In this work, blank polylactic acid (PLA) nanoparticles with unstained surface were prepared by the nano-deposition method. On the basis of the preparation, the effect of surface modification on brain microvascular endothelial cells (BMECs) targeting was examined by in vivo experiments and fluorescence microscopy. The results showed that PLA nanoparticles are less toxic than PACA nanoparticles but their BMECs targeting is similar to PACA nanoparticles. The experiments suggest that drugs can be loaded onto the particles and become more stable through adsorption on the surface of PLA nanoparticles with high surface activity. The surface of PLA nanoparticles was obviously modified and the hydrophilicity was increased as well in the presence of non-ionic surfactants on PLA nanoparticles. As a targeting moiety, polysobate 80 (T-80) can facilitate BMECs targeting of PLA nanoparticles.
Brain/*blood supply ; Brain/drug effects ; Capillaries/cytology ; Capillary Permeability/drug effects ; Drug Delivery Systems ; Endothelium, Vascular/*cytology ; Lactic Acid/*pharmacology ; Mice, Inbred Strains ; Microscopy, Fluorescence ; Nanoparticles ; Polymers/*pharmacology

ObjectivesTo explore the clinical significance of tyrosine kinase receptor RON mRNA expression and it's splicing variant in bladder tumors. Methods Sixty-three cases of transitional cell carcinoma of the bladder (TCCB), including 30 cases of pathological grade I , 15 cases of pathological grade Ⅱ and 18 cases of pathological grade Ⅲ (44 cases of clinical stage Tis + T1, 15 cases of T2 + T3 +T4), 7 inverted papilloma of the bladder ( IPB), 9 cases of papillary urothelial neoplasm of low malignant potential (PUNLMP) and 12 cases of normalbladder mucosa RT-PCR was employed with the internal standard (GAPDHmRNA) to detect the expression of RON mRNA. PCR and direct sequencing was then utilized to identify the potential RON mRNA splicing variants. Finally, the variants' positive rates of expression were analyzed among the different tissues, diverse TCCB pathological grades and clinical stages. ResultsThe expression levels of RON mRNA/GAPDH mRNA among TCCB, IPB, PUNLMP and normal control were 4. 9 × 10-3 ( 1. 8 × 10-3-1.0 × 10-2 ), 3. 8 × 10-3 (2. 4 × 10-3-1.7 × 10-2 ), 4. 9 ×10 -3 ( 1.7 × 10 -3-1.1 × 10 -2 ) and 1.0 × 10-3 (4. 5 × 10-4-2. 8 × 10-3 ) respectively. The difference had a statistical significance (x2K-W = 17. 278 ,P ＜0. 05 ). The expression levels among pathological grade I, Ⅱ andⅢ were 3.7 × 10-3( 1.3 × 10-3-7.5 × 10-3) , 4. 9 × 10-3(1.9 × 10-3-1.1 × 10-2) and 8.9 × 10-3(2. 7 ×10 -3-8.0 × 10 -2 ) respectively. The erpression levels among the clinical stage Tis + T1 and T2 + T3 + T4were 3.5 × 10-3 ( 1.2 × 10 -3-7. 7 × 10-3 ) and 9. 7 × 10 -3 ( 2. 9 × 10-3-5. 3 × 10-2 ). The differences between expression levels were of statistical significance among the different pathological grades ( x2k-W =7. 341, P ＜0. 05 ) and clinical stages ( Z = - 2. 306, P ＜ 0. 05 ). The positive rates of exon 11deletion(E11△) in TCCB, IPB and PUNLMP were 71％ (45/63), 57％ (4/7) and 67％ (6/9) respectively, andthe total positive rate in bladder tumor tissues was 70％. Meanwhile, expression of the novel RON variant wesnot detected in the normalbladder mucosa. The positive expression rate of E1 1△ has no significant correlationamong the different clinical pathological tissues (x2 = 0. 620, P ＞ 0. 05 ). There was no statistical significancein expression positive rate between different pathological grades ( Z =0. 221, P ＞0. 05 ) and clinical stages( Z = 0. 538, P ＞ 0. 05) as well. A novel RON splice variant, deletion of RON exon 11 3 476 - 3 539 ( E3476 -3539△) was fond in the pathological tissue. The positive expression rates of E3 476 -3 539 in TCCB,IPB and PUNLMP were 57％ (36/63), 43％ (3/7) and 56％ (5/9) respectively, and the total positive expression rate was 56％ (44/79). The positive rates of E3 476 -3 539△ in pathological grade I , Ⅱ and Ⅲ were 40％ ( 12/30), 67％ (10/15) and 78％ (14/18), and it's positive rates in clinical stage Tis +T1and T2 +T3 + T4 were 48％ (21/44) and 80％ (12/15). The differences in each group had significantly statistical significance ( Z = 7. 285, 5. 041, P ＜ 0. 05 ) . However, the positive rates amongdifferent pathological tissues had no significance (x2 = 0. 517, P ＞ 0. 05 ). Conclusions The expression level of RON mRNA is significantly associated with histological grading and clinical stage. RON may play an important role in the progression ofTCCB. Compared with the normal control, the increased RON variant expression may contribute to the carcinogenesis of the bladder tumor.

Objective To investigate the features of event-related potentials (ERP) P300, auditory evoked potential(AEP) and brainstem auditory evoked potential(BAEP) in senile depression patients and the dynamic chan-ges before and after treatment of sertruline. Methods P300, AEP and BAEP were recorded in 31 senile depression patients using Chinese WOND 2000C Instrument, and a comparison between the patients and 33 normal controls in terms of these evoked potentials were made. Some of the depression patients treated with oral intake of sertraline were followed electophysiologically after 12 months of treatment. Results Compared with normal controls, senile depres-sion patients showed delay of latency of P300-P3 and BAEP-Ⅲ, decreased amplitude of P300-P3, AEP-P2 and BA-EP-Ⅲ(P <0.05 or 0.01). The 12-month follow-up measures of ERP showed significant improvement in terms of la-tency and amplitude of P3/P300,AEP-P2 and BAEP-Ⅲ after treatment of sertraline. Conclusion Senile depres-sion patients showed abnormality on several ERP indexes (such as P3/P300, AEP-P2 and BAEP-Ⅲ), and these in-dexes might provide important evidences to monitor the effect of medicine.

Objective To study the relationship between the valine/leucine247 (817G/T) polymorphism in exon 7 of apolipoprotein H (apoH) gene and the generation of antiphospholipid (APL)antibodies in patients of Han nationality with systemic lupus erythematosus (SLE) in Wenzhou region.Methods This study included 165 patients with SLE and 160 healthy controls of Han nationality in Wenzhou region.Venous blood samples were obtained from all of the subjects followed by the isolation of blood plasma,sera and white blood cells.PCR and DNA sequencing were carried out to assess the Leu/Va1247 polymorphism in apoH gene.Lupus anticoagulant (LAC) was detected by Russell viper venom time (RVVT) assay.Enzyme-linked immunosorbent assay (ELISA) was carried out to quantify the serum levels of anti-β2-glycoprotein Ⅰ (GPI) antibodies and anticardiolipin antibodies (ACA).Chi-square test was carried out to compare the 817G/T polymorphism between the patients and controls,and Logistic regression analysis to evaluate the correlation between the 817G/T polymorphism and production of antiphospholipid antibodies.Results There were significant differences between the patients and controls in the genotype distribution and allele frequency at position 817 of apoH gene (both P ＜ 0.01).The TT,GT genotypes and T allele were more frequent,while GG genotype and G allele were less frequent,in the patients than in the controls.The GT genotype at position 817 was a risk factor for the production of LAC (P＜ 0.05,OR =2.33,95％CI =1.18-4.59),anti-β2GPl antibodies(P＜ 0.01,OR =5.92,95％CI =2.61-13.46) and ACA(P＜ 0.05,OR =2.52,95％CI =1.22-5.24),and the TT genotype was associated with an increased frequency of anti-β2GPI antibodies (P ＜ 0.01,OR =5.84,95％CI =1.69-20.20).Conclusions The 817G/T(Leu/Va1247) polymorphism in exon 7 of apoH gene is associated with the generation of APL antibodies in patients of Han nationality with SLE in Wenzhou region.The TT and GT genotypes at position 817 of apoH gene appear to be a risk factor for the production of APL antibodies.

In this work, blank polylactic acid (PLA) nanoparticles with unstained surface were prepared by the nano-deposition method. On the basis of the preparation, the effect of surface modification on brain microvascular endothelial cells (BMECs) targeting was examined by in vivo experiments and fluorescence microscopy. The results showed that PLA nanoparticles are less toxic than PACA nanoparticles but their BMECs targeting is similar to PACA nanoparticles. The experiments suggest that drugs can be loaded onto the particles and become more stable through adsorption on the surface of PLA nanoparticles with high surface activity. The surface of PLA nanoparticles was obviously modified and the hydrophilicity was increased as well in the presence of non-ionic surfactants on PLA nanoparticles. As a targeting moiety, polysobate 80 (T-80) can facilitate BMECs targeting of PLA nanoparticles.