Diastolic suction in heart failure: Impact of left ventricular geometry,untwist, and flow mechanics

Aims

Vector flow mapping (VFM) can be used to assess intraventricular hemodynamics quantitatively. This study assessed the magnitude of the suction flow kinetic energy with VFM and investigated the relation between left ventricular (LV) function and geometry in patients with an estimated elevated LV filling pressure.

Materials and methods

We studied 24 subjects with an elevated LV filling pressure (EFP group) and 36 normal subjects (normal group). Suction was defined as flow directed toward the apex during the period from soon after systolic ejection to before mitral inflow. The flow kinetic energy index was quantified as the sum of the product of the blood mass and velocity vector and its magnitude to the peak value was measured.

Key findings

Suction flow was observed in 12 (50%) EFP-group patients and 36 (100%) normal-group subjects. The magnitude of the suction kinetic energy index was significantly smaller in EFP versus normal group (2.7 ± 3.8 vs. 5.7 ± 4.4 g/s/cm², P < 0.01). The EFP-group patients with suction had a smaller LV end-systolic volume (ESV) (P < 0.01), greater ellipsoidal geometry (P < 0.05) and untwisting rate (P < 0.01) than the EFP-group patients without suction. A regression analysis indicated a significant linear relation between the suction kinetic energy index and LVEF (r = 0.43, P = 0.04), ESV (r = − 0.40, P = 0.05), eccentricity index (r = 0.44, P = 0.04), and untwisting rate (r = 0.51, P = 0.04).

Significance

The magnitude of the suction flow kinetic energy index derived from VFM may allow the quantitative assessment of the suction flow, which correlates with LV systolic function, geometry, and untwisting mechanics.     

Plasma lecithin:cholesterol acyltransferase activity modifies the inverse relationship of C-reactive protein with HDL cholesterol in nondiabetic men

Lecithin:cholesterol acyltransferase (LCAT) is instrumental in high-density lipoprotein (HDL) maturation, but high LCAT levels do not predict low cardiovascular risk. LCAT may affect antioxidative or anti-inflammatory properties of HDL. We determined the relationship of plasma high-sensitivity C-reactive protein (CRP) with LCAT activity and evaluated whether LCAT activity modifies the decreasing effect of HDL cholesterol (HDL-C) on CRP, as an estimate of its anti-inflammatory properties. Plasma HDL-C, apolipoprotein (apo) A-I and LCAT activity (exogenous substrate method) were measured in 260 nondiabetic men without cardiovascular disease. CRP was correlated inversely with HDL-C and apo A-I, and positively with LCAT activity (P < 0.01 to 0.001). Multivariate regression analysis demonstrated that age- and smoking-adjusted plasma CRP levels were associated negatively with HDL-C (β = − 0.224, P < 0.001) and positively with LCAT activity (β = 0.119, P = 0.034), as well as with the interaction between HDL-C and LCAT activity (β = 0.123, P = 0.026). There was also an interaction between apo A-I and LCAT activity on CRP (β = 0.159, P = 0.005). These relationships remained similar after adjustment for apo B-containing lipoproteins. In conclusion, the inverse relationship of HDL-C with CRP is attenuated by LCAT activity at higher HDL-C levels. It is hypothesized that LCAT could mitigate HDL's anti-inflammatory or antioxidative properties at higher HDL-C concentrations.     

The RTK/ERK pathway is associated with prostate cancer risk on the SNP level: A pooled analysis of 41 sets of data from case–control studies

Prostate cancer (PCa) is a malignant disease influencing numerous men worldwide every year. However, the exact pathogenesis and the genes, environment, and other factors involved have not been explained clearly. Some studies have proposed that cell signaling pathways might play a key role in the development and progression of PCa. According to our previous study, the RTK/ERK pathway containing nearly 40 genes was associated with PCa risk. On the basis of these genes, we conducted a meta-analysis with our own Chinese Consortium for Prostate Cancer Genetics (ChinaPCa) study and available studies in the databases to describe the association between the pathway and PCa on the SNP level. The results suggested that rs4764695/IGF1 (recessive model: pooled OR = 0.92, 95%CI = 0.852–0.994, P = 0.034; I² = 0%, P = 0.042; allele analysis: pooled OR = 0.915, 95%CI = 0.874–0.958, P = 0; I² = 0%, P = 0.424; codominant model: OR = 0.835, 95%CI = 0.762–0.916, P = 0; I² = 0%, P = 0.684) and rs1570360/VEGF (recessive model: OR = 0.596, 95%CI = 0.421–0.843, P = 0.003; I² = 23.9%, P = 0.269; codominant model: OR = 0.576, 95%CI = 0.404–0.820, P = 0.002; I² = 49.1%, P = 0.140) were significantly associated with PCa. In subgroup analysis, the relationship was also found in Caucasians for IGF1 (dominant model: OR = 0.834, 95%CI = 0.769–0.904, P = 0; allele analysis: OR = 0.908, 95%CI = 0.863–0.955, P = 0; AA vs CC: OR = 0.829, 95%CI = 0.750–0.916, P = 0; AC vs CC: OR = 0.837, 95%CI = 0.768–0.912, P = 0). In addition, in Asians (allele analysis: OR = 0.21, 95%CI = 0.168–0.262, P = 0) and Caucasians (recessive model: OR = 0.453, 95%CI: 0.240–0.855, P = 0.015; codominant model: OR = 0.464, 95%CI = 0.240–0.898, P = 0.023) for VEGF, the association was significant. The results indicated that rs4764695/IGF1 and rs1570360/VEGF might play a key role in the development and progression of PCa. On the SNP level, we suggest that the study gives us a new view of gene-pathway analysis and targeted therapy for PCa.     

Association of the ins/del polymorphisms of uncoupling protein 2 (UCP2) with BMI in a Korean population

To elucidate the potential impact of the variants of the UCP2 gene on obesity phenotypes, we have genotyped four polymorphisms in UCP2 among 988 Korean subjects using TaqMan^® methods, and three common haplotypes with frequency greater than 0.1 were constructed in the Korean population. No significant associations were detected with the risk of metabolic syndrome by logistic regression analyses. However, the 45 base-pair ins/del polymorphism (+3474 ins/del) in the 3′ untranslated region (3′ UTR) showed significant association with body mass index (P = 0.007, P^corr = 0.02) and waist circumference (P = 0.005). Further subgroup analysis revealed that the genetic effects were more apparent among female subjects. In addition, a summary of the controversial genetic effects on obesity mediated by UCP2 polymorphisms from previous studies is also given. Our results suggest that subjects with a 45 bp insertion allele of UCP2+3474 ins/del might have a higher risk of developing obesity, although the biological effects of this variant are not completely known.     

An obesity genetic risk score is associated with metabolic syndrome in Chinese children

Recent genome-wide association studies have identified several single nucleotide polymorphisms (SNPs) associated with body mass index (BMI)/obesity. In this study, we aim to examine the associations of obesity related loci with risk of metabolic syndrome (MetS) in a children population from China. A total of 431 children with MetS and 3046 controls were identified based on the modified ATPIII definition. 11 SNPs (FTO rs9939609, MC4R rs17782313, GNPDA2 rs10938397, BDNF rs6265, FAIM2 rs7138803, NPC1 rs1805081, SEC16B rs10913469, SH2B1 rs4788102, PCSK1rs6235, KCTD15 rs29941, BAT2 rs2844479) were genotyped by TaqMan 7900. Of 11 SNPs, GNPDA2 rs10938397, BDNF rs6265, and FAIM2 rs7138803 were nominally associated with risk of MetS (GNPDA2 rs10938397: odds ratio (OR) = 1.21, 95% confidence interval (CI) = 1.04–1.40, P = 0.016; BDNF rs6265: OR = 1.19, 95% CI = 1.03–1.39, P = 0.021; FAIM2 rs7138803: OR = 1.20, 95% CI = 1.02–1.40, P = 0.025); genetic risk score (GRS) was significantly associated with risk of MetS (OR = 1.09, 95% CI = 1.04–1.15, P = 5.26 × 10^− 4). After further adjustment for BMI, none of SNPs were associated with risk of MetS (all P > 0.05); the association between GRS and risk of MetS remained nominally (OR = 1.02, 95%CI = 0.96–1.08, P = 0.557). However, after correction for multiple testing, only GRS was statistically associated with risk of MetS in the model without adjustment for BMI. The present study demonstrated that there were nominal associations of GNPDA2 rs10938397, BDNF rs6265, and FAIM2 rs7138803 with risk of MetS. The SNPs in combination have a significant effect on risk of MetS among Chinese children. These associations above were mediated by adiposity.     

Current evidence on the relationship between five polymorphisms in the matrix metalloproteinases (MMP) gene and lung cancer risk: A meta-analysis

Purpose

Matrix metalloproteinase (MMP) 1, MMP2, MMP3 and MMP9 are important members of the MMP family. Recently, many studies have been carried out on the association between polymorphisms of MMP1-1607 1G/2G, MMP2-735 C/T, MMP2-1306 C/T, MMP3-1171 5A/6A and MMP9-1562 C/T and lung cancer risk. However the results of these studies remained inconclusive due to conflicting results from different case–control studies. To clarify these associations, we conducted a meta-analysis.

Methods

We conducted a comprehensive search in Medline, EMBASE, OVID and Chinese Biomedical Literature Database (date from Jan 2000 to Aug 2012). Overall and subgroup analysis by the ethnicity of study population was carried out. Odds ratio (OR) with 95% confidence interval (95%CI) was used to assess the strength of the association.

Results

There were 17 studies involving five polymorphic sites in four MMP genes. For MMP1-1607,increased lung cancer risk was found under dominant model (MMP1-1607 1G/2G: OR = 1.14, 95%CI = 1.03–1.26, P = 0.01), but not in the Caucasian population. For MMP2-1306 C/T, T polymorphism decreased lung cancer risk under dominant and recessive models (dominant, OR = 0.63, 95%CI = 0.46–0.88, P = 0.0006; recessive, OR = 0.61, 95%CI = 0.38–0.99, P = 0.04). For MMP9-1562 C/T, TT genotype decreased this risk under the recessive model (OR = 0.38, 95%CI = 0.19–0.75, P = 0.005), but not in the Asian population. For MMP2-735 C/T and MMP3-1171 5A/6A, there was no association between this polymorphism and lung cancer risk under the dominant and recessive models.

Conclusions

MMP1-1607 1G/2G polymorphism increased lung cancer risk in Asians. It was also found thatMMP2-1306 C/T polymorphism decreased lung cancer risk in Asians, while MMP9-1562 C/T polymorphism decreased lung cancer risk in Caucasians. No significant difference was found in any genotype of MMP2-735 C/T and MMP3-1171 5A/6A. Further studies with larger sample sizes should be carried out.     

Heterologous in vitro fertilization is a good procedure to assess the fertility of thawed ram spermatozoa

A heterologous in vitro fertilization (IVF) test using calf oocytes with zona pellucida was employed to assess the fertility of thawed ram sperm samples. Six males with significant differences in fertility (P = 0.003) were used. The males were classified as having high fertility (≥42%) and low fertility (≤41%). Male fertility was not influenced by number of inseminated ewes (P = 0.584), insemination technician (P = 0.156), insemination date (P = 0.323) or farm (P = 0.207). Thawed sperm samples were employed to assess several sperm parameters for each male: motility, acrosomal integrity, viability, membrane stability, membrane phospholipid disorder, mitochondrial membrane potential and chromatin stability. These samples were used to carry out a heterologous in vitro fertilization. In vitro-matured calf oocytes (n = 716) were inseminated with thawed ram semen and in vitro cultured for 40 h. Overall, at thawing, variability among males respect to sperm quality was high. Despite this variability, there were not differences (P < 0.05) between fertility groups. Yield of hybrid embryos ranged from 31 to 59% between males. There were not differences between males (P = 0.340). However, there were differences between fertility groups (high fertility: 55%; low fertility: 39%; P = 0.020). Multiple regression analysis showed that the heterologous in vitro fertility was the only predictive parameter for in vivo male fertility. Correlation between both parameters was fair (r² = 0.760; P = 0.025). These results indicate that heterologous in vitro fertilization tests can be useful to predict the fertility of ram spermatozoa using calf oocytes with intact-zona pellucida.     

Influence of inflammatory response,infection, and pulmonary function in cystic fibrosis

Aims

Recurrent infections and activation of the inflammatory response affect the prognosis of cystic fibrosis (CF). We investigated the relationship between inflammatory response, infection, and pulmonary function in CF.

Main methods

A clinical-cross-sectional study was conducted with 86 subjects: control group (CG, n = 31, the same age and sex of the CF group), and CF group (CFG, n = 55, age: 1–16 years), further distributed into CFG negative or positive bacteriology (CFGB⁻/CFGB⁺), and CFG negative or positive Pseudomonas aeruginosa (CFGPa⁻/CFGPa⁺). Using the Wald test, multiple linear regression (95% confidence interval) was performed between CG and CFG, and between CG and each of the CF subgroups (CFGB⁻/CFGB⁺ and CFGPa⁻/CFGPa⁺). The inflammatory markers evaluated were myeloperoxidase (MPO), adenosine deaminase (ADA) activities, interleukin-1beta (IL-1β), tumor necrosis factor-alpha (TNF-α), C-reactive protein (CRP), nitric oxide metabolites (NOx) levels, and total and differential leukocyte counts.

Key findings

After adjusting for sex and age, CFG compared to CG revealed an increase of MPO, IL-1β (P < 0.001 in all subgroups), and CRP: CFG (P = 0.002), CFGB⁻ (P = 0.007), CFGB⁺ (P = 0.009), CFGPa⁻ (P = 0.004) and CFGPa⁺ (P = 0.020). NOx (P = 0.001, P < 0.001), leukocytes (P = 0.002, P = 0.001), and neutrophils (P = 0.003, P < 0.001) were increased in CFGB⁺ and CFGPa⁺, respectively. A negative correlation between FEV₁ and leukocytes (P = 0.008) and FEV₁ and neutrophils (P = 0.031) resulted in CFG.

Significance

The inflammatory response characterized by the increase of MPO, IL-1β, and CRP is determinant for CF. Also leukocytosis due to neutrophilia determines the pulmonary function deficiency in this disease.     

A structure–activity relationship study of flavonoids as inhibitors of E. coli by membrane interaction effect

Flavonoids exhibit a broad range of biological activities including antibacterial activity. However, the mechanism of their antibacterial activity has not been fully investigated. The antibacterial activity and membrane interaction of 11 flavonoids (including 2 polymethoxyflavones and 4 isoflavonoids) against Escherichia coli were examined in this study. The antibacterial capacity was determined as flavonoids > polymethoxyflavones > isoflavonoids. Using fluorescence, it was observed that the 5 flavonoids rigidified the liposomal membrane, while the polymethoxyflavones and isoflavonoids increased membrane fluidity. There was a significant positive correlation between antibacterial capacity and membrane rigidification effect of the flavonoids. A quantitative structure–activity relationship (QSAR) study demonstrated that the activity of the flavonoid compounds can be related to molecular hydrophobicity (CLogP) and charges on C atom at position3 (C3). The QSAR model could be used to predict the antibacterial activity of flavonoids which could lead to natural compounds having important use in food and medical industry.     

Association of the common FTO-rs9939609 polymorphism with type 2 diabetes,independent of obesity-related traits in a Vietnamese population

Type 2 diabetes (T2D) is a complex disorder resulting from both genetic and environmental factors in its pathogenesis. A case − control study was designed with subjects recruited from a general population to investigate whether the association between T2D and the common T > A polymorphism (rs9939609) in fat mass and obesity associated (FTO) gene is mediated by obesity-related measurements, considering the contribution of socio-economic status and lifestyle factors. The significant association between the FTO rs9939609 polymorphism and T2D was first observed in the model unadjusted (OR per A allele = 1.61, 95% CI = 1.06–2.44, P = 0.024). It remained consistently replicated in the final model after adjustments for sex, age, systolic blood pressure, socio-economic status, lifestyle factors, and obesity-related measurements (body mass index, waist–hip ratio, body fat percentage, and body adiposity index), showing an increased T2D risk with an additive effect of the alleles (ORs per A allele = 1.80–1.92, 95% CI = 1.09–3.19, P < 0.05). The FTO-rs9939609 polymorphism, systolic blood pressure, and waist–hip ratio were the most significant independent predictors for T2D, in which the power of the adjusted prediction model was 0.769. In conclusion, the study suggested that the FTO-rs9939609 polymorphism was significantly associated with the increased risk of T2D, independent of obesity-related measurements in a Vietnamese population.     

Interleukin-23 receptor genetic variants contribute to susceptibility of multiple cancers

Aim

Interleukin-23 (IL-23) and IL-23 receptor (IL23R) play an important role during the T-helper 17 (Th17) cell-mediated inflammatory process as well as pathogenesis of multiple cancers. Several IL-23R single nucleotide polymorphisms (SNPs), especially rs6682925, rs10889677 and rs1884444 polymorphisms, are considered to have significant impacts on susceptibility of multiple cancers. A number of case-control studies have explored the role these genetic polymorphisms in development of carcinogenesis, but the conclusions are inconsistent. Therefore, we conducted this meta-analysis to systematically investigate the associations between the three genetic variants and multiple cancer risk.

Methods

A total of ten studies are eligible (12,211 patients and 14,650 controls). Pooled odds ratios (ORs) and the 95% confidence interval (95% CI) were appropriately calculated using either fixed-effect model or random-effect model.

Results

Significant associations between rs6682925 or rs10889677 polymorphism and cancer risk were found (OR = 1.11, 95% CI = 1.03–1.21, P = 0.007; or OR = 0.85, 95% CI = 0.71–0.92, P = 0.001). However, there was no such association between rs1884444 genotypes and cancer susceptibility (P > 0.05).

Conclusion

These findings reveal that the IL-23R rs6682925 and rs10889677 genetic variants play a more important part in pathogenesis of multiple cancers.     

The effect of XPD/ERCC2 Lys751Gln polymorphism on acute leukemia risk: A systematic review and meta-analysis

Aims

Epidemiological studies have assessed the association between xeroderma pigmentosum group D (XPD) Lys751Gln and acute leukemia risk with conflicting results. We performed this meta-analysis to derive a more precise estimation of the relationship. Pooled odds ratio (OR) with 95% confidence interval (95% CI) was used to assess the strength of the association.

Results

Ten published case–control studies including a total of 1494 cases and 2259 controls were identified. Overall, significant risk effects of Lys751Gln genotype was found under the dominant model (OR = 1.16; 95% CI = 1.01–1.34; P = 0.032). When stratified by clinical types, the variant genotype was associated with the acute myeloid leukemia (AML) risk under the heterozygote comparison (OR = 1.20; 95% CI = 1.00–1.43; P = 0.048), the homozygote comparison (OR = 1.35; 95% CI = 1.05–1.74; P = 0.019) and the dominant model (OR = 1.23; 95% CI = 1.04–1.45; P = 0.015), respectively. Furthermore, significantly increased risks were also pronounced in Caucasian AML patients (the homozygote comparison: OR = 1.38; 95% CI = 1.07–1.78; P = 0.013; the dominant model: OR = 1.23; 95% CI = 1.03–1.46; P = 0.020; and the recessive model: OR = 1.26; 95% CI = 1.00–1.60; P = 0.050). No evident heterogeneities were observed for the overall data under all genetic models. In addition, no statistical evidence for publication bias was found using the method of Begg's and Egger's tests.

Conclusion

This meta-analysis suggested that XPD Lys751Gln polymorphism might be a risk factor for AML and Caucasian acute leukemia patients.     

Tagging SNPs in the ERCC4 gene are associated with gastric cancer risk

ERCC4 plays an essential role in the nucleotide excision repair (NER) pathway, which is involved in the removal of a wide variety of DNA lesions. To determine whether the ERCC4 tagging SNPs (tSNPs) are associated with risk of gastric cancer, we conducted a hospital-based case-control study of 350 cases and 468 cancer-free controls. In the logistic regression (LR) analysis, we found a significantly decreased risk of gastric cancer associated with the rs744154 GC/CC genotypes [adjusted odds ratio (OR) = 0.56, 95% confidence interval (CI) = 0.42–0.75, false discovery rate (FDR) P = 0.003] compared with the wild-type GG genotype. Haplotype-based association study revealed that the CGC haplotype that containing the rs744154 C allele can decrease the risk of gastric cancer compared with the most common haplotype GGT (adjusted OR = 0.61, 95% CI = 0.46–0.81). Using the multifactor dimensionality reduction (MDR) analysis, we identified that the SNP rs744154 and smoking status were the best two predictive factors for gastric cancer with a testing accuracy of 55.76% and a perfect cross-validation consistency (CVC) of 10 (P = 0.001). Furthermore, the smokers with the rs744154 GC/CC genotypes showed a decreased risk of gastric cancer (adjusted OR = 0.55, 95% CI = 0.35–0.85) compared with the smokers with the GG genotype using multivariate LR analysis. The above findings consistently suggested that genetic variants in the ERCC4 gene may play a protective role in the etiology of gastric cancer, even in the smokers.     

High plasma CXCL10 levels are associated with HCV-genotype 1, and higher insulin resistance, fibrosis, and HIV viral load in HIV/HCV coinfected patients

Background

CXCL10 may contribute to the host immune response against the hepatitis C virus (HCV), liver disease progression, and response to HCV antiviral therapy. The aim of our study was to analyze the relationship among virological, immunological, and clinical characteristics with plasma CXCL10 levels in human immunodeficiency virus (HIV)/HCV-coinfected patients.

Methods

We carried out a cross-sectional study on 144 patients. CXCL10 and insulin were measured using an immunoassay kit. The degree of insulin resistance was estimated for each patient using the homeostatic model assessment (HOMA) method. Insulin resistance was defined as a HOMA index higher than or equal to 3.8. Aspartate aminotransferase (AST) to platelet ratio (APRI), FIB-4, Forns index, HGM1, and HGM2 were calculated.

Results

The variables associated with log₁₀ CXCL10 levels by univariate analysis were age (b = 0.013; p = 0.023), prior AIDS-defining condition (b = 0.127; p = 0.045), detectable plasma HIV viral load (b = 0.092; p = 0.006), log₁₀ HOMA (b = 0.216; p = 0.002), HCV-genotype 1 (b = 0.114; p = 0.071), and liver fibrosis assessed by all non-invasive indexes (log₁₀ APRI (b = 0.296; p = 0.001), log₁₀ FIB-4 (b = 0.436; p < 0.001), log₁₀ Forns index (b = 0.591; p < 0.001), log₁₀ HGM1 (b = 0.351; p = 0.021), and log₁₀ HGM2 (b = 0.215; p = 0.018)). However, in multivariate analysis, CXCL10 levels were only associated with HOMA, detectable plasma HIV viral load, HCV-genotype 1 and FIB-4 (R-square = 0.235; p < 0.001).

Conclusion

Plasma CXCL10 levels were influenced by several characteristics of patients related to HIV and HCV infections, insulin resistance, and liver fibrosis, indicating that CXCL10 may play an important role in the pathogenesis of both HCV and HIV infections.     

Genetic association of interleukin-10 promoter polymorphisms and susceptibility to diffuse large B-cell lymphoma: A meta-analysis

Published data on the association between interleukin-10 (IL-10) gene polymorphisms and diffuse large B-cell lymphoma (DLBCL) risk are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed, focusing on four major IL-10 gene variants in the promoter region: –3575T/A, –1082A/G, –819C/T and –592C/A. We applied the false discovery rate (FDR) method to adjust for multiple testing. A significant association between IL-10 –3575T/A polymorphism and the risk of DLBCL was observed in the pooled 10 case–control studies (A vs. T: OR = 1.16, 95% CI = 1.08–1.25, P < 0.0001; AA + TA vs. TT: OR = 1.20, 95% CI = 1.08–1.33, P = 0.0009; AA vs. TA + TT: OR = 1.25, 95% CI = 1.09–1.44, P = 0.001). The results indicated that carriers of –1082G allele (–1082GG/GA genotypes) had a nearly 30% increased risk of DLBCL, as compared with carriers of –1082AA genotype (GG + GA vs. AA: OR = 1.30, 95% CI = 1.08–1.57, P = 0.005). When P-values were not adjusted for multiple testing, the risk was significantly decreased among people with –592AA genotype (AA vs. AC + CC: OR = 0.63, 95% CI = 0.43–0.94, P = 0.02), while carriers with –819TT genotype also modestly weakened the DLBCL susceptibility at a marginal level of significance (TT vs. CT + CC: OR = 0.59, 95% CI = 0.35–0.99, P = 0.05). However, these associations were not significant after correction for multiple testing. This meta-analysis suggests that IL-10 –3575A allele confers a greater risk to DLBCL susceptibility, while –1082A/G polymorphism also has significant association with DLBCL risk. These results may help to further clarify the malignancy-risk gene signature of DLBCL, and thus have prognostic and predictive value especially for early-stage DLBCL.     

XRCC1 polymorphisms and differentiated thyroid carcinoma risk: A meta-analysis

The objective of this study is to quantitatively derive a more precise estimation of the association between X-ray repair cross-complementing group 1 (XRCC1) gene polymorphisms and differentiated thyroid carcinoma risk. A comprehensive literature search of three databases was conducted. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated with fixed-effect models and random-effect models when appropriate. Overall, no association of the XRCC1 Arg399Gln, Arg280His, and Arg194Trp polymorphisms with differentiated thyroid carcinoma risk was found. In subgroup analyses, a decreased differentiated thyroid carcinoma risk was observed among Caucasians (Gln vs. Arg, OR = 0.86, 95% CI = 0.77–0.96, P = 0.343 for heterogeneity; Gln/Arg vs. Arg/Arg, OR = 0.84, 95% CI = 0.71–0.98, P = 0.229 for heterogeneity; Gln/Gln vs. Arg/Arg, OR = 0.77, 95% CI = 0.60–0.99, P = 0.477 for heterogeneity; dominant genetic model, OR = 0.82, 95% CI = 0.71–0.95, P = 0.272 for heterogeneity), not among Asians. No publication bias was observed. Our results suggest that XRCC1 Arg399Gln polymorphism is not associated with differentiated thyroid carcinoma risk, while a decreased risk is observed among Caucasian population.     

Therapeutic outcomes of combining cryotherapy,chemotherapy and DC-CIK immunotherapy in the treatment of metastatic non-small cell lung cancer

Currently there are no effective therapies for the treatment of metastatic non-small cell lung cancer (NSCLC). Here, we conducted a retrospective study of 161 patients to evaluate the therapeutic effects of combining cryosurgery, chemotherapy and dendritic cell-activated cytokine-induced killer cells (DC-CIK) immunotherapy. The overall survival (OS) after diagnosis of metastatic NSCLC to patient death was assessed during a 5-years follow-up period. OS of patients who received comprehensive cryotherapy was (median OS, 20 months; n = 86) significantly longer than that of patients who did not received cryotherapy (median OS, 10 months; n = 75; P < 0.0001). Five treatment combinations were selected: chemotherapy (n = 44); chemo-immunotherapy (n = 31); cryo-chemotherapy (n = 32); cryo-immunotherapy (n = 21); and cryo-chemo-immunotherapy (n = 33). A combination of cryotherapy with either chemotherapy or immunotherapy lead to significantly longer OS (18 months and 17 months, respectively) compared to chemotherapy and chemo-immunotherapy (8.5 months and 12 months, respectively; P < 0.001); however, the median OS of patients who underwent cryo-chemo-immunotherapy was significantly longer (27 months) compared to the other treatment programs (P < 0.001). In conclusion, a combination of cryotherapy, chemotherapy and DC-CIK immunotherapy proved the best treatment option for metastatic NSCLC in this group of patients.     

Effects of a gliadin-combined plant superoxide dismutase extract on self-perceived fatigue in women aged 50-65 years

Fatigue syndromes exist on a continuum of severity from mild and transient to the disabling chronic fatigue syndrome, with oxidative stress linked to its pathogenesis. A thermolabile gliadin-combined plant superoxide dismutase (SOD) extract has shown potential in clinical trials as a therapeutic antioxidant. This study investigated the effects of 12 weeks of 500 mg/day of a SOD/gliadin supplement on fatigue. Thirty-eight women aged 50-65 years with self-perceived fatigue entered this randomized, double-blind, placebo-controlled trial. The primary outcome measure was general fatigue determined by the Multidimensional Fatigue Inventory (MFI). Secondary outcome measures included other measures of fatigue from the MFI and blood measures of oxidative stress, antioxidant status and hormones. There were no significant (P > 0.05) differences between, or within groups, for decreases in general fatigue (active = 1.6%, placebo = 4.1%). There were no within or between group differences (P > 0.05) in other measures of fatigue (physical fatigue, reduced activity, reduced motivation, mental fatigue and total fatigue score). In regard to the biochemical measures, there were non-significant (P > 0.05) differences in increases in plasma SOD activity (active = 7.1%, placebo = 12.2%), plasma GPx activity (active = 2.4%, placebo = 0.7%), red blood cell GPx activity (active = 9.8%, placebo = 4.4%). Markers of oxidative stress were decreased but there were no differences (P > 0.05) within or between groups; malondialdehyde (active = 4.1%, placebo = 1.6%), F-2 isoprostanes (active = 14.7%, placebo = 22.4%). There was a trend (P = 0.08) for a decrease in cortisol in the active group (24.6%), however this was not significantly different from the decrease in the placebo participants (4.1%). DHEA differences were not significant (P < 0.05) and declined 1.3% in the active group and 14.4% in the placebo group. In summary, the thermolabile SOD/gliadin supplement had no significant effect on self-perceived fatigue, antioxidants, oxidative stress or hormones in women aged 50-65 years.