AIM:To establish a physiological-based pharmacokinetic(PBPK)model of ertapen-em in elderly patients with chronic kidney disease,and to analyze the pharmacokinetic/pharmacody-namic index f％ T＞MIC at different doses.METH-ODS:The physicochemical properties and pharma-cokinetic characteristics of ertapenem were collect-ed by reviewing the literature and databases,and a healthy adult model was established in PKSim? software,and then extrapolated to the PBPK model of the elderly.The clinical pharmacokinetic re-search data were used to optimize and validate the model,and the mean folding error(MFE)was used as the index to evaluate the prediction perfor-mance of the model.The final model was used to simulate the in vivo exposure of elderly patients with chronic kidney disease after administration,and the pharmacokinetic/pharmacodynamic index of commonly used clinical dosing regimens was an-alyzed,and the recommended dosing regimens were given.RESULTS:The MFE of the area under the curve(AUC0-t),peak concentration(Cmax)and peak time(Tmmax)predicted by the established PBPK model of ertapenem in adults were 0.92,0.79 and 1.02,respectively,and the predicted value of the optimized PBPK model of ertapenem in the elderly was also consistent with the observed value of 0.5＜MFE＜2 standards,all of which have good predictive performance.With f％ T＞MIC greater than 40％as the drug efficacy target,the minimum inhibitory concentration(MIC)is 0.5-1 μg/mL for sensitive bacteria,and elderly patients with chronic kidney disease can consider reducing the drug dose as ap-propriate.CONCLUSION:The PBPK model of ertap-enem in elderly patients with renal insufficiency has been successfully established,and the model has good prediction performance and provides a reference for clinical personalized medication in el-derly patients with renal insufficiency.

AIM:To establish a physiological-based pharmacokinetic(PBPK)model of ertapen-em in elderly patients with chronic kidney disease,and to analyze the pharmacokinetic/pharmacody-namic index f％ T＞MIC at different doses.METH-ODS:The physicochemical properties and pharma-cokinetic characteristics of ertapenem were collect-ed by reviewing the literature and databases,and a healthy adult model was established in PKSim? software,and then extrapolated to the PBPK model of the elderly.The clinical pharmacokinetic re-search data were used to optimize and validate the model,and the mean folding error(MFE)was used as the index to evaluate the prediction perfor-mance of the model.The final model was used to simulate the in vivo exposure of elderly patients with chronic kidney disease after administration,and the pharmacokinetic/pharmacodynamic index of commonly used clinical dosing regimens was an-alyzed,and the recommended dosing regimens were given.RESULTS:The MFE of the area under the curve(AUC0-t),peak concentration(Cmax)and peak time(Tmmax)predicted by the established PBPK model of ertapenem in adults were 0.92,0.79 and 1.02,respectively,and the predicted value of the optimized PBPK model of ertapenem in the elderly was also consistent with the observed value of 0.5＜MFE＜2 standards,all of which have good predictive performance.With f％ T＞MIC greater than 40％as the drug efficacy target,the minimum inhibitory concentration(MIC)is 0.5-1 μg/mL for sensitive bacteria,and elderly patients with chronic kidney disease can consider reducing the drug dose as ap-propriate.CONCLUSION:The PBPK model of ertap-enem in elderly patients with renal insufficiency has been successfully established,and the model has good prediction performance and provides a reference for clinical personalized medication in el-derly patients with renal insufficiency.

Objective To explore the reaction time and attention bias characteristics of patients with first-episode depressive disorder.MethodsTotally 32 patients with first-episode depressive disorder (MD group) and 24 non-depression control participants(NC group) matched with MD group on age,gender and education level were enrolled in the study.The clinical symptoms were assessed by Beck Depression Inventory(BDI).All participants completed a dot-probe task to assess attentional preference for facial stimuli with varying valence (happy,sad and neutral facial expressions).ResultsThe reaction times(RTs) of MD group was longer than that of NC group in the dot-probe task ((468.6±87.7)ms,(451.7±82.5)ms,P<0.01).The four-way ANOVA revealed a significant main effect of prime duration,indicating overall shorter RTs on primes with longer duration ((476.9±88.4)ms vs (456.2±82.7)ms vs (447.7±83.9)ms,P<0.01).Compared with NC group,the scores of attention bias for sad faces were decreased in MD group ((7.43±26.4)ms vs (-4.97±19.5)ms,P<0.05).With the longer duration of presentation,the score of attention maintenance of emotional facies for MD group were increased (happy faces: (-11.0±4.8)ms,(2.2±6.9)ms,(6.1±8.5)ms;angry faces:(-1.6±7.5)ms,(6.5±8.6)ms,(14.9±6.7)ms).The adherence score of attention to happy faces were decreased ((1.8±5.6)ms,(-8.2±6.7)ms,(-8.7±7.1)ms),while the score of adherence score towards sad faces were increased ((-7.6±7.2)ms,(-2.6±8.5)ms,(1.5±6.2)ms) with increasing prime duration.ConclusionPatients with first-episode depressive disorder have slower response to emotional faces and associated with attentional bias for sad faces.With the increasing prime duration,it is more and more obvious to attentional bias in the two aspects of allocation and adherence.

ObjectiveTo explore and analyze the effect of simulation-based learning combined with debriefing in neonatal resuscitation training.MethodsA total of 114 clinical medical staffs attended the neonatal resuscitation training course hold by Department of Neonatology, Quzhou Maternal and Child Health Hospital from November 2014 to May 2015, and were randomly assigned to observation (n=60) and control group (n=84) by coin tossing. Staffs in the observation group adopted to training skills with simulation-based learning combined with debriefing,while those in the control group were educated with traditional method. The examinations on theoretical knowledge were taken before and after the training. Operational exam and self-confident questionnaire for all staffs on each procedure taught in the course were taken at last. Scores of the exams and self-confident questionnaire were compared between the two groups witht-test and Mann-WhitneyU test.ResultsThe mean score of theoretical test rose up significantly after the training in both observation and control group (25.19±2.62 vs 20.17±3.71,t=7.725,P<0.01; 25.44±2.64 vs 18.90±4.27,t=11.170,P<0.01), but no difference was found in this score after the training between the two groups (t=0.492,P=0.624). The practical operation examination score in the observation group was higher than that in the control (34.05±1.34 vs 31.32±4.10,t=4.183,P<0.01). All questionnaires sent to the staffs were retrieved (100%), and the total values after the training in the observation group were higher than in the control (mean rank: 92.81 vs 57.99; rank sum:5 569 vs 4 872,Z=-4.96,P<0.01).ConclusionsSimulation-based learning combined with debriefing is a much more effective teaching methods for neonatal resuscitation training, which might quickly improve the resuscitation skills of clinical staffs.

Objective To evaluate the effects of 6-week atypical antipsychotics treatment on serum brain-derived neurotrophic factor (BDNF)level,and the correlation between BDNF level and clinical efficiency in first-episode antipsychotic-na?ve schizophrenia.Methods We recruited 39 hospitalized patients with first-episode antipsychotic-na?ve schizophrenia that met with Diagnostic and Statistical Manual of Mental Disorders—4th Edition (DSM-IV).Both Positive and Negative Syndrome Scale (PANSS)and the level of serum BDNF were measured before and after 6 weeks’treatment with atypical antipsychotics.We also studied 30 healthy controls.Serum BDNF was assayed at baseline.Results Pre-treatment BDNF level was significantly lower in the schizophrenic patients than in the controls [(6.82±2.1 5 )μg/L vs .(1 1.6 ± 3.32 )μg/L,t = 7.239,P < 0.001 ].Although BDNF level increased with treatment (t =2.349,P =0.021)in the schizophrenics,post-treatment BDNF level was still lower than in the normal controls (t =4.634,P <0.001).After 6 weeks’treatment for schizophrenia,the total score of PANSS,the scores of positive and negative symptoms,and the score of general psychopathology scale were all decreased (t =6.1 64,P < 0.001;t = 4.520,P < 0.001;t = 4.132,P < 0.001;t = 5.142,P < 0.001 ).Pre-treatment BDNF levels were directly correlated not only with the rate of decreased PANSS total score (r =0.348, P <0.05),but also with the rate of decreased negative symptoms score (r = 0.35 1,P < 0.05 ).However,pre-treatment BDNF levels were not correlated with improved positive symptoms,general psychopathology (r =0.204, 0.186,P >0.05),or duration of illness (r = - 0.058,P > 0.05 ).Changes in BDNF levels with treatment were correlated with the duration of illness (r =-0.345,P <0.05),but not with psychiatric improvement (r =0.036-0.1 74,P >0.05).Conclusion BDNF level is significantly lower in patients with first-episode antipsychotic-na?ve schizophrenia than in normal controls.It could be improved by using antipsychotics.Higher pre-treatment BDNF level may predict better response to antipsychotics.

Objective To explore the influence factors of hyperarousal,personality characteristics and coping strategies on the vulnerability to stress-related sleep disturbance.Methods A total of 345 sleep good healthy volunteers were recruited bypurposive sampling technique.Every participant completed an extensive survey that included the general condition questionnaire,Ford Insomnia Response to Stress Test (FIRST),PreSleep Arousal Scale (PSAS),NEO Personality Inventory-Revised (NEOPI-R),Coping Inventory for Stressful Situations (CISS) and Heart Rate Variability(HRV).All participants were classified as High risk group andLow risk group by using the FIRST criterion.Results The high risk group was younger than the low risk group (27.91±8.22 vs 24.82±7.73,P＜0.01),and had a higher percentage of females (34.7％ vs 53.4％,P＜0.05).The high risk group showed significantly higher scores in PSAS total (30.11±6.22),pesleep cognitive arousal (17.73± 4.51),presleep somatic arousal (12.78 ± 3.23),neuroticism (3.13 ± 0.51),emotion oriented (48.98 ± 10.54),but lower score in extraversion (2.96±0.54),then those indicators of the low risk group (28.52±5.82,16.32±4.32,11.41±2.75; 3.11±0.56,2.87±0.47,46.23±11.21,3.11±0.56,P＜0.01 or 0.05).There were significant difference between the two group in LF/HF (1.51 ±0.19 vs 1.17±0.11,P＜0.01),HF((311.21 ±72.32) ms2/Hz vs (490.43 ± 91.74)ms2/Hz,P＜0.01),LF((469.49±85.67)ms2/Hzvs (573.21±98.75) ms2/Hz,P＜0.01) in HRV.Results of linear regression analysis showed that gender,and scores of PSAS total,cognitive arousal,presleep cognitive arousal,presleep somatic arousal,neuroticism,emotion oriented and LF/HF were significant correlation with FIRST score (P＜0.01 or 0.05).Conclusion Presleep cognitive and somatic arousal,neurotic character may be the premorbid characteristics of stress-related sleep disturbance,and bad stress coping strategies are easy to promote the development of insomnia.

Objective To study the features of treatment on neurochemical metabolites in prefrontal lobe and thalamus by proton magnetic resonance spectroscopy (1H-MRS) in first-episode drug-naive patients with early-onset schizophrenia (EOS).Methods Forty-two EOS (study group) met with Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition (DSM-Ⅳ) were recruited.Prefrontal lobe and thalamus were evaluated by multi-voxel 1H-MRS before and 4-week after treatment with a single atypical antipsychotic.The levels of N-acetylaspartate (NAA),creatine compounds (Cr) and choline-containing compounds (Cho) were measured.The patients also received Positive and Negative Syndrome Scale (PANSS).Forty normal controls (normal control group) underwent the same 1H-MRS detection.Results Before treatment,the NAA/Cr ratios in left prefrontal lobe,right prefrontal lobe and lefi thalamus in study group were lower than those in normal control group (1.45 ± 0.26 vs 1.60 ± 0.34,t =2.251,P =0.027;1.43 ±0.26 vs 1.60 ±0.35,t =2.505,P=0.014;1.48 ±0.27 vs 1.65 ±0.35,t =2.470,P =0.016).After 4-week treatment,the NAA/Cr ratios in both left prefrontal lobe and left thalamus of study group were significantly increased compared with those before treatment (1.58 ± 0.30 vs 1.45 ± 0.26,t =2.122,P =0.037;1.62 ± 0.32 vs 1.48 ± 0.27,t =2.167,P =0.033).After 4-week treatment in study group,the total score,positive symptom score,negative symptom score and general pathologic score of PANSS,and the total score of Clinical Global Impression (CGI) were significantly lower compared with those before treatment (59.1 ± 10.2 vs 82.0 ± 13.2,t =8.896,P=0.000;15.3 ±5.1 vs 22.9 ±7.1,t =5.634,P =0.000;16.4 ±5.2 vs 21.1 ±7.8,t =3.249,P =0.002;27.4 ±7.6 vs 38.1 ± 8.8,t =5.963,P =0.000;3.6 ± 0.4 vs 4.4 ± 0.5,t =8.097,P =0.000).There was no correlation between the changes of neurochemical metabolite levels such as NAA/Cr and Cho/Cr both in prefrontal lobe and left thalamus,and the clinical symptoms changes,such as total score and every score of PANSS,the total score of CGI in study group after treatment (all P ＞ 0.05).Conclusions The ratios of NAA/Cr are decreased not only in bilateral prefrontal lobe,but also in left thalamus,and the ratios may increase both in left prefrontal lobe and left thalamus after 4 weeks' treatment with atypical antipsychotics in EOS.The treatment outcomes of NAA/Cr do not agree with the improvement of the clinical symptoms.

Objective To investigate the effects of mental health and sleep quality of the armored military performance ,pro-viding a theoretical basis for improving the performance of military officers and soldiers .Methods 276 armored military were se-lected randomly to study the performance ,including military training program evaluation(40% ) ,armored vehicles operating assess-ment(40% ) and leadership assessment(20% ) ,the test results as a percentage of the sum to exceed 80 divided into good and poor performance for the military .Symptom Checklist(SCL-90) and Scale Pittsburgh Sleep Quality Index(PSQI) were assessed ,and to evaluate the performance differences between good and poor military .Results (1)The good performance of armored military were 61 .2% ,and 38 .8% ones were poor .(2)The SCL-90 scores ,interpersonal sensitivity ,anxiety and hostility factors of good military performance were significantly lower than those with poor military performance(P<0 .05) .(3)The PSQI scores of Good military performance was 5 .83 ± 2 .94 ,and the poor was 7 .63 ± 3 .85 ;The sleep quality ,sleep latency ,sleep efficiency and daytime dysfunc-tion factors of good military performance subjective were significantly lower than those of poor military performance(P<0 .05) . Conclusion Psychological status and quality of sleep are important factors to influence performance of military armored force .

Objective To compare with the effect of high-frequency repetitive transcranial magnetic stimulation (rTMS) between the left and the right prefrontal on refractory negative symptoms and serum brain-derived neurotrophic factor (BDNF). Methods 80 hospitalized schizophrenics with refractory negative symptoms were divided into study group (n=40) and control group (n=40) randomly. Both groups were received 4-week treatment of 10 Hz rTMS. The stimulus lo?cation of the study group was the left prefrontal, and the control group was the right prefrontal. The type and dose of anti?psychotics remained unchanged during the treatment. The evaluation of positive and negative symptom scale (PANSS) and the measurement of BDNF concentration before treatment and after 4 weeks treatment was analyzed. Results Com?pared with before treatment, the total score of PANSS after treatment significantly decreased (P<0.05) both in the study group [(71.2±13.8) vs. (63.3±11.4)] and the control group [(70.3±13.4) vs. (63.7±12.2)]. The score of negative symptoms in the study group decreased [(22.8±6.6) vs. (18.4±5.9), P<0.01]. The BDNF concentration increased in the study group ](6.78±2.16) vs. (8.74±2.76)] and the control group [(6.83±2.32) vs. (8.66±2.70)]. Conclusion 10Hz rTMS on the left pre?frontal combined with drugs are helpful to improve the refractory negative symptom of the patients with schizophrenia. Stimulation on both left and right prefrontal lobe could increase serum BDNF concentration.

Objective To evaluate the effect of repetitive transcranial magnetic stimulation (rTMS) on serum brain-derived neurotrophic factor (BDNF) level in patients with schizophrenia.Methods Eighty hospitalized schizophrenics with refractory negative symptoms,admitted to our hospital from September 2012 to October 2013 and met the diagnostic and statistical manual of Mental Disorders-4th Edition (DSM-Ⅳ),were randomly divided into study group (n=40) and sham-operated group (n=40).The rTMS of 10 Hz on left prefrontal lobe was performed in study group and sham stimulation was used in sham-operated group; and the kinds and dosages of antipsychotics were preserved as before; other 40 healthy subjects were used as control group.Positive and Negative Syndrome Scale (PANSS) was performed and serum BDNF level was measured before and 4 weeks after treatment in all patients.Results BDNF level in both study group and sham-operated group before and after treatment was significantly lower than that in the control group (P＜0.05).The total PANSS scores and negative symptom scale scores in the study group after treatment were significantly decreased as compared with those before treatment (71.2±13.8 vs.63.3±11.4,t=2.721,P=0.008; 18.4±5.9 vs.22.8±6.6,t=3.064,P=0.003),and the BDNF level was statistically increased (8.74±2.76 vs.6.78±2.16,t=3.447,P=0.001).After treatment,the study group had significantly lower negative symptom scale scores and higher BDNF concentration than sham-operated group (t=2.470,P=0.016; t=3.180,P=0.002).For total PANSS scores,negative symptom scale scores and general psychopathology scale scores,the changed values before and after treatment of study group were all significantly higher than those in the sham-operated group (7.8±3.5 vs.2.0±0.9,t=9.893,P=0.000; 4.4±1.9 vs.0.5±0.2,t=12.584,P=0.000; 2.8±1.0 vs.0.9±0.4,t=10.875,P=0.000).For the study group,the changes of BDNF concentration showed no obvious correlation with the total PANSS scores or negative symptom scale scores (r=-0.156-0.247,P＞0.05).Conclusions The rTMS of 10 Hz on the left prefrontal lobe can increase the serum BDNF concentration of the schizophrenia.There is no correlation between the changes of BDNF concentration and improved negative symptoms.