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The burden of upper motor neuron involvement is correlated with the bilateral limb involvement interval in patients with amyotrophic lateral sclerosis:a retrospective observational study

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Neural Regeneration Research 2025年第5期20卷 1505-1512页

作者： Jieying Wu Shan Ye Xiangyi Liu Yingsheng Xu Dongsheng Fan department of Neurology Peking University Third HospitalBeijingChina Beijing Municipal Key Laboratory of Biomarker and Translational Research in Neurodegenerative diseases BeijingChina Key Laboratory for Neuroscience National Health Commission/Ministry of EducationPeking UniversityBeijingChina

Amyotrophic lateral sclerosis is a rare neurodegenerative disease characterized by the involvement of both upper and lower motor *** bilateral limb involvement significantly affects patients'daily lives and may lead them to be confined to ***,the effect of upper and lower motor neuron impairment and other risk factors on bilateral limb involvement is *** address this issue,we retrospectively collected data from 586 amyotrophic lateral sclerosis patients with limb onset diagnosed at Peking University Third Hospital between January 2020 and May 2022.A univariate analysis revealed no significant differences in the time intervals of spread in different directions between individuals with upper motor neuron-dominant amyotrophic lateral sclerosis and those with classic amyotrophic lateral *** used causal directed acyclic graphs for risk factor determination and Cox proportional hazards models to investigate the association between the duration of bilateral limb involvement and clinical baseline characteristics in amyotrophic lateral sclerosis *** factor analyses revealed that higher upper motor neuron scores(hazard ratio[HR]=1.05,95%confidence interval[CI]=1.01–1.09,P=0.018),onset in the left limb(HR=0.72,95%CI=0.58–0.89,P=0.002),and a horizontal pattern of progression(HR=0.46,95%CI=0.37–0.58,P<0.001)were risk factors for a shorter interval until bilateral limb *** results demonstrated that a greater degree of upper motor neuron involvement might cause contralateral limb involvement to progress more quickly in limb-onset amyotrophic lateral sclerosis *** findings may improve the management of amyotrophic lateral sclerosis patients with limb onset and the prediction of patient prognosis.

关键词： amyotrophic lateral sclerosis bilateral limb involvement Cox proportional hazards regression model horizontal spread restricted cubic spline analysis time interval upper motor neuron vertical spread

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Protein arginine methyltransferase-6 regulates heterogeneous nuclear ribonucleoprotein-F expression and is a potential target for the treatment of neuropathic pain

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Neural Regeneration Research 2025年第9期20卷 2682-2696页

作者： Xiaoyu Zhang Yuqi Liu Fangxia Xu Chengcheng Zhou Kaimei Lu Bin Fang Lijuan Wang Lina Huang Zifeng Xu department of Anesthesiology International Peace Maternity and Child Health HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghaiChina department of Anesthesiology Shanghai General HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghaiChina Shanghai Key Laboratory of Embryo Original diseases ShanghaiChina

Protein arginine methyltransferase-6 participates in a range of biological functions,particularly RNA processing,transcription,chromatin remodeling,and endosomal ***,it remains unclear whether protein arginine methyl transferase-6 modifies neuropathic pain and,if so,what the mechanisms of this *** this study,protein arginine methyltransferase-6 expression levels and its effect on neuropathic pain were investigated in the spared nerve injury model,chronic constriction injury model and bone cancer pain model,using immunohistochemistry,western blotting,immunoprecipitation,and label-free proteomic *** results showed that protein arginine methyltransferase-6 mostly co-localized withβ-tubulinⅢin the dorsal root ganglion,and that its expression decreased following spared nerve injury,chronic constriction injury and bone cancer *** addition,PRMT6 knockout(Prmt6~(-/-))mice exhibited pain ***,the development of spared nerve injury-induced hypersensitivity to mechanical pain was attenuated by blocking the decrease in protein arginine methyltransferase-6 ***,when protein arginine methyltransferase-6 expression was downregulated in the dorsal root ganglion in mice without spared nerve injury,increased levels of phosphorylated extracellular signal-regulated kinases were observed in the ipsilateral dorsal horn,and the response to mechanical stimuli was ***,protein arginine methyltransferase-6 appeared to contribute to spared nerve injury-induced neuropathic pain by regulating the expression of heterogeneous nuclear ***,protein arginine methyltransfe rase-6-mediated modulation of hete rogeneous nuclear ribonucleoprotein-F expression required amino atids 319 to 388,but not classical H3R2 *** findings indicated that protein arginine methyltransferase-6 is a potential therapeutic target fo r the treatment of peripheral neuro pathic pain.

关键词： dorsal root ganglion heterogeneous nuclear ribonucleoprotein F neuropathic pain protein arginine methyltransferase-6 sensory neurons

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Role of Insulin-like Growth Factor II Receptor in Transdifferentiation of Free Silica-induced Primary Rat Lung Fibroblasts

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Biomedical and Environmental Sciences 2013年第12期26卷 979-985页

作者： HAO Chang Fu LI Xiao Fang YAO Wu department of occupational health and occupational Disease College of Public Health Zhengzhou University

Objective To study the role of insulin-like growth factor II receptor in free silica-induced transdifferentiation of primary rat lung fibroblasts Methods Rat lung fibroblasts and rat alveolar macrophages were cultured. A transdifferentiation model of primary rat lung fibroblasts was induced by free silica. Levels of a-SMA protein, IGF-liR protein and mRNA were measured by immunocytochemistry, Western blot and RT-PCR, respectively. Lung fibroblasts were treated with Wortmannin. Results The expression levels of a-SMA concentration and decreased after Wortmann and IGF-IIR increased with the increasing free silica n was used. Conclusion The IGF-IIR plays an important role in free silica-induced transdifferentiation of primary rat lung fibroblasts.

关键词： Transdifferentiation Lung fibroblasts Insulin-like growth factor II receptor Silicosis

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Small molecule inhibitor DDQ-treated hippocampal neuronal cells show improved neurite outgrowth and synaptic branching

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Neural Regeneration Research 2025年第9期20卷 2624-2632页

作者： Jangampalli Adi Pradeepkiran Priyanka Rawat Arubala P.Reddy Erika Orlov PHemachandra Reddy department of Internal Medicine Texas Tech University Health Sciences CenterLubbockTXUSA department of Nutritional Sciences College of Human SciencesTexas Tech UniversityLubbockTXUSA department of Pharmacology&Neuroscience Texas Tech University Health Sciences CenterLubbockTXUSA department of Neurology Texas Tech University Health Sciences CenterLubbockTXUSA department of Speech Language and Hearing SciencesTexas Tech University Health Sciences CenterLubbockTXUSA department of Public health Texas Tech University Health Sciences CenterLubbockTXUSA

The process of neurite outgrowth and branching is a crucial aspect of neuronal development and *** and dendrites,sometimes referred to as neurites,are extensions of a neuron's cellular body that are used to start *** we explored the effects of diethyl(3,4-dihydroxyphenethylamino)(quinolin-4-yl)methylphosphonate(DDQ)on neurite developmental features in HT22 neuronal *** this work,we examined the protective effects of DDQ on neuronal processes and synaptic outgrowth in differentiated HT22cells expressing mutant Tau(mTau)*** investigate DDQ chara cteristics,cell viability,biochemical,molecular,western blotting,and immunocytochemistry were *** outgrowth is evaluated through the segmentation and measurement of neural *** neural processes can be seen and measured with a fluorescence microscope by manually tracing and measuring the length of the neurite *** neuronal processes can be observed and quantified with a fluorescent microscope by manually tracing and measuring the length of the neuronal ***-treated mTau-HT22 cells(HT22 cells transfected with cDNA mutant Tau)were seen to display increased levels of synaptophysin,MAP-2,andβ-***,we confirmed and noted reduced levels of both total and p-Tau,as well as elevated levels of microtubule-associated protein 2,β-tubulin,synaptophysin,vesicular acetylcholine transporter,and the mitochondrial biogenesis protein-pe roxisome prolife rator-activated receptor-gamma coactivator-1α.In mTa u-expressed HT22 neurons,we observed DDQ enhanced the neurite characteristics and improved neurite development through increased synaptic *** findings conclude that mTa u-HT22(Alzheimer's disease)cells treated with DDQ have functional neurite developmental chara *** key finding is that,in mTa u-HT22 cells,DDQ preserves neuronal structure and may even enhance nerve development function with mTa u inhibition.

关键词： diethyl(3 4-dihydroxyphenethylamino)(quinolin-4-yl)methylphosphonate(DDQ) hippocampal neuronal cells HT22 neurite outgrowth neuronal development small molecule

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How Work Organization Affects the Prevalence of WMSDs: A Case-control Study

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Biomedical and Environmental Sciences 2015年第9期28卷 627-633页

作者： LIU Lu CHEN Song Gen TANG Shi Chuan WANG Sheng HE Li Hua GUO Ze Hua LI Jing Yun YU Shan Fa WANG Zhong Xu department of occupational and Environmental health Science Peking University School of Public Health Foshan Institute of occupational Disease Prevention and Control Beijing Key Laboratory of occupational health and Safety Beijing Municipal Institute of Labour Protection Beijing Institute of occupational Medicine for Chemical Industry Henan Provincial Institute for occupational health department of occupational health Protection Institute for Occupational Health and Poison ControlChinese Center of Disease Control and Prevention

Objective In this study, we aimed at exploring the association between work-related musculoskeletal disorders（WMSDs） and work organization based on a case-control study. Methods A total of 1938 workers who claimed to suffer from WMSDs were selected from Beijing, Henan, Hubei, and the Guangdong province. The control group consisted of 2009 workers employed in similar industries without severe disease or musculoskeletal discomforts. We used a modified version of the questionnaire developed by the NMQ and the DMQ to investigate individual and work-related factors. Results A total of 13 variables（P〈0.1） were selected by the chi-square test and finally, 7 variables entered into the equation, with 6 variables reaching statistical significance（P〈0.05）. The odds ratios（OR） of ＇work changing with season＇ and ＇sufficient rest time＇ did not reach 1（0.749 and 0.441, respectively）. In addition, ＇sufficient rest time＇ seemed to be the stronger protective factor according to its higher standardized coefficient. And ＇repetitive work every minute＇, ＇constantly repetitive work＇（every day）, ＇shortage of site personnel＇, and ＇often switching shifts with others＇ seemed to be the risk factors. Conclusion Work organization may have comprehensive effects on the occurrence of WMSDs. This pattern of associations suggests that further investigation into the mechanism of how work organization affects the prevalence of WMSDs is required.

关键词： WMSDs Work organization Case-control study Prevalence Risk factors

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The Role of NF mRNA and Calpain in NF Reduction of Acrylamide Neuropathy

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Biomedical and Environmental Sciences 2015年第6期28卷 445-448页

作者： YU Su Fang WEI Xiao Min YAN Feng Feng WANG Shu E ZHANG Cui Li YANG Xi Wei department of occupational health and occupational Medicine School of Public HealthShandong University

The purpose of this study was to study the role of neurofilament （NF） mRNA and calpain in NF reduction of acrylamide （ACR） neuropathy. Male Wistar adult rats were injected i.p. every other day with AER （20 mg/*** or 40 mg/***） for 8 weeks. NF mRNA expression was detected using RT-PCR and the calpain concentration was determined using western blot analysis. The NF mRNA expression significantly decreased while the level of m-calpain and μ-calpain significantly increased in two ACR-treated rats groups regardless of the ACR dose. The light NF （NF-L） protein expression was significantly correlated with NF-L mRNA expression. Combined with previous data, the concentrations of three NF subunits were negatively correlated with the calpain levels. These findings suggest that NF-L mRNA and calpain mediated the reduction in NF of AER neuropathy.

关键词： neuropathy acrylamide Calpain calpain injected nerves abundant neuronal splay supernatant

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Direct and rapid detection of serum amino acid and monoamine neurotransmitters to assist the diagnosis of panic disorder

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Science China Chemistry 2025年第1期68卷 377-384页

作者： Shiwen Liu Xuerui Wan Meng Zhao Jiaqi Wang Weilan Wu Linlin You Yonggui Yuan Qian Xu Rong Gao Key Laboratory of Environmental Medicine Engineering Ministry of Education School of Public Health Southeast University Key Laboratory of Modern Toxicology of Ministry of Education Department of Hygienic Analysis and Detection School of Public HealthNanjing Medical University department of Psychosomatics and Psychiatry Zhongda Hospital School of Medicine Southeast University

The measurement of amino acid and monoamine neurotransmitters（NTs） in serum plays a central role in the identification and monitoring of clinical panic disorder（PD）. However, the strong polarity and chemical heterogeneity of NTs make direct extraction and rapid detection extremely challenging. Herein, we developed a strategy that integrated solid phase extraction based on magnetic Fe3O4coated with polydopamine（Fe3O4@PDA） and direct analysis of mass spectrometry in real time（DART-MS） for quantification of 10 NTs. We systematically investigated the optimal conditions of this strategy to achieve good accuracy and precision. Compared with existing magnetic solid phase extraction methods for NTs detection in biological samples, this strategy could adsorb more targets while having similar adsorption efficiencies, and the total process time was reduced by an average of 69.42%. We rapidly determined the metabolic abnormality of 6 types of NTs in the serum of PD patients and demonstrated their diagnostic accuracy. In addition, an outstanding feature of PD in which tryptophan was more metabolized by the KYN pathway and the 5-hydroxytryptamine pathway was inhibited could be elucidated by this strategy. Our results highlighted the potential ability of Fe3O4@PDA coupled with DART-MS to assist in the clinical diagnosis of PD.

关键词： neurotransmitters panic disorder magnetic solid phase extraction direct analysis of mass spectrometry in real time

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Tuberculosis in the mines of Zambia:A case for intervention

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Asian Pacific Journal of Tropical Biomedicine 2016年第9期6卷 803-807页

作者： Pascalina Chanda-Kapata Doris Osei-Afriyie Connrad Mwansa Nathan Kapata department of Disease Surveillance Control and Research Ministry of Health department of occupational health Occupational Health and Safety Institute department of diseases Surveillance Control and Research National TB/Leprosy Control ProgramMinistry of Health

Zambia is among the sub-Saharan countries highly burdened with tuberculosis(TB) and has an estimated prevalence rate of 638 per 100 000 population in those aged 15 years and *** mining industry is the main contributor to the country's gross national product,although it is associated with public health challenges,with TB in the mines being among the occupational health diseases having a negative economic impact and threatening to delay the control of TB in the *** reviewed available evidence on the extent of the burden of TB in the mines so as to inform the development of targeted interventions for the post-2015 End TB *** was a review of published data from Medline/Pubmed,Cochrane Library and Embase,including unpublished "grey"literature on the burden of TB and the risk factors of TB in the mines of *** is limited research in Zambia to fully understand the burden of TB and risk factors associated with TB in the ***,the few studies and data available have shown that TB is a significant health problem requiring interventions to improve the quality of life of miners,ex-miners and surrounding *** is a potential problem in the mines of Zambia and the actual burden needs to be *** to silica as a risk factor needs further investigation.

关键词： Tuberculosis Zambia occupational health diseases Silica Mines

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Cortical hem signaling center: functions, development, and potential implications for evolution and brain disorders

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Neural Regeneration Research 2025年第4期20卷 1079-1080页

作者： Victor V.Chizhikov Igor Y.Iskusnykh department of Anatomy and Neurobiology University of Tennessee Health Science CenterMemphisTNUSA

Development of the telencephalon relies upon several signaling centers-localized cellular populations that supply secreted factors to pattern the cortical *** such signaling center is the cortical hem,which arises during embryonic development at the telencephalic dorsal midline,adjacent to the choroid plexus and hippocampal primordium(Figure 1A).While the cortical hem has also been described in reptiles and birds,most of our knowledge about the developmental roles of the cortical hem is derived from the analysis in *** cortical hem produces several types of secreted molecules,including wingless-related integration site(Wnt)and bone morphogenetic(Bmp)*** cortical hem is particularly important for the development of the hippocampus,which is involved in learning and memory,and the neocortex,which is the most complex brain region that mediates multiple types of behavior and higher cognitive functions(Mangale et al.,2008;Dal-Valle-Anton and Borrell,2022).

关键词： epithelium Figure center

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Characterizing drug-metabolizing enzymes and transporters that are bona fide CAR-target genes in mouse intestine

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Acta Pharmaceutica Sinica B 2016年第5期6卷 475-491页

作者： Shinhee Park Sunny Lihua Cheng Julia Yue Cui department of Environmental and occupational health Sciences University of Washington

Intestine is responsible for the biotransformation of many orally-exposed *** constitutive androstane receptor(CAR/Nr1i3) is known to up-regulate many genes encoding drugmetabolizing enzymes and transporters(drug-processing genes/DPGs) in liver,but less is known regarding its effect in ***-day-old wild-type and Car / mice were administered the CARligand TCPOBOP or vehicle once daily for 4 *** wild-type mice,Car m RNA was down-regulated by TCPOBOP in liver and *** / mice had altered basal intestinal expression of many DPGs in a section-specific *** with the liver data(Aleksunes and Klaassen,2012),TCPOBOP upregulated many DPGs(Cyp2b10,Cyp3a11,Aldh1a1,Aldh1a7,Gsta1,Gsta4,Gstm1-m4,Gstt1,Ugt1a1,Ugt2b34,Ugt2b36,and Mrp2–4) in specific sections of small intestine in a CAR-dependent ***,the m RNAs of Nqo1 and Papss2 were previously known to be up-regulated by TCPOBOP in liver but were not altered in ***,many known CAR-target genes were highest expressed in colon where CAR is minimally expressed,suggesting that additional regulators are involved in regulating their *** conclusion,CAR regulates the basal expression of many DPGs in intestine,and although many hepatic CAR-targeted DPGs were bona fide CAR-targets in intestine,pharmacological activation of CAR in liver and intestine are not identical.

关键词： Drug-processing genes Intestine Mice CAR Drug-metabolizing enzymes Transporters

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