Decoupling of gray and white matter functional networks in cognitive impairment induced by occupational aluminum exposure.

Aluminum (Al) is a low-toxic, accumulative substance with neurotoxicity properties that adversely affect human cognitive function. This study aimed to investigate the neurobiological mechanisms underlying cognitive impairment resulting from occupational Al exposure. Resting-state functional magnetic resonance imaging was conducted on 54 individuals with over 10 years of Al exposure. Al levels were measured, and cognitive function was assessed using the Montreal Cognitive Assessment (MoCA). Subsequently, the K-means clustering algorithm was employed to identify functional gray matter (GM) and white matter (WM) networks. Two-sample t-tests were conducted between the cognition impairment group and the control group. Al exhibited a negative correlation with MoCA scores. Participants with cognitive impairment demonstrated reduced functional connectivity (FC) between the middle cingulum network (WM1) and anterior cingulum network (WM2), as well as between the executive control network (WM6) and limbic network (WM10). Notably, decreased FCs were observed between the executive control network (GM5) and WM1, WM4, WM6, and WM10. Additionally, the FC of GM5-GM4 and WM1-WM2 negatively correlated with Trail Making Test Part A (TMT-A) scores. Prolonged Al accumulation detrimentally affects cognition, primarily attributable to executive control and limbic network disruptions.

Formaldehyde-Mediated Hydride Liberation of Alkylamines for Intermolecular Reactions in Hexafluoroisopropanol.

The ability of alkylamines to spontaneously liberate hydride ions is typically restrained, except under specific intramolecular reaction settings. Herein, we demonstrate that this reactivity can be unlocked through simple treatment with formaldehyde in hexafluoroisopropanol (HFIP) solvent, thereby enabling various intermolecular hydride transfer reactions of alkylamines under mild conditions. Besides transformations of small molecules, these reactions enable unique late-stage modification of complex peptides. Mechanistic investigations uncover that the key to these intermolecular hydride transfer processes lies in the accommodating conformation of solvent-mediated macrocyclic transition states, where the aggregates of HFIP molecules act as dexterous proton shuttles. Importantly, negative hyperconjugation between the lone electron pair of nitrogen and the antibonding orbital of amine's α C-H bond plays a critical role in the C-H activation, promoting its hydride liberation.

Neuropsychological insights into exercise addiction: the role of brain structure and self-efficacy in middle-older individuals.

This study aimed to investigate the relationship between exercise addiction and brain structure in middle-older individuals, and to examine the role of self-efficacy in mediating physiological changes associated with exercise addiction. A total of 133 patients exhibiting symptoms of exercise addiction were recruited for this study (male = 43, age 52.86 ± 11.78 years). Structural magnetic resonance imaging and behavioral assessments were administered to assess the study population. Voxel-based morphological analysis was conducted using SPM12 software. Mediation analysis was employed to explore the potential neuropsychological mechanism of self-efficacy in relation to exercise addiction. The findings revealed a positive correlation between exercise addiction and gray matter volume in the right inferior temporal region and the right hippocampus. Conversely, there was a negative correlation with gray matter volume in the left Rolandic operculum. Self-efficacy was found to indirectly influence exercise addiction by affecting right inferior temporal region gray matter volume and acted as a mediating variable in the relationship between the gray matter volume of right inferior temporal region and exercise addiction. In summary, this study elucidates the link between exercise addiction and brain structure among middle-older individuals. It uncovers the intricate interplay among exercise addiction, brain structure, and psychological factors. These findings enhance our comprehension of exercise addiction and offer valuable insights for the development of interventions and treatments.

Artificial Intelligence Imaging for Predicting High-risk Molecular Markers of Gliomas.

Gliomas, the most prevalent primary malignant tumors of the central nervous system, present significant challenges in diagnosis and prognosis. The fifth edition of the World Health Organization Classification of Tumors of the Central Nervous System (WHO CNS5) published in 2021, has emphasized the role of high-risk molecular markers in gliomas. These markers are crucial for enhancing glioma grading and influencing survival and prognosis. Noninvasive prediction of these high-risk molecular markers is vital. Genetic testing after biopsy, the current standard for determining molecular type, is invasive and time-consuming. Magnetic resonance imaging (MRI) offers a non-invasive alternative, providing structural and functional insights into gliomas. Advanced MRI methods can potentially reflect the pathological characteristics associated with glioma molecular markers; however, they struggle to fully represent gliomas' high heterogeneity. Artificial intelligence (AI) imaging, capable of processing vast medical image datasets, can extract critical molecular information. AI imaging thus emerges as a noninvasive and efficient method for identifying high-risk molecular markers in gliomas, a recent focus of research. This review presents a comprehensive analysis of AI imaging's role in predicting glioma high-risk molecular markers, highlighting challenges and future directions.

Preoperative Radiotherapy Does Not Change the Existing Treatment Paradigm in Stage III Breast Cancer.

INTRODUCTION: Radiotherapy (RT) plays an indispensable role in postoperative breast cancer treatment. This study aimed to assess the feasibility of preoperative RT for stage III breast cancer by comparing preoperative RT with postoperative RT in terms of overall survival (OS). METHODS: Based on the information in the Surveillance, Epidemiology, and End Results database from 2000 to 2018, patients with stage III breast cancer who had undergone radical surgery and RT were divided into two groups: a preoperative RT group and a postoperative RT group. OS was calculated using Kaplan-Meier analysis. The Cox proportional hazards model was used to evaluate independent factors associated with OS. Propensity score matching (PSM) was used to balance stratification factors. RESULTS: In total, 9,605 patients were enrolled, of whom 9,456 received postoperative RT and 149 received preoperative RT. After a median follow-up of 72 months, postoperative RT was found to be superior to preoperative RT in terms of OS (p < 0.000). Compared to the postoperative RT group, the preoperative RT group showed a significantly higher risk of overall mortality without PSM in univariate (OS: hazard ratio [HR] = 1.653, 95% confidence interval [CI]: 1.288-2.123, p < 0.000) and multivariate analyses (OS: HR = 1.409, 95% CI: 1.096-1.810, p = 0.007). After PSM, the OS of the postoperative RT group was superior to the OS in the preoperative RT group (p = 0.041). Compared with the postoperative RT group, the preoperative RT group showed a significantly higher risk of overall mortality without PSM in univariate (HR = 1.312, 95% CI: 1.010-1.704, p = 0.042) and multivariate analyses (HR = 1.466, 95% CI: 1.127-1.906, p = 0.004). CONCLUSION: Preoperative RT does not improve OS in patients with stage III breast cancer and has a worse prognosis. Preoperative RT has not changed the existing treatment paradigm in the current therapeutic context for patients with stage III breast cancer.

Clinicopathological characteristics and value of HER2-low expression evolution in breast cancer receiving neoadjuvant chemotherapy.

OBJECTIVE: The present study aimed to evaluate the clinicopathological characteristics and value of HER2-low expression evolution in breast cancer receiving neoadjuvant chemotherapy (NAC). METHODS: Patients with HER2 negative breast cancer receiving NAC from January 2017 to December 2020 were enrolled in this study. The clinicopathological characteristics, response to NAC, evolution of HER2 and prognostic value were retrospectively analyzed. RESULTS: 410 patients were included. The proportion of HR positive disease in HER2-low cases was higher than in HER2-zero population (75.8 % vs. 65.8 %, P = 0.040). No statistical significant difference in pCR rate was observed between HER2-low and HER2-zero patients (33.8 % vs. 39.3 %, P = 0.290) when pCR was defined as ypTis/0ypN0. Exploratory analysis revealed that the pCR rate of HER2-low cases was significantly lower than HER2-zero patients in the entire population (19.8 % vs. 33.3 %, P = 0.004) and HR positive population (12.6 % vs. 29.9 %, P = 0.001) when pCR was defined as ypT0ypN0. The evolution rate of HER2 expression after NAC was 31.0 % in HER2-zero patients and 24.7 % in HER2-low patients. Compared with patients with HR positive disease, patients with TNBC had higher evolution rate of HER2 expression after NAC (37.7 % vs. 23.6 %). Significant association was observed between HER2 evolution with histology type and Ki-67 index in HER2-zero patients and with lymph node involvement, HR status and Ki-67 index in HER2-low patients. Prognostic impact of HER2 evolution was not observed. CONCLUSIONS: HR positive and HR negative HER2-low breast cancer exhibit different clinicopathological features, response to NAC and HER2 evolution after treatment.

Chinese version of exercise dependence scale-revised: psychometric analysis and exploration of risk factors.

Introduction: Exercise addiction (EA) is a dysfunctional behavior characterized by exaggerated training which has adverse effects on physiology and psychology. To examine the reliability and validity of the Chinese version of the Exercise Dependence Scale-Revised (EDS-R) and the social and psychological aspects related to EA, a large sample behavioral study was conducted. Methods: College students were selected as the target group. All of them were asked to finish the scales about exercise, including the Chinese version of EDS-R and the Motives for Physical Activity Measure-Revised scales. A confirmatory factor analysis, Mann-Whitney U test, and hierarchical regression test were performed to test the reliability and validity of the Chinese version of EDS-R and find the explanatory variables of EA. Results: A total of 837 (556 female) students with a mean age of 20.38 years were recruited in the present study. The Chinese version of EDS-R showed good reliability and validity (McDonald's ω = 0.973, CR = 0.99, AVE = 0.80) in Chinese college students. EA was positively correlated with exercise frequency and ability motivation across the study sample. Besides, the Mann-Whitney U test revealed that the exercise motivation difference is the primary cause of the gender gap in EA. Conclusion: The Chinese version of EDS-R is a relatively robust and accurate instrument to assess the risk of EA. Additionally, exercise frequency and motivation may be the potential risk factors for EA. The screening of risk factors is of great significance for the early detection and prevention of EA.

Brain metastasis in de novo stage IV breast cancer.

OBJECTIVES: Information of brain metastasis (BM) in de novo stage IV breast cancer is lacking, which is an unavoidable problem and dilemma in practice. Understanding the current situation is helpful for the clinical cognition and decision-making. METHODS: We retrospectively analyzed the clinical and survival information of de novo stage IV breast cancer with BM between 2015 and 2019 from the Surveillance, Epidemiology, and End Results (SEER) database. Multivariable logistic and Cox regression analyses were performed to identify predictors of BM and factors associated with all-cause mortality in de novo stage IV breast cancer, respectively. Overall survival (OS) was calculated using Kaplan-Meier and log-rank tests. RESULTS: Our cohort consisted of 1366 patients with BM in de novo stage IV breast cancer, with an incidence of 8.38% in patients with metastatic disease to any distant site. Incidence was highest among patients with metastatic disease with HR-HER2+ (12.95%) and HR-HER2- (13.40%) subtypes. The higher the number of extracranial metastases, the higher the BM incidence. The median OS was 12.0 (95%CI: 10.426-13.574) months in BM group; it was longest in HR + HER2+ (19.0[95%CI: 11.793-26.207] months), and shortest in HR-HER2- (7.0 [95%CI:5.354-8.646] months). Marital status, subtype, and abundance of metastatic sites influenced morbidity and OS of BM in de novo stage IV breast cancer. CONCLUSIONS: Population-based estimates of the incidence and prognosis for patients with BM in de novo stage IV breast cancer were closely associated with subtype and metastatic burden. These findings may be helpful in developing diagnostic strategies, especially for brain screening.

Enantioselective synthesis of chiral quinohelicenes through sequential organocatalyzed Povarov reaction and oxidative aromatization.

Heterohelicenes are of increasing importance in the fields of materials science, molecular recognition, and asymmetric catalysis. However, enantioselective construction of these molecules, especially by organocatalytic methods, is challenging, and few methods are available. In this study, we synthesize enantioenriched 1-(3-indol)-quino[n]helicenes through chiral phosphoric acid-catalyzed Povarov reaction followed by oxidative aromatization. The method has a broad substrate scope and offers rapid access to an array of chiral quinohelicenes with enantioselectivities up to 99%. Additionally, the photochemical and electrochemical properties of selected quinohelicenes are explored.

Transition State Stabilization by SCF2 -H⋠⋠⋠O Bifurcated Hydrogen Bond.

The difluoromethylthio group (SCF2 H), which is generally considered a highly lipophilic weak hydrogen bonding donor, has attracted special interest from the pharmaceutical and agrochemical industry. Remarkably, there have been relatively few literature investigations of SCF2 H hydrogen bonding interactions. Here, we report the determination of the hydrogen bond acidity parameter A of the SCF2 H in the most popularly used electrophilic difluoromethylthiolating reagent. We present kinetic and computational evidence of the RSCF2 -H⋅⋅⋅O2 bifurcated hydrogen bond for stabilizing the SCF2 H-transferring transition state, which could cause a reversal of apparent electrophilic reactivity of difluoromethylthiolating and trifluoromethylthiolating reagents. Solvent effects on the RSCF2 -H⋅⋅⋅O2 bifurcated hydrogen bonds will also be discussed.

HER2-low expression does not affect the clinical outcomes of metastatic breast cancer treated with CDK4/6 inhibitor: A real-world study.

Background: There is accumulating evidence support human epidermal growth factor receptor 2 (HER2)-low as a biologically distinct subtype of breast cancer. The present study was conducted to explore whether HER2-low expression will affect the clinical efficacy of cyclin-dependent kinase (CDK) 4/6 inhibitor for patients with hormone receptor (HR)-positive, HER-2 negative metastatic breast cancer. Methods: Patients with HR+/HER2- metastatic breast cancer who were treated with palbociclib from January 2019 to June 2021 were retrospectively analyzed based on real-world clinical practice. HER2-zero was defined as immunohistochemistry (IHC) 0, and HER2-low was defined as IHC 1+ or IHC 2+/fluorescence in situ hybridization (FISH) negative. The primary end point was progression free survival (PFS), and the secondary end points were objective response rate (ORR), disease control rate (DCR), overall survival(OS) and safety. Results: 45 patients received palbociclib plus aromatase inhibitor (AI) or fulvestrant therapy, including 24 HER-2-zero and 21 HER-2-low patients. There were no statistically significant differences in clinicopathological characteristics between the two groups. No significant differences were observed in ORR (41.7% vs. 28.6%, P=0.360) and DCR (79.2% vs. 76.2%, P=0.811) between HER-2-zero and HER-2-low patients. And simultaneously, HER2-zero and HER2-low patients obtained similar median PFS (16.2m vs. 14.1m, P=0.263). The median OS was not reached. Neutropenia and leukopenia were the most common adverse events. Grade 3-4 adverse events(AEs) occurred in 58.3% and 57.1% of patients, respectively. Conclusions: HER2-low expression does not affect the clinical efficacy of palbociclib and our present study did not support incorporating HER2-low into systemic therapy decisions for patients with HR+/HER2- metastatic breast cancer treated with CDK4/6 inhibitor.

A real-world study of anlotinib as third-line or above therapy in patients with her-2 negative metastatic breast cancer.

Background: Antiangiogenic agents provides an optional treatment strategy for patients with metastatic breast cancer. The present study was conducted to evaluate the efficacy and safety of anlotinib as third-line or above therapy for patients with HER-2 negative metastatic breast cancer. Methods: Patients with HER-2 negative metastatic breast cancer who have failed from prior therapy and treated with anlotinib monotherapy or combined with chemotherapy or immunotherapy from June 2018 to December 2020 were retrospectively analyzed based on real-world clinical practice. The primary end point was progression free survival (PFS). Secondary end points included objective response rate (ORR), disease control rate (DCR), overall survival (OS) and safety. Results: 47 patients with HER-2 negative metastatic breast cancer received anlotinib monotherapy or combination therapy as third-line or above therapy. In the general population, 10 patients achieved PR, 25 patients had SD and 12 patients had PD. The overall ORR and DCR were 21.3% and 74.5%, respectively. Subgroup analysis suggested that there were no statistically significant differences in ORR and DCR with respect to HR status (positive vs. negative), treatment programs (monotherapy vs. combination) and treatment type in combination group (chemotherapy vs. immunotherapy). The patients who did not received previously anti-angiogenesis therapy had superior DCR (84.8% vs. 50.0%, P=0.012). Median PFS and OS were 5.0 months (95% CI=4.3-5.7) and 21.0 (95% CI=14.9-27.1) months, respectively. The PFS (6.5m vs. 3.5m, P=0.042)and OS (28.2m vs. 12.6m, P=0.040) were better in HR positive patients than HR negative patients. And simultaneously, patients who received anlotinib combination therapy obtained better PFS (5.5m vs. 3.0m, P=0.045). The incidence of Grade 3-4 adverse events(AEs) was 31.9%. Conclusions: Anlotinib monotherapy or combination therapy provide a viable third-line or above therapeutic strategy in patients with HER-2 negative metastatic breast cancer, a median PFS of 5.0 months was obtained with well tolerated toxicity.

Clinical, Pathological Complete Response, and Prognosis Characteristics of HER2-Low Breast Cancer in the Neoadjuvant Chemotherapy Setting: A Retrospective Analysis.

BACKGROUND: The present study was conducted to evaluate the clinical, pathological response, and prognosis characteristics of human epidermal growth factor receptor 2 (HER2)-low breast cancer in the neoadjuvant chemotherapy setting. METHODS: Patients with HER2-negative breast cancer who received neoadjuvant chemotherapy from January 2017 to December 2019 were retrospectively analyzed. HER2-negative breast cancer was divided into two groups: HER2-zero (defined as immunohistochemistry [IHC] 0) and HER2-low (defined as IHC 1+, or IHC 2+ and fluorescence in-situ hybridization-negative. RESULTS: Overall, 314 patients with HER2-negative breast cancer were analyzed. The proportion of HER2-low patients with hormone receptor (HR)-positive disease was higher than in triple-negative breast cancer (TNBC; 75.3% vs. 63.2%, p = 0.032). In HR-positive breast cancer, HER2-low tumors presented less nodal involvement (p = 0.023) and earlier clinical stage (p = 0.015) compared with HER2-zero tumors; however, in TNBC, HER2-low patients had a later clinical stage (p = 0.028). With the pathological complete response (pCR) defined as ypTis/0ypN0, there was no difference in pCR rates among the entire cohort, HR-positive disease, and TNBC. However, with the pCR defined as ypT0ypN0, the pCR rate in HER2-low breast cancer was significantly lower than HER2-zero breast cancer in the entire cohort (24.3% vs. 36.4%, p = 0.032) and the HR-positive subgroup (18.7% vs. 32.1%, p = 0.035), but not for TNBC. Multivariate analysis demonstrated that HER2 status (low vs. zero) was an independent predictive factor for pCR (p = 0.013) in HR-positive breast cancer. There were no statistically significant differences in 3-year disease-free survival and overall survival between HER2-low and HER2-zero breast cancer among the entire cohort, HR-positive disease, and TNBC. CONCLUSIONS: HER2-low breast cancer exhibits specific clinical features and different response to treatment associated with HR status in the neoadjuvant chemotherapy setting.

Enantioselective Synthesis of Planar-Chiral Macrocycles through Asymmetric Electrophilic Aromatic Amination.

An efficient approach for asymmetric synthesis of planar-chiral macrocycles (paracyclophanes) has been disclosed through enantioselective electrophilic aromatic aminations with azodicarboxylates enabled by chiral phosphoric acid catalysis. A wide range of chiral macrocycles bearing varied ring sizes (16 to 23-membered) and functional group-containing ansa chains were readily afforded using this method, with excellent yields and high enantioselectivities (23 examples, up to 99.5 : 0.5 er). Experimental studies and DFT calculations were performed to elucidate the mechanism and origin of stereoselectivities of these reactions. Preliminary utilization of the planar-chiral macrocycle as chiral organocatalyst showcased the potential applications of these novel chiral skeletons.

Asymmetric Synthesis of N-N Axially Chiral Compounds by Phase-Transfer-Catalyzed Alkylations.

N-N axially chiral skeletons are significant structural motifs in natural products, pharmaceuticals, and functional materials. Herein we disclose a method for the asymmetric synthesis of N-N axially chiral compounds by phase-transfer catalysis. A wide range of N-N axially chiral quinazolinone derivatives were prepared in high yields with excellent stereoselectivities. Furthermore, the synthetic utility of the protocol was proved by large-scale reaction and transformation of the product. Density functional theory calculations provide insight into the mechanism.

lncRNA PCNAP1 predicts poor prognosis in breast cancer and promotes cancer metastasis via miR­340­5p­dependent upregulation of SOX4.

The high metastatic rate of breast cancer is the significant cause of its poor prognosis. The long noncoding RNA (lncRNA) proliferating cell nuclear antigen pseudogene 1 (PCNAP1) plays important roles in the initiation and progression of cancers; however, its regulatory function and molecular mechanism in breast cancer metastasis remains unknown. Therefore, we investigated the roles of lncRNA PCNAP1 in breast cancer metastasis by modulating the microRNA (miR)­340­5p/SOX4 axis using quantitative real­time PCR, in vivo mouse models, nucleo­cytoplasmic separation, western blot analysis, scratch assays, Transwell assays, luciferase reporter assays and MS2­RIP, in vitro and in vivo. lncRNA PCNAP1 was found to be upregulated in human breast cancer tissues, and high lncRNA PCNAP1 levels predicted poor overall survival. Function assays showed that knockdown of lncRNA PCNAP1 suppressed the migration and invasion of breast cancer cells in vitro and in vivo. Mechanistically, lncRNA PCNAP1 functioned as a competing endogenous (ce)RNA for miR­340­5p to facilitate the expression of its target gene SRY­box transcription factor 4 (SOX4), promoting migration and invasion of breast cancer cells. Overall, we found that lncRNA PCNAP1 predicted a poor prognosis in breast cancer and promoted cancer metastasis via miR­340­5p­dependent upregulation of SOX4 expression. These results suggest that lncRNA PCNAP1 has potential as an alternative therapeutic target to suppress breast cancer metastasis.

Relationships between SNPs and prognosis of breast cancer and pathogenic mechanism.

BACKGROUND: Association between several single-nucleotide polymorphisms (SNPs) and breast cancer risk has been identified through genome-wide association studies (GWAS), but little is known about their significance in patients' prognosis. We screened SNPs which were related to the prognosis of breast cancer in Henan Han population, analyzed relevant genes by bioinformatics in database, and further constructed the genetic regulatory network involved in the pathogenesis of breast cancer. METHODS: We evaluated five SNPs in 232 cases of breast cancer at the Affiliated Tumor Hospital of Zhengzhou University. Relationships between five SNPs, clinical prognostic indicators, and disease-free survival (DFS) were evaluated by Kaplan-Meier analysis and Cox proportional hazards model. Gene ontology (GO) functional annotation and Kyoto Encyclopedia of genes and Genome (KEGG) analysis were carried out to preliminarily establish genetic regulation network model of breast cancer. Bayesian algorithm was used to optimize the model. RESULTS: The multivariate Cox proportional hazards model confirmed that SNP rs3803662 (TOX3/TNRC9) had correlation with DFS independently. In the multivariate Cox proportional hazards model, compared with GA/AA, GG increased the recurrent risk of breast cancer (p = .021, hazard ratio [HR] = 2.914). GO analysis showed that the function of TOX3/TNRC9 included biological_process, molecular_function, and cellular_component. According to KEGG signaling pathway database, the map of breast cancer-related gene regulatory network was obtained. IGF-IGF1R-PI3K-Akt-mTOR-S6K was the best possible pathway for the differentiation of breast cancer cells in this network and ER-TOX3/TNRC9 was the best possible pathway for the survival of tumor cells in this network by Bayesian theorem optimization. CONCLUSIONS: SNP rs3803662 (TOX3/TNRC9) is an independent prognostic factor for breast cancer in Henan Han Population. ER-TOX3/TNRC9 is the best possible pathway involved in the pathogenesis of breast cancer.

Serum ATX as a novel biomarker for breast cancer.

Recent accumulating evidence indicates the biological actions of Autotaxin-Lysophosphatidic acid (ATX-LPA) signaling axis in malignant tumors. However, the role of Autotaxin-Lysophosphatidic acid signaling axis in breast cancer has not been reported. The present study aims to examine the alterations of serum autotaxin in breast cancer and discuss whether serum autotaxin could be useful as a novel parameter of breast cancer.Serum autotaxin antigen was measured in 112 patients with breast cancer and 50 healthy volunteers by ELISA. The association of serum autotaxin antigen levels with clinicopathological parameters and outcomes of breast cancer was analyzed.Serum autotaxin antigen was significantly higher in breast cancer patients than healthy volunteers (291.32 ±â€Š38.02 ng/ml vs 254.04 ±â€Š21.03 ng/ml, respectively; P < .0001). Serum autotaxin measurement successfully discriminated breast cancer patients from normal and healthy controls (AUC = 0.798, 95% CI: 0.732-0.864) with an optimal cut-off value of 267.34 ng/ml (sensitivity = 0.741, specificity = 0.800). Increased serum autotaxin was associated with breast cancer nodal status (P = .007), Tumor-Node- Metastasis (TNM) stage (P = .009) and Ki-67 index (P = .004). Univariate and multivariate Cox regression analysis revealed that elevated serum autotaxin showed an independent prognostic value for poor Disease-free survival.Our present study confirmed the elevation, potential diagnostic, and independent prognostic value of serum autotaxin for breast cancer. Serum autotaxin could serve as a reliable novel biomarker for breast cancer.

High-concentration glucose enhances invasion in invasive ductal breast carcinoma by promoting Glut1/MMP2/MMP9 axis expression.

Type 2 diabetes mellitus (T2DM) has been considered to be a risk factor for numerous human cancers. Hyperglycemia is one of the most direct internal environmental changes for patients with T2DM. Increasing evidence reveals that a high concentration of glucose can promote tumor progression, while its role for migration and invasion of invasive ductal breast carcinoma (IDBC) cells remains unclear. In the present study, it was demonstrated that IDBC patients with T2DM suffered an increased tumor size and more frequent lymphatic and distant metastasis compared with those without T2DM (P<0.05). MCF-7 breast carcinoma cells, which were cultured in a high glucose concentration medium (25.00 mM), exhibited increased invasion (P<0.05). In addition, the expression of glucose transporters (Gluts), matrix metalloproteinase 2 (MMP2) and matrix metalloproteinase 9 (MMP9) in IDBC tissues with T2DM was significantly higher compared to those without T2DM. Downregulation of glucose transporter 1 (Glut1) by small interfering RNA may markedly suppress MCF-7 cell invasion as well as the expression of MMP2 and MMP9. These results suggest that T2DM can affect the malignant features of tumors in IDBC. The high glucose concentration in the tumor microenvironment may enhance IDBC invasion via upregulating Glut1/MMP2/MMP9 axis expression.