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Epigenetic studies demonstrate that an association may exist between methylation of the retinoic acid receptor beta2 (RARβ2) gene promoter and breast cancer onset risk, tumor stage, and histological grade, however the results of these studies are not consistent. Hence, we performed this meta-analysis to ascertain a more comprehensive and accurate association.Relevant studies were retrieved from the PubMed, Embase and Chinese National Knowledge Infrastructure databases up to February 28, 2015. After two independent reviewers screened the studies and extracted the necessary data, meta-analysis was performed using Review Manager 5.2 software.Nineteen eligible articles, including 20 studies, were included in our analysis. Compared to non-cancerous controls, the frequency of RARβ2 methylation was 7.27 times higher in patients with breast cancer (odds ratio (OR) = 7.27, 95% confidence interval (CI) = 3.01-17.52). Compared to late-stage RARβ2 methylated patients, the pooled OR of early-stage ones was 0.81 (OR = 0.81, 95% CI = 0.55-1.17). The OR of low-grade RARβ2 methylated patients was 0.96 (OR = 0.96, 95% CI = 0.74-1.25) compared to high-grade RARβ2 methylated patients.RARβ2 methylation is significantly increased in breast cancer samples when compared to non-cancerous controls. RARβ2 could serve as a potential epigenetic marker for breast cancer detection and management.

Since the late 1960s, the average global supply of fat has increased by 20 g per capita per day. While fat intake has been considered a potential risk factor for prostate cancer (Pca), the hypothesis from previous epidemiologic studies remained equivocal.Relevant cohort studies were identified through a literature search in PubMed, ScienceDirect and Wiley Online Library up to March 1, 2015. A systematic review and dose-response meta-analysis were used to assess the relationship between fat intake and the risk for Pca.We identified 14 cohort studies, which included 37,349 cases and a total of 751,030 participants. We found no evidence of a non-linear association between fat intake and the risk for Pca. Overall, the summarized relative risks for every 28.35 g increment a day was 0.99 (95%CI: 0.98, 1.01; P=0.94; n=13) for total fat intake, 1.00 (95%CI: 1.00, 1.00; P=0.72; n=9) for saturated fat, 0.99 (95%CI: 0.95, 1.03; P=0.55; n=7) for polyunsaturated fat, and 1.00 (95%CI: 0.95, 1.04; P=0.85; n=8) for monounsaturated fat. Additionally, there was no link to the risk for advanced stage Pca regarding total fat intake (RR=1.02, 95%CI: 0.96, 1.08; P=0.63; n=5), saturated fat (RR=0.96, 95%CI: 0.84, 1.11; P=0.61; n=6), polyunsaturated fat (RR=0.96, 95%CI: 0.79, 1.17; P=0.68; n=6), or monounsaturated fat (RR=0.96, 95%CI: 0.86, 1.07; P=0.42; n=6). Subgroup and sensitively analyses showed consistent results.Little evidence from published cohort studies supports the statement that total fat, saturated fat or unsaturated fat intake increases the risk for Pca or advanced stage Pca.

It is well documented that nifedipine, a commonly used dihydropyridine Ca2+ channel blocker, has also significant interactions with voltage-gated K+ (Kv) channels. But to date, little is known whether nifedipine exerted an action on Kv2.1 channels, a member of the Shab subfamily with slow inactivation. In the present study, we explored the effects of nifedipine on rat Kv2.1 channels expressed in HEK293 cells. Data from whole-cell recording showed that nifedipine substantially reduced Kv2.1 currents with the IC50 value of 37.5 ± 5.7 μM and delayed the time course of activation without effects on the activation curve. Moreover, this drug also significantly shortened the duration of inactivation and deactivation of Kv2.1 currents in a voltage-dependent manner. Interestingly, the half-maximum inactivation potential (V1/2) of Kv2.1 currents was -11.4 ± 0.9 mV in control and became -38.5 ± 0.4 mV after application of 50 μM nifedipine. The large hyperpolarizing shift (27 mV) of the inactivation curve has not been reported previously and may result in more inactivation for outward delayed rectifier K+ currents mediated by Kv2.1 channels at repolarization phases. The Y380R mutant significantly increased the binding affinity of nifedipine to Kv2.1 channels, suggesting an interaction of nifedipine with the outer mouth region of this channel. The data present here will be helpful to understand the diverse effects exerted by nifedipine on various Kv channels.

BackgroundHolmium laser enucleation (HoLEP) in surgical treatment of benign prostate hyperplasia (BPH) potentially offers advantages over transurethral resection of the prostate (TURP).MethodsPublished randomized controlled trials (RCTs) were identified from PubMed, EMBASE, Science Citation Index, and the Cochrane Library up to October 10, 2013 (updated on February 5, 2014). After methodological quality assessment and data extraction, meta-analysis was performed using STATA 12.0 and Trial Sequential Analysis (TSA) 0.9 software.ResultsFifteen studies including 8 RCTs involving 855 patients met the criteria. The results of meta-analysis showed that: a) efficacy indicators: there was no significant difference in quality of life between the two groups (P>0.05), but compared with the TURP group, Qmax was better at 3 months and 12 months, PVR was less at 6, 12 months, and IPSS was lower at 12 months in the HoLEP, b) safety indicators: compared with the TURP, HoLEP had less blood transfusion (RR 0.17, 95% CI 0.06 to 0.47), but there was no significant difference in early and late postoperative complications (P>0.05), and c) perioperative indicators: HoLEP was associated with longer operation time (WMD 14.19 min, 95% CI 6.30 to 22.08 min), shorter catheterization time (WMD -19.97 h, 95% CI -24.24 to -15.70 h) and hospital stay (WMD -25.25 h, 95% CI -29.81 to -20.68 h).ConclusionsIn conventional meta-analyses, there is no clinically relevant difference in early and late postoperative complications between the two techniques, but HoLEP is preferable due to advantage in the curative effect, less blood transfusion rate, shorter catheterization duration time and hospital stay. However, trial sequential analysis does not allow us to draw any solid conclusion in overall clinical benefit comparison between the two approaches. Further large, well-designed, multicentre/international RCTs with long-term data and the comparison between the two approaches remain open.

ObjectiveTo evaluate the effectiveness and safety of GnRH antagonist and GnRH agonist in supposed normal ovarian responders undergoing IVF.MethodsData from 6 databases were retrieved for this study. The RCTs of GnRH agonist and GnRH antagonist use during IVF-EF therapy for patients with supposed normal ovarian response were included. A meta-analysis was performed with Revman 5.1software.ResultsTwenty-three RCTs met the inclusion criteria. The number of stimulation days (mean difference (MD): -0.66, 95% confidence interval (CI): -1.04∼-0.27), Gn amount (MD: -2.92, 95% CI: -5.0∼-0.85), E2 values on the day of HCG (MD: -330.39, 95% CI: -510.51∼-150.26), Number of oocytes retrieved (MD: -1.33, 95% CI: -2.02∼-0.64), clinical pregnancy rate (odds ratio (OR): 0.87, 95% CI: 0.75-1.0), and ovarian hyperstimulation syndrome (OHSS) incidence (OR: 0.59, 95% CI: 0.42∼0.82) were significantly lower in GnRH antagonist protocol than GnRH agonist protocol. However, the endometrial thickness on the day of HCG (MD: -0.04, 95% CI: -0.23∼0.14), the ongoing pregnancy rate (OR: 0.87, 95% CI: 0.74∼1.03), live birth rate (OR: 0.89, 95% CI: 0.64∼1.24), miscarriage rate (OR: 1.17, 95% CI: 0.85∼1.61), and cycle cancellation rate (OR: 1.11, 95% CI: 0.90∼1.37) did not significantly differ between the 2 groups.ConclusionsDuring IVF treatment for patients with supposed normal responses, the incidence of OHSS were significantly lower, whereas the ongoing pregnancy and live birth rates were similar in the GnRH antagonist compared with the standard long GnRH agonist protocols.

Alzheimer's disease (AD) is the most common form of senile dementia which is characterized by abnormal amyloid beta (Aβ) accumulation and deposition in brain parenchyma and cerebral capillaries, and leads to blood-brain barrier (BBB) disruption. Despite great progress in understanding the etiology of AD, the underlying pathogenic mechanism of BBB damage is still unclear, and no effective treatment has been devised. The standard Ginkgo biloba extract EGb761 has been widely used as a potential cognitive enhancer for the treatment of AD. However, the cellular mechanism underlying the effect remain to be clarified. In this study, we employed an immortalized endothelial cell line (bEnd.3) and incubation of Aβ(1-42) oligomer, to mimic a monolayer BBB model under conditions found in the AD brain. We investigated the effect of EGb761 on BBB and found that Aβ1-42 oligomer-induced cell injury, apoptosis, and generation of intracellular reactive oxygen species (ROS), were attenuated by treatment with EGb761. Moreover, treatment of the cells with EGb761 decreased BBB permeability and increased tight junction scaffold protein levels including ZO-1, Claudin-5 and Occludin. We also found that the Aβ(1-42) oligomer-induced upregulation of the receptor for advanced glycation end-products (RAGE), which mediates Aβ cytotoxicity and plays an essential role in AD progression, was significantly decreased by treatment with EGb761. To our knowledge, we provide the first direct in vitro evidence of an effect of EGb761 on the brain endothelium exposed to Aβ(1-42) oligomer, and on the expression of tight junction (TJ) scaffold proteins and RAGE. Our results provide a new insight into a possible mechanism of action of EGb761. This study provides a rational basis for the therapeutic application of EGb761 in the treatment of AD.

Background[corrected] Epidemiological studies have shown that tooth loss is associated with risk of head and neck cancer (HNC); however, the results were inconsistent. Therefore, we conducted a meta-analysis to ascertain the relationship between tooth loss and HNC.MethodsWe searched for relevant observational studies that tested the association between tooth loss and risk of HNC from PubMed and were conducted up to January 30, 2013. Data from the eligible studies were independently extracted by two authors. The meta-analysis was performed using the Comprehensive Meta-Analysis 2.2 software. Sensitivity and subgroup analyses were conducted to evaluate the influence of various inclusions. Publication bias was also detected.ResultsTen articles involving one cohort and ten case-control studies were yielded. Based on random-effects meta-analysis, an association between tooth loss and HNC risk was identified [increased risk of 29% for 1 to 6 teeth loss (OR = 1.29, 95% CI = 0.52-3.20, p = 0.59), 58% for 6 to 15 teeth loss (OR = 1.58, 95% CI = 1.08-2.32, p = 0.02), 63% for 11+ teeth loss (OR = 1.63, 95% CI = 1.23-2.14, pConclusionsBased on the current evidence, tooth loss is probably a significant and dependent risk factor of HNC, which may have a dose-response effect. People who lost six or more teeth should pay attention to symptoms of HNC, and losing 11 teeth or 15 teeth may be the threshold.

BackgroundMany epidemiological studies have found a positive association of periodontal disease (PD) with risk of head and neck cancer (HNC), but the findings are varied or even contradictory. In this work, we performed a meta-analysis to ascertain the relationship between PD and HNC risk.MethodsWe searched the PubMed, Embase, and Cochrane Library databases for relevant observational studies on the association between PD and HNC risk published up to March 23, 2013. Data from the included studies were extracted and analyzed independently by two authors. Meta-analysis was performed using RevMan 5.2 software.ResultsWe obtained seven observational studies involving two cohort and six case-control studies. Random-effects meta-analysis indicated a significant association between PD and HNC risk (odds ratio = 2.63, 95% confidence interval = 1.1.68 - 4.14; p < 0.001), with sensitivity analysis showing that the result was robust. Subgroup analyses based on adjustment for covariates, study design, PD assessment, tumor site, and ethnicity also revealed a significant association.ConclusionsBased on currently evidence, PD is probably a significant and independent risk factor of HNC.

BackgroundTo investigate the association between XPD Asp312Asn polymorphism and head and neck cancer risk through this meta-analysis.MethodsWe performed a meta-analysis of 9 published case-control studies including 2,670 patients with head and neck cancer and 4,452 controls. An odds ratio (OR) with a 95% confidence interval (CI) was applied to assess the association between XPD Asp312Asn polymorphism and head and neck cancer risk.ResultsOverall, no significant association between XPD Asp312Asn polymorphism and head and neck cancer risk was found in this meta-analysis (Asn/Asn vs. Asp/Asp: OR = 0.95, 95%CI = 0.80-1.13, P = 0.550, P(heterogeneity) = 0.126; Asp/Asn vs. Asp/Asp: OR = 1.11, 95%CI = 0.99-1.24, P = 0.065, P(heterogeneity) = 0.663; Asn/Asn+Asp/Asn vs. Asp/Asp: OR = 1.07, 95%CI = 0.97-1.19, P = 0.189, P(heterogeneity) = 0.627; Asn/Asn vs. Asp/Asp+Asp/Asn: OR = 0.87, 95%CI = 0.68-1.10, P = 0.243, P(heterogeneity) = 0.089). In the subgroup analysis by HWE, ethnicity, and study design, there was still no significant association detected in all genetic models.ConclusionsThis meta-analysis demonstrates that XPD Asp312Asn polymorphism may not be a risk factor for developing head and neck cancer.

BackgroundMany epidemiological studies have found a positive association between periodontal disease (PD) and risk of chronic obstructive pulmonary disease (COPD), but this association is varied and even contradictory among studies. We performed a meta-analysis to ascertain the relationship between PD and COPD.MethodsPubMed and Embase database were searched up to January 10, 2012, for relevant observational studies on the association between PD and risk of COPD. Data from the studies selected were extracted and analyzed independently by two authors. The meta-analysis was performed using the Comprehensive Meta-Analysis software.ResultsFourteen observational studies (one nested case-control, eight case-control, and five cross-sectional) involving 3,988 COPD patients were yielded. Based on random-effects meta-analysis, a significant association between PD and COPD was identified (odds ratio = 2.08, 95% confidence interval = 1.48-2.91; PConclusionsBased on current evidence, PD is a significant and independent risk factor of COPD. However, whether a causal relationships exists remains unclear. Morever, we suggest performing randomized controlled trails to explore whether periodontal interventions are beneficial in regulating COPD pathogenesis and progression.

It is well documented that nifedipine, a commonly used dihydropyridine Ca2+ channel blocker, has also significant interactions with voltage-gated K+ (Kv) channels. But to date, little is known whether nifedipine exerted an action on Kv2.1 channels, a member of the Shab subfamily with slow inactivation. In the present study, we explored the effects of nifedipine on rat Kv2.1 channels expressed in HEK293 cells. Data from whole-cell recording showed that nifedipine substantially reduced Kv2.1 currents with the IC50 value of 37.5 ± 5.7 μM and delayed the time course of activation without effects on the activation curve. Moreover, this drug also significantly shortened the duration of inactivation and deactivation of Kv2.1 currents in a voltage-dependent manner. Interestingly, the half-maximum inactivation potential (V1/2) of Kv2.1 currents was -11.4 ± 0.9 mV in control and became -38.5 ± 0.4 mV after application of 50 μM nifedipine. The large hyperpolarizing shift (27 mV) of the inactivation curve has not been reported previously and may result in more inactivation for outward delayed rectifier K+ currents mediated by Kv2.1 channels at repolarization phases. The Y380R mutant significantly increased the binding affinity of nifedipine to Kv2.1 channels, suggesting an interaction of nifedipine with the outer mouth region of this channel. The data present here will be helpful to understand the diverse effects exerted by nifedipine on various Kv channels. [ABSTRACT FROM AUTHOR]

Alzheimer’s disease (AD) is the most common form of senile dementia which is characterized by abnormal amyloid beta (Aβ) accumulation and deposition in brain parenchyma and cerebral capillaries, and leads to blood-brain barrier (BBB) disruption. Despite great progress in understanding the etiology of AD, the underlying pathogenic mechanism of BBB damage is still unclear, and no effective treatment has been devised. The standard Ginkgo biloba extract EGb761 has been widely used as a potential cognitive enhancer for the treatment of AD. However, the cellular mechanism underlying the effect remain to be clarified. In this study, we employed an immortalized endothelial cell line (bEnd.3) and incubation of Aβ1–42 oligomer, to mimic a monolayer BBB model under conditions found in the AD brain. We investigated the effect of EGb761 on BBB and found that Aβ1–42 oligomer-induced cell injury, apoptosis, and generation of intracellular reactive oxygen species (ROS), were attenuated by treatment with EGb761. Moreover, treatment of the cells with EGb761 decreased BBB permeability and increased tight junction scaffold protein levels including ZO-1, Claudin-5 and Occludin. We also found that the Aβ1–42 oligomer-induced upregulation of the receptor for advanced glycation end-products (RAGE), which mediates Aβ cytotoxicity and plays an essential role in AD progression, was significantly decreased by treatment with EGb761. To our knowledge, we provide the first direct in vitro evidence of an effect of EGb761 on the brain endothelium exposed to Aβ1–42 oligomer, and on the expression of tight junction (TJ) scaffold proteins and RAGE. Our results provide a new insight into a possible mechanism of action of EGb761. This study provides a rational basis for the therapeutic application of EGb761 in the treatment of AD. [ABSTRACT FROM AUTHOR]