The in vivo study on antioxidant activity of wendan decoction in treating hyperlipidemia: a pharmacokinetic-pharmacodynamic (PK-PD) model.

Background: Wendan Decoction (WDD) is a six-herb Chinese medicine recipe that was first mentioned in about 652 AD. It is frequently used to treat hyperlipidemic patients' clinical complaints. According to reports, oxidative stress has a significant role in hyperlipidemia. Purpose: There has not yet been a thorough pharmacokinetic-pharmacodynamic (PK-PD) examination of the clinical efficacy of WDD in the context of hyperlipemia-related oxidative stress. Therefore, the goal of this research is to explore the antioxidant essence of WDD by developing a PK-PD model, ordering to assure its implication in treating hyperlipidemia in medical practice. Methods: The model rats of foodborne hyperlipidemia were established by feeding with high-fat feed, and the lipid-lowering effect of WDD was explored. The plasma drug concentration of rats at different doses were measured by UPL-MS/MS technology, and PK parameters were calculated using Phoenix WinNonlin 8.1 software. The level of lipid peroxide (LPO) in plasma at different time points was measured by enzyme labeling instrument. Finally, the PK-PD model was established by using Phoenix WinNonlin 8.1 software, to explore the lipid-lowering effect of WDD and the relation between the dynamic changes of chemical components and antioxidant effect. Results: The findings suggested that, WDD can reduce the levels of triglyceride (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) in plasma, and high-density lipoprotein cholesterol (HDL-C) was related to the dosage. Between the peak drug levels and the WDD's maximal therapeutic response, there existed a hysteresis. WDD's effect-concentration curves displayed a counterclockwise delaying loop. Alternatively, among the ten components of WDD, hesperetin, quercetin, naringenin and tangeretin might exert more significant effects in regulating the LPO levels in hyperlipidemic rats. Conclusion: This study can be helpful for other investigators to study the lipid-lowering effect of WDD.

Up-regulation of CD81 inhibits cytotrophoblast invasion and mediates maternal endothelial cell dysfunction in preeclampsia.

Preeclampsia (PE) is initiated by abnormal placentation in the early stages of pregnancy, followed by systemic activation of endothelial cells of the maternal small arterioles in the late second or third trimester (TM) of pregnancy. During normal pregnancy, placental cytotrophoblasts (CTBs) invade the maternal uterine wall and spiral arteries, whereas this process is interrupted in PE. However, it is not known how the malformed placenta triggers maternal endothelial crisis and the associated manifestations. Here, we have focused on the association of CD81 with PE. CD81, a member of the tetraspanin superfamily, plays significant roles in cell growth, adhesion, and motility. The function of CD81 in human placentation and its association with pregnancy complications are currently unknown. In the present study, we have demonstrated that CD81 was preferentially expressed in normal first TM placentas and progressively down-regulated with gestation advance. In patients with early-onset severe PE (sPE), CD81 expression was significantly up-regulated in syncytiotrophoblasts (STBs), CTBs and the cells in the villous core. In addition, high levels of CD81 were observed in the maternal sera of patients with sPE. Overexpressing CD81 in CTBs significantly decreased CTB invasion, and culturing primary human umbilical vein endothelial cells (HUVECs) in the presence of a high dose of exogenous CD81 resulted in interrupted angiogenesis and endothelial cell activation in vitro. Importantly, the phenotype of human PE was mimicked in the CD81-induced rat model.

The value of 3D-FIESTA MRI in detecting non-iatrogenic cerebrospinal fluid rhinorrhoea: correlations with endoscopic endonasal surgery.

BACKGROUND: In this study, we investigated the value of three-dimensional (3D) fast-imaging employing steady-state acquisition (FIESTA) magnetic resonance imaging (MRI) in detecting non-iatrogenic cerebrospinal fluid (CSF) rhinorrhoea and compared it with regular MRI and 3D magnetisation prepared rapid acquisition gradient echo (MPRAGE) MRI sequences, as well as high-resolution computed tomography (HRCT) imaging. We also present the endoscopic experiences of such cases. METHOD: From June 2011 to Feb 2016, 17 patients with non-iatrogenic cerebrospinal fluid rhinorrhoea were included. Seven patients had spontaneous rhinorrhoea, three patients had invasive tumours, and the remaining patients had traumatic aetiologies. All the patients underwent HRCT, regular MRI sequence imaging, 3D-MPRAGE MRI sequence imaging and 3D-FIESTA MRI sequence imaging for the preoperative evaluations of the leakages. For each patient, the CSF fistula site was confirmed by intraoperative neuronavigation and endoscopic findings. Statistical analyses were performed. All patients underwent endoscopic multilayer repair. RESULTS: The sensitivities of the HRCT, regular MRI (T1 and T2), 3D-MPRAGE and 3D-FIESTA modalities for identifying CSF leakage were 58.8 %, (11.8 % and 29.4 %), 74.7 %, and 88.2 %, respectively. The origins of the leakages included the cribriform plate (18 %), ethmoidal fovea (23 %), lateral recess of the sphenoid (17 %), sellar floor (12 %), ethmoidal roof (12 %), junction of the fovea and cribriform plate (6 %) and the junction of sellar and sphenoidal planum (6 %). Two patients required repair. The first was under local anaesthesia when the nasal packing was removed, and the second underwent repair at the same site a half-year later due to hydrocephalus. Lumbar drainage was performed in all cases. No major complications were encountered. CONCLUSIONS: The endoscopic endonasal approach is safe and effective for the treatment of CSF rhinorrhoea. The 3D-FIESTA MR modality is superior to 3D-MPRAGE MR and HRCT in the depiction of the CSF fistula site. Due to its non-invasive and reliable properties, 3D-FIESTA MR should be the preferred preoperative examination for the patients with non-iatrogenic CSF rhinorrhoea.