Evidence suggests that plasminogen activator inhibitor-1 (PAI-1) is a stress-related factor, and serum PAI-1 levels are increased in patients with major depressive disorders (MDD). Herein, we analysed PAI-1 protein levels in the brain, cerebrospinal fluid (CSF) and serum of rodents exposed to chronic unpredictable mild stress or treated with escitalopram. In addition, we examined PAI-1 concentrations in serum obtained from 17 drug-free depressed patients before and after escitalopram treatment. We found that PAI-1 expression was increased in area 1 of the cingulate cortex and prelimbic cortex of the medial prefrontal cortex as well as in the hippocampal cornu ammonis 3 and dentate gyrus in stressed rats. A downregulation of PAI-1 following chronic escitalopram treatment was also found. PAI-1 levels were higher in the CSF and serum in stressed rats than in controls, although the difference did not reach statistical significance in the serum. Escitalopram treatment significantly decreased PAI-1 levels in the serum, but not in the CSF. MDD patients had significantly greater serum PAI-1 concentrations than controls. Our results suggest that PAI-1 is implicated in the pathophysiology of depression.

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Sodium aescinate (SA) is a widely-applied triterpene saponin product derived from horse chestnut seeds, possessing vasoactive and organ-protective activities with oral or injection administration in the clinic. To date, no toxicity or adverse events in SA have been reported, by using routine models (in vivo or in vitro), which are insufficient to predict all aspects of its pharmacological and toxicological actions. In this study, taking advantage of transparent zebrafish larvae (Danio rerio), we evaluated cardiovascular toxicity of SA at doses of 1/10 MNLC, 1/3 MNLC, MNLC and LC 10 by yolk sac microinjection. The qualitative and quantitative cardiotoxicity in zebrafish was assessed at 48 h post-SA treatment, using specific phenotypic endpoints: heart rate, heart rhythm, heart malformation, pericardial edema, circulation abnormalities, thrombosis and hemorrhage. The results showed that SA at 1/10 MNLC and above doses could induce obvious cardiac and pericardial malformations, whilst 1/3 MNLC and above doses could induce significant cardiac malfunctions (heart rate and circulation decrease/absence), as compared to untreated or vehicle-treated control groups. Such cardiotoxic manifestations occurred in more than 50% to 100% of all zebrafish treated with SA at MNLC and LC 10 . Our findings have uncovered the potential cardiotoxicity of SA for the first time, suggesting more attention to the risk of its clinical application. Such a time-and cost-saving zebrafish cardiotoxicity assay is very valid and reliable for rapid prediction of compound toxicity during drug research and development.

Previous studies suggest that neurotrophic factors participate in the development of stroke and depression. So we investigated the utility of these biomarkers as predictive and distinguish model for post stroke depression (PSD). 159 individuals including PSD, stroke without depression (Non-PSD), major depressive disorder (MDD) and normal control groups were recruited and examined the protein and mRNA expression levels of vascular endothelial growth factor (VEGF), vascular endothelial growth factor receptors (VEGFR2), placental growth factor (PIGF), insulin-like growth factor (IGF-1) and insulin-like growth factor receptors (IGF-1R). The chi-square test was used to evaluate categorical variable, while nonparametric test and one-way analysis of variance were applied to continuous variables of general characteristics, clinical and biological changes. In order to explore the predictive and distinguish role of these factors in PSD, discriminant analysis and receiver operating characteristic curve were calculated. The four groups had statistical differences in these neurotrophic factors (all P < 0.05) except VEGF concentration and IGF-1R mRNA (P = 0.776, P = 0.102 respectively). We identified these mRNA expression and protein analytes with general predictive performance for PSD and Non-PSD groups [area under the curve (AUC): 0.805, 95% CI, 0.704-0.907, P < 0.001]. Importantly, there is an excellent predictive performance (AUC: 0.984, 95% CI, 0.964-1.000, P < 0.001) to differentiate PSD patients from MDD patients. This was the first study to explore the changes of neurotrophic factors family in PSD patients, the results intriguingly demonstrated that the combination of protein and mRNA expression of biological factors could use as a predictive and discriminant model for PSD.

The results suggest that VGF may be implicated in the pathophysiology of MDD and in the mechanisms underlying the action of antidepressants, and serum VGF may be regarded as a trait parameter for MDD.

Previous studies have indicated that the level of glial cell line-derived neurotrophic factor (GDNF) may be correlated with stroke and depression. Here, we investigated whether GDNF can be a discriminant indicator for post stroke depression (PSD). 159 participants were divided into four groups: PSD, stroke without depression (Non-PSD), major depressive disorder (MDD) and normal control (NC) group, and the protein and mRNA expression levels of GDNF in serum were measured. The results showed that only MDD group had statistical difference in protein and mRNA levels compared with the other three groups (Bonferroni test, P < 0.05). The results of receiver operating curve (ROC) analysis supported GDNF as general distinguishing models in PSD and MDD groups with the area under the curve (AUC) at 0.797 (P < 0.001) and 0.831 (P < 0.001) respectively. In addition, the Spearman analysis demonstrated that the GDNF protein level negatively correlated with the value of Hamilton depression rating scale (HAMD) in PSD patients (correlation coefficient = −0.328, P = 0.047). Together, these findings suggest the protein and mRNA expression levels of GDNF decreased in patients with depression. GDNF may serve as a potential biomarker for differential diagnosis of PSD from MDD patients.

Previous studies demonstrate that the protein of neuropeptide Y (NPY) is abnormal in depression patients, but the changes of NPY in different types of depression are unclear. This study was aimed to examine protein and mRNA expression levels of NPY in 159 cases with four groups including post-stroke depression (PSD) group, stroke without depression (Non-PSD) group, major depressive disorder (MDD) group and normal control (NC) group. The protein and gene expression analysis were performed by enzyme-linked immunosorbent assay (ELISA) and quantitative polymerase chain reaction-based methods. One way analysis of variance (ANOVA), chi-square tests and nonparametric test were used to evaluate general characteristics, clinical and biological materials. In order to explore the role of NPY in different types of depression, the partial correlations, binary logistic regression analysis and receiver operating characteristic (ROC) curve were calculated for PSD and MDD groups. There are significant differences of NPY protein (Fdf(3) = 5.167, P = 0.002) and mRNA expression levels (χKruskal2-Wallis, df(3) = 20.541, P < 0.001) among four groups. Bonferroni multiple comparisons found that the NPY protein was significantly decreased in PSD (FBonferroni = −7.133, P = 0.002) and Non-PSD group (FBonferroni = −5.612, P = 0.018) compared with NC group. However, contrasted with MDD group, the mRNA expression was increased in PSD and Non-PSD group by nonparametric test (all P < 0.05). In binary logistic analyses, NPY mRNA expression was independent predictors of PSD (odds ratio: 1.452, 95% CI, 1.081–1.951, P = 0.013). The ROC curve showed NPY mRNA had a general prognostic accuracy (area under the curve: 0.766, 95% CI, 0.656–0.876, P < 0.001). This is the first study to explore the distinguishing function of NPY in different types of depression. It will provide help in the identification of different subtypes of depression.

Objective. The aim of this study was to systematically summarize and form an expert consensus on the theoretical experience of tongue and facial features for the identification of nine types of traditional Chinese medicine (TCM) constitution. Additionally, we sought to explore the feasibility of TCM constitution identification through objective tongue and facial features. Methods. We used Delphi method to investigate the opinions of experts on facial and tongue feature items for identifying TCM constitution. We developed and validated a diagnostic nomogram for blood stasis constitution (BSC) based on objective facial and tongue features to demonstrate the reliability of expert consultation. Results. Eleven experts participated in two rounds of expert consultation. The recovery rates of the two rounds of expert consultation were 100.0% and 90.9%. After the first round, 39 items were screened out from 147 initial items, and 2 items were supplemented by experts. In the second round, 7 items were eliminated, leaving 34 items for 8 types of TCM constitution. The coefficient of variation in the first round was 0.11–0.49 for the 147 items and 0.11–0.29 for the included items. The coefficient of variation in the second round was 0.10–0.27 for the 41 items and 0.10–0.20 for the included items. The W value was 0.548 ( P < 0.001 ) in the first round and 0.240 ( P < 0.001 ) in the second round. Based on expert consultation, we selected BSC as an example and developed and validated a diagnostic nomogram consisting of six indicators: sex, hair volume, lip color-dark purple, susceptibility-facial pigmentation/chloasma/ecchymosis, zygomatic texture-red blood streaks, and sublingual vein-varicose and dark purple. The nomogram showed good discrimination (AUC: 0.917 [95% confidence interval [CI], 0.877–0.956] for the primary dataset, 0.902 [95% CI, 0.828–0.976] for the validation dataset) and good calibration. Decision curve analysis demonstrated that the nomogram was clinically useful. Conclusion. This is the first study to systematically summarize the existing knowledge and clinical experience to form an expert consensus on the tongue and facial features of nine types of TCM constitution. Our results will provide important prior knowledge and expert experience for future constitution identification research. Based on expert consultation, this study presents a nomogram for BSC that incorporates objective facial and tongue features, which can be conveniently used to facilitate the individualized identification of BSC.