Objective: To examine the correlation between paliperidone plasma concentration and clinical efficacy in the patients with schizophrenia. Methods:Totally 50 schizophrenia patients were treated by paliperidone. The plasma concentration of paliperidone was monitored by RP-HPLC at the weekend of the 2 nd, 4 th and 6 th week, the clinical efficacy was evaluated using the positive and negative syndrome scale ( PANSS) , and the correlation between paliperidone plasma concentration and clinical efficacy was analyzed. Results:The mean plasma concentration of paliperidone was (31. 89 ± 17. 36) ng·ml-1 at the weekend of the 6th week, and no cor-relation was found between paliperidone plasma concentration and the clinical efficacy (r=0. 146,P=0. 074). Paliperidone plasma concentration in 12 patients with adverse drug reactions (ADR) was higher than that in the patients without ADR [(45. 87 ± 19. 21)ng ·ml-1 vs (27. 06 ± 11. 13) ng·ml-1, P <0. 01]. Conclusion: Paliperidone plasma concentration shows significant individual differences. With the increase of paliperidone plasma concentration, clinical efficacy isn't necessarily improved, while the incidence of ADR may be increased. Therefore, the monitoring of paliperidone plasma concentration is recommended to optimize the therapeutic reg-imen.

ObjectiveTo investigate the effect of Genistein (GST) on cell cycle and apoptosis in PC12 cells transfected App695MT gene.MethodsPC12 cells were transfected with pIRES2-EGFP plasmid or pIRES2-EGFP/APP695MT expression plasmid,and then were divided into control vectortransfected group,APP695 transfected group and GST treatment group.Flow cytometry was applied to detect cell cycle and apoptosis,laser confocal microscope was used to observe morphological changes of cell apoptosis.ResultsCompared with control vectortransfected group,PC12 cells in APP695 transfected group increased significantly in G0 and G1 phase,and less into S phase,cell proliferation index was decreased significantly( (55.6 ±0.57)％,P＜0.0l ),apoptosis rate was increased significantly( (77.10 ± 12.53)％,P＜0.01 ).Emitted red fluorescence increased significantly when cell death,cell body swelling,organelle disintegration,nuclear condensation or fragmentation.Compared with APP695 transfected group,PC12 cells in GST( 15μ mol/L) treatment group,decreased significantly in G0 and G1 phase,and more into S phase,cell proliferation index was increased significantly ( ( 61.57 ± 0.47 ) ％,P ＜ 0.01 ),apoptosis rate was decreased significantly ( (46.00 ± 8.43 ) ％,P ＜ 0.01 ).Cell death was significantly reduced red fluorescence,emitted green fluorescence was significantly enhanced,compared with APP695 transfected group cell morphology improved.ConclusionGST can improve APP695MT gene caused cell cycle arrest,promote cell to S phase transition,reduce apoptosis rate in PC12 cells,and have a protective effect on transfected cells.

PURPOSE: This study aimed to identify the differences in functional fitness between older adults who were at risk of falling and those who were not. METHODS: A total of 104 older adults aged 65-74 years were recruited from a local community senior center. They were independent older adults without a history of falls in the preceding 12 months. Falling risk status was assessed using the Fall Risk Test. Five dimensions of functional fitness with seven testing parameters (i.e., 30-second chair stand test, 30-second arm curl test, 2-minute step test, chair sit and reach test, back scratch test, 8-foot up and go test, and body mass index) were evaluated by the Senior Fitness Test. RESULTS: Only 78 participants completed all the tests, of which 48 participants were identified with risk of falling, and 30 participants were free from risk of falling. Results from multivariate analysis of variance found significant differences on the combined outcome variables, especially in the 8-foot up and go test, 2-minute step test, and 30-second arm curl test. Results from discriminant analysis found a significant discriminant function among all the seven testing parameters, where the 8-foot up and go test, and the 2-minute step test contributed most. CONCLUSIONS: Older adults who are at the early stage of risk of falling tend to have lower functional fitness capacities, especially in agility and dynamic balance, aerobic endurance as well as in a combined relationship among all the testing parameters.
*Accidental Falls ; Aged ; Aged, 80 and over ; Aging/*physiology ; Female ; Hong Kong ; Humans ; Male ; *Physical Fitness ; Risk Factors

Objective To investigate the effects of osthole on neural stem cells ( NSCs) differentiation and explore the potential mechanism. Methods Brain-derived NSCs from newborn mice were isolated and cultured in vitro and determined by immunofluorescence. The P5 generations of NSCs were placed in culture solution with osthole at concentrations of (0,10,50, 100 μmol·L-1 ) . The neuron, astrocyte and oligodendroglia cell differentiation were determined by immunofluorescence. The mRNA expression of Notch 1 and its target genes Mash 1 and Neurogenin 2 were assessed by RT-PCR. Results The neurosphere displayed Nestin and Sox 2-postive by immunofluorescence, suggesting that the cultured cells were NSCs. Osthole promoted NSCs differentiating into more neuron(P<0. 01) and oligodendrocyte(P<0. 05), but not astrocyte. Meanwhile, osthole significantly reduced the mRNA expression of Notch 1(P<0. 01) and increased Ngn 2(P<0. 01)at the dose of 100 μmol·L-1. Conclusion Osthole enhances NSCs differentiating into more neuron and oligodendrocyte via probablly inhibiting Notch signal pathway.

AIM:To explore the protective effect of osthole on the SH-SY5Y cells transfected with APP595/596 gene, and to investigate the molecular mechanism.METHODS:The SH-SY5Y cells were transfected with APP595/596 gene in vitro for establishing a cell model to study the pathogenic role of amyloid β-protein ( Aβ) .The cell viability was detected by CCK-8 assay.The release of lactate dehydrogenase ( LDH) was determined by the colour reaction of dia-phorase-INT.The cell apoptotic rate was analyzed by flow cytometry.The expression of β-site APP cleaving enzyme 1 ( BACE1) at mRNA and protein levels was detected by RT-PCR and Western blot.The expression of Aβwas measured by the technique of immunofluorescence cytochemistry and Western blot.RESULTS: Treatment with osthole inhibited the LDH release, and increased the viability of the cells.The percentage of apoptotic cells was also significantly decreased. Osthole also inhibited the expression of BACE1 at mRNA and protein levels and the protein expression of Aβ.CONCLU-SION:Osthole has protective effect on SH-SY5Y cells transfected with APP595/596 gene.The mechanism may be associ-ation with inhibiting the mRNA and protein expression of BACE1.

Aim To investigate the effects of osthole ( Ost) on the ability of proliferation and differentiation in APP transduced neural stem cells( NSCs) , and neu-ronal apoptosis, in order to find related mechanism. Methods A model of Alzheimer′s disease( AD) cells was successfully established by transducing APP gene into NSCs in vitro. The ability of proliferation and dif-ferentiation was tested by staining. The viability of NSCs was determined by using CCK-8 assay. The cell apoptosis was tested by Hoechst 33258 staining. The expression of GSK-3β and β-catenin mRNA was deter-mined by RT-PCR. The expression of GSK-3β and β-catenin protein was determined by Western blot. Re-sults The ability of proliferation had increased by 10 . 24% with Ost treatment, compared with APP group. The ability of differentiation had increased by 6 . 74%with Ost treatment, compared with APP group. The vi-ability of NSCs had increased and cell apoptotic rate had decreased significantly. From the results of RT-PCR and Western blot, we could find the expression of GSK-3βmRNA and protein had decreased, and the ex-pression of β-catenin mRNA and protein had increased significantly, compared with APP group. Conclusion Ost could enhance the ability of proliferation and dif-ferentiation into more neurons of NSCs transducing APP gene, and reduce neuronal apoptosis. It might be relat-ed with activiting Wnt/β-catenin signaling pathway.

BACKGROUND:Neural stem cells have self-renewal and multidirectional differentiation potential, but under normal circumstances, the number of neural stem cells is less, and most cells are in the resting state. Thus, to promote the proliferation of neural stem cells is the key to the treatment of neurodegenerative diseases. OBJECTIVE:To investigate the effects of osthole on the proliferation of neural stem cells cultured in vitro, and to analyze its mechanism underlying promoting the proliferation. METHODS:Neural stem cells were cultured in vitro, and passage 3 cells were cultured with different concentrations of osthole(10, 50 and 100μmol/L). After 24 hours, cellvitality was determined by cellcounting kit-8. After 3, 5, 7 days of further culture, the radius of neurospheres was measured, and Ki67-positive cells were counted by immunofluorescence staining. Meanwhile, after 3 days of further culture, the gene expression of Notch 1, Hes 1 and Mash 1 in neural stem cells was detected by RT-PCR. RESULTS AND CONCLUSION:Compared with the control group, 50, 100μmol/L osthole could obviously promote the proliferation ability of neural stem cells. 100μmol/L osthole had the most significant effect and increased the expression of Notch 1 gene, Hes 1 gene, but it had no effect on Mash 1 gene. These results suggest that osthole can promote proliferation of neural stem cells cultured in vitro and its mechanism may be associated with activation of Notch 1 gene and Hes 1 gene in Notch signaling pathway.

Aim To investigate the effect of osthole on neuron synapses infected APP gene and its underlying mechanism. Methods The neurons were divided into three groups:GFP, APP, APP+Ost groups. The neu-rons were infected APP gene with containing mutational site in vitro for mimicking the characterstics of Alzhei-mer’ s disease ( AD) . The cell viability was assessed by CCK-8 , the expression of synapsin-1 was deter-mined by immunofluorescence, and the concentration of PSD-95 and SYP were detected by ELISA. The ex-pressions of Aβ1-42 , CAMKK2 , phoshorylated AMPKα1 , AMPKα1 protein were determined by West-ern blot. Results Strong APP staining was visible in neurons infected with APP and abundant expression of Aβ1-42 , a neurotoxic oligomer. Compared with APP group, APP+Ost group significantly increased cell vi-ability, promoted the expression of synapsin-1, up-reg-ulated the concentration of PSD-95 and SYP, and de-creased the expressions of CAMKK2 and p-AMPKα1 . Conclusions Ost can protect the neuron synapses a-gainst infected with APP gene. Its neuroprotective effect may be related to inhibiting the CAMKK2/AMPK signal pathway.

Aim To investigate the effects of neurotro-phin-3 ( NT-3 ) gene overexpression on the differentia-tion into cholinergic neuron of neural stem cells ( NSCs) in vitro and its underlying mechanism. Meth-ods Brain-derived NSCs from newborn mice were iso-lated and cultured in vitro and determined by immuno-fluorescence. The NSCs were divided into three groups: NSCs, GFP-NSCs and NT-3-NSCs groups. The expression of NT-3 was detected by immunofluo-rescence and ELISA. Then, the ability of NSCs on dif-ferentiation into cholinergic neuron was detected by im-munofluorescence and RT-PCR, and the Acetylcholine Assay Kit was used for acetylcholine ( ACh) , and the expression of Hes1 , Mash1 and Ngn1 mRNA was de-termined by RT-PCR. Results The neurosphere dis-played Nestin and Sox 2-postive by immunofluores-cence, suggesting that the cultured cells were NSCs. The proportion of ChAT immunopositive cells was sig-nificantly higher in the NT-3-NSCs group than that in the other two groups ( P <0. 01 ) . Ach secretion in NT-3-NSCs was significantly elevated compared with the other two groups ( P <0. 01 ) . NSCs transfected with NT-3 increased the levels of Mash1 and Ngn1 mR-NA, and decreased the level of Hes1 mRNA ( P <0. 05 ) . Conclusion NT-3 can significantly promote the in vitro differentiation of NSCs into cholinergic neu-rons via probablly inhibiting Notch signaling pathway.

Objective To investigate the reliability and validity of Simple Facial Grading System (SFGS) in patients with idiopathic facial palsy. Methods 80 patients with idiopathic facial palsy were evaluated with the House-Brackmann (H-B) scale and SFGS before and every 2 weeks after treatment until 12 weeks or recovery. They were assessed by 2 testers before and 2 weeks after treatment. The results were analyzed and compared. Results The Cronbach's α coefficient was 0.93 of SFGS, and 0.74 of H-B scale. The intraclass correlation coefficient (ICC) between testers was 0.84 or higher of SFGS, and 0.77 or higher of H-B scale. The Spearman's rank correlation coefficient between SFGS and H-B scale was 0.73, Kappa coefficients was 0.81 for grade II, 0.74 for grade III, 0.49 for grade IV, 0.66 for grade V, and 0.92 for grade VI. The scores of SFGS and H-B scale positively correlated with the recovery time. Conclusion SFGS is a kind of evaluation for peripheral facial paralysis with satisified reliability and validity, which can be applied to evaluate the severity and outcome during acute stage.