Objective To explore the effect of enalapril combined with folate acid on endothelial function and urine microalbumin(UMA) in patients with hypertension.Methods 120 patients with hypertension were randomly divided into two groups:control group (n =60) was given enalapril 10.0mg/d,observation group (n =60) received enalapril 10.0mg + folic acid 0.4mg/d.The total treatment period was 8 weeks.Blood pressure,plasma homocysteine (Hcy),flow mediated dilation (FMD) and UMA were examined.Results The efficacy of pressure releasinghad no significant difference between two groups.Hcy[(10.2 ± 5.8) μmol/L vs (16.6 ±-8.1) μmol/L,t =3.641],FMD[(14.8 ±5.4)％ vs (8.2±3.5)％,t =7.325] and UMA[(14.8 ±5.4)mg/L vs (31.6 ±9.5)mg/L,t =8.221] of two groups were significantly different after treatment.Conclusion Combination therapy of enalapril and folate acid can decrease plasma Hey and UMA,restore vascular endothelium function in patients with hypertension.

Objective To study the effect of compound hypertonic saline solution (HSD) on sepsis.Methods 133 male Wistar rats were divided into four groups,sham operation group (n =15),cecal ligation and puncture (CLP)group (n =45),CLP plus normal saline (NS) group (n =45),and CLP plus HSD group (n =28).A rat model of sepsis was reproduced by CLP,and the rats in sham operation group received celiotomy without ligation and puncture.All rats in four groups received subcutaneous injection of 30 mL/kg 0.9％ sodium chloride after laparotomy.The rats in CLP plus NS group and CLP plus HSD group received infusion of 5 mL/kg 0.9％ sodium chloride or 7.5％ sodium chloride/6％ dextran post CLP via jugular vein for 3 hours,with the infusion rate of 0.4 mL·kg-1·min-1.The survival rate of each group was observed 9 hours and 18 hours after laparotomy.Mean arterial pressure (MAP) at 0,9,18 hours were monitored.Blood specimens were collected from all rats 0,9 and 18 hours after laparotomy,respectively,for measurement of the plasma levels of tumor necrosis factor-α (TNF-α),interleukin-1β (IL-1β),and procalcitonin (PCT).The rats were all sacrificed,and their lung tissues were harvested for the neutrophil count in bronchoalveolar lavage fluid (BALF),myeloperoxidase (MPO) activity in lung tissue,wet/dry weight ratio (W/D) of lung,and pathological changes in lung tissue.Results There was no death in the sham operation group.The survival rates at 9 hours and 18 hours were 62.2％ and 31.1％ in the CLP group,57.8％ and 35.6％ in the CLP plus NS group,85.7％ and 64.3％ in the CLP plus HSD group,and they were all significantly higher compared with those of the CLP group and the CLP plus NS group (P ＜ 0.05 or P ＜ 0.01).MAP levels in the CLP group and the CLP plus NS group were significantly lower than those in sham operation group,and the plasma levels of TNF-α,IL-1β and PCT were significantly higher compared with those of sham operation group,while there was no difference between CLP group and the CLP plus NS group.MAP and the plasma levels of TNF-α,IL-1β and PCT in the CLP plus HSD group were significantly improved compared with those of the CLP plus NS group at 9 hours and 18 hours [MAP (mmHg,1 mmHg =0.133 kPa) at 9 hours:102±5 vs.94±6,18 hours:90±2 vs.72±3; TNF-α (ng/L) at 9 hours:284.19±57.18 vs.329.67±45.79,18 hours:263.46±42.58 vs.349.68±52.40; IL-1β (ng/L) at 9 hours:219.28±39.21 vs.263.47±32.36,18 hours:195.98±39.06 vs.250.10±41.57; PCT (μg/L) at 9 hours:2.32±0.37 vs.4.52±0.75,18 hours:2.89±0.62 vs.5.02±0.84; P ＜ 0.05 or P ＜ 0.01].The ratio of neutrophils in BALF,MPO activity and lung W/D at 18 hours in the CLP group and the CLP plus NS group were significantly higher than those of the sham operation group,while they were all significantly lower in the CLP plus HSD group than those of the CLP group and the CLP plus NS group [ratio of neutrophils in BALF:0.094±0.019 vs.0.148±0.062,0.151 ±0.055; MPO (U/g):1.19±0.45 vs.2.31 ±0.79,2.64±0.69; lung W/D ratio:4.02 ± 0.63 vs.5.14 ± 0.59,5.12 ± 0.83,all P ＜ 0.05].Under light microscope,no pathobiological changes were found in sham operation group.The lung tissues in the CLP group and the CLP plus NS group showed congestion,edema,infiltrating inflammatory changes,while the inflammatory changes in the lung tissue in the CLP plus HSD group were significantly alleviated.Conclusion HSD can obviously ameliorate the circulatory failure in septic rats,alleviate immune disturbance and acute lung injury,and improve the survival rate of rats with sepsis.

Objective To explore the difference of methylation status of CpG island in promoter re?gion of DAT1 and DRD4 genes between children with attention deficit hyperactivity disorder ( ADHD) and normal controls,and further understand the pathogenesis of ADHD from a epigenetics point of view. Methods 111 ADHD patients and 118 normal controls were enrolled in the present study. The demographic data and peripheral venous blood were collected from both groups. Bisulfite genomic sequencing ( BGS) was used to confirm the methylation status of every CpG site in promoter region of DAT1 and DRD4 genes. Results No significant differences were found between ADHD patients and normal controls on percentage of methylated CpG sites in total CpG islands for both DAT1 and DRD4 (P>0.05) . However,the percentage of methylation in No. 17 CpG site for DAT1 and No. 8 CpG site for DRD4 was higher in ADHD patients ( 23. 42% and 64.86% respectively)compared with that in normal controls(11.86% and 47.46% respectively)(P<0.05).In all samples,the percentage of methylated CpG site in total CpG island for DAT1 was higher in males com?pared with that in females(P<0.05),whereas that for DRD4 was higher in females compared with that in males (P<0.05);the same gender difference on methylation level for DAT1 was also found in ADHD patients and for DRD4 in normal controls(P<0.05) . In all samples and in ADHD patients,percentage of methylated CpG site in total CpG island for DAT1 was higher in individuals over 7 years old compared with that in indi?viduals younger than or equal to 7 years old(P<0.05). Conclusions Methylation status of CpG island in DAT1 and DRD4 genes promoter region might correlate with ADHD susceptibility.Methylation status of CpG island in DAT1 and DRD4 genes show differences in different age span and sex.

Objective To investigate the correlation of methylation status in DA T1 and DRD4 genes and severity of clinical manifestations in ADHD patients.Methods One hundrd eleven DSM-Ⅳ defined ADHD patients were enrolled in this study and the demographic data were collected.Clinical symptoms were also assessed by Attention Deficit Hyperactivity Disorder Rating Scale-Ⅳ Home Version (ADHD-RS-Ⅳ) and self-developed Oppositional Defiant Disorder (ODD) rating scale.Bisulfite genomic sequencing (BGS) was used to detect the methylation status of every CpG site in DA T1 and DRD4 promoter CpG island in peripheral venous blood.Results The DNA methylation level in total CpG island for DA T1 was higher in individuals without depression,anxiety or ADHD family history compared to individuals with above family histories (P＜0.05).The differences on methylation levels for DA T1 and DRD4 were not significant between high and low ADHD-RS-Ⅳ total score (≤30 vs.＞30),ADHD-RS-Ⅳ inattention score (≤ 17 vs.＞17),and ADHD-RS-Ⅳ hyperactivity/impulsivity score (≤13 vs.＞13) subgroups (all P＜0.05).The methylation levels in total CpG island in DA T1 was higher in individuals whose ODD score were ＜9 compared to those whose ODD score were ≥9 (P＜0.05).Conclusions Methylation status of CpG island in DAT1 may influence the severity of oppositional defiant symptom in ADHD patients,which is correlated with depression,anxiety and ADHD family histories.

Objective To explore the factors affecting methylphenidate (MHP)efficacy in children with attention deficit hyperactivity disorder (ADHD). Methods One hunadard eleven DSM-Ⅳ defined ADHD patients were enrolled for 6 weeks systemic MHP titration treatmnet. ADHD Rating Scale-Ⅳ Home Version (ADHD-RS-Ⅳ) were applied as index of clinical efficacy, and Continuous Performance Task (CPT) as index of cognition efficacy. Determining potential influential factors was analyzed on MPH efficacy including demographic,baseline clinical symptoms and cognitive factors. Results Sixty-five (59.1%) were defined as responders and 45 (40.9%) as non-reponders to MHP, respectively. CPT which were conducted in 87 patient showed that 35 (40.2%) were defined as responders on commission errors, 31 (35.6%) on omission errors and 10 (11.5%) on reaction time. Logistic analysis revealed two potential influential factors that predicted better clinical efficacy (P<0.05): better parental relationship (OR=3.516, 95% CI: 1.087~11.375) and baseline ADHD-RS-Ⅳ score above 35 points (OR=3.075, 95%CI: 1.131~8.359). Higher IQ score was the potential influential factor that predicted better commission errors efficacy (OR=1.085, 95%CI: 1.013~1.162) and omission errors efficacy (OR=1.078, 95%CI: 1.008~1.153). Conclusion MHP efficacy may result in better outcomes in children with ADHD who have higher baseline ADHD-RS-Ⅳ score, poorer baseline CPT result, younger onset age, higher IQ and better parental relationship.

In this work, retinal penetration of fluorescein was achieved in vitro by covalent attachment of taurine to fluorescein, yielding the F-Tau conjugate. Nuclear magnetic resonance (NMR) and high resolution mass spectrometry (HRMS) were used to confirm the successful synthesis of F-Tau. The cellular uptake of F-Tau in adult retinal pigment epithelial cells (ARPE-19) and human retinal microvascular endothelial cells (hRMECs) was visualized via confocal scanning microscopy. The results indicated an improvement of solubility and a reduction of logP of F-Tau compared with fluorescein. As compared with fluorescein, F-Tau showed little toxicity, and was retained longer by cells in uptake experiments. F-Tau also displayed higher transepithelial permeabilities than fluorescein in ARPE-19 and hRMECs monolayer cells (P<0.05). These results showed that taurine may be a useful ligand for targeting small-molecule hydrophobic pharmaceuticals into the retina.