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To the best of our knowledge, the output performance of a self-Q-switched Tm:YAP laser has been controlled by adjusting the cavity length for the first time. By using a concise concave-flat cavity, a pulsed laser emitting at 1993â nm is produced without any additional modulation device. Under a stable self-Q-switched mode, the maximum average output power of 9.76â W is achieved from the laser when the incident pump power is 28.78â W, corresponding to a slope efficiency of 36.9% and an optical-to-optical conversion efficacy of 33.9%. Also, the narrowest pulse width of 485â ns at 48.97â kHz is obtained from the laser with a single pulse energy of 199.3â µJ. As far as we know, this laser has the highest average power and narrowest pulse width compared to other self-Q-switched Tm:YAP lasers.
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OBJECTIVE: An analysis was conducted to explore the relationship between dietary fibre intake and stroke risk. METHODS: PubMed, EMBASE, Cochrane Library, China National Knowledge Infrastructure (CNKI) and WanFang and Weipu databases were systematically searched to obtain peer-reviewed literature on the relationship between dietary fibre and stroke risk. The search time was as of 1 April 2023. Newcastle-Ottawa Scale (NOS) was used to evaluate the quality of the included studies. The pooled hazard ratio (HR) and 95% confidence interval (CI) were calculated using Stata 16.0. The Q test and I2 statistics were used to evaluate the heterogeneity and sensitivity analysis to explore potential bias. Meta-regression analysis was conducted to explore the relationship between total dietary intake quality and stroke risk. RESULTS: Sixteen high-quality studies, involving 855,671 subjects, met the inclusion criteria and were involved in the final meta-analysis. The results showed that higher total dietary fibre (HR: 0.81; 95% CI: 0.75-0.88), fruit fibre (HR: 0.88; 95% CI: 0.82-0.93), vegetable fibre (HR: 0.85; 95% CI: 0.81-0.89), soluble fibre (HR: 0.82; 95% CI: 0.72-0.93) and insoluble fibre (HR: 0.77; 95% CI: 0.66-0.89) had a positive effect on reducing the risk of stroke. However, cereal fibre (HR: 0.90; 95% CI: 0.81-1.00) was not statistically significant in reducing the risk of stroke. For different stroke types, higher total dietary fibre was associated with ischemic stroke (HR: 0.83; 95% CI: 0.79-0.88) and had a similar positive effect but was not found in haemorrhagic stroke (HR: 0.91; 95% CI: 0.80-1.03). Stroke risk decreased with increased total dietary fibre intake (ß=-0.006189, P=0.001). No potential bias from the individual study was found from sensitivity analysis. CONCLUSION: Increasing dietary fibre intake had a positive effect on reducing the risk of stroke. Different dietary fibres have various effects on stroke.
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Accidente Cerebrovascular Hemorrágico , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Humanos , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/epidemiología , Fibras de la Dieta , ChinaRESUMEN
We report a diode-pumped passively mode-locked Tm:Sc2SiO5 (Tm:SSO) laser for the first time, to the best of our knowledge. The stable continuous-wave (CW) mode-locking is achieved with a semiconductor saturable absorber mirror (SESAM). Operating at the eye-safe wavelength of 1967.7â nm, the pulsed laser delivers a pulse duration of 16.5 ps with an average output power of 207â mW. At a fundamental repetition frequency of 81â MHz, the signal-to-noise ratio is as high as 70â dB. These results demonstrate the great potential of Tm:SSO crystal for ultrashort pulse generation.
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High quality monolayer WS2 was successfully fabricated by chemical vapor deposition method. The nonlinear optical response of monolayer WS2 is demonstrated for the first time. Due to the relatively low modulation depth of 1.4% and saturable intensity of 68.6 kW/cm2 of monolayer WS2, a robust continuous-wave mode-locked (CWML) nanosecond laser with a repetition rate of 93.1 MHz is obtained. To the best of our knowledge, this is the highest repetition rate of nanosecond pulses generated from CWML lasers. This work provides an effective approach to obtaining nanosecond pulsed lasers with repetition rates of hundred-megahertz.
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Few-layered graphdiyne (GDY) was successfully fabricated and applied as a saturable absorber to generate a watt-level ultrafast solid-state bulk laser. The maximum output power of up to 1.27 W was obtained with a pulse width of 23 ps and a repetition rate of 92.9 MHz, using Nd:YVO4 crystal as a gain medium. To the best of our knowledge, this is the first application of GDY as a mode locker in all-solid-state bulk lasers. These results indicate the promising potential of GDY for producing high-power ultrafast lasers.
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We report the first demonstration, to the best of our knowledge, of tunable and Q-switched lasers based on diode-pumped Nd,Lu:CaF2 disordered crystal. A continuous tuning range of approximately 32 nm (1047-1079 nm) was obtained for tunable operations. A passively Q-switched laser was successfully achieved using a Cr4+:YAG as a saturable absorber. The shortest pulse width of 275 ns was obtained with a repetition rate of 1.85 kHz and corresponding peak power and single pulse energy of 189 W and 51.9 µJ, respectively.
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AIM: To determine whether there is a long-term benefit of MRI-guided bilateral anterior capsulotomy in the treatment of refractory schizophrenia. METHODS: 116 patients (16 patients did not complete the follow-up evaluation) with refractory schizophrenia who underwent capsulotomy were included. The treatment effect was evaluated using a series of international rating scales. Evaluations were performed at baseline, 3 weeks and 24 months after surgery. RESULTS: The rate of effectiveness was 74% according to the Clinical Global Impression evaluation, and there was an obvious improvement based on the statistical analysis for Positive and Negative Symptom Scale (baseline vs. 24 months after surgery, 6.86 ± 8.12, 10.70 ± 8.70 vs. 26.65 ± 4.85, 21.66 ± 7.19), Brief Psychiatric Rating Scale (14.75 ± 13.21 vs. 44.97 ± 9.36), Activities of Daily Living Scale (18.06 ± 6.58 vs. 24.61 ± 8.95), Social Disability Screening Schedule (6.69 ± 6.12 vs. 15.06 ± 3.18) and Global Assessment Scale (74.35 ± 12.75 vs. 48.74 ± 9.18). Among all the symptoms of schizophrenia, aggressive behavior (82% response rate), hallucination, (71% response rate) and delusion (70% response rate) showed the best response. CONCLUSION: Our research indicates that capsulotomy is a relatively safe and effective intervention for patients with refractory schizophrenia. It could be an alternative therapy for those patients with chronic and severe schizophrenia. But there must be strict inclusion criteria considering the complications and irreversibility of this procedure.
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Cápsula Interna/cirugía , Imagen por Resonancia Magnética/métodos , Psicocirugía/métodos , Esquizofrenia/cirugía , Psicología del Esquizofrénico , Técnicas Estereotáxicas , Adolescente , Adulto , Escalas de Valoración Psiquiátrica Breve , Femenino , Estudios de Seguimiento , Humanos , Imagen por Resonancia Magnética/tendencias , Masculino , Persona de Mediana Edad , Psicocirugía/tendencias , Esquizofrenia/diagnóstico , Técnicas Estereotáxicas/tendencias , Factores de Tiempo , Adulto JovenRESUMEN
Acute myeloid leukemia (AML) is a heterogeneous disease with a poor prognosis. The current risk stratification system is essential but remains insufficient to select the best schedules. Cysteine-rich protein 1 (CSRP1) is a member of the CSRP family and associated with poor clinicopathological features in many tumors. This study aimed to explore the clinical significance and molecular mechanisms of cysteine- and glycine-rich protein 1 (CSRP1) in AML. RT-qPCR was used to detect the relative expression of CSRP1 in our clinical cohort. Functional enrichment analysis of CSRP1-related differentially expressed genes was carried out by GO/KEGG enrichment analysis, immune cell infiltration analysis, and protein-protein interaction (PPI) network. The OncoPredict algorithm was implemented to explore correlations between CSRP1 and drug resistance. CSRP1 was highly expressed in AML compared with normal samples. High CSRP1 expression was an independent poor prognostic factor. Functional enrichment analysis showed neutrophil activation and apoptosis were associated with CSRP1. In the PPI network, 19 genes were present in the most significant module, and 9 of them were correlated with AML prognosis. The high CSRP1 patients showed higher sensitivity to 5-fluorouracil, gemcitabine, rapamycin, cisplatin and lower sensitivity to fludarabine. CSRP1 may serve as a potential prognostic marker and a therapeutic target for AML in the future.
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Cisteína , Leucemia Mieloide Aguda , Humanos , Cisteína/genética , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patología , Pronóstico , Perfilación de la Expresión Génica , Glicina/genéticaRESUMEN
Background: There were bacteria in the early pancreatic juice culture of severe acute pancreatitis (SAP) patients, but during the clinical time, some patients showed more positive bacteria and some patients showed more negative bacteria. Many scholars have different test results, and further clinical research needs to be carried out to clarify this fact. To determine evidence of infection in the early stage of acute pancreatitis (AP) by pancreatic juice bacterial culture and provide a reference for the anti-infective therapy of AP. Methods: Patients with AP who underwent pancreatic juice bacterial culture in the Department of hepatobiliary surgery of the General Hospital of Ningxia Medical University from January 1, 2019 to June 30, 2020were reviewed. Endoscopic retrograde cholangiopancreatography (ERCP) was used to collect pancreatic juice, which was sent to the laboratory for culturing. The clinical data and bacterial culture results of the patients were then recorded and analyzed. According to the results of the pancreatic juice culture, the patients were divided into a positive bacterial culture group (n=64) and a negative bacterial culture group (n=92). It was compared the data results of two groups [age, gender, etiology, acute physiology and chronic health evaluation (APACHE) II score, cultured bacteria, complications, local complications, Balthazar computed tomography (CT) score, inflammatory factors, the use of antibiotics, drug sensitivity analysis results, and the patient's co-infection] and performed multivariate analysis to identify the clinically valuable indicators. Moreover, a receiver operating characteristic (ROC) curve was drawn to predict the model of positive pancreatic juice culture in AP. Results: The patients in the positive bacterial culture group and the negative bacterial culture group had statistically significant differences in gender, age, body mass index (BMI), amylase, white blood cell count and the two groups of patients were comparable. A total of 156 patients were included in the study and pathogenic bacteria were cultured in the pancreatic juice of 64 patients (41.03%) and 94 strains of bacteria were found (Gram-positive bacteria, 38.30%; Gram-negative bacteria, 58.51%; fungi, 3.19%). A history of ERCP and early pancreatic necrosis were independent influencing factors of positive pancreatic juice culture. The incidence of complications, APACHE II, and inflammatory factor levels of patients with positive pancreatic juice bacterial culture were significantly higher than those of negative pancreatic juice bacterial culture (P<0.05). Multivariate regression and the ROC curve of pancreatic infection showed that positive pancreatic and Balthazar CT score >7 on admission were independent risk factors of pancreatic. The area under the ROC curve of patients with later pancreatic infection was 0.863 [95% confidence interval (CI): 0.769-0.957], specificity was 65.30%, sensitivity was 90.50%, and the Youden index was 0.603. Conclusions: Bacterial culturing of pancreatic juice provides evidence of infection in the early stage of AP, which has certain significance for the anti-infective therapy of AP.
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Triptolide is a major active ingredient isolated from the traditional Chinese medicine Tripterygium wilfordii, which has anti-inflammatory, anti-cancer, and immunomodulatory effects. However, in clinical studies, triptolide has toxic side effects on the heart, kidney, liver and reproductive organs. With respect to female reproductive toxicity, damaging effects of triptolide on the ovary have been reported, but it has remained unknown whether oocytes are affected by triptolide. Therefore, this study established a concentration gradient of triptolide exposure in mice using 0 (control), 30, 60, and 90 µg triptolide/kg body weight/day administered by gavage. Triptolide administration for 28 d reduced body weight and ovarian weight and affected the developmental potential of oocytes. The triptolide-treated group exhibited meiotic failure of oocytes due to impaired spindle assembly, chromosome alignment, and tubulin stability. Triptolide was also found to induce mitochondrial dysfunction, autophagy and early apoptosis, iron homeostasis, and abnormal histone modifications. These adverse effects could be associated with oxidative stress induced by triptolide. In conclusion, our findings suggest detrimental effects of triptolide on mouse oocytes and, thus, on female reproduction.
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Fenantrenos , Femenino , Ratones , Animales , Fenantrenos/toxicidad , Oocitos , Estrés Oxidativo , Apoptosis , Peso CorporalRESUMEN
The utilizing light with broadband range has attracted lots of research interest for the photo induced reversible-deactivation radical polymerization (RDRP). However, it is still a challenge for a single catalyst to simultaneously respond to various lights with highly varied wavelengths. Here, we proposed a simple strategy for the preparation of a heterogeneous photocatalyst suitable for photo induced atom transfer radical polymerization (photoATRP) under full spectrum (from UV/vis light to NIR), by combining pyridine nitrogen doped carbon dots (N-CDs) and upconversion nanoparticles (UCNPs). In the presence of these robust UCNP@SiO2@N-CDs composite particles, the photoATRP could be carried on under the different irradiations of UV, blue, green, red, white, and 980 nm NIR light, with a low loading of part per million concentrations of the CuBr2/L catalyst. Moreover, the excellent solvent and aqueous compatibility allow UCNP@SiO2@N-CDs to be capable for photoATRP in both organic solvents and aqueous media, providing well-defined hydrophobic and hydrophilic polymers with low dispersity and excellent chain-end fidelity. In addition, the photoATRP with 980 nm NIR exhibited excellent penetrations through visible-light-proof barriers. The system could be used for the preparation of an injectable hydrogel that had dual curing and photoluminescence modes. Owing to the "living" characteristics of polymer chains achieved through ATRP, the hydrogel was capable to be easily repaired by using monomer as the binder.
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Lithium metal is considered as the most prospective electrode for next-generation energy storage systems due to high capacity and the lowest potential. However, uncontrollable spatial growth of lithium dendrites and the crack of solid electrolyte interphase still hinder its application. Herein, Schottky defects are motivated to tune the 4f-center electronic structures of catalysts to provide active sites to accelerate Li transport kinetics. As experimentally and theoretically confirmed, the electronic density is redistributed and affected by the Schottky defects, offering numerous active catalytic centers with stronger ion diffusion capability to guide the horizontal lithium deposition against dendrite growth. Consequently, the Li electrode with artificial electronic-modulation layer remarkably decreases the barriers of desolvation, nucleation, and diffusion, extends the dendrite-free plating lifespan up to 1200 h, and improves reversible Coulombic efficiency. With a simultaneous catalytic effect on the conversions of sulfur species at the cathodic side, the integrated Li-S full battery exhibits superior rate performance of 653 mA h g-1 at 5 C, high long-life capacity retention of 81.4% at 3 C, and a high energy density of 2264 W h kg-1 based on sulfur in a pouch cell, showing the promising potential toward high-safety and long-cycling lithium metal batteries.
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OBJECTIVE: To analyze the characteristics of gene mutation and overexpression in newly diagnosed multiple myeloma (NDMM) patients. METHODS: Bone marrow cells from 208 NDMM patients were collected and analyzed. The gene mutation of 28 genes and overexpression of 6 genes was detected by DNA sequencing. Chromosome structure abnormalities were detected by fluorescence in situ hybridization (FISH). RESULTS: Gene mutations were detected in 61 (29.33%) NDMM patients. Some mutations occurred in 5 or more cases, such as NRAS, PRDM1, FAM46C, MYC, CCND1, LTB, DIS3, KRAS, and CRBN. Overexpression of six genes (CCND1, CCND3, BCL-2, CCND2, FGFR3, and MYC) were detected in 83 (39.9%) patients, and cell cycle regulation gene was the most common. Single nucleotide polymorphisms (SNP) changes were detected in 169 (81.25%) patients, the TP53 P72R gene SNP (70.17%) was the most common. Abnormality in chromosome structure was correlated to gene overexpression. Compared to the patients with normal chromosome structure, patients with 14q32 deletion showed higher proportion of CCND1 overexpression. Similarly, patients with 13q14 deletion showed higher proportion of FGFR3 overexpression, whereas patients with 1q21 amplification showed higher proportion of CCND2, BCL-2 and FGFR3 overexpression. CONCLUSION: There are multiple gene mutations and overexpression in NDMM. However, there is no dominated single mutation or overexpression of genes. The most common gene mutations are those in the RAS/MAPK pathway and the genes of cyclin family CCND are overexpression.
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Mieloma Múltiple , Aberraciones Cromosómicas , Humanos , Hibridación Fluorescente in Situ , Mieloma Múltiple/genética , MutaciónRESUMEN
A novel composite cavity optical fiber laser (CCFL) sensor, based on weak feedback of the optical fiber end face, is proved theoretically and experimentally. The application of the vibration measurement based on the CCFL sensor is demonstrated to prove its feasibility.
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Organic modifiers have shown promising potential for regulating the activity and selectivity of heterogeneous catalysts via tuning their surface properties. Despite the increasing application of organic modification technique in regulating the redox-acid catalysis of metal oxides, control of the acidity of metal oxide catalysts for enhanced reaction selectivity without sacrificing their redox activity remains a substantial challenge. Herein, we show the successful control of redox-acid catalysis of metal oxides with aprotic tertiary amine modifiers. Robust modification of manganese dioxide catalysts with N,N-dialkylcyclohexylamine selectively blocks the Lewis acid sites, with their redox activity mostly unaffected. This enables efficient synthesis of imines in high to excellent selectivity via aerobic oxidation of structurally diverse aryl amines.
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OBJECTIVE: To investigate the inhibitory effect of adiponectin receptor agonist AdipoRon on proliferation of myeloma cell lines and its possible mechanism. METHODS: The myeloma cell lines Sp2/0-Ag14 and MPC-11 were treated with different concentration of AdipoRon. The cell proliferation was detected by CCK-8. Western blot was used to determine the protein level of the signaling pathway. RT-PCR was used to quantify the mRNA copy number of adiponectin receptor AdipoR1 and AdipoR2 in the bone marrow cells from 21 patients with multiple myeloma (MM). Twenty-three normal bone marrow samples were served as control. RESULTS: AdipoRon significantly inhibited the proliferation of MM cell lines Sp2/0-Ag14 and MPC-11 in a concentration-dependent and time-dependent manner. Western blot showed that AdipoRon induced an increase of the expression levels of apoptosis-related proteins cleaved caspase-3 and cleaved PARP. AdipoRon upregulated p-AMPK and its downstream p-ACC in MPC-11. In addition, AdipoRon upregulated LC3-II/LC3-I level and down-regulated the protein level of p62. The expression level of AdipoR1 in MM cells was significantly higher than that in normal controls, and the expression level of AdipoR2 in MM cells was significantly lower than that in normal controls. CONCLUSION: Adiponectin receptors are expressed differentially between MM patients and normal subjects. AdipoRon, an adiponectin receptor agonist, can inhibit myeloma cell proliferation and induce apoptosis, and AMPK/autophagy pathway may be one of its mechanisms.
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Autofagia , Mieloma Múltiple , Proteínas Quinasas Activadas por AMP , Apoptosis , Proliferación Celular , Humanos , Piperidinas , Receptores de Adiponectina , Transducción de SeñalRESUMEN
Objectives: The prognostic role of WT1 in acute lymphoblastic leukemia (ALL) is still controversial. No study has focused on the prognostic role of WT1 expression in adult B-ALL patients receiving chemotherapy only.Methods: Using TaqMan-based real time quantitative PCR (RQ-PCR), we detected the WT1 transcript levels of 162 de-novo adult B-ALL patients at the time of diagnosis and analysed their clinical features.Results: WT1 overexpression was defined as a transcript level higher than 0.50%, which is the upper limit in normal bone marrow. WT1 overexpression was identified in 66.0% of the patients and was an independent positive prognostic factor for CIR, RFS and OS in patients who received chemotherapy only (CIR: HR = 0.236 [95% confidence interval 0.094-0.592]; P = 0.002; RFS: HR = 0.223 [0.092-0.543]; P = 0.001; OS: HR = 0.409 [0.214-0.783]; P = 0.007) and in patients who did not have BCR-ABL fusion or KMT2A rearrangements (CIR: HR = 0.431 [0.201-0.921]; P = 0.030; RFS: HR = 0.449 [0.224-0.899]; P = 0.024; OS: HR = 0.521 [0.278-0.977]; P = 0.042). However, WT1 overexpression had no prognostic value in patients who received allogenic hematopoietic stem cell transplantation (allo-HSCT). Furthermore, allo-HSCT could improve the prognosis of patients with low WT1 expression.Conclusion: Therefore, testing for WT1 expression at the time of diagnosis may predict outcomes in adult B-ALL patients who receive only chemotherapy and who do not have the BCR-ABL fusion gene or KMT2A rearrangements. Allo-HSCT may improve the prognosis of patients with low WT1 transcript levels.
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Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Proteínas WT1/metabolismo , Adolescente , Adulto , Femenino , Humanos , Masculino , Pronóstico , Resultado del Tratamiento , Adulto JovenRESUMEN
High-quality all-carbon nanostructure graphdiyne (GDY) saturable absorber was successfully fabricated and saturable absorption properties in the 2 µm region were characterized using a commercial mode-locked laser as a pulsed source. The fabricated GDY was first used as an optical switcher in a passively Q-switched Ho laser. Under absorbed pump power of 2.4 W, the maximum average output power and shortest pulse width were 443 mW and 1.38 µs, at a repetition rate of 29.72 kHz. The results suggest that GDY nanomaterial is a promising candidate as an optical modulator for generation of short pulses in Ho-doped lasers at 2.1 µm.
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The mutational spectrum and prognostic factors of NRAS-mutated (NRASmut) acute myeloid leukemia (AML) are largely unknown. We performed next-generation sequencing (NGS) in 1,149 cases of de novo AML and discovered 152 NRASmut AML (13%). Of the 152 NRASmut AML, 89% had at least one companion mutated gene. DNA methylation-related genes confer up to 62% incidence. TET2 had the highest mutation frequency (51%), followed by ASXL1 (17%), NPM1 (14%), CEBPA (13%), DNMT3A (13%), FLT3-ITD (11%), KIT (11%), IDH2 (9%), RUNX1 (8%), U2AF1 (7%) and SF3B1(5%). Multivariate analysis suggested that age ≥ 60 years and mutations in U2AF1 were independent factors related to failure to achieve complete remission after induction therapy. Age ≥ 60 years, non-M3 types and U2AF1 mutations were independent prognostic factors for poor overall survival. Age ≥ 60 years, non-M3 types and higher risk group were independent prognostic factors for poor event-free survival (EFS) while allogenic hematopoietic stem cell transplantation was an independent prognostic factor for good EFS. Our study provided new insights into the mutational spectrum and prognostic factors of NRASmut AML.
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GTP Fosfohidrolasas/genética , Leucemia Mieloide Aguda/diagnóstico , Proteínas de la Membrana/genética , Adolescente , Adulto , Anciano , Proteínas de Unión al ADN/genética , Dioxigenasas , Supervivencia sin Enfermedad , Femenino , Humanos , Estimación de Kaplan-Meier , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/mortalidad , Masculino , Persona de Mediana Edad , Análisis Multivariante , Mutación , Nucleofosmina , Oportunidad Relativa , Pronóstico , Proteínas Proto-Oncogénicas/genética , Proteínas Represoras/genética , Factores de Riesgo , Factor de Empalme U2AF/genética , Adulto JovenRESUMEN
B-cell acute lymphoblastic leukemia (B-ALL) in adults remains a highly challenging disease. Identifying new prognostic biomarkers is necessary to help select the best therapeutic schedules and to improve prognosis. We performed bioinformatics analyses of transcriptomic data to identify aberrantly-expressed mRNA transcripts in B-ALL and focused on RASD1 (Ras-related dexamethasone-induced 1). To date, no information is available on the prognostic value of RASD1 in B-ALL. Fifty-three consecutive adults with de novo B-ALL were enrolled in this study. Our data suggested that RASD1 was abnormally overexpressed in B-ALL. High RASD1 transcript levels at diagnosis were associated with lower survival probabilities (44% [20%-61%] vs. 79% [60%-97%]; P = 0.037) and were also an independent prognostic factor in adult B-ALL (HR = 4.9 [1.5-15.9]; P = 0.008). Functional in vitro analyses and bioinformatic analyses indicated that RASD1 promoted cell proliferation, cell cycle progression and chemotherapy resistance and inhibited cell apoptosis. These data demonstrated that RASD1 might serve as a novel prognostic biomarker for adult B-ALL and as a potential therapeutic target in adult B-ALL patients.