Mechanism of Fei-Xian Formula in the Treatment of Pulmonary Fibrosis on the Basis of Network Pharmacology Analysis Combined with Molecular Docking Validation.

OBJECTIVE: This study aimed to clarify the mechanism of Fei-Xian formula (FXF) in the treatment of pulmonary fibrosis based on network pharmacology analysis combined with molecular docking validation. METHODS: Firstly, ingredients in FXF with pharmacological activities, together with specific targets, were identified based on the BATMA-TCM and TCMSP databases. Then, targets associated with pulmonary fibrosis, which included pathogenic targets as well as those known therapeutic targets, were screened against the CTD, TTD, GeneCards, and DisGeNet databases. Later, Cytoscape was employed to construct a candidate component-target network of FXF for treating pulmonary fibrosis. In addition, for nodes within the as-constructed network, topological parameters were calculated using CytoHubba plug-in, and the degree value (twice as high as the median degree value for all the nodes) was adopted to select core components as well as core targets of FXF for treating pulmonary fibrosis, which were subsequently utilized for constructing the core network. Furthermore, molecular docking study was carried out on those core active ingredients together with the core targets using AutoDock Vina for verifying results of network pharmacology analysis. At last, OmicShare was employed for enrichment analysis of the core targets. RESULTS: Altogether 12 active ingredients along with 13 core targets were identified from our constructed core component-target network of FXF for the treatment of pulmonary fibrosis. As revealed by enrichment analysis, the 13 core targets mostly concentrated in regulating biological functions, like response to external stimulus (from oxidative stress, radiation, UV, chemical substances, and virus infection), apoptosis, cell cycle, aging, immune process, and protein metabolism. In addition, several pathways, like IL-17, AGE-RAGE, TNF, HIF-1, PI3K-AKT, NOD-like receptor, T/B cell receptor, and virus infection-related pathways, exerted vital parts in FXF in the treatment of pulmonary fibrosis. CONCLUSIONS: FXF can treat pulmonary fibrosis through a "multicomponent, multitarget, and multipathway" mean. Findings in this work lay foundation for further exploration of the FXF mechanism in the treatment of pulmonary fibrosis.

[Establishment of an animal model of blunt scrotal trauma and evaluation of the lesion by conventional and contrast-enhanced ultrasonography].

OBJECTIVE: To establish an animal model of acute blunt scrotal trauma (BST) and evaluate the types of lesion by conventional ultrasonography (CUS) and contrast-enhanced ultrasonography (CEUS). METHODS: We made acute BST models in 21 healthy male New Zealand rabbits by striking 3 - 12 times the unilateral testes randomly selected with a 0. 5 kg iron ball falling freely from a 30 cm height. Then we evaluated the lesion types in the models by CUS and CEUS and verified our evaluation against pathological results. RESULTS: Acute BST models were successfully established in all the 21 animals, including contusion in 10, hematoma in 6, and rupture in 5, all confirmed by pathology. CUS clearly manifested the morphology, internal echoes, and blood flow of the testes, but had a low rate of accurate diagnosis in testicular contusion for over 6 hours as well as in complex lesions. CEUS revealed an earlier perfusion of the contrast agent and shorter arriving time (AT) and time to peak intensity ( TP) in testicular contusion than in the control testes (P <0.05) , but showed no statistically significant difference between the two groups in the half time of descending peak intensity (P>0.05). For testicular hematoma, contrast agent clearly presented its outline and a delayed low enhancement in the surrounding tissue, with significant differences from the control in AT and TTP. In severe testis rupture, occasional outflow but no perfusion of contrast agent was observed. CONCLUSION: BST models can be established in rabbits by repeated strikes of the unilateral testes lesion of contrast agent was observed. with a freely falling iron ball. Simple contusion injury can be induced by less than 6 strikes, while complex injuries can be inflicted by more than 10. Combined application of CUS and CEUS can improve the accuracy of diagnosis of different types of lesion.

[Contrast-enhanced ultrasonography for detecting testicular perfusion in acute testis contusion in rabbits].

OBJECTIVE: To evaluate contrast-enhanced ultrasonography (CEUS) in detecting testicular perfusion in acute testis contusion. METHODS: We established the model of testis contusion in 11 healthy male New Zealand rabbits by randomly hitting one side of the scrotum under general anesthesia. We examined the bilateral scrotums of all the animals before, immediately after and at 2, 4 and 6 hours after modeling by color Doppler flow imaging (CDFI) and CEUS, and analyzed the time-intensity curve (TIC), arriving time (AT), time to peak intensity (TTP), peak intensity (PI), half time of descending peak intensity (HT) and area under the curve (AUC) in the healthy and injured testis, respectively. RESULTS: CEUS exhibited a higher sensitivity in detecting tissue perfusion than CDFI. The mode of contrast agent perfusion in testicular contusion was fast in and slow out. There were no evident differences between the contused and the healthy testis in AT, TTP and PI before modeling. The contused testis showed significantly earlier AT and TTP, higher PI and larger AUC (P < 0.05) than the healthy one at different time points after modeling, but no statistically significant difference was found in HT (P > 0.05). CONCLUSION: Accurate parameters of testicular perfusion in acute testis contusion can be quantitatively obtained by CEUS, which are of important value for the diagnosis of testis contusion.