RESUMEN
Chemical tagging via possible derivatization reagents alters metabolites' retention times, leading to different retention behavior during liquid chromatography-mass spectrometry (LC-MS) analysis. Incorporation of the retention time dimension can dramatically reduce false-positive structural elucidation in chemical-tagging-based metabolomics. However, few studies predict the retention times of chemically labeled metabolites, especially requiring a simple, easy-to-access, accurate, and universal predictor or descriptor. This pilot study demonstrates the application of volume-corrected free energy (VFE) calculation and region mapping as a new criterion to describe the retention time for structure elucidation in chemical-tagging-based metabolomics. The universality of VFE calculation is first evaluated with four different types of submetabolomes including hydroxyl-group-, carbonyl-group-, carboxylic-group-, and amino-group-containing compounds and oxylipins with similar chemical structures and complex isomers on reverse-phase LC. Results indicate a good correlation (r > 0.85) between VFE values and their corresponding retention times using different technicians, instruments, and chromatographic columns, describing retention behavior in reverse-phase LC. Finally, the VFE region mapping is described for identifying 1-pentadecanol from aged camellia seed oil using three proposed steps, including public database searching, VFE region mapping for its 12 isomers, and chemical standard matching. The possibility of VFE calculation of nonderivatized compounds in retention time prediction is also investigated, demonstrating its effectiveness on retention times with different influence factors.
Asunto(s)
Metabolómica , Proyectos Piloto , Metabolómica/métodos , Cromatografía Liquida/métodos , Espectrometría de Masas/métodos , IsomerismoRESUMEN
The toxicity and environmental persistence of perfluorooctanoic acid (PFOA), and perfluorooctane sulfonate (PFOS) are of great concern for food intake in humans. However, PFASs conversion or conjugation to other substances in rice grown on PFASs polluted soil has not been explored clearly. These unknown transformed or conjugated products of PFOA and PFOS could be harmful to human health. The restriction factor in evaluating the possible transformation of PFOA and PFOS is mainly attributed to the lack of an efficient method for screening PFOA and PFOS and their related metabolites. To circumvent this challenge, we established a non-targeted screening method by combining a fluoro-cotton fiber-based solid phase extraction (FC-SPE) and liquid chromatography-high resolution mass spectrometry (LC-HRMS) to monitor the formation of possible organic fluorine compounds from rice (Oryza sativa L.) grown on PFASs. We synthesized fluoro-cotton fibers to serve as the FC-SPE packing material and characterized by field-emission scanning electron-microscope, Fourier transform infrared, and X-ray photoelectron spectroscopy measurements. The optimal extraction conditions for the prepared FC-SPE were investigated. The performance of FC-SPE in LC-MS analysis was validated by linearity, precision, recovery, and matrix effect. Then the FC-SPE combined with LC-HRMS was used to specifically capture organic fluorine compounds from complex matrices via F-F interaction, including rice seedlings grown in PFOA and PFOS polluted soil and soil samples. By the established FC-SPE LC-HRMS method, in total 429 features were found as the possible organic fluorine compounds from rice seedlings grown in PFOA polluted soil among the 1781 features from the rice seedlings. Finally, we employed a13C metabolic tracing analysis of organic fluorine compounds in combination with the FC-SPE LC-HRMS method to further identify the features that detected from rice seedlings grown in PFOA polluted soil. The final result indicated that there were not any new organic fluorine metabolites screened out from rice grown in PFOA or PFOS polluted soil.
Asunto(s)
Ácidos Alcanesulfónicos , Compuestos de Flúor , Fluorocarburos , Oryza , Humanos , Fluorocarburos/análisis , Suelo/química , Flúor , Ácidos Alcanesulfónicos/análisis , CaprilatosRESUMEN
The design of nanomedicine for cancer therapy, especially the treatment of tumor metastasis has received great attention. Proteasome inhibition is accepted as a new strategy for cancer therapy. Despite being a big breakthrough in multiple myeloma therapy, carfilzomib (CFZ), a second-in-class proteasome inhibitor is still unsatisfactory for solid tumor and metastasis therapy. In this study, hollow titanium nitride (TiN) nanoshells are synthesized as a drug carrier of CFZ. The TiN nanoshells have a high loading capacity of CFZ, and their intrinsic inhibitory effect on autophagy synergistically enhances the activity of CFZ. Due to an excellent photothermal conversion efficiency in the second near-infrared (NIR-II) region, TiN nanoshell-based photothermal therapy further induces a synergistic anticancer effect. In vivo study demonstrates that TiN nanoshells readily drain into the lymph nodes, which are responsible for tumor lymphatic metastasis. The CFZ-loaded TiN nanoshell-based chemo-photothermal therapy combined with surgery offers a remarkable therapeutic outcome in greatly inhibiting further metastatic spread of cancer cells. These findings suggest that TiN nanoshells act as an efficient carrier of CFZ for realizing enhanced outcomes for proteasome inhibitor-based cancer therapy, and this work also presents a "combined chemo-phototherapy assisted surgery" strategy, promising for future cancer treatment.
Asunto(s)
Nanocáscaras , Neoplasias , Fotoquimioterapia , Humanos , Línea Celular Tumoral , Oro , Metástasis Linfática , Neoplasias/tratamiento farmacológico , Oligopéptidos , Inhibidores de Proteasoma/farmacología , TitanioRESUMEN
This study was designed to analyze the change of metabolites in the PC12 cells and its medium induced by corticosterone (CORT) and glutamate (Glu) by proton nuclear magnetic resonance ( 1H NMR) metabolomics. The multivariate statistical analysis was employed to identify the difference between control groups and induced groups, respectively. In addition, metabolite pathway analysis was performed to explore the characteristic of CORT-induced and or Glu-induced PC12 cells depression model, and to provide the references for the selection of in vitro depression models as well as the further understanding of the mechanism on depressive disorders. We found 36 differential metabolites in CORT-induced PC12 cells and medium and 42 in Glu-induced PC12 cells. Furthermore, correlation analysis results show that serine and 2-oxoisoleucine were associated with most differential metabolites in CORT-induced PC12 cells. Lactate and glutathione were significantly correlated to the vast majority of differential metabolites in Glu-induced PC12 cells. We speculated that CORT-induced PC12 cell models may affect the fatty acid metabolism and cell membrane structure, and Glu-induced PC12 cell models may have a difference in the glycolysis and antioxidants.
Asunto(s)
Corticosterona/farmacología , Ácido Glutámico/farmacología , Metabolómica , Animales , Antioxidantes/metabolismo , Depresión/tratamiento farmacológico , Trastorno Depresivo/tratamiento farmacológico , Ácidos Grasos/metabolismo , Glucólisis , Células PC12 , Espectroscopía de Protones por Resonancia Magnética , RatasRESUMEN
The study was designed to clarify the antidepressant mechanism of supercritical CO(2) extract from Compound Chaigui Fang. We used TCMSP, HIT, Pharm GKB and Gene Cards bioinformatics software to predict and analyze the drug/disease targets and their common targets of compounds in the supercritical CO(2) extract of Compound Chaigui Fang for depression. Chronic unpredictable mild stressï¼CUMSï¼was used to induce depressed model in rats. Hippocampus and serum were collected after supercritical CO(2) extract treatment to detect the potential antidepressant targets with enzyme-linked immunosorbent assayï¼ELISAï¼. The results predicate that there are 22 chemical compounds and 78 potential therapeutic drug targets for depression. There are 177 disease markers for depression, and 14 common targets for drug intervention of depression, which includes the neurotransmitter transports/metabolic enzyme/receptors, hormone of hypothalamus-pituitary-adrenal/ thyroid/gonad axis, immune-associated factor, etc. ELISA results suggest that depression is associated with the low level of phosphate c AMP responsive element-binding protein in hippocampus and the high levels of corticosterone and interleukin 6 in serum with CUMS rat. Those were restored to normal levels by supercritical CO(2) extract of Compound Chaigui Fang. The study provides an antidepressant mechanism of supercritical CO(2) extract of Compound Chaigui Fang based on the network pharmacology, and a new strategy in the study of the effective extracts of compound Chinese traditional medicine.
Asunto(s)
Antidepresivos/farmacología , Depresión/tratamiento farmacológico , Medicamentos Herbarios Chinos/farmacología , Animales , Biología Computacional , Corticosterona/sangre , Modelos Animales de Enfermedad , Hipocampo , Interleucina-6/sangre , Ratas , Ratas Sprague-Dawley , Programas Informáticos , Estrés PsicológicoRESUMEN
To elucidate the anti-depressive effect of Fufang Chaigui prescription and its mechanism and investigate its effect on neuroendocrine hormone, rats were included into a chronic unpredictable mild stress (CUMS) model for 28 d, and drugs were administered at the same time. During the period, rats' behaviors were observed and the blood was collected by using ELISA to determine representative hormone concentrations of HPAA, HPTA and HPGA. The changes in endogenous metabolites were analyzed by using H NMR metabolomics to seek the potential biomarkers. Results showed Fufang Chaigui prescription could improve the behaviors of CUMS rats obviously, increase contents of ACTH, CORT, T3and decrease contents of TSH and TESTO and regulate the levels of lactate, α-glucose, choline, N-acetylglycoprotein, trimethylamine oxide and leucine to get closer to the contents of control group. The results of correlation analysis indicated that HPTA was associated with glycometabolism, amino acid metabolism and choline metabolism. And HPAA was related to glycometabolism and amino acid metabolism. However, HPGA was only correlated with glycometabolism. In conclusion, Fufang Chaigui prescription could show an obvious anti-depressive effect and its underlying mechanism might involve regulations of neuroendocrine function and pathways of glycometabolism, amino acid metabolism and choline metabolism.
Asunto(s)
Antidepresivos/administración & dosificación , Depresión/tratamiento farmacológico , Medicamentos Herbarios Chinos/administración & dosificación , Hormonas/metabolismo , Animales , Conducta Animal , Depresión/sangre , Depresión/metabolismo , Humanos , Masculino , Metabolómica , Sistemas Neurosecretores/efectos de los fármacos , Sistemas Neurosecretores/metabolismo , Ratas , Ratas Sprague-Dawley , Suero/química , Suero/metabolismoRESUMEN
Autophagy is a conserved process in which the cytosolic materials are degraded and eventually recycled for cellular metabolism to maintain homeostasis. The dichotomous role of autophagy in pathogenesis is complicated. Accumulating reports have suggested that cytoprotective autophagy is responsible for tumor growth and progression. Autophagy inhibitors, such as chloroquine (CQ) and hydroxychloroquine (HCQ), are promising for treating malignancies or overcoming drug resistance in chemotherapy. With the rapid development of nanotechnology, nanomaterials also show autophagy-inhibitory effects or are reported as the carriers delivering autophagy inhibitors. In this review, we summarize the small-molecule compounds and nanomaterials inhibiting autophagic flux as well as the mechanisms involved. The nanocarrier-based drug delivery systems for autophagy inhibitors and their distinct advantages are also described. The progress of autophagy inhibitors for clinical applications is finally introduced, and their future perspectives are discussed.
Asunto(s)
Autofagia , Nanoestructuras , Neoplasias , Bibliotecas de Moléculas Pequeñas , Autofagia/efectos de los fármacos , Neoplasias/tratamiento farmacológico , Bibliotecas de Moléculas Pequeñas/farmacología , Bibliotecas de Moléculas Pequeñas/uso terapéutico , Homólogo de la Proteína 1 Relacionada con la Autofagia/antagonistas & inhibidores , Resistencia a Antineoplásicos/efectos de los fármacos , Nanoestructuras/uso terapéutico , Sistema de Administración de Fármacos con Nanopartículas , Ensayos Clínicos como Asunto , HumanosRESUMEN
Dried blood spots (DBS) have been regarded as a promising alternative for therapeutic drug monitoring (TDM) of immunosuppressants (ISDs) for over fifteen years. Nonetheless, there are still three main issues impeding its preference: (i) the requirement of relatively large disc; (ii) the controversial and intricate desorption approaches; (iii) the lack of feasible extraction strategies. For improvement, this work described a new LC-MS/MS method realizing quantification of four ISDs from one piece of 3.2 mm DBS. During sample pretreatment, a modified approach (infiltrating the DBS in pure water before adding acetonitrile and zinc sulfate as protein-precipitators) was developed to completely dissociate the targets from filter paper. Afterward, effective enrichment and purification of the targets were achieved by using cold-induced phase separation technique. Benefiting from these novelties, the method exhibited satisfying throughput (15 min for sample preparation), applicability (consuming only one 3.2 mm disc), reliability (82.3-107.8% for accuracy and <14.3% for precision) and sensitivity (lower limit of quantification of 0.5, 7.6, 0.7 and 0.8 ng mL-1 for tacrolimus, cyclosporine A, everolimus and sirolimus, respectively). Without hematocrit correction, the method showed favorable interchangeability to the certified whole blood method through analyzing 120 paired clinical samples. By taking ±20% of the mean as the limit of acceptance for cross validation, over 90% of the detection met the criterion. It can be expected the developed method is able to further promote the popularization of DBS-based TDM for ISDs in practice.
Asunto(s)
Inmunosupresores , Espectrometría de Masas en Tándem , Cromatografía Liquida/métodos , Pruebas con Sangre Seca/métodos , Monitoreo de Drogas/métodos , Reproducibilidad de los Resultados , Espectrometría de Masas en Tándem/métodosRESUMEN
A novel magnetic material Fe(3)O(4)/SiO(2)/P(MAA-co-VBC-co-DVB) was prepared via the hypercrosslinking of its precursor which was produced via precipitation polymerization of methacrylic acid (MAA), vinylbenzyl chloride (VBC), and divinylbenzene (DVB) in the presence of Fe(3)O(4)/SiO(2) submicrospheres with the surface containing abundant reactive double bonds. The resultant sorbent was characterized by scan electron microscopy, N(2) adsorption, and Fourier transform infrared spectroscopy. It was found that this material had remarkable features such as large surface area (500 m(2)/g) and pore volume (0.32 cm(3)/g), as well as desirable chemical composition (including hydrophobic and ion-exchange moieties). Taking advantages of the Fe(3)O(4)/SiO(2)/P(MAA-co-VBC-co-DVB), a magnetic SPE (MSPE) coupled with capillary electrophoresis (CE) method was developed for the determination of illegal drugs in urine samples. The extraction time could be clearly shortened up to 3 min. The recoveries of these drug compounds were in the range of 84.0-123% with relative standard deviations ranging between 1.7 and 10.5%; the limit of detection was in the range of 4.0-6.0 µg/L. The proposed method is simple, effective, and low-cost, and provides an accurate and sensitive detection platform for abused drug analysis.
Asunto(s)
Anfetaminas/orina , Reactivos de Enlaces Cruzados/química , Ketamina/orina , Fenómenos Magnéticos , Polímeros/química , Extracción en Fase Sólida , Trastornos Relacionados con Sustancias/orina , Reactivos de Enlaces Cruzados/síntesis química , Humanos , Magnetismo , Valores de Referencia , Trastornos Relacionados con Sustancias/diagnósticoRESUMEN
In this contribution, a protocol was established for the selective catalytic hydrogenation of nitroarenes to the corresponding N-arylhydroxylamines. The reduction of 1-(4-chlorophenyl)-3-((2-nitrobenzyl)oxy)-1H-pyrazole, an intermediate in the synthesis of the antifungal reagent pyraclostrobin that includes carbon-chlorine bonds, benzyl groups, carbon-carbon double bonds and other structures that are easily reduced, was chosen as the model reaction for catalyst evaluation and condition optimization. Extensive passivant evaluation showed that RANEY®-nickel treated with ammonia/DMSO (1 : 10, v/v) afforded the optimal result, especially with a particle size of 400-500 mesh. To combine the modified catalyst with continuous-flow reaction technology, the reaction was conducted at room temperature, rendering the desired product with a conversion rate of 99.4% and a selectivity of 99.8%. The regeneration of catalytic activity was also studied, and an in-column strategy was developed by pumping the passivate liquid overnight. Finally, the generality of the method was explored, and 7 substrates were developed, most of which showed a good conversion rate and selectivity, indicating that the method has a certain degree of generality.
RESUMEN
Photothermal agents with strong light absorption in the second near-infrared (NIR-II) region (1000-1350 nm) are strongly desired for successful photothermal therapy (PTT). In this work, titania-coated Au nanobipyramids (NBP@TiO2) with a strong plasmon resonance in the NIR-II window were synthesized. The NBP@TiO2 nanostructures have a high photothermal conversion efficiency of (93.3 ± 5.2)% under 1064-nm laser irradiation. They are also capable for loading an anticancer drug combretastatin A-4 phosphate (CA4P). In vitro PTT studies reveal that 1064-nm laser irradiation can efficiently ablate human lung cancer A549 cells and enhance the anticancer effect of CA4P. Moreover, the CA4P-loaded NBP@TiO2 nanostructures combined with PTT induce a synergistic antiangiogenesis effect. In vivo studies show that such CA4P-loaded NBP@TiO2 nanostructures under mild 1064-nm laser irradiation at an optical power density of 0.4 W cm-2, which is lower than the skin tolerance threshold value, exhibit a superior antitumor effect. This work presents not only the development of the NBP@TiO2 nanostructures as a novel photothermal agent responsive in the NIR-II window but also a unique combined chemo-photothermal therapy strategy for cancer therapy.
RESUMEN
Targeting protein degradation is recognized as a valid approach to cancer therapy. The ubiquitin-proteasome system (UPS) and the autophagy-lysosome pathway are two major pathways for intracellular protein degradation. Proteasome inhibitors such as bortezomib are clinically approved for treating malignancies, but to date, they are still unsatisfactory for cancer therapy. This study identifies titania-coated gold nano-bipyramid (NBP/TiO2) nanostructures as an autophagic flux inhibitor, as the smallest NBP/TiO2 nanostructures induce significant autophagosome accumulation in human glioblastoma U-87 MG cells via blocking the autophagosome-lysosome fusion process and inhibiting lysosomal degradation. Further study indicates that NBP/TiO2 nanostructures reduce the intracellular level of mature cathepsin B and directly inhibit the proteolytic activity of cathepsin B, thereby further inhibiting trypsin-like proteolytic activity, which is a potential cotarget for UPS inhibition. NBP/TiO2 nanostructures interact synergistically with bortezomib to suppress the viability of U-87 MG cells, as the combined treatment synergistically induces the intracellular accumulation of ubiquitinated protein and endoplasmic reticulum stress. In addition, photothermal therapy further synergistically reduces the cell viability. In summary, this study suggests that NBP/TiO2 nanostructures function as a promising anticancer agent in combination with proteasome inhibitors.
RESUMEN
There are three types of differentiated (un-, poorly- and well-differentiated) PC12 cells, which have been widely used as a model system for depression studies after the administration of corticosterone (CORT). In order to investigate the underlying metabolic profiles of CORT-induced PC12 cells and evaluate the suitable differentiated types of PC12 cells for use in depressive studies, proton nuclear magnetic resonance (1H NMR) metabolomics coupled with network analysis approaches were employed. The results showed that CORT induced metabolic alterations in PC12 cells. There were 8 and 13 common differential metabolites in intracellular and extracellular extracts, respectively, of the three types of differentiated PC12 cells in response to CORT treatment, and the perturbed metabolic pathways were involved in amino acid metabolism, glutathione metabolism, pyruvate metabolism and inositol phosphate metabolism. Eighteen protein targets of depression were identified from the five different metabolic pathways from metabolomics and network analysis among the three types of CORT-induced differentiated PC12 cells, and these proteins were all found in the pathways that were perturbed by CORT treatment of poorly-differentiated PC12 cells. These results may indicate that the metabolism of CORT-induced PC12 cells is similar to the pathogenesis of depression, and poorly-differentiated PC12 cells are the most suitable cells for depressive research among the distinct types of differentiated PC12 cells. Thus, an effective predicative strategy to evaluate the in vitro disease models could be referenced.
Asunto(s)
Corticosterona/farmacología , Depresión/metabolismo , Modelos Animales de Enfermedad , Metabolómica , Células PC12/efectos de los fármacos , Animales , Diferenciación Celular , Depresión/inducido químicamente , Espectroscopía de Protones por Resonancia Magnética , Ratas , Transducción de Señal/efectos de los fármacosRESUMEN
The simulated smelting and founding experiment of bronze showed that the copper minerals from different regions could be distinguished clearly by using the multi-statistical analysis based on choosing the chalcophile elements determined by ICP-AES. In the present paper, the data of trace elements in bronzes from Panlongcheng Site and Ezhou, which were determined by NAA, were tried to be processed. The analytical result showed that the bronzes from Panlongcheng and Ezhou could be divided clearly, just like the results of the former simulated smelting and founding experiment of bronze. So, the feasibility of trace element analysis for the study of provenance of copper minerals in ancient bronzes was proved again.
RESUMEN
The facile synthesis of the starch hydrogel with anisotropic microstructure and dynamic behaviors was developed in the presence (A-gel) and absence of DC electric field (B-gel). The microstructures of hydrogels were characterized by environmental scanning electron microscope. Their electro-responsive property of hydrogels was investigated with their storage modulus (G'). The result demonstrates that the G' of A-gel is greater than that of B-gel, and the modulus of A-gel increases along with the external field, which signifies positive electroresponse. In addition, the G' of A-gel and B-gel ((G'(A) and G'(B)) also continuously increases with increasing starch concentration, whereas both the maximum of modulus increment (ΔG' = G'(A)−G'(B) ) and that of modulus increment sensitivity (ΔG'/G'(B)) occur with the starch weight fraction at around 36.5%. To enhance the electro-responsive effects of the hydrogels, dielectric particles were dispersed in the hydrogel. It is found that BaTiO3/chitosan core-shell composite particles significantly enhance the electroresponse of the hydrogel. The mechanism of the electro-response mode is proposed.
Asunto(s)
Materiales Biocompatibles/química , Reactivos de Enlaces Cruzados/química , Glutaral/química , Hidrogeles/química , Almidón/química , Anisotropía , Compuestos de Bario/química , Bioingeniería , Fenómenos Químicos , Quitosano/química , Sistemas de Liberación de Medicamentos , Módulo de Elasticidad , Técnicas Electroquímicas , Fenómenos Mecánicos , Microscopía Electrónica de Rastreo , Tamaño de la Partícula , Porosidad , Propiedades de Superficie , Titanio/químicaRESUMEN
Genipin, a hydrolyzed metabolite of geniposide extracted from the fruit of Gardenia jasminoides Ellis, has shown promise in alleviating depressive symptoms, however, the antidepressant mechanism of genipin remains unclear and incomprehensive. In this study, the metabolic profiles of aqueous and lipophilic extracts in liver of the chronic unpredictable mild stress (CUMS)-induced rat with genipin treatment were investigated using proton nuclear magnetic resonance ((1)H NMR) spectroscopy coupled with multivariate data analysis. Significant differences in the metabolic profiles of rats in the CUMS model group (MS) and the control group (NS) were observed with metabolic effects including decreasing in choline, glycerol and glycogen, increasing in lactate, alanine and succinate, and a disordered lipid metabolism, while the moderate dose (50mg/kg) of genipin could significantly regulate the concentrations of glycerol, lactate, alanine, succinate and the lipid to their normal levels. These biomakers were involved in metabolism pathways such as glycolysis/gluconeogensis, tricarboxylic acid (TCA) cycle and lipid metabolism, which may be helpful for understanding of antidepressant mechanism of genipin.
Asunto(s)
Antidepresivos/uso terapéutico , Depresión/tratamiento farmacológico , Iridoides/uso terapéutico , Hígado/metabolismo , Metaboloma/efectos de los fármacos , Estrés Psicológico/tratamiento farmacológico , Animales , Antidepresivos/administración & dosificación , Conducta Animal/efectos de los fármacos , Peso Corporal/efectos de los fármacos , Depresión/metabolismo , Modelos Animales de Enfermedad , Iridoides/administración & dosificación , Hígado/efectos de los fármacos , Espectroscopía de Resonancia Magnética , Masculino , Metabolómica , Ratas Sprague-Dawley , Estrés Psicológico/metabolismoRESUMEN
BACKGROUND: Acute hypoxemic respiratory failure (AHRF) often develops acute respiratory distress syndrome (ARDS), and its incidence and mortalities in critically ill pediatric patients in China were 2% and 40% respectively. This study aimed at prospectively investigating incidence, causes, mortality and its risk factors, and any relationship to initial tidal volume (V(T)) levels of mechanical ventilation, in children £5 years of age with AHRF and ARDS. METHODS: In 12 consecutive months in 23 pediatric intensive care units (PICU), AHRF and ARDS were identified in those requiring > 12 hour intratracheal mechanical ventilation and followed up for 90 days or until death or discharge. ARDS was diagnosed according to the American-European Consensus definitions. The mortality and ventilation free days (VFD) were measured as the primary outcome, and major complications, initial disease severity, and burden were measured as the secondary outcome. RESULTS: In 13 491 PICU admissions, there were 439 AHRF, of which 345 (78.6%) developed ARDS, resulting in incidences of 3.3% and 2.6%, and corresponding mortalities of 30.3% and 32.8% respectively along with 8.2 and 6.7 times of relative risk of death in those with pneumonia (62.9%) and sepsis (33.7%) as major underlying diseases respectively. No association was found in V(T) levels during the first 7 days with mortality, nor for V(T) at levels < 6, 6 - 8, 8 - 10, and > 10 ml/kg in the first 3 days with mortality or length of VFD. By binary Logistic regression analyses, higher pediatric risk of mortality score III, higher initial oxygenation index, and age < 1 year were associated with higher mortality or shorter VFD in AHRF. CONCLUSIONS: The incidence and mortalities of AHRF and ARDS in children £5 years were similar to or lower than the previously reported rates (in age up to 15 years), associated with initial disease severity and other confounders, but causal relationship for the initial V(T) levels as the independent factor to the major outcome was not found.