Yiqi Shexue formula (YQSX) is traditionally used to treat primary immune thrombocytopenia (ITP) in clinical practice of traditional Chinese medicine. However, its mechanisms of action and molecular targets for treatment of ITP are not clear. The active compounds of YQSX were collected and their targets were identified. ITP-related targets were obtained by analyzing the differential expressed genes between ITP patients and healthy individuals. Protein–protein interaction (PPI) data were then obtained and PPI networks of YQSX putative targets and ITP-related targets were visualized and merged to identify the candidate targets for YQSX against ITP. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis were carried out. The gene-pathway network was constructed to screen the key target genes. In total, 177 active compounds and 251 targets of YQSX were identified. Two hundred and thirty differential expressed genes with an P value < 0.005 and |log2(fold change)| > 1 were identified between ITP patient and control groups. One hundred and eighty-three target genes associated with ITP were finally identified. The functional annotations of target genes were found to be related to transcription, cytosol, protein binding, and so on. Twenty-four pathways including cell cycle, estrogen signaling pathway, and MAPK signaling pathway were significantly enriched. MDM2 was the core gene and other several genes including TP53, MAPK1, CDKN1A, MYC, and DDX5 were the key gens in the gene-pathway network of YQSX for treatment of ITP. The results indicated that YQSX’s effects against ITP may relate to regulation of immunological function through the specific biological processes and the related pathways. This study demonstrates the application of network pharmacology in evaluating mechanisms of action and molecular targets of complex herbal formulations.

Triple-negative breast cancer (TNBC) is one of the most difficult subtypes of breast cancer to treat due to its aggressive, metastatic behavior, and a lack of a targeted therapy. Trivalent arsenic derivatives (arsenite, AsIII) with remarkable clinical efficacy in acute promyelocytic leukemia has been demonstrated to exhibit inhibitory effect against breast cancer cells. To provide novel insight into the development of new therapeutic strategies, antitumor activity of AsIII and tetrandrine (Tetra), a Chinese plant-derived alkaloid, against the TNBC cell line MDA-MB-231 in vitro and in vivo was investigated. Cytotoxicity was evaluated using cell viability, lactate dehydrogenase leakage and cell cycle assay. Alterations of genes related to cell proliferation and death were analyzed using western blotting. In vivo antitumor activity of AsIII alone or in combination with Tetra was studied using MDA-MB-231 xenografts in nude mice. Synergistic cytotoxic effects of two drugs were observed in the cells. In vivo study also showed that co-administration of AsIII and Tetra significantly reduced tumor volume and weight, directly supporting its in vitro antitumor activity. No deaths and reduction of body-weight were observed after a long-term co-administration, indicating its good tolerability. S-phase arrest associated with the upregulation of FOXO3a, p27 along with decreased Cyclin D1 expression was observed in the cells treated with the combined regimen. A substantial upregulated p21 expression and downregulated phospho-FOXO3a and Cyclin D1 expression was observed in the tumor tissues of mice co-administered with AsIII and Tetra. Autophagy induction was observed in the combination treatment in vitro and in vivo. The addition of wortmannin, a potent autophagy inhibitor, significantly rescued MDA-MB-231 cells from their cytotoxicity of AsIII and Tetra. S-phase arrest, autophagic and necrotic cell death contribute to the cytocidal effects of the combined regimen of AsIII and Tetra. Considering our previous study showing synergistic cytotoxic effects of the combined regimen in estrogen receptor-positive breast cancer cell line MCF-7, these results suggest that development of the combination regimen of AsIII plus Tetra may offer many benefits to patients with different types of breast cancer.

Polycythemia vera (PV) is a refractory hematological disease that lack of effective therapy. Chinese traditional medicine Longchai Jiangxue formula (LCJX) has showed the powerful effects on PV. However, the active ingredients and mechanisms of this formula have not been elucidated. We explored the active ingredients and mechanisms of LCJX for treating PV. The chemical constituents of LCJX were qualitatively analyzed by UPLC/Q-TOF-MS/MS. On this basis, the TCMSP, ETCM, PubChem BioAssay and ChEMBL databases were searched to predict the potential targets of chemical components of LCJX. Then Genecards, GEO, DisGeNET, and OMIM databases were used to retrieve data of targets related to PV. Drug-disease-target network and protein-protein-interaction (PPI) network were built. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed. Finally, Molecular docking, CCK-8 assay, Annexin V-FITC/PI staining and western blot were processed so as to screen the active components related to PV and elucidate its mechanisms. A total of 84 compounds were identified from LCJX by UPLC/Q-TOF-MS/MS. After removed duplicate items, there were 143 targets linked to both disease and drugs. Crucial genes, such as MTOR, HIF1A, JAK2, VEGFA, STAT3, AKT1, TERT, MAPK1, were shown in PPI network. GO enrichment indicated that oxidative stress process, tyrosine kinase activity and phosphatase binding function, and cell membrane structure were in reference to LCJX against PV. KEGG enrichment showed that JAK-STAT signaling pathway and PI3K-Akt signaling pathway, were put in an important position of the treatment. Furthermore, Molecular docking, CCK-8 assay, Annexin V-FITC/PI staining and western blot technique proved the therapeutic effect of Saikosaponin A, main ingredient of LCJX. This study, combined with UPLC/Q-TOF-MS/MS, network pharmacology and molecular biology, provides a reference for the identification of effective components, screening of quality markers and analysis of its action mechanism of LCJX.

Additional sex combs like 1 (ASXL1) mutations are one of the most common molecular biological abnormalities in patients with primary myelofibrosis (PMF), and the effect of these mutations on prognosis remains controversial. Hence, we conducted a meta-analysis to assess the prognostic value and clinical characteristics of ASXL1 mutations in PMF patients. Eligible studies were systematically searched from PubMed, Embase, and the Cochrane Library. We extracted the hazard ratios (HRs) and their 95% confidence intervals (CIs) of overall survival (OS) and leukemia-free survival (LFS), the number of patients transformed to acute leukemia, and clinical characteristics to carry out a meta-analysis by fixed effect model or random effect model according to the heterogeneity between studies. A total of 4501 PMF patients from 16 cohorts of 14 studies were included in this meta-analysis. The results revealed that ASXL1 mutations might predict a shorter OS (HR = 2.30, 95% CI: 1.79–2.94, P < 0.00001) and a higher probability of transformation to acute leukemia (LFS: HR = 1.77, 95% CI: 1.30–2.42, P = 0.0003; the rate of acute leukemia transformation: OR = 2.06, 95% CI: 1.50–2.83, P < 0.00001). Furthermore, ASXL1 mutations were correlated with patients older than 65 years old, male, a lower level of platelet counts, and a higher risk of the international prognostic score system. These findings indicate that ASXL1 mutations have a significant adverse impact on the prognosis of PMF patients and may contribute to risk stratification and prognostic assessment for PMF patients.

Arsenic disulfide (As₂S₂) has been traditionally used to treat certain types of leukemia. However, a detailed mechanism of action of As₂S₂ is not sufficiently documented. The effects of As₂S₂ on HL-60 cells were therefore investigated by focusing on proliferation, differentiation, generation of reactive oxygen species (ROS), intracellular glutathione (GSH) depletion and activation of p38 mitogen-activated protein kinase (MAPK). As₂S₂ at 0.5-8 μM induced cell differentiation based on an increment in CD11b expression, nitroblue tetrazolium (NBT)-positive cells and cell size change. A transient increase in ROS level along with intracellular GSH level was also observed. p38 MAPK activation gradually increased after ROS generation and was sustained during cell differentiation. Decreased CD11b expression was accompanied by p38 MAPK activation, and a p38 MAPK inhibitor restored CD11b expression. The results suggest that moderate levels of oxidative stress induced by As₂S₂ correlate with HL-60 cell differentiation. Suppression of p38 MAPK can augment the efficacy of As₂S₂ to induce HL-60 cell differentiation.

The design and application of the mushroom picking robot will greatly reduce the labor cost, and it has become one of the research hotspots in the world. Therefore, we independently developed an A. bisporus (a kind of mushroom) picking robot and introduced its functional principle in this paper. At the same time, in order to improve the picking efficiency of the picking robot, a picking path optimization algorithm based on TSP model is proposed. Firstly, based on the TSP model, a picking route model for A. bisporus was established to determine the storage location of each A. bisporus. Then, an improved simulated annealing (I‐SA) search algorithm is proposed to find the optimal path sequence. By improving the path initialization module, path generation module, and temperature drop module, the I‐SA search algorithm can optimize the picking path in a short time. Finally, in order to improve the stability and reduce the running time of the I‐SA search algorithm, a parallel optimization method for global search (“rough exploration”) and local search (“precision exploration”) is proposed. Through simulation experiments, the I‐SA search algorithm can search stable and excellent path solution in a relatively short time. Through field experiments on mushroom base, the efficiency of picking A. bisporus can be improved by 14% to 18%, which verifies the effectiveness of the I‐SA search algorithm.