Identification of circular RNA-Dcaf6 as a therapeutic target for optic nerve crush-induced RGC degeneration.

The death of retinal ganglion cells (RGCs) can cause irreversible injury in visual function. Clarifying the mechanism of RGC degeneration is critical for the development of therapeutic strategies. Circular RNAs (circRNAs) are important regulators in many biological and pathological processes. Herein, we performed circRNA microarrays to identify dysregulated circRNAs following optic nerve crush (ONC). The results showed that 221 circRNAs were differentially expressed between ONC retinas and normal retinas. Notably, the levels of circular RNA-Dcaf6 (cDcaf6) expression in aqueous humor of glaucoma patients were higher than that in cataract patients. cDcaf6 silencing could reduce oxidative stress-induced RGC apoptosis in vitro and alleviate retinal neurodegeneration in vivo as shown by increased neuronal nuclei antigen (NeuN, neuronal bodies) and beta-III-tubulin (TUBB3, neuronal filaments) staining and reduced glial fibrillary acidic protein (GFAP, activated glial cells) and vimentin (activated glial cells) staining. Collectively, this study identifies a promising target for treating retinal neurodegeneration.

Identification of aberrantly expressed circular RNAs in hyperlipidemia-induced retinal vascular dysfunction in mice.

Hyperlipidemia-induced retinal vascular dysfunction is a complex pathological process. circRNAs are important regulators of biological processes and disease progression. However, the expression pattern of circRNAs in hyperlipidemia-induced retinal vascular dysfunction remains unclear. Herein, we used a murine model of hyperlipidemia and identified 317 differentially expressed circRNAs between hyperlipidemic retinas and normolipidemic retinas by circRNA microarrays. GO analysis indicated that the host genes of dysregulated circRNAs were targeted to cell differentiation (ontology: biological process), cytoplasm (ontology: cellular component), and protein binding (ontology: molecular function). Pathway analysis revealed that circRNAs-mediated network was mostly enriched in focal adhesion signaling. Notably, circLDB1 was significantly up-regulated in the serum of coronary artery disease patients and aqueous humor of age-related macular degeneration patients. circLDB1 regulated endothelial cell viability, proliferation, and apoptosis in vitro. Thus, circRNAs are the promising targets for the prediction and diagnosis of hyperlipidemia-induced vascular diseases.

The extraction of polycyclic aromatic hydrocarbons from water samples with aromatic-dithiocarbamate modified magnetic nanoparticles.

Considering the urgent need for the analysis of trace-level pollutants in water samples, the pre-concentration of micropollutants in water samples has been the focus of extensive research. Among current pretreatment methods, the solid phase extraction (SPE) technique has received enormous attention because of its low cost, ease of operation and high efficiency. In this work, a new adsorbent (Fe3O4@Au@DTC NPs) was acquired through modification of Fe3O4 nanoparticles (NPs) with gold (Au) and dithiocarbamate (DTC). To investigate their application ability, the adsorbent were utilized as an SPE adsorbent to enrich polycyclic aromatic hydrocarbons in water (PAHs, fluoranthene, pyrene, benzo anthracene, benzo fluoranthene, benzo pyrene). The obtained Fe3O4@Au@DTC NPs were confirmed by transmission electron microscope (TEM), X-ray photoelectron spectroscopy (XPS), vibrating sample magnetometer (VSM), and UV-Vis spectrum. Under optimal conditions, the calibration curves were obtained in the range of 10-500 ng L-1, while the limit of detection (LOD) ranged in 1.17-2.31 ng L-1. Furthermore, 50 mg of Fe3O4@Au@DTC NPs could extract trace PAHs from 500 mL real water samples into 1 mL eluent, and the spiked recoveries of five PAHs in river water and tap water reached 72-106% with relative standard deviations varying between 3.3-5.18%. Through the conversion of amines into DTC, we acquire desiring group modified Fe3O4 NPs, which showed great prospects in magnetic solid-phase extraction sphere and environmental field.

Warfarin use and the risk of stroke, bleeding, and mortality in older adults on dialysis with incident atrial fibrillation.

AIM: There is conflicting evidence regarding the safety and effectiveness of warfarin for atrial fibrillation (AF) treatment among older end-stage renal disease (ESRD) patients, and differences among subgroups are unclear. METHODS: Older dialysis patients who were newly diagnosed with AF (7/2007-12/2011) were identified in the United States Renal Data System. The adjusted hazard ratios (HR) of the outcomes (any stroke, ischaemic stroke, major bleeding, severe gastrointestinal bleeding, and death) by time-varying warfarin use were estimated using Cox regression accounting for the inverse probability of treatment weight. RESULTS: Among 5765 older dialysis patients with incident AF, warfarin was associated with significantly increased risk of major bleeding (HR = 1.50, 95% CI 1.33-1.68), but was not statistically associated with any stroke (HR = 0.92, 95% CI 0.75-1.12), ischaemic stroke (HR = 0.88, 95%CI 0.70-1.11) or gastrointestinal bleeding (HR = 1.03, 95% CI 0.80-1.32). Warfarin use was associated with a reduced risk of mortality (HR = 0.72, 95%CI 0.65-0.80). The association between warfarin and major bleeding differed by sex (male: HR = 1.29; 95%CI 1.08-1.55; female: HR = 1.67; 95%CI 1.44-1.93; P-value for interaction = 0.03). CONCLUSION: Older ESRD patients with AF who were treated with warfarin had a no difference in stroke risk, lower mortality risk, but increased major bleeding risk. The bleeding risk associated with warfarin was greater among women than men. The risk/benefit ratio of warfarin may be less favourable among older women.

Measurement equivalence of patient safety climate in Chinese hospitals: can we compare across physicians and nurses?

OBJECTIVE: Self-report instruments have been widely used to better understand variations in patient safety climate between physicians and nurses. Research is needed to determine whether differences in patient safety climate reflect true differences in the underlying concepts. This is known as measurement equivalence, which is a prerequisite for meaningful group comparisons. This study aims to examine the degree of measurement equivalence of the responses to a patient safety climate survey of Chinese hospitals and to demonstrate how the measurement equivalence method can be applied to self-report climate surveys for patient safety research. METHODS: Using data from the Chinese Hospital Survey of Patient Safety Climate from six Chinese hospitals in 2011, we constructed two groups: physicians and nurses (346 per group). We used multiple-group confirmatory factor analyses to examine progressively more stringent restrictions for measurement equivalence. RESULTS: We identified weak factorial equivalence across the two groups. Strong factorial equivalence was found for Organizational Learning, Unit Management Support for Safety, Adequacy of Safety Arrangements, Institutional Commitment to Safety, Error Reporting and Teamwork. Strong factorial equivalence, however, was not found for Safety System, Communication and Peer Support and Staffing. Nevertheless, further analyses suggested that nonequivalence did not meaningfully affect the conclusions regarding physician-nurse differences in patient safety climate. CONCLUSIONS: Our results provide evidence of at least partial equivalence of the survey responses between nurses and physicians, supporting mean comparisons of its constructs between the two groups. The measurement equivalence approach is essential to ensure that conclusions about group differences are valid.

Association of Magnet Status and Nurse Staffing With Improvements in Patient Experience With Hospital Care, 2008-2015.

BACKGROUND: Little is known about the longitudinal association of hospital Magnet status (an indicator of nursing excellence) and nurse-staffing level with inpatient care experience. OBJECTIVES: To examine temporal trends in hospital performance on patient experience measured using the Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) survey and the association of these trends with Magnet status and nurse-staffing level. RESEARCH DESIGN: Longitudinal study of hospital-level data from the HCAHPS survey, the American Hospital Association Annual Survey, and the American Nurses Credentialing Center. Growth curve models were used for the analysis of longitudinal associations. SUBJECTS: A total of 26,752 hospital-year observations from 3614 US hospitals that collected at least 3 years of HCAHPS data from patients discharged between 2008 and 2015. MEASURES: Dependent variables were 7 HCAHPS measures. Independent variables included linear and quadratic time terms, hospital Magnet status, and nurse-staffing level. RESULTS: There were significant improvements (P<0.001) in all 7 HCAHPS measures, but the trends were nonlinear; the improvement rates have decreased over time. Magnet hospitals and hospitals with more favorable nurse staffing consistently performed better on HCAHPS but did not improve faster than other hospitals during the study period. In subgroup analyses, HCAHPS scores did not improve for hospitals after they received Magnet recognition during the period from 2009 to 2015. CONCLUSIONS: The hospital organizational attributes that lead to Magnet recognition or better nurse staffing may be associated with higher performance on HCAHPS. Magnet status and favorable nurse staffing may be markers of hospital commitment to better patient-centered care.

Expression of CDC5L is associated with tumor progression in gliomas.

Cell division cycle 5-like (CDC5L) protein is a cell cycle regulator of the G2/M transition and has been reported to participate in the catalytic step of pre-messenger RNA (mRNA) splicing and DNA damage repair. Recently, it was also found to act as a candidate oncogene in osteosarcoma and cervical tumors. However, the role of CDC5L expression in tumor biology was still unclear. Here, we analyzed the expression and clinical significance of CDC5L in gliomas. The expression of CDC5L in fresh glioma tissues and paraffin-embedded slices was evaluated by western blot and immunohistochemistry, respectively. We found that CDC5L was highly expressed in glioma tissues. The expression of CDC5L was significantly associated with glioma pathology grade and Ki-67 expression. Univariate and multivariate analyses showed that high CDC5L expression was an independent prognostic factor for glioma patients' survival. To determine whether CDC5L could regulate the proliferation of glioma cells, we transfected glioma cells with interfering RNA target CDC5L, then investigated cell proliferation with cell counting kit (CCK)-8, flow cytometry assays and colony formation analyses. Our results indicated that knockdown of CDC5L would inhibit proliferation of glioma cells. Besides, reduced expression of CDC5L could induce the apoptosis of glioma cells. These findings suggested that CDC5L might play an important role in glioma and thus be a promising therapeutic target of glioma.

Far upstream element-binding protein 1 (FUBP1) is a potential c-Myc regulator in esophageal squamous cell carcinoma (ESCC) and its expression promotes ESCC progression.

The human far upstream element (FUSE) binding protein 1 (FUBP1) belongs to an ancient family which is required for proper regulation of the c-Myc proto-oncogene. Although c-Myc plays an important role in development of various carcinomas, the relevance of FUBP1 and their contribution to esophageal squamous cell carcinoma (ESCC) development remain unclear. In this study, we aimed to investigate the relationship between FUBP1 and c-Myc as well as their contribution to ESCC development. Western blot and immunohistochemical analyses were performed to evaluate FUBP1 expression. Coimmunoprecipitation analysis was performed to explore the correlation between FUBP1 and c-Myc in ESCC. In addition, the role of FUBP1 in ESCC proliferation was studied in ESCC cells through knocking FUBP1 down. The regulation of FUBP1 on proliferation was confirmed by Cell Counting Kit-8 (CCK-8) assay, flow cytometric assays, and clone formation assays. The expressions of FUBP1 and c-Myc were both upregulated in ESCC tissues. In addition to correlation between expression of FUBP1 and tumor grade, we also confirmed the correlation of FUBP1, c-Myc, and Ki-67 expression by twos. Moreover, upregulation of FUBP1 and c-Myc in ESCC was associated with poor survival. FUBP1 was confirmed to activate c-Myc in ESCC tissues and cells. FUBP1 was demonstrated to promote proliferation of ESCC cells. Moreover, downregulation of both FUBP1 and c-Myc was confirmed to inhibit proliferation of ESCC cells. Our results indicated that FUBP1 may potentially stimulate c-Myc expression in ESCC and its expression may promote ESCC progression.

Patient perspectives of care and process and outcome quality measures for heart failure admissions in US hospitals: how are they related in the era of public reporting?

IMPORTANCE: Process quality measure performance has improved significantly with public reporting, requiring reevaluation of process-outcome relationships and the emerging role of patient perspectives on care. OBJECTIVE: To evaluate associations between heart failure patient perspectives of care and publicly reported processes and outcomes. DESIGN: Cross-sectional study, July 2008-June 2011. SETTING: US hospitals in the Press Ganey database. PARTICIPANTS: Heart failure inpatients. MEASURES: Outcomes were Hospital Compare hospital-level risk-adjusted 30-day heart failure mortality and readmissions. Predictors included Hospital Compare heart failure processes of care, a weighted process composite and Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) domains for heart failure. Hospital characteristics included volume of heart failure patients and race, health status and education. RESULTS: Among 895 included hospitals, performance on process measures was high (median by hospital for composite, 95.6%); the median HCAHPS overall rating was 86.9. Median mortality was 11.3% and readmissions was 24.8%. No process measures were statistically significantly associated with lower mortality or readmissions in adjusted analyses. Higher ratings on HCAHPS patient perspectives of care were significantly correlated with lower readmissions in adjusted analyses, particularly those publicly reported domains conceptually related to readmissions. The magnitude was small (1.8 points higher on a 100-point scale between the highest and lowest quartiles of hospital readmissions). CONCLUSIONS: Publicly reported process quality measures were no longer associated with outcomes, but higher patient perspectives of care were associated with lower heart failure readmissions. These associations support continued reevaluation of these measures and increased emphasis on patient experience and outcomes, as planned for Value-Based Purchasing.

Racial/Ethnic disparities in patient experience with communication in hospitals: real differences or measurement errors?

BACKGROUND: An important aspect of medical care is clear and effective communication, which can be particularly challenging for individuals based on race/ethnicity. Quality of communication is measured systematically in the Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) survey, and analyzed frequently such as in the National Healthcare Disparities Report. Caution is needed to discern differences in communication quality from racial/ethnic differences in perceptions about concepts or expectations about their fulfillment. OBJECTIVES: To examine assumptions about the degree of commonality across racial/ethnic groups in their perceptions and expectations, and to investigate the validity of conclusions regarding racial/ethnic differences in communication quality. METHODS: We used 2007 HCAHPS data from the National CAHPS Benchmarking Database to construct racial/ethnic samples that controlled for other patient characteristics (828 per group). Using multiple-groups confirmatory factor analyses, we tested whether the factor structure and model parameters (ie, factor loadings, intercepts) differed across groups. RESULTS: We identified support for basic tests of equivalence across 7 racial/ethnic groups in terms of equivalent factor structure and loadings. Even stronger support was found for Communication with Doctors and Nurses. However, potentially important nonequivalence was found for Communication about Medicines, including instances of statistically significant differences between non-Hispanic whites and non-Hispanic blacks, Asians, and Native Hawaiian/other Pacific Islanders. CONCLUSIONS: Our results provide strongest support for racial/ethnic comparisons on Communication with Nurses and Doctors, and reason to caution against comparisons on Communication about Medicines due to significant differences in model parameters across groups; that is, a lack of invariance in the intercept.

Interaction with CCNH/CDK7 facilitates CtBP2 promoting esophageal squamous cell carcinoma (ESCC) metastasis via upregulating epithelial-mesenchymal transition (EMT) progression.

CtBP2, as a transcriptional corepressor of epithelial-specific genes, has been reported to promote tumor due to upregulating epithelial-mesenchymal transition (EMT) in cancer cells. CtBP2 was also demonstrated to contribute to the proliferation of esophageal squamous cell carcinoma (ESCC) cells through a negative transcriptional regulation of p16(INK4A). In this study, for the first time, we reported that CtBP2 expression, along with CCNH/CDK7, was higher in ESCC tissues with lymph node metastases than in those without lymph node metastases. Moreover, both CtBP2 and CCNH/CDK7 were positively correlated with E-cadherin, tumor grade, and tumor metastasis. However, the concrete mechanism of CtBP2's role in enhancing ESCC migration remains incompletely understood. We confirmed that CCNH/CDK7 could directly interact with CtBP2 in ESCC cells in vivo and in vitro. Furthermore, our data demonstrate for the first time that CtBP2 enhanced the migration of ESCC cells in a CCNH/CDK7-dependent manner. Our results indicated that CCNH/CDK7-CtBP2 axis may augment ESCC cell migration, and targeting the interaction of both may provide a novel therapeutic target of ESCC.

Expression and clinical role of NF45 as a novel cell cycle protein in esophageal squamous cell carcinoma (ESCC).

NF45 (also known as ILF2), as one subunit of NF-AT (nuclear factor of activated T cells), repairs DNA breaks, inhibits viral replication, and also functions as a negative regulator in the microRNA processing pathway in combination with NF90. Recently, it was found that implicated in the mitotic control of HeLa cells and deletion of endogenous NF45 decreases growth of HeLa cells. While the role of NF45 in cancer biology remains under debate. In this study, we analyzed the expression and clinical significance of NF45 in esophageal squamous cell carcinoma ESCC. The expression of NF45 was evaluated by Western blot in 8 paired fresh ESCC tissues and immunohistochemistry on 105 paraffin-embedded slices. NF45 was highly expressed in ESCC and significantly associated with ESCC cells tumor stage and Ki-67. Besides, high NF45 expression was an independent prognostic factor for ESCC patients' poor survival. To determine whether NF45 could regulate the proliferation of ESCC cells, we increased endogenous NF45 and analyzed the proliferation of TE1 ESCC cells using Western blot, CCK8, flow cytometry assays and colony formation analyses, which together indicated that overexpression of NF45 favors cell cycle progress of TE1 ESCC cells. While knockdown of NF45 resulted in cell cycle arrest at G0/G1-phase and thus abolished the cell growth. These findings suggested that NF45 might play an important role in promoting the tumorigenesis of ESCC, and thus be a promising therapeutic target to prevent ESCC progression.

Sam68 promotes cellular proliferation and predicts poor prognosis in esophageal squamous cell carcinoma.

Sam68 (Src-associated in mitosis of 68 kD) is a KH domain RNA-binding protein. The expression of Sam68 was correlated with kinds of tumors. Yet, the expression mechanisms and physiological significance of Sam68 in ESCC remains unclear. In this study, we clarified a potential role of Sam68 in the treatment of ESCC. Western blot and immunohistochemistry (IHC) analysis revealed that the protein level of Sam68 was higher in ESCC tumor tissues and cell lines. In addition, IHC stain revealed that Sam68 was positively correlated with clinical pathologic variables such as tumor grade and tumor invasion. In addition, Sam68 could be an independent prognostic indicator for patients' overall survival. In vitro studies such as starvation and refeeding assay along with Sam68-shRNA transfection assay demonstrated that Sam68 expression promoted proliferation of ESCC cells. And Sam68 downregulation caused decreased rate of cell growth and colony formation. Reasons are associated with growth arrest of cell cycle at G1/S phase. Moreover, our results clarified that Sam68 could promote ESCC cell proliferation via the activation of Akt/GSK-3ß pathway. This research indicated that Sam68 might accelerate the cell cycle progression and be considered as a new therapy target in ESCC.

Upregulation of SYF2 in esophageal squamous cell carcinoma promotes tumor cell proliferation and predicts poor prognosis.

SYF2, also known as CCNDBP1-interactor or p29, is reported in pre-mRNA splicing and cell cycle progression. However, the role of SYF2 in esophageal squamous cell carcinoma (ESCC) development remains elusive. In the present study, Western blot and immunohistochemistry assays demonstrated that SYF2 was overexpressed in ESCC tumor tissues and cell lines. In addition, immunohistochemistry analysis revealed that SYF2 expression was positively correlated with tumor grade and predicted poor prognosis of ESCC. In vitro studies using serum starvation-refeeding experiment and SYF2-siRNA transfection assay demonstrated that SYF2 expression promoted proliferation of ESCC cells, while SYF2 knockdown led to decreased cell growth rate and colony formation resulted from growth arrest of cell cycle at G0/G1 phase. Furthermore, our results indicated that SYF2 can down-regulate the sensitivity of ESCC cells for cisplatin. Our findings for the first time supported that SYF2 might play an important role in the regulation of ESCC proliferation and would provide a novel therapeutic strategy against human ESCC.

Do drug interaction alerts between a chemotherapy order-entry system and an electronic medical record affect clinician behavior?

INTRODUCTION: We developed an enhancement to a chemotherapy order-entry system that alerted prescribers to potential drug interactions between patients' usual outpatient medications and those prescribed for onsite cancer treatment. This report summarizes the interactions and analyzes the impact of alerts on clinician behavior. METHODS: We studied electronic orders created from November 2010 to December 2011 by oncology clinicians at two comprehensive cancer centers who shared a chemotherapy order-entry system and an ambulatory electronic medical record. The enhancement generated an alert if a new chemotherapy system order for an antineoplastic agent or supportive care medication interacted with an existing medication in the ambulatory record, and tracked prescribers' responses. RESULTS: New chemotherapy system orders triggered 29,592 drug interaction alerts. New orders for antineoplastic agents accounted for 495 (32.6%) of 1518 high- and medium-severity alerts. Interactions with antibiotics accounted for the majority of these alerts. New chemotherapy system orders for antiemetics triggered 352 (23.2%) alerts and more than two-thirds were attributed to interactions with analgesic opioids. High- and medium-severity alerts changed prescriber behavior in 224 (14.8%) occurrences, including potentially fatal interactions between meperidine and monoamine oxidase inhibitors. Clinicians who overrode alerts indicated that they would monitor the patient (54.6%), the patient already tolerated the combination (24.5%), and they would adjust the dose (15.1%). CONCLUSION: Cancer patients are at risk of serious interactions between medications ordered for cancer care and those provided for general medical care. Organizations and order-entry applications should develop countermeasures to identify and prevent potentially serious drug interactions.

Transcriptomic and Molecular Docking Analysis Reveal Virulence Gene Regulation-Mediated Antibacterial Effects of Benzyl Isothiocyanate Against Staphylococcus aureus.

Staphylococcus aureus (S. aureus) is a common pathogen that can cause many serious infections. Thus, efficient and practical techniques to fight S. aureus are required. In this study, transcriptomics was used to evaluate changes in S. aureus following treatment with benzyl isothiocyanate (BITC) to determine its antibacterial action. The results revealed that the BITC at subinhibitory concentrations (1/8th MIC) treated group had 94 differentially expressed genes compared to the control group, with 52 downregulated genes. Moreover, STRING analyses were used to reveal the protein interactions encoded by 36 genes. Then, we verified three significant virulence genes by qRT-PCR, including capsular polysaccharide synthesis enzyme (cp8F), capsular polysaccharide biosynthesis protein (cp5D), and thermonuclease (nuc). Furthermore, molecular docking analysis was performed to investigate the action site of BITC with the encoded proteins of cp8F, cp5D, and nuc. The results showed that the docking fraction of BITC with selected proteins ranged from - 6.00 to - 6.60 kcal/mol, predicting the stability of these complexes. BITC forms hydrophobic, hydrogen-bonded, π-π conjugated interactions with amino acids TRP (130), GLY (10), ILE (406), LYS (368), TYR (192), and ARG (114) of these proteins. These findings will aid future research into the antibacterial effects of BITC against S. aureus.

Comparative effectiveness of three platinum-doublet chemotherapy regimens in elderly patients with advanced non-small cell lung cancer.

BACKGROUND: Randomized trials report equivalent efficacy among various combinations of platinum-based regimens in advanced non-small cell lung cancer (NSCLC). Their relative effectiveness and comparability based on squamous versus nonsquamous histology is uncertain. METHODS: The authors used the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked data to identify first-line chemotherapy agents administered to Medicare beneficiaries with stage IIIB or IV NSCLC diagnosed from 2000 to 2007. Overall survival was compared between patients who received the 3 most common regimens: carboplatin-paclitaxel, carboplatin-gemcitabine, and carboplatin-docetaxel. Stratified analyses distinguished between the outcomes of patients with squamous versus nonsquamous cell histology. Multivariable Cox proportional hazards models and propensity score analyses facilitated adjustment for imbalance in measurable patient characteristics. RESULTS: Of the 15,318 patients who received first-line chemotherapy, 43.1% received carboplatin-paclitaxel, 14.3% received carboplatin-gemcitabine, 8.5% received carboplatin-docetaxel, and 34.1% received other regimens. The median survival was 8.0 months (interquartile range [IQR], 3.5-17.4 months) for carboplatin-paclitaxel, 7.3 months (IQR, 3.4-15.2 months) for carboplatin-gemcitabine, and 7.5 months (IQR, 3.2-16.0 months) for carboplatin-docetaxel. Both multivariable and propensity score-adjusted Cox models demonstrated a slight inferiority associated with carboplatin-gemcitabine or carboplatin-docetaxel versus carboplatin-paclitaxel, with a hazard ratio of 1.10 (95% confidence interval, 1.04-1.15) and 1.09 (95% confidence interval, 1.02-1.16), respectively, in propensity score-stratified models. Among the subgroup of 2063 patients with squamous carcinoma, propensity score-stratified analyses had a higher risk of death (hazard ratio, 1.20; 95% confidence interval, 1.07-1.35) associated with carboplatin-gemcitabine versus carboplatin-paclitaxel. CONCLUSIONS: Carboplatin-paclitaxel was associated with slightly better survival compared with carboplatin-gemcitabine or carboplatin-docetaxel within the Medicare population with advanced NSCLC, and this was most pronounced for patients who had squamous cell histology.

Downregulated expression of the cyclase-associated protein 1 (CAP1) reduces migration in esophageal squamous cell carcinoma.

OBJECTIVE: Overexpression of cyclase-associated proteins has been associated with poor prognosis in several human cancers. Cyclase-associated protein 1 is a member of the cyclase-associated proteins which contributes to tumor progression. The aim of the present study was to examine the expression of cyclase-associated protein 1 and to elucidate its clinicopathologic significance in a larger series of esophageal squamous cell carcinoma. METHODS: Immunohistochemical and western blot analyses were performed in esophageal squamous cell carcinoma tissues. Survival analyses were performed by using the Kaplan-Meier method. The role of cyclase-associated protein 1 in migration was studied in esophageal squamous cell carcinoma cell lines of TE1 through knocking down cyclase-associated protein 1 with siRNA and overexpression of cyclase-associated protein 1. The regulation of cyclase-associated protein 1 on migration was determined by transwell and wound-healing assays. RESULTS: Immunohistochemical analysis showed that cyclase-associated protein 1 expression was negatively associated with E-cadherin and significantly associated with lymph node metastases. Survival analysis revealed that cyclase-associated protein 1 overexpression was significantly associated with overall survival (P = 0.011). Knock down of cyclase-associated protein 1 in TE1 cells resulted in decreased vimentin and F-actin levels and the capability for migration. In addition, overexpression of cyclase-associated protein 1 promoted the migration of TE1 cells. CONCLUSIONS: These findings suggest that cyclase-associated protein 1 is involved in the metastasis of esophageal squamous cell carcinoma, and that elevated levels of cyclase-associated protein 1 expression may indicate a poor prognosis for patients with esophageal squamous cell carcinoma.

EYE-503: A Novel Retinoic Acid Drug for Treating Retinal Neurodegeneration.

Retinal neurodegeneration is a major cause of vision loss. Retinoic acid signaling is critical for the maintenance of retinal function, and its dysfunction can cause retinal neurodegeneration. However, the therapeutic effects of retinoic acid drugs on retinal neurodegeneration remain unclear. In this study, we designed a novel retinoic acid drug called EYE-503 and investigated its therapeutic effects of EYE-503 on retinal neurodegeneration. The optic nerve crush (ONC) model was selected for the retinal neurodegeneration study. H&E staining, TUNEL staining, immunofluorescence staining, and visual electrophysiology assays were performed to determine the role of EYE-503 in retinal neurodegeneration in vivo. The CCK-8 assay, EdU incorporation assay, PI staining, and flow cytometry assays were performed to investigate the effects of EYE-503 administration on retinal neurodegeneration in vitro. The potential mechanism of EYE-503 in retinal neurodegeneration was investigated by network pharmacology and Western blots. The results showed that EYE-503 administration had no detectable cytotoxicity and tissue toxicity. EYE-503 administration alleviated ONC-induced retinal injury and optic nerve injury in vivo. EYE-503 administration attenuated retinal ganglion cell apoptosis, inhibited reactive gliosis, and retarded the progression of retinal neurodegeneration. Mechanistically, EYE-503 regulated retinal neurodegeneration by targeting the JNK/p38 signaling pathway. This study suggests that EYE-503 is a promising therapeutic agent for retinal neurodegenerative diseases.

Metabolomic profiling of a neurodegenerative retina following optic nerve transection.

The degeneration of retinal ganglion cells (RGCs) often causes irreversible vision impairment. Prevention of RGC degeneration can prevent or delay the deterioration of visual function. The present study aimed to investigate retinal metabolic profiles following optic nerve transection (ONT) injury and identify the potential metabolic targets for the prevention of RGC degeneration. Retinal samples were dissected from ONT group and non­ONT group. The untargeted metabolomics were carried out using liquid chromatography­tandem mass spectrometry. The involved pathways and biomarkers were analyzed using Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and MetaboAnalyst 5.0. In the ONT group, 689 disparate metabolites were detected, including lipids and lipid­like molecules. A total of 122 metabolites were successfully annotated and enriched in 50 KEGG pathways. Among them, 'sphingolipid metabolism' and 'primary bile acid biosynthesis' were identified involved in RGC degeneration. A total of five metabolites were selected as the candidate biomarkers for detecting RGC degeneration with an AUC value of 1. The present study revealed that lipid­related metabolism was involved in the pathogenesis of retinal neurodegeneration. Taurine, taurochenodesoxycholic acid, taurocholic acid (TCA), sphingosine, and galabiosylceramide are shown as the promising biomarkers for the diagnosis of RGC degeneration.