Aim To study the mechanisms of N-demethyl-clarithromycin-induced apoptosis in human cervical cancer cell line HeLa. Methods MTT, photomicroscopical observation, DNA agarose gel electrophoresis, LDH release and Western blot were used for apoptosis assay. Results N-demethyl-clarithromycin inhibited growth of HeLa in a time-dependent manner. Apoptotic bodies were found with Hoechst 33258 staining after treatment with 60 ?mol?L-1 N-demethyl-clarithromycin. DNA fragmentation was observed in N-demethyl-clarithromycin treated HeLa cells. The Akt inhibitor and the ERK inhibitor (PD98059) increased cell death. The expression of anti-apoptotic protein Akt, phosphorylated-Akt, ERK and phosphorylated-ERK decreased. Conclusion N-demethyl-clarithromycin induces HeLa apoptosis through Akt and ERK expression and phosphorylation.

Objective To explore the effect of CYP2D6 gene polymorphism on blood concentration,therapeutic efficacy and adverse effects of anti-depression drug venlafaxine.Methods 69 cases of patients with depression were selected randomly from southern region of FuJian,China.The blood concentration of venlafaxine was detected by HPLC,and the CYP2D6 genotype was determined by sequencing with the amplified PCR products from peripheral blood DNA.The therapeutic efficacy and adverse effects of venlafaxine were evaluated by Hamilton depression scale(HAMD) and treatment emergent symptom scale(TESS) respectively.Results Subjects was divided into CC,CT,TT three groups based on rs16947 locus genotyping.The blood concentrations of venlafaxine were (157.35±15.63) ng/ml,(70.17±5.11) ng/ml,(115.72± 10.2) ng/ml respectively and there was no significant difference (F=1.257,P=0.301).The dose-corrected concentrations and normalized concentrations were not significantly different (F=1.683,1.547,P＞ 0.05).Similarly,the reduction rate of HAMD (CC:(40.6 ± 7.23) ％,CT:(51.7±7.09)％,TT:(42.8±14.1)％) and TESS scores (CC:1.3±0.21,CT:1.3±0.36,TT:1.2±0.28) were not significantly different either (P＞0.05).In 69 samples in this study,genotyping of rs3892097 locus only found GG type,and no further examination was performed.Genotyping divided rs1065852 locus into CC,CT,TT three groups.The blood concentrations of venlafaxine were (42.87±9.9) ng/ml,(64.25 ± 13.59) ng/ml,(181.56± 14.15) ng/ml respectively,and there was significant difference among the three groups (F=4.893,P=0.016).The dose-corrected concentrations and normalized concentrations were also significantly different (F=3.985,3.648,P＜0.05).The reduction rate of HAMD (CC:(42.6±8.23) ％,CT:(48.8± 10.8) ％,TT:(63.4±9.15) ％) was not significantly different (F=2.961,P=0.07).The difference of TESS scores was similar to that of HAMD reduction rate.Conclusion Among the 3 loci studied,only rs1065852 locus within CYP2D6 gene can affect its enzyme activity and then influence the therapeutic efficacy and adverse effects of venlafaxine.

Objective To study the effects of social isolation (SI)on the spatial and nonspatial cognitive ability in mice.Methods The postnatal 21 day kunming mice were divided into control group,SI 2 weeks group,SI 4 weeks group,SI 8 weeks group and SI 2 weeks gregarious group according to randomized block design,with ten animals each.SI 2 weeks group,SI 4 weeks group and SI 8 weeks group were isolated for 2,4 and 8 weeks respectively,SI 2 weeks gregarious group would be housed under normal grouped housing condition after 2 weeks isolation until adult,the relative control groups were the same age as the relative SI and SI gregarious group.All animals were measured the spatial and nonspatial cognitive ability by carrying the object recognition test(ORT) and object location test (OLT) after the treatment.Results In the ORT,compared to the relative control group,the discrimination index in the SI 2 weeks group,SI 4 weeks group and SI 8 weeks group ( ( - 0.03 ± 0.003 ),( - 0.11 ±0.02) and( - 0.21 ± 0.02 ) respectively) were strikingly lower than the relative control group ( ( 0.29 ± 0.03 ),(0.13±0.07) and (0.09 ±0.03) respectively) (P＜0.05).In the OLT,compared to the relative control group,the discrimination index in the SI 2 weeks group,SI 4 weeks group and SI 8 weeks group( ( -0.15 ±0.02),( -0.30± 0.02),( - 0.32 ± 0.02 ) respectively ) were strikingly lower than the relative control group ( (0.33 ± 0.02 ),(0.41 ± 0.03 ),(0.27 ± 0.04)respectively)(P＜ 0.05 ),while the SI 2 weeks gregarious group with the resocialization to the normal housing condition showed no change.Conclusions 2 weeks,4 weeks and 8 weeks isolation on mice lead to the spatial and nonspatial cognition deficits,while the resocialization to the normal housing condition could recover the damage.

Objective:To explore the effect of methylphenidate (MPH) sustained-release tablets on the sleep characteristics of children with attention deficit hyperactivity disorder (ADHD).Methods:A total of 23 children with ADHD were included in the MPH group, and treated with sustained variable doses of methylphenidate sustained-release tablets, and overnight polysomnograms (PSG) were performed at baseline, 2 weeks of treatment, and 6 weeks of treatment.At the same time, 21 matched normal children were recruited as control group for PSG.SPSS 22.0 was used for statistical analysis, and the mean ± standard deviation, M( P25, P75) and percentage were used for statistical description according to the type of data.Paired t test or analysis of variance was used for comparison of sleep parameters. Results:At baseline, children in MPH group had lower sleep efficiency (SE (%)) ((86.7±12.4)%, (90.9±7.5)%), longer sleep latency (SOL) ((21.1±12.4) min, (18.1 ±13.0) min), shorter rapid eye movement onset latency (ROL) ((145.2±35.2)min, (155.6±57.7)min), and the differences were statistically significant (all P<0.05). Compared with baseline, children in MPH group after 2 weeks of treatment had prolonged SOL ((27.2±6.4)min, (21.1±12.4) min), shortened ROL((127.2±32.1) min, (145.2±35.2) min) and REM phase time((70.5±13.8) min, (79.8±15.3)min) and significantly lower SE (%) ((83.1±15.4)%, (86.7±12.4)%), and the differences were statistically significant (all P<0.05). There was no significant difference in the SOL, ROL, REM phase time, and SE (%) sleep parameters of children in the MPH group after 6 weeks of treatment and baseline (all P>0.05). The sleep parameters such as %TST, number of awakenings and time of awakening of WASO in N1, N2, N3 and R phase of MPH group were not statistically significant among baseline, 2 weeks of treatment and 6 weeks of treatment (all P> 0.05). Conclusion:Children with ADHD present lower sleep efficiency, more difficulty to fall asleep, and shortened REM latency.MPH has a certain negative effect on the sleep of ADHD children in the first 2 weeks, which worsens the sleep problems of ADHD children.After 6 weeks of continuous treatment, the effect of MPH on sleep gradually improved.