Gestational dexamethasone exposure impacts hippocampal excitatory synaptic transmission and learning and memory function with transgenerational effects

The formation of learning and memory is regulated by synaptic plasticity in hippocampal neurons. Here we explored how gestational exposure to dexamethasone, a synthetic glucocorticoid commonly used in clinical practice, has lasting effects on offspring's learning and memory. Adult offspring rats of prenatal dexamethasone exposure (PDE) displayed significant impairments in novelty recognition and spatial learning memory, with some phenotypes maintained transgenerationally. PDE impaired synaptic transmission of hippocampal excitatory neurons in offspring of F1 to F3 generations, and abnormalities of neurotransmitters and receptors would impair synaptic plasticity and lead to impaired learning and memory, but these changes failed to carry over to offspring of F5 and F7 generations. Mechanistically, altered hippocampal miR-133a-3p-SIRT1-CDK5-NR2B signaling axis in PDE multigeneration caused inhibition of excitatory synaptic transmission, which might be related to oocyte-specific high expression and transmission of miR-133a-3p. Together, PDE affects hippocampal excitatory synaptic transmission, with lasting consequences across generations, and CDK5 in offspring's peripheral blood might be used as an early-warning marker for fetal-originated learning and memory impairment.

Analysis of risk factors for death in patients with corona virus disease 2019 / 中华传染病杂志

Objective:To investigate the risk factors for death in patients with corona virus disease 2019 (COVID-19).Methods:The clinical data of 141 cases of patients diagnosed with COVID-19 at Renmin Hospital of Wuhan University from February 1 to February 26, 2020 were included in this retrospective analysis. The gender, age, time of hospitalization after the onset, clinical manifestations, underlying diseases, laboratory examination indicators (inculding white blood cell counts, neutrophil counts, lymphocyte counts, lymphocyte subsets, immunoglobulin, complement 3, complement 4, D-dimer, fibrinogen), and short term prognosis were compared between the death group and the survival group. Logistic regression was used to analyze the factors influencing the death of COVID-19 patients. The t test, Mann Whitney U test or chi-square test were used for comparison between groups. Results:Of the 141 COVID-19 patients, 52 died and 89 survived. The age, hypertension, chronic respiratory diseases, cardiovascular and cerebrovascular diseases, fever and wheeze of patients in the death group were all higher than those in the survival group, which were (70.7±13.3) years old vs (50.4±15.3) years old, 51.9%(27/52) vs 14.6%(13/89), 15.4%(8/52) vs 4.5%(4/89), 30.8%(16/52) vs 7.9%(7/89), 80.8%(42/52) vs 61.8%(55/89) and 50.0%(26/52) vs 25.8%(23/89), respectively. The differences were all statistically significant ( t=7.972, χ2=22.104, 3.615, 12.392, 5.503 and 8.447, respectively, all P<0.05). The white blood cell count, neutrophil count, CD4 + /CD8 + T lymphocyte, immunoglobulin E, D-dimer, fibrinogen, CD19 + T lymphocyte proportion and CD19 + T lymphocyte count of patients in the death group were all higher than those in the survival group, which were 8.20(5.26, 13.01)×10 9/L vs 5.29(3.96, 7.04)×10 9/L, 7.40(4.54, 11.46)×10 9/L vs 3.16(2.20, 5.01)×10 9/L, 2.32(1.77, 3.11) vs 1.63(1.25, 2.08), 125.0(42.6, 275.0) IU/mL vs 66.8(38.3, 143.0) IU/mL, 7.27(2.11, 16.21) mg/L vs 0.95(0.38, 2.54) mg/L, 4.37(2.72, 6.78) g/L vs 4.10(2.78, 4.97) g/L, (23.19±13.43)% vs (15.38±6.38)%, and (181.5±115.4)/μL vs (98.89±77.64)/μL, respectively. The differences were all statistically significant ( Z=3.944, 4.210, 2.834, 1.190, 5.497, 1.180, t=3.987, 3.411, respectively, all P<0.05). The lymphocyte count, CD3 + T lymphocyte proportion, CD3 + T lymphocyte count, CD8 + T lymphocyte proportion, CD8 + T lymphocyte count, CD16 + CD56 + T lymphocyte count and CD4 + T lymphocyte count were all lower than those in survival group, which were 0.47(0.37, 0.96)×10 9/L vs 1.33(0.90, 1.55)×10 9/L, 48.72%(42.31%, 76.92%) vs 69.91%(65.05%, 75.36%), 223.0(100.0, 403.0)/μL vs 761.0(499.0, 1 092.0)/μL, 13.82%(10.32%, 19.82%) vs 24.90%(20.87%, 29.57%), 55.5(30.5, 106.0)/μL vs 318.0(162.5, 443.5)/μL, 63.0(29.0, 99.5)/μL vs 140.0(69.5, 195.5)/μL and (209.74±140.13)/μL vs (487.61±232.02)/μL, respectively. The differences were all statistically significant ( Z=6.937, 3.944, 5.883, 3.924, 5.703, 3.517 and t=7.558, respectively, all P<0.01). Age, history of hypertension, white blood cell count, D-dimer, and fibrinogen were the risk factors for death of COVID-19 (odds ratio ( OR)=1.170, 10.405, 3.055, 1.128 and 1.343, respectively, all P<0.05). Conclusion:Age, underlying hypertension, white blood cell count, D-dimer and fibrinogen are independent prognostic factors for COVID-19.

Diagnostic value of plasma heparin-binding protein and pentraxin 3 in neonatal bacterial infection diseases / 中华检验医学杂志

Objective To evaluate the diagnosis value of heparin-binding protein ( HBP ) and pentraxin 3 ( PTX3 ) in neonatal bacterial infectious diseases . Methods A retrospective study was conducted on 30 septic neonatal as neonatal sepsis group and 84 local infection neonatal as general infection group from May to November 2017 in Renmin Hospital of Wuhan University .It also selected 50 high bilirubin hematic disease but without infection or shock neonatal ( control group ) .A total of 114 neonatal bacterial infection ( neonatal sepsis group and general infection group ) were divided into shock group ( 39 cases) and non-shock group ( 75 cases ) . The levels of plasma HBP and PTX3 were tested with immunoturbidimetry and ELSIA respectively .The results of procalcitonin ( PCT ) and white blood cells (WBC) counts were collected.Non-parametric test were performed for non-normal distribution data; the diagnostic performances of data were evaluated by receiver operating characteristic ( ROC) curve; pearson correlation coefficient was performed for correlation analysis .Results Plasma levels of HBP in neonatal sepsis group, general infection group and control group were (64.41 ±78.51) ng/ml, (47.16 ±50.59) ng/ml and (31.97 ±20.76) ng/ml, respectively; plasma levels of PTX3 were (2.23 ±1.44) ng/ml, (1.76 ±0.94) ng/ml and (1.26 ±0.66) ng/ml, respectively;serum levels of PCT were (31.92 ±36.65) ng/ml,( 7.72 ±9.28 ) ng/ml and ( 1.87 ±5.02 ) ng/ml, respectively.The levels of PTX3 and PCT in neonatal sepsis group were significantly higher than in general infection group (Z=3.74, Z=5.01, all P<0.05) and control group (Z=3.98, Z=5.20, all P<0.05).The levels of HBP in neonatal sepsis group were significantly higher than in control group ( Z =2.37, P <0.05 ), but there were no significant difference in neonatal sepsis group and general infection group (Z=1.16, P>0.05).The levels of PTX3 and PCT in shock group were significantly higher than in non-shock group ( Z=2.20, Z=3.70, all P<0.05), but there were no significant difference in plasma HBP of shock and non-shock group ( Z=0.37, P>0.05).The area under curve (AUC) of HBP, PTX3 and PCT were 0.683, 0.802 and 0.869 respectively in the diagnosis of neonatal bacterial infection diseases .The biggest AUC of combined diagnosis of HBP, PTX3 and PCT was 0.910.There was a positive correlation between PTX 3 and PCT ( r=0.242, P<0.05) .Conclusions PTX3 and PCT could probably be acted as an important biomarker for diagnosis of neonatal bacterial infection diseases , and combined diagnosis of HBP , PTX3 and PCT could be superior to single biomarker diagnosis.

Expression levels and mechanism of microRNA-34a and Notch1 signaling pathway in hippocampi of temporal lobe epilepsy rats / 中华实用儿科临床杂志

Objective To explore the expression levels of microRNA(miR)-34a in hippocampus of temporal lobe epilepsy rats and the effect of miR-34a on its target signaling pathway Notch1.Methods Rats were divided randomly into experiment group (n=40) and control group (n=40) by adopting random number table method.The status epilepticus model and the temporal lobe epilepsy model were induced by using lithium-pilocarpine for experiment group.The control group rats received an injection of an equal amount of 9 g/L saline as instead of pilocarpine.Racine grading was performed at 24 hours,day 3,day 7,day 15,and 1 month after modeling to evaluate the behavior.Real-time fluorescent quantitative polymerase chain reaction was used to test the mRNA expressions of miR-34a and Notch1.Western blot was performed to explore the protein expression of Notch1.Results The expression levels of miR-34a at post-status epilepticus in 24 hours,day 3,day 7,day 15 were 2.55±0.29,2.11±0.17,1.68±0.49 and 1.84±0.42,respectively,which showed statistically significant difference compared with the control group (1.00±0.00) (t=-1.55,-1.11,-0.68,-0.84,all P<0.05).The expression levels of Notch1 mRNA at post-status epilepticus in 24 hours,day 3,day 7,day 15,1 month were 1.44±0.31,1.27±0.13,1.52±0.28,0.91±0.33,and 0.80±0.09 respectively.There were significant differences at 24 hours,day 7 in Notch1 mRNA expression (t=-0.44,-0.52,all P<0.05) compared with the control group(1.00±0.00).The expression level of Notch1 mRNA on day 15 was significantly lower than 24 hours and day 7 (t=-0.54,-0.62,all P<0.05),and the expression in 1 month was significantly lower than in 24 hours,or day 3 and day 7 (t=-0.64,-0.46,-0.72,all P<0.05).The expression levels of Notch1 protein at post-status epilepticus 24 hours,day 3,day 7,day 15,1 month were 0.78±0.09,0.57±0.13,0.55±0.16,0.42±0.13,and 0.33±0.09,respectively.There was significantly up-regulated at 24 hours of Notch1 protein expression compared with control group (0.51±0.15)(t=-0.20,P<0.05);and the expression level at day 15 were significantly lower than 24 hours (t=-0.26,P<0.05),while the expression in 1 month was significantly lower than in 24 hours and on day 3 (t=-0.36,-0.24,all P<0.05).Conclusion miR-34a is significantly up-regulated in the post-status epilepticus rat hippocampus,and it may contribute to temporal lobe epilepsy by activating Notch1 signaling pathway.

Study on relationship between serum insulin-like growth factor 1 level and children with tourette syndrome / 中国综合临床

Objective To explore the relationships between serum insulin-like growth factor 1 (IGF-1) level and children with tourette syndrome, and the significance of IGF-1 level for the diagnosis of tourette syndrome.Methods Enzyme-linked immunosorbent assay (ELISA) was adopted to detect the serum level of IGF-1 and S100B of 53 children patients with tourette syndrome and 53 children with physical examination.The receiver operating characteristic (ROC) curves were used to determine the cut-off value and assess the sensitivity,specificity and diagnostic efficiency.Results The concentration of IGF-1 was significantly lower in the children with tourette syndrome group than in normal group ((41.51±4.23) μg/L vs.(69.04±5.26) μg/ L,t=29.693,P＜0.01),and the concentration of S100B was significantly higher in the children with tourette syndrome group than in normal group((129.48±9.54) ng/L vs.(81.37±8.42) ng/L,t =27.526,P＜0.01) .When 59.28 and 93.35 ng/mL ware used as cut-off value, the sensitivity, specificity and area under curve for IGF-1 in diagnosis of children with tourette syndrome were 89.6％, 96.4％ and 0.931, respectively.The sensitivity,specificity and area under curve for S100B in diagnosis of children with tourette syndrome were 94.1％, 91.3％ and 0.969, respectively.And the diagnostic efficiency of IGF-1 was similar to that of S100B.Conclusion IGF-1 may play an important role in the development of tourette syndrome.Detection of IGF-1 in the serum is helpful in the diagnosis of children with tourette syndrome.

Temperament characteristics and its determinants in children with epilepsy / 中国医师杂志

Objective To investigate the temperament of children with epilepsy and the effects of various epilepsy-related variables on it. Methods The temperament of 60 pairs of epilepsy and normal children were assessed by temperament scale. The results of the two groups were compared. Epilepsy-related variables were analyzed. Result The scores of all dimensional variables in the epilepsy group were higher than that in normal group. The differences in adaptability and intensity of response between the two groups was statistically significant ( P <0. 05), and the differences in rhythmicity, approach-withdrawal toward new situations, emotional nature and persistence were more notable ( P <0.01). The temperament of epilepsy children was incline to difficult temperament( X2 = 10. 91, P <0.01). Age at onset of epilepsy, main caregiver and maternal education level had impaction on the temperament of epilepsy children..Conclusions The temperaments of epilepsy children tend to be negative. Children's temperaments are inclined to easy when their mothers are well educated and their main caregivers are parents, while they tend to be difficult temperament when the age of onset is early.

Changes of melatonin and cellular immunological function in children with febrile seizures and its clinical significance / 中国医师杂志

Objective To investigate the changes of melatonin and cellular immunological function in children with febrile seizures and its clinical significance. Methods 50 children, including 23 cases with complex febrile seizure (CFS) and 27 cases with simple febrile seizure (SFS) , and 25 cases with upper respiratory infections children selected as control group were enrolled in this study. Serum melato- nin was measured by enzyme-linked immunosorbent assay (ELISA) and cellular immunological function was measured by flow eytomcter. Results The levels of serum melatonin in the 3 groups of CFS, SFS, control were(14. 91±2. 61) ng/L, (20. 72±2. 54) ng/L, (23.93± 2. Ol) ng/L, respectively. The melatonin levels in CFS children were significantly decreased than that in control group and SFS children (P <0. O1). CD3 + ,CD4 +, the ratio of CD4 + /CD8 + and CD8 + in CFS group were significantly decreased than that in control group and SFS group (P <0.01). The ratio of CD4 +/CD8 + in SFS group was significantly decreased than that in control group (P <0.05), but CD3 + ,CD4 + and CD8 + had no statistics significance among these groups(P >0. 05). The serum rnelatonin level were positive related withdecreaseddegreeofCD3+,CD4+ andtberatioofCD4+ /CDS+ (r≥0. 472, P <0.05). Conclusion The disorder cfcellular immunological function was possible related with the loss of serum melatonin, and the loss of serum melatonin maybe one of the reasons for febrile seizures relapse and brain injured.

Test Methods of Helicobacter pylori Infection in Children / 中华医院感染学杂志

0.05).(2)CagA-positive H.pylori strains of children were only 21.4%. CONCLUSIONS(1)The detection of protein chips technology against H.pylori infection is compared with antral biopsy specimens.The result is without significant difference.(2)Protein chips technology can discover different types of H.pylori strains infection and determine present infection.It is a rapid,accurate method and can detect more factors.It′s a potential detecting method and worthy of using widely.