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Doxorubicin (DOX) is a powerful anti-tumor anthracycline drug. However, its clinical use is limited due to the side effect of cardiotoxicity. Tanshinone I (Tan I) is one of the major tanshinones isolated from Salvia miltiorrhiza. Studies have shown that Tan I is effective in the treatment of cardiovascular diseases. However, the potential effects of Tan I against DOX-induced cardiotoxicity (DIC) have yet to be explored.This study aimed to explore whether Tan I can protect against DIC and to reveal whether Tan I can exert anti-oxidative effect by regulating nuclear erythroid factor 2-related factor 2 (Nrf2) pathway.DIC models were established in vivo by intravenous injection of DOX. Echocardiography was used to monitor the cardiac function of mice. Transmission electron microscopy was used to assess mitochondrial damage. Oxidative stress was measured by dihydroethidium (DHE) staining and western blotting. The accumulation and nuclear translocation of Nrf2 was detected by immunofluorescence. H9C2 cellular DIC model was established in vitro to explore the pharmacological mechanism. Nrf2 small interfering (si)-RNA was applied to H9C2 cells to explore whether Tan I exerted protective effect against DIC through Nrf2 signaling pathway. The protective effects of Tan I on mitochondrial function and mitochondrial membrane permeability were measured by MitoSOX™ Red and JC-1 staining assays, respectively.In vivo experiments revealed that Tan I could improve cardiac function and protect against DOX-induced myocardial structural damages in mice models. The oxidative stress induced by DOX was suppressed and apoptosis was mitigated by Tan I treatment. Tan I protected against DOX-induced mitochondrial structural damage. Meanwhile, key proteins in Nrf2 pathways were upregulated by Tan I treatment. In vitro studies showed that Tan I attenuated DOX-induced generation of reactive oxygen species (ROS) in cultured H9C2 cells, reduced apoptotic rates, protected mitochondrial functions and up-regulated Nrf2 signaling pathway. Tan I promoted accumulation and nuclear translocation of Nrf2 protein. In addition, interference of Nrf2 abrogated the anti-oxidative effects of Tan I and reversed the expressions of key proteins in Nrf2 pathway. The protective effects of Tan I on mitochondrial integrity was also mitigated by Nrf2 interference.Tan I could reduce oxidative stress and protect against DIC through regulating Nrf2 signaling pathway. Nrf2 is a potential target and Tan I is a novel candidate agent for the treatment of DIC.

Ethnopharmacological relevance Qishen granule (QSG) is a traditional Chinese medicine formulation that is widely used in clinical practice for the treatment of myocardial infarction (MI), and its efficacy and safety have been well approved. However, the underlying mechanism by which QSG alleviates inflammation and cell pyroptosis remains unknown. Aim of the study The aim of this study was to clarify whether QSG ameliorated MI by inhibiting inflammasome activation and cell pyroptosis. Materials and methods In vivo, SD male rats were subjected to the left anterior ascending branch (LAD) ligation to construct MI model. And in vitro, OGD/R, ISO, Ang II and LPS-ATP were used to induce H9C2 cell injury. Cell viability and ROS were detected by CCK8 and DCFH-DA dye respectively. Western blots were applied to detect the expression of inflammasome-related proteins. Cell pyroptosis was evaluated by Calcein-AM/PI staining, Hoechst/PI staining and NT-GSDMD expression. Results QSG administration improved the cardiac function, as well as reduced inflammatory cell infiltration and collagen deposition. In H9C2 cells, OGD/R failed to induce inflammasome activation, while ISO, Ang II and LPS-ATP successfully induced inflammasome activation and cell pyroptosis, as evidenced by increased Caspase-1(P20) and NT-GSDMD. In LPS-ATP induced H9C2 model, ROS production and cell pyroptosis were suppressed when treated with QSG. Furthermore, QSG significantly decreased the protein levels of P65–NF-κB, NLRP3, ASC, Caspase-1 (P20), Cleaved IL-18, Cleaved IL-1β and NT-GSDMD. Conclusion This study is the first to demonstrate that QSG has cardioprotective effects by inhibiting inflammasome activation and pyroptosis, which are considered as promising therapeutic targets for MI.

This paper presents a case study of a large ground collapse (30.6 m long, 25.5 m wide, and 6.0 m deep) and water inrush and mud outburst (10540.8 m3) in the Qingdao line 4, China. This disaster caused a loss of life and property, and construction delay. After the catastrophe, the remedial measures had to be taken to guarantee the stability of the tunnels when tunnel advance resumed. Based on the geological survey and numerical modelling, the main causes of this disaster were summarized as the low strength of strata, high water pressure, stress concentration, the coupling interaction between seepage force and ground and, as a consequence, also the crash of the slice of strongly weathered tuff. Eventually, potential energy, which was derived from the collapse bodies, was transformed into kinetic energy and developed this disaster. After this disaster, a set of remedial instruments including filling the ground cave-in, reinforcing the advance core ahead of tunnel face, and conducting the porepoles to form a protective shell were proposed. After the tunnel advance resumed, these remedial instruments validated by employing monitoring data were effective to tackle this disaster.

Traditional primary support made of reinforced concrete is widely applied but can bring many problems. Therefore, to study the mechanical behavior of corrugated-plate structure as primary support, several finite-element simulations in different sizes, shapes and elements were carried out. Besides, to ensure the exactness and practicability, a verification experiment and a BP neural network for prediction were done. The result shows that the outcome of beam-element and shell-element model is similar and the main deformation and stress is respectively down and compressive. And the difference between horseshoe-shaped and circular tunnel is small in aspect of vertical displacement and stress. Then, when t (thickness) increases, d (maximum vertical deformation) and s (maximum stress) decrease more and more slowly. When w (width) ascends, d and s improve more and more slowly. When h (height) becomes bigger, d declines more and more slowly and s goes down slowly, fast and slowly again. The outcome of the experiment conforms with the simulation. Next, by BP neural network, using top load and t, w, h to predict d and s is feasible and efficient. It performs better when predicting d. This paper can provide reference for the application of corrugated-steel-plate structure as new-type primary support.