Identification of Immune-Related Genes for Risk Stratification in Multiple Myeloma Based on Whole Bone Marrow Gene Expression Profiling.

Background: Multiple myeloma (MM) is characterized by abnormal proliferation of bone marrow clonal plasma cells. Tumor immunotherapy, a new therapy that has emerged in recent years, offers hope to patients, and studying the expression characteristics of immune-related genes (IRGs) based on whole bone marrow gene expression profiling (GEP) in MM patients can help guide personalized immunotherapy. Methods: In this study, we explored the potential prognostic value of IRGs in MM by combining GEP and clinical data from the GEO database. We identified hub IRGs and transcription factors (TFs) associated with disease progression by Weighted Gene Co-expression Network Analysis (WGCNA), and modeled immune-related prognostic signature by univariate and multivariate Cox and least absolute shrinkage and selection operator (LASSO) regression analysis. Subsequently, the prognostic ability of signature was verified by multiple statistical methods. Moreover, ssGSEA and GSEA algorithm reveled different immunological characteristics and biological function variation in different risk groups. We mapped the hub IRGs by protein-protein interaction network (PPI) and extracted the top 10 ranked genes. Finally, we conducted vitro assays on two alternative IRGs. Results: Our study identified a total of 14 TFs and 88 IRGs associated with International Staging System (ISS). Ten IRGs were identified by Cox -LASSO regression analysis, and used to develop optimal prognostic signature for overall survival (OS) in MM patients. The 10-IRGs were BDNF, CETP, CD70, LMBR, LTBP1, NENF, NR1D1, NR1H2, PTK2B and SEMA4. In different groups, risk signatures showed excellent survival prediction ability, and MM patients also could be stratified at survival risk. In addition, IRF7 and SHC1 were hub IRGs in PPI network, and the vitro assays proved that they could promote tumor progression. Notably, ssGSEA and GSEA results confirmed that different risk groups could accurately indicate the status of tumor microenvironment (TME) and activation of biological pathways. Conclusion: Our study suggested that immune-related signature could be used as prognostic markers in MM patients.

LncRNA UCA1 protects cardiomyocytes against hypoxia/reoxygenation induced apoptosis through inhibiting miR-143/MDM2/p53 axis.

BACKGROUND: lncUCA1 is abundantly expressed in the heart, indicating it may be important in maintaining normal myocardial function. However, the underlying mechanism of lncUCA1 in heart disease, particularly myocardial infarction (MI), is still in its infancy. METHODS: LncUCA1 and miR-143 expression were measured in hearts of MI models. Overexpression and knockdown of lncUCA1 in neonatal rat cardiomyocytes were performed to confirm the effects of lncUCA1 in hypoxia-induced apoptosis. RESULTS: The expression of lncUCA1 decreased but miR-143 increased inversely in MI heart. Overexpressing lncUCA1 protected cardiomyocytes from H/R induced apoptosis via inhibiting miR-143, which regulates apoptosis by targeting MDM2/p53 pathway. While silencing lncUCA1 caused miR-143 upregulation and H/R-induced apoptosis increase. Moreover, miR-143 was proved to be a competitive target of lncUCA1. CONCLUSIONS: lncUCA1 might protect cardiomyocyte against H/R induced apoptosis by suppressing miR-143 and modulated the following downstream MDM2/p53 signaling pathway, indicating the therapeutic potential of targeting lncUCA1 for MI.

[Safety and efficacy of subcutaneous administration of bortezomib in the treatment of multiple myeloma].

OBJECTIVE: To analyze the efficacy and safety of subcutaneous administration of bortezomib in the treatment of multiple myeloma (MM) patients. METHODS: A total of 26 MM patients were enrolled in this study and treated with BDT (bortezomib-dexamethasone-thalidomide). In the 26 MM patients, 12 patients received subcutaneous administration of Bortezomib while 14 patients received conventional intravenous administration. The outcomes and adverse effects of two groups were retrospectively evaluated and compared. RESULTS: Overall response (OR) rates in the two groups were 75.00% and 71.43% respectively, in which complete remission (CR) plus very good complete remission (VGPR) rates were 50.00% and 47.14%, while CR rates were 16.67% and 28.57%. There were no statistically significant difference (P > 0.05). Time to achieve effectiveness in two groups was similar (P > 0.05). More than half patients in both groups achieved partial remission after the first treatment course and CR after the fourth course. Compared to the intravenous group, peripheral neuropathy rates remained significantly lower in subcutaneous group (16.67% vs. 64.29%, P = 0.021). The intravenous group had 7.14% grade 3 or worse, peripheral neuropathy but none found in the subcutaneous group. Rash occurred only in subcutaneous group (66.67%), but it was local, mild and transitional. No significant differences of other adverse events between the two groups were observed. CONCLUSION: Subcutaneous administration of bortezomib offers similar efficacy to standard intravenous administration in the treatment of multiple myelom, with an improved safety for lower rate of peripheral neuropathy.

[Heavy metals content and pollution risk assessment of cropland soils around a pesticide industrial park].

By the method of concentric circle distribution method, a total of 183 topsoil samples were collected from 30-km2 area around a pesticide industrial park in south Jiangsu Province, with the content and pollution index of soil Cd, Cr, Cu, Ni, Pb, Zn, Hg and As analyzed. The average contents of Hg, Cu, Cd, and Pb in the top soils were higher than those of the natural background values, and the contents of Hg and Cu were the highest. Taking the national standard II as the assessment criterion, the average pollution index values of Cd, Cr, Cu, Ni, Pb, Zn, and As in the top soils were all below 1, while those of the Hg and Cu were 1.59 and 1.05, respectively. In the southeast and northwest to the pesticide industrial park, soil heavy metals contamination was more serious, and, with the increasing distance to the park, the contents of soil Cd, Ni, Pb, Cr, As, Hg, Zn, and Cu increased first and then decreased to a stable level. The comprehensive pollution index of test metals indicated that the areas 200-1000 meter around the industrial park were of high risk in soil heavy metals contamination, while the areas 1000 meter beyond were safety. By using geostatistics and GIS, it was found that the pollution index of the eight heavy metals had significant spatial variability. Based on the principal component analysis and correlation analysis, it was speculated that the Zn, Ni, Cr, Pb, and As were mainly from soil parent materials, while the Hg, Cu, and Cd were mainly related to human activities.

[Characteristics of paddy field nitrogen leakage and runoff in rice-duck farming system].

A field experiment was conducted to study the characteristics of paddy field nitrogen (N) leakage and runoff under rice-duck farming (MRD), conventional farming (MR), and conventional farming with flooding (CK). Comparing with that under MR, the paddy field under MRD had a notable decrease of N (especially NO3- -N) concentration in its leaked liquid; but this concentration was tended to be increased, compared with that under CK. After 7-9 days of fertilization, the NH4+ -N and NO3- -N concentrations in paddy field surface water were higher under MRD than under MR. However, owing to the no draining and the higher band, the paddy field under MRD had a notable reduction of drainage, resulting in a marked decrease of N runoff than that under MR. Comparing with MR, the paddy field under MRD had an addition of nitrogen supply from duck dung, a reduction of N leakage and runoff, a lesser application of chemical nitrogen fertilizer, and more nitrogen uptake by rice plant. Both the reduction of N input and that of N output in rice-duck farming system were nearly equal in quantity.

[Effects of relatively high temperature at grain-filling stage on rice grain's starch viscosity profile and magnesium and potassium contents].

With rice cultivars Yangdao 6 (Indica) and Wuyujing 3 (Japonica) as test materials, the effects of relatively high temperature (RHT, mean temperature 30 degrees C) at grain-filling stage (GFS) on the starch viscosity profile and magnesium (Mg) and potassium (K) contents of rice grain were studied in a phytotron. Four temperature treatments were installed, i.e., RHT at whole GFS, RHT at early GFS and optimum temperature at later GFS, optimum temperature at early GFS and RHT at later GFS, and optimum temperature (CK, mean temperature 23 degrees C) at whole GFS. The results showed that RHT at GFS significantly influenced the characteristic values of rice grain' s starch viscosity profile, e.g., the values of gelatinization temperature, final viscosity, consistency, and setback increased, while those of peak viscosity, hot viscosity, and breakdown decreased, with Yangdao 6 and Wuyujing 3 followed the similar pattern. The RHT increased the contents of Mg, K, and N, especially of K, resulting in a marked decrease of Mg/K and Mg/(N * AC * K) in the grain. The grain's amylase content (AC) of the two cultivars showed contrasting in response to temperature treatments. Wuyujing 3 performed decrease, while Yangdao 6 exhibited increase in AC values. The RHT at whole GFS affected the starch viscosity profile and the Mg and K contents most greatly, followed by the RHT at early GFS, and the RHT at later GFS. The period within 20 days after flowering was the key period during which temperature affected the grain's starch viscosity profile and Mg and K contents. The Mg/K and Mg/ (N * AC * K) in rice grain significant correlated with the characteristic values of starch viscosity profile, which could be used as the reference indices of rice eating quality.

[Strong stem effect and physiological characteristics of rice plant under rice-duck farming].

A field plot comparison experiment was conducted to study the strong stem effect and physiological characteristics of rice plant under rice-duck farming. The results showed that under rice-duck farming, the morphology of rice plant changed obviously, and the carbohydrate content and C/N ratio of the plant as well as the dry matter output from rice stem increased significantly, due to the activities of duck in paddy field. In the meantime, the length of basal internodes decreased by 2. 88%, while the stem diameter, stem mechanical strength, and stem lodging resistant index increased by 64.90%, 11.78%, and 10.95%, respectively. Rice-duck farming increased the root mass and root vitality in deeper soil layers, and decreased the proportion of black roots by 16.63%. It was indicated that rice-duck farming benefited the formation of strong rice stem and increased the stress resistance of rice plant, which would be favorable to the stable and high-yielding of rice.