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Different frequencies of repetitive transcranial magnetic stimulation combined with local injection of botulinum toxin type A for post-stroke lower limb spasticity:study protocol for a prospective,single-center,non-randomized,controlled clinical trial

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Neural Regeneration Research 2022年第11期17卷 2491-2496页

作者： Yang Shao Yang Yang Yong-Xin Sun ai-hua xu Department of Rehabilitation Medicine the First Affiliated Hospital of China Medical UniversityShenyangLiaoning ProvinceChina

No definite consensus has currently been reached regarding the safety and efficacy of low-or high-frequency repetitive transcranial magnetic stimulation in the treatment of post-stroke muscle spasticity.The latest research indicates that when combined with local injections of botulinum toxin type A,it is more effective on post-stroke muscle spasticity than local injections of botulinum toxin type A alone.We designed a prospective,single-center,non-randomized,controlled clinical trial to investigate the safety and effica cy of different frequencies of repetitive transcranial magnetic stimulation combined with local injections of botulinum toxin type A in treating post-stroke lower limb muscle spasticity to determine an optimal therapeutic regimen.This trial will enroll 150 patients with post-stroke muscle spasticity admitted to the Department of Rehabilitation Medicine at the First Affiliated Hos pital of China Medical Unive rsity.All enrolled patients will undergo ro utine rehabilitation training and will be divided into five groups in-30 per group) according to the particular area of cerebral infa rction and treatment methods.G roup A:Patients with massive cerebral infarction will be given local injections of botulinum toxin type A and low-frequency(1 Hz)repetitive transcranial magnetic stimulation on the contralate ral side;G roup B:Patients with non-massive cerebral infarction will be given local injections of botulinum toxin type A and high-frequency(10-20 Hz) re petitive transcranial magnetic stimulation on the affected side;G roup C:Patients with massive/non-massive cerebral infarction will be given local injections of botulinum toxin type A;G roup D:Patients with massive cerebral infarction will be given low-frequency(1 Hz) repetitive transcranial magnetic stimulation on the contralate ral side;and G roup E:Patients with non-massive cerebral infa rction will be given high-frequency(10-20 Hz) repetitive transcranial magnetic stimulation on the affected side.The primary outcome measure of this trial is a mod

关键词： Botulinum toxin type A exercise lower limbs muscle spasticity neural regeneration rehabilitation training repetitive transcranial magnetic stimulation stroke

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Poly(ADP-ribose)polymerase family member 14 promotes functional recovery after spinal cord injury through regulating microglia M1/M2 polarization via STAT1/6 pathway

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Neural Regeneration Research 2023年第8期18卷 1809-1817页

作者： ai-hua xu Yang Yang Yang Shao Man-Yu Jiang Yong-Xin Sun Department of Rehabilitation Medicine The First Hospital of China Medical UniversityShenyangLiaoning ProvinceChina

Poly(ADP-ribose)polymerase family member 14(PARP14),which is an intracellular mono(ADP-ribosyl)transferase,has been reported to promote post-stroke functional recovery,but its role in spinal cord injury(SCI)remains unclear.To investigate this,a T10 spinal cord contusion model was established in C57BL/6 mice,and immediately after the injury PARP14 shRNA-carrying lentivirus was injected 1 mm from the injury site to silence PARP14 expression.We found that PARP14 was up-regulated in the injured spinal cord and that lentivirus-mediated downregulation of PARP14 aggravated functional impairment after injury,accompanied by obvious neuronal apoptosis,severe neuroinflammation,and slight bone loss.Furthermore,PARP14 levels were elevated in microglia after SCI,PARP14 knockdown activated microglia in the spinal cord and promoted a shift from M2-polarized microglia(anti-inflammatory phenotype)to M1-polarized microglia(pro-inflammatory phenotype)that may have been mediated by the signal transducers and activators of transcription(STAT)1/6 pathway.Next,microglia M1 and M2 polarization were induced in vitro using lipopolysaccharide/interferon-γand interleukin-4,respectively.The results showed that PARP14 knockdown promoted microglia M1 polarization,accompanied by activation of the STAT1 pathway.In addition,PARP14 overexpression made microglia more prone to M2 polarization and further activated the STAT6 pathway.In conclusion,these findings suggest that PARP14 may improve functional recovery after SCI by regulating the phenotypic transformation of microglia via the STAT1/6 pathway.

关键词： apoptosis M1 polarization M2 polarization microglia neuroinflammation PARP14 silencing spinal cord injury STAT1 pathway STAT6 pathway

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Research hotspots and effectiveness of repetitive transcranial magnetic stimulation in stroke rehabilitation

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Neural Regeneration Research 2020年第11期15卷 2089-2097页

作者： ai-hua xu Yong-Xin Sun Department of Rehabilitation Medicine the First Affiliated Hospital of China Medical UniversityShenyangLiaoning ProvinceChina

Repetitive transcranial magnetic stimulation, as a relatively new type of rehabilitation treatment, is a painless and non-invasive method for altering brain excitability. Repetitive transcranial magnetic stimulation has been widely used in the neurorehabilitation of stroke patients. Here, we used CiteSpace software to visually analyze 315 studies concerning repetitive transcranial magnetic stimulation for stroke rehabilitation from 1999 to 2019, indexed by Web of Science, to clarify the research hotspots in different periods and characterize the gradual process of discovery in this field. We found that four main points were generally accepted:(1) repetitive transcranial magnetic stimulation has a positive effect on motor function recovery in patients with subcortical stroke;(2) it may be more advantageous for stroke patients to receive low-frequency repetitive transcranial magnetic stimulation in the unaffected hemispheres than to receive high-frequency repetitive transcranial magnetic stimulation in affected hemisphere;(3) low-frequency repetitive transcranial magnetic stimulation has become a potential therapeutic tool for patients with non-fluent aphasia after chronic stroke for neurological rehabilitation and language recovery;and(4) there are some limitations to these classic clinical studies, such as small sample size and low test efficiency. Our assessment indicates that prospective, multi-center, large-sample, randomized controlled clinical trials are still needed to further verify the effectiveness of various repetitive transcranial magnetic stimulation programs for the rehabilitation of stroke patients.

关键词： data visualization motor recovery rehabilitation repetitive transcranial magnetic stimulation stroke stroke rehabilitation transcranial magnetic stimulation

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Exogenous brain-derived neurotrophic factor attenuates cognitive impairment induced by okadaic acid in a rat model of Alzheimer's disease

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Neural Regeneration Research 2018年第12期13卷 2173-2181页

作者： ai-hua xu Yang Yang Yong-Xin Sun Chao-Dong Zhang Department of Rehabilitation Medicine the First Affiliated Hospital of China Medical University Department of Neurology the First Affiliated Hospital of China Medical University

Decreased expression of brain-derived neurotrophic factor（BDNF） plays an important role in the pathogenesis of Alzheimer＇s disease, and a typical pathological change in Alzheimer＇s disease is neurofibrillary tangles caused by hyperphosphorylation of tau. An in vivo model of Alzheimer＇s disease was developed by injecting okadaic acid（2 μL） and exogenous BDNF（2 μL） into the hippocampi of adult male Wister rats. Spatial learning and memory abilities were assessed using the Morris water maze. The expression levels of protein phosphatase 2 A（PP2 A）, PP2 Ac-Yp307, p-tau（Thr231）, and p-tau（Ser396/404） were detected by western blot assay. The expression levels of BDNF, TrkB, and synaptophysin mRNA were measured by quantitative real-time polymerase chain reaction. Our results indicated that BDNF expression was suppressed in the hippocampus of OA-treated rats, which resulted in learning and memory deficits. Intra-hippocampal injection of BDNF attenuated this OA-induced cognitive impairment. Finally, our findings indicated an involvement of the PI3 K/GSK-3β/AKT pathway in the mechanism of BDNF in regulating cognitive function. These results indicate that BDNF has beneficial effect on Alzheimer＇s disease, and highlight the potential of BDNF as a drug target for treatment of Alzheimer＇s disease.

关键词： nerve regeneration Alzheimer＇s disease exogenous brain-derived neurotrophic factor Tau protein okadaic acid phosphorylation PP2A- Y307 glycogen synthase kinase-3~ TrkB cognitive function brain protection neural regeneration

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Effects of a Shuangling Fuzheng anticancer preparation on the proliferation of SGC-7901 cells and immune function in a cyclophosphamide-treated murine model

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World Journal of Gastroenterology 2007年第48期13卷 6575-6580页

作者： hua-Sheng Chen Jue Chen De-Li Cui Yuan-Yuan Zheng ai-hua xu Gang Chen Ling-Chang Jia Yangzhou University Medical College Yangzhou 225001 Jiangsu Province China Jiangsu Province Subei People Hospital Yangzhou 225001 Jiangsu Province China

aiM: To study the inhibitory effects of a Shuangling Fuzheng anticancer preparation (SFAP) on the human gastric cancer cell line SGC-7901 in vitro as well as its immune-modulated effects in a cyclophosphamide-treated murine model. METHODS: MTT experiments and immunocytochemistry ABC experiments were performed for detecting the proliferation of SGC-7901 cells in vitro and protein expression of c-myc. The staphylococcal protein A (SPA) rosette test was utilized for measuring the ratio of T-lymphocyte subsets from peripheral blood in a cyclophosphamide-treated murine model. Enzyme- linked immunosorbant assay (ELISA) was performed for measuring the levels of serum sIL-2R in treated mice, while immunoturbidimetry was used for measuring the levels of immunoglobulins (Ig). RESULTS: SFAP (40-640 mg/L, 48 h) inhibited the proliferation of SGC-7901 cells, and a positive correlation was noted between inhibitory effects and dosage. At a dosage of 160-320 mg/L in cultured cells, the expression of c-myc was decreased. SFAP (50-200 mg/kg) increased the percentage of CD3+ and CD4+ T-lymphocytes, the ratio of CD4/CD8, and the contents of Ig such as IgM, IgG or IgA, but decreased the levels of serum sIL-2R in peripheral blood from cyclophosphamide-treated mice. CONCLUSION: SFAP can inhibit the proliferation of SGC-7901 cells via the c-myc gene. In addition, SFAP can modulat the cellular and humoral immunity in cyclophosphamide-induced immunosuppressed mice.

关键词： SGC-7901 免疫功能细胞增生环磷酰胺抗癌药

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Design of an automated robotic microinjection system for batch injection of zebrafish embryos and larvae

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Microsystems & Nanoengineering 2024年第1期10卷 89-103页

作者： Zhongyi Guo Nana ai Wei Ge Qingsong xu Department of Electromechanical Engineering Faculty of Science and TechnologyUniversity of MacaoMacaoChina Department of Biomedical Sciences and Centre of Reproduction Development and Aging(CRDA)Faculty of Health SciencesUniversity of MacaoMacaoChina

This paper presents the design of a vision-based automated robotic microinjection system for batch injection of both zebrafish embryos and larvae.A novel visual recognition algorithm based on an automatic threshold and excessive dilatation is introduced to accurately identify the center of zebrafish embryos and larval yolks.A corresponding software system is developed using the producer-consumer model as the framework structure,and a friendly user interface is designed to allow operators to choose from a range of desired functions according to their different needs.In addition,a novel microstructural agarose device is designed and fabricated to simultaneously immobilize mixed batches of embryos and larvae.Moreover,a prototype microinjection system is fabricated by integrating hardware devices with visual algorithms.An experimental study is conducted to verify the performance of the robotic microinjection system.The results show that the reported system can accurately identify zebrafish embryos and larvae and efficiently complete batch microinjection tasks of the mixtures with an injection success rate of 92.05%in 13.88 s per sample.Compared with manual and existing microinjection systems,the proposed system demonstrates the merits of versatility,excellent efficiency,high success rate,high survival rate,and sufficient stability.

关键词： zebra automated hardware

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Reliability ensemble averaging reduces surface wind speed projection uncertainties in the 21st century over China

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Advances in Climate Change Research 2024年第2期15卷 222-229页

作者： Zheng-Tai ZHANG Chang-ai xu Key Laboratory for Semi-Arid Climate Change of the Ministry of Education College of Atmospheric SciencesLanzhou UniversityLanzhou 730000China

Accurate prediction of future surface wind speed(SWS)changes is the basis of scientific planning for wind turbines.Most studies have projected SWS changes in the 21st century over China on the basis of the multi-model ensemble(MME)of the 6th Coupled Model Intercomparison Project(CMIP6).However,the simulation capability for SWS varies greatly in CMIP6 multi-models,so the MME results still have large uncertainties.In this study,we used the reliability ensemble averaging(REA)method to assign each model different weights according to their performances in simulating historical SWS changes and project the SWS under different shared socioeconomic pathways(SSPs)in 2015-2099.The results indicate that REA considerably improves the SWS simulation capacity of CMIP6,eliminating the overestimation of SWS by the MME and increasing the simulation capacity of spatial distribution.The spatial correlations with observations increased from 0.56 for the MME to 0.85 for REA.Generally,REA could eliminate the overestimation of the SWS by 33%in 2015-2099.Except for southeastern China,the SWS generally decreases over China in the near term(2020-2049)and later term(2070-2099),particularly under high-emission scenarios.The SWS reduction projected by REA is twice as high as that by the MME in the near term,reaching-4%to-3%.REA predicts a larger area of increased SWS in the later term,which expands from southeastern China to eastern China.This study helps to reduce the projected SWS uncertainties.

关键词： Surface wind speed Uncertainty Multi-model ensemble Reliability ensemble averaging CMIP6

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Aldehyde oxidase mediated enantioselective metabolic health risk of dinotefuran

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Science China Chemistry 2024年第6期67卷 2079-2091页

作者： Liwei xu Xinxin xu hua Kuang Chuanlai xu Xiaoling Wu State Key Laboratory of Food Science and Resources Jiangnan UniversityWuxi214122China International Joint Research Laboratory for Biointerface and Biodetection and School of Food Science and Technology Jiangnan UniversityWuxi214122China Collaborative Innovation center of Food Safety and Quality Control in Jiangsu Province Jiangnan UniversityWuxi214122China

Chiral pollutants often pose significant differential environmental health risks.In this study,the biotransformation of chiral dinotefuran(DIN)and its enantioselective metabolic toxicity mechanisms have been systemically investigated.Firstly,reversedphase chromatography-high resolution mass spectrometry was developed to quantify the content of DIN R/S chiral enantiomer with pg level sensitivity,revealing a lower elimination rate constant(K_(e))of S-DIN(0.730 h^(-1))than R-DIN(0.746 h^(-1)).Secondly,the interaction mechanism between DIN metabolism and important endogenous bioactive molecules,such as aldehyde oxidase(AOX)and neurotransmitters,was revealed.The DIN nitro-group was converted into a guanidine group by the reducing site of nearby flavin adenine dinucleotide(FAD)in AOX with the preferred higher affinity of S-configuration.Meanwhile,the endogenous tryptophan(Trp)aldehyde metabolic intermediate,5-hydroxyindoleacetaldehyde(5-HIAL),provides a persistent electron donor for DIN reduction via the oxidation-catalyzed site in AOX,resulting in remarkable up-regulation of monoamine neurotransmitters such as serotonin and dopamine.Thirdly,the higher level of neurotransmitters further mediated dysregulation of oxylipin homeostasis via the serotonergic pathway,where S-DIN exhibited more pronounced liver lipid damage and environmental health risk with the accumulated lipid biomarkers,oxidized triglyceride(OxTG)and oxidized sphingomyelin(OxSM).This study elucidates the AOX-mediated enantioselectivity metabolic pathway of DIN,providing a new analytical method for chiral pollutants and paves the way for their health risk assessments.

关键词： neonicotinoid dinotefuran enantiomer aldehyde oxidase metabolomics health risk

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Dietary fiber intake and its association with diabetic kidney disease in American adults with diabetes:A cross-sectional study

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World Journal of Diabetes 2024年第3期15卷 475-487页

作者： Xin-hua Jia Sheng-Yan Wang ai-Qin Sun Department of Critical Care Medicine Dezhou People’s HospitalDezhou 253000Shandong ProvinceChina Emergency Intensive Care Unit Dezhou People’s HospitalDezhou 253000Shandong ProvinceChina

BACKGROUND Dietary fiber(DF)intake may have a protective effect against type 2 diabetes(T2D);however,its relationship with diabetic kidney disease(DKD)remains unclear.aiM To investigate the potential association between DF intake and the prevalence of DKD in individuals diagnosed with T2D.METHODS This cross-sectional study used data from the National Health and Nutrition Examination Survey collected between 2005 and 2018.DF intake was assessed through 24-h dietary recall interviews,and DKD diagnosis in individuals with T2D was based on predefined criteria,including albuminuria,impaired glomerular filtration rate,or a combination of both.Logistic regression analysis was used to assess the association between DF intake and DKD,and comprehensive subgroup and sensitivity analyses were performed.RESULTS Among the 6032 participants,38.4%had DKD.With lower DF intake-T1(≤6.4 g/1000 kcal/day)-as a reference,the adjusted odds ratio for DF and DKD for levels T2(6.5-10.0 g/1000 kcal/day)and T3(≥10.1 g/1000 kcal/day)were 0.97(95%CI:0.84-1.12,P=0.674)and 0.79(95%CI:0.68-0.92,P=0.002),respectively.The subgroup analysis yielded consistent results across various demographic and health-related subgroups,with no statistically significant interactions(all P>0.05).CONCLUSION In United States adults with T2D,increased DF intake may be related to reduced DKD incidence.Further research is required to confirm these findings.

关键词： Dietary fiber Diabetic kidney disease Type 2 diabetes National Health and Nutrition Examination Survey Crosssectional study

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Gastrointestinal contrast-enhanced ultrasonography for diagnosis and treatment of peptic ulcer in children

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World Journal of Gastroenterology 2024年第7期30卷 705-713页

作者： Yu-hua Zhang Zhi-hua xu Shuang-Shuang Ni Hong-Xia Luo Department of Ultrasound The Second Affiliated Hospital of Wenzhou Medical UniversityWenzhou 325000Zhejiang ProvinceChina

BACKGROUND The detection rate of peptic ulcer in children is improving,with development of diagnostic procedures.Gastroscopy is the gold standard for the diagnosis of peptic ulcer,but it is an invasive procedure.Gastrointestinal contrast-enhanced ultrasonography(CEUS)has the advantages of being painless,noninvasive,nonradioactive,easy to use,and safe.aiM To investigate the clinical value of CEUS for diagnosis and treatment of peptic ulcer in children.METHODS We investigated 43 children with digestive tract symptoms in our hospital from January 2021 to June 2022.All children were examined by routine ultrasound,gastrointestinal CEUS,and gastroscopy.The pathological results of gastroscopy were taken as the gold standard.Routine ultrasonography was performed before gastrointestinal CEUS.Conventional ultrasound showed the thickness of the gastroduodenal wall,gastric peristalsis,and the adjacent organs and tissues around the abdominal cavity.Gastrointestinal CEUS recorded the thickness of the gastroduodenal wall;the size,location and shape of the ulcer;gastric peristalsis;and adjacent organs and tissues around the abdominal cavity.The results of routine ultrasound and gastrointestinal ultrasound were compared with those of gastroscopy to evaluate the diagnostic results and coincidence rate of routine ultrasound and gastrointestinal CEUS.All children received informed consent from their guardians for CEUS.This study was reviewed and approved by the hospital medical ethics committee.RESULTS Among the 43 children,17(15 male,2 female)were diagnosed with peptic ulcer by gastroscopy.There were 26 children with nonpeptic ulcer.There were eight cases of peptic ulcer and 35 of nonpeptic ulcer diagnosed by conventional ultrasound.The diagnostic coincidence rate of peptic ulcer in children diagnosed by conventional ultrasound was 79.1%(34/43),which was significantly different from that of gastroscopy(P=0.033).It indicates that the coincidence rate of gastrointestinal contrast-enhanced ultrasound and gastroscope is low.Fifteen cas

关键词： Contrast-enhanced ultrasound Peptic ulcer Children Gastrointestinal tract Abdominal pain Acoustic contrast agent

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