Prognostic Significance of Circulating Tumor Cells in Non-Small-Cell Lung Cancer Patients: A Meta-Analysis

Background

The prognostic significance of circulating tumor cells (CTCs) detected in patients with non-small-cell lung cancer (NSCLC) is still inconsistent. We aimed to assess the prognostic relevance of CTCs using a meta-analysis.

Methods

We searched PubMed, Web of Science and EMBASE for relevant studies that assessed the prognostic relevance of CTCs in NSCLC. Statistical analyses were conducted to calculate the summary incidence, odds ratio, relative risks (RRs) and 95% confidence intervals (CIs) using fixed or random-effects models according to the heterogeneity of included studies.

Results

A total of 20 studies, comprising 1576 patients, met the inclusion criteria. In identified studies, CTCs were not correlated with histology (adenocarcinoma vs squamous cell carcinoma) (odds ratio [OR]  =  0.88; 95% confidence interval [CI]: 0.59–1.33; Z = –0.61; P = 0.545). However, pooled analyses showed that CTCs were associated with lymph node metastasis (OR = 2.06; 95% CI: 1.18–3.62; Z = 2.20; P = 0.027) and tumor stage (OR  = 1.95; 95% CI: 1.08–3.54; Z = 2.53; P = 0.011). Moreover, CTCs were significantly associated with shorter overall survival (relative risk [RR]  = 2.19; 95% CI: 1.53–3.12; Z = 4.32; P<0.0001) and progression-free/disease-free survival (RR  = 2.14; 95% CI: 1.36–3.38; Z = 3.28; P<0.0001).

Conclusion

The presence of CTCs indicates a poor prognosis in patients with NSCLC. Further well-designed prospective studies are required to explore the clinical applications of CTCs in lung cancer.     

Low Serum Creatine Kinase Levels in Breast Cancer Patients: A Case-Control Study

Background

Previous studies provide an ambiguous picture of creatine kinase (CK) expression and activities in malignancy. The aim of this study was to investigate the role of serum CK level in breast cancer patients.

Patients and Methods

823 female patients diagnosed with breast cancer were consecutively recruited as cases, and 823 age-match patients with benign breast disease were selected as controls. Serum CK was analyzed by commercially available standardized methods.

Results

Serum CK level was significantly associated with breast cancer (P = 0.005) and subtypes of breast cancer, including breast cancer with diameter>2 cm (P = 0.031) and stage IIIbreast cancer (P = 0.025). The mean serum CK level in patients with>2 cm tumor was significantly lower than that in≤2 cm (P = 0.0475), and the mean serum CK level of stage III breast cancer patients was significantly lower than that of stage I and II breast cancer patients (P = 0.0246). Furthermore, a significant difference (P = 0.004) was observed between serum CK level and ERBB2+breast cancer not other molecular subtypes.

Conclusions

Serum CK levels in cases was significantly lower compared with controls. Notably, our results indicated for the first time that there was a negative correlation between serum CK levels and breast cancer stage. Serum CK level, which may reflect the status of host immunity, may be an important factor in determining breast cancer development and progression.     

Body Mass Index and Breast Cancer Defined by Biological Receptor Status in Pre-Menopausal and Post-Menopausal Women: A Multicenter Study in China

Background

Few studies have investigated the association between body mass index (BMI) and breast cancer with consideration to estrogen/progesterone/human epidermal growth factor type 2 receptor status (ER/PR/HER2) in the breast tissue among Chinese pre- and post-menopausal women.

Methods

Four thousand two hundred and eleven breast cancer patients were selected randomly from seven geographic regions of China from 1999 to 2008. Demographic data, risk factors, pathologic features, and biological receptor status of cases were collected from the medical charts. Chi-square test, fisher exact test, rank-correlation analysis, and multivariate logistic regression model were adopted to explore whether BMI differed according to biological receptor status in pre- and post-menopausal women.

Results

Three thousand two hundred and eighty one eligible cases with BMI data were included. No statistically significant differences in demographic characteristics were found between the cases with BMI data and those without. In the rank-correlation analysis, the rates of PR+ and HER2+ were positively correlated with increasing BMI among post-menopausal women (r_{s BMI, PR+} = 0.867, P = 0.001; r_{s BMI, HER2+} = 0.636, P = 0.048), but the ER+ rates did not vary by increasing BMI. Controlling for confounding factors, multivariate logistic regression models with BMI<24 kg/m² as the reference group were performed and found that BMI≥24 kg/m² was only positively correlated with PR+ status among post-menopausal breast cancer cases (adjusted OR = 1.420, 95% CI: 1.116–1.808, Wald = 8.116, P = 0.004).

Conclusions

Post-menopausal women with high BMI (≥24 kg/m²) have a higher proportion of PR+ breast cancer. In addition to effects mediated via the estrogen metabolism pathway, high BMI might increase the risk of breast cancer by other routes, which should be examined further in future etiological mechanism studies.     

Mycobacterium tuberculosis Infection in Young Children: Analyzing the Performance of the Diagnostic Tests

Objective

This study evaluated the performance of the Tuberculin Skin Test (TST) and Quantiferon-TB Gold in-Tube (QFT) and the possible association of factors which may modify their results in young children (0–6 years) with recent contact with an index tuberculosis case.

Materials and Methods

A cross-sectional study including 135 children was conducted in Manaus, Amazonas-Brazil. The TST and QFT were performed and the tests results were analyzed in relation to the personal characteristics of the children studied and their relationship with the index case.

Results

The rates of positivity were 34.8% (TST) and 26.7% (QFT), with 14.1% of indeterminations by the QFT. Concordance between tests was fair (Kappa = 0.35 P<0.001). Both the TST and QFT were associated with the intensity of exposure (Linear OR = 1.286, P = 0.005; Linear OR = 1.161, P = 0.035 respectively) with only the TST being associated with the time of exposure (Linear OR = 1.149, P = 0.009). The presence of intestinal helminths in the TST+ group was associated with negative QFT results (OR = 0.064, P = 0.049). In the TST− group lower levels of ferritin were associated with QFT+ results (Linear OR = 0.956, P = 0.036).

Conclusions

Concordance between the TST and QFT was lower than expected. The factors associated with the discordant results were intestinal helminths, ferritin levels and exposure time to the index tuberculosis case. In TST+ group, helminths were associated with negative QFT results suggesting impaired cell-mediated immunity. The TST−&QFT+ group had a shorter exposure time and lower ferritin levels, suggesting that QFT is faster and ferritin may be a potential biomarker of early stages of tuberculosis infection.     

Prevalence and Risk Factors of Fluid Overload in Southern Chinese Continuous Ambulatory Peritoneal Dialysis Patients

Background

Fluid overload is frequently present in CAPD patients and one of important predictors of mortality. The aim of this study is to investigate the prevalence and associated risk factors in a cohort study of Southern Chinese CAPD patients.

Methods

The patients (receiving CAPD 3 months and more) in our center were investigated from January 1, 2008 to December 31, 2009. Multi-frequency bioelectrical impedance analysis was used to assess the patient’s body composition and fluid status.

Results

A total of 307 CAPD patients (43% male, mean age 47.8±15.3 years) were enrolled, with a median duration of PD 14.6 (5.9–30.9) months. Fluid overload (defined by Extracellular water/Total body water (ECW/TBW)≥0.40) was present in 205 (66.8%) patients. Univariate analysis indicated that ECW/TBW were inversely associated with body mass index (r = −0.11, P = 0.047), subjective global assessment score (r = −0.11, P = 0.004), body fat mass (r = −0.15, P = 0.05), serum albumin (r = −0.32, P<0.001), creatinine (r = −0.14, P = 0.02), potassium (r = −0.15, P = 0.02), and residual urine output (r = −0.14, P = 0.01), positively associated with age (r = 0.27, P<0.001), Chalrlson Comorbidity Index score (r = 0.29, P<0.001), and systolic blood pressure (r = 0.22, P<0.001). Multivariate linear regression showed that lower serum albumin (β = −0.223, P<0.001), lower body fat mass (β = −0.166, P = 0.033), old age (β = 0.268, P<0.001), higher systolic blood pressure (β = 0.16, P = 0.006), less residual urine output (β = −0.116, P = 0.042), and lower serum potassium (β = −0.126, P = 0.03) were independently associated with higher ECW/TBW. After 1 year of follow-up, the cardiac event rate was significantly higher in the patients with fluid overload (17.1% vs 6.9%, P = 0.023) than that of the normal hydrated patients.

Conclusions

The prevalence of fluid overload was high in CAPD patients. Fluid overload in CAPD patients were independently associated with protein-energy wasting, old age, and decreased residual urine output. Furthermore, CAPD patients with fluid overload had higher cardiac event rate than that of normal hydrated patents.     

New Insight into Ki67 Expression at the Invasive Front in Breast Cancer

Purpose

To investigate the distribution of Ki67+ cells in breast cancer in relation to clinical-pathological parameters and prognosis.

Materials and Methods

Ki67 expression status was detected in 1,086 breast cancer specimens using immunohistochemistry staining and examining the relationship between the Ki67+ cells'' location. Subsequently, clinical-pathological parameters and prognosis were determined.

Results

In total, Ki67 protein expression was found in 781 (71.92%) of the 1,086 breast cancer specimens. Among the 781 Ki67+ cases, 461 were defined as diffuse type and 320 were defined as borderline type. After universal correlation analysis, significant differences were observed in age, histological grade, metastatic nodes, postoperative distant metastasis, and molecular subtype between Ki67+ and Ki67− cases (P = 0.01, 0.001, 0.001, 0.001, and 0.001, respectively). After subgroup analysis, the borderline cases were found to be characterized by a high distant metastasis rate compared to the diffuse cases as well as the Ki67− cases (P = 0.001). No differences were observed between diffuse type or Ki67− cases (P = 0.105). Multivariate analysis showed that age, tumor size, histological grade, lymph node metastasis, molecular subtype, and the Ki67 distribution pattern were observed to be related to postoperative distant metastasis (all P<0.05). Furthermore, borderline type was shown to attain a significantly more distant bone and liver metastasis and worse disease-specific survival than the other types (P = 0.001). In the Cox regression test, the Ki67 distribution pattern was detected as an independent prognostic factor (P = 0.001).

Conclusion

The distribution pattern of Ki67 may be a new independent prognostic factor for breast cancer.     

Associations between TNF-α Polymorphisms and Pneumonia: A Meta-Analysis

Background

Several studies evaluated the associations of tumor necrosis factor-α (TNF-α) polymorphisms with pneumonia in different populations. However, the results were conflicting and controversial.

Methods

Databases including PubMed, Embase, Web of Science, and China National Knowledge Infrastructure (CNKI) were searched to find relevant studies. Data were extracted independently by two investigators. Crude odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were estimated.

Results

Twelve case-control studies and one cohort study were included. Overall, no association between TNF-α −308A/G polymorphism and pneumonia risk was observed for AA +AG vs. GG (OR = 1.13; 95% CI 0.99–1.30; P = 0.07). In addition, TNF-α −308A/G polymorphism was not associated with pneumonia mortality (OR = 1.96; 95% CI 0.94–4.09; P = 0.07). Furthermore, there was no association of TNF-α −238A/G polymorphism with the risk of pneumonia (OR = 1.38; 95% CI 0.84–2.28; P = 0.20).

Conclusions

TNF-α −308A/G, −238A/G polymorphisms were not associated with pneumonia risk. Moreover, TNF-α −308A/G polymorphism did not play a role in the pneumonia mortality risk.     

Detection of Circulating Tumor Cell Subpopulations in Patients with Head and Neck Squamous Cell Carcinoma (HNSCC)

Background

Since image based diagnostic tools fail to detect early metastasis in head and neck squamous cell carcinoma (HNSCC) it is crucial to develop minimal invasive diagnostic methods. A promising approach is to identify and characterize circulating tumor cells (CTC) in the peripheral blood of HNSCC patients. In this pilot study, we assessed which non-hematopoietic cell types are identifiable and whether their numbers differ in pre- and postoperative blood samples.

Methods

20 ml citrated peripheral blood was taken from 10 HNSCC patients before and after curative resection. CTC were enriched using density gradient centrifugation. CTC presence was verified by multi-immunofluorescence staining against cytokeratin (CK; epithelial), N-cadherin (mesenchymal); CD133 (stem-cell), CD45 (hematopoietic) and DAPI (nucleus). Individual cell type profiles were analyzed.

Results

We were able to detect cells with epithelial properties like CK+/N-cadherin−/CD45− and CK+/CD133−/CD45− as well as cells with mesenchymal features such as N-cadherin+/CK−/CD45− and cells with both characteristics like N-cadherin+/CK+/CD45−. We also observed cells showing stem cell-like features like CD133+/CK−/CD45− and cells with both epithelial and stem cell-like features such as CD133+/CK+/CD45−. The number of CK positive cells (p = 0.002), N-cadherin positive cells (p = 0.002) and CD133 positive cells (p = 0.01) decreased significantly after resection. Kaplan-Meier test showed that the survival was significantly shorter when N-cadherin+ cells were present after resection (p = 0.04; 474 vs. 235 days; [HR] = 3.1).

Conclusions

This is - to the best of our knowledge- the first pilot study identifying different CTC populations in peripheral blood of HNSCC patients and showing that these individual cell type profiles may have distinct clinical implications.     

A Large Scale Gene-Centric Association Study of Lung Function in Newly-Hired Female Cotton Textile Workers with Endotoxin Exposure

Background

Occupational exposure to endotoxin is associated with decrements in pulmonary function, but how much variation in this association is explained by genetic variants is not well understood.

Objective

We aimed to identify single nucleotide polymorphisms (SNPs) that are associated with the rate of forced expiratory volume in one second (FEV₁) decline by a large scale genetic association study in newly-hired healthy young female cotton textile workers.

Methods

DNA samples were genotyped using the Illumina Human CVD BeadChip. Change rate in FEV₁ was modeled as a function of each SNP genotype in linear regression model with covariate adjustment. We controlled the type 1 error in study-wide level by permutation method. The false discovery rate (FDR) and the family-wise error rate (FWER) were set to be 0.10 and 0.15 respectively.

Results

Two SNPs were found to be significant (P<6.29×10⁻⁵), including rs1910047 (P = 3.07×10⁻⁵, FDR = 0.0778) and rs9469089 (P = 6.19×10⁻⁵, FDR = 0.0967), as well as other eight suggestive (P<5×10⁻⁴) associated SNPs. Gene-gene and gene-environment interactions were also observed, such as rs1910047 and rs1049970 (P = 0.0418, FDR = 0.0895); rs9469089 and age (P = 0.0161, FDR = 0.0264). Genetic risk score analysis showed that the more risk loci the subjects carried, the larger the rate of FEV₁ decline occurred (P _trend = 3.01×10⁻¹⁸). However, the association was different among age subgroups (P = 7.11×10⁻⁶) and endotoxin subgroups (P = 1.08×10⁻²). Functional network analysis illustrates potential biological connections of all interacted genes.

Conclusions

Genetic variants together with environmental factors interact to affect the rate of FEV₁ decline in cotton textile workers.     

Impact of Three Oral Antidiabetic Drugs on Markers of β-Cell Function in Patients with Type 2 Diabetes: A Meta-Analysis

Background

The effect of metformin, pioglitazone and sitagliptin on β-cell function in the treatment of type 2 diabetes is controversial. Therefore, we performed a systematic review and meta-analysis to obtain a better understanding in the β-cell effects of metformin, pioglitazone and sitagliptin.

Methods

We searched Pubmed and the Cochrane Center Register of Controlled Trials to identify relevant studies. Trials investigating effects of sitagliptin, metformin or pioglitazone on β-cell function were identified. The primary outcomes were homeostasis model assessment of β-cells (HOMA-β) and proinsulin/insulin ratio (PI/IR). Secondary outcome was hemoglobin A1c level. We used version 2 of the Comprehensive Meta Analysis software for all statistical analyses.

Results

Metformin monotherapy was more effective than sitagliptin in improving HOMA-β (18.01% (95% CI 11.09% to 24.94%) vs. 11.29% (95% CI 9.21% to 13.37%), P = 0.040) and more effective (−0.137 (95% CI −0.082 to −0.192)) than both sitagliptin (−0.064 (95% CI −0.036 to −0.092), P = 0.019) and pioglitazone (−0.068 (95% CI −0.044 to −0.093), P = 0.015) in decreasing PI/IR. Metformin and sitagliptin combined (40.23% (95%CI 32.30% to 48.16%)) were more effective than sitagliptin and pioglitazone (11.82% (95% CI 6.61% to 17.04%), P = 0.000) and pioglitazone and metformin(9.81% (95% CI 1.67% to 17.95%), P = 0.022) in improving HOMA-β and decreasing PI/IR (−0.177 (95% CI −0.118 to −0.237); −0.080 (95% CI −0.045 to −0.114), P = 0.007; −0.038 (95% CI, −0.005 to 0.071), P = 0.023).

Limitations

The included RCTs were of short duration (12–54 weeks). We could not determine long term effects on β-cells.

Conclusions

Metformin improves β-cell function more effectively than pioglitazone or sitagliptin in type 2 diabetes patients. Metformin and sitagliptin improved HOMA-β and PI/IR more than other combinations.     

The Association between the Levels of Serum Ferritin and Sex Hormones in a Large Scale of Chinese Male Population

Background

The ferritin is an important participant of iron-storage but its regulation and related factors were not well defined. The present objective was to explore the potential association between serum ferritin levels and sex hormones.

Methods

1999 Chinese men in the Fangchenggang Area Male Health and Examination Survey (FAMHES) were recruited in this cross-sectional study. Levels of serum ferritin, total testosterone (free testosterone was calculated from the total one), estradiol and sex hormone-binding protein were detected in venous blood samples. The effects of age, BMI, smoking as well as alcohol consumption were analyzed on ferritin levels, respectively, and then the Pearson’s correlation analysis was used to evaluate the association between ferritin levels and sex hormones adjusting for the above factors.

Results

The age, BMI and alcohol consumption significantly affected serum ferritin levels, but there was no significant difference between smokers and nonsmokers. Ferritin levels were significantly and negatively associated with total testosterone (R = −0.205, P< 0.001), sex hormone-binding protein (R = −0.161, P<0.001) and free testosterone (R = −0.097, P<0.001). After age and alcohol consumption were adjusted, the above associations were still significant (R = −0.200, −0.181 and −0.083, respectively, all P<0.001). However, there was only borderline negative association between ferritin levels and estradiol (adjusted R = −0.039, P = 0.083).

Conclusion

The large scale of epidemic results showed the significantly negative associations between serum ferritin levels and sex hormones, which may provide more clues to explore the potential regulation and biological mechanism of ferritin.     

The Relationship of Retinal Vessel Diameters and Fractal Dimensions with Blood Pressure and Cardiovascular Risk Factors

Background

This study aimed to investigate the correlation between quantitative retinal vascular parameters such as central retinal arteriolar equivalent (CRAE) and retinal vascular fractal dimension (D(f)), and cardiovascular risk factors in the Chinese Han population residing in the in islands of southeast China.

Methodology/Principle Findings

In this cross-sectional study, fundus photographs were collected and semi-automated analysis software was used to analyze retinal vessel diameters and fractal dimensions. Cardiovascular risk factors such as relevant medical history, blood pressure (BP), lipids, and blood glucose data were collected. Subjects had a mean age of 51.9±12.0 years and included 812 (37.4%) males and 1,357 (62.6%) females. Of the subjects, 726 (33.5%) were overweight, 226 (10.4%) were obese, 272 (12.5%) had diabetes, 738 (34.0%) had hypertension, and 1,156 (53.3%) had metabolic syndrome. After controlling for the effects of potential confounders, multivariate analyses found that age (β = 0.06, P = 0.008), sex (β = 1.33, P = 0.015), mean arterial blood pressure (β = −0.12, P<0.001), high-sensitivity C-reactive protein (β = −0.22, P = 0.008), and CRVE (β = 0.23, P<0.001) were significantly associated with CRAE. Age (β = −0.0012, P<0.001), BP classification (prehypertension: β = −0.0075, P = 0.014; hypertension: β = −0.0131, P = 0.002), and hypertension history (β = −0.0007, P = 0.009) were significantly associated with D(f).

Conclusions/Significance

D(f) exhibits a stronger association with BP than CRAE. Thus, D(f) may become a useful indicator of cardiovascular risk.     

Gastric Bypass Surgery Is Followed by Lowered Blood Pressure and Increased Diuresis - Long Term Results from the Swedish Obese Subjects (SOS) Study

Objective

To compare two bariatric surgical principles with regard to effects on blood pressure and salt intake.

Background

In most patients bariatric surgery induces a sustained weight loss and a reduced cardiovascular risk profile but the long-term effect on blood pressure is uncertain.

Methods

Cohort study with data from the prospective, controlled Swedish Obese Subjects (SOS) study involving 480 primary health care centres and 25 surgical departments in Sweden. Obese patients treated with non-surgical methods (Controls, n = 1636 and n = 1132 at 2 y and 10 y follow up, respectively) were compared to patients treated with gastric bypass (GBP, n = 245 and n = 277, respectively) or purely restrictive procedures (vertical banded gastroplasty or gastric banding; VBG/B, n = 1534 and n = 1064, respectively).

Results

At long-term follow-up (median 10 y) GBP was associated with lowered systolic (mean: −5.1 mm Hg) and diastolic pressure (−5.6 mmHg) differing significantly from both VBG/B (−1.5 and −2.1 mmHg, respectively; p<0.001) and Controls (+1.2 and −3.8 mmHg, respectively; p<0.01). Diurnal urinary output was +100 ml (P<0.05) and +170 ml (P<0.001) higher in GBP subjects than in weight-loss matched VBG/B subjects at the 2 y and 10 y follow-ups, respectively. Urinary output was linearly associated with blood pressure only after GBP and these patients consumed approximately 1 g salt per day more at the follow-ups than did VBG/B (P<0.01).

Conclusions

The purely restrictive techniques VBG/B exerted a transient blood pressure lowering effect, whereas gastric bypass was associated with a sustained blood pressure reduction and an increased diuresis. The daily salt consumption was higher after gastric bypass than after restrictive bariatric surgery.     

Ophthalmoscopic Assessment of the Retinal Nerve Fiber Layer. The Beijing Eye Study

Purpose

To examine the retinal nerve fiber layer (RNFL) ophthalmoscopically, to search for localized RNFL defects, and to assess factors associated with RNFL visibility in a population-based setting.

Methods

The population-based cross-sectional Beijing Eye Study 2006 included 3251 subjects. Using color fundus photographs, RNFL visibility was assessed in grades from 0 to 8 in 8 fundus sectors. Localized RNFL defects were defined as wedge-shaped defects running towards the optic disc.

Results

After exclusion of subjects with optic media opacities, 2602 subjects (mean age:58.1±9.0 years) were included. RNFL visibility score was highest (P<0.001) in the temporal inferior region, followed by the temporal superior region, nasal superior region, and nasal inferior region. In multivariate analysis, higher RNFL visibility score was associated with younger age (P<0.001;standardized coefficient beta:−0.44;regression coefficient B: −0.22; 95%CI: −0.24, −0.20), female gender (P<0.001;beta:0.11;B:1.00;95%CI:0.67,1.32), higher blood concentration of low-density lipoproteins (P = 0.002;beta:0.07;B:0.34;95%CI:0.13,0.56), absence of dyslipidemia (P = 0.001;beta: −0.07;B: −0.58;95%CI: −0.93, −0.24), lower blood glucose concentration (P = 0.006;beta: −0.05;B: −0.14;95%CI: −0.24, −0.04), hyperopic refractive error (P<0.001;beta:0.15;B:0.45;95%CI:0.34,0.56), smaller optic disc size (P<0.001;beta: −0.08; B:−0.72;95% CI:−1.04, −0.40), absence of glaucomatous optic neuropathy (P<0.001;beta: −0.06;B: −2.69;95%CI:–4.18, −1.21) and absence of non-glaucomatous optic nerve damage (P = 0.001;beta: −0.06;B: −4.80;95%CI:0. −7.64, −1.96). Localized RNFL defects were detected in 96 subjects (prevalence:3.7±0.45% (95% confidence interval(CI):3.0,4.4). In multivariate analysis, prevalence of localized RNFL defects was associated with higher blood pressure (P<0.001; odds ratio (OR):1.07;95%CI:1.03,1.10), higher concentration of low-density lipoproteins (P = 0.01;OR:1.42;95%CI:1.08,1.85), higher prevalence of glaucomatous optic neuropathy (P<0.001;OR:46.8;95%CI:19.4,113) and diabetic retinopathy (P = 0.002;OR:3.20;95%CI:1.53,6.67), and lower total RNFL visibility (P<0.001;OR:0.92;95%CI:0.88,0.96).

Conclusions

In Chinese aged 45+ years, a decreased RNFL visibility was associated with older age, male gender, dyslipidemia, hyperglycemia, myopia, larger optic disc, and glaucomatous or non-glaucomatous optic neuropathy. Localized RNFL defects (prevalence:3.7±0.45%) were correlated mainly with higher blood pressure, higher concentration of low-density lipoproteins, glaucomatous optic neuropathy and diabetic retinopathy. These data are helpful for the routine ophthalmoscopic examination of the RNFL.     

VNN1 Gene Expression Levels and the G-137T Polymorphism Are Associated with HDL-C Levels in Mexican Prepubertal Children

Background

VNN1 gene expression levels and the G-137T polymorphism have been associated with high density lipoprotein cholesterol (HDL-C) levels in Mexican American adults. We aim to evaluate the contribution of VNN1 gene expression and the G-137T variant to HDL-C levels and other metabolic traits in Mexican prepubertal children.

Methodology/Principal Findings

VNN1 mRNA expression levels were quantified in peripheral blood leukocytes from 224 unrelated Mexican-Mestizo children aged 6–8 years (107 boys and 117 girls) and were genotyped for the G-137T variant (rs4897612). To account for population stratification, a panel of 10 ancestry informative markers was analyzed. After adjustment for admixture, the TT genotype was significantly associated with lower VNN1 mRNA expression levels (P = 2.9 × 10⁻⁵), decreased HDL-C levels (β = −6.19, P = 0.028) and with higher body mass index (BMI) z-score (β = 0.48, P = 0.024) in the total sample. In addition, VNN1 expression showed a positive correlation with HDL-C levels (r = 0.220; P = 0.017) and a negative correlation with BMI z-score (r = −0.225; P = 0.015) only in girls.

Conclusion/Significance

Our data suggest that VNN1 gene expression and the G-137T variant are associated with HDL-C levels in Mexican children, particularly in prepubertal girls.     

Association between Circulating Levels of IGF-1 and IGFBP-3 and Lung Cancer Risk: A Meta-Analysis

Background

The insulin-like growth factor (IGF) system was documented to play a predominant role in neoplasia. As lung cancer is one of the most malignant cancers, we conducted a meta-analysis in order to investigate the strength of association between circulating IGF-1 and IGFBP-3 levels and lung cancer.

Methodology/Principal Findings

A systematic literature search was conducted to identify all prospective case-control studies and case-control studies on circulating IGFs and IGFBPs levels. Six nested case-control studies (1 043 case subjects and 11 472 control participants) and eight case-control studies (401 case subjects and 343 control participants) were included in this meta-analysis. Pooled measure was calculated as the inverse variance-weighted mean of the natural logarithm of multivariate adjusted OR with 95% CIs for highest vs. lowest levels to assess the association of circulating IGF-1 and IGFBP-3 concentrations and lung cancer. Standard mean difference (SMD) was also calculated to indicate the difference of the circulating IGF-1 and IGFBP-3 concentrations between the lung cancer case group and the control group. Of the nested case-control studies, ORs for the highest vs. lowest levels of IGF-1 and IGFBP-3 were 1.047 (95% CI: [0.802,1.367], P = 0.736) and 0.960 (95%CI: [0.591,1.559], P = 0.868) respectively; and SMDs were −0.079 (95%CI:[ −0.169, 0.011], P = 0.086) and −0.097 (95%CI:[ −0.264,0.071], P = 0.258) for IGF-1 and IGFBP-3 respectively. As to the case-control studies, SMDs were 0.568 (95%CI:[ −0.035, 1.171], P = 0.065) and −0.780 (95%CI:[ −1.358, −0.201], P = 0.008) for IGF-1 and IGFBP-3 respectively.

Conclusions/Significance

Inverse association was shown between IGFBP-3 and lung cancer in the case-control studies,and the circulating level of IGFBP-3 underwent a decline during tumorogenesis and development of lung cancer, which suggested IGFBP-3 a promising candidate for the biomarker of lung cancer.     

Adiponectin-11377CG Gene Polymorphism and Type 2 Diabetes Mellitus in the Chinese Population: A Meta-Analysis of 6425 Subjects

Background

Although adiponectin −11377CG gene polymorphism is implied to be associated with increased type 2 diabetes mellitus (T2DM) risk, results of individual studies are inconsistent.

Objective and Methods

A meta-analysis consisting of 12 individual studies, including a total of 6425 participants, was carried out in order to investigate the association of adiponectin −11377CG gene polymorphism with T2DM. The pooled odds ratio (OR) and its corresponding confidence interval (CI) at 95% were assessed through the random- or fixed- effect model.

Results

A significant relationship was observed between adiponectin −11377CG gene polymorphism and T2DM under allelic (OR: 1.150, 95% CI: 1.060 to 1.250, P = 0.001), recessive (OR: 1.450, 95% CI: 1.180–1.770, P = 0.0004), dominant (OR: 1.071, 95% CI: 1.013–1.131, P = 0.015), additive (OR: 1.280, 95% CI: 1.090–1.510, P = 0.002), and homozygous genetic models (OR: 1.620, 95% CI: 1.310–1.990, P<0.00001). No significant association was found between them under the heterozygous genetic model (OR: 1.640, 95% CI: 0.850–3.170, P = 0.140).

Conclusions

Adiponectin −11377CG gene polymorphism was significantly associated with T2DM risk susceptibility. G allele carriers are predisposed to T2DM risk.     

Is Early Oral Feeding after Gastric Cancer Surgery Feasible? A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Aim

To assess the feasibility and safety of early oral feeding (EOF) after gastrectomy for gastric cancer through a systematic review and meta-analysis based on randomized controlled trials.

Methods

A literature search in PubMed, Embase, Web of Science and Cochrane library databases was performed for eligible studies published between January 1995 and March 2014. Systematic review was carried out to identify randomized controlled trials comparing EOF and traditional postoperative oral feeding after gastric cancer surgery. Meta-analyses were performed by either a fixed effects model or a random effects model according to the heterogeneity using RevMan 5.2 software.

Results

Six studies remained for final analysis. Included studies were published between 2005 and 2013 reporting on a total of 454 patients. No significant differences were observed for postoperative complication (RR = 0.95; 95%CI, 0.70 to 1.29; P = 0.75), the tolerability of oral feeding (RR = 0.98; 95%CI, 0.91 to 1.06; P = 0.61), readmission rate (RR = 1; 95%CI, 0.30 to 3.31; P = 1.00) and incidence of anastomotic leakage (RR = 0.31; 95%CI, 0.01 to 7.30; P = 0.47) between two groups. EOF after gastrectomy for gastric cancer was associated with significant shorter duration of the hospital stay (WMD = −2.36; 95%CI, −3.37 to −1.34; P<0.0001) and time to first flatus (WMD = −19.94; 95%CI, −32.03 to −7.84; P = 0.001). There were no significant differences in postoperative complication, tolerability of oral feeding, readmission rates, duration of hospital stay and time to first flatus among subgroups stratified by the time to start EOF or by partial and total gastrectomy or by laparoscopic and open surgery.

Conclusions

The result of this meta-analysis showed that EOF after gastric cancer surgery seems feasible and safe, even started at the day of surgery irrespective of the extent of the gastric resection and the type of surgery. However, more prospective, well-designed multicenter RCTs with more clinical outcomes are needed for further validation.     

Role of IL-4 Gene Polymorphisms in HBV-Related Hepatocellular Carcinoma in a Chinese Population

Background

Interleukin-4 (IL-4) is best known as an important mediator and modulator of immune and inflammatory responses. Hepatocellular carcinoma (HCC) is a typical inflammation-related cancer, and genetic variations in the IL-4 gene may be associated with the risk of hepatitis B virus (HBV)-related HCC. However, few studies have been conducted on their association.

Objectives

To clarify the effects of IL-4 gene polymorphisms on the risk of HBV-related HCC, two common variants, −590C/T (rs2243250) and −33C/T (rs2070874), and their relationship with HBV-related disease risk were investigated in a Chinese population.

Methods

IL-4 −590C/T and −33C/T polymorphisms were examined in 154 patients with HBV-related HCC, 62 patients with HBV-induced liver cirrhosis (LC), 129 patients with chronic hepatitis B (CHB), and 94 healthy controls, using the polymerase chain reaction-restriction fragment length polymorphism method and DNA sequencing.

Results

Overall, no significant differences were observed regarding the IL-4 −590C/T and −33C/T polymorphism genotypes, alleles, or haplotypes between the patient groups and the healthy controls. However, the CC genotypes of IL-4 −590C/T and −33C/T polymorphisms were observed to be significantly associated with CHB in subgroup analysis in males [CC versus TT (OR: 4.193, 95% CI: 1.094–16.071, P = 0.037; and OR: 3.438, 95% CI: 1.032–11.458, P = 0.044) and CC versus TT+CT (OR: 4.09, 95% CI: 1.08–15.49, P = 0.038; and OR: 3.43, 95% CI: 1.04–11.28, P = 0.042)].

Conclusions

These findings suggest that genetic variants in IL-4 −590C/T and −33C/T polymorphisms may be a risk factor for CHB in Chinese males but not for HBV-related LC or HCC.