Gastroenterology 2025年第1期31卷 68-78页

作者： Wen Gao Jing-Wen Li Hui Ye Xue-Zhi Zhang Jian-Xiang Liu Hong Cheng Department of Gastroenterology Peking University First HospitalBeijing 100034China School of medicine Tsinghua MedicineTsinghua UniversityBeijing 100034China Department of Traditional Chinese medicine and Integrative medicine Peking University First HospitalBeijing 100034China

BACKGROUND A dual therapy regimen containing amoxicillin is a common treatment option for the eradication of Helicobacter pylori(***).While substantial research supports the efficacy and safety of vonoprazan and amoxicillin(VA)dual therapy in the general population,there is still a lack of studies specifically focusing on its safety in elderly *** To evaluate efficacy and safety of VA dual therapy as first-line or rescue treatment for *** in elderly *** As a real-world retrospective study,data were collected from elderly patients aged 60 years and above who accepted VA dual therapy(vonoprazan 20 mg twice daily+amoxicillin 1000 mg thrice daily for 14 days)for *** eradication in the Department of Gastroenterology at Peking University First hospital between June 2020 and January *** status was evaluated by^(13)C-urease breath test 6 weeks after *** adverse events(AEs)during treatment were *** In total,401 cases were ***-one cases were excluded due to loss to follow-up,lack of re-examination,or unwillingness to take *** total of 380 included cases comprised 250 who received VA dual therapy as first-line treatment and 130 who received VA dual therapy as rescue *** was successfully eradicated in 239 cases(95.6%)in the first-line treatment group and 116 cases(89.2%)in the rescue treatment *** overall incidence of AEs was 9.5%for both ***,9.2%of patients experienced an AE in the first-line treatment group and 10.0%in the rescue treatment *** patients discontinued treatment due to AE,with a discontinuation rate of 1.3%.No serious AE *** The VA dual therapy regimen as a first-line treatment and a rescue therapy was effective and safe for elderly patients aged 60 and older.

关键词： Helicobacter pylori Vonoprazan Amoxicillin Dual therapy Elderly

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Establishment of human cerebral organoid systems to model early neural development and assess the central neurotoxicity of environmental toxins

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Neural Regeneration Research 2025年第1期20卷 242-252页

作者： Daiyu Hu Yuanqing Cao Chenglin Cai Guangming Wang Min Zhou Luying Peng Yantao Fan Qiong Lai Zhengliang Gao Fundamental Research Center Shanghai Yangzhi Rehabilitation Hospital(Shanghai Sunshine Rehabilitation Center)School of MedicineTongji UniversityShanghaiChina Institute of Geriatrics(Shanghai University) Affiliated Nantong Hospital of Shanghai University(The Sixth People’s Hospital of Nantong)Shanghai University School of MedicineNantongJiangsu ProvinceChina Shanghai Engineering Research Center of Organ Repair Shanghai University School of MedicineShanghaiChina Key Laboratory of Arrhythmias Ministry of EducationShanghai East HospitalSchool of MedicineTongji UniversityShanghaiChina

Human brain development is a complex process,and animal models often have significant *** address this,researchers have developed pluripotent stem cell-derived three-dimensional structures,known as brain-like organoids,to more accurately model early human brain development and *** enable more consistent and intuitive reproduction of early brain development,in this study,we incorporated forebrain organoid culture technology into the traditional unguided method of brain organoid *** involved embedding organoids in matrigel for only 7 days during the rapid expansion phase of the neural epithelium and then removing them from the matrigel for further cultivation,resulting in a new type of human brain organoid *** cerebral organoid system replicated the temporospatial characteristics of early human brain development,including neuroepithelium derivation,neural progenitor cell production and maintenance,neuron differentiation and migration,and cortical layer patterning and formation,providing more consistent and reproducible organoids for developmental modeling and toxicology *** a proof of concept,we applied the heavy metal cadmium to this newly improved organoid system to test whether it could be used to evaluate the neurotoxicity of environmental *** organoids exposed to cadmium for 7 or 14 days manifested severe damage and abnormalities in their neurodevelopmental patterns,including bursts of cortical cell death and premature *** exposure caused progressive depletion of neural progenitor cells and loss of organoid integrity,accompanied by compensatory cell proliferation at ectopic *** convenience,flexibility,and controllability of this newly developed organoid platform make it a powerful and affordable alternative to animal models for use in neurodevelopmental,neurological,and neurotoxicological studies.

关键词： cadmium cell death cell proliferation cortical development environmental toxins neural progenitor cells neurogenesis neurotoxicology organoids stem cells

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NOX4 exacerbates Parkinson's disease pathology by promoting neuronal ferroptosis and neuroinflammation

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Neural Regeneration Research 2025年第7期20卷 2038-2052页

作者： Zhihao Lin Changzhou Ying Xiaoli Si Naijia Xue Yi Liu Ran Zheng Ying Chen Jiali Pu Baorong Zhang Department of Neurology The Second Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiang ProvinceChina

Parkinson's disease is primarily caused by the loss of dopaminergic neurons in the substantia nigra ***,a novel form of regulated cell death characterized by iron accumulation and lipid peroxidation,plays a vital role in the death of dopaminergic ***,the molecular mechanisms underlying ferroptosis in dopaminergic neurons have not yet been completely *** oxidase 4 is related to oxidative stress,however,whether it regulates dopaminergic neuronal ferroptosis remains *** aim of this study was to determine whether NADPH oxidase 4 is involved in dopaminergic neuronal ferroptosis,and if so,by what *** found that the transcriptional regulator activating transcription factor 3 increased NADPH oxidase 4 expression in dopaminergic neurons and astrocytes in an 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine-induced Parkinson's disease *** oxidase 4 inhibition improved the behavioral impairments observed in the Parkinson's disease model animals and reduced the death of dopaminergic ***,NADPH oxidase 4 inhibition reduced lipid peroxidation and iron accumulation in the substantia nigra of the Parkinson's disease model ***,we found that NADPH oxidase 4 interacted with activated protein kinase Cαto prevent ferroptosis of dopaminergic ***,by lowering the astrocytic lipocalin-2 expression,NADPH oxidase 4 inhibition reduced 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine-induced *** findings demonstrate that NADPH oxidase 4 promotes ferroptosis of dopaminergic neurons and neuroinflammation,which contribute to dopaminergic neuron death,suggesting that NADPH oxidase 4 is a possible therapeutic target for Parkinson's disease.

关键词： dopaminergic neuron ferroptosis NADPH oxidase 4(NOX4) neuroinflammation Parkinson's disease

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Screening optimal target populations with symptomatic bradyarrhythmia for pharmacotherapy:a discriminant analysis pilot study

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Journal of Traditional Chinese medicine 2025年第1期45卷 160-166页

作者： ZHANG Wantong YI Danhui LU Fang YANG Qiaoning SHI Shuai LI Qiuyan WENG Weiliang WANG Xujie ZHU Baochen Institute of clinical pharmacology Xiyuan HospitalChina Academy of Chinese Medical Sciences NMPA Key Laboratory for Clinical Research and Evaluation of Traditional Chinese medicine National Clinical Research Center for Chinese medicine Cardiology Xiyuan HospitalChina Academy of Chinese Medical Sciences School of Statistics Renmin University of China Department of General medicine Guanganmen HospitalChina Academy of Chinese Medical Sciences Department of Pharmacy Dongzhimen HospitalBeijing University of Chinese Medicine

OBJECTIVE: To screen the target population with symptomatic bradyarrhythmia for pharmacotherapy. METHODS: This study use database from clinical trial that use Yuanjiang decoction(元姜方), a traditional Chinese medicinal prescription. Eligible participants were recruited and treated with Yuanjiang decoction(composed of 6 Chinese herbal medicines), 200 m L twice daily. Cross-contingency analysis, logistic regression analysis, interaction analysis, discriminant analysis and 10-fold cross validation methods were used to establish discriminant model. RESULTS: This study concluded that the clinical treatment of bradyarrhythmia has a clear effect. Low minimum heart rate, high maximum heart rate are risk factors that affect the efficacy. Patients with only one comorbid disease did not significantly affect the efficacy, but patient with two or more diseases of coronary heart disease, hypertension, paroxysmal atrial fibrillation, premature ventricular contraction and premature atrial contraction at the same time did not have a good effect. Using the discriminant analysis method to establish a efficacy prediction model, y = 0.07X1 + 0.16X2-0.65X3-1.12X4-0.71X5-0.75X6-0.91X7(X1 = 24 h mean heart rate, X2 = minimum heart rate, X3 = coronary heart disease, X4 = paroxysmal atrial fibrillation, X5 = premature ventricular contraction, X6= sinus block, X7 = atrioventricular block). CONCLUSION: Our model based on the clinical features of patients with bradyarrhythmia. Should be useful aid for predicting pharmacotherapy response and could screen the optimal pharmacotherapy target.

关键词： bradycardia discriminant analysis drug therapy health services needs and demand medicine, Chinese traditional

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