ABSTRACT
The production plan of an open-pit mine depends on the block model, so it's crucial to determine the appropriate method and size for partitioning it. This study proposes a new method based on a closed shell three-dimensional geological model for determining block model size in open-pit mines. Instead of using regular block models, the shell model is directly cut, and the discrete geological body is referred to as the "mining model." Mining parameters and the shovel-truck's performance are integrated into the method. Bench height determines the Z-axis size, bench slope angle determines the inclination angle, and shovel width determines the X-axis size of the block model. The operation efficiency of the shovel-truck considers the probability distribution of simultaneous operations, allowing the determination of the Y-axis size of block models for different types of shovels. The developed "Mining Model" module in the software "Life Cycle Mining System" is used for practical implementation. By comparing the results with traditional block models, the superiority of the proposed method is demonstrated. This study provides a more accurate model for optimizing the production plan of open-pit mines throughout their life cycle.
ABSTRACT
AIMS: Proprotein convertase subtilisin/kexin type 9 (PCSK9) modulates CD4+ T cell differentiation and inflammatory response, the latter ones mediate ulcerative colitis (UC) initiation. This study intended to explore the correlation of serum PCSK9 with disease activity, T helper (h)1/Th2/Th17 cells, and clinical response of tumor necrosis factor inhibitor (TNFi) in UC patients. METHODS: In 65 UC patients underwent TNFi treatment, serum PCSK9 was evaluated at baseline (W0), week (W)2, W6, and W12 by enzyme-linked immunosorbent assays; meanwhile, Th1/Th2/Th17 cells were determined at W0 by flow cytometry. Besides, serum PCSK9 was detected in 65 healthy controls (HCs). RESULTS: Serum PCSK9 was increased in UC patients compared to HCs (P<0.001), which also positively correlated with C-reactive protein (P=0.009), total Mayo score (P=0.018), Mayo-defined disease activity (P=0.020), Th1 (P=0.033), and Th17 (P=0.003) cells, but not Th2 cells (P=0.086) in UC patients. Interestingly, serum PCSK9 was steadily declined from W0 to W12 (P<0.001). W2-W0, W6-W0, and W12-W0 serum PCSK9 change (PCSK9 at W2, W6, or W12 minus PCSK9 at W0, respectively) was gradually becoming greater during TNFi treatment (P<0.001). Furthermore, forty-five (69.2%) patients achieved clinical response at W12, whose serum PCSK9 at W6 (P=0.041) and W12 (P=0.001) was lower, and W6-W0 (P=0.043), W12-W0 (P=0.019) serum PCSK9 change was more obvious compared to patients without clinical response at W12. CONCLUSIONS: Serum PCSK9 is positively related to disease activity, Th1, and Th17 cells in UC patients; further, its decline correlates with TNFi response achievement in these patients.
Subject(s)
Colitis, Ulcerative , Sulfonamides , Humans , Proprotein Convertase 9 , Tumor Necrosis Factor InhibitorsABSTRACT
Objective: To study the mechanisms of the Ligusticum chuanxiong Hort.-Piper longum L. herbal pair (LPHP) in the treatment of migraine using network pharmacology. Methods: The active constituents of LPHP and their targets were searched for and screened using the Chinese Medicine System Pharmacology Database. Genes related to migraine were searched on GeneCards, Online Mendelian Inheritance in Man and other databases. Cytoscape was used to construct and combine active component-target and disease-target networks. The core target was screened by network topology analysis, and the Metascape database was used for gene ontology analysis of key targets and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis to explore the molecular mechanisms in the treatment of migraine. Results: A total of 28 active constituents of LPHP were obtained through database screening and literature review, and 60 cross-linking targets were obtained. The target sites were analysed using a protein-protein interaction network to obtain six target proteins with a greater degree of relevance. These were identified as the main targets for the treatment of hypertension, and these key targets were found to be associated with 20 signalling pathways, including neuroactive ligand-receptor interaction, the calcium signalling pathway, the cGMP-PKG signalling pathway, pathways in cancer and the cyclic adenosine 3',5'-cyclic monophosphate (cAMP) signalling pathway. Conclusion: This study reveals the molecular mechanism of LPHP in the treatment of migraine from the perspective of network pharmacology and provides a basis for further research and molecular mechanism research.
