Objective To observe the instant reactions and relationship of astrocytes(ASs) and neurons(Ns) in rat forebrain after the unilateral tibia and fibula bone fracture. Methods With immunohistochemical triple staining method,the expression of Fos-protein,glial fibrillary acidic protein(GFAP) and tyrosine hydroxydase(TH) were observed. Results Here we showed 1.After the nociception of the treatment,GFAP-like immunoreactive (-LI) ASs exhibited clear character of nuclei distribution in the lateralmedial habenular nucleus(LHb),paraventricular nucleus of the hypothalamus(Pa),supraoptic nucleus(SON),suprachiasmatic nucleus(SCh),bed nucleus of of stria terminalis(BST),central amygdaloid nucleus(Ce) medial amygdaloid nucleus(Me) and cortex;2.The distribution of Fos-LI Ns and GFAP-LI ASs in above nuclei were similar,there were close relationship between Fos-LI Ns and GFAP-LI ASs.3.There were many double-labelled Fos/TH-LI Ns that were surrounded by the GFAP-LI ASs,and formed the neuron-astrocyte complex(N-ASC).Conclusion The ASs as well as Ns of the above nuclei or regions may be involved in instant response and adjustment of the lower extremity bone fracture nociception simultanneously.

OBJECTIVE:To determine the plasma concentration of Phencynonate hydrochloride(PCH)in dogs,and to calcu-late pharmacokinetic parameters. METHODS:6 Beagle dogs were given PCH tablets(2 mg and 4 mg)intragastrically. The blood samples were collected 5 min before medication and 0.17,0.25,0.5,0.75,1.0,1.25,1.5,2,3,4,6,8,10,12,14,16,18, 24 and 36 h after medication,2 ml each time. Using penehyclidine hydrochloride as internal standard,HPLC-MS/MS method was adopted to determine the plasma concentration of PCH. The medication plans were interchanged 2 weeks later. The pharmacokinetic parameters were calculated using DAS 2.0 software. RESULTS:The linear range of PCH was 0.1-15 ng/ml(r=0.999 6);the low-est limit of quantification was 0.1 ng/ml;the methodology recovery were 97.30%-103.20%;the extraction recovery were 52.30%-60.11%(RSD<11%,n=5). The main pharmacokinetic parameters of low and high doses were as follows as t1/2α of (0.678±0.525)and(0.405±0.465)h,tmax of(1.042±0.401)and(0.900±0.418)h,cmax of(14.063±6.29)and(31.580±9.673) mg/L,AUC0-36 h of(48.186±14.776)and(79.269±34.649)mg·h/L. CONCLUSIONS:The method is simple,sensitive and speci-fic,and can be used for pharmacokinetic study of PCH in dogs.

Cancer, also known as malignant tumor, is the second largest disease after heart disease, which is characterized by genomic instability and mutagenicity. Ataxia telangiectasia and RAD3-related kinase (ATR) are members of phosphatidylinositol 3-kinase (PIKK) family, belonging to serine/threonine kinase, one of the key kinases in DNA damage response (DDR) and DNA repair pathway. This paper reviews the latest progress in the ATR inhibitor field including mechanism of action (MOA), therapeutic applications, and the combination therapy from the perspective of medicinal chemistry. It also discusses the possible challenges and future directions of developing ATR inhibitor antitumor drugs, which could provide the scientists in this field the convenience for access the information and application guidance for clinical studies.

The purpose of this study is to prepare T7 and TAT dual modified liposomes (T7-TAT-LIP) to penetrate through blood brain barrier and target to brain tumor cells. The liposomes were prepared with CFPE, T7 modified PEG-DSPE, TAT modified PEG-DSPE, soybean phospholipid, PEG-DSPE and cholesterol. The CFPE was used to track the cellular uptake efficiency. The density of T7 and TAT and the length of PEG were optimized, and then the liposomes were characterized by particle size, zeta potential, morphology and stability. Afterwards, the cellular uptake by bEnd.3 and C6 cells were evaluated. The results showed that the optimized parameters were 6% of T7, 0.5% of TAT, the molecular weight of PEG for T7 was 2000 and the molecular weight of PEG for TAT was 1000. After optimization, the particle size of T7-TAT-LIP was 118 nm, the zeta potential was -6.32 mV and the particles were spherical. The turbidity and particle size of liposomes were not obviously changed after 24 h incubation in PBS at 37 °C. The particle size and polydispersity index were also stable during 1 month incubation at 4-8 °C. The cellular uptake by both bEnd.3 and C6 cells of T7-TAT-LIP was higher than that of T7 or TAT modified liposomes, suggesting dual modified liposomes possessed better blood brain barrier targeting ability and brain tumor targeting ability than the single ligand modified liposomes.
Biological Transport ; Blood-Brain Barrier ; Brain Neoplasms ; drug therapy ; Cell-Penetrating Peptides ; pharmacology ; Cholesterol ; Liposomes ; Particle Size ; Phosphatidylethanolamines ; Polyethylene Glycols

BACKGROUND:Locking compression plate and dynamic hip screw are the two major extramedul ary fixations for the femoral intertrochanteric fractures, however, the comparison of the clinical efficacy between two methods is stil controversial. OBJECTIVE:To systematical y evaluate the clinical efficacy of locking compression plate versus dynamic hip screw in the treatment of femoral intertrochanteric fractures, and provide a theoretical basis for clinical application. METHODS:Authors searched for control ed studies on locking compression plate and dynamic hip screw in the treatment of femoral intertrochanteric fractures in PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, VIP periodical database, Wanfang resource database, Chinese Biomedical Literature service systems published from January 1999 to April 2014. The inclusion and exclusion criteria were made, and the literature meeting the criteria was screened, and the methodological quality of the included studies was evaluated. Meta-analysis was carried out using the RevMan 5.2 software. RESULTS AND CONCLUSION:Ultimately 682 patients from 8 studies met the inclusion criteria, including 336 patients in the locking compression plate group and 346 patients in the dynamic hip screw group. Meta-analysis results showed that:there were no statistical y significant differences in operating time [MD=-12.07, 95%CI (-29.85, 5.71), P=0.18], peri-operative bleeding loss [MD=-15.01, 95%CI (-87.85, 57.83), P=0.69], post-operation drainage [MD=-13.62, 95%CI (-28.49, 1.26), P=0.07], ambulation time [MD=-0.14, 95%CI (-0.68, 0.41), P=0.63], length of hospitalization [MD=-0.74, 95%CI (-2.29, 0.82), P=0.35], bone union time [MD=-1.18, 95%CI (-2.78, 0.42), P=0.15] between locking compression plate and dynamic hip screw groups. The excellent and good rate of postoperative hip function reduction [OR=2.03, 95%CI (1.23, 3.36), P=0.006] was significantly higher in locking compression plate group than in the dynamic hip screw group. The incidence of coxa vara was lower in the locking compression plate group than in the dynamic hip screw group [OR=0.34, 95%CI (0.12, 0.96), P=0.04]. There were no significant differences in looseness, breakage, withdrawal of internal fixation [OR=1.20, 95%CI (0.59, 2.45), P=0.61] and the incidence of total complications [OR=0.55, 95%CI (0.24, 1.28), P=0.16] between locking compression plate and dynamic hip screw groups. However, the included studies have high possibility of selection bias and measurement bias, and wil affect proof strength of results. Therefore, more clinical randomized control ed studies with compact design are needed for verification.

Objective: To assess the effect of percutaneous transluminal septal myocardial ablation (PTSMA) on mid- to long-term left ventricular diastolic function in patients with hypertrophic obstructive cardiomyopathy (HOCM) by real-time three-dimensional echocardiography (RT-3DE). Methods: A total of 46 HOCM patients who received 2DE and RT-3DE examination before and after (with the mean of 18.8 months) PTSMA were studied. The ratios of E/A and E/Ea were analyzed, RT-3DE was conducted to collect the images, to obtain 17-segmant volume-time curve and to calculate the parameters of rEDV, rESV, rSV and rPFR respectively. Results: The follow-up echocardiography in all 46 patients indicated that the ratio of E/Ea decreased after the operation (12.04 ± 3.29) vs (15.70 ± 5.68),P<0.001, the rSV of left ventricular anterior wall middle segment and anterior septal middle segment decreased after the operation,P<0.05, while the rPFR of anterior septal middle segment, rear septal middle segment and apical segment increased,P<0.05. Conclusion: PTSMA may improve local left ventricular diastolic function in HOCM patients, RT-3DE provides a new method and viewing angle for HOCM evaluation.

BACKGROUND:The researches about the effect of retinoic acid on the proliferation of adipose-derived stem cells are rare, and the researches on the testosterone are mainly on the inhibition of cellaging. OBJECTIVE: To study the effects of retinoic acid and testosterone or combination on the cellcycle of adipose derived stem cells. METHODS:Adipose derived stem cells were isolated from adult female Sprague Dawley rats with 2 months age and cultured in vitro til passage 3 adipose derived stem cells, and then the 3rd passage adipose-derived stem cells were performed with adipogenic induction, osteogenic induction and surface marker identification. The cells were divided into six groups:(1) Control group;(2) 10-5 mol/L retinoic acid group;(3) Retinoic acid group;(4) 10-5 mol/L retinoic acid+testosterone group;(5) 10-6 mol/L retinoic acid+testosterone group;(6) Testosterone group. The adipose-derived stem cells in the control group were cultured with Dulbecco’s modified Eagle’s medium+10%fetal bovine serum culture medium, and the adipose-derived stem cells in the other five groups were induced with corresponding dose of retinoic acid and testosterone on the basis of control group. After cultured for 36 hours, the flow cytometry was used to detect the changes of cellcycle. RESULTS AND CONCLUSION:Compared with the control group, cellproportions in phase G 1 of 10-5 mol/L retinoic acid group and 10-6 mol/L retinoic acid group were increased significantly, and the cellproportions in phase S were decreased. Compared with control group, the cellproportion in phase G 1 of testosterone group was significantly reduced, and the cellproportion in phase S was increased. Compared with 10-5 mol/L retinoic acid group and 10-6 mol/L retinoic acid group, cellproportions in phase G 1 of 10-5 mol/L retinoic acid+testosterone group and 10-6 mol/L retinoic acid+testosterone group were reduced significantly and the cellproportions in phase S were increased. Retinoic acid can inhibit the cellcycle of adipose-derived stem cells in phase G 1 , and delay the process of the cellcycle from phase G1 to phase S;while testosterone can promote the cellcycle of adipose-derived stem cells from phase G1 to phase S;the combination induction of retinoic acid and testosterone can accelerate the process of the cellcycle of adipose-derived stem cells from phase G 1 to phase S.

Mitochondrial dysfunction has been implicated in the aetiology of sporadic Parkinson's disease but its role in the disease mechanism remains unclear.To investigate the effect of synuclein on mitochondrial dysfunction induced by rotenone.The human dopaminergic SH-SY5Y cells were used as a cell model.The cells over-expressed the wild-type ?-synuclein were treated with complex I inhibitor rotenone.The cell viability,complex I activity,Mitochondrial swelling and O2-content were tested at different time point-1w,2w,4w after rotenone treated.CCK-8 test results showed that the cell viability of overexpressed ?-synuclein(SH-SY5Y-Syn)was much lower than the control group(SH-SY5Y-Ctr).After administrating with rotenone about 1w or 2w the cell viability of SH-SY5Y-Syn became higher than that of SH-SY5Y-Ctr.On the 4th week the results were contrary to the first 2 weeks.Similar results were got when test the mitochondrial function.In the first 2 weeks after roteoone administrating,the mitochondrial function of SH-SY5Y-Syn was better than that of SH-SY5Y-Ctr.This suggest that the ?-synuclein could protect the mitochondrial against the injury induced by rotenone in the early stage-1w,2w,while this effect disappeared in the final stage-4w.

Objective:To identify the effect of ?-synuclein overexpression on mitochondrial membrane structure with atomic force microscopy. Methods:?-syn expression was mediated by AAV (adeno-associated viral vector) and Recombinant AAV/?-syn and AAV/LacZ viral particles were stereotaxically injected in the left side of rat substantia nigra (SN) for rat model of ?-synuclein overexpression. Mitochondria were isolated from rats SN of Brain. Mitochondria were analysis with JC-1 staining,atomic force microscopy and Western blot. Results:By 16 weeks post-infection of AAV-?-syn,the level of ?-syn increased about 2 times in mitochondrial fraction with Western blot and mitochondrial membrane potential (??) decreased with JC-1 staining. Furthermore,mitochondria swelling and porous like structure formed on the mitochondrial membrane with atomic force microscopy. Conclusion:The data suggested that ?-syn could accumulate in mitochondria,might form mitochondrial membrane pores and lead to ?? decreases. ?-syn might lead to mitochondrial dysfunction in Parkinson's disease.

A strain of yeast capable of hydrolyzing ethyl ester of racemic Ketoprofen with high enantioselectivity has been isolated from soil after two-step enrichment. The yeast was identified as Trichosporon brassicae. The process of growth and enzyme production was investigated. The catalytic performance of the resting cell of KET4 in kinetic resolution of Ketoprofen was also investigated. When the conversion of substrate reached 41% , enantiomeric excess of the (S) - Ketoprofen produced was 91 % , indicating a high enantiomeric ratio of 45.