[Study on Application of RVD Regimen Sequential Auto-HSCT in the Treatment of Multiple Myeloma Evaluated by Propensity Score Matching].

OBJECTIVE: To investigate the application effect of sequential autologous hematopoietic stem cell transplantation (Auto-HSCT) with lenalidomide, bortezomib and dexamethasone (RVD) in the treatment of multiple myeloma (MM) evaluated by propensity score matching. METHODS: The clinical data of 49 MM patients treated with RVD scheme and followed-up for 36 months in the hospital from January 2015 to January 2021 were retrospectively analyzed and included in the control group, the clinical data of 54 MM patients who received RVD scheme and sequential Auto-HSCT scheme and completed 36 months of follow-up in the hospital during the same period were collected and included in the observation group. PSM method (1∶1, caliper value=0.01) was used to match the control group with the observation group based on baseline data and laboratory indexes, covariate equilibrium samples were obtained between groups (40 cases in each group). The clinical efficacy of patients in the two groups after 18 weeks of treatment was compared; the incidence of toxic and side effects during treatment of patients in the two groups was compared; the survival of patients in the two groups was compared after 36 months of follow-up. RESULTS: The ORR and DCR in the observation group were higher than those in the control group, the difference was statistically significant (P<0.05). Compared the incidence of fatigue, rash, thrombocytopenia, anemia and nausea of patients in the two groups, there was no statistical significant difference (P>0.05). After 36 months of follow-up (no loss during follow-up), 4 cases died from illness in the observation group, with a survival rate of 90% and an average survival time of 35.61 (95% CI: 35541-35.685) months, 10 cases died from illness in the control group, with a survival rate of 75% and an average survival time of 34.70 (95% CI: 34.559-34.832) months, the survival rate of the observation group was higher than that of the control group, the difference was statistically significant (P<0.05). CONCLUSION: Sequential Auto-HSCT with RVD regimen in the treatment of MM can improve the short-term efficacy and increase the survival rate of patients, which will not increase toxic and side effects and has high safety.

A novel sigma class glutathione S-transferase gene in freshwater planarian Dugesia japonica: cloning, characterization and protective effects in herbicide glyphosate stress.

As the top-selling herbicide in the world, glyphosate distributes widely in natural environment and its influence on the ecological security and human health has attracted more and more concern. Glutathione S-transferases (GSTs) are a well-characterized superfamily of isoenzymes for cellular defense against exogenous toxic substances and therefore protect organisms from injury. In this study, the complete cDNA sequence of GST gene (named as Dja-GST) in freshwater planarian Dugesia japonica was firstly cloned by means of RACE method. The full-length Dja-GST comprises of 706 nucleotides which encodes a polypeptide of 200 amino acids. Dja-GST has two representative GST domains at the N- and C-termini. The conservative GST-N domain includes G-site Y8, F9, R14, W39, K43, P52 and S64, while the variable GST-C domain contains H-site K104, V156, D159 and L161. Sequence analysis, phylogenetic tree reconstruction and multiple alignment collectively indicate that Dja-GST belongs to the Sigma class of GST superfamily. Also, GST gene expression profile, GST enzymatic activity and MDA content in response to glyphosate exposure were systematically investigated and the correlations among them were analyzed. The results suggest that glyphosate exposure modified the mRNA transcription and enzymatic activity of GST, as well as the MDA content in planarians, indicating that Dja-GST might play an important part in organisms defending against oxidative stress induced by glyphosate. This work lays a molecular foundation for further exploring the exact functions of Dja-GST and gives an important implication for evaluating the ecological environment effects of herbicide glyphosate.

CuZnSOD and MnSOD from freshwater planarian Dugesia japonica: cDNA cloning, mRNA expression and enzyme activity in response to environmental pollutants.

As an important antioxidant enzyme, the superoxide dismutase (SOD) can protect aerobic organisms from oxidative damage through catalyzing the dismutation of superoxide into hydrogen peroxide and oxygen. The SODs have been cloned in some species and their dynamic expression or enzymatic activity in response to environmental stressors were investigated. In the current study, the full-length cDNA of two SODs from freshwater planarian Dugesia japonica were firstly cloned (named as DjCuZnSOD and DjMnSOD, respectively). The complete cDNA of DjCuZnSOD consists of 661 nucleotides encoding 186 amino acids while the 765 bp DjMnSOD encodes a polypeptide of 226 residues. Sequence analysis and multiple alignment showed that DjCuZnSOD possesses two CuZnSOD family signature motifs and an N-terminal signal peptide suggesting it is an extracellular secretory protein. DjMnSOD possesses the MnSOD family signature sequence and is predicted to be located in mitochondrion with a mitochondrial targeting sequence. Phylogenetic analysis based on CuZnSOD and MnSOD orthologs from representative species further verified that DjCuZnSOD is an extracellular CuZnSOD while DjMnSOD is a mitochondrial MnSOD. For the purpose of studying their potential role against environmental pollutants, D. japonica were exposed to glyphosate or 1-decyl-3-methylimidazolium bromide ([C10mim]Br), and the mRNA expression levels of DjCuZnSOD and DjMnSOD along with total SOD activity were measured. The results showed that DjCuZnSOD exhibited more sensitive expression profiles in response to environmental pollutants in contrast with DjMnSOD, and the total SOD activity in response to both pollutants was more related to the expression level of DjCuZnSOD than to DjMnSOD, indicating that the mRNA expression of CuZnSOD would be a more sensitive biomarker than MnSOD in monitoring the pollution of aquatic environment and CuZnSOD might play more important role than MnSOD in eliminating superoxide anions caused by pollutants in D. japonica.

ß1 integrin-mediated multicellular resistance in hepatocellular carcinoma through activation of the FAK/Akt pathway.

Objective To explore the role and mechanism of ß1 integrin in the regulation of multicellular drug resistance in hepatocellular carcinoma (HCC). Methods This in vitro study used a liquid overlay technique to obtain multicellular spheroids of two human HCC cell lines, HepG2 and Bel-7402. The morphology of the spheroids was observed by optical and electron microscopy. The effects of exposure to 5-fluorouracil (5-FU) and cisplatin (CDDP) on cell proliferation and the induction of apoptosis were assessed in monolayer cells and multicellular spheroids. The levels of ß1 integrin and the effects on the focal adhesion kinase (FAK)/protein kinase B (Akt) pathway were evaluated using Western blot analysis, immunofluorescence and flow cytometry. The role of ß1 integrin was confirmed by using an inhibitory antibody. Results Cell proliferation inhibition and cell apoptosis induced by 5-FUl and CDDP were abrogated in multicellular spheroids compared with monolayer cells. There were high levels of ß1 integrin in multicellular spheroids. ß1 integrin inhibitory antibody prevented the formation of multicellular spheroids, coupled with a significant increase in proliferation inhibition and apoptosis induction. ß1 integrin inhibitory antibody effectively suppressed activation of both FAK and Akt in multicellular spheroids. Conclusions ß1 integrin mediated multicellular drug resistance through the FAK/Akt pathway in HCC spheroids.

A common genetic variation in CEBPE and acute lymphoblastic leukemia: a meta-analysis of the available evidence.

Acute lymphoblastic leukemia (ALL) has been studied intensively for decades, but the details of its etiology and underlying mechanisms have yet to be fully elucidated. It is now generally acknowledged that genetic factors contribute greatly to the development of this disease. The gene encoding CCAAT/enhancer-binding protein ε (CEBPE) is involved in the development of leukemia, and in particular the rs2239633 single nucleotide polymorphism (SNP) of CEBPE. The association between rs2239633 and risk of ALL has been well studied, but remains unclear. Therefore, a meta-analysis was performed in this study to establish a more precise estimation of that relationship. A comprehensive literature search of the PubMed electronic database was conducted, and relevant studies published up to February 20, 2015 were selected for analysis. The references of the retrieved articles were also screened. The extracted data were analyzed statistically, and pooled odds ratios with 95% confidence intervals were calculated using Review Manager (version 5.2) to estimate the association strength. Finally, eleven studies were included in the meta-analysis. The pooled analyses revealed that rs2239633 was associated with an increased risk of childhood ALL in Caucasians under any contrast models (P<0.01). However, this SNP did not affect the risk of ALL in adulthood among Caucasians, or in childhood among East Asians. In conclusion, these findings confirm that the CEBPE rs2239633 SNP could be considered a good marker of pediatric ALL risk in Caucasians, but not in East Asians; it is not a good marker of adult ALL risk in Caucasians.

[Advance of studies on microRNA and myelodysplastic syndrome].

MicroRNA (miRNA), evolutionarily conserved, endogenous, small, noncoding RNA molecule of about 22 nucleotides in length, have been recently attributed a crucial role in numerous physiological and pathological processes including the regulation of cellular development, differentiation, proliferation, apoptosis and oncogenesis. Myelodysplastic syndrome (MDS) is a heterogeneous group of clonal hematologic disorders characterized clinically and morphologically by ineffective hematopoiesis and increased risk of leukaemic transformation. The role of miRNA abnormal expression in pathogenesis and prognosis of MDS is reviewed in this article, including miRNA related with pathogenesis, miRNA related with prognosis of MDS and so on.