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The goal of this study was to identify genes that were differentially methylated and differentially expressed and their related signaling pathways in ovarian endometriosis tissue. First, the DNA methylation and gene expression profiles in the endometrial tissue of patients with ovarian endometriosis were studied using Illumina 450K methylation microarray analysis and the GSE141549 gene expression dataset. Second, differentially methylated and differentially expressed genes, herein referred to as differentially methylated/expressed genes, were identified and protein-protein interaction networks and functional analysis of these genes were determined. Third, qPCR and immunohistochemistry of patient samples was used to confirm the differential expression of a subset of differentially methylated/expressed genes. Finally, the GSE7305 dataset was used confirm the expression profile of differentially methylated/expressed genes and to determine the potential usefulness of these genes for diagnosis of endometriosis. A total of 37 hypermethylated low-expression genes and 66 hypomethylated high-expression genes were identified in ovarian endometriosis patients. Protein-protein interaction and functional analysis highlighted 8 hypermethylated low-expression genes (KRT19, KRT8, ESR1, PRL, SFN, IL20RA, IL2RB, and PAX8) and 4 hypomethylated high-expression genes (CYP11A1, NR5A1, ME1, and GSTM1). Significantly, both of these gene sets had a diagnostic value for patients with ovarian endometriosis. Signaling pathways that were identified included JAK-STAT (involving IL20RA and IL2RB), prolactin (involving PRL and ESR1), Staphylococcus aureus infection (involving KRT19), viral protein interaction with cytokine and cytokine receptor (involving IL20RA and IL2RB), cytokine-cytokine receptor interaction (involving IL20RA and IL2RB), and drug metabolism-cytochrome P450 (involving GSTM1). The differentially methylated/expressed genes and enriched signaling pathways identified in this study are likely to be associated with the process of ovarian endometriosis.

Background: The aim of the study was to investigate the role of the genetic variation of glutathione S-transferase M1 (GSTM1) in the development of ovarian endometriosis and endometriosis-related primary infertility risk. Methods: This case-control study included 564 women with ovarian endometriosis and 576 normal women in the control group in northern China. The polymorphism of GSTM1 was genotyped by polymerase chain reaction (PCR)/ligase detection reaction method. To assess the biological significance of polymorphisms, the level of GSTM1 mRNA expression in patients’ endometrial tissues with different genotypes was detected by quantitative real-time PCR (qRT-PCR). Results: Compared with the positive genotype, the null genotype of GSTM1 was associated with the risk of developing ovarian endometriosis (OR = 1.29, 95% CI = 1.02–1.62). Further analysis showed that patients with a null genotype also had a significantly higher risk of primary infertility than patients with positive genotypes (OR = 1.59, 95% CI = 1.01–2.49). In addition, we found that GSTM1 mRNA expression was present in the endometrial tissue of all patients, but the expression level of patients with a positive genotype was nearly 10 times higher than that of patients with a negative genotype. Conclusion: Our results suggest that the GSTM1 polymorphism is not only related to the genetic susceptibility to ovarian endometriosis but also a potential molecular marker of primary infertility in patients with ovarian endometriosis.

Owing to the high morbidity and mortality, novel biomarkers in the occurrence and development of colorectal cancer (CRC) are needed nowadays. In this study, the CRC-related datasets were downloaded from the Gene Expression Omnibus (GEO) database and The Cancer Genome Atlas (TCGA) database. After screening the differentially expressed genes (DEGs) in R software, a total of 238 upregulated and 199 downregulated DEGs were revealed simultaneously. Then the Kaplan-Meier survival analysis and Cox regression analysis were used to reveal the prognostic function of these DEGs. Neurexophilin and PC-esterase domain family member 4 (NXPE4) and prostate androgen-regulated mucin-like protein 1 (PARM1) were two outstanding independent overall survival (OS) and relapse-free survival (RFS) prognostic genes of CRC in TCGA database. We next verified the expression of NXPE4 and PARM1 messenger RNA (mRNA) levels were significantly lower in CRC tumor tissue than in the adjacent noncancerous tissue in our clinical samples, and NXPE4 mRNA expression level was related to the tumor location and tumor size, while PARM1 was related to tumor location, lymph nodes metastasis, and tumor size. This study demonstrated that NXPE4 and PARM1 might be two potential novel prognostic biomarkers for CRC.

Context Patients with gastric cancer experience health-related quality of life (HRQOL) decline during adjuvant chemotherapy following gastrectomy. Objectives This pilot study aimed to evaluate the preliminary effect and feasibility of electro-acupuncture (EA) for HRQOL and symptom burden in these patients. Methods In this open-label, multicenter, parallel controlled trial, gastric cancer patients who planned to receive adjuvant chemotherapy were randomly assigned to receive high-dose EA (seven times each chemotherapy cycle for three cycles), low-dose EA (three times each chemotherapy cycle), or usual care only. The acupoints prescription consisted of bilateral ST36, PC6, SP4, and DU20, EX-HN3, and selected Back-shu points. Patients completed the Functional Assessment of Cancer Therapy-Gastric (FACT-Ga) weekly, and the Edmonton Symptom Assessment System (ESAS). The primary outcome was the difference among the groups on the gastric cancer subscale (GaCS) of the FACT-Ga. Results Of the 66 randomized patients, 58 were analyzed according to intention-to-treat principle, and 45 were in the per-protocol set (PPS). The average scores in PPS of GaCS were 52.12±9.71, 51.85±12.36, and 45.37±8.61 in high-dose EA, low-dose EA, and control groups, respectively. EA was significantly associated with improved average GaCS scores when compared with control group (51.98±10.91 vs. 45.37±8.61, P = 0.039). EA treatment also produced ESAS relief at the end of intervention (14.36 ± 12.28 vs. 23.91 ± 15.52, P = 0.027). Participants in EA groups had fewer grade ≥3 leukopenia (0% vs. 15.79%, P = 0.031) and neutropenia (2.56% vs. 26.31%, P = 0.012). Conclusion EA showed promising effects in improving HRQOL, controlling symptom burden, and reducing toxicity during adjuvant chemotherapy in gastric cancer patients. Future adequately powered trials are feasible and needed to confirm the specific effect of EA.

Background The precise etiology of anterior inferior cerebellar artery (AICA) infarction is difficult to identify because of the high anatomic variability of vertebrobasilar arteries and the limitations of conventional vascular examinations. Basi-parallel anatomic scanning magnetic resonance imaging (BPAS-MRI) can reveal the outer contour of the intracranial vertebrobasilar arteries, which may be helpful to distinguish the arteriosclerosis from congenital dysplasia and dissection. Case presentation In this study, we reported 3 cases of AICA infarction and discussed the diagnostic value of BPAS-MRI in the evaluation of vascular etiology. Conclusions The BPAS-MRI could be considered as an important supplementary in the diagnosis of vascular etiology of infarction in AICA territory.

More than 20 types of ALK fusion variant subtypes have been identified, including different fusion partner genes or EML4-ALK fusions with different breakpoints. However, different ALK fusions show different sensitivities to ALK-tyrosine kinase inhibitors (ALK-TKIs) and the emergence of rare fusions brings great challenges to the target therapy in clinic. We report a rare EML4-ALK (E6;A18) fusion in a patient with lung adenocarcinoma that responded well to alectinib. This is the second case of this rare variant reported but the first report of response to an ALK-TKI. This evidence is the first to show that alectinib may be effective for this rare fusion type of non–small cell lung cancer, and these findings have important implications for drug selection in patients with this subtype. Further studies are needed to understand the function of this variant.

Coronin 2A (CORO2A) is a novel component of the N-CoR (nuclear receptor co-repressor) complex. Abnormal CORO2A expression is associated with carcinogenesis. We used databases from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), and analyzed CORO2A expression and gene regulation networks in breast cancer. Expression was analyzed using GEO and TCGA database and further validated in breast cancer samples collected in our clinic. The prognostic value of CORO2A was explored by using the Kaplan–Meier survival analysis and Cox proportional hazards regression analysis. LinkedOmics was used to identify coexpressed genes associated with CORO2A. After analyzing the intersection of coexpressed genes correlated with CORO2A and differentially expressed genes after CORO2A silencing, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses of the intersecting genes were conducted by using FunRich software. Transwell assays were performed in breast cancer cells to determine the effect of CORO2A on cell migration. MTS, colony formation, and cell cycle distribution assays were performed in breast cancer cells to determine the effect of CORO2A on cell proliferation. Gene enrichment analysis was employed to explore the target networks of transcription factors and miRNAs. We found that CORO2A was upregulated and that the elevated expression of CORO2A was associated with poor overall survival (OS) and relapse-free survival (RFS) in TNBC patients. Further bioinformatics analysis of public sequencing data and our own RNA-Seq data revealed that CORO2A was probably involved in the epithelial-to-mesenchymal transition process and might have a significant effect on the migration of breast cancer cells, which might be mediated via pathways involving several miRNAs and MYC transcription factors. Functionally, the knockdown of CORO2A inhibited cell migration, decreased viability, and colony formation and induced cell cycle arrest in the G0/G1 phase in breast cancer cells. These results demonstrate that bioinformatics-based analysis efficiently reveals information about CORO2A expression and its potential regulatory networks in breast cancer, laying a foundation for further mechanistic research on the role of CORO2A in carcinogenesis. Moreover, CORO2A promotes the migration and proliferation of breast cancer cells and may have an important function in breast cancer progression. CORO2A is a potential prognostic predictor for TNBC patients. Targeting CORO2A may provide promising therapy strategies for breast cancer treatment.

Aim: The present study aimed to assess the association between IGF2/H19 genetic variants and susceptibility to platinum-based chemotherapy in epithelial ovarian cancer (EOC). Methods: A total of 43 platinum-resistant (PR) and 138 platinum-sensitive (PS) EOC patients were recruited in our study. 21 polymorphisms in IGF2/H19 locus were genotyped by Sequenom MassARRAY assay. Results: The frequencies of GG genotype in both rs3842761(C/G) and rs4244809(A/G) were significantly lower in PR group compared with those in PS group (9.76 vs 23.36%, p = 0.049; 9.76 vs 26.09%, p = 0.045; respectively). Compared with the AA genotype, rs4244809 GG genotype was associated with significantly reduced risk of platinum resistance (adjusted OR: 0.30; 95% CI: 0.10–0.91; p = 0.033). Further stratified analyses revealed that the SNPs of rs3842761 and rs4244809 were greatly related to PR risk in FIGO stage III–IV (rs3842761GG/CC+CG: adjusted OR: 0.15; 95% CI: 0.02–1.21; rs4244809 GG/AA+AG: adjusted OR: 0.24; 95% CI: 0.07–0.84; respectively) and serous adenocarcinoma subgroups (rs3842761 GG/CC+CG: adjusted OR: 0.21; 95% CI: 0.05–0.94; rs4244809 GG/AA+AG: adjusted OR: 0.19; 95% CI: 0.04–0.5; respectively), while rs7924316 polymorphism was associated with reduced risk of PR in serous adenocarcinoma subgroup as analyzed by a recessive model (rs7924316 GG/TT+TG: adjusted OR: 0.22; 95% CI: 0.05–0.98). In addition, both TCT haplotypes of rs3741206/rs3842761/rs7924316 and TC haplotype of rs3741206/rs3842761 were associated with elevated risk of PR (for the TCT haplotype of rs3741206/rs3842761/rs7924316: p = 0.049; OR: 1.69; 95% CI: 1.00–2.87; for the TC haplotype of rs3741206/rs3842761: p = 0.044; OR: 1.71; 95% CI: 1.01–2.88). Conclusion: These results suggest that polymorphisms in IGF2/H19 gene locus are associated with PR risk in EOC.

Breast cancer (BC) is the most malignant tumor in women. The molecular mechanisms underlying tumorigenesis still need to be further elucidated. It is necessary to investigate novel candidate genes involved in breast cancer progression and prognosis. In this study, we commit to explore candidate genes that associate with prognosis and therapy in BC by a comprehensive bioinformatic analysis. Four GEO datasets (GSE5764, GSE7904, GSE20711, and GSE29431) and the BC-related transcriptome data in TCGA database were downloaded and used to identify the differently expressed genes (DEGs). The function of DEGs was analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways enrichment analysis. The protein-protein interaction (PPI) network of DEGs was constructed to identify hub genes. Prognostic candidate genes were identified through survival analysis. In addition, potential therapeutic targets were identified by constructed gene-drug interaction network through Comparative Toxicogenomics Database. A total of 547 DEGs (302 up and 245 down) were identified. Three core-subnetwork and 25 hub genes were identified in PPI network. Seven genes (namely COL12A1, QPRT, MRPL13, KRT14, KRT15, LAMB3, and MYBPC1) were identified as crucial prognostic candidate genes, which significantly associated with breast cancer overall survival. Furthermore, two representative candidate genes (COL12A1 and LAMB3) were optionally chosen for verification by reverse transcription and quantitative real-time polymerase chain reaction (RT-PCR). What's more, the gene-drugs interaction analysis indicates several antitumor drugs that could affect the expression of these prognostic markers, such as doxorubicin, cisplatin, and tamoxifen. These results identified seven crucial candidate genes that may serve as prognosis biomarkers and novel therapeutic targets of breast cancer, which may facilitate further understanding the molecular pathogenesis and providing potential therapeutic strategies for BC.

Background: Traditional Chinese Medicine (TCM) prescriptions should be decided according to the TCM treatment principle, and the warming-yang or cooling-heat should be the guide of treatment principle outline. Methods: In order to identify which treatment principle, warming-yang or cooling-heat should be combined with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in non-small cell lung cancer (NSCLC), we combined the typical warming-yang drug, Shen-fu (SF), and the typical cooling-heat drug, Qing-kai-ling (QKL) with gefitinib in resistant NSCLC models. Results: The results demonstrated that QKL combined with gefitinib induced significantly increased cell viability inhibition and apoptosis in A549 cell line and significantly smaller tumor volume and lower tumor weight in H1975 xenograft transplanted nude mice. On the contrary, SF combined with gefitinib had significant antagonism effect on both cell viability inhibition and apoptosis in vitro , and on tumor weight in vivo . EGFR phosphorylation inhibition and the downstream PI3K/AKT and RAS/RAF/ERK pathway inhibition served an important role in the synergism effect between QKL and gefitinib in H1975 xenograft transplanted nude mice. Conclusions: The present study indicated that cooling-heat TCM treatment principle may reverse or delay NSCLC resistance to EGFR-TKIs, and combination of them warrants further study.

Polymorphisms of T cell immunoglobulin and mucin domain-containing molecule 3 (TIM-3) were reported to be associated with cancer risk and patients' survival. This study aims to investigate the correlation of TIM-3 polymorphisms with susceptibility to epithelial ovarian cancer (EOC) and patients' outcomes.A total of 700 EOC patients and 710 healthy controls from North China were included. The polymorphisms (rs10053538, rs10515746 and rs1036199) were genotyped using the polymerase chain reaction/ligase detection reaction (PCR-LDR) method. Survival data were available for 339 patients after cytoreductive surgery. The expression level of TIM-3 was detected by real-time quantitative PCR (RT-qPCR). The prognostic value of TIM3 in EOC patients was assessed using the Kaplan-Meier plotter database.The results showed that none of the TIM3 polymorphisms were associated with the risk of developing EOC. Patients with the rs10053538 CA + AA genotype had worse PFS and OS than those with the CC genotype (HR = 1.49, 95% CI = 1.05-2.09, P = 0.024 and HR = 1.57, 95%CI = 1.09-2.26, P = 0.017, respectively). The RT-qPCR results showed that the expression levels of TIM-3 mRNA in EOC tissues with the rs10053538CA + AA genotypes were significantly higher than those with the CC genotype (P = 0.006). Analysis using the Kaplan-Meier plotter database showed that high expression of TIM-3 mRNA was significantly associated with shorter PFS and OS in EOC patients (HR = 1.57, 95%CI = 1.29-1.91, P 0.001 and HR = 1.31, 95% CI = 1.06-1.63, P = 0.013, respectively).TIM-3 polymorphisms were not associated with risk of developing EOC. Both rs10053538 and the expression level of TIM-3 mRNA may be associated with its clinical outcome in EOC patients.

Background and Aim: We have previously shown that high-mobility group box 1 (HMGB1) is an independent biomarker for shortened survival of prostate cancer (PCa) patients. However, the specific role of HMGB1 in tumor development and progression remains largely unknown. In this study, we investigated the molecular mechanisms of HMGB1 in PCa tumorigenesis. Methods: Gain-of-function and loss-of-function experiments were used to determine the biological functions of HMGB1 both in vitro and in vivo. Bioinformatic analysis, immunoprecipitation, and immunofluorescence assays were applied to discern and examine the relationship between HMGB1 and its potential targets. Specimens from 64 patients with PCa were analyzed for the expression of HMGB1 and its relationship with Brahma-related gene 1 (BRG1) was examined by immunohistochemistry. Results: The results demonstrated that ectopic expression of HMGB1 facilitated growth and metastasis of PCa by enhancing Akt signaling pathway and promoting epithelial-mesenchymal transition (EMT), while silencing of HMGB1 showed the opposite effects. Mechanistically, HMGB1 exerted these functions through its interaction with BRG1 which may augment BRG1 function and activate the Akt signaling pathway thereby promoting EMT. Importantly, both HMGB1 and BRG1 expression was markedly increased in human PCa tissues. Conclusions: Taken together, these findings indicate that upregulation of HMGB1 promotes PCa development via activation of Akt and accelerates metastasis through regulating BRG1-mediated EMT. HMGB1 could be used as a novel potential target for the treatment of PCa.

Purpose The research of long non-coding RNAs (lncRNAs) has become a new passion with the discovery of abundant new lncRNAs and extensive investigation of their roles in various diseases, especially in cancers. Metastasis associated in lung adenocarcinoma transcript 1 (MALAT1) emerges as a hotspot, which has been reported to be involved in dysregulation of cell signaling and closely correlated with cancer development, progression, and response to therapy. This review is a brief update of the current knowledge related to the role of MALAT1 in cancer-associated molecular pathways and pathophysiology and possible determinants for MALAT1 to function as a biomarker, aiming to stimulate the basic investigation of lncRNA MALAT1 as well as its translation to clinical applications. Methods We have selected vast literature from electronic databases including studies associated with its clinical significance and the pivotal functions in cancer processes such as cell proliferation, apoptosis, metastasis, immunity, angiogenesis, and drug resistance. Results Studies have shown that aberrant expression of MALAT1 is related to cancer pathophysiology with the potential to be translated clinically and MALAT1 can regulate cancer processes by interacting with molecules, such as proteins, RNAs and DNAs, and further altering different signal pathways. Conclusion MALAT1 lncRNA promises to be a potential biomarker for cancer diagnosis as well as prognosis. Additionally, it might be a therapeutic target for human cancers.

Mobility and flexibility of anterior mitral leaflet (AML) are considered to be the important factor for mitral valve (MV) repair in rheumatic population, we try to use the bending angle of AML to quantify its' mobility and flexibility and investigate whether it can predict the success of rheumatic MV repair or not.Total 54 patients underwent rheumatic MV surgeries with mild lesions of subvalvular apparatus from August, 2017 to November, 2017 at the author institution, we divided the patients into MV repair and MV replacement groups which included directly MV replacement and repair attempt but failed repairing transfer to replacement intraoperatively. Patients' MV structure was carefully evaluated on transthoracic echocardiography (TTE) and scored by the Wilkins score (WS) preoperatively. The bending angle of AML was measured during systole and diastole at different level before surgery.The differences of patients' demographic characteristics between repair group and replacement group were not statistically significant (P value0.05) and the differences among B-angle, T-angle, Bs-angle, C-angle of AML between repair group and replacement groups were not statistically significant (P value0.05). Only BT-angle in repair group was significantly larger than that of replacement group (21.56°±3.84°, 10.29°±6.02°, respectively, P0.001), therefore the BT-angle was tested as a predictor of reparability by observing the receiver operating characteristic (ROC) curve (ROC area: 0.944, standard error: 0.06, 95% CI: 0.826-1), BT-angle of AML on preoperative transthoracic echo of 15.5° or more predicts feasibility of rheumatic MV repair with 100% sensitivity and 85.7% specificity in patients with mild lesions of subvalvular apparatus. Logistic regression for a single area of calcification (diameter0.8 cm) at commissure were shown that: β: 0.08, Exp (β): 1.083, P: 0.7770.05, the minor single calcified area at commissure had no effect on reparability of rheumatic MV disease. The differences of total WS and each component score between repair group and replacement group were not statistically significant (P value0.05). By observing the ROC curve for total WS (ROC area: 0.508), the WS cannot be a predictor for the rheumatic MV repair.The bending angle of AML which was considered as quantification of mobility and flexibility of AML can be a predictor for MV repair in patients with rheumatic heart disease (RHD). The small single area of commissural calcification had no effect on reparability of rheumatic MV disease. WS cannot appropriately predict the outcome of rheumatic MV repair.

Our study aimed to assess the associations of plasma magnesium with prediabetes and type 2 diabetes (T2D) among Chinese adults. We conducted a case-control analysis of 4447 participants: 867 newly diagnosed prediabetes patients, 1475 newly diagnosed T2D patients and 2105 normal glucose tolerance (NGT) individuals. In a subsample of 599 apparently healthy individuals, we measured plasma hs-CRP levels to examine their relation to plasma magnesium. Plasma magnesium and hs-CRP were measured by inductively coupled plasma mass spectrometry and an enzyme-linked immunosorbent assay, respectively. Plasma magnesium decreased from NGT to prediabetes to T2D, and was inversely associated with prediabetes and T2D. After adjustment for potential confounding factors, the ORs from the lowest to highest quartiles of plasma magnesium were 1, 0.57 (95%CI, 0.44–0.74), 0.49 (0.37–0.65) and 0.51 (0.37–0.70) for prediabetes, and 1, 0.26 (0.20–0.33), 0.15 (0.12–0.20) and 0.15 (0.11–0.20) for T2D. Consistently, plasma magnesium was inversely correlated with plasma hs-CRP in our subsample analysis; the geometric mean hs-CRP concentration for ascending quartiles of plasma magnesium were 1.29 (1.06–1.57), 1.16 (0.95–1.41), 1.00 (0.81–1.22), and 0.71 (0.58–0.88) mg/l. Plasma magnesium was independently and inversely associated with prediabetes and T2D in Chinese adults.

Objective: The relationship between the waiting time of postoperative radiotherapy and the prognosis of patients with high-grade glioma is still inconclusive, and we addressed this issue through a systematic review and meta-analysis. Methods: Twenty studies published between 1975 and 2019 about waiting times (WT) of radiotherapy with high-grade glioma were retrieved for meta-analysis.The meta-analysis was performed by converting the effect sizes of different WT into regression coefficients (β) and standard error (SE) to indicate the daily impact of delay on OS. Results: A total of 8462 high-grade glioma patients were included in the 20 studies, and no correlation between WT delay and OS was found in the unadjusted model through meta-analysis (HR=1, 95%CI=0.99-1.01, p=0.962). Meta-regression was used to adjust for other prognostic factors and no clear evidence of the relationship between WT delay and OS was found. Conclusion: This meta-analysis suggests that there is no clear evidence for the effect of delayed radiotherapy on OS with high-grade glioma patients.

Inflammatory myofibroblastic tumor (IMT), a rare sarcoma, is primarily treated via resection of the mass. However, there is no standard treatment for recurrence or unresectable tumors. Almost 50% of IMTs carry ALK gene rearrangement that can be treated using ALK inhibitors, but therapeutic options for ALK-negative tumors are limited. This report describes a woman aged 22 years with unresectable ALK-negative IMT. Next-generation sequencing revealed a TFG-ROS1 fusion, and she had a partial response to the ROS1 inhibitor ceritinib. This report provides the first published demonstration of a patient with IMT with ROS1 fusion successfully treated using ceritinib. Our study suggests that targeting ROS1 fusions using the small molecule inhibitor shows promise as an effective therapy in patients with IMT carrying this genetic alteration, but this requires further investigation in large clinical trials.

Background The purpose of this study is to develop an effective but concise long non-coding RNA (lncRNA) expression signature that can predict response to neoadjuvant chemotherapy for breast cancer (BC) patients. Methods lncRNA expression profiling in 1102 BC patients from Gene Expression Omnibus datasets was analyzed using lncRNA-mining approach. The association between lncRNA signature and pathological complete response (pCR) was analyzed using logistic regression model in the training set (GSE25066, n = 488). Validation was performed in independent testing datasets, GSE20194, GSE20271, GSE22093, and GSE23988 (n = 614). Bonferroni method was employed for multiple testing corrections. Cell proliferation assay and Western blot assay were performed to evaluate the cell viability and protein expression level, respectively. Results Three lncRNAs (AK291479, U79293, and BC032585) have been identified to be significantly associated with pCR in the training dataset (Bonferroni p-value < 0.05). Expression signature with these lncRNAs was predictive of pCR in the training (AUC = 0.74) and testing (AUC = 0.72) datasets. Weighted gene co-expression network analysis and gene functional annotation suggest that the three lncRNAs were involved in cell cycle process. To confirm the functional significance of the identified lncRNAs, BC032585 was selectively silenced using RNA interference. Knockdown of BC032585 lncRNA significantly promoted cell resistance to multiple anticancer-drugs through upregulating MDR1 expression in breast cancer cells. Conclusion These results suggest that lncRNAs such as BC032585 might be involved in chemotherapeutic response in breast cancer patients, and the three-lncRNA signature identified in the present study may serve as a useful biomarker for the selection of responsive breast cancer patients in neoadjuvant chemotherapy.

Background Preeclampsia (PE) is a severe pregnancy complication and is an important cause for maternal and child death, premature delivery, and limited intrauterine growth and development. The aim of this study was to investigate the role of NGAL and cystatin C, alone and in combination, for early prediction of PE at 10 - 14 weeks of gestation. Methods Serum levels of NGAL and cystatin C were assessed in women at 10 - 14 weeks of gestation who subsequently developed PE (n = 128) and normal pregnancy outcome (n = 183). Comparison of clinical characteristics, NGAL, and cystatin C levels between normal pregnancy and PE groups were analyzed using Mann-Whitney test. The receiver operating characteristic curve (ROC curve) was used to analyze the value of serum NGAL and cystatin C levels in predicting PE. Results The levels of cystatin C and NGAL in the serum were significantly higher in the PE group [0.64 mg/L (0.52 - 0.78)] and [34.9 ng/mL (24.4 - 55.2), respectively] than in the normal pregnancy group [0.56 mg/L (0.49 - 0.65)] and [20.2 ng/mL (13.8 - 26.9), respectively]. ROC curve analysis showed that serum NGAL levels predicted the area under the curve in the PE period 0.739 (95% CI: 0.618 to 0.860). Serum cystatin C levels predicted the area under the curve in the PE period 0.722 (95% CI: 0.592 to 0.853). The combination of serum NGAL and cystatin C levels predicted the area under the curve in the PE period 0.877 (95% CI: 0.811 to 0.943). Conclusions NGAL and cystatin C levels in serum appear to be ideal biomarkers for PE prediction at 10 - 14 weeks. The combination of NGAL and cystatin C will also be more valuable in discriminating patients at risk of developing PE from other pregnancy complications early in gestation.

TPS151 Background: The standard third-line treatment of mCRC is regofenib, fruquintinib or TAS-102. However, the efficacy was not satisfied. Because VEGF and EGFR share the downstream signal pathway, targeting these two pathways may have synergistic efficacy. Preclinical studies have confirmed the effect of the combination of regorafenib and cetuximab. The subsequent phase Ⅰb study in advanced cancer showed the combination is effective. Fruquintinib is the same anti-VEGF drugs and was approved in China. Our department has treated one patient of advanced colorectal cancer, no standard regimen after third-line treatment. The efficacy is SD and PFS time exceeded 6 months. Therefore this study explores the safety and efficacy of fruquintinib combined with cetuximab. Methods: This is a single-center, non-random, prospective, open exploratory study. Eligible pts were diagnosed as advanced RAS/BRAF wild-type colorectal cancer and had received at least two prior regimens of standard therapies. The purpose of phase Ⅰ is to confirm the safety and the appropriate dose of fruquintinib combined with cetuximab. The phase Ⅱa investigate the safety and the efficacy of fruquintinib combined with cetuximab. Phase I: The dose of cetuximab is 500mg/m2 every two weeks which is clinically tolerable, so the dose need not be adjusted. fruquintinib is taken once daily for the first 21 days of each 28-day cycle and the dose adjustment is required due to the side effects. The standard dose of fruquintinib is 5mg/d, but the side effects are serious. The dose of 3mg/d is the minimum effective dose, therefore the initial dose of fruquintinib starts from 4mg, and three patients are enrolled. If DLT appeared in less than three patients, the dose elevated to 5mg/d. Three patients were enrolled in the 5mg/d dose group. If DLT appeared in less than three patients, the right dose of fruquintinib was 5mg/d. If DLT appeared in all three patients of the 5mg/d, fruquintinib was declined to 4mg/d combined with cetuximab to carry out a phase Ⅱa study. Fruquintinib initial dose is 4mg/d. If DLT was present in all three patients, the dose was reduced to 3mg/d. The standard dose of fruquintinib (3mg/d) was determined to be MDT, and the subsequent phase Ⅱa study was conducted by giving fruquintinib 3mg/d. The phase Ⅱa study is cetuximab 500mg/m2 biweekly combined with fruquintinib according to the confirmed dose in phase Ⅰ, taking it once daily for the first 21 days of each 28-day cycle. The number of cases is 20.Response assessment via CT/MRI is to be done q8 wks (RECIST 1.1). Continue until disease progression or unacceptable toxicity. The primary objective is to estimate safety, grade 3/4 adverse, and DLT. Secondary objectives include ORR, PFS, and OS. Final analysis to be done 6 mo after enrollment of the final pt. Clinical trial information: ChiCTR2000038227 . Research Sponsor: None

Objective: The aim of this study was to identify heart failure (HF)-specific circulating micro-RNAs (miRNA), and examine whether the selected miRNAs correlate with myocardial fibrosis and are reflective of the incidence of adverse cardiovascular events in patients with stage C or D HF. Methods: Circulating miRNAs which were expressed in end-stage HF patients and matched healthy controls were detected by microarray analysis and validated by quantitative real-time polymerase chain reaction. Multivariate Cox regression analysis was performed to determine whether the selected circulating miRNAs could be prognostic factors in HF patients. Results: In a cohort of 7 healthy controls and 9 patients with stage C or D HF, 7 miRNAs were differentially expressed. These miRNAs were further investigated in a second cohort of 80 patients with stage C or D HF and 30 healthy controls. Only miR-197-5P correlated with fibrosis as seen in cardiac magnetic resonance imaging in patients under the age of 50 years with stage C or D HF (r = 0.42, p = 0.008). Multivariate analyses revealed that miR-197-5P was also a risk factor for composite endpoint events in patients under the age of 50 years with stage C or D HF. Conclusion: miR-197-5P is a circulation miRNA that correlates with MF and adverse cardiac events in HF patients under the age of 50 years.

Zinc (Zn) highly concentrates in the brain and plays a key role in memory formation and learning processes. Zn deficiency results in cognitive impairments, memory deficits, alterations of neuropsychological behavior, and motor development. Although Zn-enriched yeast (ZnY) is widely used for dietary fortification and supplementation of Zn, the effect of ZnY on cognition still remains unclear. The purpose of the study was to investigate the effect of ZnY on behavior in Zn-deficient and Zn-sufficient rats. Three-week-old rats were fed low Zn diets for 145 days to establish Zn-deficient rats. ZnY was orally administered to Zn-deficient rats at three dose levels of 1, 2, and 4 mg Zn/kg/day for 55 days. Rat appearance, body weight, plasma and brain Zn, Morris water maze test, and step-through passive avoidance test were observed. Compared to Zn-sufficient rats, body weight gain, plasma zinc level, resident time, and step-through time in Zn-deficient rats were significantly lower. Zn deficiency impaired functions of learning and memory, while ZnY as a plausible therapeutic intervention alleviated the cognitive impairments caused by Zn deficiency.

Background Distant metastasis is the major cause of treatment failure in patients with nasopharyngeal carcinoma (NPC). Although several biomarkers correlate with metastasis and prognosis, the molecular mechanisms of NPC development and progression remain unclear. Methods Quantitative RT-PCR (qRT-PCR), western blotting, cell growth, foci formation, migration and invasion assays, and xenograft mouse models were utilized to examine the expression levels and functions of the CXCL5/CXCR2 axis in NPC. A luciferase reporter assay, western blotting, immunofluorescence, and migration and invasion assays were used to identify and verify the ERK/GSK-3β/Snail signalling pathway. Results CXCL5 was significantly increased in the sera of NPC patients, and high expression levels of CXCL5/CXCR2 in NPC primary tissues indicated poor survival. CXCL5 and CXCR2 were upregulated in NPC cell lines. Ectopic expression of the CXCL5/CXCR2 axis promoted NPC cell migration and invasion in vitro and the formation of lung metastases in vivo. Mechanistically, the dual overexpression of CXCL5 and CXCR2 promoted cell spreading by inducing the epithelial-mesenchymal transition (EMT) through the activation of the ERK/GSK-3β/Snail signalling pathway. Conclusion The CXCL5/CXCR2 axis contributes to the EMT of NPC cells by activating ERK/GSK-3β/Snail signalling, and this axis may be a potential diagnostic marker and therapeutic target for patients with NPC. Electronic supplementary material The online version of this article (10.1186/s13046-018-0722-6) contains supplementary material, which is available to authorized users.

Background: Rheumatic heart disease (RHD) is a predominant health concern in developing countries. The aim of this meta-analysis was to evaluate the outcomes of mitral valve (MV) repair in patients with RHD, and identify predictors that may postoperatively affect treatment outcome. Methods: A meta-analysis of eligible studies assessing patients undergoing MV repair with RHD and reporting the outcomes of MV repair, including 30-day mortality and long-term follow-up survival, MV reoperation rate and postoperative adverse events. Relevant English articles were searched up to 1 March, 2017 in Web of Science, PubMed, Google Scholar, Cochrane Library, EmBase, Elsevier, and Science Direct. Selected studies should meet all inclusion criteria, and underwent data extraction. Results: A total of ten studies with 2,770 patients met all inclusion criteria, and were selected for assessment. Pooled analysis showed that 30-day mortality in patients with rheumatic MV disease after MV repair surgery was 1.9%, 95% confidence interval (CI) (0.8–2.9%); long-term survival was 97.3%, 95% CI (95.9–98.6%), and a freedom from reoperation rate of 93.6%, 95% CI (91.4–95.9%) was obtained; freedom from adverse events was 97.5%, 95% CI (95.2–99.8%). Conclusions: The outcome of rheumatic MV repair is outstanding in terms of low early mortality, high long-term survival and freedom from valve-related complications, which may be very common in patients after rheumatic MV replacement; meanwhile, MV reoperation rate after initial surgery is acceptable. Surgeons may try to repair MV in RHD when it is feasible

a Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart Lung and Blood Vessel Diseases, The Key Laboratory of Remodeling-related Cardiovascular Diseases, Ministry of Education, Department of Atherosclerosis, 2 Anzhen Road, ChaoYang District, Beijing 100029, China b Department of Radiology, The China–Japan Friendship Hospital, Beijing 100029, China c Department of Cardiac Surgery, Beijing Anzhen Hospital, Capital Medical University, 2 Anzhen Road, Chaoyang District, Beijing 100029, China d Department of Imaging, Beijing Anzhen Hospital, Capital Medical University, 2 Anzhen Road, Chaoyang District, Beijing 100029, China e Department of Emergency, Beijing Anzhen Hospital, Capital Medical University, 2 Anzhen Road, Chaoyang District, Beijing 100029, China f National Engineering Laboratory for Druggable Gene and Protein Screening, Northeast Normal University, Changchun 130024, Jilin, China g Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100029, China

Objective The purpose of the present study was to assess the efficacy of the long-term results after video-assisted pulmonary vein isolation and left atrial appendage excision for lone atrial fibrillation (AF) and to determine the most significant risk factors for the long-term results. Methods From December 2006 to December 2012, 332 consecutive patients with lone AF underwent minimally invasive surgical ablation at our center. Of the 332 patients, 91, who had undergone video-assisted pulmonary vein isolation >5 years earlier, were evaluated in the present study (48 with paroxysmal AF, 21 with persistent AF, and 22 with long-standing persistent AF). The median follow-up period was 66 months. The primary endpoint was the success rate of video-assisted pulmonary vein isolation, defined as the absence of any atrial arrhythmia recurrence lasting >30 seconds at the clinical visit and on the electrocardiogram or long-term cardiac rhythm recording after discharge. Results During the follow-up period, 1 patient (1.1%) experienced a stroke and 4 (4.4%) died of noncardiac disease. At the 5-year follow-up point, 43 of 78 patients (55.1%) were in normal sinus rhythm. Of the 39 patients with paroxysmal AF and 39 with nonparoxysmal AF, 27 (69.2%) and 16 (44.1%) were in normal sinus rhythm, respectively. The results of the univariate and multivariate analyses of the preoperative risk factors for AF recurrence showed a left atrial diameter of ≥44 mm (hazard ratio, 5.56; 95% confidence interval, 1.68-18.387; P = .005) and an AF duration of ≥31.5 months (hazard ratio, 3.67; 95% confidence interval, 1.50-8.95; P = .004) were the most significant independent risk factors. Conclusions Patients with lone AF with a large preoperative left atrial diameter and long AF duration will not be suitable for video-assisted pulmonary vein isolation alone and might need to undergo ablation of the lesions.

Purpose The aims of this study were to present an uncommon intracranial germinoma manifesting as skull base extension and analyze its clinical characteristics to give valuable insight into such uncommon radiologic variant. Methods This is a clinical study of a 15-year-old girl with intracranial germinoma manifesting as skull base extension. Clinical characteristics, magnetic resonance imaging scan observations, pathologic findings, and flow of the treatment procedure were presented and analyzed. Results She had a 5-month history of diuresis and diplopia. magnetic resonance imaging observation displayed a neoplasm located in the right-side central skull base and suprasellar area with wide extension into the cavernous sinus, intraorbital region, ethmoidal sinus, sphenoid sinus, and pituitary fossa. After administration of contrast medium, strong and heterogeneous enhancement of the mass was observed, with a dural tail sign along the right cerebellar tentorial. Right pterional approach was performed, and intraoperative histologic examination suspected the diagnosis of germinoma; partial resection was achieved, and postoperative radiotherapy was administered. Cranial nerve palsy improved greatly 6 months postoperatively. Conclusions Although highly unusual, germinoma should be included in the differential diagnosis of all masses with extension along the midline region of skull base, especially when it happens in young female patients.

To investigate the association of LIG1 with the risk of lung cancer, all subjects of unrelated ethnic Han Chinese in Liaoning Province were involved in a hospital-based case-control study. The case group consisted of 370 histologically diagnosed lung cancer patients; 314 controls were selected from cancer-free patients during Dec. 2009 to Dec. 2011. LIG1 rs1050298SNP were analyzed by TaqMan real-time PCR method. All statistical analyses were performed with Statistical Product and Service Solution sv13.0 (SPSS). The genotype distribution frequency of LIG1 rs1050298 SNP displayed significant difference between the case and the control group. Individuals carrying the LIG1 rs1050298 T genotype had higher risks of lung cancer, especially those with squamous cell carcinoma.

Background and Aim Ganglionated plexi (GP) ablation has been become an important strategy for treating atrial fibrillation (AF). We hypothesize that active GP is a predictor of AF recurrence after minimally invasive surgical AF ablation. Methods Eighty-nine patients with symptomatic lone AF undergoing minimally invasive surgical pulmonary vein isolation combined with GP testing and ablations were followed for a median of 50 months. Success was defined as freedom from any atrial tachyarrhythmia lasting >30 seconds duration. Results The single-procedure success rate is 56.3% for paroxysmal AF, 27.3% for persistent AF, and 25% for long-term persistent AF. A mean of 4.1 active GPs were identified in each patient. There were more active GP on the right side than on the left side (2.8 ± 2.2 vs. 1.4 ± 1.2, p 24 months, early recurrence of AF, and left atrial diameter also predicted long-term recurrences of AF. Conclusions The number of active GP is a predictor of AF recurrence after minimally invasive surgical AF ablation. Patients with more active GP were associated with markedly higher single-procedure success rates. doi: 10.1111/jocs.12299 (J Card Surg 2014;29:279–285)

Background Peripheral blood-based gene expression patterns have been investigated as biomarkers to monitor the immune system and rule out rejection after heart transplantation. Recent advances in the high-throughput deep sequencing (HTS) technologies provide new leads in transcriptome analysis. Methods By performing Solexa/Illumina's digital gene expression (DGE) profiling, we analyzed gene expression profiles of PBMCs from 6 quiescent (grade 0) and 6 rejection (grade 2R&3R) heart transplant recipients at more than 6months after transplantation. Subsequently, quantitative real-time polymerase chain reaction (qRT-PCR) was carried out in an independent validation cohort of 47 individuals from three rejection groups (ISHLT, grade 0,1R, 2R&3R). Results Through DGE sequencing and qPCR validation, 10 genes were identified as informative genes for detection of cardiac transplant rejection. A further clustering analysis showed that the 10 genes were not only effective for distinguishing patients with acute cardiac allograft rejection, but also informative for discriminating patients with renal allograft rejection based on both blood and biopsy samples. Moreover, PPI network analysis revealed that the 10 genes were connected to each other within a short interaction distance. Conclusions We proposed a 10-gene signature for heart transplant patients at high-risk of developing severe rejection, which was found to be effective as well in other organ transplant. Moreover, we supposed that these genes function systematically as biomarkers in long-time allograft rejection. Further validation in broad transplant population would be required before the non-invasive biomarkers can be generally utilized to predict the risk of transplant rejection.

To assess the activity and safety of postoperative adjuvant immunotherapy with transfusion of cytokine-induced killer (CIK) cells combined with chemotherapy in patients with colorectal cancer.We retrospectively studied 96 consecutive patients with colorectal cancer who were treated with resection between January 2010 and December 2012 as well as adjuvant chemotherapy. Twenty-one of these patients accepted at least 1 cycle of CIK cell transfusion for immunotherapy (CIK group). Disease free survival (DFS), immune cells and treatment related side effects were assessed. The patients were followed up until May 2013.By the end of follow-up, 10 patients (10.42 %) had died. Eighteen patients (18.75 %) had withdrawn. All the patients in the CIK group are still alive, and only 1 patient had withdrawn. Patients in the CIK group had significantly longer DFS than those in the control group [HR = 0.28, 95 % CI (0.09, 0.91), p = 0.034]. The 2-year DFS rates of patients in the CIK group and the control group were 59.65 ± 24.80 % and 29.35 ± 6.39 %, respectively. The CD4(+)/CD8(+) ratios were significantly lower during the period of chemotherapy than those before chemotherapy (p = 0.0038), while the ratios were significantly higher during the period of CIK cell transfusion than those before CIK therapy (p = 0.0484). There were no immediate adverse reactions to the CIK cell transfusions.Adjuvant transfusion of CIK cells prolongs DFS in patients with colorectal cancer.

Chronic inflammation plays an important role in nasopharyngeal carcinoma (NPC) development and progression. Aim of this study is to determine whether inflammation-related parameters predict distant metastasis in NPC patients.335 newly diagnosed non-metastatic NPC patients were recruited. The values of the C-reactive protein (CRP), lactate dehydrogenase, albumin, globulin, white blood cell and neutrophil at baseline were measured.Among the above six parameters, only CRP was independently associated with distant metastasis-free survival (DMFS). CRP concentration of advanced T-/TNM-classification patients was higher than those with early classification (P = 0.001). Higher-CRP (CRP ⩾ 2.46 mg/L) predicted shorter overall survival, disease-free survival and DMFS than lower-CRP (CRP2.46 mg/L). In a multivariable model, higher-CRP and advanced N-classification were independent predictors of distant metastasis. On the basis of these two parameters, a prognostic NC-model was developed as following: (1) low-risk (early N-classification and lower-CRP); (2) intermediate-risk (advanced N-classification or higher-CRP) and (3) the high-risk distant metastasis (advanced N-classification and higher-CRP). When compared with the low-risk group, the hazard ratios (HRs) for distant metastasis and death for the intermediate-/high-risk patients were 3.6/16.1 and 2.26/7.61, respectively (both P0.001).We developed a new prognostic model based on CRP and N-classification for predicting distant metastasis and death of NPC patients, which may facilitate patient counselling and individualised treatment.

The female sex is traditionally considered a favorable prognostic factor for nasopharyngeal carcinoma (NPC). However, no particular study has reported this phenomenon. To explore the prognostic impact of gender on patients with NPC after definitive radiotherapy, we reviewed the clinical data of 2063 consecutive patients treated between 1st January 2000 and 31st December 2003 in the Sun Yat-sen University Cancer Center. The median follow-up for the whole series was 81 months. The female and male patients with early stage disease comprised 49.4% and 28.1% of the patient population, respectively. Both the 5-year overall survival (OS) and disease-specific survival (DSS) rates of female patients were significantly higher than those of male patients (OS: 79% vs. 69%, P < 0.001; DSS: 81% vs. 70%, P < 0.001). For patients with locoregionally advanced NPC, the 5-year OS and DSS rates of female vs. male patients were 74% vs. 63% (P < 0.001) and 76% vs. 64%, respectively (P < 0.001). A multivariate analysis showed that gender, age, and TNM stage were independent prognostic factors for the 5-year OS and DSS of NPC patients. The favorable prognosis of female patients is not only attributed to the early diagnosis and treatment but might also be attributed to some intrinsic factors of female patients.

To investigate the protective effect of hypothermia (HT) on brain injury in moderate traumatic brain injury (TBI) rat models and the potential mechanisms, especially the involvement of RIPK1 in apoptosis and necroptosis.Adult Sprague-Dawley rats were randomized to four groups: sham+normothermia (sham+NT), sham+hypothermia (sham+HT), moderate TBI+normothermia (TBI+NT) and moderate TBI+hypothermia (TBI+HT). The sham+HT and TBI+HT groups were submitted to 32°C for 6 hours. The regional cerebral blood flow (rCBF) was assessed 24 hours after TBI; 24 and 48 hours after TBI, the modified neurological severity score (mNSS) was assessed. Immediately after behavioural tests, rats were sacrificed to harvest the brain tissues.mNSS scores were lower in the TBI+HT group compared with the TBI+NT group (p0.01) and cerebral blood flow was better (p0.01). HE staining of the cortex and ipsilateral hippocampus showed pyknotic and irregularly shaped neurons in TBI+NT rats, which were less frequent in TBI+HT rats. The TBI+NT and TBI+HT groups showed higher TNF-α, TRAIL, FasL, FADD, caspase-3, caspase-8, PARP-1, RIPK-1 and RIPK-3 levels than the sham+NT group (all p0.05), but the levels of these proteins were all lower in the TBI+HT group compared with the TBI+NT group (all p0.01).HT treatment significantly reduced RIPK-1 upregulation, which may inhibit necroptosis and apoptosis pathways after moderate TBI.

Bile duct hamartoma (BDH) is a rare liver disease with a rising incidence in recent years. A retrospective study on BDH patients between June 2007 and December 2015 was conducted. All the medical records, including clinical, imaging and pathological characteristics, were retrieved. Follow-up data were obtained by telephone communication. The majority of the patients had no symptoms and the laboratory tests were normal. The appearance on ultrasound examination was variable. The lesion exhibited low density on plain computed tomography and no enhancement in 4 cases, and inhomogeneous enhancement in 1 case. Magnetic resonance imaging examination revealed hypointensity on T1-weighted imaging (WI), hyperintensity on T2WI, no enhancement in 1 case, and enhancement in 4 cases. Two patients underwent magnetic resonance cholangiopancreatography due to jaundice and intrahepatic bile duct dilation. The preoperative diagnosis was liver cancer in 4 cases, hepatic hilar biliary obstruction in 1, chronic calculous cholecystitis in 1, suspected hepatic abscess in 1, and benign liver tumor in 2 cases. All the patients underwent surgery. Nest-like cell arrangements were observed in 2 patients, and in 1 patient the lesion transformed to intrahepatic cholangiocarcinoma, resulting in the patient's death 25 months after surgery. Thus, BDH may transform into a life-threatening cholangiocarcinoma and it should be surgically removed. Furthermore, the mechanism underlying carcinogenesis in BDH requires further investigation.

BackgroundThis study assessed the role of surgical ablation for atrial fibrillation (AF) in decreasing tricuspid regurgitation (TR) and right‐sided heart remodeling in patients after mitral valve procedure.Methods and ResultsBetween 1994 and 2014, 1568 consecutive patients withAFundergoing mitral valve procedure were identified. In 26.0% (n=408), surgical ablation ofAFwas used. Propensity‐score matching (PSM) was performed on the basis of 41 known perioperative risk variables. Survival, reoperation, stroke, and moderate‐to‐severeTR, as well as echocardiography indices in long‐term follow‐up, were compared in 406 matched patient pairs (ablated and nonablated groups). The nonablated group showed significantly higher risks of death (hazard ratio [HR], 1.644; 95%CI, 1.081–2.501;P=0.020), reoperation (HR, 2.644; 95%CI, 1.299–5.466;P=0.008), and moderate‐to‐severeTR(HR, 1.436; 95%CI, 1.059–1.948;P=0.020), associated with a significantly deteriorated cardiac function, progression ofTR, and right‐sided heart remodeling after 5‐year follow‐up. In a subgroup comparison of ablated patients with sinus rhythm versusAFrecurrence, aPSManalysis was performed at the 5‐year follow‐up. The recurrent group showed significantly higher risks of moderate‐to‐severeTR(HR, 2.427; 95%CI, 1.261–4.671;P=0.008).AFrecurrence was associated with progressiveTRand significant deterioration in right‐sided heart remodeling.ConclusionsIn a retrospectivePSManalysis, mitral valve disease withAFwas associated withTRprogression as well as right‐sided heart remodeling, which are alleviated by surgical ablation.

Papillary meningioma is an uncommon meningioma subtype of World Health Organization grade III. It could show some radiologic profiles pointing to malignant behavior, such as a cystic change, a heterogeneous enhancement, and an ill- defined border. However, to date, the radiologic profile described in this article has not been reported in previous literatures, and it is just the characteristic being considered as the major cause for patients’ death. A 16-year-old adolescent boy with a 6-month history of headache was admitted to our department on June 28, 2012. Magnetic resonance imaging showed a giant well-defined mass in the left temporal region, with a severe flow void on T2-weighted image and an abundant stripelike enhancement on T1-weighted contrast-enhanced scan. In view of its middle cranial fossa location (one predilection site for meningioma), meningioma was suspected preoperatively. A regular left frontotemporal craniotomy was performed. Unexpectedly, extreme hemorrhage happened intraoperatively, and it was difficult to stop the bleeding. After identification of no hemorrhage in the operative cavity through intraoperative magnetic resonance imaging, the operation was finished, with an overall blood loss of 15,000 mL. The patient died of brain stem dysfunction the second day after the operation.

BACKGROUND Dual-specificity phosphatase 6 (DUSP6) inactivates different target kinases to regulate cell proliferation and differentiation. Altered DUSP6 expressions or gene polymorphisms are associated with human cancer development including non-small cell lung cancer (NSCLC). DNA topoisomerase II alpha (TOP2A) regulates chromosome condensation and chromatid separation, and altered TOP2A expressions are associated with drug resistance development. This study assessed DUSP6 and TOP2A single nucleotide polymorphisms (SNPs) associated with NSCLC patient survival. METHODS This study included 152 surgically resected NSCLC patients and 277 chemoradiotherapy treated inoperable cases. DNA samples from each patient were genotyped for DUSP6 and TOP2A SNPs. Kaplan-Meier survival analysis, log-rank test, and Cox proportional hazard model were used to evaluate the association between these variants and NSCLC overall survival. RESULTS DUSP6 rs2279574 A/A genotype was associated with significantly poor inoperable NSCLC patient overall survival (A/A vs. C/C, adjusted HR = 1.549, 95% CI = 1.019-2.355). Stratification analysis against clinical stage, histology, weight loss, and ECOG performance status revealed that the DUSP6 rs2279574 A/A variant homozygous genotype is associated with a decrease in survival of stage IV NSCLC patients compared to those with the C/C genotype (log-rank, p = 0.003). No association was found among histology, weight loss, and ECOG performance status. Moreover, there was no association of TOP2A SNPs between clinicopathological and survival data. CONCLUSIONS Data obtained from the current study demonstrated that functional DUSP6 rs2279574 polymorphism was able to predict inoperable NSCLC patient survival after chemoradiotherapy.

Background The outcomes of atrial fibrillation (AF) between biatrial maze (BAM) and left atrial maze (LAM) are still controversial. The purpose of this study was to compare the clinical and rhythm outcomes between BAM and LAM in patients with AF. Methods Electronic databases and article references were systematically searched (1990-2014) to access relevant studies. Odds ratio (OR) and weight mean difference (WMD) with 95% confidence interval (CI) were reported. Results Fourteen studies with 2,075 patients were finally involved in the present meta-analysis. The rate of restored sinus rhythm (SR) was similar in BAM and LAM groups (OR: 1.25, 95% CI: 0.91-1.72, p = 0.163). BAM reduced the prevalence of atrial flutter during follow-up (OR: 0.12, 95% CI: 0.01-0.96, p = 0.046). Compared with BAM, LAM shorten aortic cross-clamping time (WMD = 9.05 minutes, 95% CI: 1.28-16.82, p = 0.023) and cardiopulmonary bypass time (WMD = 20.21 minutes, 95% CI: 7.40-33.03, p = 0.002). No significant difference was found between groups in the risk of death (OR: 1.22, 95% CI: 0.70-2.14, p = 0.233), cerebrovascular events (OR: 1.44, 95% CI: 0.51-4.06, p = 0.493), and reoperation for bleeding (OR: 1.34, 95% CI: 0.70-2.55, p = 0.374). However, the risk for implantation of permanent pacemaker was significantly higher in BAM group (OR: 2.60, 95% CI: 1.09-6.20, p = 0.031). Conclusion No significant difference was found between BAM and LAM in the rate of restored SR, the risk of death, cerebrovascular events, and reoperation for bleeding. BAM is superior to LAM in reducing the prevalence of atrial flutter during follow-up, but LAM shortens the aortic cross-clamping time and cardiopulmonary bypass time, and decreases the risk of permanent pacemaker implantation.

There is increasing concern about neurologic injury due to deep hypothermia with low flow during repair of complex congenital heart defects in neonates and infants. Twenty infants with ventricular septal defect and pulmonary hypertension were randomly assigned to cardiac repair under deep hypothermia with circulatory arrest or deep hypothermia with low flow. Measurements of static pulmonary compliance, airway resistance, and respiratory index were performed before institution of cardiopulmonary bypass and at 5 minutes and 2 hours after cessation of cardiopulmonary bypass. Both groups had significant pulmonary dysfunction in terms of static pulmonary compliance, airway resistance, and respiratory index. There was greater impairment of pulmonary compliance and respiratory index after deep hypothermia with low flow, and this group required longer intensive care unit stay.

Purpose The Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors (EGFR-TKIs) have been used as first line treatment in advanced Non-Small Cell Lung Cancer (NSCLC) with sensitive EGFR gene mutations. In clinical practice, we found that the rate of EGFR gene mutation in patients with Yin-cold syndrome type in traditional Chinese medicine (TCM) theory was higher than those with Yang-heat type syndrome. The purpose of this study was to identify the relationship between the TCM syndrome type and the EGFR gene status as well as efficacy of EGFR-TKIs in NSCLC patients. Methods From March 2013 to January 2014, we prospectively studied all the patients who are newly diagnosed with NSCLC without prior anticancer therapy, or those with recurrence with an interval of more than 6 moths from last anticancer therapy to the recurrence. The symptoms and signs which can help for the TCM syndrome type diagnosis were recorded. The EGFR gene statuses were also tested. The Yang-heat or Yin-cold syndrome types of TCM were diagnosed respectively by 3 TCM experts of our hospital to decide the TCM syndrome type. The relationship between the EGFR gene status and the TCM syndrome type were analyzed. The patients were followed up until August 2014. Results A total of 73 consecutive patients were enrolled in our study. 32 patients (43.84%) were with the Yin-cold syndrome type according to the TCM theory, while the other 41 patients (56.16%) were with the Yang-heat type. 17 patients (53.13%) in the Yin-cold group, while only 10 patients (24.39%) in the Yang-heat group, were with sensitive EGFR gene mutation (p=0.0120). 1 in the Yin-cold group and 1 in the Yang-heat group were with T790M at the exon 20 of EGFR gene. The EGFR genes were wild type in the other 44 patients. No significant difference was seen in PFS or OS between the TCM syndrome groups for those 22 patients who took EGFR-TKIs. Conclusion Patients with Yin-cold TCM syndrome type have more chance with sensitive EGFR gene mutation. However, no relationship was seen between the efficacy of EGFR-TKIs and TCM syndrome type.

Collecting evidence has shown that type 2 diabetes mellitus is a high risk factor of late-onset Alzheimer's disease (AD); the energy metabolic dysfunction is thought to be a convergent point of the two diseases. However, the underlying mechanisms of diabetes-associated AD are still unclear. In the current study, we investigated the roles of AMPK in diabetes-related AD-like pathologic features in models of intracerebroventricular-streptozotocin (ICV-STZ) animals. Rats infused with STZ (3 mg/kg, once) were followed by injection of AICAR (AMPK activator) or vehicle via ICV. We found that the level of p-AMPK (active type of AMPK) and SIRT1 activity were decreased and the level of phosphorylated tau was increased at Ser396 and Thr231 sites in ICV-STZ rats when compared with control rats. Mitochondria from ICV-STZ rats displayed a significant decrease in mitochondrial membrane potential, complex I activity, ATP level, and superoxide dismutase activity as well as an increase of reactive oxygen species production when compared with that from control rats. Meanwhile the number of apoptotic cell confirmed by cleaved caspase-3 (active type of caspase-3) staining was also stronger in ICV-STZ rats than control rats. All pathological changes including biochemistry and cognitive function could be mitigated through rescuing AMPK activity with its specific activator (AICAR) in ICV-STZ rats. Taken together, these results suggested that AMPK activation improves AD-like pathological changes via repairing mitochondrial functions in ICV-STZ rats.

Objectives: Residual tricuspid regurgitation (TR) that has developed after isolated left-sided valve surgery is not uncommon. Indications for concomitant tricuspid repair at the initial operation have not been well established. The selection of high-risk preoperative patients is of great importance in this situation. Methods: Six databases were searched to access eligible articles reporting potential risk factors for the development of residual TR. The pooled analysis of risk factors was based on odds ratios or mean differences with their 95% confidence intervals. Results: A total of 3,138 patients with 487 residual TR in 11 studies were analyzed. Of the 14 candidate parameters in our meta-analysis, 10 factors, i.e. older age, female gender, atrial fibrillation, rheumatic etiology, mitral valve surgery, previous valve surgery, a long time from onset to surgery, 2+/3+ TR and enlarged left and right atria, were found to be significantly associated with the development of residual TR. Conclusions: Our study highlights the role of the above preoperative risk factors in the development of residual TR after isolated left-sided valve surgery and emphasizes the need of further studies to investigate other potential predictors. Moreover, predictive models or scoring systems for the identification of patients at a high risk for developing late TR are urgently needed.

BACKGROUND: Ganglionated plexi (GP) ablation has been become an adjunct to pulmonary vein isolation (PVI). This study describes the long-term results of minimally invasive surgical PVI, ablation of GPs, and exclusion of the left atrial appendage for atrial fibrillation (AF). METHODS: Long-term follow-up of 55 months was performed in 139 consecutive patients (age 58.3±20.8 years) with symptomatic, drug-refractory lone AF who underwent minimally invasive surgical PVI, GPs ablation, and exclusion of the left atrial appendage. Success was defined as freedom from AF, atrial flutter, or atrial tachycardia off antiarrhythmic drugs. RESULTS: AF was paroxysmal in 77.7%, persistent in 12.2% and long-standing persistent in 10.1%. Single-procedure success rate was 71.7%, 59.4% and 46.6% at 12, 24 and 60 months respectively. Single-procedure success rate was 72.9%, 62.6% and 51.8% for paroxysmal AF, 64.7%, 35.3%, and 28.2% for persistent AF, 71.4%, 64.3% and 28.6% for long-standing persistent AF at 12, 24 and 60 months respectively. Duration of AF>24 months (hazard ratio [HR]: 3.09, 95% confidence interval [CI]: 1.51 to 6.32; p = 0.002), left atrial diameter≥40 mm (HR: 4.03, 95% CI: 1.88 to 8.65; p

Background Aberrant expression of C-X-C motif chemokine 5 (CXCL5) contributes to the progression of various cancers. This study analyzed the clinical significance of serum CXCL5 (sCXCL5) levels of nasopharyngeal carcinoma (NPC) patients, with the goal of building a novel prognostic score model. Experimental Design Serum samples were collected prior to treatment from 290 NPC patients for the detection of sCXCL5 with ELISA. Half of the patients (n = 145) were randomly assigned to the training set to generate the sCXCL5 cutoff point using receiver operator characteristic (ROC) analysis, while the other half (n = 145) were assigned to the testing set for validation. Associations between sCXCL5 levels and clinical characteristics were analyzed. A prognostic score model was built using independent predictors derived from multivariate analysis. A concordance index (C-Index) was used to evaluate prognostic ability. Results The sCXCL5 cutoff point was 0.805 ng/ml. Sex, age, histology, T classification, clinical classification and local recurrence were not associated with sCXCL5 levels. However, sCXCL5 levels were positively associated with N classification, distant metastasis and disease progression (P

The purpose of this prospective study is to investigate the predictive and prognostic significance of the Raf kinase inhibitory protein (RKIP) in locoregionally advanced nasopharyngeal carcinoma (NPC). Immunohistochemical assays were performed to detect the RKIP protein expression of samples from 212 patients with locoregionally advanced NPC. All patients were assigned randomly into the inductive chemotherapy plus radiation therapy (IC + RT) group, the concurrent chemoradiotherapy (CCRT) group, the inductive chemotherapy plus concurrent chemoradiotherapy (IC + CCRT) group, and the radiation therapy alone (RT) group. The patients in the IC + RT group were treated with IC using 2-3 cycles of cisplatin (80 mg/m(2)) and fluorouracil (500 mg/m(2)), repeated every 3 weeks, followed by radiotherapy. Those in the CCRT group were treated with weekly cisplatin (40 mg/m(2)) for 6-7 cycles during radiotherapy. In the IC + CCRT group, the chemotherapy prior to radiation was similar to the cisplatin-fluorouracil regimen in the IC + RT group, whereas it cisplatin regimen was identical to that in the CCRT group. The results show that RKIP is an independent prognostic factor for 5-year distant metastasis-free survival (DMFS), overall survival (OS), and progression-free survival (PFS). Patients with high RKIP expression benefited more from reduced metastasis in the IC + RT and the IC + CCRT group, with improved OS and PFS in each treatment group compared with that among patients with low RKIP expression. In the high RKIP expression subgroup, chemotherapy combined with radiotherapy improved the DMFS when compared with the RT group, but this effect was not observed in the low RKIP expression subgroup. RKIP was predictive of distant metastasis with good sensitivity and specificity. Clinically, high RKIP expression inhibited distant metastasis in advanced NPC, and its detection might be used to predict distant metastasis with good sensitivity and specificity. The effect of chemotherapy on distant metastasis in combined chemoradiotherapy might be related to the RKIP expression level. Patients with high RKIP expression showed more improved OS and PFS than their low RKIP expression counterparts. Higher RKIP expression improves the DMFS of patients who receive inductive high-dose cisplatin-based chemoradiotherapy, with or without concurrent cisplatin. Low RKIP expression is also a predictive marker for cancer progression and metastasis, which could be used to stratify patients with high risk of metastasis and death.

BACKGROUND The purpose of this prospective study was to investigate the predictive significance of Raf kinase inhibitory protein (RKIP) in locoregionally advanced nasopharyngeal carcinoma (NPC) and its effect on distant metastasis. METHODS The usual immunohistochemical stainings were performed to detect RKIP expression of cancer tissues from 210 patients with advanced NPC. After DNA samples from pretreatment plasma from these patients were extracted, real-time polymerase chain reaction (PCR) was performed to quantitatively analyze plasma Epstein-Barr virus (EBV) DNA. RESULTS RKIP expression was significantly different for different N classifications and WHO pathologic grades, respectively (p < .05). Cox regression confirmed RKIP and EBV DNA were independent prognostic markers for 5-year distant metastasis-free survival (DMFS). In the high RKIP expression group, chemotherapy had a positive effect on improved DMFS, but not in the low RKIP expression group. CONCLUSIONS RKIP could be identified as an independent prognostic factor on DMFS. For each combined treatment modality, the different impact of chemotherapy on distant metastasis might be related to the RKIP expression level.

To evaluate the prognostic potential of serum CCL2 (sCCL2) and serum TNF-α (sTNF-α) in nasopharyngeal carcinoma (NPC) before treatment by analysing the expression of these two markers.Both sCCL2 and sTNF-α were prospectively detected in 297 NPC patients with enzyme-linked immunosorbent assay (ELISA) before treatment. The correlations between sCCL2 level or sTNF-α level and patient's survival were evaluated.For sCCL2, the 5-year overall survival (OS) and 5-year distant metastasis-free survival (DMFS) of high expression group and low expression group were 64% versus 81% and 67% versus 84% (P0.05), respectively. For sTNF-α, the 5-year OS and 5-year DMFS of high expression group and low expression group were 62% versus 79% and 66% versus 82% (P0.05), respectively. The 5-year OS and 5-year DMFS for both positive patients, one marker positive patient and both negative patients were 53% versus 77% versus 85% and 58% versus 80% versus 86% (P0.05), respectively. Concentrations of sCCL2 and sTNF-α in patients with large skull base invasion were higher than those without or with small skull invasion (P0.05). Patients who developed bone metastasis alone after radical treatment had higher pre-treatment concentrations of sCCL2 and sTNF-α than those without metastasis (P0.001). Multifactorial Cox regression analyses demonstrated that T/N/M classification, chemotherapy, sCCL2 level and sTNF-α level were independent predictors of OS and DMFS of NPC patients.High expression levels of sCCL2 and sTNF-α predict bone invasion, post-treatment distant metastasis and poor overall survival in NPC patients.

Pentacuspid aortic valve is an extremely rare congenital aortic valve anomaly. In this case, pentacuspid aortic valve with severe aortic regurgitation was detected by transthoracic echocardiography and multiple-detector computed tomography; the patient recovered smoothly after aortic valve replacement.

To investigate the association of LIG1 with the risk of lung cancer, all subjects of unrelated ethnic Han Chinese in Liaoning Province were involved in a hospital-based case–control study. The case group consisted of 370 histologically diagnosed lung cancer patients; 314 controls were selected from cancer-free patients during Dec. 2009 to Dec. 2011. LIG1 rs1050298SNP were analyzed by TaqMan real-time PCR method. All statistical analyses were performed with Statistical Product and Service Solution sv13.0 (SPSS). The genotype distribution frequency of LIG1 rs1050298 SNP displayed significant difference between the case and the control group. Individuals carrying the LIG1 rs1050298 T genotype had higher risks of lung cancer, especially those with squamous cell carcinoma.