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1.
Artículo en Inglés | MEDLINE | ID: mdl-39068348

RESUMEN

This study aimed to apply machine learning (ML) techniques to develop and validate a risk prediction model for post-stroke lower extremity deep vein thrombosis (DVT) based on patients' limb function, activities of daily living (ADL), clinical laboratory indicators, and DVT preventive measures. We retrospectively analyzed 620 stroke patients. Eight ML models-logistic regression (LR), support vector machine (SVM), random forest (RF), decision tree (DT), neural network (NN), extreme gradient boosting (XGBoost), Bayesian (NB), and K-nearest neighbor (KNN)-were used to build the model. These models were extensively evaluated using ROC curves, AUC, PR curves, PRAUC, accuracy, sensitivity, specificity, and clinical decision curves (DCA). Shapley's additive explanation (SHAP) was used to determine feature importance. Finally, based on the optimal ML algorithm, different functional feature set models were compared with the Padua scale to select the best feature set model. Our results indicated that the RF algorithm demonstrated superior performance in various evaluation metrics, including AUC (0.74/0.73), PRAUC (0.58/0.58), accuracy (0.75/0.77), and sensitivity (0.78/0.80) in both the training set and test set. DCA analysis revealed that the RF model had the highest clinical net benefit. SHAP analysis showed that D-dimer had the most significant influence on DVT, followed by age, Brunnstrom stage (lower limb), prothrombin time (PT), and mobility ability. The RF algorithm can predict post-stroke DVT to guide clinical practice.

2.
Biochem Biophys Res Commun ; 580: 20-27, 2021 11 26.
Artículo en Inglés | MEDLINE | ID: mdl-34607259

RESUMEN

Melatonin has been well documented for its neuroprotective role through inhibiting oxidative stress against traumatic brain injury (TBI). However, the specific role of melatonin and the exact effects on cell responses (neurons, astrocytes, and microglia) in different brain regions are unclear. Here, we subjected mice to closed head injury, to establish a repeated mild TBI model and detect neuronal activity and glial responses in cognition-related brain regions after melatonin administration. Melatonin only showed cognitive enhancement if administered during early pathological stages, but not in late (chronic) stages. Additionally, we observed a significant increase in neuronal activity and inhibition of astrocyte reactivation in medial prefrontal cortex and hippocampus, but not in other cognitive deficit related brain regions. Furthermore, by activating astrocytes in these brain regions, we found neuronal activity upregulation and cognitive improvement following melatonin treatment. Therefore, we concluded that melatonin administration during the early stages of TBI is necessary to inhibit astrocyte reactivation and to promote cognitive function. Our results provide evidence for use of melatonin for cognitive improvement after TBIs.


Asunto(s)
Astrocitos/efectos de los fármacos , Lesiones Traumáticas del Encéfalo/tratamiento farmacológico , Disfunción Cognitiva/tratamiento farmacológico , Melatonina/uso terapéutico , Fármacos Neuroprotectores/uso terapéutico , Animales , Astrocitos/patología , Lesiones Traumáticas del Encéfalo/complicaciones , Lesiones Traumáticas del Encéfalo/fisiopatología , Disfunción Cognitiva/etiología , Disfunción Cognitiva/fisiopatología , Masculino , Ratones
3.
Med Sci Monit ; 27: e931601, 2021 Jul 25.
Artículo en Inglés | MEDLINE | ID: mdl-34304239

RESUMEN

BACKGROUND This study aimed to investigate the effects of repetitive transcranial magnetic stimulation (rTMS) and treadmill training (TT) on motor function recovery in rats with partial spinal cord injury (SCI). MATERIAL AND METHODS Sixty rats with moderate partial SCI at the 9th thoracic vertebral level induced by a Louisville Injury System Apparatus impactor were randomly allocated to 5 groups: Sham surgery (Intact); Sham rTMS without TT (S-rTMS/Non-TT); Sham rTMS with TT (S-rTMS/TT); rTMS without TT (rTMS/Non-TT); and rTMS with TT (rTMS/TT). Interventions commenced 8 days after SCI and continued for 8 weeks. Outcomes studied were Basso, Beattie, and Bresnahan locomotor scale scores, grid walking test, and biochemical analysis of the brain-derived neurotrophic factor (BDNF), synapsin I (SYN), and postsynaptic density protein-95 (PSD-95) in the motor cortex and spinal cord. RESULTS The rTMS/TT contributed to greater Basso, Beattie, and Bresnahan scores compared with the S-rTMS/Non-TT (P<0.01), S-rTMS/TT (P<0.05), and rTMS/Non-TT (P<0.05), and showed obviously reduced numbers of foot drops compared with the S-rTMS/Non-TT (P<0.05). The rTMS/TT significantly increased the expressions of BDNF, SYN, and PSD-95 compared with the S-rTMS/Non-TT, both in the motor cortex (P<0.01, P<0.01, P<0.001, respectively) and spinal cord (P<0.001, P<0.01, P<0.05, respectively). CONCLUSIONS In a modified rat model of SCI, combined rTMS with TT improved motor function, indicating that this combined approach promoted adaptive neuroplasticity between the motor cortex and the spinal cord. A combined app roach to improving motor function following SCI requires further evaluation to determine the possible clinical applications.


Asunto(s)
Actividad Motora/fisiología , Condicionamiento Físico Animal/métodos , Recuperación de la Función/fisiología , Traumatismos de la Médula Espinal/rehabilitación , Estimulación Magnética Transcraneal/métodos , Animales , Modelos Animales de Enfermedad , Femenino , Ratas , Ratas Sprague-Dawley , Traumatismos de la Médula Espinal/fisiopatología
4.
BMC Med Genet ; 21(1): 36, 2020 02 17.
Artículo en Inglés | MEDLINE | ID: mdl-32066403

RESUMEN

BACKGROUND: Rs4977574 (A > G) and Rs1333045 (C > T) are both single nucleotide polymorphisms (SNPs) related with coronary artery disease, locating on chromosome 9p21.3. The study aimed to identify the correlation between rs4977574 and rs1333045 polymorphism genotypes and coronary heart disease (CHD) in a Chinese population. METHODS: Blood samples were collected from 855 subjects. A case-control study was used in this experiment, and 598 cases in the CHD group and 257 subjects in the control group were enrolled. Genotyping was identified by the Agena MassARRAY system. Statistical analysis was conducted by SPSS (Ver 16.0) and plink (Ver. 1.07, Shaun Purcell). Haplotype analysis was performed using Haploview software. RESULTS: Association analysis by plink indicated a significant difference in the allele distribution for single nucleotide polymorphisms between cases and controls (rs4977574 P = 0.003, rs1333045 P = 0.035). Fisher's exact test by plink proved that allele G may be associated with a higher risk of CHD (P = 0.003, odds ratio (OR) = 1.371) and the T allele was likely to reduce the risk of coronary events (P = 0.035, OR = 0.798). The serum levels of apolipoprotein A (ApoA) were higher in subjects with the AG + AA genotype of rs4977574 compared to those with the GG genotype (P = 0.028). In the dominant model of rs1333045, the levels of ApoA were higher and LDL levels were lower in the TC + TT genotype than in the CC genotype. CONCLUSIONS: The present study examined the association between the 9p21 chromosome rs4977574 and rs1333045 polymorphism genotypes and CHD in a population of Chinese patients. The G allele of rs4977574 and the C allele of rs1333045 are the susceptibility sites of CHD.


Asunto(s)
Enfermedad Coronaria/genética , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Polimorfismo de Nucleótido Simple/genética , Anciano , Alelos , Enfermedad Coronaria/fisiopatología , Femenino , Frecuencia de los Genes , Genotipo , Haplotipos/genética , Humanos , Masculino , Persona de Mediana Edad , Factores de Riesgo
5.
J Med Virol ; 92(7): 841-848, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-32243599

RESUMEN

A novel coronavirus pneumonia, first identified in Wuhan City and referred to as COVID-19 by the World Health Organization, has been quickly spreading to other cities and countries. To control the epidemic, the Chinese government mandated a quarantine of the Wuhan city on January 23, 2020. To explore the effectiveness of the quarantine of the Wuhan city against this epidemic, transmission dynamics of COVID-19 have been estimated. A well-mixed "susceptible exposed infectious recovered" (SEIR) compartmental model was employed to describe the dynamics of the COVID-19 epidemic based on epidemiological characteristics of individuals, clinical progression of COVID-19, and quarantine intervention measures of the authority. Considering infected individuals as contagious during the latency period, the well-mixed SEIR model fitting results based on the assumed contact rate of latent individuals are within 6-18, which represented the possible impact of quarantine and isolation interventions on disease infections, whereas other parameter were suppose as unchanged under the current intervention. The present study shows that, by reducing the contact rate of latent individuals, interventions such as quarantine and isolation can effectively reduce the potential peak number of COVID-19 infections and delay the time of peak infection.


Asunto(s)
Betacoronavirus/patogenicidad , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/transmisión , Brotes de Enfermedades , Modelos Estadísticos , Neumonía Viral/epidemiología , Neumonía Viral/transmisión , Cuarentena , Adulto , COVID-19 , China/epidemiología , Control de Enfermedades Transmisibles , Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/prevención & control , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pandemias/prevención & control , Neumonía Viral/diagnóstico , Neumonía Viral/prevención & control , SARS-CoV-2 , Índice de Severidad de la Enfermedad
6.
FASEB J ; 33(9): 10425-10442, 2019 09.
Artículo en Inglés | MEDLINE | ID: mdl-31219699

RESUMEN

Triggering receptor expressed in myeloid cells (TREM)2 is a genetic high-risk factor for sporadic Alzheimer's disease (AD) and is considered a potential target for AD diagnosis and therapy, although its role in the different stages of AD remains controversial. We generated an embryonic deletion of Trem2 (whole body deletion) and induced hippocampal- and cortical-specific knockdown of microglial Trem2 at different stages of the AD process in amyloid precursor protein/Psen1 mice by adeno-associated virus (AAV) infection. AAV infection induced microglial Trem2 overexpression in the hippocampus of wild-type (WT) and thymus cell antigen 1-enhanced green fluorescent protein mice. Mice were subjected to ethological and pathologic tests. Whole body genetic deletion of Trem2 exerted different electrophysiological outcomes between different AD pathologic stages, which results from a complex integration of synaptic loss and amyloid aggregation. Interestingly, knockdown of Trem2 at the early-middle stage of AD (2-6 mo) prevents synaptic loss through directly inhibiting microglial phagocytosis, whereas knockdown of Trem2 at the middle-late stage of AD (6-10 mo) accelerates synaptic dysfunction because of more severe amyloid deposition caused by the depression of microglial phagocytosis. Additionally, hippocampal overexpression of Trem2 in WT mice results in significant synaptic impairment. Here, with transgenic technology and electrophysiological assay, we revealed that TREM2 up-regulation promotes microglial phagocytosis equally against synapse and amyloid plaques and eventually results in different outcomes. During the early-middle pathologic stage, TREM2 enhancing microglial phagocytosis mainly causes synaptic loss. However, TREM2 up-regulating microglial phagocytosis gradually supports a positive role when amyloid deposition occupies the leading position at the middle-late pathologic stage. In this study, we highlighted that TREM2 triggers synaptic loss during AD pathology development.-Sheng, L., Chen, M., Cai, K., Song, Y., Yu, D., Zhang, H., Xu, G. Microglial Trem2 induces synaptic impairment at early stage and prevents amyloidosis at late stage in APP/PS1 mice.


Asunto(s)
Enfermedad de Alzheimer/complicaciones , Precursor de Proteína beta-Amiloide/fisiología , Amiloidosis/prevención & control , Glicoproteínas de Membrana/fisiología , Placa Amiloide/patología , Presenilina-1/fisiología , Receptores Inmunológicos/fisiología , Sinapsis/patología , Amiloidosis/etiología , Amiloidosis/patología , Animales , Encéfalo/metabolismo , Encéfalo/patología , Modelos Animales de Enfermedad , Masculino , Ratones , Ratones Noqueados , Ratones Transgénicos , Microglía/metabolismo , Fagocitosis , Placa Amiloide/metabolismo , Sinapsis/metabolismo , Transmisión Sináptica
7.
J Clin Lab Anal ; 34(12): e23552, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-32889742

RESUMEN

BACKGROUND: Circular RNAs (circRNAs) may act as biomarkers of coronary artery disease (CAD). However, the relationship between expression characteristics of circRNAs and coronary atherosclerosis has not been fully explored. The aim of this study was to determine and characterize the circRNAs from human coronary artery. METHODS: The coronary artery segments were obtained from an 81-year-old male patient with sudden death of myocardial infarction at autopsy. The coronary stenosis and atherosclerosis were evaluated by hematoxylin and eosin (H&E) staining, and the circRNAs expression profile was characterized by RNA sequencing (RNA-seq). The differentially expressed circRNAs were validated by qRT-PCR. RESULTS: The analysis of H&E staining indicated that coronary atherosclerosis grade and extent in the LM was more serious than that in other coronary arteries. Twenty-seven circRNAs were selected for expression validation in coronary artery. CircRNAs corresponding cyclization sites of 3 circRNAs (hsa_circ_0016868, hsa_circ_0001364, hsa_circ_0006731) have been verified by Sanger sequencing. CONCLUSION: The 3 circRNAs are suggested to play a pathological role underlying the coronary arteries atherosclerosis and may serve as a valuable resource as diagnostic or therapeutic targets against CAD.


Asunto(s)
Enfermedad de la Arteria Coronaria , Vasos Coronarios , ARN Circular , Anciano de 80 o más Años , Enfermedad de la Arteria Coronaria/genética , Enfermedad de la Arteria Coronaria/metabolismo , Enfermedad de la Arteria Coronaria/patología , Vasos Coronarios/metabolismo , Vasos Coronarios/patología , Humanos , Masculino , ARN Circular/análisis , ARN Circular/genética , ARN Circular/metabolismo , Reacción en Cadena en Tiempo Real de la Polimerasa , Transcriptoma/genética
8.
Top Stroke Rehabil ; 22(3): 161-8, 2015 06.
Artículo en Inglés | MEDLINE | ID: mdl-26084320

RESUMEN

BACKGROUND: The effects of whole body vibration (WBV) on chronic stroke (CS) patients have been investigated by some previous studies. However, controversy still exists. OBJECTIVE: The objective of this meta-analysis was to review existing studies that assess the effects of WBV training on CS patients. METHODS: We searched Medline, Web of Science, EMBASE, and the Cochrane Library for papers published between January 2000 and January 2014.The meta-analyses were performed using Review Manage Version 5.2.Weighted mean difference (WMD) or standard mean difference (SMD) and its 95% confidence intervals (CI) were used as summary statistics. Funnel plot was used to assess the publication bias. RESULTS: Seven studies with 298 CS patients (159 patients underwent WBV training in experimental group and 139 patients underwent nothing or the same exercise without vibration or with a "placebo" vibrating platform in control group) were included. No significant difference was found in muscle strength (isometric knee extension strength: SMD = - 0.15, 95% CI, - 0.43 to 0.13, P = 0.30; isometric knee flexion strength: WMD = - 0.05, 95% CI, - 0.13 to 0.03, P = 0.22), balance (berg balance scale, WMD = - 0.23, 95% CI, - 1.54 to 1.09; P = 0.74) and gait performance (6-min walk test, WMD = - 50.40, 95% CI, - 118.14 to 17.34; P = 0.14) between groups. No indication of publication bias was found in the funnel plot. CONCLUSIONS: WBV training had no beneficial effects in muscle strength, balance and gait performance of CS patients.


Asunto(s)
Terapia por Ejercicio/métodos , Evaluación de Resultado en la Atención de Salud , Rehabilitación de Accidente Cerebrovascular/métodos , Accidente Cerebrovascular/terapia , Vibración , Humanos
9.
Ther Adv Chronic Dis ; 14: 20406223231168754, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37332390

RESUMEN

Background: Which noninvasive brain stimulation (NIBS) treatment - transcranial direct current stimulation (tDCS) or transcranial magnetic stimulation (TMS) - is more beneficial for stroke patients' cognitive rehabilitation is still up for debate. Objectives: Our goal is to provide an overview of the research on the effectiveness and safety of various NIBS protocols. Design: Systematic review and network meta-analysis (NMA) of randomized controlled trials (RCTs). Methods: This NMA compared any active NIBS versus sham stimulation in adult stroke survivors to enhance cognitive function, with a focus on global cognitive function (GCF), attention, memory, and executive function (EF) using the databases MEDLINE, Embase, Cochrane Library, Web of Science, and ClinicalTrials.gov. The NMA statistical approach was built on a frequency framework. The effect size was estimated by the standardized mean difference (SMD) and a 95% confidence interval (CI). We compiled a relative ranking of the competing interventions based on their surface under the cumulative ranking curve (SUCRA). Results: NMA showed that high-frequency repeated TMS (HF-rTMS) improved GCF compared with sham stimulation (SMD = 1.95; 95% CI: 0.47-3.43), while dual-tDCS improved memory performance versus sham stimulation significantly (SMD = 6.38; 95% CI: 3.51-9.25). However, various NIBS stimulation protocols revealed no significant impact on enhancing attention, executive function, or activities of daily living. There was no significant difference between the active stimulation protocols for TMS and tDCS and sham stimulation in terms of safety. Subgroup analysis demonstrated an effect favoring activation site of the left dorsolateral prefrontal cortex (DLPFC) (SUCRA = 89.1) for enhancing GCF and bilateral DLPFC (SUCRA = 99.9) stimulation for enhancing memory performance. Conclusion: The HF-rTMS over the left DLPFC appears to be the most promising NIBS therapeutic option for improving global cognitive performance after stroke, according to a comparison of numerous NIBS protocols. Furthermore, for patients with post-stroke memory impairment, dual-tDCS over bilateral DLPFC may be more advantageous than other NIBS protocols. Both tDCS and TMS are reasonably safe. Registration: PROSPERO ID: CRD42022304865.

10.
J Spinal Cord Med ; 46(2): 277-290, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-34139132

RESUMEN

OBJECTIVE: (1) to describe environmental barriers and participation restrictions experienced by people with spinal cord injury (SCI) from China, (2) to examine associations between lesion characteristics and participation restrictions, considering a mediating role of environmental barriers, (3) to identify those environmental barriers that have the largest influence on participation. DESIGN: Cross-sectional study. This study is part of the International Spinal Cord Injury Survey (InSCI). SETTING: Community, Jiangsu and Sichuan Province, China. PARTICIPANTS: 1355 persons with SCI. INTERVENTIONS: Not applicable. OUTCOME MEASURES: Participation restrictions were measured with items from the Model Disability Survey, Environmental Barriers were measured with the Nottwil Environmental Factors Inventory-Short Form. RESULTS: Participants experienced a median of five (IQR 1-9) environmental barriers and five (IQR 0-9) participation restrictions. Environmental barriers were mainly reported in relation to climate, insufficient resources and accessibility, and participation restrictions mainly occurred in using public transportation, taking care of others, and getting to places. In an adjusted zero-inflated Poisson model, people with more severe injuries reported a greater number of environmental barriers (complete injury: IRR = 1.31, 95%CI = [1.24,1.38]) and participation restrictions (tetraplegia: IRR = 1.15, 95%CI = [1.10,1.21]; complete injury: IRR = 1.25, 95%CI = [1.18,1.31]). Moreover, environmental barriers (IRR = 1.07, 95%CI = [1.06,1.08]) were a significant predictor of participation restrictions and partially mediated the association of lesion completeness with participation restrictions. Barriers related to accessibility of public places (IRR = 1.47, 95%CI = [1.33,1.62]), accessing homes (IRR = 1.32, 95%CI = [1.21,1.44]), long distance transportation (IRR = 1.11, 95%CI = [1.04,1.20]), communication devices (IRR = 1.07, 95%CI = [1.01,1.15]) and state services (IRR = 1.10, 95%CI = [1.02,1.19]) had the greatest negative impact on participation. CONCLUSION: Social participation of people with SCI is seriously restricted in China. Removing environmental barriers will be an important element of programs to address this problem.


Asunto(s)
Personas con Discapacidad , Traumatismos de la Médula Espinal , Humanos , Traumatismos de la Médula Espinal/epidemiología , Estudios Transversales , Vida Independiente , Participación Social , Encuestas y Cuestionarios
11.
Nanomaterials (Basel) ; 14(1)2023 Dec 22.
Artículo en Inglés | MEDLINE | ID: mdl-38202500

RESUMEN

Developing electrode materials with high voltage and high specific capacity has always been an important strategy for increasing the energy density of lithium-ion capacitors (LICs). However, organic-based electrolytes with lithium salts limit their potential for application in LICs to voltages below 3.8 V in terms of polarization reactions. In this work, we introduce Li[N(C2F5SO2)2] (lithium Bis (pentafluoroethanesulfonyl)imide or LiBETI), an electrolyte with high conductivity and superior electrochemical and mechanical stability, to construct a three-electrode LIC system. After graphite anode pre-lithiation, the anode potential was stabilized in the three-electrode LIC system, and a stable solid electrolyte interface (SEI) film formed on the anode surface as expected. Meanwhile, the LIC device using LiBETI as the electrolyte, and a self-synthesized graphene/single-walled carbon nanotube (SWCNT) composite as the cathode, showed a high voltage window, allowing the LIC to achieve an operating voltage of 4.5 V. As a result, the LIC device has a high energy density of up to 182 Wh kg-1 and a 2678 W kg-1 power density at 4.5 V. At a current density of 2 A g-1, the capacity retention rate is 72.7% after 10,000 cycles.

12.
Artículo en Inglés | MEDLINE | ID: mdl-37919235

RESUMEN

Sodium-ion batteries (SIBs) are considered the most promising alternatives to lithium-ion batteries (LIBs) due to the abundant availability of sodium and their cost-effectiveness. Transition metal selenides (TMSes) are considered promising anodes for SIBs due to their economic efficiency and high theoretical capacity. Nevertheless, overcoming the challenges of sluggish reaction kinetics and severe structural damage is crucial to improving cycle life and rate capability. Herein, a simple microwave hydrothermal process was used to synthesize a nanocomposite of CoSe2 nanoparticles uniformly anchored on reduced graphene oxide nanosheets (CoSe2/rGO). The influences of rGO on the structure and electrochemical performance and Na+ diffusion kinetics are investigated through a series of characterization and electrochemical tests. The resulting CoSe2/rGO nanocomposite exhibits a remarkable initial specific capacity of 544 mAh g-1 at 0.5 A g-1, impressive rate capability (368 mAh g-1 at 20 A g-1), and excellent cycle life and maintains 348 mAh g-1 at 5 A g-1 over 1200 cycles. In addition, the in situ electrochemical impedance spectroscopy (EIS), ex situ X-ray diffraction (XRD), and transmission electron microscopy (TEM) tests are selected to further investigate the sodium storage mechanism.

13.
Nanomaterials (Basel) ; 13(6)2023 Mar 13.
Artículo en Inglés | MEDLINE | ID: mdl-36985927

RESUMEN

As a typical binary transition metal oxide, ZnFe2O4 has attracted considerable attention for supercapacitor electrodes due to its high theoretical specific capacitance. However, the reported synthesis processes of ZnFe2O4 are complicated and ZnFe2O4 nanoparticles are easily agglomerated, leading to poor cycle life and unfavorable capacity. Herein, a facile microwave hydrothermal process was used to prepare ZnFe2O4/reduced graphene oxide (rGO) nanocomposites in this work. The influence of rGO content on the morphology, structure, and electrochemical performance of ZnFe2O4/rGO nanocomposites was systematically investigated. Due to the uniform distribution of ZnFe2O4 nanoparticles on the rGO surface and the high specific surface area and rich pore structures, the as-prepared ZnFe2O4/rGO electrode with 44.3 wt.% rGO content exhibits a high specific capacitance of 628 F g-1 and long cycle life of 89% retention over 2500 cycles at 1 A g-1. This work provides a new process for synthesizing binary transition metal oxide and developing a new strategy for realizing high-performance composites for supercapacitor electrodes.

14.
Inflammation ; 46(4): 1445-1457, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37171694

RESUMEN

Skeletal muscle is crucial for preserving glucose homeostasis. Insulin resistance and abnormalities in glucose metabolism result from a range of pathogenic factors attacking skeletal muscle in obese individuals. To relieve insulin resistance and restore glucose homeostasis, blocking the cell signaling pathways induced by those pathogenic factors seems an attractive strategy. It has been discovered that insulin sensitivity in obese people is inversely linked with the activity of NF-κB inducing kinase (NIK) in skeletal muscle. In order to evaluate NIK's pathological consequences, mechanism of action, and therapeutic values, an obese mouse model reproduced by feeding a high-fat diet was treated with a NIK inhibitor, B022. C2C12 myoblasts overexpressing NIK were utilized to assess insulin signaling and glucose uptake. B022 thus prevented high-fat diet-induced NIK activation and insulin desensitization in skeletal muscle. The insulin signaling in C2C12 myoblasts was compromised by the upregulation of NIK brought on by oxidative stress, lipid deposition, inflammation, or adenoviral vector. This inhibition of insulin action is mostly due to an inhibitory serine phosphorylation of IRS1 caused by ERK, JNK, and PKC that were activated by NIK. In summary, NIK integrates signals from several pathogenic factors to impair insulin signaling by igniting a number of IRS1-inhibiting kinases, and it also has significant therapeutic potential for treating insulin resistance.


Asunto(s)
Resistencia a la Insulina , Ratones , Animales , Ratones Obesos , Músculo Esquelético/metabolismo , Insulina/metabolismo , Fosforilación , Glucosa/metabolismo , Obesidad/metabolismo , Quinasa de Factor Nuclear kappa B
15.
Front Oncol ; 13: 1219923, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37601677

RESUMEN

Introduction: Among all cancers, endometrial cancer is most strongly associated with obesity, with more than 65% of endometrial cancers attributable to obesity and being overweight. Fatty acid synthase (FAS), a key lipogenic enzyme, is expressed in endometrial cancer tumors and is associated with a worse prognosis for this disease. Orlistat, an FAS inhibitor, is an FDA-approved weight loss medication that has demonstrated anti-tumor activity in a variety of preclinical cancer models. Methods: In this study, the Lkb1fl/flp53fl/fl mouse model of endometroid endometrial cancer was exposed to three diet interventions, including a high fat diet (obese), a low fat diet (lean) and switch from a high fat to a low fat diet, and then exposed to orlistat or placebo. Results: The mice fed a high-fat diet had significantly increased body weight and tumor weight compared to mice fed a low-fat diet. Switching from a high-fat diet to a low fat diet led to a reduction in mouse weight and suppressed tumor growth, as compared to both the high fat diet and low fat diet groups. Orlistat effectively decreased body weight in obese mice and inhibited tumor growth in obese, lean, and the high fat diet switch to low fat diet mouse groups through induction of apoptosis. Orlistat also showed anti-proliferative activity in nine of 11 primary cultures of human endometrial cancer. Discussion: Our findings provide strong evidence that dietary intervention and orlistat have anti-tumor activity in vivo and supports further investigation of orlistat in combination with dietary interventions for the prevention and treatment of endometrial cancer.

16.
Medicine (Baltimore) ; 101(44): e31585, 2022 Nov 04.
Artículo en Inglés | MEDLINE | ID: mdl-36343060

RESUMEN

To develop and validate a nomogram for individualized prediction of lower extremity deep venous thrombosis (DVT) in stroke patients based on extremity function and daily living ability of stroke patients. In this study, 423 stroke patients admitted to the Rehabilitation Medical Center of the First Affiliated Hospital of Nanjing Medical University from December 2015 to February 2019 were taken as the subjects, who were divided into the DVT group (110) and No-DVT group (313) based on the existence of DVT. Inter-group comparison of baseline data was performed by 1-way Analysis of Variance, Kruskal-Wallis rank-sum test, or Pearson chi-square test. Data dimensions and predictive variables were selected by least absolute shrinkage and selection operator (LASSO); the prediction model was developed and the nomogram was prepared by binary logistics regression analysis; the performance of the nomogram was identified by the area under the receiver operating characteristic curve (AUC), Harrell's concordance index, and calibration curve; and the clinical effectiveness of the model was analyzed by clinical decision curve analysis. Age, Brunnstrom stage (lower extremity), and D-dimer were determined to be the independent predictors affecting DVT. The independent predictors mentioned above were developed and presented as a nomogram, with AUC and concordance index of 0.724 (95% confidence interval [CI]: 0.670-0.777), indicating the satisfactory discrimination ability of the nomogram. The P value of the results of the Hosmer-Lemeshow test was 0.732, indicating good fitting of the prediction model. Decision curve analysis showed that the clinical net benefit of this model was 6% to 50%. We developed a nomogram to predict lower extremity deep venous thrombosis in stroke patients, and the results showed that the nomogram had satisfactory prediction performance and clinical efficacy.


Asunto(s)
Accidente Cerebrovascular , Trombosis de la Vena , Humanos , Nomogramas , Estudios Retrospectivos , Accidente Cerebrovascular/complicaciones , Trombosis de la Vena/etiología , Extremidad Inferior
17.
Arch Rehabil Res Clin Transl ; 4(3): 100213, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-36123984

RESUMEN

Objective: The development and validation of a nomogram for the individualized prediction of hemiplegic shoulder pain (HSP) during the inpatient rehabilitation of patients with stroke. Design: Retrospective cohort study. Setting: The rehabilitation department at a tertiary hospital. Participants: A total of 376 patients (N=376) with stroke admitted to inpatient rehabilitation from January 2018 to April 2021 were included in this study. Interventions: Not applicable. Main Outcome Measures: The outcome measure was shoulder pain on the patients' hemiplegic side occurring at rest or with movement during hospitalization. Results: Among the 376 patients with stroke, 113 (30.05%) developed HSP. Five independent predictors were included in the nomogram: subluxation, Brunnstrom stage, hand edema, spasticity, and sensory disturbance. The nomogram was a good predictor, with a C-index of 0.85 (95% confidence interval, 0.81-0.89) and corrected C-index of 0.84. The Homer-Lemeshow test (χ2=13.854, P=.086) and calibration plot suggested good calibration ability of the nomogram. The optimal cutoff value for the predicted probability of HSP was 0.30 (sensitivity, 0.73; specificity, 0.83). Moreover, the decision curve analysis revealed that the nomogram would add net clinical benefits if the threshold possibility of HSP risk was from 5%-88%. Conclusions: Our nomogram could accurately predict HSP, which may help clinicians accurately quantify the HSP risk in individuals and implement early interventions.

18.
Brain Sci ; 12(12)2022 Dec 09.
Artículo en Inglés | MEDLINE | ID: mdl-36552154

RESUMEN

This study aims to explore the effects of gaze stabilization exercises (GSEs) on gait, plantar pressure, and balance function in post-stroke patients (≤6 months). Forty post-stroke patients were randomly divided into an experimental group (n = 20) and a control group (n = 20). The experimental group performed GSEs combined with physical therapy, while the control group only performed physical therapy, once a day, 5 days a week, for 4 weeks. The Berg Balance Scale (BBS) was used to test the balance function and the risk of falling, which was the primary outcome. The Timed Up and Go test (TUGT) evaluated the walking ability and the fall risk. The envelope ellipse area and the plantar pressure proportion of the affected side were used to measure the patient's supporting capacity and stability in static standing. The anterior−posterior center of pressure displacement velocity was used to test the weight-shifting capacity. Compared to the control group, the swing phase of the affected side, swing phase's absolute symmetric index, envelope ellipse area when eyes closed, and TUGT of the experimental group had significantly decreased after GSEs (p < 0.05); the BBS scores, TUGT, the anterior−posterior COP displacement velocity, and the plantar pressure proportion of the affected side had significantly increased after 4 weeks of training (p < 0.05). In conclusion, GSEs combined with physical therapy can improve the gait and balance function of people following stroke. Furthermore, it can enhance the weight-shifting and one-leg standing capacity of the affected side, thus reducing the risk of falling.

19.
Clin Appl Thromb Hemost ; 28: 10760296221117991, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35942697

RESUMEN

Objectives: To develop a nomogram for predicting calf muscle veins thrombosis (CMVT) in stroke patients during rehabilitation. Methods: We enrolled 360 stroke patients from the Rehabilitation Medicine Center from December 2015 to February 2019. Of the participants, 123 were included in the CMVT group and 237 in the no CMVT group. The least absolute shrinkage and selection operator (LASSO) regression model was applied to optimize feature selection for the model. Multivariable logistic regression analysis was applied to construct a predictive model. Performance and clinical utility of the nomogram were generated using the Harrell's concordance index, calibration curve, and decision curve analysis (DCA). Results: Age, Brunnstrom stage (lower extremity), D-dimer, and antiplatelet therapy were associated with the occurrence of CMVT. The prediction nomogram showed satisfactory performance with a concordance index of 0.718 (95% CI: 0.663-0.773) in internal verification. The Hosmer-Lemeshow test, P = .217, suggested that the model was of goodness-of-fit. In addition, the DCA demonstrated that the CMVT nomogram had a good clinical net benefit. Conclusions: We developed a nomogram that could help clinicians identify high-risk groups of CMVT in stroke patients during rehabilitation for early intervention.


Asunto(s)
Accidente Cerebrovascular , Trombosis de la Vena , Humanos , Nomogramas , Estudios Retrospectivos , Accidente Cerebrovascular/complicaciones , Trombosis de la Vena/etiología
20.
Neurosci Lett ; 775: 136536, 2022 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-35183693

RESUMEN

Spasticity commonly emerges during the process of recovery after spinal cord injury (SCI) and critically exacerbates motor dysfunction. Given insufficient effects of individual therapies, we combined repetitive transcranial magnetic stimulation (rTMS) with treadmill training (Tr) in rats with SCI to investigate potential synergistic effects on alleviating spasticity and motor dysfunction. Animals were randomized into four groups: SCI only, rTMS, Tr, and rTMS plus Tr. At the study endpoint eight weeks after the start of interventions, the rTMS plus Tr group exhibited the largest decrease in maximal H-reflex amplitude/maximal M-wave amplitude ratio (effect size (ES): -0.082, 95% confidence interval (CI): -0.118 to -0.046, p < 0.001) as well as the greatest improvement in motor function measured with the Basso, Beattie, and Bresnahan locomotor scale (ES: 1.811, 95% CI: 1.018 to 2.603, p < 0.001; significantly different from all other groups at p < 0.01) and grid-walking test (ES: -5.1, 95% CI: -7.784 to -2.416, p < 0.001, significantly different from rTMS alone at p < 0.01). Pathological analyses demonstrated that the combined treatment facilitated the growth of serotonergic axons around the lesion site, and the upregulation of 5-hydroxytryptamine, potassium-chloride cotransporter-2, and glutamic acid decarboxylases 67 in the lumbar spinal cord distal to the injury site. All effects of combined treatment of rTMS and treadmill training were enhanced compared to treadmill training or rTMS alone. Treadmill training and rTMS intervention appear to have synergistic effects on hyperreflexia and locomotion likely related to a restored balance between facilitatory and inhibitory inputs to motoneurons.


Asunto(s)
Traumatismos de la Médula Espinal , Estimulación Magnética Transcraneal , Animales , Neuronas Motoras/patología , Espasticidad Muscular/terapia , Ratas , Reflejo Anormal , Médula Espinal/patología , Traumatismos de la Médula Espinal/complicaciones , Traumatismos de la Médula Espinal/patología , Traumatismos de la Médula Espinal/terapia
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