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BACKGROUND: Tumor budding (TB) has emerged as a promising independent prognostic biomarker in colorectal cancer (CRC). The prognostic role of TB has been extensively studied and currently affects clinical decision making in patients with stage I and II CRC. However, existing prognostic studies on TB in stage III CRC have been confined to small retrospective cohort studies. Consequently, this study investigated the correlation among TB categories, clinicopathological features, and prognosis in stage III-IV CRC to further enhance the precision and individualization of treatment through refined prognostic risk stratification. AIM: To analyze the relationship between TB categories and clinicopathological characteristics and assess their prognostic value in stage III-IV CRC to further refine the prognostic risk stratification of stage III-IV CRC. METHODS: The clinical data of 547 CRC patients were collected for this retrospective study. Infiltration at the front edge of the tumor buds was counted according to the 2016 International Tumor Budding Consensus Conference guidelines. RESULTS: Multivariate Cox proportional hazards regression analysis demonstrated that chemotherapy (P = 0.004), clinical stage IV (P < 0.001), ≥ 4 regional lymph node metastases (P = 0.004), left-sided colonic cancer (P = 0.040), and Bd 2-3 (P = 0.002) were independent prognostic factors in patients with stage III-IV CRC. Moreover, the density of tumor infiltrating lymphocytes was higher in Bd 1 than in Bd 2-3, both in the tumor stroma and its invasive margin. CONCLUSION: TB has an independent predictive prognostic value in patients with stage III-IV CRC. It is recommended to complete the TB report of stage III-IV CRC cases in the standardized pathological report to further refine risk stratification.
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Neoplasias do Colo , Neoplasias Colorretais , Humanos , Prognóstico , Estudos Retrospectivos , Estadiamento de Neoplasias , Neoplasias Colorretais/patologia , Neoplasias do Colo/patologiaRESUMO
OBJECTIVE: To investigate the safety and efficacy of novel CD19-KIRS2/Dap12-BB chimeric antigen receptor T cells (CAR-T cells) in the treatment of relapsed/refractory B-cell malignancy (R/R BCM). METHODS: Three patients with R/R BCM treated with novel CD19-KIRS2/Dap12-BB CAR-T cells from June 2020 to November 2020 were enrolled, including 1 case of B-cell acute lymphoblastic leukaemia (B-ALL) and 2 cases of non-Hodgkin's lymphoma (NHL), and the efficacy and adverse reactions were observed. RESULTS: After CAR-T cells infusion, patient with B-ALL achieved complete remission (CR) and minimal residual disease (MRD) turned negative, and 2 patients with NHL achieved partial remission (PR). Grade 2 cytokine release syndrome (CRS) occurred in B-ALL patient, grade 1 CRS occurred in 2 NHL patients, and grade II to IV hematologic adverse reactions occurred in 3 patients, all of which were controllable and reversible. The progression-free survival (PFS) of the 3 patients was 143, 199, and 91 days, and overall survival (OS) was 282, 430, and 338 days, respectively. CONCLUSION: The novel CD19-KIRS2/Dap12-BB CAR-T cells in treatment of 3 patients with R/R BCM have significant short-term efficacy and controllable adverse reactions, but the long-term efficacy needs to be further improved.
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Linfoma de Burkitt , Receptores de Antígenos Quiméricos , Humanos , Imunoterapia Adotiva , Antígenos CD19 , Neoplasia Residual , Proteínas Adaptadoras de Transdução de SinalRESUMO
Covalent organic frameworks show great potential in gas adsorption/separation, biomedicine, device, sensing, and printing arenas. However, covalent organic frameworks are generally not dispersible in common solvents resulting in the poor processability, which severely obstruct their application in practice. In this study, we develop a convenient top-down process for fabricating solution-processable covalent organic frameworks by introducing intermolecular hydrogen bonding and π-π interactions from ionic liquids. The bulk powders of imine-linked, azine-linked, and ß-ketoenamine linked covalent organic frameworks can be dispersed homogeneously in optimal ionic liquid 1-methyl-3-octylimidazolium bromide after heat treatment. The resulting high-concentration colloids are utilized to create the covalent organic framework inks that can be directly printed onto the surface. Molecular dynamics simulations and the quantum mechanical calculations suggest that CâH···π and π-π interaction between ionic liquid cations and covalent organic frameworks may promote the formation of colloidal solution. These findings offer a roadmap for preparing solution-processable covalent organic frameworks, enabling their practical applications.
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Adsorption, storage, and conversion of gases (e.g., carbon dioxide, hydrogen, and iodine) are the three critical topics in the field of clean energy and environmental mediation. Exploring new methods to prepare high-performance materials to improve gas adsorption is one of the most concerning topics in recent years. In this work, an ionic liquid solution process (ILSP), which can greatly improve the adsorption kinetic performance of covalent organic framework (COF) materials for gaseous iodine, is explored. Anionic COF TpPaSO3 H is modified by amino-triazolium cation through the ILSP method, which successfully makes the iodine adsorption kinetic performance (K80% rate) of ionic liquid (IL) modified COF AC4 tirmTpPaSO3 quintuple compared with the original COF. A series of experimental characterization and theoretical calculation results show that the improvement of adsorption kinetics is benefited from the increased weak interaction between the COF and iodine, due to the local charge separation of the COF skeleton caused by the substitution of protons by the bulky cations of ILs. This ILSP strategy has competitive help for COF materials in the field of gas adsorption, separation, or conversion, and is expected to expand and improve the application of COF materials in energy and environmental science.
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Epilepsy is one common brain disorder, which is not well controlled by current pharmacotherapy. In this study we characterized the therapeutic potential of borneol, a plant-derived bicyclic monoterpene compound, in the treatment of epilepsy and elucidated the underlying mechanisms. The anti-seizure potency and properties of borneol were assessed in both acute and chronic mouse epilepsy models. Administration of (+)-borneol (10, 30, 100 mg/kg, i.p.) dose-dependently attenuated acute epileptic seizure in maximal-electroshock seizure (MES) and pentylenetetrazol (PTZ)-induced seizure models without obvious side-effect on motor function. Meanwhile, (+)-borneol administration retarded kindling-induced epileptogenesis and relieved fully kindled seizures. Importantly, (+)-borneol administration also showed therapeutic potential in kainic acid-induced chronic spontaneous seizure model, which was considered as a drug-resistant model. We compared the anti-seizure efficacy of 3 borneol enantiomers in the acute seizure models, and found (+)-borneol being the most satisfying one with long-term anti-seizure effect. In electrophysiological study conducted in mouse brain slices containing the subiculum region, we revealed that borneol enantiomers displayed different anti-seizure mechanisms, (+)-borneol (10 µM) markedly suppressed the high frequency burst firing of subicular neurons and decreased glutamatergic synaptic transmission. In vivo calcium fiber photometry analysis further verified that administration of (+)-borneol (100 mg/kg) inhibited the enhanced glutamatergic synaptic transmission in epilepsy mice. We conclude that (+)-borneol displays broad-spectrum anti-seizure potential in different experimental models via decreasing the glutamatergic synaptic transmission without obvious side-effect, suggesting (+)-borneol as a promising anti-seizure compound for pharmacotherapy in epilepsy.
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Epilepsia , Excitação Neurológica , Camundongos , Animais , Anticonvulsivantes/farmacologia , Anticonvulsivantes/uso terapêutico , Epilepsia/induzido quimicamente , Epilepsia/tratamento farmacológico , Canfanos/uso terapêutico , Canfanos/farmacologia , Excitação Neurológica/fisiologia , Convulsões/induzido quimicamente , Convulsões/tratamento farmacológico , Modelos Animais de DoençasRESUMO
BACKGROUND: Maxillofacial deformities are skeletal discrepancies that cause occlusal, functional, and esthetic problems, and are managed by multi-disciplinary treatment, including careful orthodontic, surgical, and periodontal evaluations. However, thin periodontal phenotype is often overlooked although it affects the therapeutic outcome. Gingival augmentation and periodontal accelerated osteogenic orthodontics (PAOO) can effectively modify the periodontal phenotype and improve treatment outcome. We describe the multi-disciplinary approaches used to manage a case of skeletal Class III malocclusion and facial asymmetry, with thin periodontal phenotype limiting the correction of deformity. CASE SUMMARY: A patient with facial asymmetry and weakness in chewing had been treated with orthodontic camouflage, but the treatment outcome was not satisfactory. After examination, gingiva augmentation and PAOO were performed to increase the volume of both the gingiva and the alveolar bone to allow further tooth movement. After orthodontic decompensation, double-jaw surgery was performed to reposition the maxilla-mandibular complex. Finally, implant placement and chin molding were performed to restore the dentition and to improve the skeletal profile. The appearance and function were significantly improved, and the periodontal tissue remained healthy and stable. CONCLUSION: In patients with dentofacial deformities and a thin periodontal phenotype, multi-disciplinary treatment that includes PAOO could be effective, and could improve both the quality and safety of orthodontic-orthognathic therapy.
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It is very desirable to develop advanced sustainable biomedical materials with superior biosafety and bioactivity for clinical applications. Herein, biomass-derived multilayer-structured absorbable microparticles (MQ x T y ) composed of starches and plant polyphenols are readily constructed for the safe and effective treatment of bone defects with intractable bleeding by coating multiple layers of quaternized starch (Q+) and tannic acid onto microporous starch microparticles via facile layer-by-layer assembly. MQ x T y microparticles exhibit efficient degradability, low cytotoxicity, and good blood compatibility. Among various MQ x T y microparticles with distinct Q+/T- double layers, MQ2T2 with outmost polyphenol layer possess the unique properties of platelet adhesion/activation and red blood cell aggregation, resulting in the best hemostatic performance. In a mouse cancellous-bone-defect model, MQ2T2 exhibits the favorable hemostatic effect, low inflammation/immune responses, high biodegradability, and promoted bone repair. A proof-of-concept study of beagles further confirms the good performance of MQ2T2 in controlling intractable bleeding of bone defects. The present work demonstrates that such biomass-based multilayer-structured microparticles are very promising biomedical materials for clinical use.
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A microRNA (miRNA) is a single-stranded, small and non-coding RNA molecule that contains 20-25 nucleotides. More than 2000 miRNAs have been identified in human genes since the first miRNA was discovered in Caenorhabditis elegans in the early 1990s. miRNAs play a crucial role in various biological processes by regulating gene expression through post-transcriptional mechanisms. The alterations of their levels are associated with various diseases, such as glucometabolic disorder and lipid metabolism disorder. In recent years, miRNAs have been proved to be involved in regulating the functions of pancreatic ß-cells, insulin resistance and other biological behaviors related to glucometabolic disorder and the pathogenesis of diabetes mellitus (DM). This review summarized specific miRNAs, including miRNA-375 (miR-375), miRNA-155 (miR-155), miRNA-21 (miR-21), miRNA-33 (miR-33), the let-7 family and some other miRNAs related to glucometabolic regulation, introduced the obstacles and challenges in miRNA therapy, and discussed the prospect of new treatment methods for glucometabolic disorder.
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Glucose/metabolismo , Doenças Metabólicas/tratamento farmacológico , Doenças Metabólicas/metabolismo , MicroRNAs/metabolismo , Animais , Diabetes Mellitus/tratamento farmacológico , Diabetes Mellitus/genética , Diabetes Mellitus/metabolismo , Glucose/genética , Humanos , Hiperglicemia/tratamento farmacológico , Hiperglicemia/genética , Hiperglicemia/metabolismo , Insulina/genética , Insulina/metabolismo , Células Secretoras de Insulina/efeitos dos fármacos , Células Secretoras de Insulina/metabolismo , Doenças Metabólicas/genética , MicroRNAs/administração & dosagem , MicroRNAs/genéticaRESUMO
Tyrosine phosphorylation, as a hallmark in cellular signal transduction, is important for a diverse array of cellular processes, such as proliferation, metabolism, motility, and survival. Aberrant tyrosine phosphorylation plays a causal role in many diseases, especially the cancer. Detecting protein phosphorylation status in the cancer cells or tissues is vital for assessing the pathological phase, discovering the cancer biomarkers, and identifying the drug targets. However, the common biochemical detection methods remain through anti-pTyr antibodies, which are known to have limited sensitivity, poor reproducibility and high cost. Recent studies have proved that superbinder SH2 domain is a good replacement of anti-pTyr antibodies for the specific enrichment of pTyr peptides in phosphoproteomics analysis. In this work, we exploited a series of affinity reagents based on superbinder SH2 derived from Src protein for detecting the pTyr-containing proteins to replace anti-pY antibodies in immunoblotting and immunofluorescence techniques. The excellent performance of HRP-sSH2 and EGFP-sSH2 was verified by the analysis of several different tumor cell samples and was compared with most commonly used commercial antibodies. EGFP-sSH2-(Arg)9 might be applied as the probe for direct fluorescence imaging in live cells via efficiently penetrating cell membranes and specifically binding with pTyr proteins. In summary, we have developed three novel, convenient, sensitive, and cost-effective affinity reagents that would have wide applications in protein tyrosine phosphorylation analysis for the tumor research and clinical diagnosis.
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Arginina/química , Proteínas de Fluorescência Verde/química , Neoplasias/química , Tirosina/metabolismo , Quinases da Família src/química , Linhagem Celular Tumoral , Imunofluorescência , Humanos , Immunoblotting , Microscopia de Fluorescência , Neoplasias/patologia , Imagem Óptica , Fosforilação , Tirosina/química , Domínios de Homologia de src , Quinases da Família src/metabolismoRESUMO
Effective hemostatic materials are very important for treating trauma cases. Natural polysaccharides have been particularly appealing in the development of new hemostatic materials due to their unique functions in human bodies. In this work, different polysaccharide-based hemostatic porous sponges (SHDP or SHDQ) of cross-linked hyaluronic acid (HA)/cationized dextran were readily prepared by the self-foaming process of HA and poly((2-dimethyl amino)-ethyl methacrylate)-grafted dextran (Dex-PDM) or partially-quaternized Dex-PDM in the presence of sodium trimetaphosphate crosslinkers. SHDP and SHDQ sponges were investigated in terms of liquid-absorption ability, hemolysis, whole-blood clotting and hemostatic activity in hemorrhaging-liver models. Compared with HA/Dex-PDM sponges (HDP) without chemical cross-linking, SHDP and SHDQ sponges displayed higher porosity (>70.0% vs. 48.9%) and swelling ratios (>1000% vs. 520%). Meanwhile, hemolysis assay revealed the good blood compatibility of SHDP and SHDQ with low hemolysis ratio (below 0.5%). Furthermore, in vitro and in vivo hemostatic assay showed that SHDQ possessed better hemostatic properties than SHDP, owing to the higher cationic charges of partially-quaternized Dex-QPDM than Dex-PDM. The present study demonstrated that the self-foaming process of HA/Dex-PDM under a 'green' condition is an effective means to produce new hemostatic materials.
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Dextranos/química , Ácido Hialurônico/química , Hemostáticos , Polissacarídeos/química , PorosidadeRESUMO
OBJECTIVE: Using an experimental model of animals exposed to cold to evaluate the regulative effects of prazosin hydrochloride (Pra) and racanisodamine (Ani) on extremital skin temperature of rats and mice. METHODS: Eighty animals were randomly divided into eight groups according to the drug dosage. After been administered with drugs by intragastric at room temperature for 60 min, the animals were moved into specified temperature (5 degrees C,18 degrees C) environment and the skin temperatures at the 1/3 site at the proximal end of tail were measured by infrared camera on 180 min and 300 min. Effects of drug were evaluated by changes in tail skin temperatures. RESULTS: Pra and Ani combination raised the extremital skin temperature of experimental animals significantly in a dose-dependent manner, while single use of Pra was not potent to rats and less potent to mice, and single use of Ani could not raise extremital skin temperature of both rats and mice. Change of rectal temperature in mice showed that Pra and Ani combination did not affect core temperature. CONCLUSION: Pra and Ani combination could significantly raise extremital skin temperature of rats and mice exposed to cold, and would not affect their core (rectal) temperature.
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Temperatura Baixa , Prazosina/farmacologia , Temperatura Cutânea/efeitos dos fármacos , Alcaloides de Solanáceas/farmacologia , Animais , Temperatura Corporal , Camundongos , RatosRESUMO
OBJECTIVE: To explore the damage effects and expression of vascular endothelial growth factor (VEGF) exposed with different low-temperatures on rat dermal microvascular endothelial cells (DMVECs). METHODS: Primary DMVECs were obtained by discontinuous Percoll gradient centrifugation. The DMVECs were identified by phase contrast microscope and immunofluorescence studies for CD31 antigen. Applied 28 degrees C, 12 degrees C and 0 degrees C to interfere with rat DMVECs as cold-exposure model. The changes of cells morphology were observed under invert microscope. The membrane integrity was determined by lactate dehydrogenase (LDH) activity. RT-PCR was used to examine the expression of vascular endothelial growth factor mRNA in cells. RESULTS: The monolayer of cultured PMVECs displayed the shape of pavingstone. CD31 antigen and binding BSI results by fluorescence microscope identified the cultured cells were DMVECs. After 24 h cold exposure, the cell morphology of 0 degrees C group was shrunken, the other groups were "Fibroblast-like". The LDH activity (U/L) in the medium of 28 degrees C, 12 degrees C and 0 degrees C groups was 54.17 +/- 3.02, 64.66 +/- 3.03, 82.13 +/- 10.91 respectively, which was significantly higher than that of 37 degrees C group (12.23 +/- 3.0, P < 0.01). The VEGF mRNA expression level was up-regulated in 28 degrees C group and 12 degrees C group versus control group (P < 0.05), but unchanged in 0 degrees C group. CONCLUSION: The rat DMVECs injury severity are deteriorated with temperature decreasing, and VEGF might be involved in the regulation of membrane permeability in this period.
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Temperatura Baixa , Células Endoteliais/citologia , Endotélio Vascular/citologia , Fator A de Crescimento do Endotélio Vascular/metabolismo , Animais , Animais Recém-Nascidos , Células Cultivadas , Derme/irrigação sanguínea , Células Endoteliais/metabolismo , Ratos , Ratos WistarRESUMO
OBJECTIVE: To study the synergistic effects of hypothermia and hypoxia on the damage of pulmonary microvascular endothelial cells (PMVEC) in rat. METHODS: Primary PMVECs were obtained by complex phosphoesterasum digesting from isolated lung tissues of Wistar rats, the PMVECs were identified by phase contrast microscope and immunofluorescence studies for CD31 antigen and bandeiraea simplicifolia isolectin (BSI) binding test. Factorial design was adopted in trial according to hypothermia and hypoxia existing or not. Using corresponding kit measured the levels of lactate dehydrogenase (LDH) activity in cell medium. Level of nitric oxide (NO) concentration was measured by Griess Assay. RT-PCR was used to examine the expression of vascular endothelial growth factor (VEGF), endothelin-1 (ET-1) mRNA in PMVECs. RESULTS: The monolayer of cultured PMVECs displayed the shape of pavingstone. CD31 antigen and binding BSI results by fluorescence microscope identified the cultured cells were PMVECs. Compared to the control group, LDH activity and VEGF, ET-1 expression levels were significantly increased in hypothermia group, hypoxia group and hypoxia combined with hypothermia group. And the levels of NO concentration were reduced in these three groups. The results of One-way ANOVA showed that there was a synergistic effect between hypothermia and hypoxia. CONCLUSION: Hypothermia and hypoxia both have an effect on PMVECs whether in altering the cell permeability or in releasing of vasoactive substances including NO and ET-1. In addition, there is a synergistic effect between hypothermia and hypoxia.
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Temperatura Baixa , Células Endoteliais/citologia , Animais , Hipóxia Celular , Permeabilidade da Membrana Celular , Células Cultivadas , Células Endoteliais/metabolismo , Endotelina-1/metabolismo , Endotélio Vascular/citologia , Pulmão/irrigação sanguínea , Masculino , Óxido Nítrico/metabolismo , RNA Mensageiro/genética , Ratos , Ratos Wistar , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
Environmental DNA from soil and water samples was extracted to construct a plasmid library and a fosmid library containing 19,500 and 20,400 clones, respectively. Two esterases (EstP2K and EstF4K) were finally isolated from each library based on activity screening, and both of them were characterized in this study. The esterase EstF4K consists of 396 amino acids with an SMTK motif which belongs to family VIII esterase/lipase. The amino acid sequence of EstF4K showed 83 % identity with that of EstA3, a reported esterase isolated from uncultured organisms of soil. EstP2K is composed of 224 amino acids in size and shows only 37 % identity with a putative lipase of Neisseria elongata subsp. The purified EstF4K was optimally active at pH 8.0 and 50 °C. It was remarkably active and very stable in the presence of 30 % dimethyl sulfoxide. Activity fingerprint of EstF4K displayed a higher level of activity toward short-chain fatty acid p-nitrophenyl (pNP) esters, while EstP2K preferred bias for pNP caprylate ester. The optimum reaction temperature and pH for EstP2K are 45 °C and 7.5, respectively, and the enzyme exhibited strong tolerance in the presence of 30 % methanol. EstF4K and EstP2K showed opposite enantioselectivity for methyl 3-phenylglycidate, a chiral synthon for the synthesis of Taxol® side chain.
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Proteínas de Bactérias/química , Proteínas de Bactérias/isolamento & purificação , Esterases/química , Esterases/isolamento & purificação , Metagenoma , Motivos de Aminoácidos , Sequência de Aminoácidos , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Clonagem Molecular , Estabilidade Enzimática , Esterases/genética , Esterases/metabolismo , Água Doce/química , Biblioteca Gênica , Concentração de Íons de Hidrogênio , Dados de Sequência Molecular , Alinhamento de Sequência , Solo/química , Especificidade por Substrato , TemperaturaRESUMO
Vascular endothelium plays an important role in regulating vascular homeostasis. Over the past years, it has become clear that endothelial dysfunction is a key event of pathophysiological changes in the initiation and progression of injuries induced by extreme environmental factors. The present review summarizes current understanding of vascular endothelial dysfunction induced by hypoxia, cold and heat, and provides the information for prevention and treatment of environmental exposure injuries.
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Endotélio Vascular/fisiopatologia , Hipóxia/fisiopatologia , Lesões do Sistema Vascular , Meio Ambiente , Humanos , TemperaturaRESUMO
Acclimatization is a process of biological adaptation when exposed to environmental factors such as hypoxia, cold and heat for prolonged periods of time, where non-genetical variations play a role in allowing subjects to tolerate hypoxic, cold or hot environments. This review focuses on the characteristics and mechanisms of acclimatization found through major research advances by our institute. First, the mechanisms underlying the acclimatization to extreme environments are complex. In our investigations, the physiological changes of multiple systems including the nervous, circulatory, respiratory, and hemopoietic system were demonstrated when the acclimatization to hypoxia was developed, and the underlying significance of hypoxia-inducible factor-1 (HIF-1) was investigated. Second, it is suggested that the development of acclimatization to extreme environments is complicated. Hypoxia and cold coexist at high altitude. Our investigations revealed the characteristics of negative cross-relationship in the acclimatization to hypoxia and cold. And third, it is interesting for us to understand that acclimatization to extreme environments is transferable among individuals, and the characteristics of heat acclimatization-inducing factor (HAlF) were presented. The above findings will provide a theoretical guidance for protective operations and help to establish a solid foundation for future research related to acclimatization.
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Aclimatação/fisiologia , Altitude , Temperatura Baixa , Meio Ambiente , Temperatura Alta , Humanos , Hipóxia , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismoRESUMO
OBJECTIVE: To explore the effect of hypoxia on the peripheral blood T lymphocyte subsets and co-stimulatory molecules in rats so as to provide the basis for studying the intervention measure. METHODS: Before hypoxia and during hypoxia at 8 000 m for 8 h, 3 d, 6 d and 10 d the change of peripheral blood T lymphocyte subsets and co-stimulatory molecules in rats were detected by flowcytometer with three-color immunofluorescence label. RESULTS: Rats were exposed to hypoxia at 8 000 m for 8 hours, and CD3+, CD8+, CD8+ CD28- lymphocyte percentages were significantly decreased (P < 0.01) compared with that before hypoxia. After 3 days of hypoxia, besides aforesaid change, CD4+ CD28+ lymphocyte percentage also prominently decreased (P < 0.01) and CD4+ CD28- prominently increased (P < 0.01). After 6 and 10 days of hypoxia, CD3+, CD4+ lymphocyte percentages were further decreased, while CD8+ CD28+ lymphocyte percentage significantly increased (P < 0.01). CONCLUSION: After exposed to hypoxia at 8 000 m for 8 hours and 3 days, activation of CD8+ and CD4+ T lymphocyte was prominently decreased, while with the prolong of exposed time activation of CD8+ T lymphocyte was significantly increased.
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Hipóxia/fisiopatologia , Ativação Linfocitária/fisiologia , Linfócitos T/fisiologia , Altitude , Doença da Altitude/fisiopatologia , Animais , Linfócitos T CD4-Positivos/fisiologia , Linfócitos T CD8-Positivos/fisiologia , Hipóxia/imunologia , Masculino , Ratos , Ratos WistarRESUMO
OBJECTIVE: To study on the protective effects of new compound codonopsis tablets against acute mountain sickness (AMS). METHODS: Forty-five male plain resident soldiers stayed at 1400 m altitude for 3 months were randomly divided into two groups, control (15 men) and treatment group (30 men). Single blind trial was used in this study. The subjects in the two groups took placebo and new compound codonopsis tablets respectively for 5 days before climbing to high mountain, and continued to take for another 10 days until the 3rd day after arriving at 5200 m altitude. On the 1st , 3rd, and 5th day after they arrived at 5200 m altitude, the score and the degree of AMS symptoms of soldiers were followed up and recorded according to State Military Standard GJB1098-91--"Principles of diagnosis and treatment of benign form of acute mountain sickness", heart rate (beats/min) and arterial oxygen saturation (%) were detenrmined. On the 6th day after they arrived at high altitude, forced vital capacity(FVC), forced expired volume in one second(FEV1.0), FEV1% (FEV1.0/FVC), FEF25%-75%, peak expiratory flow (PEF) and maximal voluntary ventilation (MVV) were detected, total frequency of hands cross movement and memory of order numbers test were measured. RESULTS: Comparison with control, AMS symptoms of treatment group reduced on the 1st, 3rd, and 5th day after arriving at 5200 m high altitude (P < 0.01). The degree of AMS symptoms of treatment group was significantly different from that of control. The proportion of slight symptoms in treatment group was high, and that of relative serious symptoms in control was high. Compared with control, FVC, FEV1.0, FEF25%-75%, PEF and MVV of treatment group increased (P < 0.05, P < 0.01), and Ttis, Ctis of treatment group increased (P < 0.05, P < 0.01), Atime decreased markedly (P < 0.05), there was no statistically significant difference in Etis and Sum between the two groups. CONCLUSION: New compound codonopsis tablets could decrease the incidence of AMS, mitigate the symptoms of AMS, and improve breathing function and fingers movement function. New compound codonopsis tablets have an obvious effect on prevention and treatment of acute mountain sickness.
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Doença da Altitude/prevenção & controle , Codonopsis/química , Medicamentos de Ervas Chinesas/uso terapêutico , Fitoterapia , Doença Aguda , Adolescente , Composição de Medicamentos , Humanos , Masculino , Comprimidos , Adulto JovemRESUMO
A new chemo-enzymatic route to both isomers of 2-hydroxy-4-phenylbutyric acid is reported. The key step is the lactonase-catalyzed hydrolysis of cis- and trans-2-hydroxy-4-phenyl-4-butyrolactones followed by hydrogenation over Pd/C to afford optically pure 2-hydroxy-4-phenylbutyric acid.
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Carbono/química , Hidrolases de Éster Carboxílico/química , Paládio/química , Fenilbutiratos/química , Catálise , Hidrogenação , Estrutura Molecular , Fenilbutiratos/síntese química , EstereoisomerismoRESUMO
OBJECTIVE: To explore the characteristic of hypoxia-induced immune injury, its mechanisms and the intervention measure. METHODS: The change of immune organ index, T lymphocyte subsets of peripheral blood and immune organ in mice during hypoxia were detected. Lymphocyte apoptosis of immune organ, pathology of lung and kidney in mice were observed. Then by way of prophylaxis we studied the effect of Chinese Traditional Medicine on hypoxia-induced immune injury in mice. RESULTS: (1) Exposure to hypoxia at 8 000 m simulated altitude for 8 h resulted in marked decrease in CD4+ CD8+ thymocytes and marked increase in CD4+ CD8-, CD4- CD8+ thymocytes (P < 0.01). After 3 days of hypoxia, the mice had a much lower percentage of CD4+ T-cell (P < 0.05). The ratio of CD4+/CD8+ decreased significantly and aforesaid changes of thymocyte were further enlarged. Also mice had a pronounced increase in rates of late apoptosis or necrosis of spleen lymphocyte and thymocyte (P < 0.05). After 6 days of hypoxia, index of spleen was significantly increased (P < 0.05), index of thymus was significantly decreased (P < 0.05) and CD3+, CD4+, CD8+ lymphocyte percentage of spleen were significantly decreased (P < 0.01). Also late apoptosis or necrosis lymphocytes of spleen and thymus were further increased (P < 0.01), viable cell rates of spleen lymphocyte and thymocytes were markedly decreased (P < 0.01), early apoptosis rates of spleen lymphocyte were markedly increased (P < 0.01). There was no significant change in the percentage of CD8+ lymphocyte in peripheral blood during the whole hypoxia period. (2) New Compound Codonopsis Pilosula (NCCP), Xiang Qi Polysaccharide (XQP) and NCCP + XQP could significantly increase the number of peripheral blood CD3+, CD4+ and spleen CD4+, but had no significant influence on the number of spleen CD8+. XQP and XQP+ NCCP could significantly decrease the number of CD4+ CD8+ (P < 0.01), increase that of CD4+ CD8- (P < 0.01), and had no significant influence on CD4- CD8+ in thymus. However, NCCP didn't influence the component of thymocytes. CONCLUSION: After hypoxia at 8 000 m simulated altitude decrease of lymphocyte of periphery in mice may be related with increase of apoptosis and necrosis of lymphocyte, and with increase of distribution of lymphocyte to lung in early period of exposure. NCCP and XQP have hopeful prospect in intervention study of hypoxia-induced immune injury.