Objective To explore the inhibition effect of Cysteine-rich 61 (CCN1; Cyr61) specific siRNA expression vector on RNV in a mouse model of oxygen-induced retinopathy (OIR).Methods One hundred and twenty healthy C57BL/6J mice were chosen and randomly divided into the experimental group and control group,with 60 mice in each group.The experimental group was intravitreously injected with CCN1siRNA recombinant plasmids.The control group was injected with vector plasmids.Adenosine diphosphate-ase stained retina flat-mounts was performed to assess the retinal vascular profiles,retinal section with HE staining was applied to count the number of new vascular cell nuclei and the protein and mRNA expression of CCN1 and vascular endothelial growth factor (VEGF) were detected by immunohistochemistry,Western blot and Real-time RT-PCR.Results Compared with control group,regular distributions,good branches and reduced density of retinal neovascularization were observed in the experimental group.The number of nucleus of vascular endothelial cells breaking through the inner limiting membrane was obviously less in the experimental group than that in the control group (t=8.756,P＜ 0.05).The expression of CCN1 and VEGF were obviously decreased in the experimental group compared with the control group (all P＜0.05).Conclusion The development of RNV of ROP can be markedly inhibited by RNA interference targeting CCN1,and CCNlsiRNA may provide an effective method for preventing vascular proliferative retinopathy.

Nicotinic acid could increase high density lipoprotein and reduce serum total cholesterol, low density lipoprotein cholesterol and triglycerides in human bodies, thus is frequently applied in treating low high-density lipoprotein cholesterol and hypertriglyceridemia in clinic. However, according to the findings, nicotinic acid could also cause adverse effects, such as skin flush, beside its curative effects. In this study, bioisosterism, fragment-based search and Lipinski's Rule of Five were used to preliminarily screen out potential TCM ingredients that may have similar pharmacological effects with nicotinic acid from Traditional Chinese medicine database (TCMD). Afterwards, homology modeling and flexible docking were used to further screen out potential nicotinic acid receptor agonists. As a result, eleven candidate compounds were derived from eight commonly used traditional Chinese medicines. Specifically, all of the candidate compounds' interaction with nicotinic acid receptor was similar to nicotinic acid, and their docking scores were all higher than that of nicotinic acid, but their druggability remained to be further studied. Some of the eight source traditional Chinese medicines were used to lower lipid according to literature studies, implying that they may show effect through above means. In summary, this study provides basis and reference for extracting new nicotinic acid receptor agonists from traditional Chinese medicines and improving the medication status of hyperlipidemia.
Drug Evaluation, Preclinical ; Drugs, Chinese Herbal ; chemistry ; Humans ; Models, Molecular ; Molecular Structure ; Nicotinic Acids ; chemistry ; Nicotinic Agonists ; chemistry ; Protein Binding ; Receptors, G-Protein-Coupled ; agonists ; chemistry ; Receptors, Nicotinic ; chemistry

[Abstract ] Objective High-mobility group box-1 (HMGB1) is abundantly released in the epileptogenic brain tissue , but few reports are seen about the effect of HMGB 1 on the expression of P-glycoprotein ( P-gp) in the vascular endothelial cells of the epi-leptogenic tissue .This study is to explore whether HMGB 1 can regulate P-gp expression in the brain microvascular endothelial cells of the mouse in vitro . Methods Immortalized brain microvascular endothelial bEnd .3 cells of the mouse were cultured in vitro and al-located to different concentration groups ( treated with culture medium containing 10 , 100 , 500 , and 1000 ng/mL HMGB1 for 8 hours), treatment duration groups (treated with culture medium containing 100 ng/mL HMGB1 for 4, 8, 16, 24, and 32 hours), and a control group ( treated with culture medium without HMGB 1 ) .The mRNA expression of P-gp-encoding gene-multidrug resistance gene 1a (mdr1a) was detected by real-time qPCR, and its protein expression determined by Western blot and immunocytochemistry . Results The results of qPCR manifested that the expressions of mdr 1a mRNA were 1.646 ±0.176, 1.777 ±0.135, 1.617 ±0.043, and 1.398 ±0.182 in the 10, 100, 500, and 1000 ng/mL HMGB1 groups, respectively, significantly higher than 1.030 ±0.284 in the control group (P<0.05), and so were those in the 4, 8, 16, 24 h, and 32 h groups (2.655 ±0.112, 2.168 ±0.212, 1.823 ± 0.232, 1.418 ±0.376, and 1.445 ±0.123) than in the control (1.010 ±0.164) (P <0.05).Western blot showed a significant increase in the P-gp protein expression in all the concentration groups (P<0.05) as well as in the 8 h and 16 h treatment duration groups as compared with the control group (P<0.05).Immunocytochemis-try also revealed a higher P-gp expression in the HMGB1-treated than in the control cells (P<0.01). Conclusion HMGB1 can upregu-late the expressions of mdr1a mRNA and P-gp protein in the brain microvascular endothelial cells of the mouse , which may associated with drug resistance of central nervous system diseases , especially that of epilepsy .

Objective To evaluate if high energy spectral CT images of contrast-enhanced phase could replace the plain scan for radiation dose reduction in children with solid tumor in abdomen.Methods Thirty children with solid tumor in the abdomen underwent CT scan.Plain CT scan was performed as usual,and the contrast-enhanced scan was performed with spectral CT imaging mode.Eleven sets of monochromatic images were reconstructed from the enhanced spectral CT with energies from 40 to 140 keV with 10 keVinterval.CT values for liver,spleen,kidney,pancreas,muscle,vessel and tumors were measured on both the plain and contrast-enhanced spectral images and were statistically compared.Two board-certified radiologists reviewed both plain and contrast-enhanced spectral images for image quality,calcification and tumor characterization.Radiation dose was recorded(CTDIvol,DLP).Pair t test was used to analyze the difference.Results At 140 keV,CT values of the contrast-enhanced spectral images had good correlations with those of plain scan for various organs.The paired CT values between the 140 keV and plain phaseimages were (62.8± 1.1 vs.59.8±4.0),(69.4±2.6vs.63.1 ±5.6),(52.7 ±5.1 vs.51.4±4.0),(35.4± 5.9 vs.35.7 ±5.3),(51.4±8.6vs.50.0±5.7),(55.5±6.6vs.54.7±5.7) and (33.2± 10.4vs.35.4± 12.1) HU for vessel,liver,spleen,kidney,pancreas,muscleand tumor,respectively.There was no significant difference between two groups(t=0.335 to 2.127,P＞0.05).140 keV images of the contrast-enhanced spectral scan in pediatric tumor patients provided adequate image quality (4.4±0.8 points and 3.7±0.5 points)for describing solid tumor features and calcification.The radiation dose of plain phase and contrast-enhanced phase were [CTDIvol (1.6±0.8) mGy,DLP(46.4±36.8)mGy·cm and CTDIvol(12.7±0.1)mGy,DLP(378.6±91.4)mGy·cm.Conclusion It isfeasible to replace plain CT with 140 keV contrast-enhanced spectral images to reduce 10％ radiation dose.

0.05).The expression of EG-VEGF in the gastric cancer tissue was 41.6?13.3,which significantly higher than that in tissue near gastric cancer and normal gastric tissue(P

AIM: To study the antioxidative effect of three kinds of xanthone:methylswertianin(MET), bellidifodin(BEL) and decussatin (DEC) extracted from Swertia macrosperma C.B. clark. METHODS: Hydroxy radical was generated from H_2O_2 and VC-Fe~ 2+ system; MDA contents in liver homogenate and mitochondria were measured by thiobabituric acid assay; the hemolysis of RBC and the swelling extent of mitochondria were detected by spectrophotometric methods. RESULTS: Xanthones could inhibit the generation of MDA, the hemolysis of RBC, and the swelling of mitochondria. The inhibitory effect of BEL was stronger than that of MET and DEC. CONCLUSION: Xanthones possess a good antioxidant activity.

Objective To investigate the prevalence of adult epileptic patients with interictal depression symptoms(IDs) and identify early predictors of IDs. Methods Adult patients with epilepsy were recruited ( n =110,45 females and 65 males) ,age between 16 and 67 years ( median 24 years). The sociodemographic and clinical factors of patients were recorded. Hamilton Depression Scale ( HAMD ) were applied to evaluate interictal symptoms of depression ( at least 72 hours after the last epileptic seizure). According to HAMD score,the epileptic patients were divided into IDs ( ≥8 ) and non-IDs(＜8) groups. The sociodemographic and clinical factors were compared between the two groups to identify the prevalence and early predictors of IDs in adult epileptic patients.Results The prevalence of IDs in adult patients with epilepsy was 38.2% ,49.0% in active epilepsy and 12.1 %in seizure freedom. 30.0% ,5.5% ,and 2.7% were experiencing mild-to-moderate (HAMD score≥8),moderateto-severe ( ≥ 18 ) and severe ( ≥25 ) depression. 42 patients who met the HAMD score≥8 were classified as IDs group,and the remaining 68 patients were classified as non-IDs group. With multiple stepwise backward logistic regreasion, independent predictors of IDs were epileptic seizures ( OR = 8. 845, P = 0. 003 ); symptomatic or cryprogenic epilepsy ( OR = 3.132, P = 0. 045 ); prolonged duration of illness ( OR = 1. 106, P = 0.004 ) and employment status (OR =0. 154, P=0.001 ). There were no relationship between seizure frequency and severity of IDs ( Kruskal-Wallis test, x2 = 4.5, P = 0. 104). Conclusion IDs is a frequent psychiatric comorbidity in adult patients with epilepsy. The prevalence of IDs is higher in those with active epilepsy compared with those in seizure freedom and most of them are mild-to-moderate. Epileptic seizure, symptomatic or cryprogenic epilepsy, prolonged duration of illness and employment status are independent predictors of IDs, but seizure frequency has nothing to do with the IDs severity of patients.

AlM: To explore the expression and significance of cysteine- rich 61 ( CCN1/Cyr61 ) in oxygen - induced retinal neovascularization ( RNV) of mice and study the inhibition effect of CCN1 specific siRNA on RNV.
METHODS:Two hundred healthy C57BL/6J mice were chosen and randomly divided into control group, hyperxia group, hyperxia control group and CCN1 treated group, with 50 mice in each group. The hyperxia control group was treated with vector plasmids by intravitreal injection. The CCN1 treated group received CCN1 siRNA recombinant plasmids by intravitreal injection. Adenosine diphosphate-ase ( ADPase) stained retina flat-mounts was performed to assess the retinal vascular profiles, HE staining was applied to count the number of vascular endothelial cell nuclei breaking through the internal limiting membrane, protein and mRNA level expression of CCN1 were measured by immunohistochemistry, Western blot and RT-PCR.
RESULTS: There were large nonperfusion area and a large number of vascular endothelial cell nuclei breaking through the internal limiting membrane ( 25. 25 ± 1. 26;23. 12 ± 1. 16 ) in the hyperxia group and the hyperxia control group. Regions of nonperfusion and vascular endothelial cell nuclei (8. 47±1. 15) were decreased in the CCN1 treated group compared to the hyperxia group and the hyperxia control group. Compared with the control group, there were high protein and mRNA expression of CCN1 in the hyperxia group and the hyperxia control group. The expression of CCN1 protein and mRNA were decreased in the CCN1 treated group compared with the hyperxia group and hyperxia control group (all P<0. 05).
CONCLUSlON: The abnormal expression of CCN1 has close relation with RNV. The development of RNV can be markedly inhibited by RNA interference targeting CCN1, which, we believe, will provide new molecular targets and a rationale for clinical developing new strategy for ROP therapy.

OBJECTIVE:To study the in vitro antioxidant activity of chitosan(CTS)degradation derivatives and its preventive effects on drug-induced liver injury fibosis. METHODS:Acid hydrolysis method was used to prepare the CTS degradation deriva-tives CTS-3,CTS-6,CTS-8,CTS-10 for different hydrolysis time(3,6,8,10 h). The viscosity-average relative molecular mass and deacetylation degree of CTS and its degradation derivatives were determined,and its antioxidant activity was evaluated by de-tecting its in vitro scavenging ability on 1,1-diphenyl-2-trinitrophenylhydrazine (DPPH) and superoxide anion (O2-) radicals. Us-ing CTS-10 for in vivo liver injury fibosis prevention test,mice were randomly divided into normal control group(water),model group(water),CTS-10 high-dose,medium-dose,low-dose groups(100,50,25 mg/mL),8 in each group. Mice were intragastri-cally administrated 0.2 mL,then withdrawal after continuous 24 d. Then levofloxacin hydrochloride was intragastrically given for 7 d to establish drug-induced liver injury model(except for normal control group). Western blot method was used to detect the expres-sions of tumor necrosis factor α(TNF-α),transforming growth factor β1(TGF-β1)and Decorin protein in liver tissue of mice. RE-SULTS:The viscosity-average relative molecular mass of CTS,CTS-3,CTS-6,CTS-8,CTS-10 were 21.70×104,6.70×104,6.30× 104,5.01×104,4.87×104;and deacetylation degree were 83.44％,74.62％,67.28％,64.83％,54.23％,respectively. All of them had certain scavenging ability on DPPH and O2-,in which,CTS-10 was the strongest(25.47％ and 56.31％). Compared with nor-mal control group,expressions of TNF-α,TGF-β1 and Decorin protein in liver tissue in model group were enhanced (P<0.05). Compared with model group,expressions of TNF-α,TGF-β1 and Decorin protein in liver tissue in CTS-10 medium-dose and high-dose groups were weakened(P<0.01). CONCLUSIONS:The viscosity-average relative molecular mass and deacetylation de-gree of CTS-10 in CTS degradation derivatives are lower with stronger antioxidant activity,and show certain preventive effects on drug-induced liver injury fibosis in mice.

Objective To establish a high performance liquid chromatography (HPLC) method for the determination of baicalin and naringin inQinbei mixture.Methods The HPLC system consisted of the Fortis-C18(4.6 mm × 250 mm, 5μm) column, and the mobile phase consisted of MeOH:0.4% H3PO4 (42:58), and the flow rate was 1.0 ml/min, and the UV detector was set at 280 nm, and the column temperature was 30℃.Results The linear response range of baicalin was 0.062-0.930μg. The linear response range of naringin was 0.033-0.492μg. The average recovery of baicalin was 98.11% (RSD=1.62%). The average recovery of naringin was 96.78% (RSD=1.74%).Conclusions The method is simple, rapid, accurate and repeatable. It can be applied in determination of baicalin and naringin inQinbei mixture.