OBJECTIVES: To investigate the synergistic mechanism of the traditional Chinese medicine Rosa laevigata Michx. (RLM) for treatment of pulmonary arterial hypertension (PAH). METHODS: Network pharmacological analysis was carried out to screen the active ingredients of RLM and PAH disease targets and construct the "component-target-disease" interaction network, followed by gene enrichment analysis and molecular docking studies. In the cell experiments, primary cultures of rat pulmonary arterial smooth muscle cells were exposed to hypoxia for 24 h and treated with solvent or 100, 200 and 300 mg/mL RLM, and the changes in cell proliferation were detected using Western blotting for PCNA and immunofluorescence staining. In the animal experiment, male SD rats were randomized into 5 control group, monocrotaline (MCT) solvent group, and MCT with RLM (100, 200 and 300 mg/mL) treatment groups. HE staining and immunofluorescence staining were used to observe histopathological changes in the pulmonary blood vessels of the rats. RESULTS: Seven core active ingredients (including β-sitosterol and kaempferol) in RLM and 39 key disease targets were identified, and molecular docking showed that SRC was a high-affinity target. KEGG enrichment analysis showed that the differential genes were significantly enriched in calcium signaling and PI3K-AKT pathways. In rat pulmonary arterial smooth muscle cells, hypoxic exposure significantly up-regulated cellular expression of PCNA and phosphorylation levels of Src and AKT1, which were obviously lowered by RLM treatment. In RLM-treated rat models, the mean pulmonary artery pressure and right ventricular hypertrophy index (Fulton index) were significantly reduced, the tricuspid annular plane systolic excursion (TAPSE) was improved, and pulmonary vascular wall thickening and fibrosis were obviously ameliorated. CONCLUSIONS RLM inhibits pulmonary arterial smooth muscle cell proliferation in rat models of hypertension possibly by regulating the Src-AKT1 axis, suggesting the potential of RLM as a new natural drug for treatment of pulmonary hypertension.
Animals ; Cell Proliferation/drug effects* ; Proto-Oncogene Proteins c-akt/metabolism* ; Rats, Sprague-Dawley ; Pulmonary Artery/cytology* ; Male ; Rats ; Myocytes, Smooth Muscle/cytology* ; Hypertension, Pulmonary/pathology* ; Drugs, Chinese Herbal/pharmacology* ; Signal Transduction/drug effects* ; Muscle, Smooth, Vascular/cytology* ; src-Family Kinases/metabolism* ; Cells, Cultured

Objective: To observe the effect of edaravone combining ulinastatin on brain protection in patients of type A aortic dissection (AAD) after total arch replacement. Methods: A total of 60 AAD patients with total arch replacement in our hospital from 2014-09 to 2016-01 were prospectively studied. Based on peri-operative application of edaravone and ulinastatin, the patients were divided into 2 groups: EU group: 1) the patients received ulinastatin 300000 U/8h and edaravone 0.5mg/Kg/12h from administration to 3 days post-operation, 2) during cardiopulmonary bypass, the patients received ulinastatin 300000 U/2h and edaravone 0.5mg/Kg; Control group, the patients had no such treatment.n=30 in each group. The following items were observed:①operative condition;②blood levels of speciifc brain injury markers as S-100 and neuron speciifc enolase (NSE) at different time points: beginning of surgery (T0), opening aorta clamp (T1), right after cardiopulmonary bypass (T2), entering ICU (T3), 24h post-operation (T4) and 3 days post-operation (T5); ③post-operative condition. Results:①Durations of operation, cardiopulmonary bypass, cardiac arrest and bilateral antegrade selective cerebral perfusion (BACP), the frequency of BACP and UACP (unilateral antegrade selective cerebral perfusion), the lowest rectal temperature and blood levels of S-100, NSE at T0 were similar between 2 groups.②Compared with Control group, EU group had decreased S-100 and NSE from T1 to T5,P<0.05.③The in-hospital and ventilation time, frequency of PND and TND, the patients with CSS score≥16 before discharge and the in-hospital death rate were similar between 2 groups,P>0.05. Conclusion: Edaravone combining ulinastatin had brain protective effect in AAD patients after total arch replacement;it may reduce blood speciifc brain injury markers while the clinical signiifcance should be further investigated.

Objective To investigate a special optimization technique for computer aided measure, and provide anatomical basis for screw internal fixation in the cavitas glenoidalis through the coracoid process of scapula. Methods Thirty accurate scapula models were reconstructed from CT data sets. First, special optimization objective function was designed for single screw internal fixation configuration, and the optimal placement of screw was found automatically under constraints. Then, the placements of double screws internal fixation configuration were searched taking advantage of principal component analysis. Finally, statistical measure data were provided according to new anatomical reference landmarks for clinical use. Results For single screw internal fixation configuration, the distance from the optimal screw entry point P to the acromion process point X was (39.15±2.28) mm, to the coracoid process point Y was (28.66±2.68) mm, to the angulus superior point Z was (61.13±6.57) mm;The angle was (81.27±7.15)° between PX and PY, and (133.27±6.84)° between PX and PZ. The mean inclination of the lag screw was (104.08±4.41)° for the angle with line PX, (101.29±3.51)° with line PY, and (76.23±5.03)° with line PZ. For double screws configuration, the distance from the original single screw entry point P to the screw entry point E was (5.12±1.37)mm,to the screw entry point F was (3.88±0.94)mm. The angle between the long axis of coracoid process and line EF was (27.41±3.51)°. Conclusion The automatic optimization technique for computer aided measure is very efficient and has many advantages over the conventional manual dissection methods, and is convenient to design new anatomical reference landmark system for clinical use.