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1.
Proc Natl Acad Sci U S A ; 120(20): e2219083120, 2023 May 16.
Article in English | MEDLINE | ID: mdl-37155883

ABSTRACT

Due to their low viscosity, high mobility, and high element contents, supercritical fluids are important agents in the cycling of elements. However, the chemical composition of supercritical fluids in natural rocks is poorly understood. Here, we investigate well-preserved primary multiphase fluid inclusions (MFIs) from an ultrahigh-pressure (UHP) metamorphic vein of the Bixiling eclogite in Dabieshan, China, thus providing direct evidence for the components of supercritical fluid occurring in a natural system. Via the 3D modeling of MFIs by Raman scanning, we quantitatively determined the major composition of the fluid trapped in the MFIs. Combined with the peak-metamorphic pressure-temperature conditions and the cooccurrence of coesite, rutile, and garnet, we suggest that the trapped fluids in the MFIs represent supercritical fluids in a deep subduction zone. The strong mobility of the supercritical fluids with respect to carbon and sulfur suggests that such fluids have profound effects on global carbon and sulfur cycling.

2.
BMC Nurs ; 23(1): 194, 2024 Mar 22.
Article in English | MEDLINE | ID: mdl-38520023

ABSTRACT

OBJECTIVE: This study aims to investigate the relationship between psychological resilience, thriving at work, and work performance among nurses, as well as analyse the mediating role of thriving at work in the relationship between psychological resilience and the work performance of nurses. The findings are intended to serve as a reference for nursing managers to design tailored work performance intervention programs. METHOD: Using convenience sampling, 308 clinical nurses were selected from a tertiary hospital in Changsha City, Hunan Province, China, from February to April 2023. The Connor-Davidson Resilience Scale (CD-RISC), the Thriving at Work Scale, and the Work Performance Scale were employed for the questionnaire survey. Pearson correlation analysis was used to explore the relationship between psychological resilience, thriving at work and work performance. The SPSS 26.0 software's 'Process' plugin was utilised for mediation effect analysis. RESULTS: Significantly positive correlations were found between psychological resilience and thriving at work (r = 0.806, P < 0.01), thriving at work and work performance (r = 0.571, P < 0.01) as well as psychological resilience and work performance (r = 0.572, P < 0.01). Psychological resilience significantly predicted work performance positively (ß = 0.558, t = 11.165, P < 0.01), and this prediction remained significant when thriving at work (the mediating variable), was introduced (ß = 0.371, t = 4.772, P < 0.01). Psychological resilience significantly predicted thriving at work positively (ß = 0.731, t = 20.779, P < 0.01), and thriving at work significantly predicted work performance positively (ß = 0.256, t = 3.105, P < 0.05). The mediating effect size of thriving at work between psychological resilience and work performance was 33.49% (P < 0.05). CONCLUSION: Thriving at work plays a partial mediating role between psychological resilience and work performance. The level of work performance among clinical nurses was relatively high. Nursing managers can enhance thriving at work by fostering psychological resilience among clinical nurses, thereby further improving their work performance to ensure high-quality and efficient nursing care.

3.
Pract Neurol ; 23(6): 476-488, 2023 Nov 23.
Article in English | MEDLINE | ID: mdl-37977806

ABSTRACT

Artificial intelligence (AI) is routinely mentioned in journals and newspapers, and non-technical outsiders may have difficulty in distinguishing hyperbole from reality. We present a practical guide to help non-technical neurologists to understand healthcare AI. AI is being used to support clinical decisions in treating neurological disorders. We introduce basic concepts of AI, such as machine learning and natural language processing, and explain how AI is being used in healthcare, giving examples its benefits and challenges. We also cover how AI performance is measured, and its regulatory aspects in healthcare. An important theme is that AI is a general-purpose technology like medical statistics, with broad utility applicable in various scenarios, such that niche approaches are outpaced by approaches that are broadly applicable in many disease areas and specialties. By understanding AI basics and its potential applications, neurologists can make informed decisions when evaluating AI used in their clinical practice. This article was written by four humans, with generative AI helping with formatting and image generation.


Subject(s)
Artificial Intelligence , Neurologists , Humans , Animals , Sheep , Machine Learning
4.
Biochem Biophys Res Commun ; 621: 109-115, 2022 09 17.
Article in English | MEDLINE | ID: mdl-35820280

ABSTRACT

Cocaine as a highly addictive psychostimulant can cause changes in the body at the cellular and molecular levels over a long period of time. It reminds us that cocaine may have a potential role in post-transcriptional regulation, but the alteration of insula-expression profile in adolescent cocaine use disorder (CUD) has not been reported. To reveal the mechanisms underlying the post-transcriptional regulation of cocaine, we investigate the transcriptome in the insula of cocaine-induced mice based on high-throughput strand-specific RNA sequencing. We analyzed the alterations of messenger RNA (mRNA) expression profile in the insula of cocaine-induced condition place preference (CPP) mice and then correlated it with microRNAs to reveal their involvement in the formation of cocaine-induced CPP. In this study, a total of 27786 genes were identified, 5750 new genes (novel expressed transcripts of unannotated in the reference genome) were discovered, among which 1,205 were annotated functionally. A total of 198 differentially expressed genes (DEG) that functioned in synaptic transmission, cholinergic, developmental process, neurotransmitter metabolic process, drug catabolism, cellular response to drug, MAP kinase activity, ceramidase activity, and drug resistance were significantly enriched. Further analysis showed that 26045 mRNAs formed 45,208 network-relationship pairs with 1770 microRNAs. In the current study, our work was the first to reveal that alterations of RNAs in the insula, as a core brain region of the neural circuits of interoception, were involved in the process of cocaine-induced CPP of adolescent mice. These findings enrich the biology and expand the molecular regulatory network related to adolescence CUD. They provided the possibility that some DEGs may be used as novel biomarkers for the diagnosis or evaluation of substance use disorder, and also provided clues for elucidating the neurobiological mechanism of substance use disorder.


Subject(s)
Cocaine , MicroRNAs , Animals , Cocaine/pharmacology , Conditioning, Classical , Mice , MicroRNAs/genetics , MicroRNAs/metabolism , RNA, Messenger/genetics , RNA, Messenger/metabolism , Transcriptome
5.
Epilepsia ; 63(1): 120-129, 2022 01.
Article in English | MEDLINE | ID: mdl-34786694

ABSTRACT

OBJECTIVE: Vigabatrin (VGB) is the first-line treatment for infantile spasms (IS). Previous studies have shown that VGB exposure may cause vigabatrin-associated brain abnormalities on magnetic resonance imaging (MRI) (VABAM). Based on previous studies, this study aimed to go further to explore the possible risk factors and the incidence of VABAM. In addition, diffusion-weighted imaging (DWI) and T2-weighted imaging (T2WI) were compared to explore whether DWI should be used as a routine examination sequence when MRI is performed in children receiving VGB. METHODS: Children with IS receiving VGB were selected as the study subjects. Whether VABAM occurred or not was categorized as the VABAM group and the non-VABAM group, respectively. Their general clinical data and medication exposure were collected. The possible risk factors of VABAM and different MRI sequences were compared and statistically analyzed. RESULTS: A total of 77 children with IS were enrolled in the study, of which 25 (32.5%) developed VABAM. Twenty-three of the 25 VABAM cases have a peak dosage of VGB between 50 and 150 mg/kg/day. The earliest observation time of VABAM was 30 days. Regression analysis of relevant risk factors showed that the peak dosage of VGB was the risk factor for VABAM. Comparison between different MRI sequences showed that DWI is more sensitive than T2WI to the evaluation of VABAM. SIGNIFICANCE: In our study, the occurrence of VABAM was 32.5%, indicating a higher incidence than in most previous reports. In addition, we once again verified that the peak dosage of VGB was the risk factor of VABAM. Caution should be exercised that our data also suggest that VABAM may occur even using the conventional dosage of VGB (ie, 50-150 mg/kg/day). Therefore, even when using the conventional dosage of VGB, regular MRI examination should be required. Furthermore, DWI sequence should be used as a routine examination sequence when MRI is performed in children with IS who are receiving VGB.


Subject(s)
Spasms, Infantile , Vigabatrin , Anticonvulsants/adverse effects , Brain/diagnostic imaging , Child , Humans , Magnetic Resonance Imaging , Retrospective Studies , Spasms, Infantile/chemically induced , Spasms, Infantile/diagnostic imaging , Spasms, Infantile/drug therapy , Vigabatrin/adverse effects
6.
Childs Nerv Syst ; 38(5): 947-952, 2022 05.
Article in English | MEDLINE | ID: mdl-35083513

ABSTRACT

PURPOSE: There was no evidence whether the mammalian/mechanistic target of rapamycin pathway hyperactivation and long-term use of mTOR inhibitors have any effects on the physical development of children. The aim was to evaluate these effects by comparing the physical development of children with TSC and normal children. METHODS: A total of 120 eligible children were enrolled. They were administered sirolimus and followed for at least 12 months. Height, weight, BMI and lipid metabolism index were collected during treatment. Pearson's chi-square and Fisher's exact test were used for comparison of proportions of patients exhibiting normal and abnormal physical growth before and after 1 year of treatment. Logistic regression was used to evaluate the influence of age, sex and abnormal lipid metabolism on the increased BMIs of TSC patients after treatment. RESULTS: Most of the enrolled TSC children were in the normal height, weight and BMI ranges at baseline (91.7%, 95.8% and 78.3%, respectively). Most remained in the normal height, weight and BMI ranges after 1 year of sirolimus treatment (94.2%, 95% and 76.7%, respectively). There was no significant difference in the proportion of physical development before and after treatment (p > 0.05). Thirty-eight (38/106, 35.8%) patients had increased BMIs after 1 year of treatment, but there was no significant correlation between age, sex and lipid metabolism and increased BMI. CONCLUSIONS: Overactivation of the mTOR pathway and long-term administration of sirolimus does not affect the physical development of children with TSC.


Subject(s)
Tuberous Sclerosis , Animals , Child , Humans , Mammals , Sirolimus/adverse effects , Tuberous Sclerosis/drug therapy
7.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 53(3): 466-473, 2022 May.
Article in Zh | MEDLINE | ID: mdl-35642156

ABSTRACT

Objective: To study the status quo of the readmission of senile dementia patients in Chengdu, and to analyze the primary diagnosis, the economic burden and the influencing factors of readmission. Methods: Dementia inpatients aged 60 and above in Chengdu were the subjects of this study. The subjects were diagnosed with dementia between 2013 and 2017. Their heath insurance coverage was either the basic medical insurance for urban employees in Chengdu or the basic medical insurance for urban and rural residents of Chengdu. The rank sum test and the chi-square test were conducted to analyze the differences in readmission rate and the economic burden of hospitalization among subjects with different characteristics. Logistic regression was done to analyze the factors affecting readmission. Results: The total number of dementia inpatients over the 5-year period was 27881 patients (78820 admissions). The 30-day readmission rate was 25.14% (7011/27881) and the 5-year readmission rate was 45.79% (12767/27881). The primary diagnoses of 12767 readmitted patients mainly included dementia (28.57%), circulatory system diseases (24.26%), and respiratory system diseases (23.71%). The economic burden of hospitalization was higher for readmitted patients than that of patients who were not readmitted ( Z=33.777, P<0.001). The occurrence of readmission was correlated to the following factors, advanced age (compared to that of the 60-65 yr. group, the 70-75 yr. group: odds ratio [ OR]=1.123, 95% confidence interval [ CI]: 1.019-1.237, and the 75-80 yr. group: OR=1.123, 95% CI: 1.108-1.218), participation in the basic medical insurance for urban employees ( OR=1.674, 95% CI: 1.578-1.775), types of dementia (compared to unspecified dementia, Alzheimer's dementia group: OR=1.256, 95% CI: 1.163-1.357, Parkinson's disease dementia group: OR=1.774, 95% CI: 1.658-1.898, and mixed-type dementia group: OR=1.750, 95% CI: 1.457-2.103), disease condition (compared with patients with only dementia, those who have other diseases: OR=0.536,95% CI :0.493-0.583), length of hospital stay ( OR=1.593, 95% CI: 1.552-1.635), and staying at a lower level hospital (compared to that of tertiary hospitals, secondary hospitals: OR=1.319, 95% CI: 1.248-1.395, primary hospitals: OR=1.744, 95% CI: 1.608-1.891, and other hospitals: OR=1.465, 95% CI: 1.311-1.537). Conclusion: Senile dementia patients have a high 30-day readmission rate, and the readmission entails heavy economic burdens on the patients. For the populations covered by medical insurance, the following features are correlated to the occurrence of readmission: advanced age, coverage by the basic medical insurance for urban employees, Alzheimer's dementia, Parkinson's disease dementia, mixed-type dementia, dementia patients without other comorbidities, extended length of stay, and hospitalization at a lower level hospital. However, further research is needed for better understanding of the specific mechanisms so that readmission of senile dementia patients can be reduced and the economic burden of the disease can be minimized.


Subject(s)
Alzheimer Disease , Dementia , Insurance , Parkinson Disease , Dementia/epidemiology , Humans , Patient Readmission , Retrospective Studies , Risk Factors
8.
Zhongguo Zhong Yao Za Zhi ; 47(13): 3562-3568, 2022 Jul.
Article in Zh | MEDLINE | ID: mdl-35850810

ABSTRACT

Based on the theory of activating spleen and generating blood, this study explored the effect of Rehmanniae Radix Prae-parata on the spleen metabolome of the rat model with blood deficiency syndrome.The rat model of blood deficiency syndrome was established by combining with cyclophosphamide(CTX) and N-acetyl-phenylhydrazine(APH), and the metabolomes of the spleen samples were analyzed with ultra performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS).Principal component analysis(PCA) and orthogonal partial least squares-discriminant analysis(OPLS-DA) were carried out for the metabolite profiles of spleen samples.The MEV heatmap and metabolic network were established based on the potential biomarkers.Finally, the blood routine indexes were combined with the metabolomic profile to reveal the mechanism of Rehmanniae Radix Praeparata in activating spleen and generating blood.The treatment with CTX and APH decreased the blood routine indexes such as white blood cell count(WBC), red blood cell count(RBC), platelet(PLT), and hematocrit(HCT), indicating that the rat model of blood deficiency syndrome was successfully established.The administration of Rehmanniae Radix Praeparata significantly improved the blood routine indexes, which suggested that Rehmanniae Radix Praeparata played a role in replenishing blood.In addition, the metabolomics analysis identified 41 potential biomarkers.The PCA and MEV heatmap also showed significant improvement effect of Rehmanniae Radix Praeparata on the spleen metabolic profile.These potential biomarkers were mainly involved in tricarboxylic acid cycle, niacin and nicotinamide metabolism, phenylalanine metabolism, tyrosine metabolism, taurine and hypotaurine metabolism, and sphingolipid metabolism.Therefore, we hypothesize that Rehmanniae Radix Praeparata may regulate energy metabolism, peripheral blood production, and oxidative injury of hemocytes to tonify blood.


Subject(s)
Drugs, Chinese Herbal , Animals , Biomarkers , Drugs, Chinese Herbal/pharmacology , Metabolomics , Plant Extracts , Rats , Rehmannia , Spleen
9.
J Pediatr ; 233: 150-155.e4, 2021 06.
Article in English | MEDLINE | ID: mdl-33631166

ABSTRACT

OBJECTIVES: To investigate the efficacy and safety of sirolimus in the treatment of cardiac rhabdomyomas associated with tuberous sclerosis complex and the specific benefits in different subgroups. STUDY DESIGN: The study was a prospective cohort and self-controlled case series study. Based on the prevalence of cardiac rhabdomyoma at different ages, we estimated the natural tumor disappearance rate. The subgroup analysis was done by Cox regression. Self-controlled case series method was used to assess the magnitude and duration of the drug effect. Adverse events were described. RESULTS: A total of 217 patients were included in the cohort study. Tumor disappearance rate was higher in younger age groups (hazard ratio = 0.99, P = .027) and female patients (hazard ratio = 2.08, P = .015). The age-adjusted incidence ratio showed that the disappearance of rhabdomyomas between 3 and 6 months was more related to sirolimus. Adverse events were observed 60 times in 42 of 217 children, mainly stomatitis. CONCLUSIONS: Sirolimus can increase the disappearance rate of cardiac rhabdomyoma in the tuberous sclerosis complex population. Efficacy varies by sex and age: female and younger patients have higher tumor disappearance rate. Sirolimus is well-tolerated.


Subject(s)
Antibiotics, Antineoplastic/therapeutic use , Heart Neoplasms/drug therapy , Rhabdomyoma/drug therapy , Sirolimus/therapeutic use , Tuberous Sclerosis/complications , Age Factors , Child, Preschool , Cohort Studies , Female , Heart Neoplasms/etiology , Humans , Infant , Male , Rhabdomyoma/etiology , Sex Factors
10.
Am J Med Genet A ; 185(2): 377-383, 2021 02.
Article in English | MEDLINE | ID: mdl-33205896

ABSTRACT

Developmental and epileptic encephalopathy (DEE) is a severe encephalopathy in infants and early childhood. In this study we reported a recurrent de novo variant (c.3985C>T, p.R1330W) in HECW2 (HECT, C2 and WW domain containing E3 ubiquitin protein ligase 2) (MIM# 617245) identified by screening 240 patients with DEE and summarized clinical features of published DEE patients with HECW2 variants. Functionally, transcriptional knockdown of zebrafish hecw2a led to early morphological abnormalities in the brain tissues. These results suggest a potential functional link between HECW2 dysfunction and brain development.


Subject(s)
Brain Diseases/genetics , Intellectual Disability/genetics , Ubiquitin-Protein Ligases/genetics , Zebrafish Proteins/genetics , Adolescent , Animals , Brain Diseases/epidemiology , Brain Diseases/pathology , Child , Child, Preschool , Disease Models, Animal , Genetic Predisposition to Disease , Humans , Infant , Intellectual Disability/epidemiology , Intellectual Disability/pathology , Male , Mutation/genetics , Exome Sequencing , Zebrafish/genetics
11.
J Child Psychol Psychiatry ; 62(10): 1246-1254, 2021 10.
Article in English | MEDLINE | ID: mdl-33738808

ABSTRACT

BACKGROUND: Symptom improvement in children with tic disorder (TD) following fecal microbiota transplantation led us to investigate the gut microbiota in TD. This exploratory study aims to depict the gut microbial profile in patients with TD and explore the impact of dopamine receptor antagonist (DRA) drugs on the composition and metabolic function of the gut microbiota. METHODS: The gut microbiota were profiled in fecal samples of 49 children with TD and 50 matched healthy controls (HC) using shotgun metagenomic sequencing. A random forest (RF) model was constructed using the gut bacterial species to distinguish TD from HC. Associations between clinical metadata and microbial abundance or function were analyzed using MaAsLin2 and Spearman correlation. RESULTS: The gut microbiota in children with TD was featured by higher abundances of Bacteroides plebeius and Ruminococcus lactaris (a potential pro-inflammatory taxon) and lower abundances of Prevotella stercorea and Streptococcus lutetiensis compared to HC. The constructed RF model accurately distinguished TD from HC based on the gut microbiota profile, resulting in an AUC of 0.884. Significant correlations were observed between tic symptom severity and the abundances of multiple bacterial species and gut microbiota metabolic functions. Multivariate analysis identified an upregulation of 4-aminobutanoate (GABA) degradation in the gut microbiota associated with TD status. The gut microbiota of DRA-treated TD children showed a distinct gut microbiota compared to the treatment-naïve group, represented by an increase in some potential enteric pathogens such as Escherichia coli, a decline in several species including Akkermansia muciniphila, and alterations in various metabolic functions. CONCLUSIONS: Bacterial species promoting inflammatory responses and those modulating neurotransmitters such as GABA may be involved in the pathogenesis of TD. The use of DRA drugs is likely to induce overgrowth of some enteric pathogens and alter the gut microbiota metabolism.


Subject(s)
Gastrointestinal Microbiome , Tic Disorders , Bacteroides , Child , Humans , Prevotella , Ruminococcus , Streptococcus
12.
Pflugers Arch ; 472(1): 117-133, 2020 01.
Article in English | MEDLINE | ID: mdl-31875236

ABSTRACT

Complexin I (CPLX1), a presynaptic small molecule protein, forms SNARE complex in the central nervous system involved in the anchoring, pre-excitation, and fusion of axonal end vesicles. Abnormal expression of CPLX1 occurs in several neurodegenerative and psychiatric disorders that exhibit disrupted neurobehaviors. CPLX1 gene knockout induces severe ataxia and social behavioral deficits in mice, which has been poorly demonstrated. Here, to address the limitations of single-species models and to provide translational insights relevant to human diseases, we used CPLX1 knockout rats to further explore the function of the CPLX1 gene. The CRISPR/Cas9 gene editing system was adopted to generate CPLX1 knockout rats (CPLX1-/-). Then, we characterized the survival rate and behavioral phenotype of CPLX1-/- rats using behavioral analysis. To further explain this phenomenon, we performed blood glucose testing, Nissl staining, hematoxylin-eosin staining, and Golgi staining. We found that CPLX1-/- rats showed profound ataxia, dystonia, movement and exploratory deficits, and increased anxiety and sensory deficits but had normal cognitive function. Nevertheless, CPLX1-/- rats could swim without training. The abnormal histomorphology of the stomach and intestine were related to decreased weight and early death in these rats. Decreased dendritic branching was also found in spinal motor neurons in CPLX1-/- rats. In conclusion, CPLX1 gene knockout induced the abnormal histomorphology of the stomach and intestine and decreased dendritic branching in spinal motor neurons, causing different phenotypes between CPLX1-/- rats and mice, even though both of these phenotypes showed profound ataxia. These findings provide a new perspective for understanding the role of CPLX1.


Subject(s)
Adaptor Proteins, Vesicular Transport/metabolism , Ataxia/genetics , Dystonia/genetics , Gene Deletion , Longevity/genetics , Nerve Tissue Proteins/metabolism , Phenotype , Adaptor Proteins, Vesicular Transport/genetics , Animals , Ataxia/pathology , Dendrites/pathology , Dystonia/pathology , Exploratory Behavior , Intestines/pathology , Motor Neurons/pathology , Movement , Nerve Tissue Proteins/genetics , Rats , Rats, Sprague-Dawley , Stomach/pathology
13.
Cytokine ; 115: 8-12, 2019 03.
Article in English | MEDLINE | ID: mdl-30616035

ABSTRACT

OBJECTIVE: To evaluate whether the macrophage migration inhibitory factor (MIF) level in serum of ischemic stroke patients was associated with their clinical severity and early outcome. METHODS: During February 2017-March 2018, consecutive patients admitted to our hospital because of first-ever ischemic stroke were identified. The prognostic value of MIF was set for predicting the outcome of these patients at discharge. The results were compared with existing methods, including National Institutes of Health Stroke Scale (NIHSS) score and validated indicators. RESULTS: 289 patients were enrolled. The serum level of all patients was determined (median: 20.6 ng/ml). At admission, 131 patients (45.3%) were evaluated as minor stroke (NIHSS < 5). When serum level of MIF was increased by each 1 ng/ml, the unadjusted and adjusted risk of moderate-to-high clinical severity was elevated by 5% (OR = 1.05 [95% CI: 1.01-1.09], P = 0.006) and 3% (1.03 [1.00-1.08], P = 0.02), respectively. At discharge, 82 patients (28.4%) had poor functional outcomes. The median serum level of MIF was lower in group with good outcomes than that observed in poor outcomes (19.4[15.8-24.2] vs. 24.0[19.9-29.4] ng/ml; P < 0.001). When serum level of MIF was increased by each 1 ng/ml, the unadjusted and adjusted risk of poor outcomes was elevated by 9% (1.09 [1.05-1.13], P < 0.001) and 6% (1.06 [1.02-1.10], P < 0.01), respectively. CONCLUSIONS: High MIF levels are independently related to the moderate to high clinical severity in ischemic stroke patients, as well as the poor outcome at discharge.


Subject(s)
Brain Ischemia/blood , Brain Ischemia/pathology , Intramolecular Oxidoreductases/blood , Macrophage Migration-Inhibitory Factors/blood , Stroke/blood , Stroke/pathology , Aged , Female , Hospitalization , Humans , Male , Middle Aged , Prognosis , Severity of Illness Index
14.
Cell Mol Neurobiol ; 39(3): 451-460, 2019 Apr.
Article in English | MEDLINE | ID: mdl-30778712

ABSTRACT

Various studies demonstrate that CD137 (TNFRSF9, 4-1BB) promotes atherosclerosis and vascular inflammation in experimental models via interactions with the CD137 ligand (CD137L). However, the exact role of CD137 in ischemic stroke remains unclear. In this study, we analyzed dynamic changes of peripheral CD137 expression on T cells in a mouse model of cerebral ischemia-middle cerebral artery occlusion (MCAO), as well as alternation of neurological function, infarct size and cerebral inflammatory status after inhibition of the CD137/CD137L pathway using an anti-CD137L monoclonal antibody. MCAO mice showed elevated surface expression of CD137 on T cells in both peripheral blood and lymphoid tissues during early cerebral ischemia. Remarkably, blockade of the CD137/CD137L pathway reduced the post-ischemic brain damage. Our findings indicate that enhanced CD137 costimulation occurs in early cerebral ischemia and promotes T cell activation, which in turn upregulates inflammatory immune response and possibly exerting deleterious effects on cerebral ischemia.


Subject(s)
4-1BB Ligand/metabolism , Brain Ischemia/metabolism , 4-1BB Ligand/blood , Animals , B-Lymphocytes/metabolism , Brain Ischemia/etiology , Brain Ischemia/immunology , Brain Ischemia/pathology , CD4-Positive T-Lymphocytes/metabolism , CD8-Positive T-Lymphocytes/metabolism , Cell Membrane/metabolism , Cytokines/genetics , Cytokines/metabolism , Disease Models, Animal , Female , Gene Expression Regulation , Infarction, Middle Cerebral Artery/complications , Infarction, Middle Cerebral Artery/pathology , Matrix Metalloproteinase 9/genetics , Matrix Metalloproteinase 9/metabolism , Mice, Inbred C57BL , RNA, Messenger/genetics , RNA, Messenger/metabolism
15.
J Pineal Res ; 66(1): e12532, 2019 Jan.
Article in English | MEDLINE | ID: mdl-30320949

ABSTRACT

Paraquat (PQ), a broad-spectrum agricultural pesticide, causes cellular toxicity by increasing oxidative stress levels in various biological systems, including the reproductive system. PQ exposure causes embryotoxicity and reduces the developmental abilities of embryos. However, there is little information regarding the toxic effects of PQ on oocyte maturation. In this study, we studied the toxic effects of PQ exposure and the effects of melatonin on PQ-induced damage in bovine oocytes. PQ exposure disrupted nuclear and cytoplasmic maturation, which was manifested as decreased cumulus cell expansion, reduced first polar body extrusion, and abnormal distribution patterns of cortical granules and mitochondria. In addition, PQ treatment severely disrupted the ability of the resulted in vitro-produced embryos to develop to the blastocyst stage. Moreover, PQ exposure significantly increased the intracellular reactive oxygen species (ROS) level and early apoptotic rate, and decreased the glutathione (GSH) level, antioxidative CAT and GPx4 mRNA, and apoptotic-related Bcl-2/Bax mRNA ratio. These results indicated that PQ causes reproductive toxicity in bovine oocytes. Melatonin application resulted in significant protection against the toxic effects of PQ in PQ-exposed oocytes. The mechanisms underlying the role of melatonin included the inhibition of PQ-induced p38 mitogen-activated protein kinase (MAPK) activation, and restoration of abnormal trimethyl-histone H3 lysine 4 (H3K4me3) and trimethyl-histone H3 lysine 9 (H3K9me3) levels. These results reveal that melatonin serves as a powerful agent against experimental PQ-induced toxicity during bovine oocyte maturation and could form a basis for further studies to develop therapeutic strategies against PQ poisoning.


Subject(s)
Melatonin/pharmacology , Oocytes/drug effects , Paraquat/toxicity , Animals , Antioxidants/metabolism , Cattle , Female , Glutathione/metabolism , Reactive Oxygen Species/metabolism
16.
BMC Neurol ; 19(1): 30, 2019 Feb 21.
Article in English | MEDLINE | ID: mdl-30791893

ABSTRACT

BACKGROUND: Posterior reversible encephalopathy syndrome (PRES) is a complication that occurs during various diseases' treatment. Imaging examination is the gold standard for diagnosis. PRES frequently occurrence in patients with hematological malignancies results in poorer prognosis and higher mortality. We aim to establish a practical and operable scale for early prediction, assessment of the severity of the Posterior Reversible Encephalopathy Syndrome, and timely intervention for better prognosis. METHODS: The scale designed by reviewing the literature and by referring to clinical practice. We assessed the reliability and validity of the scale. Scale-based assessment of children undergoing chemotherapy for acute lymphoblastic leukemia conducted as early warning and intervention for those who may have PRES. RESULTS: Establishment of Posterior Reversible Encephalopathy Syndrome early warning scoring (PEWS) scale included three parts, as follows: (1) risk factors, including underlying disease, hypertension, Infection, and drug toxicity; (2) clinical features, including high cranial pressure, visual symptoms, seizure, and disturbance of consciousness; and (3) EEG features, including slow wave and epileptiform discharges. Utility assessment of PEWS scale showed that in 57 patients with acute lymphoblastic leukemia, 54 scored less than 10 and none of them detected as PRES. The other two had scores of 12 and 13 both diagnosed with PRES by brain MRI scan. CONCLUSIONS: PEWS scale can predict PRES early. PRES was highly suspected when the score was 10 points and more. Thus, prophylactic intervention can give to improve the prognosis of PRES.


Subject(s)
Early Diagnosis , Posterior Leukoencephalopathy Syndrome/diagnosis , Adolescent , Child , Child, Preschool , Electroencephalography , Female , Humans , Infant , Magnetic Resonance Imaging , Male , Reproducibility of Results , Risk Factors
18.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 50(4): 478-482, 2019 Jul.
Article in Zh | MEDLINE | ID: mdl-31642222

ABSTRACT

OBJECTIVE: To determine the potential value of the two-dimensional (2D) cardiac magnetic resonance imaging (CMR) tissue tracking (CMR-TT) method in assessing the cardiac function of tree shrew at 7T. METHODS: Healthy adult tree shrews (male, n=8) and spraguedawley rats(male, n=8) were selected for this study. CMR was performed to acquire the short-axis images of left ventricle at 7T using the same appropriative coil and cine sequence for all experimental animals. The CMR images were processed using the professional cardiac analysis software, calculating ejection fraction (EF), radial peak sysolic strain (Err), circumferential peak sysolic strain (Ecc), radial peak sysolic displacement (DR), and LVM/BM 〔the ratio of left ventricular mass (LVM) to body mass (BM)〕. RESULTS: Cine imaging for the tree shrews was 100% successful following the CMR protocol for the rats, with clearly visible main segments of cardiac. Significant differences in EF, Err, Ecc and DR were found between the two groups of animals (P < 0.01). The tree shrews has lower EF, Err and Ecc than the rats. Err and Ecc appeared in the fifteenth phase in left ventriclar systole in the tree shrews, compared with the tenth phase in the rats.The tree shrews also had higher LVM/BM than the rats. CONCLUSION: The cardiac function of tree shrew can be assessed using the 2D CMR-TT method despite significant differences across species.


Subject(s)
Heart/diagnostic imaging , Magnetic Resonance Imaging, Cine , Tupaiidae , Ventricular Function, Left , Animals , Magnetic Resonance Imaging , Male , Rats , Rats, Sprague-Dawley , Reproducibility of Results , Stroke Volume , Systole
19.
BMC Neurol ; 17(1): 164, 2017 Aug 25.
Article in English | MEDLINE | ID: mdl-28841844

ABSTRACT

BACKGROUND: Acute autonomic neuropathy (AAN) is rare disorder with anecdotal report, especially for childhood onset patients. Misdiagnosis or delays in treatment can always be found in clinical practice. We conducted this study to give a description of the manifestations and treatment of AAN in children and therefore help clinicians to make the accurate diagnosis early so that the prognosis of the patients can be improved. METHODS: A systematic record from 3 clinical centers was used to identify 11 subject, 3 males and 8 females, with clinical diagnosed AAN. RESULT: The age ranged from 2 years and 4 months to 14 years and 6 months (mean, 9 ± 3.6 years old) and the course from onset to diagnosis ranged from 7 days to 8 months. All children shared prominent initial symptoms, 7 with frequent vomiting and 4 with motor dysfunctions. The condition of 9 patients improved after treatment of IVIg and intravenous glucocorticoid. CONCLUSION: The clinical manifestations of AAN are diverse, generalized, and non-specific. Gastrointestinal disorders were the most common initial symptoms. Symptoms of gastrointestinal system and abnormal secretion of glands were severe and more common than other symptoms. The mechanism of AAN remains unknown. Although IVIg and intravenous glucocorticoid can be used in clinical practice, there is still no treatment recommendation and further study is needed.


Subject(s)
Autonomic Nervous System Diseases , Gastrointestinal Diseases , Child , Child, Preschool , Female , Humans , Male
20.
Epilepsy Behav ; 77: 13-18, 2017 12.
Article in English | MEDLINE | ID: mdl-29073472

ABSTRACT

Mental retardation (MR) is one of the most common cognitive comorbidities in children with tuberous sclerosis, and there are enormous studies about its risk factors. The genetic difference and the severity of epilepsy are the two main factors, but their weight in the occurrence of MR is still unclear. Two hundred twenty-three patients with tuberous sclerosis who received intelligence assessment, genetic mutation analysis, and the epilepsy severity assessment were included in our study. Genotype-neurocognitive phenotype correlations and epilepsy-neurocognitive phenotype correlations were analyzed by binary logistic regression analysis. No statistical significant result was found on genotype-neurocognitive phenotype correlations, which contrasted the previous report. The prevalence of MR was 50.0% for the patients with tuberous sclerosis complex-1 (TSC1) mutation, 54.5% for TSC2 (p=0.561), 54.7% for patients with protein-truncating (PT) and 50.0% for patients with nontruncating (NT) (p=0.791), and 54.3% for patients with family history and 53.7% for patients without family history (p=0.748). Statistical significant results were found on epilepsy-neurocognitive phenotype correlations, both on E-chess score (p=0.01) and the occurrence of infantile spasms (p=0.014), which was consistent to the previous study. For children with tuberous sclerosis, instead of genetic factors, epilepsy may play the main role for the presence of mental retardation. Patients with mental retardation tend to have earlier seizure attack, take more AEDs, have more seizure types, and have higher seizure frequency. Among the four cognitive functions in Denver II, social ability and language ability are more vulnerable to be influenced than fine and gross motor ability.


Subject(s)
Epilepsy/complications , Intellectual Disability/etiology , Intelligence/physiology , Seizures/complications , Tuberous Sclerosis/complications , Child, Preschool , Cognition/physiology , DNA Mutational Analysis , Epilepsy/genetics , Epilepsy/psychology , Female , Genetic Association Studies , Humans , Intellectual Disability/genetics , Intellectual Disability/psychology , Male , Mutation , Neuropsychological Tests , Phenotype , Retrospective Studies , Risk Factors , Seizures/genetics , Seizures/psychology , Social Skills , Tuberous Sclerosis/genetics , Tuberous Sclerosis/psychology
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