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1.
Eur J Cancer Prev ; 33(4): 376-385, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38842873

ABSTRACT

OBJECTIVE: The tumor, node and metastasis stage is widely applied to classify lung cancer and is the foundation of clinical decisions. However, increasing studies have pointed out that this staging system is not precise enough for the N status. In this study, we aim to build a convenient survival prediction model that incorporates the current items of lymph node status. METHODS: We performed a retrospective cohort study and collected the data from resectable nonsmall cell lung cancer (NSCLC) (IA-IIIB) patients from the Surveillance, Epidemiology, and End Results database (2006-2015). The x-tile program was applied to calculate the optimal threshold of metastatic lymph node ratio (MLNR). Then, independent prognostic factors were determined by multivariable Cox regression analysis and enrolled to build a nomogram model. The calibration curve as well as the Concordance Index (C-index) were selected to evaluate the nomogram. Finally, patients were grouped based on their specified risk points and divided into three risk levels. The prognostic value of MLNR and examined lymph node numbers (ELNs) were presented in subgroups. RESULTS TOTALLY,: 40853 NSCLC patients after surgery were finally enrolled and analyzed. Age, metastatic lymph node ratio, histology type, adjuvant treatment and American Joint Committee on Cancer 8th T stage were deemed as independent prognostic parameters after multivariable Cox regression analysis. A nomogram was built using those variables, and its efficiency in predicting patients' survival was better than the conventional American Joint Committee on Cancer stage system after evaluation. Our new model has a significantly higher concordance Index (C-index) (training set, 0.683 v 0.641, respectively; P < 0.01; testing set, 0.676 v 0.638, respectively; P < 0.05). Similarly, the calibration curve shows the nomogram was in better accordance with the actual observations in both cohorts. Then, after risk stratification, we found that MLNR is more reliable than ELNs in predicting overall survival. CONCLUSION: We developed a nomogram model for NSCLC patients after surgery. This novel and useful tool outperforms the widely used tumor, node and metastasis staging system and could benefit clinicians in treatment options and cancer control.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Lymph Nodes , Lymphatic Metastasis , Nomograms , Humans , Carcinoma, Non-Small-Cell Lung/surgery , Carcinoma, Non-Small-Cell Lung/mortality , Carcinoma, Non-Small-Cell Lung/pathology , Lung Neoplasms/surgery , Lung Neoplasms/mortality , Lung Neoplasms/pathology , Female , Male , Retrospective Studies , Middle Aged , Lymphatic Metastasis/pathology , Lymph Nodes/pathology , Lymph Nodes/surgery , Aged , Prognosis , Survival Rate , Neoplasm Staging , SEER Program/statistics & numerical data , Lymph Node Ratio , Follow-Up Studies , Pneumonectomy/mortality , Pneumonectomy/methods
2.
Heliyon ; 10(11): e32314, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38868029

ABSTRACT

With the rapid development of clinical diagnosis and treatment, many traditional and conventional in vitro diagnosis technologies are unable to meet the demands of clinical medicine development. In this situation, nanomaterials are rapidly developing and widely used in the field of in vitro diagnosis. Nanomaterials have distinct size-dependent physical or chemical properties, and their optical, magnetic, electrical, thermal, and biological properties can be modulated at the nanoscale by changing their size, shape, chemical composition, and surface functional groups, particularly because they have a larger specific surface area than macromaterials. They provide an amount of space to modify different molecules on their surface, allowing them to detect small substances, nucleic acids, proteins, and microorganisms. Combining nanomaterials with in vitro diagnosis is expected to result in lower detection limits, higher sensitivity, and stronger selectivity. In this review, we will discuss the classfication and properties of some common nanomaterials, as well as their applications in protein, nucleic acids, and other aspect detection and analysis for in vitro diagnosis, especially on aging-related nanodiagnostics. Finally, it is summarized with guidelines for in vitro diagnosis.

3.
J Control Release ; 365: 1-15, 2024 01.
Article in English | MEDLINE | ID: mdl-37972763

ABSTRACT

Dry eye disease (DED) is a multifactorial ocular surface disorder mutually promoted by reactive oxygen species (ROS) and ocular surface inflammation. NLRP3 is the key regulator for inducing ocular surface inflammation in DED. However, the mechanism by which ROS influences the bio-effects of NLRP3, and the consequent development of DED, largely remains elusive. In the present study, we uncovered that robust ROS can oxidate mitochondrial DNA (ox-mtDNA) along with loss of mitochondria compaction causing the cytosolic release of ox-mtDNA and subsequent co-localization with cytosolic NLRP3, which can promote the activation of NLRP3 inflammasome and stimulate NLRP3-mediated inflammation. Visomitin (also known as SkQ1), a mitochondria-targeted anti-oxidant, could reverse such a process by in situ scavenging of mitochondrial ROS. To effectively deliver SkQ1, we further developed a novel mitochondria-targeted SkQ1 nanoparticle (SkQ1 NP) using a charge-driven self-assembly strategy. Compared with free SkQ1, SkQ1 NPs exhibited significantly higher cytosolic- and mitochondrial-ROS scavenging activity (1.7 and 1.9 times compared to levels of the free SkQ1 group), thus exerting a better in vitro protective effect against H2O2-induced cell death in human corneal epithelial cells (HCECs). After topical administration, SkQ1 NPs significantly reduced in vivo mtDNA oxidation, while suppressing the expressions of NLRP3, Caspase-1, and IL-1ß, which consequently resulted in better therapeutic effects against DED. Results suggested that by efficiently scavenging mitochondrial ROS, SkQ1 NPs could in situ inhibit DED-induced mtDNA oxidation, thus blocking the interaction of ox-mtDNA and NLRP3; this, in turn, suppressed NLRP3 inflammasome activation and NLRP3-mediated inflammatory signaling. Results suggested that SkQ1 NPs have great potential as a new treatment for DED.


Subject(s)
Dry Eye Syndromes , Nanoparticles , Humans , Inflammasomes/metabolism , Inflammasomes/pharmacology , NLR Family, Pyrin Domain-Containing 3 Protein , DNA, Mitochondrial , Reactive Oxygen Species/metabolism , Hydrogen Peroxide/metabolism , Mitochondria , Inflammation/metabolism
4.
Int J Nanomedicine ; 18: 2447-2463, 2023.
Article in English | MEDLINE | ID: mdl-37192892

ABSTRACT

Introduction: Benzalkonium chloride (BAC) is widely employed as a preservative in eye drops, which will cause the death of corneal epithelial cells due to ROS production, DNA strand breakage, and mitochondrial dysfunction, resulting in dry eye disease (DED)-like changes in ocular surface tissues. In this study, Melatonin (MT) liposomes (TAT-MT-LIPs) designed by loading MT into TAT-modified liposomes have been developed, characterized, and used for inhibiting BAC-induced DED (BAC-DED). Methods: The TAT was chemically grafted onto the Mal-PEG2000-DSPE by Michael's addition between the sulfhydryl group in TAT and the maleimide group in Mal-PEG2000-DSPE. TAT-MT-LIPs were prepared using film dispersion followed by the extrusion method and topically treated in rats once a day. BAC-DED was induced in rats by topical administration with 0.2% BAC twice daily. Defects, edema, and inflammation of the corneas, as well as IOP, were examined. Histologic analyses of corneas were performed to assess the change of mitochondrial DNA oxidation and NLRP3/Caspase-1/GSDMD signaling transduction. Results: After topical administration, TAT-MT-LIPs significantly alleviated DED-clinical symptoms of experimental animals by inhibiting tissue inflammation and preventing the loss of the corneal epithelium and conjunctival goblet cells. Our data suggested continuous ocular surface exposure of BAC-induced NLRP3/Caspase-1/GSDMD mediated corneal epithelium pyroptosis, which was not reported before. BAC caused substantial mt-DNA oxidation, which promoted the transduction of NLRP3/Caspase-1/GSDMD and consequent corneal epithelium pyroptosis. TAT-MT-LIPs could efficiently suppress the BAC-induced corneal epithelium pyroptosis and inflammation by inhibiting mt-DNA oxidation and the subsequent signal transmission. Conclusion: NLRP3/Caspase-1/GSDMD mediated corneal epithelium pyroptosis is involved in the development of BAC-DED. The present study provided new insights into the adverse effects of BAC, which can serve as a new target for protecting corneal epithelium when applying BAC as a preservative in eye drops. The developed TAT-MT-LIPs can efficiently inhibit BAC-DED and give great potential to be developed as a new DED treatment.


Subject(s)
Dry Eye Syndromes , Epithelium, Corneal , Melatonin , Rats , Animals , Epithelium, Corneal/pathology , Benzalkonium Compounds/toxicity , Caspase 1 , Pyroptosis , NLR Family, Pyrin Domain-Containing 3 Protein , Liposomes/pharmacology , Melatonin/pharmacology , Inflammation/pathology , Dry Eye Syndromes/chemically induced , Dry Eye Syndromes/drug therapy , Dry Eye Syndromes/pathology , Ophthalmic Solutions/pharmacology
5.
Adv Healthc Mater ; 12(21): e2203242, 2023 08.
Article in English | MEDLINE | ID: mdl-37171892

ABSTRACT

Nanoparticles self-assembled by amphiphilic copolymers for loading hydrophobic molecules are intensively investigated. However, their hydrophobic molecule-loading capacity is low due to the limitation of hydrophobic groups in these copolymers. In this regard, new lysine oligomer-based multi-hydrophobic side chain polymers (MHCPs) are synthesized by polymerization of γ-benzyl-l glutamate N-carboxy anhydride initiated by side-chain primary amino groups in lysine oligomer. Each hydrophobic side chain in MHCPs can be self-assembled by hydrophobic interaction to form multi-hydrophobic-core nanoparticles (MHC-NPs) with silkworm cocoon-, grape cluster-, and butterfly-like shapes (depending on hydrophobic-side-chains lengths). To increase their stability, MHC-NPs are dually self-assembled with polyethylene glycol-polyglutamic acid through charge interaction. Each hydrophobic core in MHC-NPs serves as a carrier for hydrophobic molecules, endowing their nanostructure with high loading capacity. MHC-NPs are employed to load tacrolimus (also known as FK506), and the loading amount is 18% and the loading efficiency is 80%, which are higher than those of previously reported nanomicelles self-assembled by linear amphiphilic copolymers. Topical administration of FK506-loaded nanoparticle (FK506-NP) can significantly prolong retention of FK506 on the eye surface. FK506-NP exhibits higher in vivo immunosuppressive effects than free FK506 and commercial FK506 eye drop, as well as a better protective effect against immunotoxicity in the corneal grafts after keratoplasty.


Subject(s)
Corneal Transplantation , Nanoparticles , Tacrolimus/pharmacology , Tacrolimus/chemistry , Lysine , Polyethylene Glycols/chemistry , Polymers/chemistry , Nanoparticles/chemistry , Hydrophobic and Hydrophilic Interactions , Drug Carriers/chemistry
6.
Sci Total Environ ; 865: 161089, 2023 Mar 20.
Article in English | MEDLINE | ID: mdl-36587706

ABSTRACT

Weather aging may cause more severe degradation on asphalt than thermal-oxidative aging due to the synergistic effect among oxygen, heat, ultraviolet (UV) radiation, and moisture. This study aimed to investigate weather aging effects and anti-aging mechanisms on asphalt modified with rubber-polyethylene (PE) composites. The modified binder blends and asphalt mixtures were subjected to outdoor weather aging. Dynamic shear rheometer (DSR), Fourier transform infrared spectroscopy (FTIR), Gel permeation chromatography (GPC), and optical microscopy tests were adopted to characterize the rheological properties, aging resistance, polymer degradation, and anti-aging mechanisms of modified binder blends, respectively. Mixture performance tests including Asphalt Pavement Analyzer (APA) and Ideal-CT tests were used to evaluate rutting and cracking resistance of asphalt mixtures. Results showed that weather aging can cause more severe aging to asphalt binders than pressure aging vessel (PAV) due to the severe degradation of PE particles. Rubber-PE composites alloyed with an extruder proved to stabilize PE particles in asphalt and significantly improve the aging resistance of modified binder blends. The enhanced aging resistance is attributed to the dispersion of PE particles and carbon black released by soluble rubbers.

7.
Materials (Basel) ; 15(23)2022 Nov 23.
Article in English | MEDLINE | ID: mdl-36499827

ABSTRACT

The air void system purposely introduced by an air-entraining admixture (AEA) is of great significance for the protection of concrete from freeze-thaw damage. Fly ash has been globally used in concrete, while the unburnt carbon in fly ash can adsorb AEA molecules and, thus, increase the AEA demand. Previous studies primarily focused on the air content of fresh fly ash concrete. This paper aimed to explore the stability and distribution of air voids in fly ash concrete at the fresh state. To achieve this goal, eleven different fresh fly ash concrete mixtures with an initial air content of 6 ± 1% were prepared in the laboratory. Samples were taken at various times within 75 min after initial mixing to investigate the air content and air void distribution in fly ash concrete at the fresh state using a super air meter (SAM). The results indicated that there was no significant correlation between loss on ignition (LOI) of fly ash and AEA demand to achieve the initial air content of 6 ± 1%. Class C fly ash concrete tended to have a better air content retention than Class F fly ash concrete. Compared with LOI, AEA demand had a stronger correlation with air content retention. Most of the fly ash concrete mixtures had a satisfactory air void system immediately after mixing, but the SAM number showed an increasing trend over time, suggesting the coarsening of the air void system with time.

8.
Biomater Adv ; 138: 212936, 2022 Jul.
Article in English | MEDLINE | ID: mdl-35913229

ABSTRACT

Traumatic optic neuropathy (TON) is the major contributor to optic nerve damage, where the retinal ganglion cells (RGCs) are substantially lost. However, the underlying pathological mechanisms for these conditions remain largely elusive. Present work conducted a study on TON rat model, where the iron-dependent cyclooxygenase-2 (COX-2) overexpression and lipid peroxidation were observed in RGCs, suggesting ferroptosis, an iron-dependent non-apoptotic cell death, is involved in TON-induced death of RGCs. Hence, the newly formulated hyaluronic acid (HA)-based deferoxamine (DFO) nanoparticles (DFO-NPs) were intravitreally administrated in the rat model. It was hypothesized that the effective delivery of DFO, iron chelator, to the RGCs might rescue RGC ferroptosis from TON-induced injury. Also, since DFO is poor in bioavailability and of very short half-life in vivo, its safe and efficient intravitreal delivery is critical. Therefore, DFO-NPs were prepared by chemical grafting DFO onto HA molecules, and then crosslinking them in microemulsion bubbles for nanoparticles formulation. The nanoparticles were highly accumulated around the ganglionic cells and DFO uptake was increased in RGCs, accompanied by the significantly inhibited the overexpression of COX-2 and inactivation of glutathione peroxidase 4 (GPX4). These results indicate that DFO-NPs acted as an effective ferroptosis inhibitor, for the prevention of TON-induced RGC death. The current study provides new insights into the underlying mechanism of TON-induced RGC death, which may help to explore a novel strategy for the treatment of TON.


Subject(s)
Ferroptosis , Nanoparticles , Optic Nerve Injuries , Animals , Cyclooxygenase 2/metabolism , Deferoxamine/pharmacology , Iron/metabolism , Nanoparticles/therapeutic use , Optic Nerve Injuries/drug therapy , Rats , Retinal Ganglion Cells
9.
J Hazard Mater ; 403: 123632, 2021 Feb 05.
Article in English | MEDLINE | ID: mdl-32846257

ABSTRACT

Geopolymer has received increasing amounts of attention recently due to its potential utilization of industrial and urban wastes. However, the variability of source materials and the complexity of mixture design hinder geopolymer applications derived from various waste streams. There is a need for a practical and quick scanning tool for material evaluation and mixture design optimization. Six types of industrial and urban wastes, two types of reagents, and two curing temperatures were employed in this study to systematically evaluate the feasibility of using isothermal calorimetry to optimize the geopolymer mixture design and predict the three-day strength. Test results show that isothermal calorimetry has the potential to quantify the compositional differences between source materials, identify the different kinetics of geopolymers, and determine the mechanical properties of final products. For the source materials with similar microstructure and fineness, fairly strong correlations between heat and strength could be found with R2 = 0.91 for the NaOH solution and R2 = 0.90 for the composite solution.

10.
J Safety Res ; 75: 57-66, 2020 12.
Article in English | MEDLINE | ID: mdl-33334493

ABSTRACT

INTRODUCTION: Although the term "golden hour" is a well-known concept among trauma system and emergency medical service providers, the relationship between time and trauma patient outcome and the process of prehospital care for road trauma patients in rural settings are poorly understood. As the underlying basis for triage decision-making, the estimated transport interval to trauma center is usually absent in the existing studies. METHOD: In this study, the crash data between 2013 and 2017 were obtained from the Fatality Analysis Reporting System, and the estimated intervals were calculated by using a Geographic Information System software. By comparing the estimated intervals with actual emergency medical services records, the field triage patterns for road patients were investigated at the state and county levels. RESULTS AND CONCLUSIONS: With the help of the interval prediction maps, the different triage patterns among counties were identified. Further, the average fatalities per 100,000 population by county from the National Highway Traffic Safety Administration were adopted to clarify the associated outcomes. The linear regression analysis results revealed that, for most states, all intervals except the notification interval had a significant correlation with the mortality. The estimated interval had a more significant relationship with the mortality than the actual transport interval. Practical applications: These findings indicated that adhering to the "golden hour" without regarding the destination may not be helpful for the survival of road trauma patients. The regression analyses and the interval maps can be used to identify patterns of inappropriate destination selection so that prospective decision-making can be improved.


Subject(s)
Accidents, Traffic/statistics & numerical data , Triage/statistics & numerical data , Wounds and Injuries/therapy , Humans , United States , Wounds and Injuries/etiology
11.
Drug Deliv ; 27(1): 556-564, 2020 Jan 01.
Article in English | MEDLINE | ID: mdl-32351142

ABSTRACT

Following the traumatic axonal injury in the optic nerve, the failure of retrograde axonal transport to continuously supply neurotrophins from the brain to retina results in deprivation of neurotrophins in retinal ganglion cells (RGCs), which in turn can modulate the fate of RGCs toward apoptosis and thereby impede axon regeneration. In this study, a ciliary neurotrophic factor (CNTF) loaded thermo-sensitive hydrogel was designed and developed as a localized drug depot to restore neurotrophins supply following axon injury. Besides, following traumatic axon injury, overactive immune responses cause neurotoxicity and induce scar formation which together constitutes the major hindrances for axon regeneration. Thus, the FK506, a hydrophobic macrolide immunosuppressant, was co-loaded into the hydrogel after encapsulating it into a polymeric micelle. The materials can undergo sol-to-gel transition within minutes under a physiological pH of 37 °C. The release of drugs from the hydrogel exhibited a sustainable profile in vitro. The optic nerve was exposed by surgical procedure and the animal model was prepared by crushing the nerve with a reverse clamp. For the localized delivery to the optic nerve, a pre-hydrogel liquid containing chitosan, FK506 (in micelle), CNTF, and the gelling agent was directly smeared on the injured site, which gelled under physiological condition. This co-delivery system exhibited in vivo RGCs protective effect against the adverse effects caused by traumatic optic nerve injury, indicating the potential of this drug delivery system for effective optic nerve repair and this strategy may provide promising platforms for localized drug delivery in various other therapies.


Subject(s)
Ciliary Neurotrophic Factor/administration & dosage , Drug Carriers/chemistry , Hydrogels/chemistry , Nanoparticles/chemistry , Optic Nerve Injuries/drug therapy , Retinal Ganglion Cells/drug effects , Tacrolimus/administration & dosage , Animals , Axons/drug effects , Axons/pathology , Cell Survival/drug effects , Cells, Cultured , Ciliary Neurotrophic Factor/pharmacokinetics , Ciliary Neurotrophic Factor/therapeutic use , Disease Models, Animal , Drug Liberation , Hot Temperature , Micelles , Nerve Regeneration/drug effects , Optic Nerve/drug effects , Optic Nerve/pathology , Rabbits , Rats , Rats, Sprague-Dawley , Retinal Ganglion Cells/pathology , Rheology , Tacrolimus/pharmacokinetics , Tacrolimus/therapeutic use
12.
Materials (Basel) ; 12(9)2019 May 08.
Article in English | MEDLINE | ID: mdl-31072007

ABSTRACT

A two-step method involving continuous screw-extrusion steam explosion (CSESE) pretreatment and esterification in supercritical carbon dioxide (scCO2) is used to prepare long-chain fatty acid-modified jute fiber. The weight gain percentage (WG %) of CSESE-pretreated jute laurate (JL) was 110.7% when esterification was carried out in scCO2 at 14 MPa and 100 °C for 2 h. The corresponding WG % was 105.5% when esterification was instead carried out in pyridine at 100 °C for 2 h. Scanning electron microscopy and X-ray diffraction indicated that CSESE pretreatment enhanced the reactivity of jute fiber, with esterification in scCO2 simultaneously occurring on the fibers surface and internal walls. The glass transition temperature of esterified jute was approximately 119 °C, indicating that it could be hot processed over a wide temperature range. The esterified jute had an oil absorption ratio of 17.01 g/g, so it can be used as an oil absorption material.

13.
J Hazard Mater ; 369: 503-511, 2019 05 05.
Article in English | MEDLINE | ID: mdl-30807990

ABSTRACT

As an industrial waste characterized by huge volume and high alkalinity, red mud has become a serious environmental problem. The reuse of red mud has been explored in previous studies, including as building materials and for soil and waste water treatment. In this study, an innovation was made for the reuse of red mud to create a synergistic effect. Red mud was first used in flue gas desulfurization (FGD), and then the desulfurized red mud was again reused to make a geopolymer material. By using one type of original red mud and three types of fly ash, this study revealed that with high alkalinity and desulfurization capacity, the red mud could serve as an excellent FGD sorbent. After FGD, the sodium sulfate in the desulfurized red mud acted as a chemical activator for geopolymer made with class C fly ash. A 25% increase in strength was observed between the geopolymers with the red mud after FGD and with the original one. There are no significant benefits of FGD on the class F fly ash-based geopolymers and further study is required.

14.
J Safety Res ; 65: 21-27, 2018 06.
Article in English | MEDLINE | ID: mdl-29776526

ABSTRACT

INTRODUCTION: Existing research indicates that around 90% of all U.S. residents have access to at least one level I or II trauma center within 60min. However, a limitation of these estimates lies in that they are based on where people live and not where people are injured, which may overestimate the access to trauma centers for seriously injured patients in fatal crashes. METHOD: In this study, the Fatality Analysis Reporting System (FARS) data between 2013 and 2014 were collected and analyzed to quantify the access of injured patients to trauma centers for fatal crashes across states. Two types of distance, linear distance and route distance, were calculated using ArcGIS. The estimated transport time to the nearest level I/II trauma center was also calculated and compared to the recorded on-scene and transport time. RESULTS AND CONCLUSIONS: The Northeast region had the nearest average linear and route distance between fatal crash and trauma center (25.3km and 31.7km, respectively), followed by the Midwest (44.4km and 54.1km), the South (47.3km and 57.0km), and the West (50.9km and 67.5km). The comparison between the estimated and actual transport time revealed that the different states adopted different trauma triage protocols, resulting in different utilization rates of the level I/II trauma center among states. A linear regression analysis demonstrated that the longer the average route distance, the less the seriously injured patients in fatal crashes were taken to level I/II trauma center directly. Practical applications: These findings may help to identify the access to trauma centers for road crashes and the variation of delivery ratio to trauma center among the states, therefore a better utilization of trauma centers for road crashes can be achieved for the emergency medical services (EMS) systems.


Subject(s)
Accidents, Traffic/statistics & numerical data , Trauma Centers/supply & distribution , Humans , Linear Models , Trauma Centers/statistics & numerical data , United States
15.
Int J Inj Contr Saf Promot ; 25(3): 329-335, 2018 Sep.
Article in English | MEDLINE | ID: mdl-29460672

ABSTRACT

Although supported by little scientific evidence, the concept of 'golden hour,' which claims that mortality for trauma patients rises significantly over rescue time, plays a vital role in the design of our current trauma system. Only the contrary results could be found by using Fatality Analysis Reporting System data from 2010 to 2012. The results of logistic regression showed that longer total time intervals were associated with lower traffic mortality, with an odds ratio (OR) of 0.993 per minute. Utilizing the closest facility solver in the Geographic Information System, the effect of 'reverse causation' and the difference between trauma centre and non-trauma centre on the time-mortality relationship were discussed. Furthermore, based on the Kentucky Collision Analysis for the Public data from 2010 to 2012, the results of logistic regression showed that the mortality increased with each additional mile to the trauma centre with an OR of 1.011 per mile.


Subject(s)
Accidents, Traffic/mortality , Geographic Information Systems , Health Services Accessibility , Trauma Centers , Humans , Kentucky/epidemiology , Logistic Models , Time Factors , Wounds and Injuries/mortality
16.
J Biol Chem ; 293(6): 2137-2148, 2018 02 09.
Article in English | MEDLINE | ID: mdl-29273633

ABSTRACT

The progenitor cells in the cerebral cortex coordinate proliferation and mitotic exit to generate the correct number of neurons and glial cells during development. However, mechanisms for regulating the mitotic cycle of cortical progenitors are not fully understood. Otx1 is one of the homeobox-containing transcription factors frequently implicated in the development of the central nervous system. Mice bearing a targeted deletion of Otx1 exhibit brain hypoplasia and a decrease in the number of cortical neurons. We hypothesized that Otx1 might be crucial to the proliferation and differentiation of cortical progenitors. Otx1 knockdown by in utero electroporation in the mouse brain reduced the proportion of the G1 phase while increasing the S and M phases of progenitor cells. The knockdown diminished Tbr1+ neurons but increased GFAP+ astrocytes in the early postnatal cortex as revealed by lineage tracing study. Tbr2+ basal progenitors lacking Otx1 were held at the transit-amplifying stage. In contrast, overexpression of wildtype Otx1 but not an astrocytoma-related mutant Y320C inhibited proliferation of the progenitor cells in embryonic cortex. This study demonstrates that Otx1 is one of the key elements regulating cortical neurogenesis, and a loss-of-function in Otx1 may contribute to the overproduction of astrocytes in vivo.


Subject(s)
Cell Cycle , Cerebral Cortex/cytology , Neural Stem Cells/cytology , Otx Transcription Factors/physiology , Animals , Astrocytes/cytology , Cell Count , Cell Differentiation , Cell Proliferation , Cerebral Cortex/embryology , Cerebral Cortex/growth & development , Mice , Neurogenesis , Neurons/cytology
17.
Biochem Biophys Res Commun ; 494(3-4): 569-574, 2017 12 16.
Article in English | MEDLINE | ID: mdl-29066351

ABSTRACT

MicroRNAs are important regulators of the pathogenesis of B-cell acute lymphoblastic leukaemia (B-ALL). In this study, we identified miR-3173 and its predicted target gene PTK2 were correspondingly differentially expressed in B-ALL patients. In B-ALL cell lines, CCK-8 proliferation assay revealed that miR-3173 could inhibit the cell proliferation. Moreover, transwell assay revealed that miR-3173 could also inhibit cell migration and invasion in B-ALL cell lines. Luciferase assays revealed that miR-3173 directly bound to the 3'untranslated region of PTK2, and western blotting showed that miR-3173 suppressed the expression of PTK2 at the protein level. Generally, this study indicates that miR-3173 negatively regulates PTK2 and inhibits proliferation and invasion of B-ALL cell lines. Thus, miR-3173 may represent a potential therapeutic molecule for B-ALL intervention.


Subject(s)
Focal Adhesion Kinase 1/metabolism , MicroRNAs/metabolism , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/metabolism , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma/pathology , Adolescent , Adult , Cell Movement , Child , Child, Preschool , Down-Regulation , Female , Humans , Infant , Male , Neoplasm Invasiveness , Tumor Cells, Cultured , Young Adult
18.
Int J Inj Contr Saf Promot ; 24(2): 208-221, 2017 Jun.
Article in English | MEDLINE | ID: mdl-27094620

ABSTRACT

Recent research demonstrates the appropriateness of multivariate regression models in crash count modelling when one specific type of crash counts needs to be analysed, since they can better handle the correlated issues in multiple crash counts. In this paper, a random-parameter multivariate zero-inflated Poisson (RMZIP) regression model is proposed as an alternative multivariate methodology for jointly modelling crash counts simultaneously. Using this RMZIP model, we are able to account for the heterogeneity due to the unobserved roadway geometric design features and traffic characteristics. Our formulation also has the merit of handling excess zeros in correlated crash counts, a phenomenon that is commonly found in practice. The Bayesian method is employed to estimate the model parameters. We use the proposed modelling framework to predict crash frequencies at urban signalized intersections in Tennessee. To investigate the model performances, three models - a fixed-parameter MZIP model, a random-parameter multivariate negative binomial (RMNB) model, and a random-parameter multivariate zero-inflated negative binomial (RMZINB) model - have been employed as the comparison methods. The comparison results show that the proposed RMZIP models provide a satisfied statistical fit with more variables producing statistically significant parameters. In other word, the RMZIP models have the potential to provide a fuller understanding of how the factors affect crash frequencies on specific roadway intersections. A variety of variables are found to significantly influence the crash frequencies by varying magnitudes. These variables result in random parameters and thereby their effects on crash frequencies are found to vary significantly across the sampled intersections.


Subject(s)
Accidents, Traffic , Accidents, Traffic/statistics & numerical data , Environment Design , Models, Statistical , Poisson Distribution
19.
Int J Clin Exp Pathol ; 8(4): 4001-7, 2015.
Article in English | MEDLINE | ID: mdl-26097587

ABSTRACT

Cullin1 (Cul1) is a scaffold protein of the ubiquitin E3 ligase Skp1/Cullin1/Rbx1/F-box protein complex, which ubiquitinates a broad range of proteins involved in cell-cycle progression, signal transduction, and transcription. To investigate the role of Cul1 in the development of hepatocellular carcinoma (HCC), we evaluated the Cul1 expression by immunohistochemistry using a tissue microarray (TMA) containing 90 cases HCC tissues and paired adjacent non-cancerous tissues. We analyzed the correlation between Cul1 expression and clinicopathologic variables and patients survival using two independent HCC cohorts TMA. Our data showed that Cul1 expression was apparently increased in HCC tissues compared with paired adjacent non-tumor tissues. We also demonstrated that Cul1 staining was significantly correlated with tumor size, histology grade and TNM stage. Furthermore, we showed a strong correlation between high Cul1 expression and worse 5-year overall and disease-specific survival rates in HCC patients. Finally, univariate and multivariate Cox proportional hazards regression analysis investigated that high Cul1 expression was a strong independent prognostic indicator of HCC. Our data indicated that Cul1 may be an important prognosis marker for human HCC.


Subject(s)
Biomarkers, Tumor/analysis , Carcinoma, Hepatocellular/enzymology , Cullin Proteins/analysis , Liver Neoplasms/enzymology , Carcinoma, Hepatocellular/mortality , Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/therapy , Disease Progression , Disease-Free Survival , Female , Humans , Immunohistochemistry , Kaplan-Meier Estimate , Liver Neoplasms/mortality , Liver Neoplasms/pathology , Liver Neoplasms/therapy , Male , Middle Aged , Multivariate Analysis , Neoplasm Grading , Neoplasm Staging , Predictive Value of Tests , Proportional Hazards Models , Risk Factors , Time Factors , Tissue Array Analysis , Treatment Outcome , Tumor Burden , Up-Regulation
20.
Int J Inj Contr Saf Promot ; 22(2): 116-26, 2015.
Article in English | MEDLINE | ID: mdl-24134451

ABSTRACT

To address the dilemma between the need for truck transportation and the costs related to truck-involved crashes, the key is to identify the risk factors that significantly affect truck-involved crashes. The objective of this research is to estimate the effects of the characteristics of traffic, driver, geometry, and environment on severity of truck-involved crashes. Based on four crash severity categories (fatal/incapacitating, non-incapacitating, possible injury, and no injury/property damage only), a multinomial logit model is conducted to identify the risk factors. The investigation of risk ratios indicates that lower traffic volume with higher truck percentage is associated with more serious traffic crash with fatal/incapacitating injury while a non-standard geometric design is the main cause of non-incapacitating crashes. The influences of weather are significant for the possible-injury crashes while driver condition is the principal cause of no-injury/property-damage-only crashes. In addition, the statistical results demonstrate that the influence of the truck percentage is significant. One-unit change in the truck percentage will cause more than one times probability of being in an injury.


Subject(s)
Accidents, Traffic/classification , Accidents, Traffic/statistics & numerical data , Motor Vehicles/statistics & numerical data , Adult , Driving Under the Influence , Environment Design , Equipment Design , Female , Humans , Injury Severity Score , Male , Middle Aged , Models, Statistical , Risk Factors , Risk-Taking , Sex Factors , Tennessee , Weather
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