Objective The study is to evaluate autonomic nervous activity and its circadian rhythm over a 24 hour period in children with beta adrenergic receptor (? AR) hypersensitivity and hyperthyroidism by analysis of heart rate variability (HRV), and to discuss the diagnosis value of autonomic nervous tone change in children with ? AR hypersensitivity Methods Indexes of HRV are measured in 23 children with ? AR hypersensitivity, and 13 hyperthyroidism and 26 healthy control Time domain indexes and spectral indexes of HRV are derived and the night day difference of HRV is analyzed Results 1 Spectral indexes over a 24 hour period: In patients with ? AR hypersensitivity and hyperthyroidism, there are significant increases both in low frequency (LF) to high frequency (HF) ratio (LF/HF) and HF normalized units (HF UN ) compared with the control group Whereas there are no significant changes compared with ? AR hypersensitivity and hyperthyroidism 2 Spectral indexes during waking hours: In patients with? AR hypersensitivity and hyperthyroidism, there are no significant difference in LF normalized units (LF UN ), HF UN and LF/HF; whereas there are significance changes compared with normal subject 3 Spectral indexes during sleeping hours: there are no significantly differences in indexes of HF, LF UN and HF UN compared with ? AR hypersensitivity and normal subject, whereas these indexes significance changes compared with hyperthyroidism 4 Time domain indexes change over a 24 hour period: There are significant changes of the night day difference in time domain indexes with? AR hypersensitivity or control group, in which rMSSD and pNN50 are most sensitive indexes Whereas there are significant difference in patients with hyperthyroidism in any time domain indexes of HRV compared with control group or ? AR hypersensitivity, and the night day difference in HRV is significantly smaller compared with ? AR hypersensitivity or control group, the circadian rhythm is almost disappeared Conclusion It is showed that the children with? AR hypersensitivity have no difference from normal subjects in autonomic nervous system activity, but these patients respond differently to the catecholamine stimulus, which results in changes in autonomic balance, and relatively increase of sympathetic nervous activity But cardiac autonomic nervous activity still has a circadian rhythm, which is similar to normal subject The analysis of HRV may play an important role in diagnosis? AR hypersensitivity

Objective To explore the dynamic change of serum leptin interleukin-6(IL-6),and interleukin-8(IL-8)during cerebral infarction,and to analyze the possible relationship between these factors and the severity of the disease.Method The levels of serum leptin,IL-6 and IL-8 were measured by radioimmunoassay in 60 patients with acute cerebral infarction,who were admitted to the hospital within 24 hours after stroke.Patients' neurologic impairment were evaluated by European Stroke Scale(ESS)at 1,3 and 7 days respectively after hospitalization.At the same time,another 30 normal adults were enrolled set as control group. Results The levels of serum Leptin,IL-8 in patients group after at 1 days,3 and 7 days were higher than those in the controls(P0.05).The ESS of these patients were 76.77?26.42,70.02?29.17,74.65?28.42 respectively,after 1,3 and 7 days.It shown that ESS simply correlated to the level of IL-8(P0.05).Statistic analysis was carried,but by using t test and linear correlation.(SPSS11.5 statistical package).Conclusion Leptin,IL-6 and IL-8 probably play a role in the inflammatory,reaction during acute cerebral infarction.The IL-8 may reflect the severity of the disease.

Objective To construct a tyrosine kinase B(TrkB) targeted RNA interference (RNAi) lentiviral vector.Methods Four oligonucleotides targeting rat TrkB gene were synthesized and cloned into lentiviral vector pXZRNAi 1.0 to construct recombinant lentiviral vectors pXZRNAi-shTrkB-1,2,3,4.Neural stem cells prepared from rat hippocampus were infected with these high-titer viruses.Real-time PCR was employed to detect the TrkB mRNA expression and western blot was used to assess the gene silencing efficacy of these recombinants.Results Enzyme digestion and DNA sequencing results demonstrated that these shRNAs were correctly inserted into lentiviral vectors and the four recombinants were constructed successfully with the titer of 8.6 × 105cfu/ml.The infection efficiency of the letivirus on neural stem cells reached 80％.Compared with the uninfection group,the expression levels of TrkB mRNA in neural stem cells decreased significantly after transfected with pXZRNAi-shTrkB-3 and 4((66.7 ± 5.5) ％ and(76.8 ± 4.9) ％ respectively,P ＜ 0.05) ; and the protein expression levels were also significantly decreased ((68.5 ± 4.3)％ and (78.2 ± 5.1)％ respectively,P ＜ 0.05).Conclusion The lentiviral vectors for TrkB have been successfully constructed with high yield of lentivirus,which provides versatile method for assessing gene function in neural stem cells.

Objective To study the effect of social isolation( SI) on the exploratory behavior and working memory in mice. Methods The Kunming mice of postnatal 21 days were divided into the control group,SI 2 weeks group,SI 2 weeks gregarious group,SI 4 weeks group and SI 8 weeks group,according to randomized design with ten animals each. All isolated mice were isolated for 2, 4 and 8 weeks respectively, the gregarious group were housed under normal grouped housing enviroment after isolation until adult, the mice with the relative same age were control groups. All animals were measured for exploratory behavior and working memory by performing open field and T?maze after the treatment. Results In the open field,compared to the relative control group,the central area of the total time in the SI 4 weeks group(0.07±0.04) was less than the control (0.10±0.04) obviously. The central area percentage of total time in SI 8 weeks group (0.64±0.12) were more than the control (0.43±0.08). In the T?maze,the alteration times in SI 2 weeks group (first day (5.92±0.79),second day (6.67±1.3),third day (7.42±1.08),fourth day (8.17±1.27)) were less than the control (first day (6.80±1.14); second day (7.60± 0.84);third day (8.30±0.95);forth day (9.20±1.32)). However,the alteration times of gregarious group showed no obvious change. Both the alteration times of SI 4 weeks (8.18±1.99) in the second day and that of SI 8 weeks (8.29±3.04) in the forth day were more than the control (6.60±2.11) and (7.80±2.53) respectively.Conclu?sions Working memory of SI 2 weeks rats decrease,which can be improved by the resocialization.SI 4 weeks and 8 weeks rats show the decreasing exploring ability and increasing anxiety and work memory.

Objective To study the effects of social isolation (SI)on the spatial and nonspatial cognitive ability in mice.Methods The postnatal 21 day kunming mice were divided into control group,SI 2 weeks group,SI 4 weeks group,SI 8 weeks group and SI 2 weeks gregarious group according to randomized block design,with ten animals each.SI 2 weeks group,SI 4 weeks group and SI 8 weeks group were isolated for 2,4 and 8 weeks respectively,SI 2 weeks gregarious group would be housed under normal grouped housing condition after 2 weeks isolation until adult,the relative control groups were the same age as the relative SI and SI gregarious group.All animals were measured the spatial and nonspatial cognitive ability by carrying the object recognition test(ORT) and object location test (OLT) after the treatment.Results In the ORT,compared to the relative control group,the discrimination index in the SI 2 weeks group,SI 4 weeks group and SI 8 weeks group ( ( - 0.03 ± 0.003 ),( - 0.11 ±0.02) and( - 0.21 ± 0.02 ) respectively) were strikingly lower than the relative control group ( ( 0.29 ± 0.03 ),(0.13±0.07) and (0.09 ±0.03) respectively) (P＜0.05).In the OLT,compared to the relative control group,the discrimination index in the SI 2 weeks group,SI 4 weeks group and SI 8 weeks group( ( -0.15 ±0.02),( -0.30± 0.02),( - 0.32 ± 0.02 ) respectively ) were strikingly lower than the relative control group ( (0.33 ± 0.02 ),(0.41 ± 0.03 ),(0.27 ± 0.04)respectively)(P＜ 0.05 ),while the SI 2 weeks gregarious group with the resocialization to the normal housing condition showed no change.Conclusions 2 weeks,4 weeks and 8 weeks isolation on mice lead to the spatial and nonspatial cognition deficits,while the resocialization to the normal housing condition could recover the damage.

Objective To explore the effects of ADAR1 inducer and inhibitor on cognition and ADAR1 expression of isolated BALB/c mice.Methods Sixty healthy BALB/c mice were divided into 6 groups according to randomized design with 10 animals each group,the gregarious control group (GH),social isolation model group (SI),ADAR1 inducer treated gregarious group (GH+IFN-γ),ADAR1 inhibitor treated gregarious group (GH+EHNA),ADAR1 inducer treated isolation group (SI+IFN-γ) and ADAR1 inhibitor treated isolation group (SI+EHNA).Mice in drug treatment groups were treated with ADAR1 inducer (5.0? 104 U/kg,20 ml/kg,ip) and inhibitor (10 mg/kg,20 ml/kg,ip).Objection recognition test was used to measure cognition.Immunohistochenmistry was used to measure ADARI immunoreactivity and Western blotwas used to measure ADAR1 protein expression.Results In the objection recognition test,the non-spatial discrimination index of mice in SI group (-0.16±0.09) was significantly lower than that of GH group (0.41 ±0.17,P＜0.01),the non-spatial discrimination index of mice in SI+IFN-γ group (0.20±0.09) and in SI+ EHNA group (-0.29±0.12) was higher (P＜0.01) and lower (P＜0.05) than that of the SI group respectively.The immunohistochemistry results showed that the ADAR1 immunoreactivity in hippocampus of mice in SI group (Hilus:(0.013±0.003),CAI:(0.021±0.005)) decreased significantly compared to those of GH group(Hilus:(0.021 ±0.002),(0.047±0.004);both P＜0.05).And GH+IFN-γgroup mice showed increased ADAR1 immunoreactivity obviously in Hilus ((0.013±0.003) vs (0.023±0.004),P＜0.01) and in CA1 ((0.021±0.005) vs (0.040±0.005),P＜0.01) compared with that of SI group,ADAR1 inducer recovered the above abnornal ADAR1 immunoreactivity.Western blot results showed that the ADAR1 protein expression of mice in SI group (0.48 ±0.07) in hippocampus was significantly decreased (P＜0.01) compared to that of GH group (1.00 ±0.00).The level of ADAR1 protein in SI+IFN-γgroup(0.82 ±0.04) increased compared with that of SI group.Conclusions Four weeks of social isolation can reduce the non-spatial cognitive ability of BALB/c mice and decrease the expression of ADAR1 in the hippocampus.The ADAR1 inducers and inhibitors can reverse and aggravate the cognitive impairment caused by social isolation respectively.The related mechanisms may be related to the expression of ADAR1.

Objective:To investigate the effect of adenosine deaminase acting on RNA 1 (ADAR1) on 5-serotonin-2c receptor in alleviating aggression in socially isolated mice.Methods:Sixty healthy male BALB / c mice aged 21 days were randomly divided into six groups: social isolation group, social control group, ADAR1 inducer social isolation group, ADAR1 inhibitor social isolation group, ADAR1 inducer social control group and ADAR1 inhibitor control group.The mice fed in single cage for 4 weeks were used as social isolation model while the mice fed in group were used as control group.ADAR1 inducer (5.0×10 4 U/kg) and inhibitor (10 mg/kg) were given intraperitoneally to mice in the ADAR1 inducer social isolation group and the ADAR1 inhibitor social isolation group respectively.The aggressive behavior of mice was evaluated by resident-intruder test.The expression of ADAR1 and 5-serotonin-2c receptors in the brain of mice was detected by immunohistochemistry and Western blot. Results:The attack latency of social isolation group was significantly lower than that of social control group ((43.15±6.99) s, (542.40±30.50) s; t=15.906, P<0.01), and the latency of attack ((256.70±29.49) s) in the ADAR1 inducer social isolation group was significantly higher than that in the social isolation group ( t=7.046, P<0.01). The latency of attack ((15.25±2.18)s) in the ADAR1 inhibitor social isolation group was significantly lower than that in the social isolation group ( t=3.809, P<0.01). The optical density of ADAR1 immunoreactive cells in the amygdala of the social isolation group mice was significantly lower than that in the corresponding brain area of the social control group (BLA: (0.038±0.002), (0.074±0.004); LaDL: (0.033±0.002), (0.060±0.002); LaVM: (0.045±0.003), (0.073±0.004); Lavl area: (0.044±0.003), (0.070±0.003); t=8.428, 9.037, 6.462, 5.698, all P<0.01). The optical density of ADAR1 immunoreactive positive cells in the amygdala (BLA: (0.060±0.003), LaDL: (0.042±0.002), LaVM: (0.056±0.004), Lavl: (0.054±0.003) in the ADAR1 inducer social isolation group was significantly higher than those in the corresponding brain area of the social isolation group mice ( t=6.055, 2.876, 2.312, 2.492; all P<0.05). The expression of ADAR1 protein and 5-serotonin-2c receptor protein in amygdala of social isolation group were significantly lower than those of social isolation group ( t=11.37, 12.65; P<0.01). The expression of ADAR1 protein and 5-serotonin-2c receptor protein in the amygdala of the ADAR1 inducer social isolation group were significantly higher than those of the social isolation group ( t=3.02, 4.401; P<0.05). Conclusion:ADAR1 inducer alleviates the aggressive behavior of social isolated BALB / c mice by enhancing the protein expression of 5-serotonin-2c receptor in the amygdala of social isolated BALB/c mice.

Rabdosia serra(R.serra),an important component of Chinese herbal tea,has traditionally been used to treat hepatitis,jaundice,cholecystitis,and colitis.However,the chemical composition of R.serra and its effect against colitis remain unclear.In this study,the chemical composition of the water extract of R.serra was analyzed using ultra performance liquid chromatography coupled with a hybrid linear ion trap quadrupole-orbitrap mass spectrometer(UPLC-LTQ-Orbitrap-MS).A total of 46 compounds,comprising ent-kaurane diterpenoids,flavonoids,phenolic acids,and steroids,were identified in the water extract of R.serra,and the extract could significantly alleviate dextran sulfate sodium salt-induced colitis by improving colon length,upregulating anti-inflammatory factors,downregulating proinflammatory fac-tors,and restoring the balance of T helper 17/T regulatory cells.R.serra also preserved intestinal barrier function by increasing the level of tight junction proteins(zonula occludens 1 and occludin)in mouse colonic tissue.In addition,R.serra modulated the gut microbiota composition by increasing bacterial richness and diversity,increasing the abundance of beneficial bacteria(Muribaculaceae,Bacteroides,Lactobacillus,and Prevotellaceae_UCG-O01),and decreasing the abundance of pathogenic bacteria(Turi-cibacter,Eubacterium_fissicatena_group,and Eubacterium_xylanophilum_group).Gut microbiota depletion by antibiotics further confirmed that R.serra alleviated colitis in a microbiota-dependent manner.Overall,our findings provide chemical and biological evidence for the potential application of R.serra in the management of colitis.

Objective:To investigate the blood pressure change in patients with acute ischemic stroke (AIS) and hypertension treated with cinepazide maleate injection.Methods:This was a subgroup analysis of post-marketing clinical confirmation study of cinepazide maleate injection for acute ischemic stroke: a randomized, double-blinded, multicenter, placebo-parallel controlled trial, which conducted in China from August 2016 to February 2019. Eligible patients fulfilled the inclusive criteria of acute anterior circulation ischemic stroke with National Institutes of Health Stroke Scale (NIHSS) scores of 7-25. The primary endpoints were mean blood pressure of AIS patients treated with cinepazide maleate or control, which were assessed during the treatment period (14 days), and the proportion of the patients with normal blood pressure was analyzed after the treatment period. Furthermore, a subgroup analysis was performed to investigate a possible effect of the history of hypertension on outcomes.Results:This analysis included 809 patients with hypertension. There was no significant difference in patients blood pressure and the proportion of patients with normal blood pressure (60.5% vs. 59.0%, P>0.05) between cinepazide maleate group and control group. Conclusion:Administration of cinepazide maleate injection does not affect the management of clinical blood pressure in patients with AIS.