Objective:To study the cognitive function and brain white matter fiber change in major depressive patients prior and post-treatment.Methods:Eleven major depressed patients were given antidepressants for 10 weeks, and their conditions were evaluated using 24-item Hamilton Depression Scale(HAMD).The cognitive function was determined by using Wisconsin Card Sorting Test(WCST),part of Wechsler memory scale and diffusion tensor ima- ging(DTI)was scanned before and after treatment.11 healthy people as control group were involved and given the same tests at the same time.Results:(1)The WCST scores of patients increased significantly after treatment(prior treatment Cc:1.6?1.6,Re:67.9?20.0,Rpe:51.5?24.8;post treatment Ce:4.0?2.1,Re:43.2?18.8,Rpe:22.8?16.0,P=0.001/0.000/0.003).There was no difference in number sequence memory in Wechsler memory scale.No difference was found between patients after treatment and control group in either WCST or number sequence memory.The patients made significant improvement in the total score of HAMD after treatment(16?14/54?13,t=6.60,P

Objective To evaluate the multi-slice spiral CT scan of liver dynamic dual-phase three-dimensional vascular imaging portal phase clinical value. Methods 80 cases in clinic, who were patients with liver function and imaging diagno- sis of liver and portal hypertension in liver cirrhosis, and 20 cases of healthy persons were carried out multi-slice spiral CT dual-phase scanning. The workstation used volume rendering techniques (VR) and maximum density multi-planar recon- struction technique for reconstruction. Results The hepatic arterial phase VR image and MIP MPR images can clearly show the celiac trunk, splenic artery, hepatic artery or artery and its branches, including 2-3 grade tumor blood supply variation of blood vessels and blood vessels, the portal venous phase, VR images and MIP MPR images clearly show the 1-6 level structure and the portal vein and hepatic vein branches of 1-3, with strong three-dimensional sense of space. Conclusion The multi-slice spiral CT three-dimensional reconstruction of portal vein imaging is a fast and effective non-invasive an- giography techniques, contributing to the clinical choice of reasonable efficacy of treatment programs and follow-up.

AlM: To observe the influence on the incidence of diffuse lamellar keratitis ( DLK ) after laser in situ keratomileusis ( LASlK ) whether or not wearing sterile gloves with talc during operation, and to confirm the role of residual talc in the occurrence of DLK.
METHODS: Totally 563 patients ( 1 126 eyes ) accepted operation with the method of surgical hand antisepsis only were set as the experimental group, while 592 patients ( 1 184 eyes ) with the method of surgical hand antisepsis and sterile gloves as the control group. Each patient was rechecked to observe the occurrence of DLK on the first day and the seventh day after the operation. Then the data of DLK were statistically analyzed byχ2 test and rank sum test.
RESULTS:On the first postoperative day, the incidence of DLK was 7. 4% (83 eyes) in experimental group and 12. 2% (144 eyes) in control group. ln the former group, stage Ⅰ of DLK accounted for 4. 6% (52 eyes) and stageⅡ for 2. 8% (31 eyes);while in the latter, stage l did for 7. 7% (91 eyes) and stageⅡfor 4. 5% (53 eyes). On the seventh day, all DLK were cured. The other 2 cases ( 3 eyes) occurred in stage Ⅳ DLK ( the first time recheck was on the eighth day after operation and fluorometholone ophthalmic solution was not used on time ) . The incidence and the severity were both significant lower in the experimental group than in the control (both P<0. 01).
CONCLUSlON: Talc is one of the most important factors resulting in DLK after LASlK. The method of surgical hand antisepsis without wearing gloves could avoid the stimulation of talc and reduce the incidence of DLK obviously.

The present study is to establish Caco-2/HT29-MTX co-cultured cells and investigate the transport capability of PLGA nanoparticles with different surface chemical properties across Caco-2/HT29-MTX co-cultured cells. PLGA-NPs, mPEG-PLGA-NPs and chitosan coated PLGA-NPs were prepared by nanoprecipitation method using poly(lactic-co-glycolic acid) as carrier material with surface modified by methoxy poly(ethylene glycol) and chitosan. The particle size and zeta potential of nanoparticles were measured by dynamic light scattering. Coumarin 6 was used as a fluorescent marker in the transport of nanoparticles investigated by confocal laser scanning microscopy. The transport of furanodiene (FDE) loaded nanoparticles was quantitively determined by high performance liquid chromatography. Colchicine and nocodazole were used in the transport study to explore the involved endocytosis mechanisms of nanoparticles. Distribution of the tight junction proteins ZO-1 was also analyzed by immunofluorescence staining. The results showed that the nanoparticles dispersed uniformly. The zeta potential of PLGA-NPs was negative, the mPEG-PLGA-NPs was close to neutral and the CS-PLGA-NPs was positive. The entrapment efficiency of FDE in all nanoparticles was higher than 75%. The transport capability of mPEG-PLGA-NPs across Caco-2/HT29-MTX co-cultured cells was higher than that of PLGA-NPs and CS-PLGA-NPs. Colchicine and nocodazole could significantly decrease the transport amount of nanoparticles. mPEG-PLGA-NPs could obviously reduce the distribution of ZO-1 protein than PLGA-NPs and CS-PLGA-NPs. The transport mechanism of PLGA-NPs and mPEG-PLGA-NPs were indicated to be a combination of endocytosis and paracellular way, while CS-PLGA-NPs mainly relied on the endocytosis way. PEG coating could shield the surface charge and enhance the hydrophilicity of PLGA nanoparticles, which leads mPEG-PLGA-NPs to possess higher anti-adhesion activity. As a result, mPEG-PLGA-NPs could penetrate the mucus layer rapidly and transport across Caco-2/HT29-MTX co-cultured cells.
Biological Transport ; Caco-2 Cells ; Chitosan ; chemistry ; Coated Materials, Biocompatible ; chemistry ; Coculture Techniques ; Drug Carriers ; Furans ; administration & dosage ; chemistry ; metabolism ; HT29 Cells ; Heterocyclic Compounds, 2-Ring ; administration & dosage ; chemistry ; metabolism ; Humans ; Lactic Acid ; chemistry ; Nanoparticles ; Particle Size ; Polyethylene Glycols ; chemistry ; Polyglycolic Acid ; chemistry ; Zonula Occludens-1 Protein ; metabolism

Objective To explore the relationship between receptor of advanced glycaton end products(RAGE)gene Gly82Ser polymorphism and patients with transient ischemia attack(TIA).Methods The Gly82Ser gene at the position of RAGE gene exon 3 was identified by a polymerase chain reaction- restriction fragment length polymorphism(PCR-RFLP)method in 70 cases of TIA & Diabetes(DM), 60 of simply TIA and 66 healthy control subjects.Results The genotypes of RAGE gene Gly82Ser identified were GG, GS and SS.The frequencies of RAGE gene Gly82Ser GS heterozygous genotype of TIA & DM and control were respectively 62.9% and 43.9%, significantly higher in TIA & DM patients than in control subjects(OR 2.036, 95% CI 1.021--4.062, P=0.042), however no significant difference was found between simply TIA and control(53.3% vs 43.9%, OR 1.299,95% CI O.644--2.618, P=0.465). Significant difference of the frequency of S allele was found neither between TIA & control and control(being 34.3% and 26.5%, respectively, OR 1.446,95% CI 0.859--2.434, P=0.164), nor between simple TIA and control(28.3% vs 26.5%, OR 1.096,95%CI 0.630--1.907, P=0.746).Conclusions RAGE gene Gly82Ser GS heterozygous genotype may be associated with TIA & DM patients.RAGE gene Gly82Ser polymorphism is a risky factor for TIA & DM patients, but not for TIA patients.

To investigate the effects of oleanolic acid (OA) on the proliferation, migration and the formation of tube-like structure in human vascular endothelial cells (HUVECs). MTT assay, flat plate scarification, Transwell plates and matrigel-induced tube formation assay were performed to detect the effects of OA on proliferation, migration and tube formation. MTT assay showed that the inhibition rates of HUVECs treated with 60 and 100 microg x mL(-1) of OA for 24 h were 19% and 83% respectively. Treatment of HUVECs significantly inhibited the cell migration in a dose-dependent manner. The vascular indexes of HUVECs treated with 40 and 60 microg x mL(-1) OA were 33% and 20% respectively. Western blotting analysis showed that treatment of the cells with OA significantly attenuated the expression and secretion of VEGF. Additionally, VEGF could in part reverse the effects of OA on migration and tube formation of HUVECs. In conclusion, OA inhibits the proliferation, and VEGF plays an important role in OA induced decreased migration and tube formation of HUVECs.
Cell Movement ; drug effects ; Cell Proliferation ; drug effects ; Cells, Cultured ; Dose-Response Relationship, Drug ; Human Umbilical Vein Endothelial Cells ; cytology ; metabolism ; Humans ; Neovascularization, Physiologic ; drug effects ; Oleanolic Acid ; administration & dosage ; pharmacology ; Signal Transduction ; drug effects ; Vascular Endothelial Growth Factor A ; metabolism ; secretion

To investigate the effects of particle size, mPEG molecular weight, coating density and zeta potential of monomethoxyl poly(ethylene glycol)-poly(lactic-co-glycolic acid) (mPEG-PLGA) nanoparticles on their transportation across the rat nasal mucosa, mPEG-PLGA-NPs with different mPEG molecular weights (M(r) 1 000, 2 000) and coating density (0, 5%, 10%, 15%) and chitosan coated PLGA-NP, which loaded coumarin-6 as fluorescent marker, were prepared with the nanoprecipitation method and emulsion-solvent evaporation method, and determine their particle size, zeta potential, the efficiency of fluorescent labeling, in vitro leakage rate and the stability with the lysozyme were determined. The effects of physical and chemical properties on the transmucosal transport of the fluorescent nanoparticles were investigated by confocal laser scanning microscopy (CLSM). The result showed that the size of nanoparticles prepared with nanoprecipitation method varied between 120 and 200 nm; the size of nanoparticles prepared with emulsion-solvent evaporation method varied between 420 and 450 nm. Nanoparticles dispersed uniformly; the zeta potential of PLGA-NPs was negative; mPEG-PLGA-NPs was close to neutral; chitosan coated PLGA-NPs was positive; and the efficiency of fluorescent labeling were higher than 80%. In vitro leak was less than 5% within 4 h and nanoparticles were basically stable with lysozyme. The CLSM results show that the transportation efficiency of mPEG-PLGA-NPs with a high PEG coating density and high mPEG molecular weight was significantly higher than that of uncoated PLGA nanoparticles and also that of chitosan coated PLGA-NPs (P < 0.05). The hydrophilcity, zeta potential and particle size of nanoparticles play important roles on the efficiency of mPEG-PLGA nanoparticles to transport across the rat nasal mucosa.
Animals ; Biological Transport ; Chitosan ; chemistry ; Drug Carriers ; chemistry ; Female ; Male ; Microscopy, Confocal ; Molecular Weight ; Nanoparticles ; Nasal Mucosa ; metabolism ; Particle Size ; Polyesters ; chemistry ; pharmacokinetics ; Polyethylene Glycols ; chemistry ; pharmacokinetics ; Rats ; Rats, Sprague-Dawley

Antibody-drug conjugate (ADC) is a new class of therapeutics composed of a monoclonal antibody and small cytotoxin moieties conjugated through a chemical linker. ADC molecules bind to the target antigens expressed on the tumor cell surfaces guided by the monoclonal antibody component. The binding ADC molecules can be internalized and subsequently the toxin moieties can be released within the tumor cells via chemical and/or enzymatic reactions to kill the target cells. The conjugation combines the merits of both components, i.e., the high target specificity of the monoclonal antibody and the highly potent cell killing activity of the cytotoxin moieties. However, such complexities make the pharmacokinetic and metabolic studies of ADCs highly challenging. The major challenges should include characterization of absorption, distribution, metabolism and excretion, investigation of underlying mechanisms, assessment of pharmacokinetic- pharmacodynamic relationship, and analytical method development of ADC drugs. This review will discuss common pharmacokinetic issues and considerations, as well as tools and strategies that can be utilized to characterize the pharmacokinetic and metabolic properties of ADCs.
Antibodies, Monoclonal ; pharmacokinetics ; Cytotoxins ; pharmacokinetics ; Humans ; Immunoconjugates ; pharmacokinetics ; Neoplasms ; drug therapy

ObjectiveTo investigate the influence of recombinant thioredoxin (TRX)on apoptosis of myocardium cell in viral myocarditis of mice.MethodsTwenty-four Balb/c mice,weighting 12 - 14 g,were randomly divided into 3 groups:the control group,the virus group and the protective group,8 mice in each group.The virus group and the protective group were injected with 0.1 ml 100TCID50 Coxackie virus B3 (CVB3)intraperitoneally,and the control group was injected equal volume of saline.Therewithal the protective group was injected with TRX(2 mg/kg) by tail vein,and the virus group was injected saline the same way.After 14 days all mice were killed and hearts were taken.Changes of myocardial histopathology was observed with optical microscope,cell apoptosis was checked by TUNEL technique,and the expression of apoptosis-related proteins (Bcl-2,caspase-3)in infiltrated cell of myocardium was determined by immunohistochemistry.Results(①)Lymphocyte infiltration and necrosis were observed in survivals of the virus group,sporadic coagulation necrosis and ballooning degeneration of cells were observed in the protective group,however no myocardial lesion was found in the control group.(②)TUNEL technique showed that the positive ratio of apoptosis in the virus group and the protective group[(90.23 ± 3.63)％,(20.02 ± 2.41)％] was significantly higher than that of the control group(0.00 ± 0.00,all P ＜ 0.05),the positive ratio of apoptosis in the protective group was significantly lower than that of the virus group (P ＜ 0.05 ).(③)Immunohistochemistry showed that the expression of protein Bcl-2(+,++,+++) in the virus group and the protective group was significantly higher than that of the control group (all P ＜ 0.05).The expression of protein Bcl-2 in the protective group was significantly higher than that of the virus group(P ＜ 0.05).The expression of caspase-3 (+,++) was significantly higher in the virus group and the protective group than the control group (all P ＜ 0.05).Compared with the virus group,the expression of caspase-3 in the protective group was significantly lower(P ＜ 0.05).ConclusionTRX could inhibit cardiomyocyte apoptosis in viral myocarditis mice and the inhibition is related to regulation of apoptosis-related protein expression.

OBJECTIVE: To study the role of dopamine D3 receptor involved in the amphetamine-induced conditioned place preference (CPP) in mice. METHODS: The CPP was observed in D3 receptor knock-out (D3RKO) mice and C57BL/6 wild-type control mice after administration of amphetamine. The data were analyzed with a two-way ANOVA using the SPSS 13.0 software. RESULTS: D3RKO mice showed a significant amphetamine-induced CPP (P<0.001), compared with the ones administered with saline in C57BL/6 control mice. CONCLUSION The results indicate that amphetamine can produce significant CPP in dopamine D3 receptor knock-out mice, suggesting that amphetamine-induced addiction can be inhibited by dopamine D3 receptor.
Amphetamine/pharmacology* ; Animals ; Behavior, Animal/drug effects* ; Conditioning, Operant/drug effects* ; Disease Models, Animal ; Female ; Gene Knockout Techniques ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Motor Activity/drug effects* ; Reaction Time ; Receptors, Dopamine D3/physiology*