Highly efficient field-free switching of perpendicular yttrium iron garnet with collinear spin current.

Yttrium iron garnet, a material possessing ultralow magnetic damping and extraordinarily long magnon diffusion length, is the most widely studied magnetic insulator in spintronics and magnonics. Field-free electrical control of perpendicular yttrium iron garnet magnetization with considerable efficiency is highly desired for excellent device performance. Here, we demonstrate such an accomplishment with a collinear spin current, whose spin polarization and propagation direction are both perpendicular to the interface. Remarkably, the field-free magnetization switching is achieved not only with a heavy-metal-free material, Permalloy, but also with a higher efficiency as compared with a typical heavy metal, Pt. Combined with the direct and inverse effect measurements, we ascribe the collinear spin current to the anomalous spin Hall effect in Permalloy. Our findings provide a new insight into spin current generation in Permalloy and open an avenue in spintronic devices.

Risk prediction of CISS classification in endovascular treatment of basilar artery stenosis.

Objective: To investigate the incidence of ischemic stroke complications after endovascular treatment for basilar artery stenosis used preoperative high-resolution magnetic resonance vascular wall imaging (HRMR/VWI) and diffusion-weighted imaging (DWI). Methods: The clinical data of 47 patients with severe symptomatic basilar artery stenosis (stenosis rate ≥70 %) treated with endovascular therapy at the Neuro-interventional Center from December 2017 to December 2021 were retrospectively analyzed. High-resolution magnetic resonance angiography (HRMR VWI) and DWI were used to evaluate the location of atherosclerotic plaque at basilar artery stenosis and the distribution of cerebral infarction lesions in all patients before surgery.According to the CISS classification system for ischemic stroke, patients were divided into a perforation group and a hypoperfusion group, and the general situation, plaque distribution, and incidence of ischemic stroke complications 7 days after endovascular treatment in the two groups were analyzed. Results: There was no significant difference in baseline data between the two groups. After 7 days of intravascular treatment, the incidence of ischemic stroke was higher in the perforation group (20.0 %) than in the hypoperfusion group (0.0 %), and the difference was statistically significant (P = 0.027). A significant association was found between the perforation group and the hypoperfusion group for the incidence of ischemic stroke at 7 days (P = 0.003, OR = 2.347; 95 % CI = 2.056-4.268). There were a higher proportion of ventral plaques (74.1 %) and a lower proportion of dorsal plaques (33.3 %) in the hypoperfusion group, which were 15.0 % and 90.0 % in the perforation group, respectively (χ2 = 16.045, P < 0.001; χ2 = 15.092, P < 0.001). There was no significant difference in the proportion of left and right plaques between the two groups. Conclusions: The risk of ischemic stroke is greater in patients with perforator artery obstruction undergoing endovascular therapy, and lower in patients with hypoperfusion/embolus removal.

MARK3 kinase: Regulation and physiologic roles.

Microtubule affinity-regulating kinase 3 (MARK3), a member of the MARK family, regulates several essential pathways, including the cell cycle, ciliated cell differentiation, and osteoclast differentiation. It is important to understand the control of their activities as MARK3 contains an N-terminal serine/threonine kinase domain, ubiquitin-associated domain, and C-terminal kinase-associated domain, which perform multiple regulatory functions. These functions include post-translational modification (e.g., phosphorylation) and interaction with scaffolding and other proteins. Differences in the amino acid sequence and domain position result in different three-dimensional protein structures and affect the function of MARK3, which distinguish it from the other MARK family members. Recent data indicate a potential role of MARK3 in several pathological conditions, including congenital blepharophimosis syndrome, osteoporosis, and tumorigenesis. The present review focuses on the physiological and pathological role of MARK3, its regulation, and recent developments in the small molecule inhibitors of the MARK3 signalling cascade.

Performances of whole-brain dynamic and static functional connectivity fingerprinting in machine learning-based classification of major depressive disorder.

Background: Alterations in static and dynamic functional connectivity during resting state have been widely reported in major depressive disorder (MDD). The objective of this study was to compare the performances of whole-brain dynamic and static functional connectivity combined with machine learning approach in differentiating MDD patients from healthy controls at the individual subject level. Given the dynamic nature of brain activity, we hypothesized that dynamic connectivity would outperform static connectivity in the classification. Methods: Seventy-one MDD patients and seventy-one well-matched healthy controls underwent resting-state functional magnetic resonance imaging scans. Whole-brain dynamic and static functional connectivity patterns were calculated and utilized as classification features. Linear kernel support vector machine was employed to design the classifier and a leave-one-out cross-validation strategy was used to assess classifier performance. Results: Experimental results of dynamic functional connectivity-based classification showed that MDD patients could be discriminated from healthy controls with an excellent accuracy of 100% irrespective of whether or not global signal regression (GSR) was performed (permutation test with P < 0.0002). Brain regions with the most discriminating dynamic connectivity were mainly and reliably located within the default mode network, cerebellum, and subcortical network. In contrast, the static functional connectivity-based classifiers exhibited unstable classification performances, i.e., a low accuracy of 38.0% without GSR (P = 0.9926) while a high accuracy of 96.5% with GSR (P < 0.0002); moreover, there was a considerable variability in the distribution of brain regions with static connectivity most informative for classification. Conclusion: These findings suggest the superiority of dynamic functional connectivity in machine learning-based classification of depression, which may be helpful for a better understanding of the neural basis of MDD as well as for the development of effective computer-aided diagnosis tools in clinical settings.

Associations of rs1799794 and rs1799796 polymorphisms with risk of breast cancer: A meta-analysis.

BACKGROUND: The aim of this meta-analysis was to investigate the rs1799794 and rs1799796 polymorphisms of X-ray repair cross-complementing group 3 (XRCC3) in relation to breast cancer susceptibility. MATERIALS AND METHODS: PubMed, Embase, the Cochrane Library, Web of Science, and Scopus were searched for eligible studies published until June 24, 2019. All analyses were carried out using Stata 14.0 software. Subgroup analyses were performed according to cancer types, ethnicity, source of controls, and method. RESULTS: Our meta-analysis included articles reporting 13 studies of SNP rs1799794 and seven articles reporting 10 studies of SNP rs1799796. Overall, significant associations were observed between the XRCC3 rs1799794 polymorphism and breast cancer risk in the dominant model and heterozygote model (GG + AG vs. AA: odds ratio [OR] =1.06, 95% confidence interval [CI]: 1.00-1.11, P = 0.037, I2 = 47%; AG vs. AA: OR = 1.08, 95% CI: 1.02-1.13, P = 0.006, I2 = 42.3%) and between the XRCC3 rs1799796 polymorphism and breast cancer risk in the homozygote model (GG vs. AA: OR = 0.91, 95% CI: 0.84-0.99, P = 0.021, I2 = 33.3%). CONCLUSIONS: The results of this meta-analysis suggest that the variant G allele of the XRCC3 rs1799794 polymorphism is a low-penetrant risk factor for developing breast cancer, whereas the variant G allele of the XRCC3 rs1799796 polymorphism has a protective effect against breast cancer development.

Detection of age related differences in CBF with PCASL using 2 post label delays.

BACKGROUND: The brain is reliant on an abundant and uninterrupted CBF for normal neural function because it is an organ with high metabolic activity and limited ability to store energy. PURPOSE: This study aimed to compare age-related variations in CBF measured with PCASL. METHODS: This prospective study included healthy volunteers at the Radiology Department of Shanxi Cardiovascular Hospital between October 2018 and July 2019. The volunteers were divided into three groups (n = 30 per group): young (≤44 years), middle-aged (45-59 years) and elderly (≥60 years). CBF was measured by PCASL using 2 post label delays (PLD) (PLD = 1.5 s, 2.5 s), and compared between PLDs and groups. The relation between CBF value and age was assessed by Pearson correlation analysis. RESULTS: For PLD = 1.5 s, CBF differed significantly between groups for all brain regions (P < 0.05), with higher values in the young group and lower values in the elderly group. For PLD = 2.5 s, the young and middle-aged groups had broadly comparable CBF values, whereas the elderly group had higher CBF values (P < 0.05) for most brain regions. For both PLDs, no brain regions showed significant differences in CBF values between males and females. The CBF of all brain regions was negatively correlated with age for PLD = 1.5 s (P < 0.05) but not PLD = 2.5 s. Compared with PLD = 1.5 s, PLD = 2.5 s yielded lower CBF values for the young group and higher CBF values for the elderly group. CONCLUSION: 3D-pCASL with dual PLDs can non-invasively evaluate age-related changes in CBF in healthy people.

GATA1-Activated HNF1A-AS1 Facilitates the Progression of Triple-Negative Breast Cancer via Sponging miR-32-5p to Upregulate RNF38.

BACKGROUND: Triple-negative breast cancer (TNBC) is a highly invasive subtype of breast cancer with a high mortality rate. Recently, long non-coding RNAs (lncRNAs) are confirmed to modulate the progression of assorted cancers, including TNBC. However, the functions of lncRNA HNF1 homeobox A antisense RNA 1 (HNF1A-AS1) in TNBC are still unclear. AIM: We aimed to investigate the function and mechanism of HNF1A-AS1 in TNBC. METHODS: The expression of genes in TNBC cells was tested by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot. In vitro loss-of-function assays and in vivo xenograft experiments were conducted for evaluating the impact of HNF1A-AS1 on TNBC progression. RNA pull-down, luciferase reporter and RNA immunoprecipitation (RIP) assays were utilized for assessing the correlations between molecules. RESULTS: We discovered that HNF1A-AS1 was highly expressed in TNBC tissues and cells. Knockdown of HNF1A-AS1 restrained cell proliferation but accelerated cell apoptosis. Besides, GATA-binding protein 1 (GATA1) activated HNF1A-AS1 transcription in TNBC. MicroRNA-32-5p (miR-32-5p) was slowly expressed in TNBC cells and sponged by HNF1A-AS1, and its overexpression hinders TNBC cell growth. Ring finger protein 38 (RNF38) was verified as the target of miR-32-5p, and HNF1A-AS1 was a competing endogenous RNA (ceRNA) of RNF38 through sponging miR-32-5p. Rescue experiments indicated that upregulation of RNF38 reversed the inhibited impacts of silencing HNF1A-AS1 on TNBC cell growth. CONCLUSION: GATA1-activated HNF1A-AS1 facilitated TNBC progression via miR-32-5p/RNF38 axis. The findings may provide new roads for developing targeted therapies of TNBC.

The value of intravoxel incoherent motion imaging in predicting the survival of patients with astrocytoma.

BACKGROUND: The evaluation of the prognosis of gliomas may have great value in individualized treatment. PURPOSE: To evaluate the value of intravoxel incoherent motion (IVIM) in predicting the survival of patients with astrocytoma and comparing it to apparent diffusion coefficients (ADC). MATERIAL AND METHODS: Sixty patients with pathologically confirmed cerebral astrocytomas underwent IVIM scans before any treatment was performed. Patients were divided into death group and survival group according to a two-year follow-up. ADC and quantitative parameters of IVIM including D, D*, and f were measured. Independent sample t test was used to compare the two groups of parameters. The accuracy of each parameter for two-year survival rate was analyzed by receiver operating characteristic (ROC) curve and Kaplan-Meier survival curves. The correlation between quantitative parameters and survival days was analyzed by Pearson correlation analysis. RESULTS: The ADC, D*, and f values were statistically significant different between the death and the survival groups (P < 0.05). The AUC of the ADC, D*, and f were 0.811, 0.858, and 0.892, respectively. The ADC cut-off value of 0.668 × 10-3 mm2/s corresponded to 82.6% sensitivity and 73% specificity. The D* cut-off value of 3.913 × 10-3 mm2/s corresponded to 78.4% sensitivity and 87% specificity. The f cut-off value of 0.487 corresponded to 83.8% sensitivity and 87% specificity. Significant log rank test was performed for each parameter to predict overall survival (P < 0.05). There was a correlation between ADC (r = 0.625, P = 0.023), D* (r = -0.655, P = 0.012), f (r = -0.725, P = 0.000) and survival days. CONCLUSION: The D* and f values demonstrated great potential in predicting the two-year survival rate for patients with astrocytoma.

Kaempferol Regulates miR-15b/Bcl-2/TLR4 to Alleviate OGD-Induced Injury in H9c2 Cells.

Ischemic heart disease (IHD) is one of the world's leading causes of human death. Kaempferol (Kae) was proved to have anti-inflammatory, antioxidant, and anticancer effects. Such properties suggested that it might play protective roles in IHD. In this study, we have attempted to disclose the potential regulating mechanisms of Kae in primary cardiomyocytes and H9c2 cells.Cells were first stimulated by oxygen-glucose deprivation (OGD) and then exposed to Kae. CCK-8 assay and flow cytometry were used to examine cell characteristics. Quantitative reverse-transcription polymerase chain reaction was utilized to test the expression levels of miR-15b and TLR4. Afterward, cell transfection, dual-luciferase activity assay, and western blot were used to explore the potential mechanisms.OGD treatment suppressed cell viability, whereas it enhanced cell apoptosis. Besides, OGD treatment enhanced the expression of apoptosis-associated proteins. Kae exposure, however, attenuated the effects that OGD-induced. Further experiments showed that Kae exposure promoted down-regulation of miR-15b, Bcl-2 and TLR4 were a target of miR-15b. Moreover, Kae enhanced the expression of key factors involved in PI3K/AKT and Wnt/ß-catenin pathways, whereas miR-15b mimic reversed the Kae-triggered effects.This investigation revealed that Kae diminished OGD-triggered cell damage through down-regulating miR-15b expression via activating PI3K/AKT and Wnt3a/ß-catenin pathways.

The efficacy and safety of probiotics in patients with irritable bowel syndrome: Evidence based on 35 randomized controlled trials.

BACKGROUND & OBJECTIVES: Irritable bowel syndrome (IBS) is a functional bowel disorder that may involve disturbance of the gastrointestinal microbiota. We performed a systematic review and meta-analysis of the efficacy and safety of probiotics in patients with IBS. METHODS: We searched the Cochrane Library, PubMed, EMBASE and Web of Science databases up to 1 April, 2019. Randomized controlled trials (RCTs) involving adults with IBS that compared probiotics to placebo or no therapy were eligible for the analysis. Dichotomous symptom data were pooled to calculate the relative risk (RR) with a 95% confidence interval (CI) of remaining symptoms after therapy. Continuous data were pooled using a standardized mean difference (SMD) with the 95% CI. Two reviewers assessed trial quality and extracted data independently. RESULTS: Thirty-five RCTs involving 3,452 patients were included in the analysis. Compared with placebo, patients using probiotics had a lower incidence of persistence of symptoms (RR 0.79, 95% CI 0.70 to 0.89, P < 0.0001). Also, probiotics exerted a beneficial effect on global symptoms and the abdominal pain score (SMD -0.25, 95% CI -0.36 to -0.14, P < 0.00001), bloating score (SMD -0.15, 95% CI -0.27 to -0.03, P = 0.01), and flatulence score (SMD -0.20, 95% CI -0.35 to -0.05, P = 0.01). However, patients treated with probiotics had a higher incidence of any adverse event (RR 1.21; 95% CI 1.02 to 1.44). CONCLUSIONS: Supplementation with multi-strain probiotics can improve IBS symptoms. Further research is required if probiotics are to be adopted as a treatment for IBS.

FoxP3 promotes lymph node metastasis in patients with papillary thyroid carcinoma complicated with Hashimoto's thyroiditis.

BACKGROUND: To investigate the effect of Treg cells on patients with PTC complicated with HT. METHODS: We collected thyroid fresh tissue of human after surgery, paraffin tissue and serum samples (cancer tissue which was diagnosed by pathology). Analysed the expression of nuclear specific marker gene FoxP3 in Treg cells by Envision immunohistochemical staining. Transwell cell chamber was used to simulate the co-action environment of umbilical cord blood initial T lymphocytes and thyroid papillary carcinoma cells (TPC-1and K1). Compared with human normal thyroid follicular epithelial cell line Nthy-ori 3-1. Flow cytometry was used to detect the proportion of Treg cells (CD4+CD25+CD127-/CD4+CD25+%) at 0, 24, 36, 48, 60 h after co-administration of thyroid papillary carcinoma cell lines (TPC-1 and K1) and umbilical cord blood initial T lymphocytes. The expression of FoxP3 protein in co-acting T lymphocytes was detected by Western blot. RESULTS: The results showed that the positive expression of FoxP3 in the tumor microenvironment of PTC patients with or without HT promoted lymph node metastasis of tumors and played a role in inhibiting tumor immunity. PTC cancer cells could induce initial T lymphocyte differentiating into Treg cells. At 36 h, the ratio of Th17 cells and Treg cells which were differentiated was the highest. The balance of Th17/Treg was significantly biased toward Th17. The proportion of FoxP3 induced by K1 cell line with lymph node metastasis was higher than that of TPC-1 cell line without lymph node metastasis. CONCLUSIONS: FoxP3 could promote lymph node metastasis to inhibit tumor immunity by dysregulation of Th17/Treg balance in PTC patients complicated with HT.

miR-148b-3p, miR-190b, and miR-429 Regulate Cell Progression and Act as Potential Biomarkers for Breast Cancer.

PURPOSE: Breast cancer is the most frequently diagnosed malignancy in women worldwide. MicroRNAs (miRNAs) are thought to serve as potential biomarkers in various cancers, including breast cancer. METHODS: We evaluated the miRNA expression profiles in 1,083 breast cancer samples and 104 normal breast tissues from The Cancer Genome Atlas database. We used the edgeR package of R software to analyze the differentially expressed miRNAs in normal and cancer tissues, and screened survival-related miRNAs by Kaplan-Meier analysis. A receiver operating characteristic curve was generated to evaluate the accuracy of these miRNAs as molecular markers for breast cancer diagnosis. Furthermore, the functional role of these miRNAs was verified using cell experiments. Targets of candidate miRNAs were predicted using 9 online databases, and Gene Ontology (GO) functional annotation and pathway analyses were conducted using Database for Annotation, Visualization and Integrated Discovery online tool. RESULTS: A total of 68 miRNAs showed significantly different expression patterns between the groups (p < 0.001), and 13 of these miRNAs were significantly associated with poor survival (p < 0.05). Three miRNAs with high specificity and sensitivity, namely, miR-148b-3p, miR-190b, and miR-429, were selected. In vitro experiments showed that the overexpression of these 3 miRNAs significantly promoted the proliferation and migration of MDA-MB-468 and T47D cells and reduced the apoptosis of T47D cells. GO and pathway enrichment analyses revealed that the targets of these dysregulated miRNAs were involved in many critical cancer-related biological processes and pathways. CONCLUSION: The miR-148b-3p, miR-190b, and miR-429 may serve as potential diagnostic and prognostic markers for breast cancer. This study demonstrated the roles of these 3 miRNAs in the initiation and progression of breast cancer.

Changes in white-matter functional network efficiency across the adult lifespan.

Previous studies have used resting-state functional MRI (rs-fMRI) and graph-theory approaches to investigate the lifespan trajectory of the topological organization of the gray-matter functional networks. Recent evidences have suggested that rs-fMRI data can also be used to estimate white-matter function, challenging the conventional practice of taking white-matter signals as noise or artifacts. Here, we examined the correlation between age and white-matter functional network efficiency by applying graph-theory to a large sample of rs-fMRI data of 435 participants. We found that age was correlated negatively with both global and local efficiency of the white-matter functional networks. These findings suggest decreasing white-matter functional network efficiency during the aging process, which provides a complement to conventional gray-matter functional network studies.

Positive effect of RORγt on the prognosis of thyroid papillary carcinoma patients combined with Hashimoto's thyroiditis.

OBJECTIVES: To investigate the positive effect of Th17 cells on the prognosis of patients with PTC and HT. METHODS: The expression of nuclear specific marker RORγt of Th17 cells in fresh and paraffin thyroid tissues and serum specimens were analyzed. Flow cytometry was used to detect the formation rates of Th17 cells (CD3+CD8-IL-17A+/CD3+CD8-%) at different time points after co-culture of thyroid papillary carcinoma cell line (TPC-1 and K1) and umbilical cord blood initial T lymphocytes. The protein expression of RORγt in T lymphocytes after co-culture was detected. Preoperative serum levels of Th17 (IL-17) cytokines were measured. RESULTS: The positive expression of RORγt in the tumor microenvironment of PTC patients with or without HT could inhibit the lymph node metastasis of the tumor. PTC cancer cells could induce initial T lymphocyte to differentiate into Th17 cells, and the K1 cell line with lymph node metastasis induced a higher proportion of RORγt protein than that in TPC-1 cell line without lymph node metastasis. In PTC patients with HT, serum IL-17 concentration was negatively correlated with lymph node metastasis in the central group. CONCLUSIONS: RORγt may play an anti-tumor role in reducing thyroid cell damage by reducing the thyroid autoimmune antibodies TPOAb and TGAb in the PTC population in Yunnan plateau region.

Comparison of OnabotulinumtoxinA versus sacral neuromodulation for refractory urinary urge incontinence: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND & AIM: Both intradetrusor OnabotulinumtoxinA (BTX) and Sacral neuromodulation (SNM) as third-line therapies for urgency urinary incontinence (UUI) are increasingly being utilized. However, there are differences in preference between patients and medical personnel in clinical practice. This meta-analysis was designed to compare BTX versus SNM in treatment of UUI. METHODS: We searched the Cochrane Library, PubMed, EMBASE and Web of Science from January 1, 1992 to April 22, 2018. Mean differences (MDs) and risk ratio (RR) with its 95% confidence intervals (CIs) were estimated to compare the outcomes of the groups. All the MDs were after subtracting OnabotulinumtoxinA data from Sacral neuromodulation data. RRs were acquired from comparing OnabotulinumtoxinA data to Sacral neuromodulation data. Two reviewers assessed trial quality and extracted data independently. All statistical analyses were performed using standard statistical procedures provided in Review Manager 5.2. This work has been reported in line with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) and AMSTAR (Assessing the methodological quality of systematic reviews) Guidelines. RESULTS: Seven randomized controlled trials and two retrospective studies (N = 1649 participants) were identified for the present analysis. In change from baseline in UUI episodes (UUIE) per day, comparing BTX groups with SNM groups, the effects were observed through 1, 2, 4, 5 and 6 month, with pooled MDs of -0.62, -0.55, -0.38, -1.02 and -0.50 respectively. In UUIE reduction post treatment, the pooled RRs of complete UUIE reductions through 4 and 6 months respectively were 5.13 and 6.63. Significant results were observed through overall times in more than 75% UUIE reduction. No significance was found in more than 50% UUIE reduction. Significant results were observed in urinary tract infection. More treatment satisfaction were found in BTX groups than that in SNM groups (RR 1.14, 95% CI 1.01-1.29; P = 0.004). CONCLUSIONS: Generally, BTX seems superior to SNM in treatment of UUI but inferior regarding safety. Patients receiving BTX experienced a higher treatment satisfaction.

Distribution and prognostic value of tumor­infiltrating T cells in breast cancer.

Tumor-infiltrating lymphocytes are associated with the response to neoadjuvent chemotherapy and prognosis in breast cancer. However, the distribution, interaction and prognostic value of tumor­infiltrating T cells, the main component of the tumor microenvironment, have seldom been reported. In the present study, surgical specimens of 72 breast cancer patients were analyzed. Tumor­infiltrating T cell subsets [cluster of differentiation (CD)4+T, CD8+T and regulatory T cells] and expression of their cytokines [interferon­Î³, interleukin (IL)­4, and IL­17] were evaluated by flow cytometry. These parameters together with The Cancer Genome Atlas database were used to demonstrate the distribution, interaction and prognostic value of tumor­infiltrating T cells in breast cancer. Tumor­infiltrating lymphocytes were closely associated with histological grade (P=0.03), estrogen receptor status (P=0.006), human epidermal growth factor receptor 2 status (P=0.047) and molecular subtype in breast cancer (P=0.012). The gene expression of CD4, CD8A and forkhead box protein P3 in the tumor was increased compared with healthy breast tissue, and was positively associated with the prognosis of breast cancer patients. HER2+ and triple­negative breast cancer exhibited a significantly increased percentage of CD4+T cells (P=0.01) and regulatory T cells (P=0.035), and a decreased percentage of CD8+T cells (P=0.006) compared with the luminal subtype. Furthermore, the regulatory T cell number was positively correlated with CD8+T cell number in tumors (R=0.7, P=1.5x10­162) and significantly inhibited the cytokine secretion of T cells. These results reveal the distribution and interaction of tumor­infiltrating T cell subsets, and indicate that CD8+T cells and regulatory T cells may be used as reliable predictors of prognosis in breast cancer.

The relationship between RASSF1A promoter methylation and thyroid carcinoma: A meta-analysis of 14 articles and a bioinformatics of 2 databases (PRISMA).

BACKGROUND: DNA promoter methylation can suppresses gene expression and shows an important role in the biological functions of Ras association domain family 1A (RASSF1A). Many studies have performed to elucidate the role of RASSF1A promoter methylation in thyroid carcinoma, while the results were conflicting and heterogeneous. Here, we analyzed the data of databases to determine the relationship between RASSF1A promoter methylation and thyroid carcinoma. METHODS: We used the data from 14 cancer-normal studies and Gene Expression Omnibus (GEO) database to analyze RASSF1A promoter methylation in thyroid carcinoma susceptibility. The data from the Cancer Genome Atlas project (TCGA) database was used to analyze the relationship between RASSF1A promoter methylation and thyroid carcinoma susceptibility, clinical characteristics, prognosis. Odds ratios were estimated for thyroid carcinoma susceptibility and hazard ratios were estimated for thyroid carcinoma prognosis. The heterogeneity between studies of meta-analysis was explored using H, I values, and meta-regression. We adopted quality criteria to classify the studies of meta-analysis. Subgroup analyses were done for thyroid carcinoma susceptibility according to ethnicity, methods, and primers. RESULTS: Result of meta-analysis indicated that RASSF1A promoter methylation is associated with higher susceptibility to thyroid carcinoma with small heterogeneity. Similarly, the result from GEO database also showed that a significant association between RASSF1A gene promoter methylation and thyroid carcinoma susceptibility. For the results of TCGA database, we found that RASSF1A promoter methylation is associated with susceptibility and poor disease-free survival (DFS) of thyroid carcinoma. In addition, we also found a close association between RASSF1A promoter methylation and patient tumor stage and age, but not in patients of different genders. CONCLUSIONS: The methylation status of RASSF1A promoter is strongly associated with thyroid carcinoma susceptibility and DFS. The RASSF1A promoter methylation test can be applied in the clinical diagnosis of thyroid carcinoma.

Predictive role of the overexpression for CXCR4, C-Met, and VEGF-C among breast cancer patients: A meta-analysis.

BACKGROUND: The overexpression of CXCR4, C-Met and VEGF-C present widely in breast tumors, they may be markers of resistance to treatment. However, the studies are still controversial. Thus, this meta-analysis aims to research the relationship between the overexpression of CXCR4, C-Met, VEGF-C and clinical prognosis among breast cancer patients. METHODS: PubMed and EMBASE databases were searched for eligible literature. The outcomes of interest were progression-free survival (PFS), relapse-free survival (RFS) and overall survival (OS). All tests of statistical significance were two sided. RESULTS: A total of 7830 patients from 28 eligible studies were assessed. The overexpression of the CXCR4 and C-Met both implied significantly worse PFS compared with normal expression [HR = 2.56, 95% CI = 1.34-4.91, P = 0.005; and HR = 1.63 95% CI = 1.20-2.22, P = 0.002]. Meanwhile, if patients had high expression of CXCR4, they would have worse OS [HR = 2.56 95% CI = 1.52-4.31, P = 0.000]. However, the overexpression of C-Met did not relate to OS for breast cancer patients [HR = 1.16, 95% CI = 0.69-1.95, P = 0.570]. Meanwhile, no statistically significant different was observed with respect to PFS and OS between VEGF-C overexpression and normal expression [HR = 0.99, 95% CI = 0.64-1.52, P = 0.968; and HR = 0.76, 95% CI = 0.43-1.33, P = 0.333]. CONCLUSIONS: Our meta-analysis showed that CXCR4 and C-Met were efficient prognostic factors for breast cancer. Nevertheless, highly expressing VEGF-C was not related to progression-free survival and overall survival. Due to the small samples and insufficient date, further studies should be conducted to clarify the association between the overexpression of CXCR4 or C-Met or VEGF-C and the prognosis about breast cancer patients.

A Systematic Analysis of the Relationship of CDH13 Promoter Methylation and Breast Cancer Risk and Prognosis.

BACKGROUND: CDH13 (cadherin 13) is a special cadherin cell adhesion molecule, and the methylation of its promoter causes inactivation in a considerable number of human cancers. To explore the association between CDH13 promoter methylation and breast cancer risk and prognosis, we systematically integrated published articles to investigate the diagnostic performance of the CDH13 methylation test for breast cancer. An independent DNA methylation microarray dataset from The Cancer Genome Atlas project (TCGA) project was used to validate the results of the meta-analysis. METHODS: The relevant literature was searched using the PubMed, Cochrane Library, Web of Science and Google Scholar databases for articles published in English up to May 2015. Data were analyzed using random effect or fixed effect models. The effect sizes were estimated by measuring an odds ratio (OR) or hazard ratio (HR) with a 95% confidence interval (CI). A chi-squared based Q test and sensitivity analysis were performed to examine the between-study heterogeneity and the contribution of single studies to the final results, respectively. Funnel plots were constructed to evaluate publication bias. RESULTS: Seven hundred and twenty-six breast tumor samples and 422 controls were collected from 13 published studies. The data from the TCGA set include both tumor and normal samples. A significant association was observed between CDH13 promoter methylation and breast cancer, with an aggregated OR equal to 13.73 (95%CI: 8.09~23.31, z = 9.70, p<0.0001) as measured using the fixed effect model and 14.23 (95%CI: 5.06~40.05, z = 5.03, p<0.0001) as measured using a random effect model. The HR values were calculated as 0.77 (95%CI: 0.27~2.21, z = -0.49, p = 0.622) and 0.38 (95%CI: 0.09~1.69, z = -1.27, p = 0.20) for overall survival (OS) and disease-free survival (DFS), respectively, using the random effect model. This result indicated that breast cancer patients with CDH13 promoter methylation correlated non-significantly with prognosis and is therefore similar to the findings of the TCGA project. CONCLUSIONS: The methylation status of CDH13 promoter was strongly associated with breast cancer risk. However, CDH13 promoter methylation was not significantly related to the OS and DFS of breast cancer and may have limited prognostic value for breast cancer patients.