Systemic lupus erythematosus combined with Aspergillus fumigatus brain abscess in 2 cases / 中华神经科杂志

Systemic lupus erythematosus (SLE) complicated with Aspergillus fumigatus brain abscess is rare and needs to be differentiated from bacterial brain abscess and neuropsychiatric lupus. This article reports 2 cases of surgically diagnosed SLE combined with Aspergillus fumigatus brain abscess. The first patient was a 34-year-old woman. Six months after the diagnosis of SLE, she developed convulsions and unconsciousness. She was diagnosed as neuropsychiatric lupus at the first hospitalization because of negative imaging. After discharge, repeated head magnetic resonance imaging revealed abscess-like signals. The second patient, a 20-year-old male, developed high fever, convulsions, and unconsciousness 3 years after the diagnosis of SLE, and head imaging showed an abscess-like signal. The etiology of the cerebrospinal fluid of the 2 patients was both negative, and the Aspergillus fumigatus brain abscess was diagnosed by pathology through abscess resection or drainage. After treatment with voriconazole, the symptoms were relieved and the lesions were subsided.

Analysis of vitamin A and E levels in children of different ages with different respiratory diseases / 中国医师杂志

Objective:To investigate the difference of vitamin A and E levels in children with different respiratory diseases at different ages.Methods:A total of 671 children in Hunan Children's Hospital from July 2017 to October 2019 were selected as the disease group, including 197 cases of pneumonia, 152 cases of recurrent respiratory tract infection, 91 cases of asthma, 88 cases of cough variant asthma and 143 cases of Mycoplasma pneumoniae pneumonia; At the same time, 245 healthy children were selected as the normal group. The serum vitamin A and vitamin E levels of the two groups were detected by high performance liquid chromatography (HPLC).Results:⑴ The vitamin A level [(0.31±0.09)mg/L] of the disease group was lower than the normal group [(0.35±0.25)mg/L], and the vitamin E level [(8.92±2.57)mg/L] was lower than the normal group [(9.62±2.79)mg/L], with statistically significant difference ( P<0.05); ⑵ The level of vitamin A in the disease group at the age of >1-3 years [(0.32±0.09)mg/L] was lower than that in the normal group of the same age group [(0.35±0.08)mg/L]; the level of vitamin A in the disease group at the age of >3-6 years old [(0.30±0.08)mg/L] was lower than that of the same age group [(0.32±0.07)mg/L], with statistically significant difference ( P<0.05); ⑶ The vitamin E level of the disease group at >1-3 years old [(9.23±2.56)mg/L], >3-6 [(8.02±1.86)mg/L] and >6-14 years old [(8.02±1.82)mg/L] were lower than that of the same age normal group [(9.76±2.81)mg/L, (9.67±2.87)mg/L, (9.19±2.58)mg/L], with statistically significant difference ( P<0.05); ⑷ There were significant differences in vitamin A levels among different age in disease group ( P<0.05). Among them, the children with high risk of subclinical deficiency accounted for the largest proportion (45.78%) in the 6-month-1-year-old group, and the proportion of children with normal vitamin A levels in other age groups was the largest; ⑸ There are significant differences in vitamin E levels in different age groups in the disease group ( P<0.05), the levels in the normal range accounts for the largest proportion of all ages; ⑹ The levels of vitamin A and vitamin E in mycoplasma pneumoniae infection group were increased compared with in recurrent respiratory infection group , asthma group, and cough variant asthma group, and the difference was statistically significant ( P<0.05). Compared with the pneumonia group, the level of vitamin E increased in the recurrent respiratory infection group, and the difference was statistically significant ( P<0.05); The vitamin E levels in the cough variant asthma group were reduced compared with the repeated respiratory infection group, asthma group and pneumonia group ( P<0.05). Conclusions:The Vitamin A and E levels of children suffering from respiratory diseases are lower than those of normal children. The Vitamin A and E levels of different respiratory diseases and different age groups are different. Vitamin A and E supplementation may be significantly targeted according to different ages and different respiratory diseases in clinical practice.

Study on the effect of serum vitamin A and E on children with mycoplasma pneumoniae pneumonia based on propensity score matching / 中国医师杂志

Objective To explore the association between Vitamin A,E and mycoplasma pneumoniae pneumonia in children.Methods 153 children with mycoplasma pneumoniae pneumonia and 653 health children were selected as cases and controls,respectively.Propensity score matching (PSM) analysis were conducted to reducing confounding bias between groups.Blood samples were collected to test serum levels of vitamin A and E using high performance liquid chromatography (HPLC).Logistic regression was implemented to determine odds ratios (OR) and 95％ confidence intervals (CI) for evaluating the association of mycoplasma pneumoniae pneumonia with the serum levels of Vitamin A and E.Results Mter propensity score matching,the study cohort included 153 cases with mycoplasma pneumoniae pneumonia and 306 health children as controls.Before matching,with age and gender adjusted,logistic regression analysis indicated that higher serum levels of Vitamin A and E led to a lower risk of mycoplasma pneumoniae pneumonia (OR =0.075,95％ CI:0.007-0.815;OR =0.854,95％ CI:0.792-0.986).After matching,higher serum level of Vitamin E had a significantly lower risk of mycoplasma pneumoniae pneumonia (OR =0.877,95％ CI:0.810-0.950).Conclusions The serum levels of Vitamin A didnt have a statistically significant association with mycoplasma pneumoniae pneumonia.However,we observed an obvious association between Vitamin E and mycoplasma pneumoniae pneumonia.Hence Vitamin E clinical monitoring and supplementation are vital for preventing and treating mycoplasma pneumoniae pneumonia.

Study on the effect of serum vitamin A and E on children with mycoplasma pneumoniae pneumonia based on propensity score matching / 中国医师杂志

Objective@#To explore the association between Vitamin A, E and mycoplasma pneumoniae pneumonia in children.@*Methods@#153 children with mycoplasma pneumoniae pneumonia and 653 health children were selected as cases and controls, respectively. Propensity score matching (PSM) analysis were conducted to reducing confounding bias between groups. Blood samples were collected to test serum levels of vitamin A and E using high performance liquid chromatography (HPLC). Logistic regression was implemented to determine odds ratios (OR) and 95% confidence intervals (CI) for evaluating the association of mycoplasma pneumoniae pneumonia with the serum levels of Vitamin A and E.@*Results@#After propensity score matching, the study cohort included 153 cases with mycoplasma pneumoniae pneumonia and 306 health children as controls. Before matching, with age and gender adjusted, logistic regression analysis indicated that higher serum levels of Vitamin A and E led to a lower risk of mycoplasma pneumoniae pneumonia (OR=0.075, 95% CI: 0.007-0.815; OR=0.854, 95% CI: 0.792-0.986). After matching, higher serum level of Vitamin E had a significantly lower risk of mycoplasma pneumoniae pneumonia (OR=0.877, 95% CI: 0.810-0.950).@*Conclusions@#The serum levels of Vitamin A didn't have a statistically significant association with mycoplasma pneumoniae pneumonia. However, we observed an obvious association between Vitamin E and mycoplasma pneumoniae pneumonia. Hence Vitamin E clinical monitoring and supplementation are vital for preventing and treating mycoplasma pneumoniae pneumonia.

Mice deficient in the C-terminal domain of TAR DNA-binding protein 43 develop age-dependent motor dysfunction associated with impaired Notch1-Akt signaling pathway.

Intracellular mislocalization of TAR DNA-binding protein 43 (TDP-43), a nuclear DNA/RNA-binding protein involved in RNA metabolism, is a pathological hallmark of amyotrophic lateral sclerosis (ALS). Although the aggregation-prone, TDP-43 C-terminal domain is widely considered as a key component of TDP-43 pathology in ALS, recent studies including ours suggest that TDP-43 N-terminal fragments (TDP-∆C) may also contribute to the motor dysfunction in ALS. However, the specific pathological functions of TDP-43 N-terminal fragments in mice have not been elucidated. Here, we established TDP-∆C knock-in mice missing a part of exon 6 of murine Tardbp gene, which encodes the C-terminal region of TDP-43. Homozygous TDP-∆C mice showed embryonic lethality, indicating that the N-terminal domain of TDP-43 alone is not sufficient for normal development. In contrast, heterozygous TDP-∆C mice developed normally but exhibited age-dependent mild motor dysfunction with a loss of C-boutons, large cholinergic synaptic terminals on spinal α-motor neurons. TDP-∆C protein broadly perturbed gene expression in the spinal cords of aged heterozygous TDP-∆C mice, including downregulation of Notch1 mRNA. Moreover, the level of Notch1 mRNA was suppressed both by TDP-43 depletion and TDP-∆C expression in Neuro2a cells. Decreased Notch1 mRNA expression in aged TDP-∆C mice was associated with the age-dependent motor dysfunction and loss of Akt surviving signal. Our findings indicate that the N-terminal region of TDP-43 derived from TDP-∆C induces the age-dependent motor dysfunction associated with impaired Notch1-Akt axis in mice.

Neuregulin 1 confers neuroprotection in SOD1-linked amyotrophic lateral sclerosis mice via restoration of C-boutons of spinal motor neurons.

INTRODUCTION: Increasing evidence implicates the role of the cell types surrounding motor neurons, such as interneurons and glial cells, in non-cell autonomous neurodegeneration of amyotrophic lateral sclerosis (ALS). C-boutons, the large cholinergic synapses that innervate spinal α-motor neurons to control their excitability, are progressively lost from motor neurons in both human ALS and mutant Cu/Zn superoxide dismutase 1 (SOD1)-ALS mice. Neuregulin-1 (NRG1), a trophic factor implicated in neural development, transmission, and synaptic plasticity, has been reported to localize in the synapse of C-boutons. However, the roles of NRG1 in maintenance of motor neuron health and activity, as well as the functional consequences of its alteration in motor neuron disease, are not fully understood. RESULTS: NRG1 was localized to the post-synaptic face of C-boutons and its expression was significantly lost in SOD1-ALS mice and human ALS patients. Losses of NRG1 expression and C-boutons occurred almost contemporaneously in SOD1-ALS mice. In addition, expressions of ErbB3 and ErbB4, receptors for NRG1, were reduced in the motor neurons of SOD1-ALS mice. Furthermore, viral-mediated delivery of type III-NRG1 to the spinal cord restored the number of C-boutons and extended the survival time of SOD1-ALS mice. CONCLUSIONS: These results suggest that maintenance of NRG1-ErbB4/3 axis by supplementation of NRG1 confers neuroprotection in motor neuron disease, partly through the maintenance of C-boutons of spinal motor neurons.

Analysis of the risk factors of chronic cough in children / 中国医师杂志

Objective To explore the risk factors of chronic cough in children.Methods A hospital-based case-control study was conducted.A total of 60 children with chronic cough and 120 non-chronic cough children were interviewed with standard questionnaires.Non-conditional multivariable logistic model was performed to analyze the risk factors.Results Among 192 children that were performed questionnaire survey,180 cases were obtained the complete data with a questionnaire response rate of 93.75％.No significant difference in age,gender,and permanent residence was found between chronic cough and control groups,respectively (P ＞0.05).As shown in multivariable logistic model,parents with sensitive history (OR =1.924),mother or father smoking (mother:OR =1.989 ; father:OR =2.156),poor ventilation (OR =27.906),and interior decoration less than 3 months stay (OR =4.652) increased the risk of chronic cough in children.Conclusions Many factors,even the domestic environmental factors,are associated with chronic cough in children.It's time to strengthen the intervention of risk factors for reducing the occurrence of chronic cough in children.

The gap-junction inhibitor carbenoxolone suppresses the differentiation of Th17 cells through inhibition of IL-23 expression in antigen presenting cells.

Carbenoxolone (CBX) is a widely used gap-junction inhibitor. We have previously shown that treatment with CBX significantly delayed the onset of experimental autoimmune encephalomyelitis (EAE). However, the mechanism by which CBX delays the onset of EAE remains to be elucidated. Here, we show that CBX specifically inhibits the production of IL-23 by dendritic cells (DCs) and microglia in vitro. CBX treatment significantly reduced the population of Th17 cells in EAE mice. Furthermore, CBX downregulated the expression of IL-23 p19 via increased production of protein phosphatase 2A (PP2A). Thus, CBX may be an effective therapeutic strategy against Th17-mediated autoimmune diseases, such as multiple sclerosis.

Blockade of glutamate release from microglia attenuates experimental autoimmune encephalomyelitis in mice.

Multiple sclerosis (MS) is a chronic inflammatory demyelinating and neurodegenerative disease of the central nervous system. Despite a variety of anti-inflammatory or immunomodulation drugs including interferon-beta are effective to reduce relapse risk, most patients have progressive neurological deterioration due to axonal degeneration. Accumulation of activated microglia is a pathological hallmark of active MS lesion. Microglia can act as not only antigen-presenting cells but also effector cells to damage other cells in the central nervous system. Especially, glutamate released by activated microglia induces excito-neurotoxicity and may contribute to neurodegeneration in MS. Gap junction is a major cell-to-cell channel and is composed of paired hemichannels on coupled cells. Recent studies showed that cells release various small molecules (including ions, ATP, and amino acids) from unpaired hemichannel of gap junction that is openly exposed to the extracellular space. We have previously revealed that activated microglia produce glutamate via glutaminase and release it through hemichannels of gap junctions. Thus, in this study, we examined whether the glutaminase inhibitor and the gap junction blocker relieved experimental autoimmune encephalomyelitis (EAE) that is an animal model of MS. Here we show that the gap junction blocker carbenoxolone (CBX) and the glutaminase inhibitor 6-diazo-5-oxo-L-norleucine (DON) decreased glutamate release from activated microglia and rescued neuronal death in a dose-dependent manner in vitro. In EAE mice, treatment with CBX or DON also attenuated EAE clinical symptoms. Thus, blockade of glutamate release from activated microglia with CBX or DON may be an effective therapeutic strategy against neurodegeneration in MS.