Targeted depletion of monocyte/macrophage suppresses aortic dissection with the spatial regulation of MMP-9 in the aorta.

AIM: Aortic dissection (AD) is a devastating disease with rapid progression and high mortality, while the initiation mechanism of AD is far from clear. MAIN METHODS: AD was established by feeding mice with ß-aminopropionitrile in the diet and usage of angiotensin II (AngII) to trigger the rupture of aorta. LysMiDTR mice were constructed by crossing of LysM-Cre mice with ROSA26iDTR mice and characterized by diphtheria toxin receptor (DTR) expression in monocytes/macrophages specifically. Then, monocyte/macrophage depletion in LysMiDTR mice was conducted to evaluate the function of monocyte/macrophage in AD. Finally, the underlying mechanism was elucidated by proteomics, Western blot analysis, immunofluorescence staining and bioinformatics analysis. KEY FINDINGS: First, we detected T lymphocytes, macrophages and neutrophils infiltrated into the aorta simultaneously when AD occurred, and macrophages were the most abundant cell type. Then, targeted depletion of monocyte/macrophage in LysMiDTR mice considerably inhibited the occurrence of AD and infiltration of T lymphocytes and neutrophils. Furthermore, monocyte transfusion into LysMiDTR mice augmented the rupture of aorta, jointly supporting the key roles of monocytes/macrophages in AD development. Mechanistically, a total of 347 proteins exhibited significant differences in intensity after monocyte/macrophage depletion according to quantitative mass spectrometry. Specifically, increased matrix metalloprotein-9 (MMP-9) level in AD may be of concern due to its functions in vascular remodeling. The infiltration of macrophages considerably up-regulated MMP-9, and MMP-9 co-localized with macrophages at the tearing area of aorta. SIGNIFICANCE: Macrophages infiltrated into the tear sites of the aortic wall, regulated extracellular remodeling pathway, functioned as initiators to switch on the occurrence of AD.

A glimpse into the psychological status of E.N.T inpatients in China: A cross-sectional survey of three hospitals in different regions.

OBJECTIVE: To determine whether E.N.T inpatients have a higher prevalence of mental illness than the general population and whether certain diseases are more likely to be associated with mental illness than other diseases. METHODS: This cross-sectional survey was conducted in the E.N.T departments of three hospitals in different cities in China. The psychological status of all consecutive adult inpatients was assessed within 1-2 days following hospital admission using the Symptom Checklist-90 (SCL-90), Zung Self-Rating Depression Scale (SDS) and Zung Self-Rating Anxiety Scale (SAS). Inpatients from the general surgery and pneumology departments at the same hospital were enrolled and surveyed as control groups. RESULTS: The 439 patients enrolled in the final analysis accounted for 88.0% of all E.N.T inpatients during the study period. Of these patients, 16.4% were in an anxious state and 79.5% were in a depressive state. The overall anxiety (41.7 ± 9.7) and depression (55.9 ± 29.2) scores were much higher than Chinese norm (29.8 ± 10.0 and 33.5 ± 8.6, respectively), and significant differences were observed (t = 20.89, P < 0.01 and t = 13.12, P < 0.01, respectively). Although 18.7% of the E.N.T patients were psychiatric distress, these patients scored lower on the SCL-90 than the Chinese norm. Furthermore, the patients in the E.N.T department had a higher prevalence of anxiety and depression than those in the general surgery department but a similar prevalence to those in the respiratory department. CONCLUSION: Psychological distress, particularly anxiety and depression, are widespread in patients with otolaryngological diseases. Therefore, the identification and treatment of co-occurring psychiatric disorders in this high risk and clinically challenging group of patients are urgent in China.

The difference between blood-associated and water-associated herbs of Danggui-Shaoyao San in theory of TCM, based on serum pharmacochemistry.

Danggui-Shaoyao San (DSS) is a famous Chinese formula for activating blood circulation and promoting urination. This study was to investigate the difference of material basis between a blood-associated herbs group and a water-associated herbs group. According to the theory of traditional Chinese medicine, the formula can be divided into a blood-associated herbs group (Angelica sinensis, Paeonia lactiflora and Ligusticum chuanxiong) and a water-associated herbs group (Atractylodes macrocephala, Alisma orientale and Poria cocos). The HPLC fingerprint of the formula was established for quality control. Serum samples from rats, orally administrated DSS, and the decomposed recipes of DSS, were analyzed by HPLC-DAD and the transitional blood components of DSS were identified. Twenty-one common peaks were identified in the fingerprint of DSS. Contents of paeoniflorin, albiflorin, ferulic acid and alisol B 23-acetate in co-decoction were significantly higher than those in individual decoction. Eleven peaks belonged to the blood-associated herbs group (four metabolites and seven prototype components; paeoniflorin and ferulic acid appeared in prototype components), whereas six peaks belonged to the water-associated herbs group (three metabolites and three prototype components). It was concluded that the serum pharmacochemistry is a meaningful approach for clarifying the difference between blood-associated and water-associated herbs in chemical composition.

A Pharmacometabonomic Approach To Predicting Metabolic Phenotypes and Pharmacokinetic Parameters of Atorvastatin in Healthy Volunteers.

Genetic polymorphism and environment each influence individual variability in drug metabolism and disposition. It is preferable to predict such variability, which may affect drug efficacy and toxicity, before drug administration. We examined individual differences in the pharmacokinetics of atorvastatin by applying gas chromatography-mass spectrometry-based metabolic profiling to predose plasma samples from 48 healthy volunteers. We determined the level of atorvastatin in plasma using liquid chromatography-tandem mass spectrometry. With the endogenous molecules, which showed a good correlation with pharmacokinetic parameters, a refined partial least-squares model was calculated based on predose data from a training set of 36 individuals and exhibited good predictive capability for the other 12 individuals in the prediction set. In addition, the model was successfully used to predictively classify individual pharmacokinetic responses into subgroups. Metabolites such as tryptophan, alanine, arachidonic acid, 2-hydroxybutyric acid, cholesterol, and isoleucine were indicated as candidate markers for predicting by showing better predictive capability for explaining individual differences than a conventional physiological index. These results suggest that a pharmacometabonomic approach offers the potential to predict individual differences in pharmacokinetics and therefore to facilitate individualized drug therapy.

Anti-depression effects of Danggui-Shaoyao-San, a fixed combination of Traditional Chinese Medicine, on depression model in mice and rats.

Anti-depression effects of Danggui-Shaoyao-San (DSS, 1.8-7.2g/kg, orally), a famous Chinese compound prescription with a fixed combination, on forced swimming test (FST) and chronic unpredictable mild stress (CUMS) model were investigated. DSS (7.2g/kg, orally, 7 days) shortened immobility time in FST model and DSS (3.6 or 7.2g/kg, orally, 21 days) increased the open-field activities and the percentage of sugar preference in CUMS model. DSS (7.2g/kg, orally, 21 days) also decreased the content of arginine vasopressin (AVP) in the pituitary and the expression of AVP mRNA in hypothalamus compared with the stress control group. These results demonstrated for the first time DSS has anti-depression effect and it may be influencing the central AVP system.