MicroRNAs (miRNAs) expression profiles were screened in plasma samples from pediatric patients with acute lymphoblastic leukemia (ALL) and healthy controls, using qRT-PCR-based TaqMan low-density miRNA arrays. MiR-652-3p (a circulating miRNA) was downregulated in new diagnosis (ND) patients compared with healthy controls. The levels of miR652-3p were restored in complete remission (CR) but were downregulated again in disease relapse (RE). The expression pattern of miR-652-3p was validated in bone marrow (BM) samples from other pediatric ALL patients. MiR-652-3p was significantly upregulated in BM when the patients (n=86) achieved CR, as compared with the matched ND samples (p<0.001). Moreover, the miR-652-3p levels in BM decreased again in two patients at RE. In addition, the lymphoblastic leukemia cell lines Reh and RS4:11 were found to have lower levels of miR-625-3p than the normal B-cell line. Overexpression of miR-652-3p using agomir increased the sensitivity to vincristine and cytarabine (all p<0.05) and promoted apoptosis (both p<0.05) in Reh and RS4:11 cells. In conclusion, the results suggested that a low level of miR-652-3p might be involved in the pathogenesis of pediatric ALL. Overexpression of miR-652-3p might suppress lymphoblastic leukemia cells, promoting apoptosis and increasing sensitivity to chemotherapeutic drugs.

Qi-Jing-Sheng-Bai granule (QJSB) is a newly developed traditional Chinese medicine (TCM) formula. Clinically, it has been used for the treatment of leucopenia. However, its pharmacological mechanism needs more investigation. In this study, we firstly tested the effects of QJSB on leucopenia using mice induced by cyclophosphamide. Our results suggested that QJSB significantly raised the number of peripheral white blood cells, platelets and nucleated bone marrow cells. Additionally, it markedly enhanced the cell viability and promoted the colony formation of bone marrow mononuclear cells. Furthermore, it reversed the serum cytokines IL-6 and G-CSF disorders. Then, using transcriptomics datasets and metabonomic datasets, we integrated transcriptomics-based network pharmacology and metabolomics technologies to investigate the mechanism of action of QJSB. We found that QJSB regulated a series of biological processes such as hematopoietic cell lineage, homeostasis of number of cells, lymphocyte differentiation, metabolic processes (including lipid, amino acid, and nucleotide metabolism), B cell receptor signaling pathway, T cell activation and NOD-like receptor signaling pathway. In a summary, QJSB has protective effects to leucopenia in mice probably through accelerating cell proliferation and differentiation, regulating metabolism response pathways and modulating immunologic function at a system level.

The rock mass is one of the key parameters in engineering design. Accurate rock mass classification is also essential to ensure operational safety. Over the past decades, various models have been proposed to evaluate and predict rock mass. Among these models, artificial intelligence (AI) based models are becoming more popular due to their outstanding prediction results and generalization ability for multiinfluential factors. In order to develop an easy-to-use rock mass classification model, support vector machine (SVM) techniques are adopted as the basic prediction tools, and three types of optimization algorithms, i.e., particle swarm optimization (PSO), genetic algorithm (GA) and grey wolf optimization (GWO), are implemented to improve the prediction classification and optimize the hyper-parameters. A database was assembled, consisting of 80 sets of real engineering data, involving four influencing factors. The three combined models are compared in accuracy, precision, recall, F1 value and computational time. The results reveal that among three models, the GWO-SVC-based model shows the best classification performance by training. The accuracy of training and testing sets of GWO-SVC are 90.6250% (58/64) and 93.7500% (15/16), respectively. For Grades I, II, III, IV and V, the precision value is 1, 0.93, 0.90, 0.92, 0.83, the recall value is 1, 1, 0.93, 0.73, 0.83, and the F1 value is 1, 0.96, 0.92, 0.81, 0.83, respectively. Sensitivity analysis is performed to understand the influence of input parameters on rock mass classification. It shows that the sensitive factor in rock mass quality is the RQD. Finally, the GWO-SVC is employed to assess the quality of rocks from the southeastern ore body of the Chambishi copper mine. Overall, the current study demonstrates the potential of using artificial intelligence methods in rock mass assessment, rendering far better results than the previous reports.

PURPOSE Homoharringtonine (HHT) is commonly used for the treatment of Chinese adult AML, and all-trans retinoic acid (ATRA) has been verified in acute promyelocytic leukemia (APL). However, the efficacy and safety of HHT-based induction therapy have not been confirmed for childhood AML, and ATRA-based treatment has not been evaluated among patients with non-APL AML. PATIENTS AND METHODS This open-label, multicenter, randomized Chinese Children's Leukemia Group-AML 2015 study was performed across 35 centers in China. Patients with newly diagnosed childhood AML were first randomly assigned to receive an HHT-based (H arm) or etoposide-based (E arm) induction regimen and then randomly allocated to receive cytarabine-based (AC arm) or ATRA-based (AT arm) maintenance therapy. The primary end points were the complete remission (CR) rate after induction therapy, and the secondary end points were the overall survival (OS) and event-free survival (EFS) at 3 years. RESULTS We enrolled 1,258 patients, of whom 1,253 were included in the intent-to-treat analysis. The overall CR rate was significantly higher in the H arm than in the E arm (79.9% v 73.9%, P = .014). According to the intention-to-treat analysis, the 3-year OS was 69.2% (95% CI, 65.1 to 72.9) in the H arm and 62.8% (95% CI, 58.7 to 66.6) in the E arm ( P = .025); the 3-year EFS was 61.1% (95% CI, 56.8 to 65.0) in the H arm and 53.4% (95% CI, 49.2 to 57.3) in the E arm ( P = .022). Among the per-protocol population, who received maintenance therapy, the 3-year EFS did not differ significantly across the four arms (H + AT arm: 70.7%, 95% CI, 61.1 to 78.3; H + AC arm: 74.8%, 95% CI, 67.0 to 81.0, P = .933; E + AC arm: 72.9%, 95% CI, 65.1 to 79.2, P = .789; E + AT arm: 66.2%, 95% CI, 56.8 to 74.0, P = .336). CONCLUSION HHT is an alternative combination regimen for childhood AML. The effects of ATRA-based maintenance are comparable with those of cytarabine-based maintenance therapy.