Thalidomide-induced serious RR interval prolongation (longest interval >5.0 s) in multiple myeloma patient with rectal cancer: A case report.

Primary secondary tumor increased recently with the use of immunomodulatory drugs in patients with multiple myeloma (MM). However, MM with prior diagnosis of primary secondary tumor is relatively rare. In this study, we reported an MM patient with prior diagnosis of rectal cancer. In brief, an 85-year-old man was first diagnosed with rectal cancer. Given the age, heart failure and small-cell hypochromic anemia (hemoglobin level: 54 g/L), rectal cancer resection was not advised and symptomatic treatments were performed (including sufficient iron supplementation). Eight months later, the patient was diagnosed with MM due to worsening anemia. Anemia and heart failure were corrected after three cycles of treatment with thalidomide, dexamethasone and capecitabine. Radical resection of rectal carcinoma (Hartmann) was finally performed due to acute abdominal distension. Meanwhile, RR interval prolongation (longest interval >5.0 s) and atrial fibrillation occurred in the fifth cycle treatment. One month after discontinuation of thalidomide, RR interval returned to normal range, while atrial fibrillation developed into persistent atrial fibrillation.

Identification of long non-coding RNA MVIH as a prognostic marker and therapeutic target in acute myeloid leukemia.

BACKGROUND: This study aimed to investigate the correlation of long non-coding RNA microvascular invasion in hepatocellular carcinoma (lncRNA MVIH) with disease risk, disease conditions, and prognosis of acute myeloid leukemia (AML), and also to investigate the influence of lncRNA MVIH on AML cell activities in vitro. METHODS: A total of 212 AML patients and 70 controls were consecutively recruited. Their bone marrow mononuclear cells (BMMCs) were isolated, and lncRNA MVIH was detected by reverse transcription quantitative-polymerase chain reaction. In AML patients, complete remission (CR), event-free survival (EFS), and overall survival (OS) were assessed. In vitro, lncRNA MVIH expression in AML cell lines was determined, and the effect of lncRNA MVIH on AML cell proliferation and apoptosis was assessed. RESULTS: LncRNA MVIH expression was increased in AML patients compared to controls, and receiver operating characteristic curve showed that lncRNA MVIH predicted elevated AML risk (area under curve: 0.742 [95% CI: 0.674-0.810]). In AML patients, no correlation of lncRNA MVIH expression with French-American-British classification was observed, while lncRNA MVIH high expression correlated with worse risk stratification. Moreover, lncRNA MVIH expression negatively correlated with CR achievement, EFS and OS. In vitro, lncRNA MVIH was overexpressed in AML cell lines (KG-1, ME-1, and HT-93) compared to normal BMMCs. Furthermore, lncRNA MVIH downregulation reduced KG-1 cell proliferation but increased apoptosis, whereas lncRNA MVIH upregulation raised HL-60 cell proliferation but decreased apoptosis. CONCLUSION: LncRNA MVIH may not only serve as a prognostic marker but also act as a therapeutic target in AML.

Screening of prognostic risk microRNAs for acute myeloid leukemia.

Objectives This study aimed to investigate the risk miRNAs (microRNAs) for AML (acute myeloid leukemia) prognosis and related regulatory mechanisms. Methods MiRNA and gene expression data, as well as clinical data of 176 patients were first downloaded from TCGA. Then miRNAs and genes significantly affecting the survival time based on KM survival curve were identified using Log Rank test. Next, COX proportional-hazard regression analysis was performed to screen the risk miRNAs (P-value < 0.05). Common genes from survival analysis and predicted by miRWalk were used to construct the miRNA regulatory network with the risk miRNAs. Finally, a protein-protein interaction (PPI) network was constructed, as well as functional annotation and pathway enrichment analysis. Results The survival analysis revealed 33 miRNAs and 1,377 genes significantly affecting the survival time. HR values of nine miRNAs (up-regulated hsa-mir-606, 520a, 137, 362, 599, 600, 202, 639and down-regulated 502) were either >1 or <1. The miRNA regulatory network contained 477 nodes and 944 edges. The top ten genes of the constructed PPI network were EGFR, EIF4G1, REL, TOP1, COL14A1, HDAC3, MRPL49, PSMA2, TOP2A and VCAM1 successively. According to pathway enrichment analysis, 6 KEGG pathways and 6 REACTOME pathways were obtained respectively. Conclusion Up-regulated hsa-mir-520a, 599, 606, 137 and 362 may increase the prognostic risk for AML patients via regulating the expression of corresponding target genes, especially COL14A1, HDAC3, REL, EGFR, PSMA2, EIF4G1, MRPL49 and TOP1.

Clinical study of pai-neng-da capsule in the treatment of chronic aplastic anemia.

OBJECTIVE: To evaluate the efficacy and safety of Pai-Neng-Da Capsule (panaxadiol saponins component, PND), a new Chinese patent medicine, on patients with chronic aplastic anemia (CAA) and to explore the optimal therapeutic regimen for CAA. METHOD: A total of 36 patients with CAA were enrolled and divided into three groups: the AP group (20 cases, andriol 120 mg/day + PND 240 mg/day), the ACP group (13 cases, andriol 120 mg/day + cyclosporine 3-6 mg kd(-1) day(-1) + PND 240 mg/day), and the PND group (3 cases, PND 240 mg/day). All patients were treated and followed up for 6 months. Peripheral blood counts, renal and hepatic function and Chinese medical (CM) symptoms of patients were assessed and all indices were gathered at the beginning and end of the study. RESULT: In the AP group, no significant hematologic difference was observed at the end of 6-month treatment comparing with the beginning. In the ACP group, the blood counts were maintained at the same level after the 6-month treatment. In the PND group, trilineage hematologic improvement was displayed at the end of 6-month treatment comparing with the beginning. No significant difference was showed in renal and hepatic function in all patients. All patients' clinical symptom improved according to CM symptom score. The effective rates were 95%, 73% and 100%, respectively. CONCLUSION: PND improved the efficacy and decreased side effects by cutting down the dosage of andriol, and it could also improve patients' clinical symptom and quality of life. PND were effective and safe in the treatment of CAA, it could be used alone or in combination with pharmacological agents such as andriol and cyclosporine.

Identification of key genes affecting disease free survival time of pediatric acute lymphoblastic leukemia based on bioinformatic analysis.

The poor prognosis of pediatric acute lymphoblastic leukemia (ALL) indicates the existence of key candidate genes that affect pediatric ALL and its prognosis. The limma package in R was applied to screen differentially expressed genes (DEGs), and the Survival package and KMsurv package in R were used to screen disease free survival time related genes (prognosis genes). Then, based on latent pathway identification analysis (LPIA), latent pathways were identified, and pathway-pathway interaction network was constructed and visualized by Cytoscape. Based on the expression values of 8284 genes in 126 chips, 2796 DEGs and 353 prognosis genes were screened out. After overlapping DEGs and prognosis genes, 75 key genes were identified, which were most significantly enriched in 25 GO functions and chronic myeloid leukemia pathway. For the 75 key genes, 27 disease risk sub-pathways were identified, and HK3, HNMT, SULT2B1, KYNU, and PTGS2 were the significant key genes which were enriched in these sub-pathways. Furthermore, based on pathway-pathway interaction analysis, HK3 and PTGS2 were predicted as the most important genes. Through glycolysis and arachidonic acid metabolism, HK3 and PTGS2 might play important roles in pediatric ALL and its prognosis, and thus, might be potential targets for therapeutic intervention to suppress pediatric ALL.

Stachydrine, a major constituent of the Chinese herb leonurus heterophyllus sweet, ameliorates human umbilical vein endothelial cells injury induced by anoxia-reoxygenation.

Stachydrine is a major constituent of Chinese herb leonurus heterophyllus sweet, which is used in clinics to promote blood circulation and dispel blood stasis. Our study aimed to investigate the role of stachydrine in human umbilical vein endothelial cells (HUVECs) injury induced by anoxia-reoxygenation. Cultured HUVECs were divided randomly into control group, anoxia-reoxygenation (A/R) group and 4 A/R+stachydrine groups. HUVECs in the control group were exposed to normoxia for 5 hours, while in all A/R groups, HUVECs underwent 3 hours anoxia followed by 2 hours reoxygenation, and HUVECs in the 4 A/R+stachydrine groups were treated with 10(-8) M, 10(-7) M, 10(-6) M and 10(-5) M (final concentration) of stachydrine respectively. After anoxia-reoxygenation, tissue factor (TF) was over-expressed, cell viability and the concentrations of SOD, GSH-PX and NO were declined, while LDH, MDA and ET-1 were over-produced (p < 0.05 to 0.001 vs. the control group). However, in stachydrine treated groups, TF expression was inhibited at both mRNA and protein levels, while the declined cell viability and SOD, GSH-PX, NO as well as the enhanced LDH, MDA and ET-1 levels occurred during anoxia-reoxygenation were ameliorated and reversed effectively (p < 0.05 to 0.01 versus A/R group). Consequently, our findings indicate that TF plays an important role in the development of anoxia-reoxygenation injury of HUVECs, stachydrine ameliorates HUVECs injury induced by anoxia-reoxygenation and its putative mechanisms are related to inhibition of TF expression.