Polymorphism of Estrogen Receptor Genes and Its Interactions With Neurodevelopmental Genes in Attention Deficit Hyperactivity Disorder Among Chinese Han Descent

Objective@#Attention deficit hyperactivity disorder (ADHD) is a polygenic neurodevelopmental disorder with significant gender differences. The sexual dimorphism of ADHD may be associated with estrogen acting through estrogen receptors (ESR). This study investigates the impact of ESR gene polymorphism and its interactions with neurodevelopmental genes on ADHD susceptibility. @*Methods@#The study compared genotyping data of single nucleotide polymorphisms in ESR1 and ESR2 in 1,035 ADHD cases and 962 controls. The gene-gene interactions between ESR genes and three neurodevelopmental genes (brain-derived neurotrophic factor [BDNF], synaptosomal-associated protein of 25 kDa gene [SNAP25], and cadherin-13 [CDH13]) in ADHD were investigated using generalized multifactor dimensionality reduction and verified by logistic regression analysis. @*Results@#The G allele of rs960070/ESR2 (empirical p=0.0076) and the A allele of rs8017441/ESR2 (empirical p=0.0426) were found significantly higher in ADHD cases than in the controls but not in male or female subgroups. Though no difference was found in all subjects or females, the A allele of rs9340817/ESR1 (empirical p=0.0344) was found significantly higher in ADHD cases than controls in males. We also found genetic interaction models between ESR2 gene, neurodevelopmental genes and ADHD susceptibility in males (ESR2 rs960070/BDNF rs6265/BDNF rs2049046/SNAP25 rs362987/CDH13 rs6565113) and females (ESR2 rs960070/BDNF rs6265/BDNF rs2049046) separately, though it was negative in overall subjects. @*Conclusion@#The ESR gene polymorphism associates with ADHD among Chinese Han children, with interactions between ESR genes and neurodevelopmental genes potentially influencing the susceptibility of ADHD.

AMBMP activates WNT pathway and alleviates stress-induced behaviors in maternal separation and chronic stress models.

Depressive disorders are both prevalent and debilitating, and a proportion of patients have treatment resistance to classic antidepressants. Recent evidence has implicated the intracellular WNT signaling pathway as having a key role in the pathogenesis of major depressive disorder. In the present study, we investigated the role of ß-catenin and transcription factor-4 (TCF4) in the depression-like and anxiety-like behaviors exhibited by mice exposed to maternal separation, or chronic mild stress. Both rodent models of childhood and adulthood stress showed depression and anxiety-like behaviors. During the last three weeks of medication, we applied AMBMP (2-Amino-4-[3,4- (methylenedioxy)benzylamino]-6-(3-methoxyphenyl)pyrimidine) to the maternal separation and chronic stress model for the first time. The drug alleviated the depression-like index in saccharin preference test (SPT) and forced swim test (FST), and anxiety-like index in open field test (OFT) and elevated-plus maze (EPM), and reversed the disruption of ß-catenin and TCF4 in stressed mice by upregulating the WNT pathway specifically. Therefore, the WNT pathway may be involved in the mediation of patient recovery and could be a target for novel antidepressants.

Effect of different holmium laser fiber on regional temperature during lithotripsy with pediatric ureteroscope / 中华泌尿外科杂志

In order to assess the thermal effect of different holmium laser fiber during lithotripsy with WOLF F4.5/6.5 pediatric ureteroscope, we established an impacted ureter calculi model. Under 100mmHg irrigation pressure, regional temperature of different holmium laser fiber with varied working time and power were recorded. We found that the regional temperature was related with laser fiber diameters, power and working time settings. With 550 μm laser fiber, laser firing time longer than 3 s or 365 μm laser fiber firing more than 6 s, regional temperature exceeded 42℃, which would bring thermal injury towards ureter and subsequently cause ureter stricture.

Effects of sodium butyrate on activity of RAW264.7 cells and osteoclast differentiation / 中华创伤骨科杂志

Objective To investigate the effects of sodium butyrate on the activity of RAW264.7 cells and the osteoclast differentiation.Methods The RAW264.7 cells were treated by sodium butyrate at concentrations of 0,0.25,0.50,1.00,2.00,3.00,4.00 and 5.00 mmol/L,with 3 double pores for each concentration.The cytotoxicity of sodium butyrate on RAW264.7 cells was detected by a CCK-8 kit.The effects of sodium butyrate (0,0.25,0.50 and 1.00 mmol/L) on apoptosis of RAW264.7 cells were detected by Hoechst33342 staining.RAW264.7 cells were induced into osteoclasts by osteoclast differentiation factors.The experiment was carried out in 2 groups (n =3).After induced maturation,the experimental group was treated with 1.00 mmol/L sodium butyrate and the control medium was added only with the same volume of solvent.The number of osteoclasts and the area of bone resorption were observed and compared.The differentiation of RAW264.7 cells was detected by tartrate-resistant acid phosphatase (TRAP) staining.Western blotting was used to detect the effects of sodium butyrate (0,0.25,0.50 and 1.00 mmol/L) on NF-κB-related signaling pathway in RAW264.7 cells.Results Compared with the group of 0 mmol/L sodium butyrate,the activity of cells treated with 1.00,2.00,3.00,4.00 and 5.00 mmol/L sodium butyrate for 24 h was significantly decreased (P ＜ 0.05).Treatment with 1.00 mmol/L sodium butyrate for 24 h induced apoptosis.The number of osteoclasts in the control group and the experimental group were 9.33 ± 2.08 and 4.67 ± 1.16,respectively,showing a significant difference between the 2 groups (t =3.395,P =0.027).The percentages of bone resorption area in the control group and the experimental group were 52.43％ ± 5.38％ and 14.28％ ± 2.72％,respectively,also showing a significant difference between the 2 groups (t =10.970,P ＜ 0.001).Western blot results showed that,compared with other concentrations of sodium butyrate,treatment with 1 mmol/L sodium butyrate on RAW264.7 cells for 24 h led to an increase in the expression levels of cytoplasmic p65,B lymphoma-2 associated X protein and cleaved-caspase 3 and the acetylation of Histone H3 but a decrease in the phosphorylation level of α/β subunit of NF-κB kinase.Conclusions With the increased concentration of sodium butyratecan,the activity of NF-κB may be suppressed and the number of apoptotic cells may increase.1.00 mmol/L sodium butyrate can reduce osteoclast formation and bone resorption area.