It has been suggested that melatonin is involved in learning and memory. In the present study, we investigated the effects of melatonin on spatial learning and memory in rats, using Morris water maze and electrophysiological methods. The results are as follows. (1) During a six-day water maze training, the mean escape latency of melatonin group in the last 4 days was 30.02+/-3.6 s, and that of control group was 18.44+/-2.7 s (P<0.01). The crossing annulus coefficient of melatonin group was 25.68+/-2.32%, and that of control group was 43.33+/-2.85% (P<0.01). (2) Microinjection of melatonin into CA1 area inhibited long-term potentiation (LTP). Sixty minutes after tetanus, the field excitory postsynaptic potentials (fEPSP) slope of group C (n=7 0.5 microliter saline) was 169.71+/-6.48 % of the baseline, and that of group M2 (n=6, 2 microgram melatonin) was 114.28+/-1.80% of the baseline. The difference is significant (P<0.01). (3) We also investigated the effects of melatonin on LTP after administration of scopolamine. Sixty minutes after tetanus, the fEPSP slope of group SM (n=6, 2 microgram scopolamine before 2 microgram melatonin) was 113.70+/-5.55% of the baseline. It showed a significant decrease compared with group C (P<0.01). However, there was no difference between groups SM and M2 (P>0.05, i.v.). The results obtained by applying melatonin after bicuculline were different from those after scopolamine. Sixty minutes after tetanus, the fEPSP slope of group BM (n=7, 1 microgram bicuculline before 2 microgram melatonin) was 162.29+/>10.52% of the baseline. Compared with group C, there is no significant difference (P>0.05); but compared with group M2, the difference is significant (P<0.01). Our results showed that application of melatonin in rats significantly inhibited not only spatial learning and memory, but also LTP in CA1 area. Furthermore, the results indicate that the inhibition of LTP by melatonin may not be mediated by cholinergic system, but may be through the modulation of GABAergic system.
Animals ; Bicuculline ; pharmacology ; Female ; Hippocampus ; drug effects ; physiology ; Learning ; drug effects ; Long-Term Potentiation ; drug effects ; Male ; Melatonin ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Scopolamine Hydrobromide ; pharmacology ; Space Perception ; drug effects

The drug-loading system of DMF (dextran - magnetic layered double hydroxide - fluorouracil) was synthesized by "co-precipitation intercalated assembly - dextran composite in situ - solvent conversion" technology. The crystal-phase characteristic and slow-release performance of DMF were investigated through X-ray diffraction (XRD), infrared spectrum (IR), transmission electron microscopy (TEM), thermogravimetry (TG) and in vitro release experiment. The targeted transshipment and slow-release effect of DMF system were evaluated by in vivo animal experiment. It was showed that the XRD of DMF matched with R-sixtetragonum type layered double hydroxide and Fd-3m cubic type ferrite. IR test demonstrated that the DMF system was a supra-molecular complex consisted of Dextran (DET), magnetic layered double hydroxide (MLDH) and fluorouracil (FU) components. The two-level supra-molecular MLDH-FU presented six-edge lozenge TEM morphology, with layered characteristics. DET on the surface of DMF was capable of protecting the layered structure of MLDH-FU, improving particle dispersion properties, and strengthening the slow-release performance of the drug delivery system. The drug release model of DMF at pH 7.35 of PBS in vitro fit to the zero-order kinetics equation C = 1.1716 x 10(-5) + 4.4626 x 10(-7) t. The drug delivery system DMF could transport drugs principally to in vivo target organs with a local effect, targeted specificity, and excellent circulation transshipment performance. The pharmacokinetic process of DMF presented multi-peak phenomenon with peak attenuation and cyclic growth. The peaks appeared at 0.25, 1, 3, 5 and 9 d separately after dosing intervention. The first peak process of DMF accorded with a pharmacokinetic equation of C(FU) = 14.34 e(-0.530t) + 36.04 e(-0.321t) + 24.18 e(-0.96t), and presented the characteristic of slow absorption and fast elimination. As for subsequent peak processes, half-life increased, bioavailability increased, and plasma clearance decreased. The highest peak value of DMF was 1/37 of original value of FU, and the relative bioavailability was 419% to original FU.

Objective To explore the mechanisln of action of Jianpiyishen Decotion on renal fibrosis and provide experimental evidence for chnieal application.Methods The Wistar male rats were randomly divided into four groups.They were normal control group(N group),model group(M group),low dose treatment group(L group)and high dose treatment group(H group).AⅡanimal models were made of CRF with subtotal renal ablation except the N group.Interference began at one week after operation.After being interfered for 8 weeks,blood serunl and nephridial tissues were taken out.Serum urea nitrogen(BUN)and creatinine(Scr)and fibronectin(FN)were detected.Results In N group。There were light expression in renal tubniointerstitial substance,cellula epithelialis basal meulbnule and Vascular smooth muscle.In M group,FN was strong expressed in renal tubulointerstitial substance and renal tubde,and also in glomerular mesangium.There was significant difference between N and M group(P

Objective :To study therapeutic effect of compound Danshen dripping pills (CSDP) combined nicorandil on patients with coronary heart disease (CHD) and angina pectoris after percutaneous coronary intervention (PAP). Methods :A total of 176 PAP patients treated in our hospital from Jan 2014 to Dec 2017 were randomly and equally divided into nicorandil group and combined treatment group (received nicorandil + CSDP) ,each group received routine treatment simultaneously for eight weeks .Each dimension score and total score of Seattle angina question‐naire (SAQ) ,serum levels of hsCRP ,interleukin (IL)‐6 ,tumor necrosis factor (TNF)‐α ,heart type fatty acid binding protein (H‐FABP) ,creatine kinase isoenzyme MB (CK‐MB) ,cardiac troponin I (cTnI) ,endothelin (ET)‐1 ,nitric oxide (NO) and NO synthase (NOS) were observed and compared between two groups before and after treatment .Results :Compared with nicorandil group after treatment ,there were significant rise in each dimension score and total score [ (79. 90 ± 8.17) scores vs .(95.13 ± 9. 74) scores] of SAQ , serum levels of NO [ (62.54 ± 6.30) pg／ml vs.(82.41 ± 8.24) pg／ml] , NOS [ (24.13 ± 2.58) U／ml vs .(30.19 ± 3.11) U／ml] , significant re‐ductions in serum levels of hsCRP [ (5.96 ± 0.62) mg／L vs.(3.68 ± 0.37) mg／L] ,IL‐6 [ (25.89 ± 2.61) ng／L vs. (20.89 ± 2.18) ng／L] ,TNF‐α [ (10. 01 ± 1. 13) pg／ml vs .(6. 97 ± 0.73) pg／ml] ,H‐FABP [ (1.01 ± 0.10) ng／ml vs.(0.89 ± 0. 09) ng／ml] ,CK‐MB [ (14. 08 ± 1.42) U／L vs.(11.54 ± 1. 17) U／L] ,cTnI [ (0.26 ± 0.03) ng／ml vs.(0.22 ± 0.02) ng／ml] ,ET‐1 [ (70.76 ± 7.19) pg／ml vs.(52.96 ± 5.33) pg／ml] in combined treatment group , P＝0. 001 all.Conclusion :Compound Danshen dripping pills combined nicorandil can significantly reduce inflamma‐tory factor levels ,protect myocardial cells ,reduce myocardial injury and relieve angina pectoris symptoms in PAP patients .

OBJECTIVE: To establish a feasible evaluation index and method to identify composition of remaining metal particles on ferrochrome kitchen knife. METHODS: The small samples of remaining metal particles were rubbed from the knives using filter paper. The composition of remaining metal particles was detected by scanning electron microscopy and energy dispersive X-ray spectrometer (SEM-EDX) and GSR particle analysis function, using mathematical methods to calculate the ratio (relative amount) of Fe and Cr in remaining metal particles. RESULTS: The ratio (relative amount) of Fe and Cr of remaining metal particles had significant differences among most ferrochrome kitchen knives (P < 0.05). CONCLUSION Using GSR particle analysis function to quantitatively detect the ratio (relative amount) of Fe and Cr of remaining metal particles on ferrochrome kitchen knife, which can establish the feasible evaluation method to estimate such injury tool.
China ; Chromium/isolation & purification* ; Forensic Medicine/methods* ; Iron/isolation & purification* ; Metals/chemistry* ; Microscopy, Electron, Scanning/methods* ; Spectrometry, X-Ray Emission/methods* ; Wounds, Nonpenetrating/pathology*

OBJECTIVETo investigate the inhibiting effect of salianic-acid B (SA-B) on mitogen-activated protein kinase (MAPK) Signaling in activated rat hepatic stellate cells (HSCs).

METHODSHSCs were isolated from normal rat by in situ perfusion and Nycodenz density-gradient centrifugation method. HSCs were primarily cultured on uncoated plastic for 7 days. Then cells were stimulated with 10ng/ml transforming growth factor-beta1 (TGF-beta1) after incubated with 10-6 M/L SA-B. The effects of SA-B on Extracellular-regulated kinase (ERK) expression and its phosphorylation. Transforming growth factor beta1 receptor I (TbetaR I) and transforming growth factor beta1 receptor II (TbetaR II) on HSCs, type I collagen expression in HSC Induced by TGF-beta1 were detected with western blot assay. Quantity of Type I collagen in the medium of HSCs was detected by ELISA. Matrix metalloproteinase 2, 9, 13 (MMP-2, MMP-9 and MMP-13) in the medium of HSCs was tested by Zymography.

RESULTSThe phosphorylation of ERK1/2 in HSCs with or without TGF-beta1 was inhibited by SA-B. The expression of TbetaR I and TbetaR II on HSCs can not be affected by SA-B. The synthesization of Type I collagen in HSCs was decreased by SA-B; The synthesization and secretion of type I collagen in HSCs with TGF-beta1 were reduced by SA-B too. SA-B had no effect on the activity of MMP-2 and MMP-13, but induced the activity of MMP-13.

CONCLUSIONSA-B inhibits ERK signaling induced by TGF-b1 in HSC. This inhibition has no association with the expression of TbetaR I and TbetaR II on HSCs. SA-B reduces the synthesization and secretion of Type I collagen in HSC by means of inhibiting TGF-beta1 signaling, which might be not related to the degrading activities of MMPs.

Animals ; Benzofurans ; pharmacology ; Cells, Cultured ; Extracellular Signal-Regulated MAP Kinases ; metabolism ; Liver ; cytology ; drug effects ; enzymology ; Male ; Mitogen-Activated Protein Kinase Kinases ; metabolism ; Rats ; Rats, Sprague-Dawley ; Signal Transduction ; drug effects ; Transforming Growth Factor beta ; pharmacology

OBJECTIVETo explore the anti-hepatic fibrosis mechanisms of salvianolic acid B (SA-B).

METHODSHepatic stellate cells (HSCs) isolated from rats were primarily cultured in uncoated plastic culture dish for 7 days, then were incubated with 10(-6) mmol/L SA-B and stimulated with 10 ng/ml transforming growth factor-beta1 (TGF-beta1) or platelet-derived growth factor-BB (PDGF-BB). Expressions of extracellular-regulated kinase (ERK) and its phosphorylation in HSC, and expressions of TGF beta1, receptor I (TbetaR I) and II (TbetaR II) and PDGF receptor beta (PDGFR-beta) on the surface of HSC induced by TGF-beta1 or PDGF-BB were detected with Western blot assay.

RESULTSSA-B inhibited the phosphorylation of ERK1/2 in HSC primary normally cultivated for 9 days stimulated or un-stimulated by TGF-beta1, but could not affect the expressions of TbetaR I and TbetaR II on the HSC surface; it down-regulated the expression of PDGFR-beta, but had no obvious effect on the phosphorylation of ERK1/2 in those HSC stimulated or un-stimulated by PDGF-BB.

CONCLUSIONSA-B inhibits the ERK signal transduction induced by TGF-beta1 in HSC, which is independent of the expressions of TbetaR on HSC surface and also free from the ERK signal transduction stimulated by PDGF-BB. And its inhibition on PDGF-BB signal transduction in HSC is by way of restraining the expression of PDGFR in HSC.

Animals ; Benzofurans ; pharmacology ; Cells, Cultured ; Hepatocytes ; cytology ; metabolism ; Male ; Mitogen-Activated Protein Kinase 1 ; metabolism ; Mitogen-Activated Protein Kinase 3 ; metabolism ; Platelet-Derived Growth Factor ; biosynthesis ; genetics ; Proto-Oncogene Proteins c-sis ; Rats ; Rats, Sprague-Dawley ; Signal Transduction ; Transforming Growth Factor beta ; biosynthesis ; genetics

Objective To explore the effects of lamotrigine on the cognitive function and the quality of life in epilepsy patients.Methods This was a prospective study and 91 newly diagnosed epilepsy patients were enrolled.The neuropsychological tests score and the quality of life in epilepsy inventory(QOLIE-31) were obtained before and after the treatment with lamotrigine.A battery of neuropsychological tests comprised the auditory verbal learning test(AVLT), the logical memory test(LMT), the digital symbol test(DST), the stroop color word test(SCWT), the trail making test(TMT), the verbal fluency test(VFT), the WAIS block design test(WBDT), the WAIS digital span test(WDST)and the Boston naming test(BNT). Results The repeated assessments in the patients taking lamotrigine were associated with significant improvements in many domains.The greatest changes were observed in the immediate and delayed recall of AVLT, DST, the time consuming of SCWT card C and TMT test A and B, the immediate and delayed recall of LMT, VFT, WBDT and BNT.For the quality of life, significant improvements were recorded in the fields of the seizure worry(38.81?16.06 vs 45.68?15.18), the overall quality of life(59.12?13.50 vs 64.99?13.33), the social function(64.59?25.14 vs 69.41?22.70)and the self-health evaluation (71.18?13.73 vs 76.75?11.30).Conclusion Improvements of the cognitive function and the quality of life can be observed in the initial period of medication with lamotrigine in epilepsy patients.

Establishment of quality management system (QMS) plays a critical role in the clinical data management (CDM). The objectives of CDM are to ensure the quality and integrity of the trial data. Thus, every stage or element that may impact the quality outcomes of clinical studies should be in the controlled manner, which is referred to the full life cycle of CDM associated with the data collection, handling and statistical analysis of trial data. Based on the QMS, this paper provides consensus on how to develop a compliant clinical data management plan (CDMP). According to the essential requirements of the CDM, the CDMP should encompass each process of data collection, data capture and cleaning, medical coding, data verification and reconciliation, database monitoring and management, external data transmission and integration, data documentation and data quality assurance and so on. Creating and following up data management plan in each designed data management steps, dynamically record systems used, actions taken, parties involved will build and confirm regulated data management processes, standard operational procedures and effective quality metrics in all data management activities. CDMP is one of most important data management documents that is the solid foundation for clinical data quality.
Clinical Trials as Topic ; Data Collection ; standards ; Database Management Systems ; standards ; Information Storage and Retrieval ; standards

Objective To explore the changes of carcino-embryonic antigen (CEA) and carbohydrate antigen-199 (CA-199) before and after radiotherapy and chemotherapy in patients with local advanced gastric cancer, and to analyze the significance of the changes. Methods A total of 38 patients with local advanced gastric cancer who received radiotherapy and chemotherapy in our hospital from July 2003 to June 2011 were selected, and another 38 healthy subjects who received physical examination in our hospital at the same period of time were randomly selected. CEA and CA-199 levels of patients with gastric cancer before and after radiotherapy and chemotherapy, as well as the levels of healthy subjects were measured respectively. Venous blood samples were collected for all subjects at early morning under fast-ing condition, and the blood samples were tested by electro-chemiluminescence before gastric cancer was diagnosed by levels of CEA and CA-199 indices. Results The levels of CEA and CA-199 in patients with advanced gastric cancer were higher than those in the healthy subjects. After radiotherapy and chemotherapy, levels of CEA and CA-199 signifi-cantly reduced, and significantly lower than those before radiotherapy and chemotherapy. Accuracy, specificity and sen-sitivity of CEA were 91.67%, 96.67% and 86.67% respectively, and accuracy, specificity and sensitivity of CA-199 were 76.67%, 83.33% and 76.00% respectively. Total positive rate for all patients after radiotherapy and chemother-apy reduced to 42.11%(16/38). Total positive rate for patients with decreased CEA was lower, and 3-year total survival rate was higher. The total positive rate for patients with decreased CA-199 was lower, and the disease free survival rate and 2-year total survival rate were both higher, the differences were statistically significant (P<0.05 for both). Con-clusion The levels of CEA and CA-199 significantly reduce after radiotherapy and chemotherapy for patients with local advanced gastric cancer, and the accuracy of CEA and CA-199 for diagnosing local advanced gastric cancer is high. The possibilities of poor prognosis significantly rise when levels of CEA and CA-199 after radiotherapy increase. The levels of CEA and CA-199 after the treatment are positively correlated with the proportion of positive patients, disease free survival rate and 3-year survival rate.