Epidemiological studies have shown that patients with diabetes are prone to have depression and anxiety.This article reviews the evidence,mechanism,complications and strategy of selective serotonin reuptake inhibitors paroxetine in treatment of depression and anxiety in patients with type 2 diabetes mellitus.

Objective To investigate the influence of social support on the depression and anxiety of standardized training residents.Methods Three hundred and eighteen standardized training residents selected by random sampling method from 4 training bases in Shanghai participated in this survey.ResultsThe average score of PHQ-9 was(7.24±5.20), and 67.30%(n=214)of participants had different degrees of depression;the average score of GAD-7 was(5.57±4.55), and 55.03%(n=175)of participants had different degrees of anxiety.One-way analysis of variances showed that standardized training residents who had work experience, longer training years and less salary satisfaction got higher scores in PHQ-9 and GAD-7.Male physicians had higher scores in GAD-7 than female ones.The scores of PHQ-9 (r=-0.390, P<0.01) and GAD-7 (r=-0.376, P<0.01) were both negatively correlated with social support.Regression analysis showed that training years,salary satisfaction,objective social support and the availability of support were significant for predicting the scores of PHQ-9(adjusted R2=0.242,F=17.893), work experience, salary satisfaction,objective social support and the availability of support were significant for predicting the scores of GAD-7(adjusted R2=0.228,F=14.390).After controlled the demographic variables, social support explained the variation rate of 0.119 to the score of PHQ-9 and 0.126 to the score of GAD-7.Conclusion The depression and anxiety of standardized training residents in this study is in a serious situation.Providing the objective social support and the availability of support as well as improving the salary satisfaction of standardized training residents may relieve the depression and anxiety and enhance their mental health.

Objective To evaluate the clinical effect of group cognitive behavioral therapy on blood glucose levels,anxiety and depression in patients with type2 diabetes mellitus.Methods Ninety three patients with type 2 diabetes mellitus were recruited and randomly divided into intervention group (n =48) and control group (n =45).Both groups received diabetes health education,patients in intervention group received additional group cognitive behavioral therapy.The glucose tolerance,glycosylated hemoglobin A1c were measured; the HAMA(Hamilton Anxiety Scale)scores,HAMD(Hamilton Depression Scale)scores and CSQ (Coping Styles Questionnaire) scores in patients were analyzed before and 6 months after treatment.Results After 6-month treatment the fasting blood glucose (6.33 mmol/L vs.5.94 mmol/L),1 h postprandial plasma glucose(12.40 mmol/L vs.11.46 rmool/L),2 h postprandial plasma glucose (10.24 mmol/L vs.9.13 mmol/L),A1 c (6.31％ vs.6.07％) in intervention group were decreased significantly,compared to baseline values (all P ＜ 0.05).The HAMA total score (9.98 vs.8.14),somatic anxiety (3.98 vs.3.48),psychic anxiety(6.00 vs.4.67),HAMD total score(10.74 vs.6.93),anxiety somatic(5.02 vs.3.26),block(2.24 vs.1.38)and sleep disorders(2.40 vs.1.40)in intervention group were all decreased significantly(P ＜ 0.01 or 0.05).There were significant differences in HAMA total score (8.14 vs.9.15),HAMD total score(6.93 vs.9.33),anxiety somatic(3.26 vs.4.38),block(1.38 vs.1.98)and sleep disorders(1.40 vs.2.03)between the intervention group and control group(P ＜ 0.01 or 0.05).And the negative coping style scores in intervention group was also lower than that of the baseline (26.74 vs..29.43).Conclusion The group cognitive behavioral therapy combined with diabetes health education for patients with type 2 diabetes mellitus may improve the glucose metabolism and depression and anxiety status of patients.

In this study, we evaluated the influence of different variance from each of the parameters on the output of tacrolimus population pharmacokinetic (PopPK) model in Chinese healthy volunteers, using Fourier amplitude sensitivity test (FAST). Besides, we estimated the index of sensitivity within whole course of blood sampling, designed different sampling times, and evaluated the quality of parameters' and the efficiency of prediction. It was observed that besides CL1/F, the index of sensitivity for all of the other four parameters (V1/F, V2/F, CL2/F and k(a)) in tacrolimus PopPK model showed relatively high level and changed fast with the time passing. With the increase of the variance of k(a), its indices of sensitivity increased obviously, associated with significant decrease in sensitivity index for the other parameters, and obvious change in peak time as well. According to the simulation of NONMEM and the comparison among different fitting results, we found that the sampling time points designed according to FAST surpassed the other time points. It suggests that FAST can access the sensitivities of model parameters effectively, and assist the design of clinical sampling times and the construction of PopPK model.

Pharmacometrics,developed from the conventional pharmacokinetics,is the science of applying mathe-matical and statistical methods to characterize,understand,and predict a drug's pharmacokinetic,phannacodyna-mic,and biomarker-outcome behaviors.Pharmacometrics has been widely valued for its utility of modeling and simulation in drug research and development,therapeutic drug monitoring and individualized therapy.This paper reviewed the advances of pharmacometrics employed in new drug research and development and therapeutic drug monitoring both at home and abroad.

Objective To evaluate the curative effects of sitagliptin in the treatment of type 2 diabetes mellitus complicated with nonalcoholic fatty liver disease(NAFLD).Methods 200 type 2 diabetes mellitus patients with NAFLD were selected and randomly divided into the observation group and the control group,100 cases in each group.The observation group received sitagliptin treatment,while the control group was treated with metformin.Before and 3,6 months after treatment,the body weight,body mass index(BMI),liver function(AST,ALT,GGT),OGCT synchronous exsanguinate assay(fasting and 2 h after breakfast glucose,insulin),blood lipid(TC,TG)and glycosylated hemoglobin(HbAlc),and other biochemical indicators were monitored and compared,as well as 1HMRS scan images. Results In the two groups after treatment,ALT,GGT,AST,FPG and 2h PG all improved significantly(t≥2.35,P <0.05),but ALT,GGT,AST,FPG and 2h PG in the observation group all improved better than those in the control group(t≥4.99,all P <0.05).In the two groups after treatment,TC,TG,HbAlc,BMI,HOMA -IR all improved significantly(t≥5.63,all P <0.05),but those of the observation group improved more significantly(t≥3.90,all P <0.05 ).In the observation group after treatment,liver lipid content (IHCL)was (10.3 ±2.9 )%,which was significantly lower than (27.8 ±4.5)% before treatment(t =32.69,P <0.05).In the control group after treatment, IHCL was (18.4 ±3.5)%,which was significantly lower than (26.9 ±4.6)% before treatment(t =14.70,P <0.05),but in the observation group after treatment IHCL was significantly lower than that in the control group after treatment(t =17.82,P <0.05).Conclusion Sitagliptin can significantly improve the blood glucose,blood lipid, liver function,insulin resistance in type 2 diabetes mellitus patients with NAFLD,which has good clinical curative effects and is worthy of clinical promoting.

Objective To investigate the effect of valsartan (angiotensinⅡtypeⅠreceptor antagonists) on neointimal proliferation and expression of CD34 after angioplasty in rabbits.Method Twenty-four male New Zealand White rabbits were randomly divided into three groups:the control group,fed up with common diet;the model group and the valsartan group,fed up with hypercholesterolemic diet for 4 weeks,f then and ballon angioplasty.At 4 weeks after operation,the model group was fed up with common diet,whereas the valsartan group was fed up with the admixture of valsartan 10 mg?kg~(-1)?d~(-1) and common diet.All the rabbits were killed at the end of the 12th weeks.The abdominal aorta was performed with pathologic and morphologic analysis,and expression of CD34 in endothelial cells was analyzed with immunohistochemical method.Results Compared with the model group,the neointimal thickness and area of the valsartan group decreased by 56.58%and 66.81%, respectively.The expression of CD34 of the valsartan group was significantly higher (P

In this study, we evaluated the influence of different variance from each of the parameters on the output of tacrolimus population pharmacokinetic (PopPK) model in Chinese healthy volunteers, using Fourier amplitude sensitivity test (FAST). Besides, we estimated the index of sensitivity within whole course of blood sampling, designed different sampling times, and evaluated the quality of parameters' and the efficiency of prediction. It was observed that besides CL1/F, the index of sensitivity for all of the other four parameters (V1/F, V2/F, CL2/F and k(a)) in tacrolimus PopPK model showed relatively high level and changed fast with the time passing. With the increase of the variance of k(a), its indices of sensitivity increased obviously, associated with significant decrease in sensitivity index for the other parameters, and obvious change in peak time as well. According to the simulation of NONMEM and the comparison among different fitting results, we found that the sampling time points designed according to FAST surpassed the other time points. It suggests that FAST can access the sensitivities of model parameters effectively, and assist the design of clinical sampling times and the construction of PopPK model.
Administration, Oral ; Adult ; Asian Continental Ancestry Group ; Fourier Analysis ; Humans ; Immunosuppressive Agents ; administration & dosage ; blood ; pharmacokinetics ; Models, Biological ; Nonlinear Dynamics ; Sensitivity and Specificity ; Tacrolimus ; administration & dosage ; blood ; pharmacokinetics ; Young Adult

Objective To detect the clinical factors related with liver metastasis in young patients with rectal cancer.Methods Three hundred and fifty young patients with rectal cancer were collected to set up the database.Single and multi-factor Logistic regression was applied to indicate the independent factors relating to liver metastasis.The regression equation to predict probability of liver metastasis from rectal cancer was established.Results Liver metastasis was 120 cases (34.3%).Single-factor analysis revealed that patho-organization type,pathologytype,infiltration extent,blood vessel invasion (BVI),TNM stage,operation character,the preoperative level of carcino-embryonic antigen,histology grading were related with liver metastasis.Multi-factor analysis revealed that only BVI (P=0.001),TNM stage (P=0.001),pathoorganization type (P=0.005),the preoperative level of CEA (P=0.008) and operation character (P=0.032) were independent factors to predict probability of liver metastasis.Conclusions Rectal cancer of young patients who being with BVI,advanced phase,high preoperative level of CEA,radical operation or poor differentiation degree,are apt to develop liver metastasis.They should be given further individualized intensive adjuvant treatment.

Objective To investigate the expression changes of aspartic proteinase (cathepsin D) and cysteine proteinase (cathepsin K) in photoaged fibroblasts. Methods The senescence of human fibroblasts was induced via culture in the presence of 8-methoxypsralen (MOP) of 50 mg/L in darkness for 24 hours followed by irradiation with UVA of 80 kJ/m~2. Then, aged fibroblasts were confirmed by senescence-associated β-galactosidase (SA-β-gal) staining. Real-time RT-PCR and Western blot were carried out to detect the mRNA and protein expressions of cathepsin D and cathepsin K in photoaged and normal control fibroblasts, respectively. Results Western blot showed a significant difference between photoaged and control fibroblasts in the grey scale of cathepsin D and cathepsin K (3.25 ± 0.33 vs 14.18 ± 2.25, f = 30.61, P < 0.01; 2.39 ± 0.66 vs 29.38 ± 4.62, t = 12.63, P< 0.01). The △Ct values for cathepsin D and cathepsin K mRNA were 2.79 ± 0.17 and -0.92 ± 0.06, respectively, in photoaged fibroblasts, significantly lower than those in the control fibroblasts (4.54 ± 0.34, 2.57 ± 0.13, t = 20.78, 28.50, respectively, both P < 0.01). According to the value of 2~(-△△Ct), the expression of cathepsin D and cathepsin K mRNA decreased 0.24 ± 0.021 and 0.09 ± 0.005 folds, respectively, in photoaged fibroblasts compared with the control fibroblasts. Conclusion The expression of cathepsin D and cathepsin K is decreased in photoaged fibroblasts.