Identification of the potential biomarkers in patients with glioma: a weighted gene co-expression network analysis.

Glioma is the most common brain tumor with high mortality. However, there are still challenges for the timely and accurate diagnosis and effective treatment of the tumor. One hundred and twenty-one samples with grades II, III and IV from the Gene Expression Omnibus database were used to construct gene co-expression networks to identify hub modules closely related to glioma grade, and performed pathway enrichment analysis on genes from significant modules. In gene co-expression network constructed by 2345 differentially expressed genes from 121 gene expression profiles for glioma, we identified the black and blue modules that associated with grading. The module preservation analysis based on 118 samples indicates that the two modules were replicable. Enrichment analysis showed that the extracellular matrix genes were enriched for blue module, while cell division genes were enriched for black module. According to survival analysis, 21 hub genes were significantly up-regulated and one gene was significantly down-regulated. What's more, IKBIP, SEC24D, and FAM46A are the genes with little attention among the 22 hub genes. In this study, IKBIP, SEC24D, and FAM46A related to glioma were mentioned for the first time to the current knowledge, which might provide a new idea for us to study the disease in the future. IKBIP, SEC24D and FAM46A among the 22 hub genes identified that are related to the malignancy degree of glioma might be used as new biomarkers to improve the diagnosis, treatment and prognosis of glioma.

Ethnicity and survival in bladder cancer: a population-based study based on the SEER database.

BACKGROUND: Bladder cancer is the most common cancer in the urinary system and the fourth most common cancer in males. This study aimed to examine differences in the survival of bladder cancer patients of different ethnicities. METHOD: We used the SEER database to obtain data pertaining to bladder cancer patients from 2010 to 2015. Univariate and multivariate Cox proportional hazards regression analyses were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between ethnicity and death. Kaplan-Meier survival and nomogram analyses were used to compare survival differences among patients with different ethnicities. RESULTS: Among 101,364 bladder cancer patients, 90,910 were white, 5893 were black, 337 were American Indian/Alaska Native (AIAN), and 4224 were Asian or Pacific Islander (API). Our multivariate analysis identified differences between different ethnicities. Compared to the API group, the AIAN (HR = 1.31, 95% CI = 1.09-1.57, P < 0.001), black (HR = 1.56, 95% CI = 1.46-1.67, P < 0.001), and white (HR = 1.18, 95% CI = 1.12-1.25, P < 0.001) groups showed lower survival probabilities. Based on data from all Kaplan-Meier survival curves, there was no significant difference in survival between the black and AIAN groups, but the survival of these two races was worse than that of the white and API groups. We also used a nomogram to estimate patient survival and validated its predictive value. CONCLUSION: Our results suggest that ethnic differences exist in patients with bladder cancer, that the survival of black and AIAN bladder cancer patients is worse than that of other ethnicities and that the survival of API patients is the best. The significant prognostic factors of overall survival, which include age, sex, ethnicity, summary stage, American Joint Committee on Cancer stage, surgery type, and histologic type, should be applied to bladder cancer patient prognostication.

The application of enhanced recovery after surgery for upper gastrointestinal surgery: Meta-analysis.

BACKGROUND: Although enhanced recovery after surgery (ERAS) has made great progress in the field of surgery, the guidelines point to the lack of high-quality evidence in upper gastrointestinal surgery. METHODS: Randomized controlled trials in four electronic databases that involved ERAS protocols for upper gastrointestinal surgery were searched through December 12, 2018. The primary endpoints were lung infection, urinary tract infection, surgical site infection, postoperative anastomotic leakage and ileus. The secondary endpoints were postoperative length of stay, the time from end of surgery to first flatus and defecation, and readmission rates. Subgroup analysis was performed based on the type of surgery. RESULTS: A total of 17 studies were included. The results of the meta-analysis indicate that there was a decrease in rates of lung infection (RR = 0.50, 95%CI: 0.33 to 0.75), postoperative length of stay (MD = -2.53, 95%CI: - 3.42 to - 1.65), time until first postoperative flatus (MD = -0.64, 95%CI: - 0.84 to - 0.45) and time until first postoperative defecation (MD = -1.10, 95%CI: - 1.74 to - 0.47) in patients who received ERAS, compared to conventional care. However, other outcomes were not significant difference. There was no significant difference between ERAS and conventional care in rates of urinary tract infection (P = 0.10), surgical site infection (P = 0.42), postoperative anastomotic leakage (P = 0.45), readmissions (P = 0.31) and ileus (P = 0.25). CONCLUSIONS: ERAS protocols can reduce the risk of postoperative lung infection and accelerating patient recovery time. Nevertheless, we should also consider further research ERAS should be performed undergoing gastrectomy and esophagectomy.

Analysis of differentially expressed circular RNAs for the identification of a coexpression RNA network and signature in colorectal cancer.

Circular RNAs (circRNAs) play an important regulatory role in tumorigenesis. The aim of the present study was to analyze the circRNA expression network and elucidate its potential implications in colorectal cancer (CRC). The circRNA expression profile was analyzed in CRC tissues by RNA sequencing, and the functions of differentially expressed genes were analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. The circRNA network was predicted with bioinformatics. On the basis of the results, we identified 23 differentially expressed circRNAs in CRC; GO and KEGG analyses demonstrated that the changes in circRNAs were mainly associated with regulation of biological and metabolic processes through binding to other molecules. In addition, based on the predicted coexpression network, we identified a hub circRNA, hsa_circ_0009022. Subsequently, the results of sequencing were confirmed by reverse transcription-quantitative polymerase chain reaction, and hsa_circ_0000826 was found to be downregulated in CRC. Taken together, these findings indicate a set of differentially expressed circRNAs that may serve as a candidate diagnostic biomarker and a promising therapeutic target in CRC.

Autoregulation of RBM10 and cross-regulation of RBM10/RBM5 via alternative splicing-coupled nonsense-mediated decay.

Mutations in the spliceosomal RNA binding protein RBM10 cause TARP syndrome and are frequently observed in lung adenocarcinoma (LUAD). We have previously shown that RBM10 enhances exon skipping of its target genes, including its paralog RBM5. Here, we report that RBM10 negatively regulates its own mRNA and protein expression and that of RBM5 by promoting alternative splicing-coupled nonsense-mediated mRNA decay (AS-NMD). Through computational analysis and experimental validation, we identified RBM10-promoted skipping of exon 6 or 12 in RBM10 and exon 6 or 16 in RBM5 as the underlying AS-NMD events. Importantly, we showed that LUAD-associated mutations affecting splice sites of RBM10 exons 6 or 12 abolished exon inclusion and correlated with reduced expression of RBM10 RNA. Together, our investigations have revealed novel molecular mechanisms underlying RBM10 autoregulation and cross-regulation of RBM5, thereby providing insights concerning the functions of RBM10 under various physiological and pathological conditions. Our combined computational and experimental approach should be useful for elucidating the role of AS-NMD in auto- and cross-regulation by other splicing regulators.

Stepwise Aggregation Control of PEDOT:PSS Enabled High-Conductivity, High-Resolution Printing of Polymer Electrodes for Transparent Organic Phototransistors.

Electrohydrodynamic (EHD) jet printing is a widely employed technology to create high-resolution patterns and thus has enormous potential for circuit production. However, achieving both high conductivity and high resolution in printed polymer electrodes is a challenging task. Here, by modulating the aggregation state of the conducting polymer in the solution and solid phases, a stable and continuous jetting of PEDOT:PSS is realized, and high-conductivity electrode arrays are prepared. The line width reaches less than 5 µm with a record-high conductivity of 1250 S/cm. Organic field-effect transistors (OFETs) are further developed by combining printed source/drain electrodes with ultrathin organic semiconductor crystals. These OFETs show great light sensitivity, with a specific detectivity (D*) value of 2.86 × 1014 Jones. In addition, a proof-of-concept fully transparent phototransistor is demonstrated, which opens up new pathways to multidimensional optical imaging.

Overcoming the Unfavorable Effects of "Boltzmann Tyranny:" Ultra-Low Subthreshold Swing in Organic Phototransistors via One-Transistor-One-Memristor Architecture.

Organic phototransistors (OPTs), as photosensitive organic field-effect transistors (OFETs), have gained significant attention due to their pivotal roles in imaging, optical communication, and night vision. However, their performance is fundamentally limited by the Boltzmann distribution of charge carriers, which constrains the average subthreshold swing (SSave) to a minimum of 60 mV/decade at room temperature. In this study, an innovative one-transistor-one-memristor (1T1R) architecture is proposed to overcome the Boltzmann limit in conventional OFETs. By replacing the source electrode in an OFET with a memristor, the 1T1R device exploits the memristor's sharp resistance state transitions to achieve an ultra-low SSave of 18 mV/decade. Consequently, the 1T1R devices demonstrate remarkable sensitivity to photo illumination, with a high specific detectivity of 3.9 × 109 cm W-1Hz1/2, outperforming conventional OPTs (4.9 × 104 cm W-1Hz1/2) by more than four orders of magnitude. The 1T1R architecture presents a potentially universal solution for overcoming the detrimental effects of "Boltzmann tyranny," setting the stage for the development of ultra-low SSave devices in various optoelectronic applications.

Anticoagulant drugs for patients with atrial fibrillation on dialysis: a systematic analysis and network meta-analysis.

Objective: A lack of clarity persists regarding the efficacy and risks associated with direct oral anticoagulants (DOACs) in end-stage renal disease (ESRD) patients with atrial fibrillation (AF) undergoing dialysis, primarily due to limited retrospective studies. Therefore, the objective of this study was to evaluate the existing data and propose a practical protocol for the clinical utilization of DOACs in ESRD patients with AF undergoing dialysis. Methods: PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials were searched for clinical studies evaluating DOACs in ESRD patients with AF on dialysis published up to 2 February 2023. DOACs included warfarin, dabigatran, apixaban, edoxaban, and rivaroxaban. The outcomes were mortality, ischemic stroke, hemorrhagic stroke, any stroke, gastrointestinal bleeding, major bleeding, intracranial bleeding, and minor bleeding. Results: Compared with placebo, apixaban (HR = 0.97, 95% CI: 0.88-1.07), rivaroxaban (HR = 0.91, 95% CI: 0.76-1.10), and warfarin (HR = 0.96, 95% CI: 0.90-1.01) did not reduce mortality. Regarding direct comparisons of mortality, the comparisons of warfarin vs. apixaban (HR = 0.99, 95% CI: 0.92-1.06), placebo vs. warfarin (HR = 1.04, 95% CI: 0.99-1.11), and rivaroxaban vs. warfarin (HR = 0.96, 95% CI: 0.80-1.14) did not significantly reduce mortality. Based on the surface under the cumulative ranking curve, rivaroxaban (75.53%), warfarin (62.14%), and apixaban (45.6%) were the most effective interventions for managing mortality, and placebo (16.74%) was the worst. Conclusion: In conclusion, rivaroxaban demonstrated efficacy in reducing mortality and the incidence of ischemic stroke, gastrointestinal bleeding, and intracranial hemorrhage. Dabigatran is recommended for the prevention of hemorrhagic stroke. However, caution should be exercised due to the risk of major bleeding. Warfarin can effectively reduce minor bleeding but does not offer significant protection against gastrointestinal or intracranial bleeding. Apixaban was not recommended for mortality reduction or for preventing ischemic or hemorrhagic strokes. Further research will be necessary to establish specific clinical protocols.

Selection of characteristic wavelengths using SMA for laser induced fluorescence spectroscopy of power transformer oil.

As the core component of the power system, the accurate analysis of its state and fault type is very important for the maintenance and repair of the transformer. The detection method represented by the transformer oil dissolved gas has the disadvantages of complicated processing steps and high operation requirements. Here, laser induced fluorescence (LIF) spectroscopy was applied for the analysis of transformer oil. Specifically, the slime mould algorithm (SMA) was used to select the characteristic wavelengths of the transformer oil fluorescence spectrum, and on this basis, a transformer fault diagnosis model was constructed. First, samples of transformer oil in different states were collected, and the fluorescence spectrum of the transformer oil was obtained with the help of the LIF acquisition system. Then, different spectral pretreatments were performed on the original fluorescence spectra, and it was found that the pretreatment effect of Savitzky-Golay smoothing (SG) was the best. Then, SMA was used to screen the characteristic wavelengths of the fluorescence spectrum, and 137 characteristic wavelengths were screened out to realize the accurate identification of the fluorescence spectrum of the transformer oil. In addition, the advantages of SMA for feature wavelength screening of transformer oil fluorescence spectra were demonstrated by comparing with traditional feature extraction strategies using principal components analysis (PCA). The research results show that it is effective to use SMA to screen the characteristic wavelengths of the LIF spectroscopy of transformer oil and use it for transformer fault diagnosis, which is of great significance for promoting the development of transformer fault diagnosis technology.

PUF60 promotes cell cycle and lung cancer progression by regulating alternative splicing of CDC25C.

Alternative splicing (AS) has been implicated in cell cycle regulation and cancer, but the underlying mechanisms are poorly understood. The poly(U)-binding splicing factor 60 (PUF60) is essential for embryonic development and is overexpressed in multiple types of cancer. Here, we report that PUF60 promotes mitotic cell cycle and lung cancer progression by controlling AS of the cell division cycle 25C (CDC25C). Systematic analysis of splicing factors deregulated in lung adenocarcinoma (LUAD) identifies that elevated copy number and expression of PUF60 correlate with poor prognosis. PUF60 depletion inhibits LUAD cell-cycle G2/M transition, cell proliferation, and tumor development. Mechanistically, PUF60 knockdown leads to exon skipping enriched in mitotic cell cycle genes, including CDC25C. Exon 3 skipping in the full-length CDC25C results in nonsense-mediated mRNA decay and a decrease of CDC25C protein, thereby inhibiting cell proliferation. This study establishes PUF60 as a cell cycle regulator and an oncogenic splicing factor in lung cancer.

A Pan-Cancer Analysis Reveals the Prognostic and Immunotherapeutic Value of Stanniocalcin-2 (STC2).

Background: Stanniocalcin-2 (STC2) is a secreted glycoprotein which plays an important role in regulating the homeostasis of calcium, glucose homeostasis, and phosphorus metastasis. Accumulating evidence suggests that STC2 is implicated in cancer mechanisms. However, the effects of STC2 on cancer development and progression across pan-cancer are not yet completely known. Methods: Data were downloaded from The Cancer Genome Atlas database to obtain differentially expressed genes significantly associated with prognosis (key genes). A gene was selected for subsequent correlation studies by integrating the significance of prognosis and the time-dependent ROC curve. Gene expression of different tumor types was analyzed based on the UCSC XENA website. Furthermore, our study investigated the correlation of STC2 expression between prognosis, immune cell infiltration, immune checkpoint genes (ICGs), mismatch repair genes (MMRs), tumor mutation burden (TMB), microsatellite instability (MSI), and drug sensitivity in various malignant tumors. Gene set enrichment analysis (GSEA) was conducted for correlated genes of STC2 to explore potential mechanisms. Results: A total of 3,429 differentially expressed genes and 397 prognosis-related genes were identified from the TCGA database. Twenty-six key genes were found by crossing the former and the latter, and the highest risk gene, STC2, was selected for subsequent correlation studies. STC2 had good diagnostic performance for HNSCC, and was closely related to the survival status and clinicopathological stage of HNSCC patients. In pan-cancer analysis, STC2 was upregulated in 20 cancers and downregulated in seven cancers. STC2 overexpression was overall negatively correlated with overall survival, disease-free survival, disease-specific survival, and progress-free survival. STC2 was profoundly correlated with the tumor immune microenvironment, including immune cell infiltration, ICGs, MMRs, TMB, and MSI. Moreover, STC2 was significantly negatively correlated with the sensitivity or resistance of multiple drugs. Conclusion: STC2 was a potential prognostic biomarker for pan-cancer and a new immunotherapy target.

Rutin attenuates Sorafenib-induced Chemoresistance and Autophagy in Hepatocellular Carcinoma by regulating BANCR/miRNA-590-5P/OLR1 Axis.

Rutin, the main component of Potentilla discolor Bunge, was proven to exhibit anti-tumor properties. Sorafenib (SO) is conventionally used in chemotherapy against hepatocellular carcinoma (HCC), but acquired resistance developed during long-term therapy limits its benefits. This study aimed to explore the molecular mechanism of rutin in SO-induced autophagy and chemoresistance in HCC. Sixty-eight paired HCC patients who received the same chemotherapy treatment were obtained. We also established two SO resistance cell lines and then utilized high-throughput RNA sequencing to explore their long non-coding RNA (lncRNA) expression profiles. The target microRNA (miRNA) and downstream mRNA were also explored. Our results indicated that rutin treatment attenuates autophagy and BANCR expression in SO resistance cells. Transmission electron microscopy clearly showed a significantly decreased number of autophagosomes after rutin-treated HepG2/SO and HCCLM3/SO cells. BANCR knockdown promotes the sensitivity of SO resistance cells to SO. Further study found that BANCR acts as a molecular sponge of miR-590-5P to sequester miR-590-5P away from oxidized low-density lipoprotein receptor 1 (OLR1) in HCC cells. Furthermore, in vivo study demonstrated that rutin could inhibit autophagy through the BANCR/miRNA-590-5P/OLR1 axis. Our findings suggest that rutin could regulate autophagy by regulating BANCR/miRNA-590-5P/OLR1 axis.

Voltage-dependent modulation of TRPA1 currents by diphenhydramine.

Diphenhydramine (DPH) has been broadly used to treat allergy. When used as a topical medicine, DPH temporarily relieves itching and pain. Although transient receptor potential type A1 (TRPA1) channel is known to play roles in both acute and chronic itch and pain, whether DPH affects the activities of TRPA1 remains unclear. Using whole-cell patch clamp recordings, we demonstrated that DPH modulates the voltage-dependence of TRPA1. When co-applied with a TRPA1 agonist, DPH significantly enhanced the inward currents while suppressing the outward currents of TRPA1, converting the channel from outwardly rectifying to inwardly rectifying. This effect of DPH occurred no matter TRPA1 was activated by an electrophilic or non-electrophilic agonist and for both mouse and human TRPA1. The modulation of TRPA1 by DPH was maintained in the L906C mutant, which by itself also causes inward rectification of TRPA1, indicating that additional acting sites are present for the modulation of TRPA1 currents by DPH. Our recordings also revealed that DPH partially blocked capsaicin evoked TRPV1 currents. These data suggest that DPH may exert its therapeutic effects on itch and pain, through modulation of TRPA1 in a voltage-dependent fashion.

RNA binding motif protein 10 suppresses lung cancer progression by controlling alternative splicing of eukaryotic translation initiation factor 4H.

BACKGROUND: RNA splicing defects are emerging molecular hallmarks of cancer. The gene encoding splicing factor RNA binding motif protein 10 (RBM10) has been found frequently mutated in various types of cancer, particularly lung adenocarcinoma (LUAD), but how RBM10 affects cancer pathogenesis remains to be determined. Moreover, the functional roles and clinical significance of RBM10 mutation-associated splicing events in LUAD are largely unknown. METHODS: RBM10 mutations and their functional impacts were examined in LUAD patients from a Chinese patient cohort and The Cancer Genome Atlas (TCGA). Alternative splicing (AS) changes induced by RBM10 mutations in LUAD were identified by RNA sequencing and correlated with patient survival. Functions of RBM10 and the splice variants of eukaryotic translation initiation factor 4H containing or lacking exon 5 (EIF4H-L and EIF4H-S respectively) in LUAD development and progression were examined by cellular phenotypic assays and xenograft tumour formation. FINDINGS: RBM10 mutations in LUAD generally lead to loss-of-function and cause extensive alterations in splicing events that can serve as prognostic predictors. RBM10 suppresses LUADprogression largely by regulating alternative splicing of EIF4H exon 5. Loss of RBM10 in LUAD enhances the expression of EIF4H-L in LUAD. EIF4H-L, but not EIF4H-S, is critical for LUAD cell proliferation, survival and tumourigenesis. INTERPRETATION: Our study demonstrates a new molecular mechanism underlying RBM10 suppressive functions in lung cancer and the therapeutic value of RBM10-regulated AS events, providing important mechanistic and translational insights into splicing defects in cancer.

Enhanced Recovery After Surgery for Breast Reconstruction: Pooled Meta-Analysis of 10 Observational Studies Involving 1,838 Patients.

Purpose: This study aims to explore the effectiveness and safety of the enhanced recovery after surgery (ERAS) protocol vs. traditional perioperative care programs for breast reconstruction. Methods: Three electronic databases (PubMed, EMBASE, and Cochrane Library) were searched for observational studies comparing an ERAS program with a traditional perioperative care program from database inception to 5 May 2018. Two reviewers independently screened the literature according to the inclusion and exclusion criteria, extracted the data, and evaluated study quality using the Newcastle-Ottawa Scale. Subgroup and sensitivity analyses were performed. The outcomes included the length of hospital stay (LOS), complication rates, pain control, costs, emergency department visits, hospital readmission, and unplanned reoperation. Results: Ten studies were included in the meta-analysis. Compared with a conventional program, ERAS was associated with significantly decreased LOS, morphine administration (including postoperative patient-controlled analgesia usage rate and duration; intravenous morphine administration on postoperative day [POD] 0, 1, 2, and 4; total intravenous morphine administration on POD 0-3; oral morphine consumption on POD 0-4; and total postoperative oral morphine consumption), and pain scores (postoperative pain score on POD 0 and total pain score on POD 0-3). The other variables did not differ significantly. Conclusion: Our results suggest that ERAS protocols can decrease LOS and morphine equivalent dosing; therefore, further larger, and better-quality studies that report on bleeding amount and patient satisfaction are needed to validate our findings.

Oxidative coupling of coumarins catalyzed by laccase.

Laccase (LAC) belongs to the blue multi­copper lignolytic oxidase enzymes, and has been regarded as an important tool to produce some important dimers in the application of biotechnology. In this study, sixteen coumarins 1-16 were screened to investigate the catalytic ability of LAC, and three coumarins 6, 7, and 16 could be catalyzed to produce three coumarin derivative coupling with acetone 6a, 7a, and 16a. The potential interaction mechanisms of three coumarins 6, 7, and 16 with LAC were analyzed by molecular docking. The kinetic analyses of catalytic reactions for coumarins 6, 7, and 16 with LAC were performed by using the transformed products 6a, 7a, and 16a as standard substances. Km values of coumarins 6, 7, and 16 were ranged from 0.87 ±â€¯0.07 µM to 2.74 ±â€¯0.29 µM, respectively. This finding suggested that LAC was a reliable method to catalyze oxidative coupling.

Combination therapy versus pharmacotherapy, endoscopic variceal ligation, or the transjugular intrahepatic portosystemic shunt alone in the secondary prevention of esophageal variceal bleeding: a meta-analysis of randomized controlled trials.

Patients with liver cirrhosis and variceal hemorrhage are at increased risk of rebleeding. We performed a meta-analysis toassess the clinical efficacy of combination therapy (pharmacotherapy and endoscopic variceal ligation (EVL)) compared with pharmacotherapy, EVL, or transjugular intrahepatic portosystemic shunt (TIPS) alone in the prevention of rebleeding and mortality. A literature search of MEDLINE, EMBASE, and the Cochrane Controlled Trials Register, up until November 2016, identified relevant randomized controlled trials. Data analysis was performed using Stata 12.0. Regarding overall mortality, combination therapy was as effective as EVL, pharmacotherapy, and TIPS (relative risk (RR) = 0.62, 95% confidence interval (CI): 0.36-1.08, RR=1.05, 95% CI: 0.68-1.63, and RR=1.39, 95% CI: 0.92-2.09, respectively). Combination therapy was as effective as EVL and pharmacotherapy alone in reducing blood-related mortality (RR=0.43, 95% CI: 0.15-1.25, and RR=0.42, 95% CI: 0.17-1.06), whereas TIPS was more effective than combination therapy (RR=5.66, 95% CI: 1.02-31.40). This was also the case for rebleeding; combination therapy was more effective than EVL and pharmacotherapy alone (RR=0.57, 95% CI: 0.41-0.79, and RR=0.65, 95% CI: 0.48-0.88), whereas TIPS was more effective than combination therapy (RR=9.42, 95% CI: 2.99-29.65). Finally, regarding rebleeding from esophageal varices, combination therapy was as effective as EVL alone (RR=0.59, 95% CI: 0.33-1.06) and was more effective than pharmacotherapy alone (RR=0.58, 95% CI: 0.40-0.85), although was less effective than TIPS (RR=2.20, 95% CI: 1.22-3.99). TIPS was recommended as the first choice of therapy in the secondary prevention of esophageal variceal bleeding.

Quantitative assessment of the effect of epidermal growth factor 61A/G polymorphism on the risk of hepatocellular carcinoma.

The association between hepatocellular carcinoma (HCC) and the epidermal growth factor (EGF) 61A/G polymorphism has been analyzed in several studies, but results remain inconsistent. Therefore, the aim of the present study was to quantitatively summarize the association between the EGF 61A/G polymorphism and the risk of HCC. The PubMed and EMBASE databases were searched for studies published prior to May 1, 2014. The overall, subgroup and sensitivity analyses were conducted using Comprehensive Meta-Analysis software, version 2.2. In total, 12 published case-control studies, consisting of 2,095 patients with HCC and 3,766 control individuals, were included in the present study. Meta-analysis of the included studies revealed that EGF 61A/G polymorphism contributed to the risk of HCC under all four genetic models, consisting of the G vs. A (OR, 1.25; 95% CI, 1.11-1.40), GG vs. AA (OR, 1.53; 95% CI, 1.26-1.85), GG vs. AG + AA (OR, 1.34; 95% CI, 1.13-1.58) and GG + AG vs. AA (OR, 1.27; 95% CI, 1.08-1.49) comparisons. Subgroup analysis further suggested that EGF 61A/G polymorphism was associated with the risk of HCC in patients and control individuals with liver disease, based on ethnicity and source of control, respectively. No other significance in residual subgroup analysis was observed. The present meta-analysis suggests that the EGF 61A/G polymorphism is associated with an increased risk of HCC and may be a potential marker for liver disease, such as hepatitis B virus infection, hepatitis C virus infection and liver cirrhosis.

Long-Term Coffee Consumption and Risk of Gastric Cancer: A PRISMA-Compliant Dose-Response Meta-Analysis of Prospective Cohort Studies.

Association between coffee consumption and gastric cancer risk remains controversial. Hence, we performed a meta-analysis to investigate and quantify the potential dose-response association between long-term coffee consumption and risk of gastric cancer.Pertinent studies were identified by searching PubMed and Embase from January 1996 through February 10, 2015 and by reviewing the reference lists of retrieved publications. Prospective cohort studies in which authors reported effect sizes and corresponding 95% confidence intervals (CIs) of gastric cancer for 3 or more categories of coffee consumption were eligible. Results from eligible studies were aggregated using a random effect model. All analyses were carried out using the STATA 12.0 software.Nine studies involving 15 independent prospective cohorts were finally included. A total of 2019 incident cases of gastric cancer were ascertained among 1,289,314 participants with mean follow-up periods ranging from 8 to 18 years. No nonlinear relationship of coffee consumption with gastric cancer risk was indentified (P for nonlinearity = 0.53; P for heterogeneity = 0.004). The linear regression model showed that the combined relative risk (RR) of every 3 cups/day increment of total coffee consumption was 1.07 (95% CI = 0.95-1.21). Compared with the lowest category of coffee consumption, the RR of gastric cancer was 1.18 (95% CI = 0.90-1.55) for the highest (median 6.5 cups/day) category, 1.06 (95% CI = 0.85-1.32) for the second highest category (median 3.5 cups/day), and 0.97 (95% CI = 0.79-1.20) for the third highest category (median 1.5 cups/day). Subgroup analysis showed an elevated risk in the US population (RR = 1.36, 95% CI = 1.06-1.75) and no adjustment for smoking (RR = 1.67, 95% CI = 1.08-2.59) for 6.5 cups/day.Current evidence indicated there was no nonlinear association between coffee consumption and gastric cancer risk. However, high coffee consumption (more than 6.5 cups/day) might increase the risk of gastric cancer in the US population. More high quality studies were warranted to further investigate the association.

Promoter Methylation of the Retinoic Acid Receptor Beta2 (RARß2) Is Associated with Increased Risk of Breast Cancer: A PRISMA Compliant Meta-Analysis.

BACKGROUND: Epigenetic studies demonstrate that an association may exist between methylation of the retinoic acid receptor beta2 (RARß2) 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. MATERIALS AND METHODS: 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. RESULTS: Nineteen eligible articles, including 20 studies, were included in our analysis. Compared to non-cancerous controls, the frequency of RARß2 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 RARß2 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 RARß2 methylated patients was 0.96 (OR = 0.96, 95% CI = 0.74-1.25) compared to high-grade RARß2 methylated patients. CONCLUSION: RARß2 methylation is significantly increased in breast cancer samples when compared to non-cancerous controls. RARß2 could serve as a potential epigenetic marker for breast cancer detection and management.