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A model construction of systemic acute leukemia is challenging. Herein, we established a systemic leukemia mouse model using highly immunodeficient NPG mice without any immunosuppressive treatments. NPG mice received tail intravenous injection of SHI-1 cells at the concentration of 1×107 cells (group A) or 5×107 cells (group B) and randomly sacrificed each seven days post-inoculation. Tumor development was monitored using nested-PCR, peripheral blood-smear analysis, flow cytometry, pathological examinations, and immunohistochemistry. The median survival of mice in groups A and B were 33.0 and 30.0 days, respectively. Blast cells in peripheral blood appeared on day 14 in group B, and on day 21 in group A. In addition, SHI-1 cell specific MLL-AF6 mRNA was detected in both spleen and bone marrow on day 14 post-inoculation. 21 days after inoculation, we observed human CD45+CD33+ cells with an SH-1-immunophenotype in the peripheral blood, spleen, and bone marrow, as well as solid neoplasms in multiple organs. Moreover, the histologically infiltrated leukemic cells expressed CD45. In conclusion, the current study demonstrated the normal growth of SHI-1 cells in the NPG mice without immunosuppression, which caused systemic leukemia similar to that observed in acute leukemia patients. We developed an efficient and reproducible model to study leukemia pathogenesis and progression.
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This study investigated the effect of rapamycin alone and in combination with chemotherapy (doxorubicin and cytarabine) on AML. Human acute monocytic leukemia cell line SHI-1 and NPG AML model mice created by intravenous injection of SHI-1 cell were treated with rapamycin, chemotherapy, or rapamycin plus chemotherapy. Analysis by cell counting kit-8, western blot, flow cytometry, and immunohistochemistry was performed, and results suggested that both rapamycin and chemotherapy inhibited proliferation of SHI-1 cells both in vitro and in vivo, suppressed neoplasm growth in vivo, and promoted survival of NPG AML mice. The antitumor effect of rapamycin plus chemotherapy was better than that of rapamycin alone and chemotherapy alone. In addition, western blot results demonstrated that rapamycin inhibited the phosphorylation of mTOR downstream targets 4EBP1 and S6K1 in SHI-1 cells, and increased the pro-apoptosis-related protein Bax and autophagy-associated proteins Beclin-1, LC3B-II, and ATG5 while reducing the anti-apoptosis-related protein Bcl-2. In conclusion, the results of this study indicate that rapamycin acts synergistically with doxorubicin and cytarabine in AML treatment, and its underlying mechanism might be associated with mTORC1 pathway-mediated apoptosis and autophagy.
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Apoptose , Autofagia , Doxorrubicina , Alvo Mecanístico do Complexo 1 de Rapamicina , Transdução de Sinais , Sirolimo , Animais , Autofagia/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Humanos , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Camundongos , Sirolimo/farmacologia , Linhagem Celular Tumoral , Doxorrubicina/farmacologia , Transdução de Sinais/efeitos dos fármacos , Citarabina/farmacologia , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/patologia , Sinergismo Farmacológico , Ensaios Antitumorais Modelo de Xenoenxerto , Proliferação de Células/efeitos dos fármacos , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêuticoRESUMO
Fibrosing mediastinitis (FM) is a rare disease caused by different causes. If left untreated, the prognosis is poor. The common causes of FM are Tuberculosis and Histoplasma capsulatum infection. Esophageal perforation is also a rare condition that is often easily under- and mis-diagnosed due to the lack of specificity of symptoms. Here we report a case of FM caused by esophageal perforation.
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Cementitious composite is one of the most widely used construction materials around the world, but cement production is accompanied by energy waste and CO2 emission. Wollastonite, a natural fibrous silicate mineral, can be a potential supplementary cementing materials (SCMs) for cementitious composite owing to its similar calcium silicate system, and it has an eco-friendly and convenient production process. Furthermore, its unique fibrous structure can possibly act as reinforcement for the cement matrix. In view of this, this study aimed to investigate the effects of different sizes (the median diameter of 3 µm, 6 µm, 9 µm and 12 µm) and contents (0%, 5%, 10%, 15% and 20% by mass) of wollastonite combined with 5% silica fume on the mechanical strength, durability and microstructure of cementitious composite by compressive test, flexural test, shear test, rapid chloride migration test, sulfate corrosion test, X-ray diffraction(XRD), scanning electron microscope (SEM) and fourier transform infrared spectrometer (FTIR). The results showed that the strength and durability of samples increased and then decreased as wollastonite content increased. An addition of 10% wollastonite into the cement matrix increased compressive strength, flexural strength and shear strength by 6.22%, 29.3% and 18.4%, respectively. However, an addition of 5% wollastonite was found to be more beneficial for improving resistance to chloride and sulfate corrosion. Additionally, samples prepared with 3 µm wollastonite performed better, which can be attributed to the fact that the small size of wollastonite contributed to both the filling effect and the skeletal support and bridging effect of microfibers. The CO2 emissions of cementitious composites decreased as the wollastonite percentage increased. The findings confirm that natural wollastonite as SCMs for cementitious composite has performance enhancement and environmental benefits, however, it is recommended that the wollastonite content should not exceed 15%.
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Dióxido de Carbono , Cloretos , Silicatos , CarbonoRESUMO
There has been some controversy over the use of radiobiological models when modeling the dose-response curves of ionizing radiation (IR)-induced chromosome aberration and tumor prevalence, as those curves usually show obvious non-targeted effects (NTEs) at low doses of high linear energy transfer (LET) radiation. The lack of understanding the contribution of NTEs to IR-induced carcinogenesis can lead to distinct deviations of relative biological effectiveness (RBE) estimations of carcinogenic potential, which are widely used in radiation risk assessment and radiation protection. In this work, based on the initial pattern of two classes of IR-induced DNA double-strand breaks (DSBs) clustering in chromatin domains and the subsequent incorrect repair processes, we proposed a novel radiobiological model to describe the dose-response curves of two carcinogenic-related endpoints within the same theoretical framework. The representative experimental data was used to verify the consistency and validity of the present model. The fitting results indicated that, compared with targeted effect (TE) and NTE models, the current model has better fitting ability when dealing with the experimental data of chromosome aberration and tumor prevalence induced by multiple types of IR with different LETs. Notably, the present model without introducing an NTE term was adequate to describe the dose-response curves of IR-induced chromosome aberration and tumor prevalence with NTEs in low-dose regions. Based on the fitting parameters, the LET-dependent RBE values were calculated for three given low doses. Our results showed that the RBE values predicted by the current model gradually decrease with the increase of doses for the endpoints of chromosome aberration and tumor prevalence. In addition, the calculated RBE was also compared with those evaluated from other models. These analyses show that the proposed model can be used as an alternative tool to well describe dose-response curves of multiple carcinogenic-related endpoints and effectively estimate RBE in low-dose regions.
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Quebras de DNA de Cadeia Dupla , Neoplasias , Humanos , Cromatina , Prevalência , Transferência Linear de Energia , Radiação Ionizante , Aberrações Cromossômicas , DNA/efeitos da radiação , Análise por Conglomerados , Relação Dose-Resposta à RadiaçãoRESUMO
During spaceflight, multiple unique hazardous factors, particularly microgravity and space radiation, can induce different types of DNA damage, which pose a constant threat to genomic integrity and stability of living organisms. Although organisms have evolved different kinds of conserved DNA repair pathways to eliminate this DNA damage on Earth, the impact of space microgravity on the expressions of these DNA repair genes and their regulatory miRNAs has not been fully explored. In this study, we integrated all existing datasets, including both transcriptional and miRNA microarrays in wild-type (WT) Caenorhabditis elegans that were exposed to the treatments of spaceflight (SF), spaceflight control with a 1g centrifugal device (SC), and ground control (GC) in three space experiments with the periods of 4, 8 and 16.5 days. The results of principal component analysis showed the gene expression patterns for five major DNA repair pathways (i.e., non-homologous end joining (NHEJ), homologous recombination (HR), mismatch repair (MMR), nucleotide excision repair (NER), and base excision repair (BER)) were well separated and clustered between SF/GC and SC/GC treatments after three spaceflights. In the 16.5-days space experiment, we also selected the datasets of dys-1 mutant and ced-1 mutant of C. elegans, which respectively presented microgravity-insensitivity and radiosensitivity. Compared to the WT C. elegans flown in the 16.5-days spaceflight, the separation distances between SF and SC samples were significantly reduced in the dys-1 mutant, while greatly enhanced in the ced-1 mutant for five DNA repair pathways. By comparing the results of differential expression analysis in SF/GC versus SC/GC samples, we found the DNA repair genes annotated in the pathways of BER and NER were prominently down-regulated under microgravity during both the 4- and 8-days spaceflights. While, under microgravity, the genes annotated in MMR were dominatingly up-regulated during the 4-days spaceflight, and those annotated in HR were mainly up-regulated during the 8-days spaceflight. And, most of the DNA repair genes annotated in the pathways of BER, NER, MMR, and HR were up-regulated under microgravity during the 16.5-days spaceflight. Using miRNA-mRNA integrated analysis, we determined the regulatory networks of differentially expressed DNA repair genes and their regulatory miRNAs in WT C. elegans after three spaceflights. Compared to GC conditions, the differentially expressed miRNAs were analyzed under SF and SC treatments of three spaceflights, and some altered miRNAs that responded to SF and SC could regulate the expressions of corresponding DNA repair genes annotated in different DNA repair pathways. In summary, these findings indicate that microgravity can significantly alter the expression patterns of DNA repair genes and their regulatory miRNAs in space-flown C. elegans. The alterations of the expressions of DNA repair genes and the dominating DNA repair pathways under microgravity are possibly related to the spaceflight period. In addition, the key miRNAs are identified as the post-transcriptional regulators to regulate the expressions of various DNA repair genes under microgravity. These altered miRNAs that responded to microgravity can be implicated in regulating diverse DNA repair processes in space-flown C. elegans.
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Proteínas de Caenorhabditis elegans , MicroRNAs , Voo Espacial , Ausência de Peso , Animais , Caenorhabditis elegans/genética , MicroRNAs/genética , Reparo do DNA/genética , Distrofina/genética , Proteínas de Caenorhabditis elegans/genéticaRESUMO
Recovering finite and non-substitutable phosphorus from liquid waste streams through bio-mediated techniques has attracted increasing interest, but current approaches are incredibly dependent on ammonium. Herein, a process to recover phosphorus from wastewater under multiple nitrogen species conditions was developed. This study compared the effects of nitrogen species on the recovery of phosphorus resources by a bacterial consortium. It found that the consortium could not only efficiently utilize ammonium to enable phosphorus recovery but also utilize nitrate via dissimilatory nitrate reduction to ammonium (DNRA) to recover phosphorus. The characteristics of the generated phosphorus-bearing minerals, including magnesium phosphate and struvite, were evaluated. Furthermore, nitrogen loading positively influenced the stability of the bacterial community structure. The genus Acinetobacter was dominant under nitrate and ammonium conditions, with a relatively stable abundance of 89.01% and 88.54%, respectively. The finding may provide new insights into nutrient biorecovery from phosphorus-containing wastewater contaminated with multiple nitrogen species.
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Compostos de Amônio , Águas Residuárias , Fósforo , Nitratos , Nitrogênio , Fosfatos , Estruvita/química , BactériasRESUMO
A seepage model based on smoothed particle hydrodynamics (SPH) was developed for the seepage simulation of pore water in porous rock mass media. Then, the effectiveness of the seepage model was proved by a two-dimensional seepage benchmark example. Under the framework of SPH based on the total Lagrangian formula, an extended hydro-mechanical coupling model (EHM-TLF-SPH) was proposed to simulate the crack propagation and coalescence process of rock samples with prefabricated flaws under hydraulic and compressive loads. In the SPH program, the Lagrangian kernel was used to approximate the equations of motion of particles. Then, the influence of flaw water pressure on crack propagation and coalescence models of rock samples with single or two parallel prefabricated flaws was studied by two numerical examples. The simulation results agreed well with the test results, verifying the validity and accuracy of the EHM-TLF-SPH model. The results showed that with the increase in flaw water pressure, the crack initiation angle and stress of the wing crack decreased gradually. The crack initiation location of the wing crack moved to the prefabricated flaw tip, while the crack initiation location of the shear crack was far away from the prefabricated flaw tip. In addition, the influence of the permeability coefficient and flaw water pressure on the osmotic pressure was also investigated, which revealed the fracturing mechanism of hydraulic cracking engineering.
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BACKGROUND: Chronic myeloid leukemia (CML) is a malignant hematologic malignancy that can progress to blast phase with a myeloid or lymphoid phenotype. Some patients with CML can also progress to blast crisis phase; however, the transformation of CML into Philadelphia-positive lymphoma is extremely rare. CASE SUMMARY: We present a patient with CML who experienced a sudden transformation to anaplastic large-cell lymphoma (ALCL) after 7 mo of treatment with imatinib, during which she had achieved partial cytogenetic response as well as early molecular response. The patient noticed a mass in her left shoulder, the biopsy data of which were consistent with ALCL; moreover, her lymphoma cells exhibited BCR-ABL gene fusion. The patient was diagnosed with Philadelphia-positive ALCL that progressed from CML, and was thus treated with the second generation tyrosine kinase inhibitor nilotinib. Six months later, the mass had totally disappeared and the BCR-ABL fusion gene was undetectable in the peripheral blood. To our knowledge, this is the first patient known to have developed Philadelphia-positive ALCL transformed from CML. CONCLUSION: Unexplained lymphadenopathy or an extramedullary mass in a patient with CML may warrant a biopsy and testing for BCR-ABL fusion.
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Currently, the connectivity calculation of complex pipeline networks is mostly simplified or ignores the influence of nodes such as elbows and tees on the connectivity reliability of the entire network. Historical earthquake damage shows that the seismic performance of municipal buried pipelines depends on the ability of nodes and interfaces to resist deformation. The influence of node reliability on network connectivity under reciprocal loading is a key issue to be addressed. Therefore, based on the general connectivity probabilistic analysis algorithm, this paper embeds the reliability of nodes into the reliability of edges, and derives a more detailed and comprehensive on-intersecting minimum path recursive decomposition algorithm considering elbows, tees, and other nodes; then, based on the reliability calculation theory of various pipeline components, the reliability of various nodes in different soil is calculated using finite element numerical simulation; finally, the reliability of a small simple pipeline network and a large complex pipeline network are used as examples to reveal the importance of considering nodes in the connectivity calculation of pipeline network. The reliability of the network system decreases significantly after considering the nodes such as elbows and tees. The damage of one node usually causes the failure of the whole pipes of the path. The damage probability is greater in the area with dense elbow and tee nodes. In this study, all types of nodes that are more prone to damage are considered in detail in the calculation. As a result, the proposed algorithm has been improved in computational accuracy, which lays the foundation for further accurate calculation of pipeline network connectivity.
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Algoritmos , Terremotos , Simulação por Computador , Probabilidade , Reprodutibilidade dos TestesRESUMO
Supported-adsorbents growing on the substrate in situ are equipped with the advantages of high adsorption capacity, excellent regeneration performance, and adaptability to complex wastewater. However, the effects of substrate on the adsorption properties of supported-adsorbent are rarely considered, which will hinder its development and scale-up applications. In this study, the influences of different substrates (Ti, Mo, W, CC) on the Ag+ adsorption behavior of supported-MoS2 adsorbents were investigated. The adsorption kinetics, adsorption mechanism, and the renewability of these supported-MoS2 were compared orderly. As a result, MoS2 grown on a tungsten substrate (MoS2-W) exhibits a remarkable adsorption capacity for Ag+ (1.98 mg cm-2 and 598.80 mg g-1), which is 6.38-33 times more than the other three supported-MoS2. Moreover, the MoS2-W also possesses an ultrahigh distribution coefficient (24.80 mL cm-2) for Ag+, and the selection coefficient can reach 1984. XRD and electrochemical characterization analysis indicated that Ag+ adsorption performance of supported-MoS2 is positively correlated with the degree of its amorphous structure. Substrate W with the terrific electrical properties which may facilitate the disordered growth of MoS2, resulting in more active sites exposed, and endow MoS2-W with outstanding Ag+ capture performance. Finally, the supported-MoS2 retains a high removal efficiency of Ag+ after 5 cycles of adsorption and desorption. This study provides a novel perspective for promoting the practical application of supported-sorbents to recycle heavy metals.
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Metais Pesados , Poluentes Químicos da Água , Adsorção , Cinética , Metais Pesados/análise , Molibdênio/química , Águas Residuárias/química , Poluentes Químicos da Água/análiseRESUMO
Thirty-five legacy and emerging per- and polyfluoroalkyl substances (PFAS) were analyzed in surface water and sediments collected from Poyang Lake, the largest freshwater lake in China. The Æ©PFAS concentrations ranged from 23 to 1000 ng/L in water dissolved phase, 1.3-9.8 ng/L in suspended particulate matters, and 0.26-2.9 ng/g dry weight in sediments. Short-chain and emerging PFAS were predominant in surface water and sediments, rather than legacy perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS). Hexafluoropropylene oxide dimer/trimer acid (HFPO-DA/TA), 6:2 and 8:2 chlorinated polyfluorinated ether sulfonic acids (6:2 and 8:2 Cl-PFESAs), 6:2 fluorotelomer sulfonate (6:2 FTS), and sodium p-perfluorous nonenoxybenzene sulfonate (OBS) were detected in all samples, indicating that these emerging PFAS have been widely produced and used in this region. The high concentrations of HFPO-DA/TA, 6:2 FTS, 6:2, 8:2 Cl-PFESAs, and OBS in sediments and their higher water-sediment distribution coefficients than those of predecessors (PFOA or PFOS) suggest that lake sediments could be an important long-term sink for these emerging alternatives. The positive matrix factorization model demonstrated that food packaging and textile treatments (50%) and fluoropolymer manufacturing (26% for alternative sources and 8.2% for legacy sources) were the two major sources of PFAS in Poyang Lake. The influx and outflux of total PFAS in Poyang Lake were 9.0 and 12.8 ton/year, respectively, and the OBS flux was estimated for the first time. The results provide insights into the environmental behavior and fate of emerging PFAS in freshwater ecosystems.
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Ácidos Alcanossulfônicos , Fluorocarbonos , Poluentes Químicos da Água , Ácidos Alcanossulfônicos/análise , China , Ecossistema , Monitoramento Ambiental , Fluorocarbonos/análise , Lagos , Água , Poluentes Químicos da Água/análiseRESUMO
The objective of this study was to elucidate the molecular characteristics of a Chinese family with Glanzmann's thrombasthenia (GT). The proband was diagnosed with GT based on clinical manifestations, platelet aggregation, and the expression of CD41 and CD61 in platelets. Whole-exome and Sanger sequencing were used to detect genetic defects related to GT in the proband and the family of the pedigree. Whole-exome sequencing showed a c.1784-1802delinsGTCACA, p. S595Cfs*70 homozygous mutation in exon 11 of the ITGB3 gene in the proband. Heterozygous mutations were found in the proband's parents, grandmother, uncle, aunt, and younger brother. This novel p. S595Cfs*70 ITGB3 gene mutation is not present in the 1000 Genomes and ExAC databases.
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Bases de Dados de Ácidos Nucleicos , Éxons , Mutação da Fase de Leitura , Homozigoto , Integrina beta3 , Trombastenia/genética , Adolescente , Feminino , Humanos , Sequenciamento do ExomaRESUMO
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematological malignancy characterized by recurrent skin nodules, an aggressive clinical course with rapid involvement of hematological organs, and a poor prognosis with poor overall survival. BPDCN is derived from plasmacytoid dendritic cells (pDCs) and its pathogenesis is unclear. The tumor cells show aberrant expression of CD4, CD56, interleukin-3 receptor alpha chain (CD123), blood dendritic cell antigen 2 (BDCA 2/CD303), blood dendritic cell antigen 4 (BDCA4) and transcription factor (E protein) E2-2 (TCF4). The best treatment drugs are based on experience by adopting those used for either leukemia or lymphoma. Relapse with drug resistance generally occurs quickly. Stem cell transplantation after the first complete remission is recommended and tagraxofusp is the first targeted therapy. In this review, we summarize the differentiation of BPDCN from its cell origin, its connection with normal pDCs, clinical characteristics, genetic mutations and advances in treatment of BPDCN. This review provides insights into the mechanisms of and new therapeutic approaches for BPDCN.
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Células Dendríticas/patologia , Neoplasias Hematológicas/genética , Neoplasias Cutâneas/genética , Doença Aguda/epidemiologia , Antígenos de Superfície/genética , Antígenos CD4/genética , Antígeno CD56/genética , Diferenciação Celular/genética , Células Dendríticas/metabolismo , Progressão da Doença , Neoplasias Hematológicas/patologia , Humanos , Subunidade alfa de Receptor de Interleucina-3/genética , Lectinas Tipo C/genética , Glicoproteínas de Membrana/genética , Receptores Imunológicos/genética , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/terapia , Fator de Transcrição 4/genéticaRESUMO
OBJECTIVE: To explore the application value of goal-directed fluid therapy (GDFT) in patients undergoing laparoscopy-assisted radical gastrectomy with fast-track anesthesia. METHODS: From December 2016 to December 2019, 74 patients who underwent laparoscopy-assisted radical gastrectomy under the concept of enhanced recovery after surgery (ERAS) in gastrointestinal Surgery department of Tongling People's Hospital were selected as research participants. They were divided into two groups: the routine group (patients were treated with conventional fluids) (n=37) and the GDFT group (patients were treated with GDFT) (n=37). In the two groups, patients were compared in terms of intraoperative fluid inflow and outflow, hemodynamic indexes before operation for 30 min (T0), after anesthesia induction for 30 min (T1), during operation for 0.5 h (T2) and 1.5 h (T3) and after operation (T4), postoperative complications, postoperative recovery, mini-mental state examination (MMSE) scores on the first day (d0) before operation and the first day (d1), the third day (d2) and the seventh day (d3) after operation, and inflammatory factor levels. RESULTS: The amount of crystal input, colloid, blood loss, fluid replacement and urine volume in the GDFT group were significantly less than those in the routine group (P < 0.05). From T1 to T4, the values of mean arterial pressure (MAP) and central venous pressure (CVP) in the GDFT group were higher than those in the routine group (p < 0.05). The total incidence of postoperative complications in the GDFT group was lower than that in the routine group (P < 0.05). Compared with those in the routine group, the postoperative anus exhaust time, the first time of starting to eat, the time of leaving bed, the duration of stay in the postanesthesia care unit and the hospital stay were significantly shorter in the GDFT group (P < 0.05). From D1 to D3, the MMSE score in the GDFT group was higher than that in the routine group, while the levels of C-reactive protein (CPR), interleukin 6 (IL-6) and procalcitonin (PCT) were lower than those in the routine group (P < 0.05). CONCLUSION: GDFT has a better effect on the rapid rehabilitation of patients undergoing laparoscopy-assisted radical gastrectomy during fast-track anesthesia, and it also has a positive effect on maintaining the stability of hemodynamics, reducing systemic inflammation and decreasing postoperative complications.
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Transient ground displacement (TGD) that is caused by earthquakes can damage underground pipes. This damage is especially critical for the joints, elbows and tees of the pipes which play an important role in the operation of a pipe network. In this study, a scale pipe network with both elbows and tees, as well as some components of the pipe network with only tees or elbows, has been investigated. The response of the nodes of a pipe network, when installed in non-uniform geology, was analyzed using the shaking table test and ABAQUS finite element simulation. This paper has firstly introduced the preparation of the test and the developed finite element model. Then the system response in terms of strain, the friction, the bending deformation, the node deformation amplification coefficient and the pipe-soil relative displacement along the pipe axis of the pipe network and two pipe network components have been analyzed explaining the correlation between these responses. Finally, the influence of elbows and tees on the pipe network was analyzed, and the conclusions that have been reached about how tees and elbows can change the response of a pipe network during an earthquake can provide theoretical support for the seismic design and layout of an underground pipe network.
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Terremotos , Teste de Materiais/métodos , Indústria de Petróleo e Gás/instrumentação , Geologia , Humanos , Modelos Estatísticos , Estresse MecânicoRESUMO
Due to cause the deterioration of water quality and can produce toxic nitrite, the nitrate constituted of great threatens to human health and eco-systematic safety. Among most well-known biotechnology to remove nitrate, the integrated heterotrophic and autotrophic denitrification (IHAD) process is promising, especially for the organic-limited polluted water. In this work, the IHAD coupled manganese oxidation (IHAD-MnO) process was developed by using Pseudomonas sp. SZF15 (Gram negative strain, and rod-shaped morphology with 2.3 µm in length) in the glass serum bottles. It was found that limited organic content could accelerate nitrate removal rate, and manganese oxidation efficiency can reach up to 60.08%. To further explain carbon conversion characteristics of the process, pure heterotrophic condition assays were conducted, the results confirmed that inorganic carbon will be generated by organic carbon metabolism in heterotrophic condition, the maximum accumulation content of inorganic carbon was 142.21 mg/L (when the initial organic carbon level was 293 mg-C/L). Subsequently, since the consumption of organic carbon, biogenic inorganic carbon can be further utilized by microorganisms to support autotrophic denitrification (AuDN). Besides, X-ray photoelectron spectroscopy (XPS) was employed to analyze precipitation products produced from the process. The magnified Mn 2p spectra results showed that a typical characteristic peak of manganese dioxide was observed with the intense peak at 641.8 eV and a satellite peak at 653.7 eV, respectively. This showed that Mn(II) was oxidized to manganese dioxide by the process, which may be a functional material with adsorption properties. The process posed a highly efficient and cost effective solution with less carbon consumption and less greenhouse gas emission for sustainable water treatment technologies.
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Nitratos , Águas Residuárias , Reatores Biológicos , Carbono , Desnitrificação , Humanos , Manganês , NitrogênioRESUMO
In this study, an experimental investigation was conducted on the mechanical properties of lightweight aggregate concrete (LWAC) with different chopped fibers, including basalt fiber (BF) and polyacrylonitrile fiber (PANF). The LWAC performance was studied in regard to compressive strength, splitting tensile strength and shear strength at age of 28 days. In addition, the oven-dried density and water absorption were measured as well to confirm whether the specimens match the requirement of standard. In total, seven different mixture groups were designed and approximately 104 LWAC samples were tested. The test results showed that the oven-dried densities of the LWAC mixtures were in range of 1.819-1.844 t/m3 which satisfied the definition of LWAC by Chinese Standard. Additionally, water absorption decreased with the increasing of fiber content. The development tendency of the specific strength of LWAC was the same as that of the cube compressive strength. The addition of fibers had a significant effect on reducing water absorption. Adding BF and PANF into concrete had a relatively slight impact on the compressive strength but had an obvious effect on splitting tensile strength, flexural strength and shear strength enhancement, respectively. In that regard, a 1.5% fiber volume fraction of BF and PANF showed the maximum increase in strength. The use of BF and PANF could change the failure morphologies of splitting tensile and flexural destruction but almost had slight impact on the shear failure morphology. The strength enhancement parameter ß was proposed to quantify the improvement effect of fibers on cube compressive strength, splitting tensile strength, flexural strength and shear strength, respectively. And the calculation results showed good agreement with test value.
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B-cell receptor (BCR) signaling is important for the development and maturation of normal B-cells and plays a key role in B-cell malignancies. Bruton's tyrosine kinase (BTK), a crucial terminal kinase enzyme in BCR signaling, has emerged as an attractive target and has been successfully applied in the treatment of hematological malignancies. Ibrutinib, a BTK inhibitor, has demonstrated marked efficacy and tolerability in treatment-naïve, relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and mantle cell lymphoma (MCL). Ibrutinib has been approved by the Food and Drug Administration (FDA) for the treatment of CLL/SLL, MCL, marginal zone lymphoma and Waldenström macroglobulinemia and by the China FDA for the treatment of CLL/SLL and MCL. Clinical trials of ibrutinib, as a single agent or combined with chemoimmunotherapy and other promising novel agents in the treatment of B-cell malignancy therapy, such as diffuse large B-cell lymphoma, follicular lymphoma, multiple myeloma, primary and secondary CNS lymphoma and acute lymphoblastic leukemia, T-cell lymphoma and myelodysplastic syndrome, are ongoing (https://clinicaltrials.gov/). The aim of the present review was mainly to cover the clinical developments regarding the use of ibrutinib in the treatment of CLL/SLL, as well as its safety and toxicity profile.
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Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Pirazóis/uso terapêutico , Pirimidinas/uso terapêutico , Transdução de Sinais/efeitos dos fármacos , Adenina/análogos & derivados , Animais , Humanos , PiperidinasRESUMO
BACKGROUND: Recent studies have revealed that long noncoding RNAs (lncRNAs) may hold crucial triggers of the pathogenesis of hematological malignancies, while the studies evaluating the expression pattern of lncRNA in acute myeloid leukemia (AML) are few. Thus, this study aimed to investigate the implication of lncRNA expression pattern in AML development and progression. METHODS: Bone marrow samples from four AML patients and four controls were subjected to lncRNA sequencing. Then, bone marrow samples from 110 AML patients and 40 controls were proposed to real-time quantitative polymerase chain reaction (RT-qPCR) validation for 10 candidate lncRNAs. Clinical data and survival profiles were recorded in AML patients. Furthermore, lncRNA RP4-576H24.2 expression in AML cell lines and its effect on AML cell proliferation and apoptosis were detected. RESULTS: LncRNA expression pattern by sequencing clearly distinguished AML patients from controls, and 630 upregulated and 621 downregulated lncRNAs were identified in AML patients compared to controls, which were mainly enriched in AML oncogene-related biological process and pathways (such as neutrophil degranulation, leukocyte transendothelial migration, and hematopoietic cell lineage). RT-qPCR validation observed that six lncRNAs correlated with AML risk, one lncRNA associated with risk stratification, and three lncRNAs correlated with survivals, among which lncRNA RP4-576H24.2 was the only one correlated with AML susceptibility, risk stratification, and survivals. Further in vitro experiments showed that lncRNA RP4-576H24.2 was upregulated in AML cell lines compared to normal bone marrow mononuclear cells (BMMCs), and promoted proliferation while inhibited apoptosis in HL-60 and KG-1 cells. CONCLUSIONS: LncRNA expression pattern is closely involved in the development and progression of AML, and several specific lncRNAs exhibit potential to be biomarkers for AML risk and prognosis. Besides, lncRNA RP4-576H24.2 might be a potential oncogene in AML pathogenesis.