Association of interleukin-18 gene polymorphism and its protein expression with the lower extremity deep venous thrombosis in the chinese han population: A case-control study.

OBJECTIVE: We aim to explain the correlation among IL-18 gene polymorphism, its protein expression and LEDVT in the Chinese Han population. METHODS: A total of 138 LEDVT patients and 150 healthy people volunteered as LEDVT and control groups. All the data, including the gender, age, BMI, levels of TG, LDL/HDL, TC, GLU, APTT, BUN, Cr, ALT, AST, ApoA1, ApoB, and Fg was detected. IL-18 level, IL-18 -137G/C and -607C/A polymorphism, and risk factors of LEDVT were detected using ELISA, PCR-RFLP and multivariate logistic regression analysis, respectively. RESULTS: Increased BMI, GLU, Fg, BUN, ApoB and IL-18 and decreased APTT were found in the LEDVT group. The GC + CC genotype and C allele in -137G/C polymorphism was elevated in the control group when compared to that in the LEDVT group. The IL-18 level was elevated in the case group when compared to the control group with respect to the same genotype in -607C/A and -137G/C polymorphisms, and in the LEDVT group, IL-18 level was higher in the GG genotype than that in the GC + CC genotype of -137G/C polymorphism. BUN, GG genotype and IL-18 level were independent risk factors, but APTT was a protective factor of LEDVT. CONCLUSION: On the basis of our results, we concluded that the GG genotype of -137G/C polymorphism and IL-18 level are independent risk factors of LEDVT, and IL-18 gene polymorphism affects the level of IL-18 in LEDVT patients.

Anticarcinogenic effect of Umbelliferone in human prostate carcinoma: An in vitro study.

PURPOSE: To explore the chemoprotective effect of umbelliferone (UF) on prostate cancer cell lines, i.e. primary stage (LnCap) and last stage (PC3) prostate cancer together with the effect on the induction of apoptosis and alteration on cell cycle arrest. METHODS: Various concentrations of UF were evaluated against the different prostate cancer cell lines. Lipopolysaccharide (LPS) induced cytokines related factor profiling, proinflammatory cytokines, and inflammatory mediators were studied using Western blot analysis. RESULTS: UF showed significant apoptotic effect. Moreover, treatment with UF did not show apoptosis or cell cycle arrest on the non-cancerous cells including BHP-1, suggesting a selective tumor cell specific effect. UF treatment also enhanced the expression of Bax in PC3 cells, but had no significant effect on the activation of nuclear factor κB (NF-κB). Thus, the apoptosis induction was independent of NF-κB activation. CONCLUSION: The results of the present investigation confirmed the chemoprotective effect of UF in early-stage (Ln- Cap) and late-stage (PC3) prostate cancer cells.

The impact of lipid-metabolizing genetic polymorphisms on body mass index and their interactions with soybean food intake: a study in a Chinese population.

OBJECTIVE: To evaluate the association of known polymorphisms in the lipid metabolic pathway with body mass index (BMI), and estimate their interactions with soybean food intake. METHODS: A community-based cross-sectional survey was conducted in a Chinese Han population. BMI, soybean food intake, and single nucleotide polymorphisms of rs599839, rs3846662, rs3846663, rs12916, rs174547, rs174570, rs4938303, and rs1558861 were measured in 944 subjects. A multivariate logistic regression was used to analyze the association of the studied polymorphisms with BMIs. The expectation-maximization algorithm was employed to evaluate the extent of linkage disequilibrium between pairwise polymorphisms. The gene-environment interaction was assessed in the general multifactor dimensionality reduction model. RESULTS: The polymorphisms of rs3846662 and rs3846663 were associated with 10% highest BMIs when comparing to the 10% lowest values both in individuals and haplotype-based association tests. Although no statistically significant gene-environment interactions were found, people with the haplotype composed of C allele in rs3846662 and T allele in rs3846663 and low frequency of soybean intake had significantly higher risk to overweight and obesity as compared with those with the haplotype consisting of T allele in rs3846662 and C allele in rs3846663 and highly frequent soybean food intake, with an odds ratio of 1.64 (95% confidence interval: 1.15-2.34, P<0.01) after adjusting for the common confounders. CONCLUSION: Our study has suggested that rs3846662 and rs3846663 may be the potential candidate polymorphisms for obesity, and their effect on the pathogenesis could be mediated by the frequency of soybean food intake.

Efficacy of vitamin D plus calcium with/without alendronate on bone metabolism in immunologic thrombocytopenic purpura patients with steroid treatment: Nine-month results of a randomized, double-blinded, controlled trial.

Bone loss is a prominent complication in immunologic thrombocytopenic purpura (ITP) patients with steroid treatment. Anti-osteoporotic medications are applied as a therapeutic strategy to prevent bone deterioration in ITP patients. However, the skeletal protective effect of alendronate (ALN) in ITP patients has been rarely reported. The present study was performed to determine whether ALN reduces bone loss in ITP patients. A total of 40 ITP patients with steroid treatment were randomized into a placebo group [n=20; caltrate D (CalD)] and an ALN (10 mg/day) + CalD group (n=20). The patients received CalD or CalD + ALN treatment for 9 months. The primary outcomes were bone mineral density (BMD) in the lumbar vertebrae (L1-L4), femoral neck and total hip, as well as bone metabolism markers. The results indicated that the BMD of the lumbar vertebrae (L1-L4), femoral neck and total hip was significantly increased after ALN + CalD treatment for at 6 and 9 months compared with the baseline. Compared with CalD treatment alone, CalD combined with ALN significantly elevated the BMD at the three skeletal sites at 9 months. Compared with the baseline levels or CalD treatment alone, ALN together with CalD treatment markedly reduced urinary Ca excretion and the serum levels of the bone resorption markers tartrate resistant acid phosphatase 5b and C-terminal telopeptides of type 1 collagen, at 9 months. In conclusion, treatment with ALN together with CalD significantly elevated the BMD at three skeletal sites, and inhibited urinary Ca excretion and the activity of bone resorption markers in patients with ITP.

ENPP1 K121Q (rs1044498 C > A) genetic polymorphism confers a high risk of susceptibility to coronary heart disease: A PRISMA-compliant article.

BACKGROUND: Previous studies suggested an association between K121Q (rs1044498 C > A) in ecto-nucleotide pyrophosphatase phosphodiesterase 1 (ENPP1) gene and the risk of coronary heart disease (CHD), but the results have been inconsistent. In this study, we performed a meta-analysis of several trials to systematically summarize their potential association. METHODS: Relevant articles were identified by searching electronic databases for studies published prior to March 2018. We carefully reviewed published studies on ENPP1 genetic polymorphism in relation to CHD susceptibility. The data extracted from selected high-quality studies were analyzed using STATA statistical software (StataCorp LP, College Station, TX, USA). RESULTS: Nine eligible studies which contained a combined total of 1547 CHD cases and 2213 healthy controls were chosen in the present meta-analysis. Our results indicated that K121Q strongly correlated with increased risk of CHD. The subgroup analysis on race, sample source, disease type, sex, age, and genotype showed that in Caucasians, K121Q strongly correlated with increased risk of CHD, but no difference was found in Chinese. Both single factor and multiple factor regression showed that race, sample origin, disease type, sex, age, and genotype were not the source of heterogeneity. CONCLUSIONS: Our meta-analysis revealed that the K121Q (rs1044498 C > A) in the ENPP1 gene is a risk factor for CHD.

Glycogen Phosphorylase Isoenzyme Bb, Myoglobin and BNP in ANT-Induced Cardiotoxicity.

Anthracyline (ANT) has been demonstrated as a useful treatment for leukemia and solid tumors. However, ANT has previously reported cardiotoxic effects, which can reduce the therapeutic index for cancer treatment. This study aimed to investigate the associations of glycogen phosphorylase isoenzyme BB (GPBB), myoglobin (Mb), and brain natriuretic peptide (BNP) with anthracycline (ANT-induced cardiotoxicity (AIC)) amongst the Chinese population. Patients suffering from leukemia were recruited. Electrocardiogram and echocardiography were used along with chemotherapy to determine left ventricular ejection fraction (LVEF), mitral ratio of peak early to late diastolic filling velocity (E/A), E-wave deceleration time (EDT), and isovolumic relaxation time (IVRT). Double-antibody sandwich enzyme-linked immunosorbent assay (DAS-ELISA) was employed to examine and compare serum GPBB, Mb, and BNP levels. Following chemotherapy, the patients presented higher levels of serum GPBB, Mb, and BNP than before chemotherapy treatment. The levels of LVEF (%), E/A, and IVRT were significantly decreased after chemotherapy, while EDT was markedly increased. The cumulative ANT dose was positively corelated to serum GPBB, Mb, and BNP levels while it was negatively corelated to LVEF levels. In conclusion, serum GPBB, Mb, and BNP levels in combination might provide higher diagnostic accuracy in the early detection of AIC compared with other single indicators.

[Genetic epidemiological study on discordant sib pairs of ischemic stroke in Beijing Fangshan District].

OBJECTIVE: To investigate the association among serum lipids, blood pressure, -514C/T polymorphism of hepatic lipase gene and subtypes of ischemic stroke in the discordant sib pairs. METHODS: Ischemic stroke cases were enrolled from a hospital-based stroke registry, the proband-initiated contact was used to recruit pedigrees, and participants' information and blood samples were collected through the community-based health care networks in rural areas of China. Statistical analysis was performed by using the Wilcoxon signed rank test to compare quantitative differences between sib pairs and the McNemar test to compare qualitative differences. Generalized estimating equation (GEE) was used to adjust for within-family correlation in analysis of discordant sib pairs. Family based association test (FBAT) was applied to associations between serum lipids, blood pressure and the -514T allele in hepatic lipase gene. RESULTS: Totally 107 discordant sib pairs from 71 ischemic stroke patients pedigrees were analyzed by univariate and multivariate methods. The blood pressure and serum lipids were associated with ischemic stroke (P<0.05) The lipid level was higher in large-artery atherosclerosis ischemic stroke than in the subtype of small-vessel occlusion, while the blood pressure was higher in the latter. The -514T allele in hepatic lipase gene was associated with low density lipoprotein-cholesterol (LDL-C) and diastolic blood pressure in additive model by FBAT analysis (Z=2.366, P<0.05), and it was also associated with diastolic blood pressure in additive model (Z=-2.277, P<0.05) and recessive model (Z=-2.244,P< 0.05), but not associated with ischemic stroke or its subtypes. CONCLUSION: In these discordant sib pairs, the abnormalities of blood pressure and serum lipids may increase risks of ischemic stroke, and different subtypes of ischemic stroke may differ from each other in etiology. The -514T allele in hepatic lipase gene may be associated with LDL-C and diastolic blood pressure.

IRF-3 gene polymorphisms are associated with the susceptibility to and the survival in chronic lymphocytic leukemia and could also serve as an auxiliary index.

The objective of this article was to investigate the relationship between IRF-3 gene polymorphisms and the susceptibility and prognosis of CLL. Between January 2011 and August 2012, 108 CLL patients and 112 healthy were enrolled in the study. DHPLC and Shesis software were applied in our study. In rs7251, CG genotype may increase the CLL risk. In the rs2304206, the alleles T may increase the CLL risk. The GTC haplotype can decrease the CLL risk in normal people, the GTT haplotype can increase the CLL risk in normal people. After treatment, in the rs7251, the event-free survival (EFS) in patients carrying CC genotype was higher than those carrying CG + GG genotype. In the rs2304206, the EFS in patients carrying CC genotype was higher than those carrying CT + TT genotype. IRF-3 gene polymorphisms were associated with the susceptibility and prognosis of CLL, it can be used as an auxiliary index for clinical detection of CLL.

BRAF kinase inhibitor exerts anti-tumor activity against breast cancer cells via inhibition of FGFR2.

Most anti-angiogenic therapies currently being evaluated in clinical trials targetvascular endothelial growth factor (VEGF) pathway; however, the tumor vasculature can acquire resistance to VEGF-targeted therapy by shifting to other angiogenesis mechanisms. Therefore, other potential therapeutic agents that block non-VEGF angiogenic pathways need to be evaluated. Here we identified BRAF kinase inhibitor, vemurafenibas an agent with potential anti-angiogenic and anti-breast cancer activities. Vemurafenib demonstrated inhibition of endothelial cell proliferation, migration, and tube formation in response to basic fibroblast growth factor (bFGF). In ex vivo and in vivo angiogenesis assays, vemurafenib suppressed bFGF-induced microvessel sprouting of rat aortic rings and angiogenesis in vivo. To understand the underlying molecular basis, we examined the effects of vemurafenib on different molecular components in treated endothelial cell, and found that vemurafenib suppressed bFGF-triggered activation of FGFR2 and protein kinase B (AKT). Moreover, vemurafenib directly inhibited proliferation and blocked the oncogenic signaling pathways in breast cancer cell. In vivo, using xenograft models of breast cancer cells MDA-MB-231, vemurafenib showed growth-inhibitory activity associated with inhibition of tumor angiogenesis. Taken together, our results indicate that vemurafenib targets the FGFR2-mediated AKT signaling pathway in endothelial cells, leading to the suppression of tumor growth and angiogenesis.

Exploration of molecular mechanisms of diffuse large B-cell lymphoma development using a microarray.

OBJECTIVE: We aimed to identify key genes, pathways and function modules in the development of diffuse large B-cell lymphoma (DLBCL) with microarray data and interaction network analysis. METHODS: Microarray data sets for 7 DLBCL samples and 7 normal controls was downloaded from the Gene Expression Omnibus (GEO) database and differentially expressed genes (DEGs) were identified with Student's t-test. KEGG functional enrichment analysis was performed to uncover their biological functions. Three global networks were established for immune system, signaling molecules and interactions and cancer genes. The DEGs were compared with the networks to observe their distributions and determine important key genes, pathways and modules. RESULTS: A total of 945 DEGs were obtained, 272 up-regulated and 673 down-regulated. KEGG analysis revealed that two groups of pathways were significantly enriched: immune function and signaling molecules and interactions. Following interaction network analysis further confirmed the association of DEGs in immune system, signaling molecules and interactions and cancer genes. CONCLUSIONS: Our study could systemically characterize gene expression changes in DLBCL with microarray technology. A range of key genes, pathways and function modules were revealed. Utility in diagnosis and treatment may be expected with further focused research.

[Modified radical operation for early breast cancer for preserving nipple-areolar complex and breast reconstruction using transverse rectus abdominis myocutaneous (TRAM) flap].

BACKGROUND & OBJECTIVE: Modified radical mastectomy (MRM) operation has become an important surgical therapy for early stage breast cancer, but how to reconstruct breast and preserve nipple-areolar complex (NAC) is controversial. In this study, we applied a modified radical mastectomy for early stage breast cancer for preserving NAC and breast reconstruction using transverse rectus abdominis myocutaneous (TRAM) flap. METHODS: During operation we performed the subcutaneous glandular excision and axillary dissection, and reconstructed the breast using TRAM flap in 10 patients with early stage breast cancer; meanwhile, maximam extent of breast skin and NAC were preserved. RESULTS: The appearance of the reconstructed breast was better preserved after operation. No local recurrence and distant metastasis occurred in the patients during the follow up time (range 24-48 months). No skin flap necrosis, atrophy, and scleroses surround the NAC were observed; and no abdominal wall hernia occurred at the donor site. The nipple sensation was recovered half a year after surgery. CONCLUSION: Modified radical operation for preserving NAC and breast reconstruction using TRAM flap may be a better way for breast cancer patients in early stage who request well preserving of breast. More samples are needed for proving the effects of this operation.