[Prognostic Value of IGF2BP3 Gene Expression Levels in Patients with Acute Myeloid Leukemia].

OBJECTIVE: To investigate the relationship between IGF2BP3 gene expression and prognosis in patients with acute myeloid leukemia (AML). METHODS: High throughput transcriptome sequencing was performed on bone marrow primary leukemia cells from 27 patients with AML in our center, the relationship between IGF2BP3 expression levels and clinical characteristics were analyzed and verify the samples from patients with newly treated AML and refractory AML. The expression level of IGF2BP3 gene were analyzed in 20 healthy subjects and 26 patients with AML. The expression of IGF2BP3 in two anthracycline-resistant cell lines (HL60/ADR, K562/ADR) was detected by RT-qPCR and Western blot, and the expression difference of IGF2BP3 was compared with that in sensitive cells (HL60, K562). The relationship between the expression level of IGF2BP3 in patients with AML and prognostic were analyzed through data analysis of 746 patients with AML, and the prognostic value of IGF2BP3 in AML was analyzed by multivariate Cox regression analysis. RESULTS: In the bone marrow primary leukemia cells of 27 AML patients in our center, the expression level of IGF2BP3 in patients with refractory AML was significantly higher than that in chemotherapy sensitive patients (P =0.0343). The expression of IGF2BP3 in leukemia patients with extramedullary infiltration (EMI) was significantly higher than that in AML patients without extramedullary infiltration (P =0.0049). Compared with healthy subjects (n=20), IGF2BP3 expression in AML patients (n=26) was higher (P =0.0009). The expression of IGF2BP3 mRNA in the anthracycline resistant cell lines (HL60/ADR, K562/ADR) was significantly higher than that in the sensitive cell lines (K562/ADR vs K562,P =0.0430; HL60/ADR vs HL60, P =0.7369). Western blot results showed that the expression of IGF2BP3 protein in mycin resistant cells was significantly higher than that in sensitive cells (P < 0.001). qPCR results showed that the expression level of IGF2BP3 mRNA in refractory AML patients was significantly higher than that in patients with chemotherapy sensitive (P =0.002). High expression of IGF2BP3 was associated with poor prognosis in AML (P < 0.05) in 3 large sample cohorts of AML patients. Univariate and multivariate prognostic analyses demonstrated that high expression of IGF2BP3 was significantly associated with shorter event-free survival (EFS, HR=1.887, P =0.024) and overall survival (OS, HR=1.619, P =0.016). CONCLUSION: The high expression of IGF2BP3 gene may be an important factor in the poor prognosis of AML, suggesting that IGF2BP3 gene may be a new molecular marker for the clinical prognosis evaluation and treatment strategy of AML.

Dexmedetomidine modulates neuronal activity of horizontal limbs of diagonal band via α2 adrenergic receptor in mice.

BACKGROUND AND OBJECTIVES: Dexmedetomidine (DEX) is widely used in clinical sedation which has little effect on cardiopulmonary inhibition, however the mechanism remains to be elucidated. The basal forebrain (BF) is a key nucleus that controls sleep-wake cycle. The horizontal limbs of diagonal bundle (HDB) is one subregions of the BF. The purpose of this study was to examine whether the possible mechanism of DEX is through the α2 adrenergic receptor of BF (HDB). METHODS: In this study, we investigated the effects of DEX on the BF (HDB) by using whole cell patch clamp recordings. The threshold stimulus intensity, the inter-spike-intervals (ISIs) and the frequency of action potential firing in the BF (HDB) neurons were recorded by application of DEX (2 µM) and co-application of a α2 adrenergic receptor antagonist phentolamine (PHEN) (10 µM). RESULTS: DEX (2 µM) increased the threshold stimulus intensity, inhibited the frequency of action potential firing and enlarged the inter-spike-interval (ISI) in the BF (HDB) neurons. These effects were reversed by co-application of PHEN (10 µM). CONCLUSION: Taken together, our findings revealed DEX decreased the discharge activity of BF (HDB) neuron via α2 adrenergic receptors.

Tai Chi as a complementary exercise for pulmonary rehabilitation in chronic obstructive pulmonary disease: A randomised controlled trial.

OBJECTIVES: With the characteristics of mindfulness and breathing techniques, Tai Chi has been recommended with therapeutic values in chronic obstructive pulmonary disease (COPD). However, its strengths as a complementary exercise for conventional pulmonary rehabilitation (PR) remain unclear. DESIGN AND SETTING: This single-blinded randomised controlled trial recruited patients with mild to severe stable COPD. Eligible participants were randomly assigned to the group with usual care (control), total body recumbent stepper (TBRS) exercise, Tai Chi (TC), or combined TBRS exercise and Tai Chi (TBRS-TC). Patients received a two-month hospital-based supervised exercise, followed by a ten-month community- or home-based rehabilitation program. RESULTS: A total of 120 participants were recruited, and 102 were included in the per-protocol analysis. The mean changes in St George's Respiratory Questionnaire (SGRQ) total score from baseline to the post-hospital exercise in the control group, TBRS group, TC group, and TBRS-TC group was 2.62 (95 % CI -8.99 to 8.99), -9.28 (95 % CI -13.96 to -4.60), -10.19 (95 % CI -13.72 to -6.67), and -16.75 (95 % CI -20.25 to -13.24), respectively, with a statistically significant difference between groups in favor of the TBRS-TC exercise (P < 0.001). The remarkable effect of TBRS-TC exercise in improving the quality of life maintained until the end of the community- or home-based rehabilitation training (P < 0.001). Besides, a statistically better effect with the TBRS-TC exercise was also observed in the outcomes regarding exercise capacity, pulmonary function, symptom burden, and systemic inflammation after the whole process of 12-month integrative PR exercise programme. CONCLUSIONS: Based on the results, a novel integrated exercise modality combining Tai Chi and conventional pulmonary rehabilitation was developed. It might contribute to more positive effects in patients with stable COPD. REGISTRATION: The study was registered with the Chinese Clinical Trial Registry (ChiCTR-IOR-15006874) prior to commencing recruitment.

MAIT Cell Activation and Functions.

Mucosal associated invariant T (MAIT) cells are striking in their abundance and their strict conservation across 150 million years of mammalian evolution, implying they must fulfill critical immunological function(s). MAIT cells are defined by their expression of a semi-invariant αß TCR which recognizes biosynthetic derivatives of riboflavin synthesis presented on MR1. Initial studies focused on their role in detecting predominantly intracellular bacterial and mycobacterial infections. However, it is now recognized that there are several modes of MAIT cell activation and these are related to activation of distinct transcriptional programmes, each associated with distinct functional roles. In this minireview, we summarize current knowledge from human and animal studies of MAIT cell activation induced (1) in an MR1-TCR dependent manner in the context of inflammatory danger signals and associated with antibacterial host defense; (2) in an MR1-TCR independent manner by the cytokines interleukin(IL)-12/-15/-18 and type I interferon, which is associated with antiviral responses; and (3) a recently-described TCR-dependent "tissue repair" programme which is associated with accelerated wound healing in the context of commensal microbiota. Because of this capability for diverse functional responses in diverse immunological contexts, these intriguing cells now appear to be multifunctional effectors central to the interface of innate and adaptive immunity.

Dissection of Pharmacological Mechanism of Chinese Herbal Medicine Yihuo Huatan Formula on Chronic Obstructive Pulmonary Disease: A Systems Pharmacology-Based Study.

Chronic obstructive pulmonary disease (COPD) is one of the most common respiratory diseases. Yihuo Huatan Formula (YHF), as a proven Chinese Herbal Medicine (CHM), has been verified to be effective in the treatment of stable COPD through years' of practice. Nevertheless, its working mechanism is still unclear. We sought to systematically decipher the mechanism of YHF for treating stable COPD using systems pharmacology-based method that integrates pharmacokinetic screening, target prediction, network analyses, GO and KEGG enrichment analyses. Firstly, a total of 1267 chemicals out of 15 herbal components were included in YHF chemical database. Among them, 180 potential active molecules were screened out through pharmacokinetic evaluation. Then 258 targets of the active molecules were predicted, of which 84 were chosen for further analyses. Finally, the network analyses and GO and KEGG enrichment methods suggested a therapeutic effect of YHF on the alleviation of airway inflammation, decrease of mucus secretion, maintenance of immune homeostasis and benefit of COPD comorbidities, by regulating multiple targets and pathways. The systems pharmacology-based approach helps to understand the underlying working mechanism of YHF in stable COPD from a holistic perspective, and offers an exemplification for systematically uncovering the action mechanisms of CHM.

Chinese Herbal Medicine for Advanced Non-Small-Cell Lung Cancer: A Systematic Review and Meta-Analysis.

Chinese herbal medicine (CHM) has been widely used in the treatment of advanced non-small-cell lung cancer (NSCLC), but their efficacy and safety remain controversial. We sought to comprehensively aggregate and evaluate the available evidence on the efficacy and safety of the combination treatment with CHM and epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in NSCLC patients. Our exhausted and systematical searching strategy yielded 64 related randomized controlled trials involving 4384 patients. Compared with EGFR-TKIs therapy alone, meta-analysis showed significant differences favoring the combination treatment in progression-free survival ([Formula: see text]), median survival time ([Formula: see text]), one-year survival rate ([Formula: see text]), two-year survival rate ([Formula: see text]), probability of severe toxicities ([Formula: see text]), objective response rate ([Formula: see text]), Karnofsky performance status ([Formula: see text]), and improvement in percentage of CD3[Formula: see text] T lymphocyte ([Formula: see text]) and CD4[Formula: see text] T lymphocyte ([Formula: see text]). Though these results require further confirmation, they are prone to show a potential therapeutic value of CHM in improving the clinical effect, overcoming the drug resistance and toxicities as an adjunctive therapy to EGFR-TKIs.