Efficacy and safety of venetoclax in patients with relapsed/refractory multiple myeloma: a meta-analysis.

BACKGROUND: Venetoclax is clinically active in treating relapsed/refractory multiple myeloma (RRMM). This study evaluated the efficacy and safety of venetoclax or venetoclax with other agents in treating RRMM. METHODS: PubMed, Web of Science, Embase, and Cochrane Library were comprehensively searched. We included studies investigating the efficacy and safety of venetoclax or venetoclax with other agents in treating RRMM. Overall response rates (ORR), stringent complete response rates (sCR), complete response rates (CR), very good partial response rates (VGPR), partial response rates (PR), stable disease (SD), progressive disease (PD) and adverse events were synthesized using either a random-effects model or a fixed-effects model. RESULTS: A total of 7 clinical trials with 482 patients with RRMM were included. Concerning venetoclax with other agents, the pooled ORR, sCR, CR, VGPR, PR, SD, and PD were 0.76 (95% CIs: 0.62, 0.87), 0.11 (95% CIs: 0.04, 0.21), 0.18 (95% CIs: 0.11, 0.26), 0.16 (95% CIs: 0.12, 0.25), 0.29 (95% CIs: 0.25, 0.34), 0.07 (95% CIs: 0.05, 0.10), and 0.11 (95% CIs: 0.04, 0.23). The overall rate of adverse events ≥ Grade 3 was 0.84 (95% CIs: 0.77, 0.91). The most common non-hematologic adverse events were nausea, diarrhea, fatigue, back pain, and vomiting; hematologic adverse events included thrombocytopenia, neutropenia, anemia, leukopenia, and lymphopenia. CONCLUSIONS: This study indicates that venetoclax alone or in combination with other agents reveals favorable treatment responses and acceptable adverse events in treating RRMM.

In Situ Precision Cell Electrospinning as an Efficient Stem Cell Delivery Approach for Cutaneous Wound Healing.

Mesenchymal stem cell (MSC) therapies have been brought forward as a promising treatment modality for cutaneous wound healing. However, current approaches for stem cell delivery have many drawbacks, such as lack of targetability and cell loss, leading to poor efficacy of stem cell therapy. To overcome these problems, in the present study, an in situ cell electrospinning system is developed as an attractive approach for stem cell delivery. MSCs have a high cell viability of over 90% even with a high applied voltage of 15 kV post-cell electrospinning process. In addition, cell electrospinning does not show any negative effect on the surface marker expression and differentiation capacity of MSCs. In vivo studies demonstrate that in situ cell electrospinning treatment can promote cutaneous wound healing through direct deposition of bioactive fish gelatin fibers and MSCs onto wound sites, leading to a synergic therapeutic effect. The approach enhances extracellular matrix remodeling by increasing collagen deposition, promotes angiogenesis by increasing the expression of vascular endothelial growth factor (VEGF) and forming small blood vessels, and dramatically reduces the expression of interleukin-6 (IL-6) during wound healing. The use of in situ cell electrospinning system potentially provides a rapid, no touch, personalized treatment for cutaneous wound healing.

Load Effect of Automated Truck Platooning on Highway Bridges and Loading Strategy.

Automated truck platooning (ATP) has gained growing attention due to its advantage in reducing fuel consumption and carbon emissions. However, it poses serious challenges to highway bridges due to the load effect of multiple closely spaced heavy-duty trucks on the bridge. In China, ATP also has great application prospects in the massive and ever-increasing highway freight market. Therefore, the load effects of ATP on bridges need to be thoroughly investigated. In this study, typical Chinese highway bridges and trucks were adopted. ATP load models were designed according to the current Chinese road traffic regulations. The load effects of ATP on highway bridges were calculated using the influence line method and evaluated based on the Chinese bridge design specifications. Results show that the load effect of ATP on bridges increases with the increase in the gross vehicle mass and the truck platooning size but decreases with the increasing inter-truck spacing and the critical wheelbase. The Grade-I (best quality standard) highway bridges are generally capable of withstanding the ATP loads, while caution should be exercised for other bridges. Strategies for preventing serious adverse impacts of ATP load on highway bridges are proposed.

Decitabine inhibits the proliferation of human T-cell acute lymphoblastic leukemia molt4 cells and promotes apoptosis partly by regulating the PI3K/AKT/mTOR pathway.

T cell acute lymphoblastic leukemia (T-ALL) is a highly aggressive hematological cancer; however, there is a lack of effective chemotherapeutic or targeted drugs for the treatment of T-ALL. Decitabine is a DNA demethylation agent but it has not been used for T-ALL treatment. Therefore, the present study aimed to assess the inhibitory effect of decitabine on T-ALL molt4 cells and determine its regulatory role in the PI3K/AKT/mTOR pathway. Molt4 cells were stimulated with decitabine in vitro, after which cell proliferation, apoptosis and cell cycle analyses were performed to assess cell viability. Subcellular morphology was observed using transmission electron microscopy. Expression levels of phosphate and tension homology (PTEN), genes involved in the PI3K/AKT/mTOR pathway and the corresponding downstream genes were analyzed using reverse transcription-quantitative PCR and western blotting. The results showed that decitabine induced apoptosis, inhibited proliferation and arrested molt4 cells in the G2 phase. Following decitabine intervention, an increase in the number of lipid droplets, autophagosomes and mitochondrial damage was observed. At concentrations of 1 and 10 µM, decitabine downregulated the expression of PI3K, AKT, mTOR, P70S6 and eukaryotic initiating factor 4E-binding protein 1, which in turn upregulated PTEN expression; however, 50 µM decitabine downregulated PTEN levels. Overall, these results demonstrated that decitabine reduced the viability of molt4 cells partly by inhibiting the PI3K/AKT/mTOR pathway via PTEN, especially at low decitabine concentrations.

The effect of rat nerve growth factor combined with vitamin B on peripheral neuropathy in multiple myeloma patients.

Background: Peripheral neuropathy can induce marked disability and negative effects on quality of life and is the most common therapy-related complication in multiple myeloma patients treated with bortezomib. Currently, there is no useful method to prevent or treat it. So, it is necessary to study the clinical efficacy of rat nerve growth factor combined with vitamin B for the treatment of peripheral neuropathy in multiple myeloma patients. Methods: Sixty multiple myeloma patients who developed peripheral neuropathy after bortezomib-based chemotherapy in Jiaxing First Hospital from October 2015 to May 2018 were randomly divided into treatment and control groups. Changes in serum NGF level and electromyograms before and after treatment were analyzed, and the effects were evaluated via a FACT/GOG-Ntx questionnaire score. Results: After treatment, the NGF level in the treatment group (13.2 ± 3.73 pg/ml) was higher than that in the control group (9.22 ± 2.93 pg/ml, P < 0.05). Improvements in the electromyograms were more pronounced in treatment group than those in the control group, with statistical significance. The FACT/GOG-Ntx questionnaire scores, both in the treatment group and the control group, were decreased (4.00 ± 1.58 vs. 5.20 ± 2.33; P < 0.05), and the alleviation of the symptoms in the treatment group were more obvious. Conclusion: Rat nerve growth factor combined with vitamin B is a safe and effective method for treating peripheral neuropathy in multiple myeloma patients.

Characterization of a 4 lncRNAs-based prognostic risk scoring system in adults with acute myeloid leukemia.

PURPOSE: The study aims to develop a prognostic scoring system based on prognostic lncRNAs for acute myeloid leukemia (AML). METHODS: Based on lncRNA expression profiles downloaded from The Cancer Genome Atlas (TCGA), differentially expressed long noncoding RNAs (DELs) between good prognosis and bad prognosis samples were screened, from which prognosis-related lncRNAs were selected using uni-variate and multi-variate Cox regression analysis. Based on the expression profiles of these signature prognosis-related lncRNAs, a risk scoring system was developed and applied to a training set and validated on a testing set. With sample-matched mRNAs of the signature lncRNAs, lncRNA-mRNA networks were built, followed by function analysis for the mRNAs in these networks. RESULT: Total 66 DELs were identified between good prognosis and bad prognosis samples. Among these DELs, LINC01003, CTD-2234N14, RP1-137K24, and RP11-834C111 were found to be independent predictors of prognosis. A risk scoring system based on the expressions of the 4 signature lncRNAs was developed. Kaplan-Meier survival analysis found that the risk score system could classify patients into high-risk and low-risk groups with significantly different survival outcomes. Function analysis showed that the mRNAs in these lncRNA-mRNA networks were significantly linked to mTOR signaling pathway, apoptosis, Fc epsilon RI signaling pathway, B cell receptor signaling pathway, natural killer cell mediated cytotoxicity, and T cell receptor signaling pathway. CONCLUSION: This study suggested a promising 4 prognostic lncRNAs-based risk scoring system in AML. These 4 lncRNAs may play roles in regulating prognosis partly via mTOR signaling pathway, apoptosis, and some immune-related pathways.

A novel scoring system for acute myeloid leukemia risk assessment based on the expression levels of six genes.

Acute myeloid leukemia (AML) is the most common type of acute leukemia and is a heterogeneous clonal disorder. At present, the pathogenesis of AML and potential methods to effectively prevent AML have become areas of interest in research. In the present study, two messenger ribonucleic acid sequencing datasets of patients with AML were downloaded from the Cancer Genome Atlas and Gene Expression Omnibus databases. The differentially expressed genes (DEGs) of the poor and good prognosis groups were screened using the Linear Models for Microarray Data package, and the prognosis­related genes were screened using univariate Cox regression analysis. A total of 206 significant DEGs were identified. Following univariate and multivariate Cox regression analysis, 14 genes significantly associated with prognosis were screened and six of these genes, including triggering receptor expressed on myeloid cells 2 (TREML2), cysteine­glutamate transporter (SLC7A11), NACHT, LRR, and PYD domains­containing protein 2 (NLRP2), DNA damage­inducible transcript 4 protein (DDIT4), lymphocyte­specific protein 1 (LSP1) and C­type lectin domain family 11 member A (CLEC11A), were used to construct model equations for risk assessment. The prognostic scoring system was used to evaluate risk for each patient, and the results showed that patients in the low­risk group had a longer survival time, compared with those in the high­risk group (P=9.59e­06 for the training dataset and P=0.00543 for the validation dataset). A total of eight main Kyoto Encyclopedia of Genes and Genomes pathways were identified, the top three of which were hematopoietic cell lineage, focal adhesion, and regulation of actin cytoskeleton. Taken together, the results showed that the scoring system established in the present study was credible and that the six genes were identified, which were significantly associated with the risk assessment of AML, offer potential as prognostic biomarkers. These findings may provide clues for further clarifying the pathogenesis of AML.