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Air pollution is a growing public health burden associated with several negative health effects, especially cardiovascular disease. Shenlian extract (SL), a traditional Chinese medicine, has the effects of clearing heat‐toxin and promoting blood circulation for removing blood stasis, and it has long been used to treat cardiovascular diseases and atherosclerosis. This study explored the underlying action mechanism of SL against ultrafine particle‐induced myocardial ischemic injury (UFP‐MI) through network pharmacology prediction and experimental verification. Male Sprague–Dawley rats with UFP‐MI were pre‐treated with SL intragastrically for 7 days. All the rats were then euthanized. Inflammatory cytokine detection and histopathological analysis were performed to assess the protective effects of SL. For the mechanism study, differentially expressed genes (DEGs) were identified in UFP‐MI rats treated with SL through transcriptomic analysis. Subsequently, in combination with network pharmacology, potential pathways involved in the effects of SL treatment were identified using the Internet‐based Computation Platform (http://www.tcmip.cn) and Cytoscape 3.6.0. Further validation experiments were performed to reveal the mechanism of the therapeutic effects of SL on UFP‐MI. The results show that SL significantly suppressed inflammatory cell infiltration into myocardial tissue and exhibited significant anti‐inflammatory activity. Transcriptomic analysis revealed that the DEGs after SL treatment had significant anti‐inflammatory, immunomodulatory, and anti‐viral activities. Network pharmacology analysis illustrated that the targets of SL were mainly involved in regulation of the inflammatory response, apoptotic process, innate immune response, platelet activation, and coagulation process. By combining transcriptomic and network pharmacology data, we found that SL may exert anti‐inflammatory effects by acting on the NOD‐like signaling pathway to regulate immune response activation and inhibit systemic inflammation. Verification experiments revealed that SL can suppress the secretion of the inflammatory cytokines Interleukin‐1 (IL‐1), Interleukin‐18(IL‐18) and Interleukin‐33(IL‐33) and suppress NLRP3 inflammasome activity. The results suggested that SL can directly inhibit the activation of NLRP3 inflammasomes and reduce the release of cytokines to protect against ultrafine particulate matter‐aggravated myocardial ischemic injury.

Background and Purpose: Ultrafine particulate matter (UFPM) induces oxidative stress (OS) and is considered to be a risk factor of myocardial ischemia (MI). Shengmai formula (SMF) is a traditional Chinese medicine with antioxidant properties and has been used to treat cardiovascular diseases for a long time. The aim of this study was to explore the protective role of SMF and the mechanism by which it prevents myocardial injury in UFPM-exposed rats with MI.Methods: An MI rat model was established. Animals were randomly divided into five groups: sham, UFPM + MI, SMF (1.08 mg/kg⋅d) + UFPM + MI, SMF (2.16 mg/kg⋅d) + UFPM + MI, and SMF (4.32 mg/kg⋅d) + UFPM + MI. SMF or saline was administrated 7 days before UFPM instillation (100 μg/kg), followed by 24 h of ischemia. Physiological and biochemical parameters were measured, and histopathological examinations were conducted to evaluate myocardial damage. We also explored the potential mechanism of the protective role of SMF using a system pharmacology approach and an in vitro myoblast cell model with small molecule inhibitors.Results: UFPM produced myocardial injuries on myocardial infarct size; serum levels of LDH, CK-MB, and cardiac troponin; and OS responses in the rats with MI. Pretreatment with SMF significantly attenuated these damages via reversing the biomarkers. SMF also improved histopathology induced by UFPM and significantly altered the PI3K/AKT/MAPK and OS signaling pathways. The expression patterns of Cat, Gstk1, and Cyba in the UFPM model group were reversed in the SMF-treated group. In in vitro studies, SMF attenuated UFPM-induced reactive oxygen species production, mitochondrial damage, and OS responses. The PI3K/AKT/p38 MAPK/Nrf2 pathway was significantly changed in the SMF group compared with that in the UFPM group, whereas opposite results were obtained for pathway inhibition.Conclusion: These findings indicate that SMF prevents OS responses and exerts beneficial effects against myocardial injury induced by UFPM + MI in rats. Furthermore, the PI3K/AKT/p38 MAPK/Nrf2 signaling pathway might be involved in the protective effects of SMF.

Cerebral malaria (CM) is caused by Plasmodium falciparum, resulting in severe sequelae; one of its pathogenic factors is the low bioavailability of nitric oxide (NO). Our previous study suggested that the combination of artesunate (AS) and tetramethylpyrazine (TMP) exerts an adjuvant therapeutic effect on the symptoms of experimental CM (ECM) and that NO regulation plays an important role. In the present study, we further verified the effects of AS+TMP on cerebral blood flow (CBF) and detected NO-related indicators. We focused on the role of NO through S-nitrosoproteome based on previous proteomics data and explored the mechanism of AS+TMP for improving pathological ECM symptoms. We observed that AS+TMP reduces adhesion, increases CBF, and regulates NO synthase (NOS) activity, thereby regulating the level of S-nitrosothiols, such as metabolism-related or neuro-associated receptors, for improving ECM symptoms. These results demonstrated that AS+TMP could be an effective strategy in adjuvant therapy of CM.

Most of the existing studies on high dams under seismic action use stable ground motions, which cannot simulate the non-stationary process of practical ground motions well. Although many scholars have studied the special characteristics of ground motion frequency and intensity lately, relatively few systematic studies have been carried out for the residual deformation of practical high dam projects. In this paper, considering the special characteristics of ground motions, 144 non-stationary stochastic seismic acceleration time histories are generated by the spectral expression-random function method, and stochastic dynamic calculations are carried out for four three-dimensional models of Gushui, Lava, Dashixia, and Ciha Gorge, respectively. We analyze the acceleration and residual deformation laws of four concrete face rockfill dams (CFRDs) based on the generalized probability density evolution method (GPDEM) and extreme value distribution theory. According to the results, the reference value of the dam body deformation of the 250 m panel under different seismic intensities is given, and the settlement at the dam crest is proposed. When the safety control standard is 1.0~1.1%, the ultimate seismic capacity of the 250 m face rockfill dam is 0.7~0.8 g.