Objective:To investigate the pharmacokinetics of mycophenolic acid( MPA)and its metabolites in different stages af-ter the administration of enteric-coated mycophenolate sodium( EC-MPS)tablets in Chinese liver transplant recipients. Methods:The blood samples of 24 patients were collected in 0-12h of the 1st and 3rd week after the administration of EC-MPS. The concentrations of MPA,AcMPAG and MPAG in plasma were measured by LC-MS/MS developed in our lab. The pharmacokinetic parameters of MPA and its metabolites were estimated by non-compartmental method. Results:After 1-and 3-week therapy with EC-MPS,Cmax ,AUC0-12 and t1/2 was(18. 1 ± 8. 75)and(20. 7 ± 16. 0)μg ml-1 ,(42. 7 ± 17. 5)and(47. 1 ± 23. 9)μg·h·ml-1 ,(3. 33 ± 2. 81)and (3.30 ±1.89)h for MPA;(2.50 ±1.86)and(1.78 ±1.72)μg·ml-1,(14.5 ±11.7)and(6.97 ±6.57)μg·h·ml-1, (4. 48 ± 2. 53)and(3. 76 ± 1. 8)h for AcMPAG;(171. 6 ± 135. 4)and(152. 2 ± 115. 9)μg·ml-1 ,(1299 ± 1 204)and(1 051 ± 561)μg·h·ml-1 ,(8. 73 ± 4. 25)and(7. 75 ± 2. 87)h for MPAG,respectively. There was no significant difference in the PK parameters of MPA after the 1-and 3-week therapy. The Cmax ,Tmax and t1/2 of MPA in the patients received EC-MPS were significantly higher than those in the patients received MMF(P<0. 05). Cmax and AUC0-12 of MPAG in the patients received EC-MPS were signifi-cantly higher than those in the patients received MMF after the 3-week therapy(P<0. 05). Conclusion:There is no significant accu-mulation of MPA after the therapy with EC-MPS at different stages. The absorption of MPA is delayed after the therapy with EC-MPS compared with that with MMF. There is no difference in MPA exposure between EC-MPS and MMF in Chinese liver transplant patients.

ObjectiveTosurvey obsessive-compulsivesymptomof childrenandadolescents.Methods4335 children and adolescents aged ( 13.88 ± 2.44) year-old (47.7％ male) were measured with leyton obsessional inventory-child version (LOI-CV).ResultsThe frequency of total yes/no score of LOI-CV manifests as normal distribution,while the frequency of total interfering score manifests as J curve.Total yes/no scores of female were higher than that of male ( ( 8.55 ± 3.87 ),(8.21 ± 3.99),t =2.86,P ＜ 0.01 ) ; the difference of country and city were not significant ( ( 8.57 ± 3.86),( 8.35 ± 3.9 ),t =1.32,P ＞ 0.05 ).Primary school ( n =937 ),junior high school ( n =1906 ),senior high school ( n =1492 ) exited significant difference ( (7.86 ± 3.82),( 8.52 ± 3.93 ),( 8.55 ± 3.891 ) respectively,F =11.03,P ＜ 0.01 ).The total interfering scores of male were higher than that of female ( ( 11.35 ± 9.10),( 10.76 ± 8.84),t =2.18,P =0.03 ).The total interfering scores of country were higher than that of city( ( 11.86 ±9.18),( 10.88 ±8.92),t=2.61,P＜0.01 ) ;the difference of primary school,junior high school and senior high school were significant ( ( 10.05 ± 8.76 ),( 11.73 ± 9.17),( 10.77 ± 8.76),F =12.088,P ＜ 0.01 ).The total interfering score from grade four of primary school to grade three of senior high school were( 10.0 ± 8.78),( 10.01 ± 8.64),( 10.19 ± 8.92),( 11.43 ±9.16),(11.40 ±8.67),(12.58 ±9.76),(10.32 ±8.42),(10.19 ±8.38),(12.48 ±9.69) respectively(F=5.90,P＜0.01 ).The two grades of the highest total interfering score were grade three of junior high school and grade three of senior high school.ConclusionObsessive-compulsive symptom are common in children and adolescents.Children and adolescents of male grade three of junior high school or senior high school in the country are more probably interfered by obsessive-compulsive symptom.

Objective To investigate the dose-response relationship of the treatment temperatures and heating time on human cervical carcinoma hela cells,aiming at providing experimental evidences for clinical hy-perthermia. Methods Hela cells were heated at 37 ～ 70 ℃ in temperature-controlled water baths, the tempera-ture was divided into nine groups,each time was divided into eight subgroups (1 ～ 30 min). The morphology changes of cells after hyperthermia were detected by inverted microscope. Proliferation rates were measured by MTT colorimetric assay. The apoptesis rates were determined by flow eytometric analyse. The levels of prolifera-ring cell nuclear antigen (PCNA) were measured with immunohistochemistry. Results lnereaseing the heating time at the same temperature, or increaseing heating temperature at the same time, the cell proliferation, survival rates and PCNA expression decreased. There was no significant morphological change about cells ,but have small amount of apoptosis and a direct role of the suppression and destruction at 41 ℃ and 43 ℃ group. A large num-ber of cells shrinked to round and a major role for apoptosis at 46℃ group. Cell necrosis was major role at 50 ℃and 55 ℃ group. More than 55 ℃ for necrotic cells. Conclusion With the increase of heating temperature and heating time, its treatment of Hela cells gradually enhance. So combining dose-effect relationship of hyperthermia temperature and time can reach the best therapeutic effects.

Objective:To optimize the parameters of the equation of sagittal craniofacial structures with different classes of malocclusion using genetic algorithms(GAS), and to explore the rules .Methods:A total of 240 patients with average angle malocclusion aged 8-18 years old were divided into three groups: Angle Class Ⅰ(n=79), Angle Class Ⅱ(n=76)and Angle Class Ⅲ(n=85) groups.In each group 10 cases were randomly selected as the test samples, the rest as the experimental samples.The cephalometric analysis was performed on all the patients'' cephalograms, and the results of Ba-N,Ba-A,Ba-S,S-Ptm,Ptm-A,Ba-Ar,Ar-Go,Go-PoG,Ba-PoG and N-S-Ar were analyzed by two independent samples t-test and One-Way ANOVA. The relevant influencing factors of craniofacial structures were found.The parameters of the equation was optimized to obtain the relevant equations using GAS.The predicted values of the optimized equation were compared with the measured values.Results:There were no significant differences in sex between Angle Class Ⅰ, Class Ⅱ and Class Ⅲ groups(P> 0.05);when the men and women with the same type were combined,the Ba-A,Ptm-A,Ar-Go,and Ba-PoG had statistically significant differences between Angle Class Ⅰ, Class Ⅱ, and Class Ⅲ groups (P<0.05).The correlation analysis results showed that in Angle Class Ⅰgroup:Ba-A was positively correlated with Ba-N (r=0.683),Ptm-A was positively correlated with Go-PoG (r=0.738), Ar-Go was positively correlated with Ba-PoG (r=0.833), and negatively correlated with Go-PoG (r=-0.560) and Ba-PoG was positively correlated with Go-PoG (r=0.669);in Angle class Ⅱ group,Ba-A was positively correlated with Ba-PoG and Ba-N(r=0.884,r=0.883), Ptm-A was positively correlated with Ba-A (r=0.742),Ar-Go was positively correlated with Ba-PoG (r=0.401)and negatively correlated with Go-PoG (r=-0.317) and Ba-PoG was positively correlated with Ba-A and Go-PoG(r=0.883,r=0.488);in Angle Class Ⅲ group,Ba-A was positively correlated with Ba-N and Ba-PoG(r=0.891,r=0.829),Ptm-A was positively correlated with Ba-A (r=0.807)and negatively correlated with Ba-S (r=-0.404),Ar-Go was positively correlated with S-Ptm (r=0.548) and Ba-PoG was positively correlated with Ba-A (r=0.829).The equation of sagittal craniofacial structure with different occlusal classes was established by GAS.In Angle Class Ⅰgroup:Ba-A(mm)=10.963 9+0.859 8×Ba-N,Ptm-A(mm)=6.897 6+0.557 0×Go-PoG,Ar-Go(mm)=-2.548 2+0.511 8×Ba-PoG-0.5272×Go-PoG,Ba-PoG(mm)=17.515 6+1.021 3×GO-POG;in Angle Class Ⅱ group:Ba-A(mm)=-2.121 3+0.567 6× Ba-PoG+0.513 2× Ba-N,Ptm-A(mm)=13.788 7+0.349 4×Ba-A,Ar-Go(mm)=2.447 7+0.368 8×Ba-PoG-0.427 9×Go-PoG,Ba-PoG(mm)=-7.140 2+0.751 3×Ba-A+0.295 4×Go-PoG;in Angle Class Ⅲgroup:Ba-A(mm)=3.281 0+0.545 3×Ba-N+0.394 4× Ba-PoG,Ptm-A(mm)=3.535 8+0.63 1×Ba-A-0.614 2×Ba-S,Ar-Go(mm)=-9.002 1+1.004 3×S-Ptm,Ba-PoG(mm)=-2.091 2+1.057 5×Ba-A.There were no significant differences between the predicted values of GAS and the measured data (P> 0.05), and the error was small.Conclusion: The optimal relation equation of craniofacial structure of sagittal malocclusion is established by GAS with the quantitative regularity.

Objective:To establish the quantitative relationship equation of the crantiofacial vertical points in the skeletal classⅡ malocclusion patients with various vertical types by using genetic algorithms method,and to express the measured values in the patients with different gender with the same formula.Methods:A total of 155 skeletal class Ⅱ malocclusion patients without treatment,aged from 10 to 18 years old,were selected and divided into high-angle group(n=50),average-angle group(n=58),low-angle group(n=47);5 samples were randomly selected in each group as the test samples,the rest as the experimental sample.The cephalometic radiographs were performed and measured.The relevant influencing factors of craniofacial structure were ensured.The genetic algorithm was used to optimize the equation parameters to obtain the correlation equation.The error between the predicted value and the measured value was compared.Results:The various parameters had no significant differences between different gender in high-angle,average-angle and low-angle groups(P>0.05);then the men and the women with same type were combined,most of the indicators had statistically significant differences between three groups (P<0.05).The correlation analysis results showed that there was a positive correlation between age and Ans-U1(r=0.470),there was a positive correlation between N-Me and Ans-Me(r=0.964);for Ans-U1 ,there was a positive correlation with Ans-Me(r=0.805)and negative correlation with facial angle;there was a positive correlation between N-Go and N-Me (r=0.926);for L1-Me,there was a positive correlation with Ans-Me(r=0.898)and negative correlation with the angle of Go(r=-0.468)in high-angle group. In average-angle group,there was a positive correlation between age and N-Me (r=0.531);for Ans-U1,there was a positive correlation with Ans-Me(r=0.878)and negative correlation with the facial angle(r=-0.262);for Ans-Me,there was a positive correlation with N-Me(r=0.920), negative correlation with N-Ans(r=-0.560)and negative correlation with Ar-Go(r=-0.652);for N-Go,there was a positive correlation with S-Go(r=0.867), positive correlation with N-Ans(r=0.252)and positive correlation with L1-Me(r=0.754).For S-Ar,there was a positive correlation with S-Go(r=0.671), negative correlation with Ar-Go(r=-0.250),and positive correlation with L1-Me(r=0.552).In low-angle group,for age,there was a positive correlation with S-Go(r=0.602), negative correlation with the angle of Go(r=-0.346),and positive correlation with L1-Me(r=0.576);for N-Me,there was a positive correlation with Ans-Me(r=0.869),and positive correlation with N-Go(r=0.859),and negative correlation with the facial angle(r=-0.177);for N-Ans,there was a positive correlation with N-Me(r=0.605) and negative correlation with Ans-U1(r=-0.113);for Ans-Me,there was a positive correlation with N-Me(r=0.869),positive correlation with the facial angle(r=0.070),and positive correlation with Ans-U1(r=0.785);for N-Go,there was a positive correlation with N-Me(r=0.859)and positive correlation with S-Go(r=0.829).The quantitative relationship equations of the crantiofacial vertical points in skeletal class Ⅱmalocclusion patients with various vertical types in each group were established by using genetic algorithms.In high-angle group:Age=5.883 6+0.269×Ans-U1,N-M=22.026 6+1.494 5×Ans-Me,Ans-U1=34.959 4+0.454 5×Ans-Me-0.409 7×Facial angle,N-Go=-4.588 2+0.472 4×N-Me,L1-Me=-12.590 5+0.5322×Ans-Me+0.124 3×∠Go.In average-angle group:Age=-2.944 1+0.146 8×N-Me,Ans-U1=18.917+0.476 4×Ans-Me-0.230 2×Facial angle,Ans-Me=-0.620 5+1.014 5×N-Me-0.974 1×N-Ans-0.057 6×Ar-Go,N-Go=1.631 1+0.897 8×S-Go+0.919 7×N-S+0.168 8×L1-Me,S-Ar=-1.823 1+0.845 3×S-Go-0.867 0×Ar-Go+0.202 4×L1-Me.In low-angle group:Age=11.740 6+0.152 7×S-Go-0.169 9×∠Go+0.252 5×L1-Me,N-Me=61.153 0+0.964 3×Ans-Me+0.628 6×N-Go-0.689 2×Facialangle,N-Ans=-4.949 2+1.065 8×N-Me-2.316 5×Ans-U1,Ans-Me=-25.180 0+0.418 4×N-Me+0.280 3×Facial angle+0.477 6×Ans-U1,N-Go=8.684 2+0.409 9×N-Me+0.403 3×S-Go.There was no significant difference between the predicted values of equation established with genetic algorithms and the measured data (P>0.05).Conclusion:The quantitative relationship equation of the crantiofacial vertical points in the skeletal class Ⅱmalocclusion patients with various vertical types established with genetic algorithms may show the vertical quantitative relationship and predict the growth to a certain degree.

Objective: To investigate the effect of chrysotile exposure on ribosomal DNA (rDNA) copy number and DNA damage response, so as to provide insights into the mechanism of asbestos-induced carcinogenesis. Methods: Human pleural mesothelial MeT-5A cells were treated with chrysotile suspensions at doses of 1.25, 2.5 and 5 μg/cm2 (low-, medium-, high-dose group), while PBS served as controls. MeT-5A cells were harvested 6, 24, 48 and 72 h post-treatment, and the rDNA copy numbers and the BIRC5, HRAS, GINS4 and RRM2 mRNA expression were determined using a quantitative real-time PCR (qPCR) assay. The apoptosis of MeT-5A cells and DNA damage were detected using Muse cell analyzer. The rDNA copy numbers, DNA damage responses and BIRC5, HRAS, GINS4 and RRM2 mRNA expression were compared in MeT-5A cells treated with different doses of chrysotile suspensions. Results: There were significant differences in 45S rDNA copy numbers among low-, medium-, high-dose groups and the control groups 6, 48 and 72 h post-treatment with chrysotile suspensions, and significantly lower 45S rDNA copy numbers were measured in low-, medium- and high-dose groups than in the control group 6 h post-treatment, while significantly higher 45S rDNA copy numbers were found in the high-dose group than in low- and medium-dose groups 48 and 72 h post-treatment (all P<0.05). There were significant differences in 5S rDNA copy numbers among low-, medium-, high-dose groups and the control groups 24, 48 and 72 h post-treatment with chrysotile suspensions, and significantly lower 5S rDNA copy numbers were measured in medium- and high-dose groups than in the control group 24 and 48 h post-treatment, while significantly lower 5S rDNA copy numbers were found in medium- and high-dose groups than in the low-dose group 24, 72 h post-treatment (all P<0.05). There were significant differences in the overall apoptotic rate of MeT-5A cells among groups at different time points, and the overall apoptotic rate of MeT-5A cells were significantly higher in medium- and high-dose groups than in the control group (all P<0.05), with late-stage apoptosis predominantly detected. There were significant differences in the rates of ATM activation and DNA double-strand break in MeT-5A cells among groups 72 h post-treatment, and higher rates of ATM activation and DNA double-strand break were measured in medium- and high-dose groups than in the control group (all P<0.05). In addition, there were significant differences in the relative mRNA expression of BIRC5, HRAS, GINS4 and RRM2 genes among groups 24 and 48 h post-treatment, and significantly lower BIRC5, HRAS, GINS4 and RRM2 mRNA expression was quantified in medium- and high-dose groups than in the control group (all P<0.05). Conclusion Exposure to chrysotile may induce rDNA copy number variations and altered expression of nucleolar proteins in human pleural mesothelial cells, which may be involved in the regulation of DNA damage responses.

ObjectiveTo develop school refusal reason inventory (SRRI)for children and adolescents in China and assess its reliability and validity.MethodsThe primary SSRI was made based on clinical interviews and literatures.Pretest was carried out in a small sample from a clinic.Then the final SSRI was developed after qualitative analysis and item analysis.SRRI,the Screen for Child Anxiety Related Emotional Disorders(SCARED) and Child Depression Inventory(CDI) were administered to school refusers from 7 schools in Shenyang.All the schools were selected from Shenyang City and its countryside by cluster sampling.Some of the students were retested after one month.Descriptive statistics and exploratory factor analysis were carried out to examine the reliability and validity of SRRI based on all the data.Results Item analysis indicated correlation coefficients between all the items and the total marks were higher than 0.3,and they were significant.All the critical ratios of the items were higher than 0.3.The 43 items were divided into six factors ( educational modality,factor of teachers,relationship with classmates,separated anxiety,study attitude and study environment) by exploratory factor analysis.The factor loading values were 0.372 ～0.848.The cronbach's α of each factor was 0.827,0.831,0.759,0.623,0.821 and 0.808.Retest reliability was 0.644 (P ＜ 0.01 ).Its correlation coefficient with SCARED was 0.452 and 0.548 with CDI.ConclusionAccording to Chinese cultural back ground,the SSRI corresponds with psychometric indexes.There are good reliability and validity.It is helpful to understand the reasons of school refusal behavior in children and adolescents.

Objective: To explore the functional connectivity between the visual brain regions and whole brain in children with autism spectrum disorder (ASD) at resting state, and to further analyze the correlation with their clinical manifestations. Methods: The functional magnetic resonance imaging (fMRI) data of 34 boys with ASD enrolled from ASD designated rehabilitation institutions and 29 healthy boys enrolled from several kindergartens in Heilongjiang were collected. Based on the resting-state functional connectivity magnetic resonance imaging (rs-fc MRI) analysis, the BA17 of the primary visual brain region and the BA18/19 of the higher visual brain region were taken as the regions of interest (ROI) to calculate the functional connectivity level between the visual brain regions and whole brain, and the differences between the two groups were compared. Multiple developmental scales were used to evaluate the behavior of ASD children, and Pearson correlation analysis was used to explore the relationship between functional connection strength and autistic behavior. Results: The ASD group had decreased positive connectivity between BA17 and the right fusiform gyrus (FFG), and was negatively correlated with social interaction of ADI-R and the total scores of CARS (r=-0.41, -0.48, P<0.05); ASD group had decreased positive connectivity between BA17 and the left FFG, there was a negative correlation with social motivation of SRS (r=-0.43, P<0.05); ASD group had decreased positive connectivity between BA17 and the left posterior cingulate gyrus (PCG). Children with ASD had decreased positive connectivity between BA18/19 and left calcarine fissure and surrounding cortex (CAL), which was positively correlated with attention conversion of AQ, total scores of CARS (r=0.43, 0.40, P<0.05), and the children with ASD had deceased positive connectivity between BA18/19 and right precuneus (PCUN). Conclusion In resting state, the functional connectivity of primary and higher visual brain regions and whole brain of ASD children is different from that in healthy children, and there is a significant correlation between abnormal level and autistic behaviors.

Objective To evaluate the effect of high flow nasal catheter oxygen (HFNCO) therapy on extubation failure rate,reintubation rate,and incidence of related complications within 48 h after extubation in mechanically ventilation patients.Methods A prospective,single-center,randomized controlled trial was conducted in the ICU of a teaching hospital affiliated to a medical university.A total of 77 patients with mechanical ventilation duration of ≥ 48 h and met the condition of spontaneous breathing test (SBT) were selected.The patients whose LUS ≥ 14 at 30 min of SBT were enrolled,and were randomly (random number) divided into 3 groups according to different oxygen therapies:the traditional oxygen therapy group,the noninvasive ventilation (NIV) group,and the HFNCO group.The effect of oxygen therapy and outcomes after extubation were compared among the three groups.The measurement data were presented as the mean±standard deviation (SD),and the numeration data were expressed as ratio or constituent ratio.The independent sample t test and LSD-t test were used for the comparisons between the two groups and the one-way ANOVA for differences between multiple groups.The differences between enumeration data were assessed by chi-square test.A P＜0.05 was considered statistically significant.Results There was no significant difference in gender,age and other general conditions between the two groups (P＞0.05).The NIV group and HFNCO group had lower extubation failure rate (14.29％,15.38％ vs 34.87％) and reintubation rate (10.7％,11.54％ vs 21.74％) than the convertional oxygen therapy group (P＜0.05).In addition,the traditional oxygen therapy group had longer mechanical ventilation duration [(24.33±4.42) d vs (8.58±1.09) d,(8.37±2.43) d],antibiotic use time [(19.21±4.37) d vs (8.34±2.54) d,(7.41±1.06) d],and ICU hospitalization time [(27.27±4.24) d vs (10.38±2.07) d,(9.44±0.79) d],all P＜0.05.Conclusions Treatment with HFNCO or NIV after extubation can effectively reduce the rates of extubation failure and reintubation,and improve the outcome of the mechanical ventilation.There is no difference in clinical efficiency between the NIV group and HFNCO group.However,compared with NIV,HFNCO can effectively reduce respiratory rate and avoid the retention of CO2,which has a wider application prospect in clinical practice.

Objective: To identify the functional connectivity characteristics of insula, sensory and social related brain regions in boys with autism spectrum disorder(ASD), to explore the central nervous basis of sensory abnormality affecting core symptoms in boys with ASD. Methods: Resting state functional magnetic resonance imaging (rs fMRI) data were collected from 34 boys with ASD and 29 typical development boys (TD group). Based on functional connectivity analysis, the sensory related brain regions, insula, and social related brain regions were taken as regions of interest to calculate the functional connectivity (FC) level between the regions of interest, the differences between the two groups were compared and the results were corrected by FDR. The Autism Diagnostic Observation Schedule (ADOS), Childhood Autism Rating Scale (CARS) and Autism Spectrum Quotient-Children s Version (AQ-Child) were used to assess the core phenotypes of boys with ASD. Results: Compared with the TD group, the levels of FC between tactile brain regions and insula, olfactory brain regions and insula, auditory brain regions and insula in boys with ASD group were significantly increased. The level of FC between the insula and bilateral amygdala，insula and the medial prefrontal cortex(mPFC) were significantly increased( P <0.05).Pearson correlation analysis showed that the level of FC between auditory brain region(BA42)and left insula in ASD group was negatively correlated with the scores of communication subscale of ADOS( r =-0.44)，social interaction subscale of ADOS( r =-0.43), communication & social interaction subscale of ADOS( r =-0.49),attention to details subscale of AQ-Child( r =-0.41). The level of FC between the right insula and right amygdala was positively correlated with the attention switch subscale of AQ-Child( r =0.38), the level of FC between right insula and mPFC was positively correlated with the scores of repetitive behavior subscale of ADOS( r =0.48), the attention switch subscale of AQ-Child( r =0.49), total scale subscale of AQ-Child( r =0.41), total scale of CARS( r =0.41)( P < 0.05 ). Conclusion The levels of FC between insula and sensory related, social related brain regions are abnormal in children with ASD, which have significant correlations with clinical symptoms. In depth studies can be conducted to explore underlying neutral mechanisms.