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Background The aim of this study was to develop comprehensive and effective nomograms for predicting overall survival (OS) and cancer-specific survival (CSS) rates in patients with colorectal mucinous adenocarcinoma (CRMA). Methods A total of 4711 CRMA patients who underwent radical surgery between 2010 and 2018 from the Surveillance, Epidemiology, and End Results (SEER) database were collected and randomized into development (n=3299) and validation (n=1412) cohorts at a ratio of 7:3 for model development and validation. OS and CSS nomograms were developed using the prognostic factors from the development cohort after multivariable Cox regression analysis. The performance of the nomograms was evaluated using Harrell’s concordance index (C-index), calibration diagrams, receiver operating characteristic (ROC) curves, and decision curve analysis (DCA). Results The study included 4711 patients. Multivariate Cox regression analysis demonstrated that age, tumor size, grade, pT stage, pN stage, M stage, carcinoembryonic antigen, perineural invasion, tumor deposits, regional nodes examined, and chemotherapy were correlated with OS and CSS. Marital status was independently related to OS. In the development and validation cohorts, the C-index of OS was 0.766 and 0.744, respectively, and the C-index of CSS was 0.826 and 0.809, respectively. Calibration curves and ROC curves showed predictive accuracy. DCA showed that the nomograms had excellent potency over the 8th edition of the TNM staging system with higher clinical net benefits. Significant differences in OS and CSS were observed among low-, medium-, and high-risk groups. Conclusions Nomograms were developed for the first time to predict personalized 1-, 3-, and 5-year OS and CSS in CRMA postoperative patients. External and internal validation confirmed the excellent discrimination and calibration ability of the nomograms. The nomograms can help clinicians design personalized treatment strategies and assist with clinical decisions.

Endometriosis is considered a benign gynaecological disease with cancer‐like characterizations, which has a high incidence among women of reproductive age. However, this disease has so far lacked timely diagnosis and effective treatment owing to its unclear aetiology. In this study, we identified aberrant high expression of circ_0007331 in ectopic endometrial cells by comparing the endometrial samples from patients with and without endometriosis. Further functional experiments revealed that circ_0007331 knock‐down effectively suppressed the viability, proliferation and invasive capacity of ectopic endometrial cells. Additionally, we attempted to define the molecular mechanism of circ_0007331 in the initiation and progression of endometriosis. Circ_0007331 acted as a miRNA sponge for miR‐200c‐3p to indirectly regulate the function of HIF‐1α, which plays a key role in the local angiogenesis and hypoxic mechanisms of ectopic endometrium. A final in vivo experiment confirmed that circ_0007331 knock‐down could suppress the development of endometriosis through down‐regulating the expression of HIF‐1α. Collectively, we preliminarily characterized the role and possible insights of circ_0007331/miR‐200c‐3p/HIF‐1α axis in the proliferation and invasion of ectopic endometrial cells. We hope that by exploring the potential function and molecular mechanism of circ_0007331, we can increase our biological insight into the pathogenesis of endometriosis, which will bring the new ways for the diagnosis and therapy of this disease.

Background: Single nucleotide polymorphisms (SNPs) in transcription factor binding sites (TFBS) can change their binding strength, affecting the function of transcription factors (TFs). Small mother against decapentaplegic (SMAD) proteins are known as a family of TFs involved in tumorigenesis. We performed this study to investigate whether SNPs in SMADs binding sites affect the susceptibility or prognosis of gastric cancer (GC). Methods: Using bioinformatics tools, we focused on the association between rs9911630 polymorphism and GC. We performed this case-control study in 1275 GC patients and 1426 cancer-free subjects using TaqMan allelic discrimination method. Results: We found that rs9911630 A>G polymorphism was associate to an increased risk of gastric cancer (adjusted OR for additive model = 1.16; 95% CI = 1.03-1.30). Furthermore, we assess whether rs9911630 polymorphism affected the prognosis of GC. However, no significant association was discovered between rs9911630 A>G polymorphism and overall survival time of GC patients (HR for addictive model = 1.01; 95%CI = 0.88-1.15). Conclusions: Our results suggested that rs9911630 polymorphism in SMADs target site might influence susceptibility but not prognosis of gastric cancer.

Background: Gastric cancer (GC) is one of the most common cancers in the world. Patients with GC who experienced early relapse have poor prognosis. We aim to develop an early relapse-associated gene signature to optimize prognosis prediction in patients with replapsing GC. Methods: The GC cohorts including GSE62254 set (N=300) and GSE15459 set (N=192) were extracted from Gene Expression Omnibus (GEO) database. Propensity score matching (1:1) based on pathological stage was executed between patients with early relapse and long-term survival from GSE62254 set. Global transcriptome analysis was performed between the two groups to identify early relapse-associated gene. Based on the differentially expressed genes, we developed a classifier incorporating 5 genes that using LASSO Cox regression model. The signature’s prognostic value was internally validated in 210 GC patients and validated in GSE15459 set externally. The patients from GSE62254 set could be divided into high-risk or low-risk group.Results: In the train set, patients in high-risk group had poor prognosis as compared to those in low-risk group [hazard ratio (HR): 3.002, 95% confidence interval (CI): 2.132-4.226, PConclusions: This study suggest that an early relapse-associated gene signature that can robustly divide gastric cancer patients into two groups with distinctive prognosis. This classifier may contribute to select gastric cancer patients with poor prognosis who require more frequent follow-up and more aggressive therapeutic intervention.

In spite of the achievement in treatment, the gastric cancer (GC) mortality still remains high. MicroRNAs (miRNAs) are a group of small noncoding RNAs that play a crucial part in tumor progression. In this study, we explored the expression and function of microRNA-501-5p (miR-501-5p) in GC cell lines. Quantitative real-time polymerase chain reaction assay results suggested that miR-501-5p was significantly upregulated in GC tissues and cell lines. And, the Cell Counting Kit-8 colony formation and cell migration assay results showed that the downregulation of miR-501-5p decreased GC cell proliferation and migration. Besides that, we found that GC cell cycle was arrested in G2 phase and cell apoptosis rate was increased by silencing the expression of miR-501-5p in GC cell lines using the flow cytometry. We also found that miR-501-5p could directly target lysophosphatidic acid receptor 1 (LPAR1) and negatively regulate LPAR1 expression in GC cell lines by performing dual-luciferase reporter gene assay and Western blot analysis. And, LPAR1 was significantly downregulated in GC tissues and inversely correlated with miR-501-5p expression. Furthermore, LPAR1 downregulation promoted cell proliferation and migration, which were attenuated by cotransfection of miR-501-5p inhibitor in GC cells. In conclusion, miR-501-5p can promote GC cell proliferation and migration by targeting and downregulating LPAR1. miR-501-5p/LPAR1 may become a potential therapeutic target for GC treatment.

Background lncRNA NKILA is a newly discovered long non-coding RNA, and some studies have shown that lncRNA NKILA has certain clinical prognostic value in malignant tumors. In this study, we used meta-analysis to integrate existing literature to further evaluate the clinic relevance between lncRNA NKILA expression level and cancers. Materials and Methods We conducted a meta-analysis based on literature reporting lncRNA NKILA expression in various cancers published before 25, May 2020 by PubMed, Embase, and Web of Science. The quality ratings of the included studies were assessed according to the Newcastle-Ottawa Scale. After rigorous screening, a total of 8 articles and 859 patients were included in our study. Hazard ratios (HRs) and odds ratios (ORs) were used to demonstrate the relationship between NKILA and prognosis by using Stata 15.0 software. Results The results show overexpression level of lncRNA NKILA is significantly associated with better overall survival (pooled HR = 0.45, 95%CI:0.35–0.59, P

The integrated analytical strategy identified both genetic and epigenetic biomarkers for gastric cancer etiology., The biological effects of susceptibility loci are rarely reported in gastric tumorigenesis. We conducted a large-scale cross-ancestry genetic study in 18,852 individuals and identified the potential causal variant rs3850997 T>G at 16p13 significantly associated with a decreased risk of gastric cancer [odds ratio (OR) = 0.87, 95% confidence interval (CI) = 0.83 to 0.91, P = 2.13 × 10−9]. This risk effect was mediated through the mapped long noncoding RNA GCLET (Gastric Cancer Low-Expressed Transcript; ORindirect = 0.987, 95% CI = 0.975 to 0.999, P = 0.018). Mechanistically, rs3850997 exerted an allele-specific long-range regulatory effect on GCLET by affecting the binding affinity of CTCF. Furthermore, GCLET increased FOXP2 expression by competing with miR-27a-3p, and this regulation remarkably affected in vitro, in vivo, and clinical gastric cancer phenotypes. The findings highlight the genetic functions and implications for the etiology and pathology of cancers.

Increasing microRNAs are shown to be participate in polycystic ovarian syndrome (PCOS) pathogenesis. Nevertheless, the biological effects of miR-144-3p and its detailed mechanisms in PCOS are to be investigated. The purpose of our work was to study the function of miR-144-3p in PCOS. Currently, Expression of miR-144-3p was greatly reduced in PCOS patients and PCOS rat models. In addition, HSP-70 expression was greatly elevated PCOS. Cell proliferation assays and flow cytometry assay were carried out following the overexpression of miR-144-3p in ovarian granulosa cells from PCOS rat models. We observed that miR-144-3p overexpression induced the proliferation and repressed cell apoptosis while loss of miR-144-3p demonstrated an opposite process. Then, PCOS rat models were classified to four groups: LV-NC group, LV-miR-144-3p group, Anti-control group, and Anti-miR-144-3p group. In response to loss of miR-144-3p, we found E2, T, and LH serum levels were elevated and FSH serum level was inhibited. Upregulation of miR-144-3p exhibited an opposite process. Moreover, HSP-70 was a direct target of miR-144-3p. Furthermore, increased expression of HSP-70 rescued the effects of miR-144-3p on ovarian granulosa cell growth and apoptosis. In addition, knockdown of HSP-70 alleviated endocrine disorders and abnormal ovarian weight in vivo. To sum up, miR-144-3p might function as a novel target for PCOS treatment via targeting HSP-70.

The Hedgehog signaling pathway participates in the occurrence and progression of cancers including gastric cancer. We conducted this study to evaluate whether genetic variants in the Hedgehog signaling pathway genes would affect gastric cancer risk. Multi-marker Analysis of GenoMic Annotation (MAGMA) was used to investigate the aggregated genetic effects of single nucleotide polymorphisms (SNPs) assigned to candidate genes. The relationship between SNPs and gastric cancer risk was estimated by multivariate logistic regression analyses. Gene expression was calculated using databases obtained from The Cancer Genome Atlas (TCGA) and The Gene Expression Omnibus (GEO). Kaplan-Meier plotter was used to evaluate the association between gene expression with gastric cancer survival. Tumor Immune Estimation Resource 2.0 (TIMER 2.0) was applied to determine the correlation between selected gene expression and the immune cell infiltration degree. We identified that the G allele of rs2990912 in

PI3K/Akt/mTOR pathway is involved in tumor initiation and progression, including gastric cancer (GC). However, the single nucleotide polymorphisms (SNPs) in this pathway and underlying molecular mechanism remain largely unexplored. A case-control study of 1275 GC patients and 1436 controls was performed to explore the associations of potentially functional SNPs in PI3K/Akt/mTOR pathway genes with the risk of GC. In the logistic regression analyses, one SNP rs7536272 out of the four candidate SNPs showed a significant association with GC risk (additive model: OR = 1.16, 95% CI = 1.03–1.30; co-dominant model: AG vs. AA, OR = 1.30, 95% CI = 1.11–1.53; dominant model: AG/GG vs. AA, OR = 1.28, 95% CI = 1.10–1.49).The luciferase assay indicated that rs7536272 G allele significantly enhanced the transcriptional activity, compared with A allele. Further expression quantitative trait loci (eQTL) analysis showed that GC patients with rs7536272 AG/GG genotypes had remarkably higher PIK3R3 levels than those with AA genotype, suggesting that rs7536272 polymorphism influenced the expression of PIK3R3. Additionally, we observed that GC patients with high expression of PIK3R3 had significant poorer outcome than those with low expression (HR = 1.29, 95% CI = 1.09–1.53). Our result demonstrated that SNP rs7536272, a functional risk variant located in the promoter region of PIK3R3, showed association with increased transcriptional activity and upregulation of PIK3R3 expression, thus involved in GC development.

Background The purpose of the study was to evaluate the safety and feasibility of a new surgical procedure named modularized laparoscopic regional En bloc mesogastrium excision (rEME) based on the membrane anatomy in distal laparoscopic radical gastrectomy for gastric cancer. Methods From January 2014 to June 2017, 92 consecutive cases of patients with stages I–III distal gastric cancer were divided into 2 groups: laparoscopic radical gastrectomy plus standard D2 lymph node dissection (SD group, n = 44) and modularized rEME (rEME group, n = 48). Evaluations were made in terms of the operative data, pathological results, recovery time of digestive tract functions, complications, and length of stay. Results 85 patients (SD group, n = 40 and rEME group, n = 45) were finally included for analysis. There were no significant differences in the median total numbers of dissected LNs (31.98 ± 10.48 vs. 34.93 ± 13.12, p = 0.261), LNs in the greater curvature (12.18 ± 6.55 vs. 13.62 ± 8.09, p = 0.444), LNs in the lesser curvature (19.55 ± 7.40 vs. 17.98 ± 8.31, p = 0.365) between the SD and rEME groups. The rEME group showed lower loss of blood volume (107.11 ± 60.13 ml vs. 146.25 ± 85.78 ml, p = 0.019). No significant differences were found in recovery time of digestive tract functions, postoperative complication rates and length of hospital stay between the two groups. Conclusion Laparoscopic radical gastrectomy plus modularized rEME based on the membrane anatomy is a safe and feasible procedure for distal gastric cancer.

Objectives: The result of the relationship between the MUC1 rs4072037 polymorphism and cancer risk is controversial, we take this meta-analysis to investigate a more precise result. Methods: Electronic database Pubmed, Web of science and Cochrane library had been used to search relevant articles concerning the relationship between MUC1 rs4072037 polymorphism and cancer risk. We used odds ratios (ORs) and 95% confidence intervals (CIs) to assess the strength of the gene-disease association. We also conducted subgroup analysis, sensitivity analyses and publication bias in the meta-analysis. Results: In our meta-analysis, we involved 17 studies (19 datasets) with 12551 cases and 13436 controls eventually. It showed the MUC1 rs4072037 polymorphism was associated with decreased cancer risk in four genetic models (G vs. A: OR=0.79, 95%CI: 0.71-0.89, P< 0.001; AG vs. AA: OR=0.72, 95%CI: 0.62-0.82, P< 0.001; GG vs. AA: OR=0.78, 95%CI: 0.69-0.88, P< 0.001; AG+GG vs. AA: OR=0.72, 95%CI: 0.63-0.83, P< 0.001). In subgroup analysis, it showed a decreased cancer risk among Asians but not Caucasians and a significant decreased gastric cancer risk in all genetic models. Conclusion: MUC1 rs4072037 polymorphism is associated with decreased cancer risk and can probably be used as a tumor marker, especially for gastric cancer and for Asians.

Background: MicroRNA-497(miR-497) has been studied for its irreplaceable role of predicting the prognosis of various cancers, but there has been no systematic study to summarize the data. Consequently, we performed this meta-analysis to reveal the association between the expression level of miR-497 and cancer prognosis systematically. Materials and Methods: PubMed was searched for appropriate studies and a total of 12 eligible publications with 989 cancer patients were recruited into our analysis to assess the strength of the association. Hazard ratios (HRs) and odds ratios (ORs) were analyzed to finish this work. Results: The cancer patients who have high expressing level of miR-497 are less possible to have lymph node metastasis (OR = 0.25, 95% CI: 0.16-0.40, P < 0.001) and more likely to have favourable tumor-node-metastasis stage (OR = 0.29, 95% CI: 0.17-0.49, P < 0.001). Also, high miR-497 expression level was notably connected to better overall survival (pooled HR = 0.41, 95% CI: 0.32-0.53, P < 0.001). Conclusions: High expressing levels of miR-497 might be a potential biomarker which can be used to predict the better prognosis of different cancer types.

// Liyang Liu 1, * , Jianfei Wen 2, * , Xi Gu 1, * , Dongdong Wu 1 , Ming Lu 1 and Qinghong Zhao 1 1 Department of General Surgery, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China 2 Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China * These authors contributed equally to this work and Co-first authors Correspondence to: Qinghong Zhao, email: njzhqh@sina.com Keywords: LINC00152, cancer, metastasis, prognosis, meta-analysis Received: July 20, 2017 Accepted: September 21, 2017 Published: October 12, 2017 ABSTRACT The role of long intergenic non-coding RNA 152 (LINC00152) in predicting the prognosis of cancer has been investigated but results remain inconclusive and inconsistent. A meta-analysis was performed to explore the effect of LINC00152 on cancer prognosis. PubMed and ScienceDirect were searched for suitable studies and the results of 10 studies with a total of 775 patients were pooled. Pooled hazard ratios (HRs) and odds ratios (ORs) were calculated to assess the prognostic value of LINC00152. The results revealed that tumour patients with high LINC00152 expression were more likely to have lymph node metastasis (OR = 2.94, 95% CI 1.97–4.40, P < 0.001) and unfavourable tumour–node–metastasis stage (grade III/IV vs. I/II: OR = 3.07, 95% CI 1.69–5.59, P < 0.001). In addition, high LINC00152 expression levels were significantly associated with poor overall survival (pooled HR = 1.99, 95% CI 1.54–2.56, P < 0.001). The results suggest that high LINC00152 expression may serve as a predictive biomarker for the poor prognosis of various cancers in the Chinese population.

Although gastric cancer (GC) in young adults (≤ 45 years) accounts for fewer than 10% of newly diagnosed cases, the young patients are more likely to have advanced disease at presentation compared with elderly patients. Previous studies have identified that the DNA methylation of genomes are different during aging. Our study aimed to explore the association between DNA methylation and the onset of GC. We applied Illumina HumanMethylation450 BeadChip to examine methylation expression profiles and compared methylation expression patterns in five early onset GC patients and seven elderly patients. Additionally, we evaluated the associations of methylation expression with different clinicopathological characteristics of GC. Our results showed that the pattern of genome-wide methylation expression was significantly different between early onset and elderly GC. The top 10 hypomethylation and hypermethylation CpG sites were selected for further analyses in The Cancer Genome Atlas (TCGA) database. We found that the hypermethylation of cg11037477, located at the promoter of EIF4E, was significantly associated with age at diagnosis and the expression of EIF4E. Besides, GC patients with high level of cg11037477 were more likely to have advance disease with T3/T4 invasion and III/IV stage. The cg11037477 hypermethylation and EIF4E down-expression were significantly related to poor survival of GC patients. Our study provides new insights into the molecular mechanism of early onset patients with GC and suggests that methylation of cg11037477 and expression of EIF4E may act as prognostic markers in GC.

// Zhonghua Ma 1, 2, * , Hesuyuan Huang 3, 6, * , Jirong Wang 2, * , Yan Zhou 4, * , Fuxing Pu 5 , Qinghong Zhao 6 , Peng Peng 7 , Bingqing Hui 1, 2 , Hao Ji 1, 2 and Keming Wang 1, 2 1 The Second Clinical Medical College of Nanjing Medical University, Nanjing 210000, Jiangsu, People’s Republic of China 2 Department of Oncology, Second Affiliated Hospital, Nanjing Medical University, Nanjing 210000, Jiangsu, People’s Republic of China 3 Department of Cardiothoracic Surgery, Children’s Hospital of Nanjing Medical University, Nanjing 210008, Jiangsu, People’s Republic of China 4 Department of Oncology, The Affiliated Yixing Hospital of Jiangsu University, Wuxi 214200, Jiangsu, People’s Republic of China 5 Department of Medical Center for Digestive Diseases, Second Affiliated Hospital, Nanjing Medical University, Nanjing 210000, Jiangsu, People’s Republic of China 6 Department of General Surgery, Second Affiliated Hospital, Nanjing Medical University, Nanjing 210000, Jiangsu, People’s Republic of China 7 Department of Oncology, Second Hospital of Nanjing, Nanjing 210000, Jiangsu, People's Republic of China * These authors have contributed equally to this work Correspondence to: Keming Wang, email: kemingwang@njmu.edu.cn Keywords: long noncoding RNA, SNHG15, pancreatic cancer, proliferation, P15 and KLF2 Received: March 14, 2017 Accepted: May 29, 2017 Published: August 18, 2017 ABSTRACT Long non-coding RNA (lncRNA) is emerging as an critical regulator in multiple cancers, including pancreatic cancer (PC). Recently, lncRNA SNHG15 was found to be up-regulated in gastric cancer and hepatocellular carcinoma, exerting oncogenic effects. Nevertheless, the biological function and regulatory mechanism of SNHG15 remain unclear in pancreatic cancer (PC). In this study, we reported that SNHG15 expression was also upregulated in PC tissues, and its overexpression was remarkably associated with tumor size, tumor node metastasis (TNM) stage and lymph node metastasis in patients with PC. SNHG15 knockdown inhibited proliferative capacities and suppressed apoptotic rate of PC cells in vitro , and impaired in-vivo tumorigenicity. Additionally, RNA immunoprecipitation (RIP) assays showed that SNHG15 epigenetically repressed the P15 and Kruppel-like factor 2 (KLF2) expression via binding to enhancer of zeste homolog 2 (EZH2), and chromatin immunoprecipitation assays (CHIP) assays demonstrated that EZH2 was capable of binding to promoter regions of P15 and KLF2 to induce histone H3 lysine 27 trimethylation (H3K27me3). Furthermore, rescue experiments indicated that SNHG15 oncogenic function partially involved P15 and KLF2 repression. Consistently, an inverse correlation between the expression of SNHG15 and traget genes were found in PC tissues. Our results reported that SNHG15 could act as an oncogene in PC, revealing its potential value as a biomarker for early detection and individualized therapy.

Background and Aim In our previous study, we demonstrated that four microRNAs (miRNAs) (miR-26a, miR-142-3p, miR-148a, and miR-195) that were downregulated in both plasma and tumor tissues were confirmed to be promising non-invasive diagnostic biomarkers for gastric cancer (GC). Methods We used the quantitative reverse transcription polymerase chain reaction to assess the expression levels of the four miRNAs from paraffin-embedded surgical specimens of GC patients. Kaplan–Meier curves and log-rank test were applied to predict the correlation between miRNAs and cumulative overall survival (OS) of patients with GC. Besides, we performed in vitro assays including cell proliferation, migration, invasion and colony formation, and apoptosis. Results The median of miRNA expression in paraffin-embedded tissues were used as the cutoff value to classify patients into high or low expression groups. Down-regulation of miR-26a and miR-148a was significantly associated with shorter OS of GC patients either in the test set (miR-26a: P = 0.009; miR-148a: P = 0.005) or the validation set (miR-26a: P = 0.011; miR-148a: P = 0.024). When two sets were combined, Cox regression analysis demonstrated that both of miR-26a and miR-148a were independent prognostic factors for predicting OS of patients with GC (miR-26a: HR = 0.76, 95% CI = 0.61–0.94; miR-148a: HR = 0.73, 95% CI = 0.58–0.91). Furthermore, elevated expression of miR-26 significantly suppressed cell proliferation, migration, invasion and colony formation, and induced apoptosis of MGC-803 cells compared with negative control groups (P

Congenital skeletal deformity of fetus varies and may be attributed to a range of reasons. Congenital skeletal deformity seriously affects body function or even leads to neonatal death directly. The disease brings great pain to victim and their family. We reviewed the fetal prenatal ultrasonic data conducted during period from Jan. 2013 to June 2016, and there were 84 fetuses with skeletal abnormalities among 12 000 cases, and 3 fetuses with thanatophoric dysplasia. Our report described and reviewed three common types of thanatophoric dysplasia, aiming to explore the value of standardized prenatal ultrasonic diagnosis of fetal abnormalities in the skeletal system.

Correction for ‘Long non-coding RNA SNHG17 is an unfavourable prognostic factor and promotes cell proliferation by epigenetically silencing P57 in colorectal cancer’ by Zhonghua Ma et al., Mol. BioSyst., 2017, 13, 2350–2361.

In recent years, the overall development of China’s construction industry has been relatively good, but due to the continuous improvement of people’s daily life quality, the requirements for building structures have become higher and higher. This paper analyzes the structural earthquake resistance of modern buildings and the application of corresponding vibration control technology, and analyzes the specific application of vibration isolation and control technology to provide effective guarantee for the stability of modern building structures.

Background Previous genome-wide association studies (GWASs) have identified that several single nucleotide polymorphisms (SNPs) are implicated in gastric cancer (GC) risk. However, the multiple statistical comparisons of GWASs may reject some true biological positives with subthreshold P values. Methods This study annotated the genomic locations of all CpG islands in the genome using the Encyclopedia of DNA Elements (ENCODE). The SNPs in the regions were then genotyped using the Illumina 660W Quad chip. The effects of the prominent variations on GC risk were further confirmed in the other independent cohorts. Results SNP rs2990245, which is located in the promoter of pseudogene GBAP1, was associated with GC risk using GWASs data. An additional cohort of 1275 GC patients and 1424 controls validated that individuals with the CC genotype had a 62% decreased risk of GC compared with those who carried the TT genotype (P = 2.01E-04) in the codominant model. The significant association was observed in the additive, dominant, and recessive models. A meta-analysis combining the results from the GWASs and replication studies revealed that rs2990245 was significantly associated with decreased GC risk (P = 5.59E-12). Importantly, rs2990245 can regulate the expression of GBAP1 by influencing the methylation status of the GBAP1 promoter. GBAP1 can act as a competing endogenous RNA by binding competitively with micro-RNA-212-3p and then promoting GBA expression. Conclusion rs2990245 is significantly associated with a decreased risk of GC. Pseudogene GBAP1 contributes to the development and progression of GC by sequestering the miR-212-3p from binding to GBA.

Although long non-coding RNAs (lncRNAs) are regarded as useful plasma-based biomarkers for cancer detection, the potential diagnostic value of lncRNAs in gastric cancer (GC) remains unclear. To screen promising lncRNAs biomarkers for GC, we performed genome-wide lncRNA microarray assay between five GC cases plasma and matched healthy controls plasma. The expression of candidate plasma-related lncRNAs were validated in two-phase validation of 446 subjects. The receiver operating characteristic curve was constructed for evaluating diagnostic accuracy. We also determined the origin and stability of plasma lncRNAs, and investigated biological effects of candidate lncRNAs on cellular phenotypes. A total of 3878 lncRNAs were expressed differentially in GC plasma, among which the top 10 up-regulated lncRNAs were selected for further validation. A two-stage validation revealed that plasma levels of three lncRNAs (FAM49B-AS, GUSBP11, and CTDHUT) were significantly higher in GC plasma as compared with healthy controls (P

Bioresorbable scaffold (BRS) represents a new technique for percutaneous coronary intervention (PCI). Through providing temporary support to the vessel, it guarantees patency and acute benefits of the vessel in the early treatment stage. When completing its "mission", BRS gradually disappears by resorption. So it allows late vessel positive remodeling without "metal cage" effect and leaves only healed natural vessel after the full absorption, especially in the bifurcation lesion, the branch of the vessels can eventually achieve stent-free interference. This unique performance can not be achieved by the traditional permanent metal stent, so BRS has attracted more and more attention since its appearance. This article reviewed the research background, current status and challenges of BRS, then discussed its future development trends.

Vena cava filter (VCF)has been increasingly applied in clinical to efficiently prevent the pulmonary embolism (PE) with the rapid development of VCF. This article summarized the development of VCF, analyzed the relationship between structure and function, described the clinical behaviour of VCF, and final y forecasted the development trend of VCF products.

Aim: Natural killer (NK) cells, as key regulatory cells, accumulate at the maternal-fetal interface in large numbers. This study explored the effect of miR-30e on regulating the activity and function of peripheral blood NK cells (PB-NK cells) and decidua NK cells (D-NK cells) by targeting PRF1 in immune tolerance of maternal-fetal interface. Methods: Expressions of miR-30e in PB and decidua tissues from 49 patients with recurrent spontaneous abortion and 52 normal pregnant women were measured using PCR. NK cells were isolated from PB and decidua tissues and identified by flow cytometry (FCM). In PB-NK cells and D-NK cells activated by IFN-α, expressions of miR-30e and PRF1 were determined by PCR and Western blot. Negative controls of miR-30e mimics/inhibitors and siRNA against PRF1 were transfected in PB-NK cells and D-NK cells. Expressions of miR-30e and PRF1 were determined and their relationship was verified. Expressions of KIR2DL1, NKp44, IFN-γ, TNF-α, IL-4 and IL-10 were determined by FCM. Cytotoxicity kit was used to identify the cytotoxicity of NK cells. PCR and ELISA were employed to measure expression of VEGF, Ang-2 and PGF in D-NK cells. Results: After activation by IFN-α, D-NK cells and PB-NK cells showed decreased miR-30e expression and increased PRF1 expression in normal non-pregnant women. PRF1 is a target gene of miR-30e and miR-30e negatively regulated PRF1 expression. The treatment of miR-30e mimics elevated KIR2DL1 expression and decreased NKp44 expression in PB-NK or D-NK cells. Moreover, up-regulation of miR-30e expression suppressed cytotoxicity, corresponding to increased expression of IL-4and IL-10 and reduced expression of IFN-γ and TNF-α in PB-NK and D-NK cells, as well as enhanced expression of VEGF, Ang-2 and PGF in D-NK cells. Transfection of miR-30e inhibitors could reverse the tendencies. Conclusion: Up-regulated miR-30e can reduce the cytotoxicity of PB-NK cells and D-NK cells by targeting PRF1, whereby inhibiting Th1 tolerance phenotype and inducing Th2 immunodominance. miR-30e may be contributive to creating a micro-immune tolerance environment of maternal-fetal interface.

Figure S1-S10 (Online). Table S1. The top 10 significantly upregulated and downregulated lncRNAs identified by Arraystar Human lncRNA/mRNA chip. Table S2. The prime sequences of target genes used in real-time PCR. (DOCX 1257Â kb)

Carbon aerogel (CA) with ultra-low density and three dimensional network nanostructures is investigated as the electrocatalyst for tri-iodide (I 3 − ) reduction in dye-sensitized solar cells (DSSCs). The catalytic properties of CA and platinum (Pt) counter electrodes are analyzed and compared by electrochemical impedance spectroscopy (EIS) and Tafel polarization measurements. The devices applying CA counter electrode exhibit a lower charge-transfer resistance (1.60 Ω cm 2 ) and larger diffusion coefficient (3.39 × 10 −6 cm 2 s −1 ) compared to the devices with conventional Pt counter electrode. As a new kind of porous carbon materials, CA counter electrode has high active surface area and conductance. These factors improve the power conversion efficiency ( η ) up to 8.04%, which is better than that of the reference Pt based DSSC (6.79%). This paper indicates that carbon aerogel with good catalytic activity can potentially be used as a promising alternative to the expensive Pt counter electrode in a high-performance DSSC device design.

The prognostic impact of excision repair cross-complementation group 1 (ERCC1) expression in gastric cancer (GC) has been investigated for decades, but has yielded controversial results. The aim of the present study was to provide a precise evaluation of whether the expression levels of ERCC1 are associated with overall survival (OS) in patients with GC. A systematic search of Medline and Embase was conducted. Original studies concerning OS and ERCC1 expression were included for critical appraisal. A total of 15 studies comprising 1,425 patients with GC were identified. The results revealed that high/positive ERCC1 expression was an indicator of poor survival in patients with GC [hazard ratio (HR) 1.48; 95% confidence interval (CI) 1.02-2.10; P=0.036; I2=83.8%; random-effects model] compared with low/negative ERCC1 expression. Subgroup analysis indicated that high/positive ERCC1 expression had a significant unfavorable impact on OS in the group of patients evaluated by reverse transcription polymerase chain reaction (RT-PCR; HR 2.57; 95% CI 1.49-4.45). Furthermore, high/positive ERCC1 expression was found to be associated with poor survival in patients receiving platinum-based chemotherapy in the RT-PCR group (HR 2.13; 95% CI 1.06-4.27). These data suggest that ERCC1 may be a useful prognostic factor for GC. In addition, low mRNA levels of ERCC1 appear to be associated with a significant favorable OS benefit from platinum-based chemotherapy.

Single nucleotide polymorphisms (SNPs) in the 3′-untranslated regions (UTRs) targeted by putative mircoRNAs (miRNAs) could influence the susceptibility of cancer. Recently, miR-29c has been reported to be down-regulated in gastric cancer (GC) and serve as a tumor suppressor that regulated tumor progression. The present study was aimed at investigating whether the miR-29c binding site SNPs within the 3′-UTRs of target genes affected the gastric cancer risk. Using bioinformatics tools, we chose three SNPs (IGHMBP2 rs3750980, LAMTOR3 rs11944405 and WWOX rs2288035) located in miR-29c binding sites. We genotyped these three SNPs to assess their associations with GC risk in a case-control study comprising 753 GC cases and 950 controls. Among these three SNPs, we found a significantly decreased risk of GC associated with the LAMTOR3 rs11944405 T > C polymorphism [TC vs. TT, adjusted odds ratio (OR) = 0.79, 95% confidence interval (CI) = 0.63–0.99; TC/CC vs. TT, adjusted OR = 0.81, 95% CI = 0.65–1.00]. The significant association was also presented in the subgroup analysis by age (≤ 65), sex (female), depth of invasion (T3/T4), lymph node metastasis (N1-3), distant metastasis (M0) and TNM stage (III/IV). However, no significant association was detected for IGHMBP2 rs3750980 and WWOX rs2288035. Our results suggested that the LAMTOR3 rs11944405 polymorphism may be a potential biomarker for genetic susceptibility to GC.

Recently, substantial evidence has demonstrated that long non-coding RNAs (lncRNAs) play critical roles in multiple cancers including colorectal cancer (CRC). Utilizing publicly available lncRNA-expression-profiling data from the Gene Expression Omnibus (GEO) dataset GSE21510, we screened SNHG17 as a new candidate lncRNA associated with CRC development and progression. We further demonstrated that SNHG17 was upregulated in CRC tissues, and that its overexpression was significantly correlated with tumor size, TNM stage, and lymph node metastasis in CRC patients. Moreover, SNHG17 knockdown significantly inhibited the proliferation of CRC cells, and induced cell cycle G1/G0 phase arrest and cell apoptosis. Consistent with these findings, SNHG17 silencing inhibited tumor growth in vivo. Mechanistic studies revealed the capability of lncRNA SNHG17 to epigenetically suppress P57 by binding to enhancer of zeste homolog 2 (a key component of polycomb repressive complex 2) in CRC cells, and quantitative real-time polymerase chain reaction assays demonstrated that SNHG17 expression levels were inversely correlated with those of P57 in CRC tissues. Furthermore, rescue experiments confirmed that SNHG17 exerted oncogenic functions partly through regulating P57 expression. These findings represent the first reporting of the roles and mechanisms associated with SNHG17 in CRC progression, highlighting SNHG17 as a potential therapeutic target for CRC patients.

Background Emerging evidence has shown that dysregulation function of long non-coding RNAs (lncRNAs) implicated in gastric cancer (GC). However, the role of the differentially expressed lncRNAs in GC has not fully explained. Methods LncRNA expression profiles were determined by lncRNA microarray in five pairs of normal and GC tissues, further validated in another 75 paired tissues by quantitative real-time PCR (qRT-PCR). Overexpression of lncRNA MT1JP was conducted to assess the effect of MT1JP in vitro and in vivo. The biological functions were demonstrated by luciferase reporter assay, western blotting and rescue experiments. Results LncRNA MT1JP was significantly lower in GC tissues than adjacent normal tissues, and higher MT1JP was remarkably related to lymph node metastasis and advance stage. Besides, GC patients with higher MT1JP expression had a well survival. Functionally, overexpression of lncRNA MT1JP inhibited cell proliferation, migration, invasion and promoted cell apoptosis in vitro, and inhibited tumor growth and metastasis in vivo. Functional analysis showed that lncRNA MT1JP regulated FBXW7 expression by competitively binding to miR-92a-3p. MiR-92a-3p and down-regulated FBXW7 reversed cell phenotypes caused by lncRNA MT1JP by rescue analysis. Conclusion MT1JP, a down-regulated lncRNA in GC, was associated with malignant tumor phenotypes and survival of GC. MT1JP regulated the progression of GC by functioning as a competing endogenous RNA (ceRNA) to competitively bind to miR-92a-3p and regulate FBXW7 expression. Our study provided new insight into the post-transcriptional regulation mechanism of lncRNA MT1JP, and suggested that MT1JP may act as a potential therapeutic target and prognosis biomarker for GC. Electronic supplementary material The online version of this article (10.1186/s12943-018-0829-6) contains supplementary material, which is available to authorized users.

Objective We explored the association between single nucleotide polymorphisms (SNPs) rs207454 and rs494852 located in xanthine dehydrogenase (XDH) and gastric cancer (GC) survival. Methods A total of 940 patients with gastric cancer were enrolled and genotyped using TaqMan allelic discrimination method. The Kaplan–Meier test and log-rank examine were used to assess the effect of genetic variation. Results Patients carrying rs207454 CC genotype had a longer survival time than those with the AA genotype (P = 0.042). The similar association was detected in the recessive model (P = 0.017). We conducted expression quantitative trait loci (eQTL) analysis and found that gastric cancer patients carrying rs207454 CC genotype had significant lower XDH levels than those with AA/AC genotype, suggesting that rs207454 polymorphism effected the expression of XDH. Additionally, the Kaplan-Meier curves showed that gastric cancer patients with high expression of XDH had remarkably poor survival outcome than those with low expression (hazard ratio [HR] = 1.53, 95% confidence interval [CI] = 1.29–1.82). Conclusions Genetic variants in XDH were associated with the survival of gastric cancer and may act as prognostic markers for individual suffered from gastric cancer.

Background Inactivation of tumor suppressor genes by promoter hypermethylation plays a key role in the tumorgenesis. It is necessary to uncover the detailed pattern of whole genome-wide abnormal DNA methylation during the development of gastric cancer (GC). Method We performed a genome-wide methylation detection using 12 paired of GC tissues and their corresponding normal tissues. Methylation-specific PCR (MSP) and bisulphite sequencing (BSP) were used to measure methylation status of specific CpG site. Based on the bioinformatic analysis, the cell phenotypes and mouse model experiments were constructed to detect effect of the target gene. Using the Kaplan–Meier survival curve, the clinical value of KCNMA1 was assessed in GC patients. Results The CpG site cg24113782 located at the promoter of KCNMA1 showed the most significant difference, contributing to the commonly silenced KCNMA1in gastric cancer cells and primary GC tissues. The promoter methylation of KCNMA1 was detected in 68.7% (77/112) of tumor tissues, compared with 16.2% (18/112) of normal tissues (P

Clinical characteristics of 12 gastric cancer cases selected in microarray analysis. Table S2. Sequences of primers used in RT-PCR and MSP assay. (PDF 113 kb)

Supplementary materials. (PDF 82 kb)

Supplementary figure. (PDF 387 kb)

Purpose Studies have demonstrated that single nucleotide polymorphisms (SNPs) in miRNAs may lead to varying functional outcomes by altering miRNAs expression, even leading to the development of cancers. The association between a single nucleotide polymorphism (SNP) in miR-146a rs2910164 and susceptibility to gastric cancer has been studied during the recent years, but the results are still inconclusive and inconsistent. We performed a meta-analysis to evaluate the relationship between miR-146a rs2910164 polymorphism and the risk of gastric cancer. Materials and methods The databases of PubMed, MEDLINE and Web of Science were searched for suitable studies. A total of 8 published case–control studies on miR-146a rs2910164 polymorphism and gastric cancer risk including 4308 cases and 6370 controls were included. Results Overall, significant association was observed between rs2910164 and gastric cancer risk in allele model (OR = 1.11, 95% CI = 1.02–1.21); homozygote model (OR = 1.26, 95% CI = 1.10–1.43) and dominant model (OR = 1.21, 95% CI = 1.09–1.34). Stratified analysis by ethnicity showed significant association between rs2910164 polymorphism and gastric cancer susceptibility in Asians (OR = 1.10, 95% CI = 1.00–1.23 for G vs. C; OR = 1.25, 95% CI = 1.09–1.43 for GG vs. CC; OR = 1.19, 95% CI = 1.07–1.33 for GG vs. GC+CC, respectively). When stratified by genotyping methods and sample size, increased gastric cancer risk was only observed with the method by TaqMan and the sample size more than 1000. Conclusion In summary, this meta-analysis indicated that miR-146a rs2910164 polymorphism was associated with the susceptibility to gastric cancer, especially in Asian population.

The association of red meat consumption with the risk of stomach cancer has been reported by many studies, with inconclusive results. We performed a meta-analysis of cohort and case–control studies to provide a quantitative assessment of this association. Relevant studies were identified by searching PubMed and Embase before December 2013 without restrictions. A total of 18 studies involving 1,228,327 subjects were included in this meta-analysis. Summary relative risks were estimated using random effects models. The pooled relative risks of gastric cancer were 1.37 (95 % CI 1.18–1.59) for the highest versus lowest categories of red meat intake with significant heterogeneity among studies (P heterogeneity

Objective Intrauterine administration of autologous peripheral blood mononuclear cells (PBMCs) activated by HCG in vitro is reported to improve implantation rates in patients with repeated failure of IVF-ET. In this article, the impact of intrauterine administration of PBMCs on embryo implantation, pregnancy rate and the underlying mechanisms will be investigated. Methods Pregnant mice were randomly divided into three groups, including control group; embryo implantation dysfunction (EID) group; EID with PBMCs group. Uterine horns were excised to determine the number of pregnant mice and implantation sites on the Day 7.5 postcoitum. The expression levels of LIF and VEGF during the implantation window were detected with immunohistochemistry and Real Time-PCR analysis. Results Embryo implantation dysfunction model group showed a significant decrease in pregnancy rate, implantation sites and the expression of both the endometrial LIF and VEGF during the implantation window. EID with PBMCs group showed a higher pregnancy rate and endometrial LIF and VEGF expression compared to EID group. Conclusion Intrauterine administration of mouse PBMCs derived from unpregnant mice prior to embryo implant has a good influence on endometrial receptivity and embryonic implantation in EID mice.