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

BACKGROUND:Conventional therapies for lumbar spondylolisthesis can result in trauma,bleeding and low back pain.With the vigorous development of spinal biomechanics and novel spinal fixation systems,we have more understanding on the reduction and fusion after spondylolisthesis.OBJECTIVE:To observe the clinical effects of transforaminal lumbar interbody fusionvia the quadrant system on lumbar spondylolisthesis and related biomechanical changes.METHODS:A retrospective analysis was done in 23 patients with lumbar spondylolisthesis undergoing transforaminal lumbar interbody fusionviathe quadrant system admitted from June 2012 to September 2013.Oswestry disability index and visual analog scale score were detected at 3 months and 1 year after treatment,as wel as fusion conditions and internal fixation with or without loosening or breakage.RESULTS AND CONCLUSION:Al patients were successfuly treated,with no cerebrospinal fluid leakage and nerve injury.Incisions were healed wel in al cases except one case suffered from incision infection that wascontroled after 10 days of antibiotic treatment.Al the patients were folowed up.The Oswestry disability indexes and visual analog scale scores were significantly improved at 3 months and 1 year after treatment (P ＜0.05),but there was no difference in these two scores at 3 months and 1 year after treatment (P＞0.05).The improvement rates of Oswestry disability index and visual analog scale score were (65.3±14.8)％and (58.2±12.0)％,respectively.These findings indicate that the transforaminal lumbar interbody fusionvia the quadrant system is safe and effective to correct lumbar spondylolisthesis,maintains the biomechanical stability,improves patient's symptoms,reduces the incidence of low back pain and improves the quality of life.

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.

[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 the value of N-terminal prohormone brain natriuretic peptide (NT-proBNP) and tissue Doppler imaging (TDI) in patients with left ventricular diastolic dysfunction.Methods Forty-three patients with diastolic heart failure were enrolled. Pulsed wave (PW) Doppler technology was used to detect early diastolic mitral velocity (E) and TDI was performed to determine the mitral annulus velocity of early diastolic phase (Em). According to the E/Em, patients were divided into three groups: group Ⅰ (E/Em ＜8),group Ⅱ (E/Em 8-15) and group Ⅲ (E/Em ＞ 15). The plasma NT-proBNP was measured. Results The plasma NT-proBNP in group Ⅲ [( 1119 ± 3123) ng/L] was higher than that in group Ⅱ [(684± 1742) ng/L] and group Ⅰ [(276±438) ng/L] (P＜0.01),and the plasma NT-proBNP in group Ⅱ was higher than that in group Ⅰ (P ＜ 0.01 ). The plasma NT-proBNP had positive correlation with E/Em (r = 0.438,P ＜ 0.01 ). Conclusion The plasma NT-proBNP and TDI are useful to evaluate the left ventricular diastolic dysfunction.

Objective: To investigate the relationship between Bilirubin blood lipid comprehensive index and ifbrinogen (FIB) to severity of coronary lesions in patients with coronary artery disease (CAD).
Methods: A total of 324 patients with angiography (CAG) conifrmed diagnosis were divided into 2 sets of groups.①By CAG examination, the patients were divided into 2 groups: CAD group,n=262 and Non-CAD group,n=62.②By Gensini scoring system, the patients were divided into 4 quartile groups: 1st quartile group,n=58, 2nd quartile group,n=110, 3rd group, n=80 and 4th quartile group,n=76. The blood levels of total bilirubin (TBIL), total cholesterol (TC), LDL-C, HDL-C, TG and ifbrinogen were measured and bilirubin blood lipid comprehensive index, TC/(HDL-C+TBIL) and LDL-C/(HDL-C+TBIL) were calculated respectively.
Results:①By CAG examination, compared with Non-CAD group, CAD group had increased TC, LDL-C, ratios of TC/(HDL-C+TBIL), LDL-C/(HDL-C+TBIL) and FIB,P<0.05; decreased TBIL and indirect bilirubin (IBIL),P<0.05.②By Gensini scoring system, the level of TBIL, IBIL, ratios of LDL-C/(HDL-C+TBIL), TC/(HDL-C+TBIL), HDL-C and FIB were different among 4 groups,P<0.05.③ Logistic regression analysis indicated that with excluded interactional factors, the bilirubin blood lipid comprehensive index was the independent risk factor for CAD[TC/(HDL-C+TBIL): OR: 1.668, 95% CI:1.065~2.784,P=0.028; LDL-C/(HDL-C+TBIL ): OR: 1.786, 95% CI: 1.021~2.879,P=0.030].④Correlation analysis presented that TC/(HDL-C+TBIL), LDL-C/(HDL-C+TBIL) and FIB were positively related to Gensini scoring system (r=0.423,P<0.01), (r=0.417,P<0.01) and (r= 0.293,P <0.01) respectively.
Conclusion: Bilirubin blood lipid comprehensive index and ifbrinogen were positively related to severity of coronary lesions in CAD patients.

Objective To observe the roles of nuclear factor-κB (NF-κB) and hypoxia-inducible factor-1 o (HIF-1 α) in hippocampal neurodegeneration of status epilepticus (SE) rats, and explore whether HIF-1α activation is regulated by NF-κB.Methods A total of 110 male Sprague-Dawley rats were randomly divided into seven groups : (1) Control group treated with saline (control, n =15), (2) sham group implanted cannula into lateral ventricle and treated with saline (sham, n =15), (3) SE group treated with pilocarpine (SE, n =20), (4) NF-κB activity inhibitor pyrrolidine dithiocarbamate (PDTC) group treated only with PDTC (PDTC, n =15), (5) SE + PDTC group treated with pilocarpine plus PDTC (SE + PDTC, n =15), (6) SE + HIF-1o siRNA group implanted cannula into lateral ventricle and treated with pilocarpine plus HIF-1 α siRNA (SE + HIF-1α siRNA, n =15), (7) SE + control siRNA group implanted cannula into lateral ventricle and treated pilocarpine plus control siRNA (n =15).SE was induced by injecting lithium chloride and pilocarpine.The seizure of rats was observed.The protein expressions of NF-κB and HIF-1 α in hippocampus of rats were examined by Western blotting.The degenerating neurons in hippocampus were detected by Fluoro-Jade C (FJC) staining.Results Twenty-four hours after termination of SE, the nuclear protein expressions of NF-κB and HIF-1α in hippocampus of rats were increased in SE group (0.57 × 0.06, 0.47 ± 0.07) compared with those in control group (0.23 ± 0.03, 0.20 ± 0.03;P ＜0.05);and compared with SE group PDTC significantly decreased the nuclear protein expressions of NF-κB and HIF-1 α in SE + PDTC group (0.23 ± 0.03, 0.14 ± 0.03;P ＜ 0.05);in SE + PDTC group the numbers of FJC positive cells in CA1 area (28.33 ±5.03) were decreased compared with that in SE group (76.67 ± 13.32);HIF-1 o siRNA injected into lateral ventricle of rats significantly decreased the expression of HIF-1α in hippocampus (0.22 ±0.03) and the number of FJC positive cell in CA1 area (27.34 ±7.02) in SE + HIF-1α siRNA group compared with those in SE group (0.39 ±0.06, 76.67 ± 13.32;P ＜0.05).Conclusions These data suggest that SE can result in activation of NF-κB/HIF-1o pathway in brain.Inhibition of the pathway can attenuate hippocampal neurodegeneration caused by SE, which has the brain protective effect.

Objective:To evaluate the bone alteration subject to remodeling and analyze the esthetic result following immediate implant placement of incisors.Methods:In this study,20 patients (1 3 women,7 men)were involved,who needed implants for incisors of maxilla.The patients received 23 im-mediate implants totally.On the day of surgery and 6 months after the implants were placed,Cone beam CT (CBCT)was taken.The thickness of the alveolar ridge and the vertical change of marginal bone levels onthe mesial and distal aspects of theimplants were measured using the computer software (Planme-caRomexis Viewer 3.6.0.R).The evaluation of esthetic result by labial convexity score (LCS)and pa-pilla index score (PIS)were analyzed pre-operation and one year after the final crown was delivered.The statistics with paired-t test for the measurement data and Willcoxon test for rating data were done by SPSS 20.0.Results:The survival rate in the two-year follow-up was 1 00%.The measuring point 1 (MP1 ), MP2,MP3 and MP4 (0,2,4,6 mm apical to the implant platform,respectively)got significant altera-tions after 6 months of the follow-up.These differences were statistically significant (P<0.05 ).The major alteration happened at MP1 and MP4,which got (-0.89 ±2.06)mm and (-0.75 ±1 .28)mm reduction of the alveolar,respectively.The marginal alveolar ridge resorption was (-0.42 ±1 .24)mm and(-0.91 ±1 .96)mm for Ankylos System and Replace System,respectively,and the difference was not statistical significant .The esthetic results were quite acceptable.Before treatment,1 8 incisors rated 3 for LCS,and 2 incisors rated 4 for LCS;after final restoration,only 5 incisors rated 3 for LCS,and 1 4 incisors rated 2 for LCS.Before treatment,1 5 incisors rated 3 for PIS;after final restoration,1 3 incisors rated 3 for PIS.There was no statistically significant difference for the PIS pre-operation and 1 year after final restoration,while there was statistically significant negative change for LCS.Conclusion:Even fol-lowing the proper surgical technique,the alveolar ridge wall still can’t be maintained after immediate im-plant placed in fresh socket of incisors.The inter-dental papilla could be well maintained,while due to the remodeling of labial bone,labial convexity will inevitably collapse.Therefore immediate implant still has esthetic risk.

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.