Pharmacokinetic and pharmacodynamic evaluation study of etomidate: a randomized, open-label, 2-period crossover study in healthy Chinese subjects.

Etomidate is a sedative and hypnotic drug through intravenous administration that act on the central nervous system through GABA (Gamma-Amino Butyric Acid) receptors, which is widely used in anesthesia induction and maintenance and long-term sedation in severe patients. The study aimed to evaluate the pharmacokinetic and pharmacodynamic properties of two etomidate fat emulsions after administration through the intravenous infusion pump in healthy Chinese subjects. A randomized, open-label, 2-period crossover study was performed in 52 healthy subjects. The wash-out period was 7 days. Blood samples and pharmacodynamic index values were collected at the specified time points. Etomidate concentrations were measured using validated liquid chromatography-tandem mass spectrometry. Pharmacokinetic parameters were analyzed using a non-compartment model method. Pharmacodynamic parameters were calculated using pharmacodynamic index values. The study also evaluated the safety of the etomidate. Both the pharmacokinetic parameters and pharmacodynamic parameters result of the test and reference formulation were very similar. The 90% confidence intervals (CI) of the geometric least-squares mean (GLSM) ratios of the test to reference formulation were 91.33-104.96% for the maximum plasma concentration (Cmax), 97.21-102.03% for the area under the plasma concentration time curve from time 0 to the time of the last measurable concentration (AUC0-t), and 97.22-102.33% for the area under the plasma concentration time curve from time 0 to infinity (AUC0-∞). Meanwhile, the 90% CI of the GLSM ratios of the test to reference formulation were 102.28-110.69% for the minimal BIS value (BISmin), 99.23-101.17% for the area under the BIS time curve from time 0-60 min after administration (BISAUC0-60 min), respectively. The 90% CI of these pharmacokinetic and pharmacodynamic parameters all fall in the accepted bioequivalence range of 80.00-125.00%. No serious adverse events occurred during the study. This study has shown that the etomidate fat emulsion test and reference formulation had similar pharmacokinetic and pharmacodynamic characteristics in vivo. The two formulations exhibited good safety and well-tolerance.Clinical trials registration number: http://www.chinadrugtrials.org.cn/index.html . # CTR20191836.

A prospective study of psychological resilience and depression among left-behind children in China.

This prospective study examined the longitudinal effects of psychological resilience on depression in a Chinese sample of left-behind children. A total of 386 left-behind children completed both a baseline and a 1-year follow-up survey. The prevalence of depression at the baseline and 1-year follow-up was 12.7 and 8.5 per cent, respectively. Multivariate analysis revealed that older age and baseline depressive symptoms were positively associated with follow-up depression, while psychological resilience and quality of life were negatively related to follow-up depression. Our findings provided preliminary evidence that higher psychological resilience was a significantly protective factor of developing depression among left-behind children.

Prevalence of Internet addiction and its association with social support and other related factors among adolescents in China.

A cross-sectional study design was applied amongst a random sample (n = 10158) of Chinese adolescents. Self-completed questionnaires, including demographic characteristics, Internet use situation, Youth Internet Addiction Test, Youth Social Support Rating Scale and Zung Self-rating Depression Scale were utilized to examine the study objectives. Among the study population, the prevalence rate of Internet addiction was 10.4%, with 1038 (10.2%) moderately and 21 (0.2%) severely addicted to the Internet. Results from the multivariate logistic regression analyses suggested that a variety of related factors have significant effects on Internet addiction (parental control, per capita annual household income, academic performance, the access to Internet, online activities). The correlation coefficients showed that Internet addiction was negatively correlated with social support and positively associated with depression. Social support had a significant negative predictive effect on Internet addiction. The mediating effect of depression between social support and Internet addiction was remarkable.

Associations of Angiotensin-Converting Enzyme Insertion/Deletion, Angiotensin II Receptor A1166C, and Endothelial Nitric Oxide Synthase 4b/a Gene Polymorphisms With Pregnancy Hypertensive Disorders: A Meta-Analysis.

There have been numerous studies concerning the associations of angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D), angiotensin II receptor 1 (AT1R) gene A1166C, and endothelial nitric oxide synthase (eNOS) gene 4b/a polymorphisms with risk of pregnancy hypertensive disorders (PHDs). However, the results are inconsistent. A total of 83 eligible studies (10,354/18,446 cases/controls) were included in this meta-analysis. Pooled odds ratios with corresponding 95% confidence intervals were used to calculate these associations. The effects of ethnicity and types of PHDs were also considered. Results showed significant associations between the ACE gene polymorphism and PHDs in all of the populations except that in Africa. The associations also existed in AT1R, eNOS gene polymorphism and PHDs in part of the gene models in the overall population. These results indicated the ACE gene polymorphism was associated with an increased risk of PHDs, whereas the eNOS and AT1R gene polymorphism only have increased susceptibility to PHDs in part of the gene models.

Association between apolipoprotein E gene polymorphism and depression.

We performed an updated meta-analysis to obtain a more precise estimation of the relationship between apolipoprotein E (ApoE) gene polymorphism and susceptibility to depression, as previous reports have been inconsistent. Twenty studies with 2286 depression patients and 3845 controls were included. Odds ratios (OR) with 95% confidence intervals (CI) were calculated to assess the association between ApoE gene polymorphism and depression using a random effects model. Results showed a significant association between ApoE gene polymorphism and susceptibility to depression in the overall population (ε2/ε3 genotype versus ε3/ε3: OR 0.76, 95% CI 0.59-0.99). Subgroup analyses indicated an association in the Caucasian population (ε2 allele versus ε3: OR 0.75, 95% CI 0.58-0.97) as well as in late-life depression (LLD) patients (ε3/ε4 genotype versus ε3/ε3: OR 1.34, 95% CI 1.07-1.68, and ε4 allele versus ε3: OR 1.30, 95% CI 1.06-1.59). We concluded that the ε2/ε3 genotype likely provided a protective effect against depression in the overall population and the ε2 allele acted as a protective factor for depression in the Caucasian population while the ε4 allele and ε3/ε4 genotype were associated with an increased risk of depression in the LLD subjects.

Methylenetetrahydrofolate reductase (MTHFR) polymorphism susceptibility to schizophrenia and bipolar disorder: an updated meta-analysis.

Previous studies examining the possible role of the methylenetetrahydrofolate reductase (MTHFR) polymorphisms in the development of schizophrenia (SZ) and bipolar disorder (BPD) have provided inconclusive findings, this meta-analysis was therefore designed to get a more reliable assessment. A total of 38 articles were identified through a search of electronic databases, up to 27 February 2014. Odds ratios (ORs) with 95% confidence interval (CIs) were calculated using random effects models. Meta-analysis showed that MTHFR C677T was significantly associated with SZ, the highest OR was found for the recessive model (for TT vs. CT + CC: OR = 1.34, 95% CI: 1.18-1.53); a marginal association of MTHFR C677T with increased risk of BPD has also been found for the recessive model (OR = 1.26, 95% CI: 1.00-1.59). Subgroup analysis by ethnicity indicated that the significant association with SZ and BPD existed among Asian and African populations, but not for the white. MTHFR A1298C was significant associated with SZ, the highest OR for the dominant model (OR = 1.13, 95% CI: 1.03-1.24). Subgroup analysis indicated a significant association with SZ existed in Asian populations, not among the white populations and no significant association was detected between the MTHFR A1298C and BPD in all groups. We conclude that MTHFR polymorphism is associated with SZ and BPD among Asian, African populations, but not the white.

Association between methylenetetrahydrofolate reductase (MTHFR) C677T/A1298C polymorphisms and essential hypertension: a systematic review and meta-analysis.

OBJECTIVE: Many studies have investigated the role of 5,10-methylenetetrahydrofolate reductase gene (MTHFR) C677T/A1298C polymorphisms in essential hypertension (EH), but results are inconclusive. The purpose of this meta-analysis was to clarify the effects of MTHFR C677T/A1298C polymorphisms on the risk of EH. METHODS: Electronic databases were searched to identify relevant studies published until January 2014. Data were extracted by two independent authors. Odds ratios (ORs) with 95%confidence intervals (CIs) were used to assess the association between MTHFR C677T/A1298C polymorphisms and the risk of EH using random effect models or fixed effect models. Finally,30 studies with 5207 cases and 5383 controls were included for C677T polymorphism and 6 studies with 1009 cases and 994 controls were included for A1298C polymorphism. RESULTS: Meta-analysis results indicated that MTHFR C677T polymorphism contributed to an increased risk of EH (for T vs. C: OR=1.30, 95%CI=1.18­1.43; for TT+CT vs. CC: OR=1.34, 95%CI=1.24­1.46; for TT vs. CC: OR=1.62, 95%CI=1.32­1.99; for TT vs. CT+CC: OR=1.41, 95%CI=1.26­1.59). However, no significant association was detected between MTHFR A1298C polymorphism and the risk of EH. CONCLUSION: This meta-analysis supports that MTHFR C677T polymorphism plays a role in developing EH. MTHFR A1298C polymorphism may not be associated with an increased risk of EH. Further large and well-designed studies are warranted to confirm these findings.

Association of microtubule associated protein tau/Saitohin (MAPT/STH) MAPT_238bp/STH Q7R polymorphisms and Parkinson's disease: A meta-analysis.

BACKGROUND: The association between the extended tau haplotype (H1) and susceptibility to Parkinson's disease (PD) was controversial in previous studies. Therefore, we performed this meta-analysis to determine whether the additional polymorphisms in MAPT_238bp and STH Q7R which both included in H1 are associated with PD. METHODS: 19 studies were identified by a search of PubMed, PDGENE, Elsevier, Springer Link, CBM (Chinese Biomedical Database), CNKI (Chinese National Knowledge Infrastructure), VIP (Chinese), and Wanfang (Chinese) databases, up to May 2014. Additionally, manual retrieval of the references of identified articles was performed. Odds ratios (ORs) with 95% confidence interval (CI) were calculated using random effects model or fixed effects model based on the between-study heterogeneity. The subgroup analyses were performed by the ethnicity. All the statistical tests were conducted using Stata 9.0. RESULTS: Both of MAPT_238bp/STH Q7R polymorphisms had a significant association with PD risk in all genetic models. Subgroup analyses by ethnicity showed that the association between MAPT_238bp polymorphism and PD existed in Caucasian populations. CONCLUSIONS: The results of this meta-analysis suggested that MAPT_238bp/STH Q7R polymorphisms might modulate the risk of PD susceptibility. Certainly, additional well-designed studies are required to confirm these findings.

Cytochrome P450 1A1 (CYP1A1) polymorphism and susceptibility to esophageal cancer: an updated meta-analysis of 27 studies.

Cytochrome P450 1A1 (CYP1A1) polymorphisms are known to play a crucial role in the development and metastasis of malignant diseases including esophageal cancer. However, the results of previous studies investigating the association between CYP1A1 polymorphisms and esophageal cancer risk have been inconsistent. This meta-analysis of 27 eligible studies, encompassing 4,215 esophageal cancer cases and 6,339 control subjects, pooled the odds ratios (ORs) with corresponding 95 % confidence intervals (95 % CI) to assess this association. The effects of ethnicity (Caucasian and Asian) and histopathology type (esophageal squamous cell carcinoma and esophageal adenocarcinoma) were considered in subgroup analyses. A significant association was observed between the CYP1A1 Ile/Val gene polymorphism and esophageal cancer in all of the genetic models (Ile/Val vs. Ile/Ile, OR = 1.41, 95 % CI = 1.25-1.58; Val/Val vs. Ile/Ile, OR = 1.94, 95 % CI = 1.34-2.82; Ile/Val + Val/Val vs. Ile/Ile, OR = 1.49, 95 % CI = 1.33-1.66). The subgroup analysis based on ethnicity showed that the association between the CYP1A1 Ile/Val polymorphism and esophageal cancer existed in Asian and Caucasian populations. However, no association was observed between the CYP1A1 MspI polymorphism and esophageal cancer in either subgroup or in the overall population. These results suggested that the CYP1A1 Ile/Val polymorphism was associated with an increased risk of esophageal cancer, whereas the CYP1A1 MspI polymorphism may not have increased susceptibility to esophageal cancer. Further studies are required to confirm these findings.