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After ingestion of toxin-contaminated food, the brain initiates a series of defensive responses (e.g., nausea, retching, and vomiting). How the brain detects ingested toxin and coordinates diverse defensive responses remains poorly understood. Here, we developed a mouse-based paradigm to study defensive responses induced by bacterial toxins. Using this paradigm, we identified a set of molecularly defined gut-to-brain and brain circuits that jointly mediate toxin-induced defensive responses. The gut-to-brain circuit consists of a subset of Htr3a+ vagal sensory neurons that transmit toxin-related signals from intestinal enterochromaffin cells to Tac1+ neurons in the dorsal vagal complex (DVC). Tac1+ DVC neurons drive retching-like behavior and conditioned flavor avoidance via divergent projections to the rostral ventral respiratory group and lateral parabrachial nucleus, respectively. Manipulating these circuits also interferes with defensive responses induced by the chemotherapeutic drug doxorubicin. These results suggest that food poisoning and chemotherapy recruit similar circuit modules to initiate defensive responses.
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Eje Cerebro-Intestino , Núcleos Parabraquiales , Nervio Vago , Animales , Ratones , Neuronas/fisiología , Neuronas Aferentes/fisiología , Nervio Vago/fisiologíaRESUMEN
Caspase-11, a cytosolic endotoxin (lipopolysaccharide: LPS) receptor, mediates pyroptosis, a lytic form of cell death. Caspase-11-dependent pyroptosis mediates lethality in endotoxemia, but it is unclear how LPS is delivered into the cytosol for the activation of caspase-11. Here we discovered that hepatocyte-released high mobility group box 1 (HMGB1) was required for caspase-11-dependent pyroptosis and lethality in endotoxemia and bacterial sepsis. Mechanistically, hepatocyte-released HMGB1 bound LPS and targeted its internalization into the lysosomes of macrophages and endothelial cells via the receptor for advanced glycation end-products (RAGE). Subsequently, HMGB1 permeabilized the phospholipid bilayer in the acidic environment of lysosomes. This resulted in LPS leakage into the cytosol and caspase-11 activation. Depletion of hepatocyte HMGB1, inhibition of hepatocyte HMGB1 release, neutralizing extracellular HMGB1, or RAGE deficiency prevented caspase-11-dependent pyroptosis and death in endotoxemia and bacterial sepsis. These findings indicate that HMGB1 interacts with LPS to mediate caspase-11-dependent pyroptosis in lethal sepsis.
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Caspasas/inmunología , Endotoxinas/inmunología , Proteína HMGB1/inmunología , Piroptosis/inmunología , Sepsis/inmunología , Animales , Caspasas/genética , Caspasas/metabolismo , Células Cultivadas , Células Endoteliales/inmunología , Células Endoteliales/metabolismo , Endotoxinas/metabolismo , Células HEK293 , Proteína HMGB1/genética , Proteína HMGB1/metabolismo , Humanos , Lipopolisacáridos/inmunología , Lipopolisacáridos/metabolismo , Macrófagos/inmunología , Macrófagos/metabolismo , Masculino , Ratones Endogámicos C57BL , Ratones Noqueados , Receptor para Productos Finales de Glicación Avanzada/inmunología , Receptor para Productos Finales de Glicación Avanzada/metabolismo , Sepsis/genética , Sepsis/metabolismo , Células THP-1RESUMEN
A central principle of synaptic transmission is that action potential-induced presynaptic neurotransmitter release occurs exclusively via Ca2+ -dependent secretion (CDS). The discovery and mechanistic investigations of Ca2+ -independent but voltage-dependent secretion (CiVDS) have demonstrated that the action potential per se is sufficient to trigger neurotransmission in the somata of primary sensory and sympathetic neurons in mammals. One key question remains, however, whether CiVDS contributes to central synaptic transmission. Here, we report, in the central transmission from presynaptic (dorsal root ganglion) to postsynaptic (spinal dorsal horn) neurons in vitro, (i) excitatory postsynaptic currents (EPSCs) are mediated by glutamate transmission through both CiVDS (up to 87%) and CDS; (ii) CiVDS-mediated EPSCs are independent of extracellular and intracellular Ca2+ ; (iii) CiVDS is faster than CDS in vesicle recycling with much less short-term depression; (iv) the fusion machinery of CiVDS includes Cav2.2 (voltage sensor) and SNARE (fusion pore). Together, an essential component of activity-induced EPSCs is mediated by CiVDS in a central synapse.
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Ganglios Espinales , Células del Asta Posterior , Animales , Células del Asta Posterior/fisiología , Transmisión Sináptica/fisiología , Potenciales Postsinápticos Excitadores/fisiología , Sinapsis , MamíferosRESUMEN
KEY MESSAGE: The candidate gene AhLBA1 controlling lateral branch angel of peanut was fine-mapped to a 136.65-kb physical region on chromosome 15 using the BSA-seq and QTL mapping. Lateral branch angel (LBA) is an important plant architecture trait of peanut, which plays key role in lodging, peg soil penetration and pod yield. However, there are few reports of fine mapping and quantitative trait loci (QTLs)/cloned genes for LBA in peanut. In this project, a mapping population was constructed using a spreading variety Tifrunner and the erect variety Fuhuasheng. Through bulked segregant analysis sequencing (BSA-seq), a major gene related to LBA, named as AhLBA1, was preliminarily mapped at the region of Chr.15: 150-160 Mb. Then, using traditional QTL approach, AhLBA1 was narrowed to a 1.12 cM region, corresponding to a 136.65-kb physical interval of the reference genome. Of the nine genes housed in this region, three of them were involved in hormone metabolism and regulation, including one "F-box protein" and two "2-oxoglutarate (2OG) and Fe(II)-dependent oxygenase (2OG oxygenase)" encoding genes. In addition, we found that the level of some classes of cytokinin (CK), auxin and ethylene showed significant differences between spreading and erect peanuts at the junction of main stem and lateral branch. These findings will aid further elucidation of the genetic mechanism of LBA in peanut and facilitating marker-assisted selection (MAS) in the future breeding program.
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Arachis , Sitios de Carácter Cuantitativo , Arachis/genética , Fitomejoramiento , Mapeo Cromosómico , Fenotipo , Oxigenasas/genéticaRESUMEN
BACKGROUND: Basic fibroblast growth factor (bFGF) has been increasingly investigated due to its neuroprotection in neurodegenerative disorders. Because there are still no cures for any of these disorders, it is crucial to identify new therapeutic targets and screen potential drugs. The increased phosphorylation of tau at Ser396 leads to intracellular tau accumulation, which forms neurofibrillary tangles in Parkinson's disease (PD). In this study, neuroprotection by bFGF was observed, and the mechanisms related to its regulation of phosphorylated tau were investigated. METHODS: bFGF-loaded liposome carriers were intranasally administered to rats. The neuroprotective effects of bFGF were assessed in a PD model induced by 6-hydroxydopamine (6-OHDA) in vivo and in vitro. The phosphorylation of tau was measured, and the PI3K/Akt-GSK3ß signaling pathway was investigated. RESULTS: Our study demonstrated that liposomes markedly assisted in the delivery of bFGF to the striatum and substantia nigra of rats and enhanced the neuroprotective effects of bFGF on dopaminergic neurons. bFGF treatment significantly ameliorated the behavioral deficits induced by 6-OHDA, rescued the loss of tyrosine hydroxylase-positive neurons and increased the number of Nissl bodies. bFGF reduced the phosphorylation of tau and GSK3ß and increased the phosphorylation of PI3K/Akt. CONCLUSION: Liposomes markedly assisted in the delivery of bFGF to the brain and enhanced the neuroprotective effects of bFGF by inhibiting the phosphorylation of tau. bFGF down-regulated the phosphorylation of tau by increasing the phosphorylation of GSK3ß via the PI3K/Akt signaling pathway. These findings provide a new vision of bFGF as a potential therapy for PD.
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Encéfalo/metabolismo , Factor 2 de Crecimiento de Fibroblastos/administración & dosificación , Fármacos Neuroprotectores/administración & dosificación , Enfermedad de Parkinson/metabolismo , Transducción de Señal/efectos de los fármacos , Proteínas tau/metabolismo , Administración Intranasal , Animales , Encéfalo/efectos de los fármacos , Línea Celular Tumoral , Cuerpo Estriado/efectos de los fármacos , Cuerpo Estriado/metabolismo , Modelos Animales de Enfermedad , Neuronas Dopaminérgicas/efectos de los fármacos , Neuronas Dopaminérgicas/metabolismo , Portadores de Fármacos/administración & dosificación , Portadores de Fármacos/farmacología , Factor 2 de Crecimiento de Fibroblastos/uso terapéutico , Glucógeno Sintasa Quinasa 3 beta/metabolismo , Humanos , Liposomas/administración & dosificación , Liposomas/farmacología , Masculino , Actividad Motora/efectos de los fármacos , Fármacos Neuroprotectores/uso terapéutico , Oxidopamina , Enfermedad de Parkinson/tratamiento farmacológico , Trastornos Parkinsonianos/tratamiento farmacológico , Trastornos Parkinsonianos/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Fosforilación , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ratas , Ratas Sprague-Dawley , Tirosina 3-Monooxigenasa/metabolismoRESUMEN
Reasons for abrupt capacity fading in commercial LiNi0.8Co0.1Mn0.1O2 (NCM811)/SiO x -graphite pouch batteries were evaluated using electrochemical methods. These approaches consist of charge and discharge curves, differential curves and electrochemical impedance spectroscopy (EIS), and some advanced verification techniques constituting scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS) and X-ray diffraction (XRD). The predominance testament concerning capacity attenuation through experimental verification after the battery is disassembled proves that the silicon-based anode material deteriorates further, bringing about a significant number of cracks with the progression of cycles. In addition, electrolyte enters into the cracks, generating the excessive growth of the solid electrolyte interface (SEI) and the expansion of impedance, which eventually causes the failure of conductive networks, dilemma of ion transmission and increment in polarization, ultimately contributing to lithium dendrites.
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Mesenchymal stem cells (MSCs) can be isolated from numerous tissues and have the potential for self-renewal and multidirectional differentiation. Evidence is accumulating which suggests that MSCs are also present in the gingival tissue. This study aimed to evaluate the feasibility of collecting, purifying, and amplifying gingival-derived MSCs (GMSCs) from canine gingiva and to obtain GMSC-derived exosomes (GMSC-exo). GMSCs were isolated and cultured; furthermore, cellular immunofluorescence demonstrated that GMSCs possess characteristic MSC markers, and in vitro differentiation was induced, indicating that GMSCs can differentiate into multiple lineages. GMSC-exo was successfully extracted from GMSCs supernatant and found that they exhibit the typical characteristics of exosomes as analyzed by transmission electron microscopy, nanoflow analysis, and western blotting. GMSC-exo promoted the proliferation and migration of Madin-Darby canine kidney cells. It was concluded that canine gingiva is a good source of MSCs. Additionally, GMSC-exo is a potentially promising cell-free therapeutic tool for the treatment of canine gingival diseases.
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Peanut is one of the most important cash crops with high quality oil, high protein content, and many other nutritional elements, and grown globally. Cultivated peanut (Arachis hypogaea L.) is allotetraploid with a narrow genetic base, and its genetics and molecular mechanisms controlling the agronomic traits are poorly understood. Here, we report a comprehensive genome variation map based on the genotyping of a panel of 178 peanut cultivars using Axiom_Arachis2 SNP array, including 163 representative varieties of different provinces in China, and 15 cultivars from 9 other countries. According to principal component analysis (PCA) and phylogenetic analysis, the peanut varieties were divided into 7 groups, notable genetic divergences between the different areas were shaped by environment and domestication. Using genome-wide association study (GWAS) analysis, we identified several marker-trait associations (MTAs) and candidate genes potentially involved in regulating several agronomic traits of peanut, including one MTA related with hundred seed weight, one MTA related with total number of branches, and 14 MTAs related with pod shape. This study outlines the genetic basis of these peanut cultivars and provides 13,125 polymorphic SNP markers for further distinguishing and utility of these elite cultivars. In addition, the candidate loci and genes provide valuable information for further fine mapping of QTLs and improving the quality and yield of peanut using a genomic-assisted breeding method.
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Currently, due to the lack of long-term postoperative follow-up outcomes of the congenital divided eyelid nevus, we described our surgical approaches and presented the functional and cosmetic results of 13 patients with an average of 5-year follow-up. Based on the surgical treatments and the follow-ups, the selection of total or subtotal excision depends on the lesion location and the use of blepharoplasty approaches is determined by defect size. The CO2 laser may be a useful second-stage procedure to ablate remnant lesions, but long-term monitoring is required.
Étant donné le peu de suivi postopératoire à long terme sur les résultats cliniques de la réparation du nævus palpébral congénital en miroir, les chercheurs décrivent les méthodes chirurgicales utilisées et présentent les résultats fonctionnels et esthétiques chez 13 patients, suivis sur une période moyenne de cinq ans. D'après les traitements chirurgicaux et les suivis, le choix d'une excision totale ou partielle dépend du foyer de la lésion, et le mode de blépharoplastie repose sur la dimension de l'anomalie. Le laser CO2 peut être utilisé en deuxième phase pour faire disparaître les vestiges des lésions, mais une surveillance à long terme s'impose.
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BACKGROUND: Nurse competence is a combination of knowledge, performance, skills, and attitudes that are required in fulfilling one's role as a nurse. So far, few comprehensive studies have explored the influencing factors of nurse competence. METHOD: The competence levels of 160 RNs in a Chinese hospital were evaluated using a questionnaire method, and the relationship between competence results and nursing characteristics was analyzed. RESULTS: The competence of participating nurses was at a medium level. Among all the characteristics, education and staffing levels were two main factors influencing nurse competence. CONCLUSION: Quantity of nurses and quality of nursing service are two main issues facing the modern nursing system. The findings from this study provide useful information and suggestions on how to improve nurse competence to nurse industry personnel, including nurses, nursing employers, educators, and students. [J Contin Educ Nurs. 2019;50(12):572-580.].
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Actitud del Personal de Salud , Competencia Clínica/normas , Rol de la Enfermera/psicología , Enfermeras y Enfermeros/psicología , Enfermeras y Enfermeros/normas , Autoimagen , Adulto , China , Femenino , Humanos , Masculino , Persona de Mediana Edad , Encuestas y CuestionariosRESUMEN
The monotypic genus Leifia was previously considered to be a later synonym of Odonticium. With the morphological and phylogenetic evidence provided by an additional four East Asian specimens, we propose to reinstate Leifia as an independent genus in Hymenochaetales. Leifia morphologically differs from Odonticium by its grandinioid hymenophore with hyphal strands, numerous thick-walled cystidia with an invaginated apical end and narrowly and thick-walled basidia. The phylogeny generated from the current data set of ITS and 28S regions indicates that Leifia forms a sister clade to Odonticium. Besides the generic type Leifiaflabelliradiata in the Leifia clade, two specimens, collected from Hubei, Central China, are newly introduced as Leifiabrevispora. This new species is the second species of Leifia and differs from the generic type by its shorter basidiospores and distribution in warm-temperate to subtropical areas in East Asia. The additional two specimens, collected from Da Lat, Viet Nam, differ morphologically, both from each other and from known species of Leifia, but more samples need to be examined before further taxonomic decisions can be made.
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OBJECTIVE: To explore the relationship of cell apoptosis and expression regularity of hypoxia-inducible transcription factor (HIF)-1 alpha after severe burn with delayed fluid resuscitation in areas of different altitude. METHODS: A total of 240 male Wistar rats, which were raised in areas of different altitude (1,517 and 3,840 meters), were employed as the experimental models [They received a 30% total body surface area (TBSA)III degree scald injury], and then they were randomly divided into 3 groups: delayed fluid resuscitation group (DFR, n=50), immediate fluid resuscitation group (IFR, n=60) and control group (CG, n=10). Renal tissue samples were harvested at 1, 6, 12, 24, 72 and 168 hours after burn, respectively. Cell apoptosis was detected by tissue chip technology and terminal deoxynucleotidyl transferase-mediated dUTP biotin nick end labeling (TUNEL). The expression of HIF-1 alpha was assessed by immunohistochemistry and image analysis. RESULTS: With increase in altitude, cellular edema, degeneration, necrosis and disintegration of renal tissue were gradually worsening, the capillaries of renal glomeruli became dilated and engorged, with degeneration and necrosis of endothelial cells, engorgement and edema of renal interstitium, and infiltration of inflammatory cells. Pathological changes in DFR group were more serious than that of IFR group. Cell apoptosis and the expression of HIF-1 alpha were both enhanced, the latter mainly appeared in nuclei of renal cells, and they were more marked at 3,840 meters compared with those at 1,517 meters. They were more marked in experimental groups than in control group, especially so in DFR group (P<0.01). Cell apoptosis was positively correlated with the expression of HIF-1 alpha (r= -0.651, P<0.01). CONCLUSION: Severe burn at high attitude plateau results in high expression of HIF-1 alpha and an increase in apoptosis of renal cells. HIF-1 alpha plays a role in kidney cell apoptosis.
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Altitud , Apoptosis , Quemaduras/patología , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Riñón/patología , Animales , Quemaduras/metabolismo , Quemaduras/terapia , Modelos Animales de Enfermedad , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Riñón/citología , Riñón/metabolismo , Masculino , ARN Mensajero/genética , Distribución Aleatoria , Ratas , Ratas Wistar , Resucitación/métodosRESUMEN
Stearoyl lysophosphatidylcholine (LPC) exerts protective effect during endotoxemia and in experimental sepsis, but the underlying mechanism is unclear. Here, we demonstrated that stearoyl LPC could block caspase-11-mediated macrophage pyroptosis. In vitro, stearoyl LPC significantly decreased caspase-11 activation and pyroptosis induced by lipopolysaccharide (LPS) plus cholera toxin subunit B independent of the receptor G2A. Stearoyl LPC did not affect LPS uptake by mouse peritoneal macrophages but did significantly inhibit the interaction between LPS and caspase-11. Moreover, stearoyl LPC treatment conferred significant protection against lethal endotoxemia and significantly reduced the release of IL-1α and IL-1ß. These findings identify stearoyl LPC as an inhibitor of LPS-mediated caspase-11 activation. This mechanism could explain the protective action of stearoyl LPC in experimental sepsis and endotoxemia.
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Caspasas/metabolismo , Lipopolisacáridos/toxicidad , Lisofosfatidilcolinas/farmacología , Macrófagos Peritoneales/metabolismo , Animales , Caspasas Iniciadoras , Endotoxemia/metabolismo , Endotoxemia/patología , Activación Enzimática/efectos de los fármacos , Interleucina-1alfa/metabolismo , Interleucina-1beta/metabolismo , Macrófagos Peritoneales/patología , RatonesRESUMEN
BACKGROUND: The purpose of this study was to preliminarily assess a constant pressure and quantity fat granule injection device for minimal invasive properties in clinic. METHODS: A retrospective controlled study was carried out, from October 2013 to January 2015, on 76 female healthy patients aged between 26 and 53 years at the General Hospital of Lanzhou Military Command, China. To achieve small volume, high thrust, and precision requirements of facial fat grafting, an integrated handheld controller and motor design was adopted, reducing the volume and weight of the fat transplantation injection device. The 76 patients underwent 90 procedures each side of the face; each patient was treated with the aforementioned device on the face's left side, while a conventional hand-push injection device was used on the right side as control. The outcome was assessed on pre- and postoperative images, with 6-24 months follow-up. RESULTS: The current device consistently allowed deposition of fat threads at about 55 µL/cm after cannula withdrawal; the volume of fat injected could be precisely adjusted to 0.04 mL/s. This device had the advantages of small-volume injection and convenient operation. The patients exhibited a good, stable shape and a smooth contour line in both sides. The long term satisfaction was higher for the left side than for the right one. Nodules and unevenness occurred only on the right side. Ecchymosis occurred significantly less frequent on the left side than the right one. Intraoperative pain was significantly lower for the left side than the right one. CONCLUSIONS: This device offered superior control compared with the conventional one and constitutes a promising tool for surgeons practicing lipotransfer.
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Congenital enlargement of one or several digits of the foot, known as macrodactyly, is a rare malformation. Macrodactyly impedes foot development and affects function and gait. Here, we describe a surgical technique used to correct macrodactyly in two pediatric patients. We performed amputation of the enlarged phalanx and debulking of the soft tissues to construct a normal-sized digit. This precise technique involves a simple surgical plan that preserves the metatarsus and cuneiform and does not result in a wide plantapedis. Both patients subsequently showed improved gait and were able to wear normal shoes.
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Deformidades Congénitas del Pie/cirugía , Dedos del Pie/anomalías , Dedos del Pie/cirugía , Amputación Quirúrgica , Niño , Humanos , Lactante , Masculino , TenotomíaRESUMEN
OBJECTIVE: To study the effectiveness of facial meticulous fat grafting by fat granules injection asistor. METHODS: Between January and August 2015, 46 patients received facial autologous fat grafting for rejuvenation. There were 7 males and 39 females, aged 21-65 years (mean, 34 years). Firstly, the faces were divided into 10 cosmetic zonations according to facial aesthetic criteria, then autologous fat grafting was carried out by fat granules injection asistor. The autologous fat was filled into 1, 2, 3, 4, 5, 6, 7, 8, and 9 cosmetic zonations in 3, 7, 5, 3, 8, 4, 2, 10, and 4 cases respectively; the injected fat amount was 2-110 mL (mean, 47 mL). RESULTS: The swelling period was from 5 to 15 days after operation (mean, 7 days), and there were no complications of infection, cyst, introvascular thrombogenesis, and so on. They were followed up 1-7 months (mean, 3 months). The effect of face rejuvenation was satisfactory. CONCLUSIONS: Cosmetic zonation of face is helpful for preoperative evaluation of autologous fat grafting, and the fat granules injection asistor is beneficial to reach better effect of face rejuvenation.
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OBJECTIVE: To explore changes in endothelin-1 (ET-1) and calcitonin gene-related peptide (CGRP) in the myocardium after severe burn and delayed fluid resuscitation in rats at different altitudes. METHODS: Two hundred and forty male Wistar rats were employed as the experimental models with full-thickness burn of 30% total body surface area (TBSA), and they were randomly divided into three groups: delayed fluid resuscitation group (DFR), immediate fluid resuscitation group (IFR) and control group (CG). Samples of myocardial tissue were harvested at 1 hour, 6 hours, 12 hours, 24 hours, 72 hours, 168 hours postburn respectively. The changes in ET-1 and CGRP contents were determined by means of radio immunological assay. RESULTS: (1)The contents of ET-1 and CGRP in DFR group tended to increase at 6 hours after burn, ET-1 was higher 2.8, 3.6 fold, while CGRP higher by 2.2, 1.5 fold (P<0.01), compared with that of CG respectively at 1517 m and 3840 m. The tendency of rise of ET-1 and CGRP was significantly less conspicuous in IFR group than that in DFR group. (2)The contents of ET-1 in DFR group tended to increase at 6 hours and reached the peak at 24 hours after burn at 1517 m, while the levels reached the peak at 72 hours after burn at 3840 m, and the change lasted for 168 hours in DFR group. The contents of CGRP increased significantly at 6 hours and reached the peak at 12 hours at 1517 m, while they reached the peak at 72 hours after burn at 3840 m. CONCLUSION: The myocardial contents of ET-1 tend to increase significantly with the elevation of altitude after severe burn in rats, but the contents of CGRP increased lagged behind. The result show that the higher the altitude is, the more the exhaustion of protective agents of the myocardium, thus resulting in changes in ET-1/CGRP.
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Altitud , Quemaduras/metabolismo , Péptido Relacionado con Gen de Calcitonina/metabolismo , Endotelina-1/metabolismo , Miocardio/metabolismo , Animales , Modelos Animales de Enfermedad , Masculino , Distribución Aleatoria , Ratas , Ratas Wistar , Resucitación/métodosRESUMEN
OBJECTIVE: To compare the diagnostic parameters of acute respiratory distress syndrome/multiple organ dysfunction syndrome (ARDS/MODS) at high altitude (H-ARDS/MODS) with that on plain, and to establish a more practical diagnostic criterion of H-ARDS/MODS. METHODS: Five hundred and five cases fulfilled the criteria for the diagnosis of ARDS/MODS were divided into three groups according to the altitude of their habitation: control group including inhabitants (<430 m) on plain (CG, n=113), moderate high altitude group 1 inhabitants at the altitude of 1,517 m (H1G, n=314), moderate high altitude group 2 inhabitants at the altitude of 2,261 m to 2,400 m (H2G, n=78). The ARDS/MODS scores of the three groups were made according to the diagnostic criteria of Lushan conference, Marshall(1995) and Lanzhou criteria drafted by the authors respectively to set up three data analyzing models, followed by plotting of receiver operating characteristic curves (ROC curve) and calculation of the Yordon Index and the optimum cutoff points of the parameters,in order to study the accuracy of the three diagnostic criteria in predicting the outcome of the patients suffering from ARDS/MODS. RESULTS: In CG group, the differences were not significant in area of ROC, the maximal Yordon Index, the optimum cutoff points and the sensitivity and the specificity for three criteria; but the differences were significant for the three criteria in H1G group. Further investigation in comparing the ROC values of lung, brain, heart and kidney, the Lanzhou criteria were more advantageous in the high altitude than the other criteria. CONCLUSION: (1)The current diagnostic criteria of ARDS/MODS are not suitable for the diagnosis of these syndromes in moderately high or high altitude areas. It is necessary to revise the diagnostic criteria of H-ARDS/MODS. (2)One thousand five hundred and seventeen meters in altitude might be considered to be an important borderline, above with the diagnostic criteria of ARDS/MODS for patients inhabiting on plain could not be suitably applied to those living above this level.
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Altitud , Insuficiencia Multiorgánica/diagnóstico , Síndrome de Dificultad Respiratoria/diagnóstico , Humanos , Guías de Práctica Clínica como Asunto , Estudios Retrospectivos , Índice de Severidad de la EnfermedadRESUMEN
Centrosome amplification is frequent in cancer, but the underlying mechanisms remain unclear. Here we report that disruption of the Kruppel-like factor 14 (KLF14) gene in mice causes centrosome amplification, aneuploidy and spontaneous tumorigenesis. Molecularly, KLF14 functions as a transcriptional repressor of Plk4, a polo-like kinase whose overexpression induces centrosome overduplication. Transient knockdown of KLF14 is sufficient to induce Plk4-directed centrosome amplification. Clinically, KLF14 transcription is significantly downregulated, whereas Plk4 transcription is upregulated in multiple types of cancers, and there exists an inverse correlation between KLF14 and Plk4 protein expression in human breast and colon cancers. Moreover, KLF14 depletion promotes AOM/DSS-induced colon tumorigenesis. Our findings reveal that KLF14 reduction serves as a mechanism leading to centrosome amplification and tumorigenesis. On the other hand, forced expression of KLF14 leads to mitotic catastrophe. Collectively, our findings identify KLF14 as a tumour suppressor and highlight its potential as biomarker and therapeutic target for cancer.
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Carcinogénesis/genética , Centrosoma/metabolismo , Factores de Transcripción de Tipo Kruppel/genética , Proteínas Serina-Treonina Quinasas/genética , ARN Mensajero/metabolismo , Factores de Transcripción Sp/genética , Aneuploidia , Animales , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Línea Celular Tumoral , Inmunoprecipitación de Cromatina , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/metabolismo , Femenino , Técnicas de Silenciamiento del Gen , Células HCT116 , Células HeLa , Humanos , Inmunohistoquímica , Masculino , Ratones , Ratones Noqueados , Mitosis/genética , Proteínas Serina-Treonina Quinasas/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
OBJECTIVE: To sum up the clinical characteristics, surgical management, and effectiveness of pressure sore of sinus type. METHODS: Between January 2009 and April 2013, 17 patients with 19 pressure sores of sinus type after traumatic paraplegia were treated, and the clinical data were analyzed retrospectively. There were 11 males and 6 females with an average age of 27.4 years (range, 17-49 years). The median disease duration was 1.5 years (range, 6 months to 7 years). Of 17 cases, there were 14 primary cases and 3 recurrent cases; 10 focuses of 8 cases were classified as simple sinus type, and 9 focuses of 9 cases as complex sinus type, which had a false synovial sheath complicated with one to four "second sinus". The pressure sore of sinus type majorly located at the ischial tuberosity. The size of pressure sore ranged from 1.5 cm x 1.0 cm to 3.0 cm X 2.0 cm, and the length of "second sinus" ranged from 8 to 32 cm with an average of 17 cm. After the false synovial sheath was totally excised, the wound was repaired by local sliding or rhombus flaps at the first or second stage in patients with simple sinus type pressure sore. On the basis of excising the false synovial sheath, the "second sinus" was totally removed in the patients with complex sinus type pressure sore. RESULTS: Wound dehiscence occurred in 1 case of simple sinus type pressure sore at 4 days, which was cured after it was sutured again. Wound infection occurred at 9, 17, and 23 days respectively in 3 cases of complex sinus type pressure sore, which was cured after second debridement and necrosis tissues removal. The other wounds healed by first intention, and the flaps totally survived. All patients were followed up 6-12 months (mean, 9.3 months). No recurrence was observed. CONCLUSION: According to the clinical characteristics, pressure sore of sinus type could be divided into simple sinus type and complex sinus type. The key of successful treatment is to thoroughly excise false synovial sheath and "second sinus".