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Purpose/aim of the study: Posterior circulation stroke (PCS) accounts for 20% of ischemic stroke, and vertebrobasilar stenosis is an important cause of PCS. Notably, not all patients with artery stenosis progress to ischemic stroke, and one of the important reason is that collateral circulation construction plays important protection role in this process.Clinical presentation: Here, we present the case of a 71-year-old male who presented with lightheadedness and three episodes of loss of consciousness after bilateral subclavian artery stenting. Digital subtraction angiography (DSA) demonstrated severe stenosis of the left vertebral artery, and the bilateral subclavian artery was kept open. The patient was then given the left vertebral artery stenting in an effort to resolve the vascular stenosis. As expected, he achieved a complete remission after stenting. However, six months later the patient suffered from loss of consciousness again. Repeat DSA confirmed restenosis of the left vertebral artery, and revealed a collateral flow to the left vertebral artery which fed by external carotid collateral branches. Then DSA was performed after 12 months, and another collateral circulation involving thyrocervical trunk was also found supplying flow to the left vertebral artery. In this process, the frequency of loss of consciousness gradually decreased as the collateral circulation construction.Conclusion: Through this case, we observe the whole process of the collateral circulation construction. Moreover, this case serves as a testament to the variability and complexity of vertebrobasilar arteriopathies, suggesting promotion of collateral flow offers the opportunity for outcome improvement.

Introduction The association between interleukin-6 (IL-6) gene −572 G^C polymorphism and myocardial infarction (MI) risk has not been established. We adopted this meta-analysis for further insight into the case–control studies. Materials and methods To investigate the genetic association, we searched multiple databases, including Web of Science, EMbase, CBM disc, PubMed and CNKI. Also, we manually identified the searched references. All the statistical analyses were conducted using Stata 11.0. Results A total of five studies were identified, involving 2,526 MI cases and 3,027 controls. The results revealed a significant association between IL-6 gene −572 G^C polymorphism and MI, implying that the IL-6 gene −572 C allele may be a protective factor for MI (for C allele vs K allele: OR = 0.85, 95% CI = 0.73–0.99, p = 0.041; for C/C vs G/G: OR = 0.55, 95% CI = 0.31–0.98, p = 0.044; for C/C vs G/C + G/G: OR = 0.60, 95% CI = 0.41–0.89, p = 0.011). However, in the subgroup analysis with regard to ethnicity, no significant correlation was identified between IL-6 gene −572 G^C polymorphism and MI among Europeans. Conclusion The IL-6 gene −572 C allele may be a protective factor for MI. Future studies involving larger sample bases are still recommended.

Background DL-3-n-butylphthalide (NBP) was demonstrated to increase the cerebral blood flow (CBF) in the animal models, but there are no clinic studies to verify this. We aimed to explore the effect of NBP on improving cerebral hypoperfusion caused by cerebral large-vessel stenosis. Methods In this single-center, randomized, double-blind, placebo-controlled study, 120 patients with severe carotid atherosclerotic stenosis and cerebral hypoperfusion in the ipsilateral middle cerebral artery (MCA) were included and randomly assigned into NBP or placebo group as 1:1 radio. Patients in NBP or placebo group received 200 mg or 20 mg of NBP capsules three times daily for four weeks respectively. Single photon emission computed tomography (SPECT) was used to assess regional CBF (rCBF) in four regions of interest (ROIs) corresponding to MCA before and 12 weeks after the treatment. After therapy, the rCBF change for every ROI and the whole CBF change in MCA territory for every patient were classified into amelioration, stabilization and deterioration respectively. Results 48 NBP patients (6 with bilateral stenosis) and 46 placebo patients (8 with bilateral stenosis) completed the trial. Overall, both groups had 54 stenotic carotid arteries and 216 ROIs for rCBF change analysis. After therapy, the rCBF in ROIs increased in NBP group (83.5% ± 11.4% vs. 85.8% ± 12.5%, p = 0.000), whereas no change was found in placebo group (86.9% ± 11.6% vs. 87.8% ± 11.7%, p = 0.331). Besides, there was higher percentages of ROIs with rCBF amelioration and stabilization in NBP group than in placebo group (93.1% vs. 79.2%, p = 0.000). Furthermore, ordinal regression analysis showed that compared with placebo, NBP independently made more patients to have whole CBF amelioration in ipsilateral MCA (Wald-χ2 = 5.247, OR = 3.31, p = 0.022). Conclusions NBP might improve the cerebral hypoperfusion in the patients with carotid artery atherosclerotic stenosis. Trial registration Chinese Clinical Trial Registry, ChiCTR1900028005, registered December 8th 2019- Retrospectively registered (http://www.chictr.org.cn/index.aspx).

Objective Subclavian steal syndrome results from hemodynamic impairment due to stenosis or occlusion of subclavian artery. Therefore, it is important for subclavian steal syndrome patients to assess hemodynamic status during endovascular therapy. Methods Eleven subclavian steal syndrome patients undergoing endovascular therapy attended this study. Pressure wire was used to measure trans-stenosis pressure difference (ΔP). Digital subtraction angiography, Transcranial Doppler and Electronic sphygmomanometer were introduced to assess stenotic rate, steal grade and inter-arm systolic pressure difference, respectively. Clinical symptoms and restenosis were followed up after endovascular therapy. The associations of ΔP with stenotic rate, inter-arm pressure difference, steal degree, clinic symptoms and restenosis were analyzed in this paper. Results Prior to the therapy, ΔP moderately correlated with stenotic rate (r = 0.757, p = 0.007) and inter-arm pressure difference (r = 0.701, p = 0.016). ΔP was ≥6 mmHg in all patients, and 6–9 mmHg for grade 1 steal and ≥10 mmHg for grade 2 and 3 steals. After the therapy, all patients had technique success, and 10 patients had clinic success, and 1 patient appeared restenosis. ΔP was ≤3 mmHg and steal disappeared in the patients with clinical success. ΔP was 18 mmHg and grade 3 steal still existed in one patient without clinical success. One patient with 1 mmHg of ΔP after therapy appeared restenosis in the follow-up. Conclusion The trans-stenosis pressure difference is closely related to steal degree and clinical symptoms. The measurement of hemodynamic status by pressure wire is very useful to guide endovascular therapy in subclavian steal syndrome patients. However, the restenosis may still occur, even though the hemodynamic impairment is improved.

Early detection of nasopharyngeal carcinoma (NPC) is of vital importance for improving prognosis and survival rates. MicroRNA (miRNA) are a class of short and non-coding RNA molecules that are capable of inhibiting the translation of mRNA of target genes. Previous studies have revealed that miRNA are involved in tumorigenesis and cancer development. The RNase-resistance of circulating miRNA have made them valuable non-invasive biomarkers, and has therefore drawn particular attention to their therapeutic potential. The aim of the present study was to investigate the expression of the previously uncharacterized miR-639 in NPC. In a study population of 139 patients, higher expression of miR-639 was associated with metastasis, more advanced cancer stages, and lower disease-free survival rates. In vitro experiments involving transfection of human NPC C666-1 and NPC/HK1 cell lines with miR-639 mimics and antagomir indicated that overexpressing miR-639 promoted cell proliferation and migration, suppression of miR-639 inhibited proliferation and migration. The present study provides evidence that miR-639 is differentially expressed in NPC tissues of varying cancer stages, and suggests that quantifying circulating miR-639 may be of importance for non-invasive diagnosis and prognostic evaluation, and may have potential therapeutic utility.

Silent brain infarct (SBI) is associated with symptomatic stroke, but the association between SBI and acute ischemic stroke severity is uncertain. We aimed at investigating the association between SBI number and stroke severity in patients with first-ever ischemic stroke without advanced leukoaraiosis.This study included 115 patients with first-ever ischemic stroke without advanced leukoaraiosis. National Institutes of Health Stroke Scale (NIHSS) scores were measured. Magnetic resonance imaging (MRI) was performed to detect the acute ischemic infarct and SBI. The location of infarct was divided into anterior and posterior circulations. The size of infarct was divided into large (≥15 mm) and small (15 mm) infarctions. The number of SBIs was divided into single and multiple (r2) subgroups. The association between SBI and the NIHSS score was analyzed by stratification of stroke locations. The associations between SBI and the NIHSS score and the size of the acute ischemic infarct were analyzed by logistic regression.Of the 74 patients with SBI, single SBI was 30 (40.5%) and multiple SBIs were 44 (59.5%). Age (odds ratio [OR] = 1.125, P .001) and hypertension (OR = 3.562, P .05) were independent risk factors for SBI. When adjusted for all the other vascular risk factors, multiple SBIs had a higher percentage of more than 3 NIHSS scores (OR = 3.59, 95% confidence interval [CI]: 1.00-12.99, P = .048) and a large acute ischemic infarct (OR = 3.71, 95% CI: 1.23-11.22, P = .020) than no SBI.Multiple SBIs have severer neurological deficits and larger infarcts for ischemic stroke than no SBI, which may suggest the large-artery or cardiovascular vasculopathy evolution and poor collateral circulation in patients with multiple SBIs.

Purpose/Aim of the study: Cerebrovascular reactivity (CVR) is an important marker for assessing cerebrovascular disease. This study assessed the CVR by perfusion computed tomography (CT) and CO2 inhalation tests in patients with unilateral middle cerebral artery (MCA) stenosis disease. Materials and Methods: Thirty-one patients with unilateral MCA stenosis disease diagnosed by digital subtraction angiography were studied. Patients were divided into two groups according to the degree of stenosis: severe and moderate. The regional cerebral blood flow (CBF) before and after CO2 inhalation was determined by perfusion CT. Regional CVR values were obtained by the following formula: increase (%) = (post-CBF) − (pre-CBF)/(pre-CBF) × 100%. Results: No significant differences in the mean CBF in the MCA stenosis region were found between the affected and contralateral sides before the CO2 inhalation test; after the test, CBF was more significantly decreased on the affected side than on the contralateral side. The ch...

The aim of this study was to explore whether interleukin-6 (IL-6) gene (-174 G/C and -572 C/G) polymorphisms are associated with susceptibility to coronary artery disease (CAD) risk in Chinese population. All the statistical tests were performed using Stata version 11.0. Twelve articles involving 16 studies were included in this meta-analysis, covering a total of 2309 CAD cases and 2273 controls. For IL-6 gene -572 C/G polymorphism, the results showed evidence for significant association between IL-6 gene -572 C/G polymorphism and CAD risk (for G allele vs. C allele: OR=1.48, 95% CI=1.26-1.74, p0.001; for G/G vs. C/C: OR=2.60, 95% CI=1.54-4.39, p0.001; for G/G vs. G/C+C/C: OR=2.15, 95% CI=1.35-3.42, p=0.001; for G/G+G/C vs. C/C: OR=1.55, 95% CI=1.29-1.85, p0.001). However, for IL-6 gene -174 G/C polymorphism, no significant association was found between this variation and CAD risk. In summary, our meta-analysis showed evidence that IL-6 gene -572 C/G polymorphism may be a risk factor for CAD susceptibility. For IL-6 gene -174 G/C polymorphism, no significant association was found between this variation and CAD risk.

Several lines of evidence suggest that estrogen receptor alpha (ER-α) gene polymorphism may influence the development of osteoarthritis (OA). However, the results are inconsistent. The aim of this study was to explore using a meta-analysis whether rs2234693 (ER-α PvuII T/C) polymorphism confers significant susceptibility to OA.A systematic search of all relevant studies published through 17 August 2014 was conducted using the PubMed, Web of Science, Embase, Cochrane database, Current Controlled Trials, Clinicaltrials.gov, Chinese Clinical Trial Registry, CBMdisc, CNKI and Google Scholar. All statistical analyses were done with Review Manager 5.1.4. Twelve articles involving 15 studies were included in the final meta-analysis, which contained 6417 OA cases and 8605 controls. Overall, no significant association was found between the rs2234693 polymorphism and OA risk when all studies were pooled into the meta-analysis (for C allele vs. T allele: OR = 0.99, 95% CI = 0.94-1.04, p = 0.63; for C/C vs. T/T: OR = 0.97, 95% CI = 0.87-1.08, p = 0.53; for C/C vs. T/C + T/T: OR = 0.96, 95% CI = 0.88-1.06, p = 0.43; for C/C + T/C vs. T/T: OR = 1.00, 95% CI = 0.89-1.14, p = 0.94). In the subgroup analysis, significant association was found between the rs2234693 polymorphism and the OA risk in the knee osteoarthritis (KOA) group (for C/C + T/C vs. T/T: OR = 1.15, 95% CI = 1.02-1.29, p = 0.02).The present meta-analysis suggests that the rs2234693 polymorphism is associated with an increased KOA risk. Additional well designed genome-wide association studies are required to confirm the result.

Introduction ATP-binding cassette transporter 1 (ABCA1), a member of the ATP-binding cassette family, plays a critical role in the development of atherosclerosis (AS). This meta-analysis was performed to assess the associations of ABCA1 C69T and V825I polymorphisms with AS susceptibility. Materials and methods A comprehensive search was conducted to identify all eligible studies from PubMed, Embase, Web of Science, Cochrane database, CBMdisc, CNKI and Google Scholar. Additionally, hand searching of the references of identified articles was performed. All statistical analyses were done with Review Manager 5.1.4 and Stata 11.0. Results Eleven articles involving 14 studies were included in the final meta-analysis. For the ABCA1 C69T polymorphism, six studies involving 1854 AS cases and 5744 controls were combined showing significant association between this variant and AS risk (for T allele vs. C allele: OR = 1.44, 95% CI = 1.04-1.24, p = 0.005; for T/T vs. C/C: OR = 1.39, 95% CI = 1.12-1.73, p = 0.003; for T/T vs. C/T + C/C: OR = 1.34, 95% CI = 1.09-1.65, p = 0.006; for T/T + C/T vs. C/C: OR = 1.13, 95% CI = 1.01-1.27, p = 0.040). For the ABCA1 V825I polymorphism, eight studies involving 2026 AS cases and 8696 controls were combined. There was no significant association between the variant and AS risk (for I allele vs. V allele: OR = 1.18, 95% CI = 0.90-1.53, p = 0.230; for I/I vs. V/V: OR = 1.29, 95% CI = 0.75-2.23, p = 0.360; for I/I vs. V/I + V/V: OR = 1.40, 95% CI = 0.87-2.26, p = 0.160; for I/I + V/I vs. V/V: OR = 1.15, 95% CI = 1.00-1.33, p = 0.060). Conclusions This meta-analysis suggested that the ABCA1 C69T polymorphism was associated with an increased AS risk. Furthermore, there was no significant association between the ABCA1 V825I polymorphism and AS risk.

Purpose/aim of the study: Cerebrovascular reactivity (CVR) reflects the vasodilatory reserve of cerebral resistance vessels, which is an important marker for assessing cerebrovascular disease. The present study is to investigate whether CVR impairment increases adverse long-term outcome risk of patients with ≥ 50% symptomatic unilateral middle cerebral artery (MCA) stenosis (ischemic stroke (IS) or transient ischemic attack (TIA)).Digital subtraction angiography (DSA) was used to assess the degree of stenosis, and perfusion CT and 5% COSeventy-three patients with ≥ 50% symptomatic unilateral MCA stenosis, involving 31 non-CVR impairment cases and 42 CVR impairment cases, were included in the present study. Finally, IS occurred in six CVR impairment patients, and no endpoint happened in the non-CVR impairment group. Therefore, the annual rate of IS was 14.29% in the CVR impairment group and 0% in the non-CVR impairment group (P = 0.035). Besides, further Kaplan-Meier analysis found CVR impairment was closely associated with the IS risk (Kaplan-Meier Log-rank 4.719, P = 0.030).Our results showed that for patients with ≥ 50% symptomatic unilateral MCA stenosis, there was significant difference between non-CVR impairment cases and CVR impairment cases in the annual rate of IS. It suggests that CVR impairment increases the risk of adverse long-term outcomes.

The association between large-artery atherosclerosis and leukoaraiosis (LA) has been increasingly reported with inconsistent conclusion. This systematic review examines the relationship between LA and carotid atherosclerosis, manifested as atherosclerotic stenosis, plaques and increased intima-media thickness (IMT). PubMed, Embase, and Web of Science were searched for articles published up to February 2014. Thirty-two studies that examined the relationship between LA and carotid atherosclerosis were included. All statistical analysis was conducted with Review Manager 5.2.4. Finally, 32 studies including 17,721 patients were identified. There were 7 (30%) out of 23 studies reporting significant association between LA and carotid stenosis; 11 (79%) out of 14 studies reporting significant association between LA and carotid plaque; all 9 studies reporting significant association between LA and carotid IMT; one study showing an association between LA and CAWT (similar to the role of the IMT). The quantitative meta-analysis of 10 studies showed that carotid atherosclerosis was not associated with LA (OR: 1.10; 95% CI: 0.61-1.98). A significant association was found between LA and carotid plaque (OR = 3.53; 95% CI = 1.83-6.79), and the result of IMT group showed that IMT increased risk of LA (MD = 0.11; 95% CI = 0.01-0.22). This systematic review suggested that LA has a tendency of association with carotid plaques but no association with simple carotid stenosis.

Published data regarding the association between apolipoprotein E (ApoE) gene polymorphism and type 2 diabetes mellitus (T2DM) risk in Chinese Han population were inconclusive. To derive a more precise estimation of the relationship between this variant and T2DM risk in Chinese Han population, we performed this meta-analysis.A computerized literature search was conducted to identify the relevant studies from PubMed, EMbase, Web of Science, CBMdisc, CNKI, and Google Scholar. Additionally, hand searching of the references of identified articles was performed. All the statistical tests were performed using Stata 11.0.A total of 29 articles with 4615 T2DM cases and 2867 controls were included in the present meta-analysis. The results showed evidence for significant association between ApoE gene polymorphism and T2DM risk (for ε2/ε3 vs. ε3/ε3: OR=1.37, 95% CI=1.12-1.68, P0.01; for ε3/ε4 vs. ε3/ε3: OR=1.53, 95% CI=1.23-1.91, P0.01; for ε4/ε4 vs. ε3/ε3: OR=1.86, 95% CI=1.22-2.84, P0.01; for ε2 allele vs. ε3 allele: OR=1.28, 95% CI=1.08-1.52, P=0.01; for ε4 allele vs. ε3 allele: OR=1.43, 95% CI=1.22-1.68, P0.01). In addition, significant association was also found between ApoE gene polymorphism and diabetic nephropathy (DN) risk.The results of this meta-analysis suggest that the ApoE ε2 and ε4 alleles may be associated with increased risks of T2DM and DN in Chinese Han population. Additional well-designed genome-wide association studies are required to confirm these results.

It remains controversial regarding the association between toll-like receptor 4 (TLR4) gene Asp299Gly (+896 A/G) polymorphism and myocardial infarction (MI) risk. Thus, a large-scale meta-analysis evaluating the potential association between this gene variant and MI risk is required. PubMed, Embase, Web of Science, CBMdisc, CNKI, and Google Scholar were searched until February 6, 2013. All the statistical tests were performed using Stata 11.0. Nine articles involving 10 studies were included in the final meta-analysis, covering a total of 8299 MI cases and 6849 controls. Overall, no significant association was found between the TLR4 gene Asp299Gly polymorphism and MI risk (G allele vs. A allele: OR = 0.95, 95% CI = 0.74–1.22, p = 0.71; G/G vs. A/A: OR = 1.03, 95% CI = 0.54–1.98, p = 0.93; G/G vs. A/G + A/A: OR = 1.05, 95% CI = 0.55–2.03, p = 0.87; G/G + A/G vs. A/A: OR = 0.92, 95% CI = 0.75–1.13, p = 0.42). In the subgroup analysis based on source of controls, there was also lack of evidence for significant association between the TLR4 gene Asp299Gly polymorphism and MI risk. In summary, the present meta-analysis indicated that the TLR4 gene Asp299Gly polymorphism was not associated with MI risk.

Background: The association between methylenetetrahydrofolate reductase (MTHFR) gene A1298C polymorphism and adult stroke remains controversial. The present article was designed to clarify this relationship through pooled analysis of the numerous epidemiological studies focusing on this association. Methods: We comprehensively searched all published papers in electronic database including PubMed, Embase, Web of Science, Chinese Biomedical Literature on disc (CBMdisc) and China National Knowledge Infrastructure (CNKI) up to 2013. The pooled odds ratios (ORs) with 95% confidence intervals (CIs) for allelic (C allele vs. A allele), additive (CC vs. AA), dominant (CC+AC vs. AA), and recessive (CC vs. AA+AC) models were calculated. Subgroup and sensitivity analyses were performed to detect the heterogeneity and examine the reliability of results, respectively. Begg's funnel plots and Egger's regression test were used to assess the potential publication bias. Results: A total of fifteen studies containing 2,361 cases and 2,653 controls were included in the final meta-analysis. The combined results of overall analysis showed that there was significant association between MTHFR gene A1298C polymorphism and adult stroke (allelic model: OR = 1.36, 95% CI = 1.11-1.67; additive model: OR = 1.88, 95% CI = 1.12-3.18; dominant model: OR = 1.33, 95% CI = 1.08-1.65 and recessive model: OR = 1.77, 95% CI = 1.07-2.94, respectively). On subgroup analysis by ethnicity of study population, significant association was shown in meta-analysis based on Asian population (allelic model: OR = 1.40, 95% CI = 1.19-1.65; additive model: OR = 2.58, 95% CI = 1.34-4.96; dominant model: OR = 1.44, 95% CI = 1.20-1.73 and recessive model: OR = 2.12, 95% CI = 1.20-3.76, respectively), but not in Caucasian population (allelic model: OR = 1.30, 95% CI = 0.93-1.82; additive model: OR = 1.65, 95% CI = 0.81-3.33; dominant model: OR = 1.17, 95% CI = 0.86-1.61 and recessive model: OR = 1.70, 95% CI = 0.83-3.50, respectively). In addition, the heterogeneity was effectively removed or decreased by limiting the included studies with population of Asian ethnicity. Furthermore, the corresponding pooled ORs were not materially changed in all genetic models of meta-analysis after limiting the included studies with population-based controls. However, except the recessive model, publication bias presented in the allelic, additive, dominant models identified by the Begg's funnel plots and Egger's regression test. Conclusions: In conclusion, the overall analysis suggests that MTHFR gene A1298C polymorphism plays an important role in the development of adult stroke. Genotype CC of MTHFR-1298A/C could increase the risk of stroke and may act as a predictor for clinical evaluation, especially in the Asian population. More studies with large-scale and different ethnicities are required to further confirm our findings. i 2014 S. Karger AG, Basel

Laryngeal cancer ranks as the foremost head and neck malignant tumor. The abnormal expression of microRNAs (miRNAs) has been reported due to its role in cancer development with ability to regulate ...

Increasing epidemiological studies have focused on the associations between interleukin-6 (IL-6) gene -174G>C polymorphism and atherosclerotic diseases, but the results are still controversial. This meta-analysis was designed to identify whether this association exists. PubMed, Embase, Web of Science, Cochrane database, Clinicaltrials.gov and Current Controlled Trials, Chinese Clinical Trial Registry, CBMdisc, CNKI and Google Scholar were searched to get the genetic association studies. The crude odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) were used to estimate the association between the IL-6 gene -174G>C polymorphism and atherosclerosis ( AS ) risk. The subgroup analyses were made on the following: ethnicity, atherosclerotic diseases and source of controls. Finally, 50 studies (15,029 cases and 18,485 controls) were included in this meta-analysis. Overall, no significant association was found between the IL-6 gene -174G>C polymorphism and AS risk (for C allele vs. G allele: OR=1.02, 95% CI=0.94-1.11, p=0.64; for C/C vs. G/G: OR=1.01, 95% CI=0.85-1.21, p=0.88; for C/C vs. C/G+G/G: OR=0.97, 95% CI=0.84-1.12, p=0.68; for C/C+C/G vs. G/G: OR=1.07, 95% CI=0.97-1.17, p=0.18). In the subgroup analyses, significant associations were found between the IL-6 gene -174G>C polymorphism and AS in non-Caucasian group (for CC+CG vs. GG: OR=1.22, 95% CI=1.06-1.41, p=0.005), other atherosclerotic diseases group (for C allele vs. G allele: OR =0.75, 95% CI=0.61-0.93, p=0.008; for C/C vs. G/G: OR=0.56, 95% CI=0.38-0.81, p=0.002; for C/C vs. C/G+G/G: OR=0.60, 95% CI=0.45-0.79, p=0.0004) and population-based group (for C allele vs. G allele: OR=1.09, 95% CI=1.00-1.18, p=0.04; for CC+CG vs. GG: OR=1.15, 95% CI=1.04-1.27, p=0.005). In summary, the present meta-analysis suggests that the IL-6 gene -174G C polymorphism is associated with the susceptibility to AS. However, due to the high heterogeneity in the meta-analysis, the results should be interpreted with caution.

This meta-analysis was to compare clinical outcomes of intravenous recombinant tissue plasminogen activator (IV rtPA) administered within 3 hours versus 3-4.5 hours after symptom onset.We collected all interventional or observational studies that compared clinical outcomes of IV rtPA treatment within 3 hours and 3-4.5 hours after acute ischemic stroke onset by searching PubMed (up to October 2012), Embase (1966 to October 2012) and Web of Science (2003 to October 2012) as well as manually searching the references of articles retrieved. The combined effect was calculated by odds ratios (ORs) and 95% confidence intervals (CIs) to analyze favorable functional outcome, mortality and symptomatic intracranial hemorrhage (sICH) at 90 days. Publication bias was analyzed by Begg's funnel plot and Egger's regression test.Our initial search identified a total of 27,391 articles. After reviewing the titles, abstracts and full text, a total of six studies and more than 25,000 patients were included in the final meta-analysis. The combined analyses demonstrated significant differences in the favorable outcome (modified Rankin scale, mRS: 0-2): OR = 0.89, 95% CI = 0.81-0.98 and very favorable outcomes (mRS: 0-1): OR = 0.86, 95% CI = 0.78-0.94 between two groups, which were both in favor of the 3-4.5 hours group. When all studies reporting data on sICH were combined, the overall summary OR indicated no differences in the two groups. The combined analyses showed no significant differences in 90 day mortality and 7 day mortality between within 3 hours and 3-4.5 hours.This meta-analysis does not provide any evidence that treatment with rtPA within 3-4.5 hours is less safe than treatment within 3 hours. It suggests that treatment with IV rtPA may be recommended to ischemic stroke patients that present within 4.5 hours of onset, although every effort should be made to give those patients IV rtPA within 3 hours of symptom onset.

Epidemiological studies have evaluated the association between interleukin-6 (IL-6) gene -174 G/C polymorphism and type 1 diabetes mellitus (T1DM) risk, but results of different studies have been inconsistent. The present meta-analysis was therefore designed to clarify these controversies. PubMed, Embase and Web of Science were searched from the first available year to March 25, 2012, as well as hand searching of the references of identified articles were performed. All studies investigating the association between IL-6 gene -174 G/C polymorphism and T1DM risk were included. Data analyses were carried out by Review Manager 5.1.2 and Stata 11.0. Seven studies were included in the final meta-analysis, covering a total of 9697 T1DM cases and 8455 controls. The results showed no evidence for significant association between IL-6 gene -174 G/C polymorphism and T1DM risk (for C/C+C/G vs. G/G: OR=1.30, 95% CI=0.84-2.00, p=0.24; for C/C vs. C/G+G/G: OR=1.10, 95% CI=0.75-1.60, p=0.63; for C/C vs. G/G: OR=1.34, 95% CI=0.75-2.42, p=0.33; for C allele vs. G allele: OR=1.16, 95% CI=0.88-1.53, p=0.30). In addition, the similar results were obtained in the subgroup analysis based on ethnicity. In summary, the present meta-analysis suggests that IL-6 gene -174 G/C polymorphism is not associated with T1DM risk. However, due to the small sample size in most of the included studies and the selection bias existed in some studies, the results should be interpreted with caution.

Summary The association between the interleukin-6 (IL-6) gene −572 C/G (rs1800796) polymorphism and type 2 diabetes mellitus (T2DM) risk remains controversial. Thus, we performed this meta-analysis by searching PubMed, Embase, Web of Science, CBMdisc and CNKI databases until January 30, 2012. In addition, hand searching of the references of identified articles was performed. A total of 10 case–control studies including 11,681 subjects were selected to evaluate the possible association. Our results showed evidence for significant association between the IL-6 gene −572 C/G polymorphism and T2DM risk (for G allele vs. C allele: odds ratio [OR] = 1.29, 95% confidence interval [CI] = 1.09–1.52, P = 0.002, P = 0.008 after Bonferroni testing; for G/G vs. C/C: OR = 1.89, 95% CI = 1.51–2.37, P < 0.00001, P < 0.00004 after Bonferroni testing; for GG vs. G/C + C/C: OR = 1.75, 95% CI = 1.20–2.56, P = 0.004, P = 0.016 after Bonferroni testing; for G/G + G/C vs. C/C: OR = 1.32, 95% CI = 1.11–1.57, P = 0.001, P = 0.004 after Bonferroni testing). In addition, similar results were obtained in the subgroup analysis based on ethnicity. In summary, the present meta-analysis suggests a significant association between the IL-6 gene −572 G allele and increased risk of T2DM.

It remains controversial regarding the association between interleukin-8 (IL-8) gene −251 T/A polymorphism and peptic ulcer disease (PUD) risk. Thus, a large-scale meta-analysis evaluating the precise association between this gene variant and PUD risk is required. We searched the PubMed, Embase, Web of Science, and Google Scholar until April 25, 2012. Additionally, hand searching of the references of identified articles were performed. All the statistical tests were performed using Stata 11.0. A total of eight studies (3105 subjects) were included in this meta-analysis. Overall, no significant association was found between IL-8 gene −251 T/A polymorphism and PUD risk (for A allele vs. T allele: OR = 1.17, 95% CI = 0.97–1.41, p = 0.094; for A/A vs. T/T: OR = 1.33, 95% CI = 0.94–1.90, p = 0.108; for A/A vs. A/T + T/T: OR = 1.22, 95% CI = 0.97–1.52, p = 0.083; for A/A + A/T vs. T/T: OR = 1.26, 95% CI = 0.95–1.67, p = 0.113). However, in the subgroup analyses by ethnicity, H. pylori infection and the subtype of PUD, significant associations were found between IL-8 gene −251 T/A polymorphism and PUD risk in Asians, H. pylori+, duodenal ulcer disease (DUD) and gastric ulcer disease (GUD), respectively. In summary, the present meta-analysis suggests that IL-8 gene −251 T/A polymorphism is associated with increased PUD risk among Asians, and especially for the subgroups of H. pylori+, DUD and GUD.

Background Epidemiologic studies have evaluated the association between tumor necrosis factor-alpha (TNF-α) gene -308A/G polymorphism and the risk of acute pancreatitis (AP), but the results are inconsistent. In order to derive a more precise estimation of the associations, a meta-analysis was performed. Materials and methods Systematic searches of electronic databases PubMed, Embase, and Web of Science, as well as hand searching of the references of identified articles, were performed. All case-control studies investigating the association between TNF-α gene -308A/G polymorphism and AP risk were included. The association was assessed by odds ratio (OR) with 95% confidence intervals (CIs). Publication bias was analyzed by Begg's funnel plot and Egger's regression test. Results The initial search revealed 818 potentially eligible studies. Having read the title, abstract, or full text, we included six relevant studies in the final meta-analysis, which contained 1,006 AP cases and 782 controls. Overall, no significant association was found between TNF-α gene -308A/G polymorphism and AP risk when all studies were pooled into the meta-analysis (for A/A+A/G versus G/G: OR = 1.03, 95% CI = 0.83-1.28, P = 0.79; for A/A versus A/G+G/G: OR = 0.97, 95% CI = 0.65-1.45, P = 0.87; for A/A versus G/G: OR = 1.23, 95% CI = 0.79-1.91, P = 0.37; for A allele versus G allele: OR = 0.99, 95% CI = 0.83-1.18, P = 0.90). In addition, the similar results were obtained in the subgroup analysis based on the ethnicity and subtype of AP. Conclusions The present meta-analysis reveals that the TNF-α gene -308A/G polymorphism is not associated with AP risk. However, due to the small number of subjects included in analysis and the selection bias in some studies, the results should be interpreted with caution.

Epidemiological studies have evaluated the association between interleukin-1 (IL-1)α C(-889)T polymorphism and Alzheimer's disease (AD), but the results remain inconclusive. This meta-analysis was, therefore, designed to clarify these controversies. Systematic searches of electronic databases Embase, PubMed, and Web of Science as well as hand searching of the references of identified articles and the meeting abstracts were performed. Statistical analyses were performed using software Review Manager (Version 5.1.2) and Stata (Version 11.0). The pooled odds ratios (ORs) with 95 % confidence intervals (95 % CIs) were calculated. A total of 28 publications including 29 studies were involved. There was a significant association between IL-1α C(-889)T polymorphism and AD (for T allele vs. C allele: OR = 1.14, 95 % CI = 1.07-1.21; for T/T vs. C/C: OR = 1.39, 95 % CI = 1.18-1.63; for dominant model: OR = 1.13, 95 % CI = 1.04-1.22; and for recessive model: OR = 1.39, 95 % CI = 1.20-1.60). Significant association was found for Asians, Caucasians, and early-onset Alzheimer's disease (EOAD) but for late-onset Alzheimer's disease (LOAD). This meta-analysis indicates that there is a significant association between IL-1α C(-889)T polymorphism and AD as well as EOAD.

The association between estrogen receptor alpha (ESR1) c.454-397T>C and c.454-351A>G polymorphism and ischemic stroke remains controversial. The aim of this study was to perform a meta-analysis to investigate a more authentic association between c.454-397T>C and c.454-351A>G mutation and ischemic stroke. Systematic searches of electronic databases Embase, PubMed, Web of Science as well as hand-searching of the references of identified articles and the meeting abstracts were performed. Study selection, data abstraction and study quality evaluation were independently conducted in duplicate. Statistical analyses were performed using software Stata 11.0. The pooled odds ratios (ORs) with 95 % confidence intervals (95 % CIs) were performed. Different effect models were used according to the difference in heterogeneity. Publication bias was tested by Begg's funnel plot and Egger's regression test. For c.454-397T>C mutation, five studies were combined. Significant association was found in allelic model (OR = 1.12, 95 % CI = 1.01-1.25, p = 0.03), additive model (OR = 1.25, 95 % CI = 1.01-1.54, p = 0.04), and recessive model (OR = 1.23, 95 % CI = 1.02-1.49, p = 0.03), whereas no evidence of association was found for dominant model (OR = 1.10, 95 % CI = 0.85-1.42, p = 0.47). For c.454-351A>G mutation, no evidence of association was found for all genetic models. Our meta-analysis suggests that ESR1 c.454-397T>C mutation is significantly associated with increased risk of ischemic stroke, whereas no evidence of association was found for ESR1 c.454-351A>G mutation.

Interleukin-6 (IL-6) gene − 174 G/C polymorphism has been reported to be associated with coronary heart disease (CHD), but the results remain inconclusive. The present meta-analysis was therefore designed to clarify these controversies. This meta-analysis was performed by searching PubMed, Embase and Web of Science databases. A total of 20 studies including 9619 CHD cases and 10,919 controls were combined showing no evidence of association between IL-6 gene − 174 G/C polymorphism and CHD risk (for C/C + C/G vs. G/G: OR = 1.10, 95% CI = 0.99–1.22, p = 0.07; for C/C vs. C/G + G/G: OR = 1.08, 95% CI = 0.93–1.24, p = 0.33; for C/C vs. G/G: OR = 1.16, 95% CI = 0.97–1.39, p = 0.11; for C allele vs. G allele: OR = 1.10, 95% CI = 1.00–1.21, p = 0.06). Moreover, we also did not find significant association between IL-6 gene − 174 G/C polymorphism and myocardial infarction (MI) risk. However, in the subgroup analysis by ethnicity, significant association was found among Asians (for C/C + C/G vs. G/G: OR = 1.35, 95% CI = 1.05–1.63, p = 0.02). In summary, the present meta-analysis suggests that IL-6 gene − 174 G/C polymorphism is associated with increased CHD risk among Asians. However, due to the small subjects included in the subgroup analysis of Asians, the results should be interpreted with caution.

Background and Objectives Epidemiological studies have evaluated the associations between interleukin-6 (IL-6) gene −174 C/G (rs1800795) and −572 C/G (rs1800796) polymorphisms and gastric cancer (GC) risk, but results and conclusions remain controversial. In order to derive a more precise estimation of the associations, we performed this meta-analysis. Methods A meta-analysis was conducted to estimate the associations between IL-6 gene −174 C/G and −572 C/G polymorphisms and GC risk. Results Nine articles involving 13 studies were included in the final meta-analysis, covering a total of 1,581 GC cases and 2,563 controls. For IL-6 gene −174 C/G polymorphism, nine studies were combined showing no evidence for associations between IL-6 gene −174 C/G polymorphism and GC risk. For IL-6 gene −572 C/G polymorphism, four studies were combined. There was also lack of evidence for significant association between IL-6 gene −572 C/G polymorphism and GC risk. In addition, the similar results were obtained in the subgroup analyses and cumulative meta-analysis. Conclusions The present meta-analysis suggests that IL-6 gene −174 C/G and −572 C/G polymorphisms are not associated with GC risk. However, due to the small subjects included in analysis and the selection bias in some studies, the results should be interpreted with caution. J. Surg. Oncol. 2012; 106: 987–993. © 2012 Wiley Periodicals, Inc.

The histone acetyltransferase GCN5 has been suggested to be involved in promoting cancer cell growth. But its role in human colon cancer development remains unknown. Herein we discovered that GCN5 expression is significantly upregulated in human colon adenocarcinoma tissues. We further demonstrate that GCN5 is upregulated in human colon cancer at the mRNA level. Surprisingly, two transcription factors, the oncogenic c-Myc and the proapoptotic E2F1, are responsible for GCN5 mRNA transcription. Knockdown of c-Myc inhibited colon cancer cell proliferation largely through downregulating GCN5 transcription, which can be fully rescued by the ectopic GCN5 expression. In contrast, E2F1 expression induced human colon cancer cell death, and suppression of GCN5 expression in cells with E2F1 overexpression further facilitated cell apoptosis, suggesting that GCN5 expression is induced by E2F1 as a possible negative feedback in suppressing E2F1-mediated cell apoptosis. In addition, suppression of GCN5 with its specific inhibitor CPTH2 inhibited human colon cancer cell growth. Our studies reveal that GCN5 plays a positive role in human colon cancer development, and its suppression holds a great therapeutic potential in antitumor therapy.

Objective To observe the neuroprotective effect of different doses of melatonin on early lipid peroxidation level and ultra-structure in experimental spinal cord injury(SCI) rats.Methods The SCI model of rat was established by an aneurysm clip at the level of T10.Sixty model rats were randomly divided into 6 groups(10 each): model I group received only laminectomy;model II group received laminectomy and aneurysm clip;the SCI rats in control group were given 0.2ml of 5% ethanol immediately after injury;the SCI rats in methylprednisolone treatment group were given 30mg/kg of methylprednisolone;melatonin treatment I and II group received melatonin with dosage of 50 and 100 mg/kg,respectively.The malonaldehyde(MDA) level at the injured sites of the spinal cord at 24 hours after trauma was detected,and the score of ultrastructural histopathological changes was also made.Results The MDA levels in model I and all treatment groups were significantly lower than those in model II and control group(P < 0.05).There were no statistical difference between melatonin and methylprednisolone treatment group(P > 0.05),and the same was between the two melatonin treatment groups(P > 0.05).The scoring of ultrastructural histopathological changes showed that melatonin treatment II group had the same neuroprotective effect as in methylprednisolone group(P > 0.05),while the effect of melatonin treatment II group was significantly better than that of melatonin treatment I group(P < 0.05).Conclusions Melatonin can inhibit the early lipid peroxidation of experimental spinal cord injury,and possess the neuroprotective effect on the ultra-structure.

Objectives To assess the association between polymorphism in the interleukin (IL)-10 promoter region of 1082 G/A and the risk of cervical cancer and/or cervical intraepithelial neoplasia (CIN), using meta-analysis. Methods The electronic literature databases PubMed®, Embase®, Web of Science, CBMdisc and CNKI were searched for relevant studies. The strength of association between IL-10 gene −1082 G/A polymorphism and cervical cancer and/or CIN was measured using pooled odds ratios with 95% confidence intervals in four genetic models: allelic model (A allele versus G allele); additive model (A/A versus G/G); recessive model (A/A versus G/A+G/G); dominant model (A/A+G/A versus G/G). Results Eight studies involving 1983 cases and 1618 controls were identified and included in the meta-analysis. No significant associations were found between IL-10 gene −1082 G/A polymorphism and cervical cancer and/or CIN in any of the genetic models. Conclusions IL-10 gene −1082 G/A polymorphism does not appear to be associated with the risk of cervical cancer and/or CIN.

The transient receptor potential vanilloid type 1 (TRPV1) channel, a ligand-gated cation channel of the TRP subfamily, can be activated by multiple stimuli, including capsaicin. Currently, cumulative studies have demonstrated an interesting link between TRPV1 and cardiovascular diseases, including hypertension. Additionally, the protective effect of TRPV1 against hypertension and its related disorders has been proved to be partly involved with the improved action of vascular smooth muscle cells (VSMCs). This review focuses on the current knowledge of TRPV1 in improving VSMC function and attenuating hypertension.

The present study is to investigate whether diabetes mellitus (DM) increases risk of adverse long-term outcomes after intracranial stent placement. Patients receiving intracranial stenting were assigned to DM group and non-DM group according to diabetes status. The long-term follow-up endpoint was composite of any stroke and death within 30 days, any ischemic stroke beyond 30 days, and transient ischemic attack in the territory of the stented artery at any time. A total of 44 stenoses in 43 patients were retrospectively analyzed. The cumulative probability of the composite outcomes were 15.4% (95% CI 15.3-47.3%) at 1 year and 30.8% (95% CI 26.5-33.6%) at 2 years for DM group; 17.5% (95% CI 16.0-31.2%) at both 1 year and 2 years for non-DM group (log-rank test, P = 0.424). After adjusting for the confounders, the risk of DM versus non-DM for composite outcomes remained insignificant (hazard ratio: 2.84, 95% CI 0.46-17.66; P = 0.26). Our results showed that there is no significant difference between patients with DM and without DM in cumulative probability of the composite outcomes. It suggests that based on our data, there is no evidence that DM increases the risk of adverse long-term outcomes after intracranial stent placement.

Aims Toll-like receptor 4 (TLR4) gene Asp299Gly and Thr399Ile polymorphisms have been reported to be associated with susceptibility to type 2 diabetes mellitus (T2DM) with inconsistent results. In an effort to clarify earlier inconclusive results, a meta-analysis evaluating the precise associations between TLR4 gene Asp299Gly and Thr399Ile polymorphisms and T2DM risk was performed. Methods We searched the PubMed, Embase, Web of Science, CBMdisc, CNKI, and Google Scholar until July 17, 2014. Additionally, hand searching of the references of identified articles were performed. Original observational studies dealing with the associations between TLR4 gene Asp299Gly and Thr399Ile polymorphisms and T2DM risk were selected. Heterogeneity and publication bias were determined and the meta-analysis was performed by Review Manager 5.1.4 and Stata 11.0. Results Seventeen articles involving 25 studies were included in the final meta-analysis, covering a total of 5963 T2DM cases and 9096 controls. For TLR4 gene Asp299Gly polymorphism, 17 studies were combined showing no evidence for association between TLR4 gene Asp299Gly polymorphism and T2DM risk. For TLR4 gene Thr399Ile polymorphism, eight studies were combined. There was also lack of evidence for significant association between TLR4 gene Thr399Ile polymorphism and T2DM risk. In addition, the similar results were obtained in the sensitivity analyses. Conclusions The present meta-analysis indicates that TLR4 gene Asp299Gly and Thr399Ile polymorphisms are not associated with increased T2DM risk.

Osteoarthritis (OA) is one of the most common skeletal disease, which seriously affects the quality of life of patients, particularly in the middle-aged and elderly individuals. We aimed to explore whether rs9340799 [estrogen receptor alpha (ER-α) XbaI A/G] polymorphism was associated with OA using a meta-analysis. A literature search for eligible studies published before March 28, 2014 was conducted in the PubMed, Web of Science, Embase, Cochrane database, Current Controlled Trials, Clinicaltrials.gov, Chinese Clinical Trial Registry, CBMdisc, CNKI, Google Scholar and Baidu Library. The association between the rs9340799 polymorphism and OA risk was assessed by odds ratios (ORs) together with their 95 % confidence intervals (CIs). A total of 663 articles were found. After article review and quality assessment, 10 articles involving 2,924 OA cases and 5,868 controls were included in the final meta-analysis. The combined evidence suggested that rs9340799 polymorphism contributed significantly to an increased risk of OA (for G allele vs. A allele: OR = 1.21, 95 % CI 1.03–1.43, p = 0.02; for G/G vs. A/A: OR = 1.30, 95 % CI 1.07–1.57, p = 0.009). In the subgroup analyses, significant associations were found between the rs9340799 polymorphism and the OA risk in the European group, Asian group, and knee osteoarthritis group, respectively. These results suggested that the rs9340799 polymorphism might be associated with the risk of OA. However, the results should be interpreted with caution because of the publication bias.

Several epidemiologic studies have evaluated the association between intercellular adhesion molecule-1 (ICAM-1) gene K469E polymorphism and stroke, but the results were inconsistent. The present meta-analysis was performed to investigate the relationship between K469E polymorphism and stroke in the Chinese population. A comprehensive search for related studies from the electronic databases of PubMed, Embase, Web of Science, CBMdisc and CNKI as well as a manual search of the references of identified articles was performed. Data were extracted to calculate for allelic, additive, dominant and recessive models using pooled odds ratios (ORs) along with 95% confidence intervals (CIs) by Review Manager 5.0 and Stata 11.0. Different effect models, subgroup analysis, sensitivity analysis, publication bias and power calculations were used to improve the comprehensive analysis. Finally, a total of 12 studies containing 1593 cases and 1555 controls were included in the final meta-analysis. No evidence of significant association between ICAM-1 gene K469E polymorphism and stroke was found in all four models (allelic model: OR = 1.07, 95%CI = 0.78-1.47; additive model: OR = 1.21, 95% CI = 0.67-2.16 (EE vs. KK); OR = 1.04, 95%CI = 0.75-1.45 (EK vs. KK); dominant model: OR = 1.07, 95% CI = 0.73-1.56; and recessive model: OR = 1.18, 95% CI = 0.77-1.83, respectively) based on the overall population, as well as subgroup analysis and sensitivity analysis. In conclusion, the present meta-analysis showed no evidence of significant association between ICAM-1 gene K469E polymorphism and stroke in the Chinese population. Nonetheless, this conclusion should be interpreted cautiously due to the low statistical power and considerable heterogeneity. Therefore, larger sample-size studies with homogeneous cases and well-matched controls are needed to further address this correlation.

Foam cell formation is the hallmark of atherosclerosis. Both telmisartan and autophagy protect against the development of atherosclerosis. However, it has yet to be elucidated whether telmisartan prevents vascular smooth muscle cell (VSMC)-derived foam cell formation. Vascular smooth muscle cells isolated from the thoracic aorta of male C57BL/6J mice were used for this study. To induce foam cell formation, primary VSMCs were incubated in 80 μg/ml oxLDL for 24 h. LC3, beclin-1, PPARγ, AMPK, p-AMPK, mTOR and p-mTOR expression were determined via Western blot. Lipid accumulation was evaluated via oil red O staining and intracellular total cholesterol level measurement. Our study demonstrated that telmisartan dose-dependently increased the expression of beclin-1, the LC3II/LC3I ratio and the quantity of GFP-labeled autophagosomes, displaying a peak effect at 10 μM. In control siRNA-transfected VSMCs, telmisartan (10 μM) decreased lipid droplet accumulation and the total cholesterol level significantly. In contrast, in Atg7 siRNA-transfected VSMCs, telmisartan failed to attenuate lipid accumulation. In addition, telmisartan dose-dependently increased the expression of PPARγ and p-AMPK and decreased the expression of p-mTOR. GW9662 attenuated the telmisartan-induced increase in PPARγ expression, the LC3-II/LC3-I ratio and p-AMPK expression and the telmisartan-induced decrease in p-mTOR expression. Compound C restored mTOR activity and abolished the increase in the LC3-II/LC3-I ratio. Rapamycin significantly reduced p-mTOR expression and increased the LC3-II/LC3-I ratio. In conclusion, this study provides evidence that the chronic pharmacological activation of the PPARγ-mediated autophagy pathway using telmisartan may represent a promising therapeutic strategy for atherosclerosis.

BACKGROUND Several studies have investigated whether the polymorphism in the apolipoprotein A5 (APOA5) is associated with type 2 diabetes mellitus (T2DM) risk. However, those studies have produced inconsistent results. The purpose of this study was to investigate whether the APOA5 -1131T/C polymorphism (rs662799) confers significant susceptibility to T2DM using a meta-analysis. METHODS PubMed, Embase, Web of Science, Cochrane database, CBMdisc, CNKI and Google Scholar were searched to get the genetic association studies. All statistical analyses were done with Stata 11.0. RESULTS A total of 19 studies included 4,767 T2DM cases and 10,370 controls (four studies involving 555 T2DM cases and 2958 controls were performed among Europeans and 15 studies involving 4212 T2DM cases and 7412 controls were performed among Asians) were combined showing significant association between the APOA5 -1131T/C polymorphism and T2DM risk (for C allele vs. T allele: OR = 1.28, 95% CI = 1.17-1.40, p

A number of epidemiological studies have explored the association between NAD(P)H oxidase P22 phox gene C242T (rs4673) polymorphism and susceptibility to type 2 diabetes mellitus (T2DM), but the results are still debatable. Therefore, we conducted a meta-analysis to assess the potential association between the NAD(P)H oxidase P22 phox gene C242T polymorphism and T2DM risk.Electronic literature searches of the PubMed, Embase, Web of Science, CBMdisc, CNKI and Google Scholar were performed up to June 15, 2013. Additionally, hand searching of the references of identified articles was performed. Data analyses were carried out by Stata 11.0.Seven studies were included in the final meta-analysis, covering a total of 1661 T2DM cases and 1265 controls. The results showed evidence for significant association between the NAD(P)H oxidase P22 phox gene C242T polymorphism and T2DM risk (for T/T vs. T/C: OR=1.61, 95% CI=1.14-2.26, p=0.007; for T/T vs. T/C+C/C: OR=1.50, 95% CI=1.10-2.05, p=0.009). In the subgroup analysis, there was also evidence for significant association between the NAD(P)H oxidase P22 phox gene C242T polymorphism and T2DM risk, either for Asians (T/T vs. T/C+C/C: OR=1.74, 95% CI=1.15-2.64, p=0.009) or for non-Asians (for T allele vs C allele: OR=1.30, 95% CI=1.04-1.61, p=0.02).The present meta-analysis indicates that the NAD(P)H oxidase P22 phox gene 242 T allele might be associated with an increased T2DM risk.

A variety of epidemiological studies have evaluated the association between methylenetetrahydrofolate reductase (MTHFR) gene C677T polymorphism and cerebrovascular disease, but the results were inconsistent. The present meta-analysis was therefore performed to investigate the relationship between C677T polymorphism and cerebrovascular disease in Chinese population. Systematically searching for related studies from PubMed, Embase, Web of Science, CBMdisc and CNKI databases up to 20 September 2013 and manual searching of the reference lists of identified articles was performed. Information was extracted to calculate for the additive, dominant, and recessive models using the pooled odds ratios (ORs) along with 95 % confidence intervals (CIs), using Review Manager 5.0, STATA 11.0 and SPSS 17. Logistic regression, fixed or random effects model, subgroup analysis, sensitivity analysis, meta-regression analysis and publication bias were conducted to improve the comprehensive analysis. A total of 68 case–control studies containing 7,990 cases and 6,941 controls were included in the final meta-analysis. Evidence of significant association between C677T polymorphism and risk of cerebrovascular disease was found in all three genetic models (additive model OR 1.472, 95 % CI 1.368–1.585, P L

Tumor necrosis factor alpha (TNF-α) gene (-238 G/A [rs361525] and -308 G/A [rs1800629]) polymorphisms have been extensively studied in relation to various diseases, several epidemiologic studies have been performed to investigate the associations of TNF-α gene polymorphisms with pneumoconiosis; however, the results of these studies were not entirely consistent. In an effort to clarify earlier inconclusive results, we performed this meta-analysis of case-control genetic association studies.We identified eligible studies by searching the relevant databases, including PubMed, Embase, Web of Science, CBMdisc, CNKI, and Google Scholar, until February 15, 2013. Additionally, hand searching of the references of identified articles were performed. Heterogeneity and publication bias across studies were determined and the meta-analysis was performed by Stata 11.0.Fourteen articles involving 20 studies were included in the final meta-analysis, covering a total of 1935 pneumoconiosis cases and 3753 controls. The results showed evidence for significant association between TNF-α gene -308 G/A polymorphism and pneumoconiosis risk, suggesting that TNF-α gene -308 A allele may be a risk factor for pneumoconiosis (for A allele vs. G allele: OR = 1.41, 95% CI = 1.10-1.81, p = 0.01; for A/A + G/A vs. G/G: OR = 1.52, 95% CI = 1.21-1.91, p0.01). For TNF-α gene -238 G/A polymorphism, no significant association was found between this genetic variation and pneumoconiosis risk.This meta-analysis indicates that TNF-α gene -308 G/A polymorphism is associated with an increased pneumoconiosis risk.

BACKGROUND: Numerous epidemiological studies have evaluated the associations between ATP-binding cassette transporter 1 (ABCA1) R219K (rs2230806) and M883I (rs4149313) polymorphisms and atherosclerosis (AS), but results remain controversial. The purpose of the present study is to investigate whether these two polymorphisms facilitate the susceptibility to AS using a meta-analysis. METHODS: PubMed, Embase, Web of Science, Medline, Cochrane database, Clinicaltrials.gov, Current Controlled Trials, Chinese Clinical Trial Registry, CBMdisc, CNKI, Google Scholar and Baidu Library were searched to get the genetic association studies. All statistical analyses were done with Stata 11.0. RESULTS: Forty-seven articles involving 58 studies were included in the final meta-analysis. For the ABCA1 R219K polymorphism, 42 studies involving 12,551 AS cases and 19,548 controls were combined showing significant association between this variant and AS risk (for K allele vs. R allele: OR = 0.77, 95% CI = 0.71-0.84, P

BACKGROUND: Epidemiological studies have evaluated the association between apolipoprotein E (ApoE) gene polymorphism and coronary artery disease (CAD) risk which developed inconsistent conclusions. To derive a more precise estimation of the relationship in Chinese population, we performed this meta-analysis. METHODS: Databases, including PubMed, EMbase, Web of Science, CBMdisc and CNKI, were searched to get the genetic association studies. Additionally, hand searching of the references of identified articles were performed. All the statistical tests were performed using Review Manager 5.1.2 and Stata 11.0. RESULTS: We identified a total of 40 studies, including 4,564 CAD cases and 3,985 controls. The results showed evidence for significant association between ApoE ε4 allele and CAD risk (for ε2/ε4 vs. ε3/ε3: OR = 1.86, 95% CI = 1.42-2.43, p

Increasing evidence showed that abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) are common event in the pathophysiology of many vascular diseases, including atherosclerosis and restenosis after angioplasty. Among the underlying mechanisms, oxidative stress is one of the principal contributors to the proliferation and migration of VSMCs. Oxidative stress occurs as a result of persistent production of reactive oxygen species (ROS). Recently, the protective effects of peroxisome proliferator-activated receptor γ (PPARγ) against oxidative stress/ROS in other cell types provide new insights to inhibit the suggests that PPARγ may regulate VSMCs function. However, it remains unclear whether activation of PPARγ can attenuate oxidative stress and further inhibit VSMC proliferation and migration. In this study, we therefore investigated the effect of PPARγ on inhibiting VSMC oxidative stress and the capability of proliferation and migration, and the potential role of mitochondrial uncoupling protein 2 (UCP2) in oxidative stress. It was found that platelet derived growth factor-BB (PDGF-BB) induced VSMC proliferation and migration as well as ROS production; PPARγ inhibited PDGF-BB-induced VSMC proliferation, migration and oxidative stress; PPARγ activation upregulated UCP2 expression in VSMCs; PPARγ inhibited PDGF-BB-induced ROS in VSMCs by upregulating UCP2 expression; PPARγ ameliorated injury-induced oxidative stress and intimal hyperplasia (IH) in UCP2-dependent manner. In conclusion, our study provides evidence that activation of PPARγ can attenuate ROS and VSMC proliferation and migration by upregulating UCP2 expression, and thus inhibit IH following carotid injury. These findings suggest PPARγ may represent a prospective target for the prevention and treatment of IH-associated vascular diseases.

BACKGROUND: Epidemiological studies have evaluated the association between nicotinamide adenine dinucleotide phosphate (NADPH) oxidase p22(phox) C242T polymorphism and risk of ischemic cerebrovascular disease (ICVD), but the results remain inconclusive. This meta-analysis was therefore designed to clarify these controversies. METHODOLOGY/PRINCIPAL FINDINGS: Systematic searches of electronic databases Embase, PubMed and Web of Science, as well as hand searching of the references of identified articles and the meeting abstracts were performed. Statistical analyses were performed using software Review Manager (Version 5.1.7) and Stata (Version 11.0). The pooled odds ratios (ORs) with 95% confidence intervals (95%CIs) were performed. Fixed or random effects model was separately used depending on the heterogeneity between studies. Publication bias was tested by Begg's funnel plot and Egger's regression test. A total of 6 studies including 1,948 cases and 2,357 controls were combined showing no statistical evidence of association between NADPH oxidase p22(phox) C242T polymorphism and overall ICVD (allelic model: OR = 1.08, 95%CI = 0.93-1.26; additive model: OR = 1.33, 95%CI = 0.81-2.17; dominant model: OR = 1.00, 95%CI = 0.86-1.15; recessive model: OR = 1.06, 95%CI = 0.77-1.45). Significant association was found in large-artery atherosclerotic stroke subgroup (allelic model: OR = 1.12, 95%CI = 0.88-1.41; additive model: OR = 1.36, 95%CI = 0.60-3.09; dominant model: OR = 1.25, 95%CI = 0.74-2.11; recessive model: OR = 2.17, 95%CI = 1.11-4.23). No statistical evidence of significant association was observed for small-vessel occlusive stroke, as well as Asian subgroup and Caucasian subgroup. Statistical powers on the combined sample size (total and subgroup) were all lower than 80%. CONCLUSIONS/SIGNIFICANCE: This meta-analysis indicates that NADPH oxidase p22(phox) C242T polymorphism is more associated with large-artery atherosclerotic stroke than small-vessel occlusive stroke. However, this conclusion should be interpreted with caution due to the small sample size. Larger sample-size studies with homogeneous ICVD patients and well-matched controls are required.