Objective To investigate the association SLC25A12 and SCN2A2 gene single nucleotide polymorphisms(SNPs) and susceptibility to autism among 105 Japanese family trios consisting of fathers,mothers,and affected offsprings with autism.Methods Genomic DNA was isolated from the whole blood samples.The PCR-single stranded conformational polymorphism(SSCP) technique was used to test genotype of SNPs(rs3770448,rs3769955) at SLC25A12 and SCN2A2 genes.Results The distributions of genotypic and allelic frequencies of rs3770448 and rs3769955 were not deviated from the Hardy-Weinberg equilibrium.The results of transmission disequilibrium test(TDT) indicated that the allelic frequency transmitted from the heterozygote parents didn′t deviate 50%.Conclusion The polymorphism of rs3770448 in the SLC25A12 and rs3769955 in the SCN2A2 locus may not be associated with autism.But the association of the other SNPs at the SLC25A12 and SCN2A2 locus with the illness can not be ruled out.

Autophagy occurs in all types of eukaryotic cells, which has a rigid connection with the normal or abnormal development of cells and is associated with many diseases. There're lots of molecular control elements and multiple signaling pathways involved in regulating autophagy. As a form of type Ⅱ programmed cell death, autophagy participates in maintaining cell homeostasis and pathogenesis of various of diseases through interacting with apoptotic pathway. Recent studies show that autophagy has effects on the occurrence and development of tumor cells through influencing on cell cycle, apoptosis-associated factors and angiogenesis.

.This study is to investigate the analgesic effect produced by intrathecal injection (ith) of oxysophoridine (OSR) and the mechanism of GABAA receptor. Warm water tail-flick test was used to detect the analgesic effect of OSR (12.5, 6.25, and 3.13 mg.kg-1 ith) and to observe the influence of GABA (gamma aminobutyric acid) agonist or antagonist on the analgesic effect of OSR in mice. Immunohistochemistry method were used to detect the influence of OSR (12.5 mg.kg-1, ith) on the GABAARalpha1 protein expression in spinal cord. The results obtained covers that OSR (12.5 and 6.25 mg.kg-, ith) alleviates pain significantly with the warm water tail-flick test (P<0.05, P<0.01), the rate of pain threshold increases by 68.45%; GABA and muscimol (MUS) produces analgesic synergism together with the OSR, picrotoxin (PTX) and bicuculline (BIC) antagonize the analgesic effect of OSR; OSR (12.5 mg.kg-1, ith) significantly increase the positive number of GABAARalpha1 nerve cell in spinal cord (P<0.01) and significantly decrease the average grey levels (P<0.01). In conclusion, OSR intrathecal injection has significant analgesic effect. And GABAA receptor in spinal cord is involved in the analgesic mechanism.

Combined with method of ketoconazole resistance screening, a 7alpha,15alpha-diOH-DHEA high-producing mutant Colletotrichum lini ST-1 was obtained by compound mutation of NTG and low energy N+ ion beam implantation. With the substrate concentration of 10 g/L DHEA, the molar yield of 7alpha,15alpha-diOH-DHEA reached 34.2%, increased by 46.2% than that of the original strain. Then we optimized the medium. First, Plackett-Burman design was used to evaluate the effects of medium components on molar yield of the product. Results show that glucose, yeast extract and MgSO4 x 7H2O were the important parameters for the biotransformation process. Subsequently, the path of steepest ascent was used to approach the optimal levels. To obtain the optimal levels, central composite design and response surface analysis were carried out. The optimal medium was as follows (g/L): glucose 26.34, yeast extract 12.15, corn flour 3.00, FeSO4 x 7H2O 0.015, MgSO4 x 7H2O 0.14, KH2PO4 0.90. Under the optimal conditions, the molar yield of 7alpha,15alpha-diOH-DHEA reached 49.3%, which was 44.2% higher than that of using the medium before optimization.
Biotransformation ; Colletotrichum ; metabolism ; Dehydroepiandrosterone ; chemistry ; Fermentation ; Hydroxylation ; Industrial Microbiology ; Mutation

Pulsatile drug delivery system,capable of releasing drug at the predetermined times according to clinical therapeutic requirements,can be used to treat several rhythmic diseases.Majority of individuals experience the rise in the blood pressure in the early morning hours,which potentially leads to serious cardiovascular complications.The purpose of the study was to develop pulsatile candesartan cilexetil core-in-cup tablets according to human circadian rhythm of blood pressure.The factors influencing t_(lag) were evaluated by in vitro drug release and tablet erosion observations.In addition,the jugular artery pressures vs times courses of rabbits were recorded after oral administration of commercial candesartan cilexetil tablets or the developed core-in-cup tablets.The quantity and characteristics of the excipients in top layers in the tablets were found to modify t_(lag).In vivo studies showed that the onset times indicating the decreases in the blood pressures of commercial tablets and core-in-cup tablets were (98 ± 17) min and (278 ±29) min,respevtively.In vivo t_(lag) of the prepared core-in-cup tablets was (180 ± 34) min in rabbits,which is consistent with the goal of design.

Objective To discuss the effect of QGY/CDDP hepatoma lines multi-drug resistance (MDR) reversed by gene transfection of mdr1,mrp-ASODN+ultrasound contrast agent+ultrasound.Methods The QGY/CDDP cells were transfected by mdr1,mrp ASODN+ultrasound contrast agent+ultrasound irradiation respectively and detected of the various indicators:cell adhesion rate,cell sensitivity to cell drug-resistance,the mRNA expression of mdr1 and mrp gene,the expression of P-gp and MRP protein. Results After mdr1-ASODN transfection,the drug sensitivity and expression of P-gp,MRP protein of QGY/CDDP cells were smaller changes(P＞0.05),and the rate of cells adherent and expression of resistance gene mRNA were obvious changes(P＜0.05).After mrp-ASODN transfection,the cells adherent rate,the drug sensitivity,the expression of resistance gene mRNA and P-gp,MRP protein were obvious changes respectively(P＜0.05),the experiment group(group 2')had bigger effects(P＜0.05).Conclusions mdr1. mrp-ASODN+ultrasound contrast agent+ultrasound irradiation could safely partly reverse MDR of hepatoma cells,which is a potential new approach for gene therapy.

Objective To study the early protective effect of NADPH on human umbilical vein endothelial cells (HUVECs) and the expression of occludin and MMP9 induced by oxygen glucose deprivation and reoxygenation (OGD/R). Methods HUVECs were cultured and divided into blank control group, OGD/R group and OGD/R+NADPH 20 μmol/L group. The proliferation of HUVECs after treatment was detected by CCK-8 assay. The cytotoxicity was detected by LDH release assay. The morphological changes of HUVECs were observed by inverted microscope. Superoxide dismutase (SOD MDA) activity and malondialdehyde (MDA) were detected by commercially available kit. The expressions of occludin and MMP9 were detected by Western blot assay. Results Compared with the OGD/R, NADPH enhanced the cell viability significantly (P<0.05), reduced the release of LDH (P<0.05), promoted the maintance of HUVECs morphology, reduced MDA generation (P<0.05) and increased SOD activity (P<0.05). Following OGD/R,the treatment of NADPH can inhibit MMP9 level (P<0.05) and promote the recovery of occludin level (P<0.05). Conclusion NADPH can protect HUVECs from the damage induced by OGD/R by reducing oxidative stress and regulating the expressions of MMP9 and occludin.

Objective To investigate the efficacy and safety of citrate anticoagulation for continuous renal placement therapy (CRRT) in patients at high risk of bleeding. Methods Forty-seven patients who needed to CRRT and were admitted into the department of critical care medicine from January 2015 to October 2016 were enrolled in this study. According to the patient′s actual condition, they were divided into citrate groups (24 cases) and saline group (23 cases). Patients in saline group were given saline wash. The efficacy and safety were compared between the two groups. The filter lifetime, after treatment the activated partial thromboplastin time (APTT), hemoglobin (Hb), blood gas indexes were compared between the two groups. Results The citrate group used 76 filters while the 0.9% sodium chloride group used 87 filters. The average filter lifetime in citrate group was (22.4 ± 12.7) h which was longer than (8.6±3.3) h in 0.9%sodium chloride group (t=9.79, P<0.01). The incidence of coagulation in extracorporeal circulation was 3.9%(3/76) which was lower than 16.1%(14/87) in 0.9%sodium chloride group(χ2=5.20, P<0.05). Conclusions Regional citrate anticoagulation is a safe and effective option for CRRT in patients at high risk of bleeding.

This paper retrospectively analyzed nursing care of 20 critically ill patients with human infections of avian influenza A(H7N9) virus treated by oxygen therapy.According to the severity of hypoxia in patients admitted to the hospital,individualized oxygen therapy strategy was selected,such as humidified high flow nasal cannula or mechanical ventilation.Oxygen therapy strategy was adjusted in a timely manner according to patients' condition,such as prone position ventilation and extracorporeal membrane oxygenation.As a resuh,15 cases were transferred to the general ward when the virus associated test was negative,and 5 cases died.

Objective To sutdy the anti-inflammatory action and pharmacodynamics of Liushen Cataplasm (LC). Methods The anti-inflammatory action of LC was observed on mice models of xylene-induced ear swelling and on the rat models of carrageenan-induced pedal swelling. With the decrease of pedal swelling as the parameter,the pharmacodynamics of LC was studied. The apparent parameters of pharmacodynamics were estimated based on the time-effect curve. Results LC showed a potent anti-inflammatory effect. The effect-time curve can be described by the one-compartment model. The main pharmacodynamic parameters were as follows:t1/2(Ka)=2.11727h,t1/2(Ke)=3.13464h,AUC=3.33131 mg?kg?h-1,respectively. Conclusion Liushen Cataplasm shows a potent anti-inflammatory effect. The effect-time curve can be described by the one-compartment model.