Brain-targeting non-viral gene delivery systems could efficiently mediate gene drugs to cross blood-brain barrier and reach the diseased regions. Many researches have demonstrated that enhanced brain accumulation and gene expression could be achieved via appropriate mechanisms such as specific ligand-receptor binding function. In this review, progress on brain-targeting non-viral gene delivery systems mainly based on receptor- and adsorptive-mediated mechanisms is reviewed.

AIM: To investigate the role of catecholamine, angiotensin converting enzyme(ACE) and adenosine triphosphatase in ischemic preconditioning in isolated rat hearts. METHODS: Isolated perfused rat heart was subjected to global ischemia for 40 min followed by reperfusion for 10 min (I/R). Preconditioning (PC) was induced by 5 min of ischemia and 10 min of reperfusion. The tissue concentrations in NE, and ACE, ATPase activities were determined in left ventricle in the PC and I/R groups by fluorometry and spectrophotometry. RESULTS: There were no significant difference in NE and ACE between PC and I/R groups. PC hearts showed improved recovery of the contractile function after 40 min ischemia/10 min reperfusion, but activities of the myocardial total ATPase, Mg2＋-ATPase, Na＋K＋-ATPase were inhibited markedly compared with I/R group. CONCLUSION: The inhibited myocardial ATPase may be involved in the mechanism of ischemic preconditioning protection in the isolated rat heart. Endogenous myocardial norepinephrine and ACE activation are not essential for ischemic preconditioning in the isolated rat heart.

Abstract: Objective To explore the effects of continuous light and benzene exposure on peripheral blood erythrocyte - Methods parameters and expression of miR 144/451 in the bone marrow of mice. This was a 2×2 factorial design. Photoperiod ， ， factor was set as normal and continuous light levels and mice were treated for 12 hours/12 hours light/dark or 24 hours light - respectively. The benzene exposure factor was set as non exposure and exposure levels. Mice were exposed to benzene by static 3 ， inhalation with a mass concentration of 0.0 and 32.5 mg/m for three hours per day five days per week for a total of four weeks. ， ， Specific pathogen free male C57BL/6 J mice were randomly divided into negative control group simple continuous light group - - ， ， simple benzene exposure group and combined exposure group with 12 mice per group. After benzene exposure peripheral ， blood was collected for the detection of erythrocyte parameters in four periods. After the mice were sacrificed the expression of - - - - miR 451a and miR 144 5p was detected by real time fluorescence quantitative polymerase chain reaction in bone marrow Results （ ）， ， tissues. The hematocrit volume HCT mean corpuscular volume mean corpuscular hemoglobin concentration （ ） - MCHC and mean corpuscular hemoglobin in peripheral blood and the relative expression of miR 451a in bone marrow tissue （ P< ） ， were statistically significant only in mice with benzene exposure all 0.05 . Among them the MCHC of benzene exposed （P< ）， （ P< ） - mice increased 0.05 but the other four indexes decreased all 0.05 compared with non benzene exposed mice. In thenegative control group the change of red blood cells count hemoglobin level and HCT in peripheral blood were rhythmical all P < ） ， （ P > ） rhythmical 0.05 . However the indexes above were out of rhythm all rhythmical 0.05 in the simple continuous light group and the - （ P > combined exposure group. The change of hemoglobin level and HCT of peripheral blood were also out of rhythm all rhythmical ） - - 0.05 in the simple benzene exposure group. The relative expression of miR 451a in bone marrow tissues of negative control （ P < ）， - group and simple continuous light group was rhythmical all rhythmical 0.05 while the relative expression of miR 451a in simple - - （ P > ）Conclusion benzene exposure group and combined exposure group was out of rhythm all rhythmical 0.05 . Benzene exposure ， induced changes in erythrocyte parameters of mice are independent effect and its mechanism may be related to the rhythmic - ， expression disorder of miR 451a in bone marrow tissues. Continuous light exposure benzene exposure and their interactions can ， interfere with the circadian rhythm of erythrocyte parameters such as red blood cell count hemoglobin and HCT to some extent.

Background Clinical research showed that the corneal endothelial cell density value from different corneal specula microscopies exist diversity.The relevant literature of SP02,Tomey EM-3000 and SP3000P is still seldom up to now. Objective This research was to assess the repeatability of endothelial cell density measurements by SP02,Tomey EM-3000 and SP3000P respectively and the agreement among 3 kinds of endothelial microscopes.MethodsFifty-four healthy volunteers with the age 17-38 years old were included this research.The written informed consent was obtained from each subject before examination.The corneal endothelial cell densities in the right eyes were analyzed with SP02,Tomey EM-3000 and SP3000P respectively for 3 times under the automatic mode,and the analytical procedure of SP3000P measurement were divided into automatic mode SP3000P (A) and manual correction modes SP3000P( M).The repeatability of each specula microscopy was analyzed by calculating the intraclass correlation coefficients (ICC) and coefficient of variation ( CV ),and the 95％ confidence intervals and plotting Bland-Altman graphs were used to analyze the agreement among these methods.ResultsThe mean corneal endothelial cell densities in the population ＜24 years were significantly higher than the ones ≥ 24 years (t =3.692,P＜0.05 ),but no statistical difference was found between different gender ( t =0.335,P =0.739 ).The mean corneal endothelial cell densities were ( 3058 ± 260 ),( 2954 ± 229 ),( 2668 ± 258 ),( 2734 ± 268 ) cell/mm2 ; the ICCs were 0.957,0.940,0.972 and 0.972 and the CV were 0.063,0.061,0.056,0.058 for SP02,Tomey EM-3000,SP3000P (A) and SP3000P ( M ) respectively.The 95％ confidence intervals were ( - 100.8 - 306.8 ),( 162.6 - 617.4 ),( 109.9-494.1 ) and ( -0.6 - 132.6 ) cell/mm2 for between SP02 and Tomey EM-3000,SP3000P ( A ) and SP02,SP3000P(A) and Tomey EM-3000,SP3000P(A) and SP 3000P(M) respectively.ConclusionsSP02,Tomey EM-3000 and SP3000P(A) have good repeatability in the measurement of corneal endothelial cell density,however the outcome is different.Therefore,it is not interchangeable for the detection of corneal endothelial cell density.The differences of corneal endothelial cell density obtained from these instruments shall be paid high attention for their differences.SP3000P(A) and SP3000P(M) can be used interehangeably and SP3000P(A) is a preferable choice due to its convenience and quickness.

Background Central corneal thickness (CCT)is an important parameter to evaluate corneal healthy status and is crucial for surgical planning.However,clinical study found that the center of cornea does not correspond to the thinnest point of cornea.Thus,it is essential to characterize the minimum corneal thickness(MCT) and its location.Objective Present study was to determine the thickness and location of MCT and its relationship to the fellow eye using Pentacam High Resolution technique.Methods The 564 eyes from 282 Chinese myopic patients were reviewed in this study.The CCT,MCT,pupillary central corneal thickness(PCT) and x-y coordinate of thinnest point were bilaterally measured.Written informed consent was obtained prior to the ocular biomedical measurement.Results CCT was (540.07±31.78) μm in the right eyes and (539.24±31.06) μm in the lefi eyes; PCT was (540.25±30.75)μm in the right eyes and (539.48±31.00)μm in the left eyes.MCT was (537.87± 31.91)μm in the right eyes and (536.35±31.24)μm in the left eyes,showing significant differences in all the parameters between the right eyes and left eyes expect for PCT(CCT:P=0.046;PCT:P=0.065 ;MCT:P=0.000).The C CT,PCT and M CT were significantly correlated between the right eyes and left eyes (r =0.97,0.97,0.98,P＜ 0.01).Bland-Altman plot showed a good consistence between the both eyes.The mean distance from the center was (0.50±0.21) mm in the right eyes and (0.56±0.22)mm in the left eyes,showing a significant difference (P =0.000).The difference between CCT and MCT was approximately (2.20±1.74)μm in the right eyes and (2.88±1.75) μm in the left eyes.The location of MCT in both the right eyes and left eyes tended to symmetry along the vertical midline.The distance between the R (x,y) to transformed L (x,y) was (0.29 ± 0.17)mm and the angular distance was (28.28±28.21)degree.Conclusions This study offers a range of MCT and its location in Chinese myopic patients.The difference exists between the CCT and MCT in bilateral eyes.The location of the thinnest point tends to be symmetrical along the vertical midline between the both eyes.The changes of these parameters may be helpful for the diagnosis of some corneal diseases.

BackgroundIn an ideal eye there would be no light scattering at all,but the eye media is not optically ideal.Intraocular straylight causes a veil of light and reduction in the contrast of the retinal image and thus decrease the quality of vision.ObjectiveThe present study was to investigate the repeatability and reproducibility of C-Quant straylight meter( Oculus,Germany)in measuring retinal straylight of myopia and post-laser in situ keratomileusis(LASIK) corneas.MethodsThis is a prospective research.The consecutive 35 eyes of 21 myopic patients and 34 eyes of 22 patients who received LASIK were included in this trail.Retinal straylight was measured for 7 times at a period of time and analyzed quantificational to evaluate the repeatability of measurement.Thirty-eight eyes of 19 patients were measured again at 3-7 days for 3 times at a period of time to assess the reproducibility of C-Quant straylight meter.The mean standard difference (SD) and coefficient of variation (CV) were used as the credibility evaluation.This clinical study complied with Helsinki Declaration and the informed consent was obtained prior to the medical procedure.ResultsThe straylight Log(s) of 7 times measurement were all less than 0.95.The mean Log(s) were 0.92±0.12 and 0.93±0.17 respectively in myopia group and post-LASIK group,without statistically significant differences among 7 times measurement( F=0.335,P=0.812;F=1.000,P=0.409).The mean SD for the 7 times measurement was 0.07 Log units.SD and CV increased with the number of measurements.The differences of mean SD and CV between 3 times result and 6 times result were significant different (t =-2.080,P =0.045;t =-2.190,P =0.035 ).No difference was found between different time periods( t =-0.531,P=0.598 ).The difference of the results between two measurements from the same patient was 0.013.ConclusionsC-Quant is a noncontact,noninvade,rapid and convenient method for the measurement of straylight in myopia and post-LASIK eyes due to the high repeatability and reproducibility.

Objective To assess the inlfuence of depth on liver stiffness measurement with real-time shear wave elastography (SWE) and determine the optimal depth for SWE in liver. Methods SWE of liver was performed on 89 healthy volunteers between May 2012 and November 2012. The depths of each liver were varied from 0 cm to 7 cm (from the liver capsule) in 1 cm increment and there were 8 depth groups in total. Then the elastic modulus of liver in each depth group were measured three times by SWE. The body mass index (BMI) and the distance from body surface to liver capsule were documented. The success rates and the mean elastic modulus of each group were calculated. Results The success rates of 0-7 cm were 0, 98.9%(88/89), 98.9%(88/89), 98.9%(88/89), 71.9%(64/89), 24.7%(22/89), 3.4%(3/89) and 0, respectively. The success rates were highest in 1 cm, 2 cm and 3 cm groups but signiifcant decreased with the increasement of depths in 4 cm, 5 cm and 6 cm groups ( 3 cm vs 4 cm, χ2=25.94, P<0.001; 4 cm vs 5 cm, χ2=39.68, P<0.001;5 cm vs 6 cm,χ2=16.79, P<0.001). The mean elastic modulus of 1 cm, 2 cm, 3 cm, 4 cm and 5 cm groups were (4.77±0.99), (4.68±0.99), (4.76±0.95), (5.19±1.10) and (5.41±0.95) kPa, respectively. The mean elastic modulus of 4 cm and 5 cm groups were signiifcant higher than those of 1 cm, 2 cm, 3 cm groups (4 cm vs 1 cm, t=-2.85, P=0.005;4 cm vs 2 cm, t=-3.49, P=0.001;4 cm vs 3 cm, t=-2.76, P=0.006;5 cm vs 1 cm, t=-3.13, P=0.002;5 cm vs 2 cm, t=-3.66, P=0.000;5 cm vs 3 cm, t=-3.05, P=0.003). In the group of 4 cm, the BMI and the distance from body surface to liver capsule of the volunteers performed successfully and unsuccessfully were (20.70±2.87), (22.07±2.42) kg/m2 and (1.45±0.25 ), (1.60±0.29) cm, respectively. In the group of 5 cm, the BMI and the distance from body surface to liver capsule of the volunteers performed successfully and unsuccessfully were (19.82±2.76), (21.49±2.72) kg/m2 and (1.35±0.21), (1.54±0.26) cm respectively. The BMI had no signiifcant difference between the successful and unsuccessful groups (t=-2.83, P=0.108 for 4 cm;t=0.77, P=0.709 for 5 cm), but the distance from body surface to liver capsule was signiifcantly different (t=26.51, P=0.012 for 4 cm;t=79.57, P=0.004 for 5 cm). Conclusions The success rates and elastic modulus were different at different depths. SWE should be performed at the depths of 1-3 cm from the liver capsule.

The results of open-field test,step-through passive avoidance task and radial-arm maze experiment showed that changes of locomotor activity,anxiety-related behaviour and ability of learning and memory were associated with the increased apoptosis of neurons in hippocampus in rats with perinatal hypothyroidism.

Background and purpose: Although crizotinib could manifest marked antitumor activity in anaplastic lymphoma kinase (ALK)-rearrangement-positive non-small cell lung cancer (NSCLC) patients, but brain metastases is always occured in such patients. This study aimed to explore the efifcacy and treatment mode of crizotinib for brain metastases in ALK-rearrangement-positive NSCLC. Methods: The clinical data of 6 patients with brain metastases in ALK-rearrangement-positive NSCLC treated in 81 Hospital of PLA from Jan. 2011 to Aug. 2014 were analyzed retrospectively. Results: Three patients had brain metastases before crizotinib administration, 1 obtained partial response (PR) and 2 obtained stable disease (SD) in intracraninal tumors. The median progression free survival (PFS)for the ifrst period of crizotinib administration were 5.7 months, and the sites of ifrst disease progression were brains. All the 6 patients continued to receive crizotinib after radiotherapy with the median PFS of 4 months. One patient even experienced a median PFS of 23.3 months for the second period of crizotinib administration, and her brain tumors obtained complete response (CR). Conclusion:The data of this study suggest that crizotinib is effective for brain metastases in ALK-rearrangement-positive NSCLC, and continued administration of crizotinib after radiotherapy for isolated intracraninal tumor progression is a elective treatment option for such patients.

Aim To investigate the effects of airway epithelial cell-derived insulin-like growth factor-1 (IGF1) on CD8 +T cell polarization. Methods Hu-man airway epithelial cell line, RPMI2650 cells, was cultured in the presence of a mice allergen, Der p1, for 72 h. IGF1 expression was checked with quantita-tive RT-PCR and Western blot. Der p1-primed RP-MI2650 cells, recombinant IGF1 and anti-IGF1 anti-body was cocultured respectively with CD8 + T cells, which were activated by anti-CD3/CD8 Ab. Apoptotic cells frequency was calculated with flow cytometry. The alteration of p53 gene hypermethylation in CD8 + T cells elicited by Der p1-primed airway epithelial cell and IGF1 was plotted. Results Both mRNA(23. 1%± 5. 2% vs 5. 2% ± 2. 3%, P < 0. 01 ) and protein (33. 4 ± 6. 4 vs 9. 2 ± 4. 6, P <0. 01 ) expression of IGF1 in RPMI2650 cells markedly increased after ex-posure to Der p1 . The increase of apoptotic CD3/CD28 Ab-activated CD8 + T cells was abolished by the pres-ence of Derp1-primed epithelial cells ( 41. 7% ± 8. 2%vs 5. 2% ± 1. 8%, P <0. 01 ) . The results were con-firmed by the addition of recombinant IGF1 . Anti-IGF1 antibody abolished the effect of the epithelial cells. Derp1-primed epithelial cells inhibited p53 gene mR-NA( 29. 1% ± 5. 9% vs 16. 2% ± 4. 3%, P <0. 01 ) and protein ( 63. 3 ± 8. 9 vs 26. 9 ± 5. 6 , P <0. 01 ) ex-pression. Anti-IGF1 antibody abolished the effect. Re-combinant IGF1 promoted CD8 + T cells′p53 gene hy-permethylation. Conclusion Der p1 induces RP-MI2650 cells to produce IGF1 , and this factor prevents CD8 + T cell apoptosis by inducing p53 gene hyperm-ethylation.