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1.
Nature ; 606(7916): 873-877, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35676486

RESUMO

The dispersive sweep of fast radio bursts (FRBs) has been used to probe the ionized baryon content of the intergalactic medium1, which is assumed to dominate the total extragalactic dispersion. Although the host-galaxy contributions to the dispersion measure appear to be small for most FRBs2, in at least one case there is evidence for an extreme magneto-ionic local environment3,4 and a compact persistent radio source5. Here we report the detection and localization of the repeating FRB 20190520B, which is co-located with a compact, persistent radio source and associated with a dwarf host galaxy of high specific-star-formation rate at a redshift of 0.241 ± 0.001. The estimated host-galaxy dispersion measure of approximately [Formula: see text] parsecs per cubic centimetre, which is nearly an order of magnitude higher than the average of FRB host galaxies2,6, far exceeds the dispersion-measure contribution of the intergalactic medium. Caution is thus warranted in inferring redshifts for FRBs without accurate host-galaxy identifications.

2.
Nature ; 609(7928): 685-688, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-36131036

RESUMO

Fast radio bursts (FRBs) are highly dispersed, millisecond-duration radio bursts1-3. Recent observations of a Galactic FRB4-8 suggest that at least some FRBs originate from magnetars, but the origin of cosmological FRBs is still not settled. Here we report the detection of 1,863 bursts in 82 h over 54 days from the repeating source FRB 20201124A (ref. 9). These observations show irregular short-time variation of the Faraday rotation measure (RM), which scrutinizes the density-weighted line-of-sight magnetic field strength, of individual bursts during the first 36 days, followed by a constant RM. We detected circular polarization in more than half of the burst sample, including one burst reaching a high fractional circular polarization of 75%. Oscillations in fractional linear and circular polarizations, as well as polarization angle as a function of wavelength, were detected. All of these features provide evidence for a complicated, dynamically evolving, magnetized immediate environment within about an astronomical unit (AU; Earth-Sun distance) of the source. Our optical observations of its Milky-Way-sized, metal-rich host galaxy10-12 show a barred spiral, with the FRB source residing in a low-stellar-density interarm region at an intermediate galactocentric distance. This environment is inconsistent with a young magnetar engine formed during an extreme explosion of a massive star that resulted in a long gamma-ray burst or superluminous supernova.

3.
Nature ; 598(7880): 267-271, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34645999

RESUMO

The event rate, energy distribution and time-domain behaviour of repeating fast radio bursts (FRBs) contain essential information regarding their physical nature and central engine, which are as yet unknown1,2. As the first precisely localized source, FRB 121102 (refs. 3-5) has been extensively observed and shows non-Poisson clustering of bursts over time and a power-law energy distribution6-8. However, the extent of the energy distribution towards the fainter end was not known. Here we report the detection of 1,652 independent bursts with a peak burst rate of 122 h-1, in 59.5 hours spanning 47 days. A peak in the isotropic equivalent energy distribution is found to be approximately 4.8 × 1037 erg at 1.25 GHz, below which the detection of bursts is suppressed. The burst energy distribution is bimodal, and well characterized by a combination of a log-normal function and a generalized Cauchy function. The large number of bursts in hour-long spans allows sensitive periodicity searches between 1 ms and 1,000 s. The non-detection of any periodicity or quasi-periodicity poses challenges for models involving a single rotating compact object. The high burst rate also implies that FRBs must be generated with a high radiative efficiency, disfavouring emission mechanisms with large energy requirements or contrived triggering conditions.

4.
Nature ; 587(7832): 63-65, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33149293

RESUMO

Fast radio bursts (FRBs) are millisecond-duration radio transients of unknown physical origin observed at extragalactic distances1-3. It has long been speculated that magnetars are the engine powering repeating bursts from FRB sources4-13, but no convincing evidence has been collected so far14. Recently, the Galactic magnetar SRG 1935+2154 entered an active phase by emitting intense soft γ-ray bursts15. One FRB-like event with two peaks (FRB 200428) and a luminosity slightly lower than the faintest extragalactic FRBs was detected from the source, in association with a soft γ-ray/hard-X-ray flare18-21. Here we report an eight-hour targeted radio observational campaign comprising four sessions and assisted by multi-wavelength (optical and hard-X-ray) data. During the third session, 29 soft-γ-ray repeater (SGR) bursts were detected in γ-ray energies. Throughout the observing period, we detected no single dispersed pulsed emission coincident with the arrivals of SGR bursts, but unfortunately we were not observing when the FRB was detected. The non-detection places a fluence upper limit that is eight orders of magnitude lower than the fluence of FRB 200428. Our results suggest that FRB-SGR burst associations are rare. FRBs may be highly relativistic and geometrically beamed, or FRB-like events associated with SGR bursts may have narrow spectra and characteristic frequencies outside the observed band. It is also possible that the physical conditions required to achieve coherent radiation in SGR bursts are difficult to satisfy, and that only under extreme conditions could an FRB be associated with an SGR burst.

5.
Zhonghua Xin Xue Guan Bing Za Zhi ; 52(1): 72-78, 2024 Jan 24.
Artigo em Zh | MEDLINE | ID: mdl-38220458

RESUMO

Objective: To investigate the effects of exosome derived from miR-133a-3p engineered human umbilical cord blood mesenchymal stem cells (ucMSC) on myocardial repair after acute myocardial infarction (AMI) in rats. Methods: UcMSC was amplified and cultured in vitro. Lentiviral carrying miR-133a-3p and negative control vectors were transfected into ucMSC. Exosomes secreted by the transfected ucMSC were named miR-133a-3p-Exo and miR-NC-Exo, respectively. The AMI model of rats was established by ligation of the left anterior descending coronary artery. MiR-133a-3p-Exo or miR-NC-Exo were then injected into the border zone of the infarct area. Cardiac function was assessed by echocardiography after twenty-eight days of intervention, and Masson staining was used to evaluate the area of myocardial fibrosis post-AMI. The myocardial apoptosis after infarction was evaluated by TUNEL staining and the angiogenesis after infarction was evaluated by immunofluorescence staining in the current study. Results: Compared with the miR-NC-Exo group, the left ventricular ejection fraction in the miR-133a-3p-Exo group was significantly increased ((47.4%±9.8%) vs. (64.2%±8.9%), P<0.05). While the myocardial fibrosis area ((31.2%±7.3%) vs. (18.0%±1.5%), P<0.01) and the percentage of apoptotic cardiomyocytes ((25.6%±3.6%) vs. (15.1%±4.4%), P<0.05) was significantly reduced in the miR-133a-Exo group. Besides, the expression of CD31 and α-smooth muscle actin (α-SMA) were also increased significantly in the miR-133a-3p-Exo group compared to the miR-NC-Exo group (CD31: (2.9±0.9) vs. (13.9±2.0), P<0.000 1, α-SMA: (3.5±0.9) vs. (11.0±1.6), P<0.000 1). Conclusion: Exosome derived from miR-133a-3p engineered ucMSC effectively inhibited myocardial apoptosis and promoted angiogenesis, thus improving the cardiac function after myocardial infarction in rats.


Assuntos
Cardiomiopatias , Exossomos , Células-Tronco Mesenquimais , MicroRNAs , Infarto do Miocárdio , Ratos , Humanos , Animais , Exossomos/metabolismo , Volume Sistólico , Ratos Sprague-Dawley , MicroRNAs/genética , Função Ventricular Esquerda , Infarto do Miocárdio/genética , Cardiomiopatias/metabolismo , Fibrose , Células-Tronco Mesenquimais/metabolismo , Apoptose
9.
Nature ; 531(7593): 202-5, 2016 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-26934226

RESUMO

Fast radio bursts are millisecond-duration astronomical radio pulses of unknown physical origin that appear to come from extragalactic distances. Previous follow-up observations have failed to find additional bursts at the same dispersion measure (that is, the integrated column density of free electrons between source and telescope) and sky position as the original detections. The apparent non-repeating nature of these bursts has led to the suggestion that they originate in cataclysmic events. Here we report observations of ten additional bursts from the direction of the fast radio burst FRB 121102. These bursts have dispersion measures and sky positions consistent with the original burst. This unambiguously identifies FRB 121102 as repeating and demonstrates that its source survives the energetic events that cause the bursts. Additionally, the bursts from FRB 121102 show a wide range of spectral shapes that appear to be predominantly intrinsic to the source and which vary on timescales of minutes or less. Although there may be multiple physical origins for the population of fast radio bursts, these repeat bursts with high dispersion measure and variable spectra specifically seen from the direction of FRB 121102 support an origin in a young, highly magnetized, extragalactic neutron star.

10.
Br J Surg ; 106(13): 1747-1760, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31386192

RESUMO

BACKGROUND: Primary tumour location is emerging as an important prognostic factor in localized and metastatic colorectal cancers. However, its prognostic role in colorectal liver metastasis (CRLM) after hepatectomy remains controversial. A systematic review and meta-analysis was undertaken to evaluate its prognostic value. METHODS: References were identified through searches of PubMed, Embase, Web of Science and the Cochrane Library comparing overall or disease-free survival after hepatic resection between patients with CRLM originating from right- or left-sided colorectal cancers. Data were pooled using hazard ratios (HRs) and 95 per cent confidence intervals according to a random-effects model. Meta-regression and subgroup analyses were conducted to assess the effect of underlying confounding factors on HR estimates and to adjust for this. RESULTS: The final analysis included 21 953 patients from 45 study cohorts. Compared with left-sided primary tumour location, right-sided location was associated with worse overall survival (HR 1·39, 95 per cent c.i. 1·28 to 1·51; P < 0·001; prediction interval 1·00 to 1·93), and also tended to have a negative impact on disease-free survival (HR 1·18, 1·06 to 1·32; P = 0·004; prediction interval 0·79 to 1·75). Subgroup analysis showed that the negative effect of right-sided primary tumour location on overall survival was more prominent in the non-Asian population (HR 1·47, 1·33 to 1·62) than the Asian population (HR 1·18, 1·05 to 1·32) (P for interaction <0·01). CONCLUSION: This study demonstrated a prognostic role for primary tumour location in patients with CRLM receiving hepatectomy, especially regarding overall survival. Adding primary tumour location may provide important optimization of prognosis prediction models for CRLM in current use.


ANTECEDENTES: La ubicación del tumor primario (primary tumor location, PTL) ha surgido como un factor pronóstico importante en los cánceres colorrectales (colorectal cancers, CRCs) localizados y metastásicos. Sin embargo, todavía se discute su relevancia como factor pronóstico tras la resección de metástasis hepáticas de cáncer colorrectal (colorectal liver metastases, CRLM). Se realizó una revisión sistemática y un metaanálisis para determinar su valor pronóstico. MÉTODOS: En PubMed, EMBASE, Web of Science y la Biblioteca Cochrane se identificaron los trabajos que compararon la supervivencia global (overall survival, OS) y la supervivencia libre de enfermedad (disease-free survival, DFS) tras la resección hepática de CRLM cuyo CRCs estuviese situado en el lado derecho o izquierdo. Los datos se expresaron en forma del cociente de riesgos instantáneos (hazard ratio, HR) e intervalos de confianza del 95% (i.c. del 95%) de acuerdo con un modelo de efectos aleatorios. Se efectuaron análisis de metarregresión y de subgrupos para evaluar el efecto de los factors de confusión existentes en las estimaciones de HR, ajustando por los mismos. RESULTADOS: El análisis final incluyó 21.953 pacientes de cohortes de 45 estudios. La PTL en el lado derecho en comparación con el lado izquierdo se asoció con una peor supervivencia global (HR 1,39; i.c. del 95% 1,28-1,51; P < 0,001; intervalo de predicción 1,00-1,93) y una tendencia a un impacto negativo en la DFS (HR 1,18; i.c. del 95% 1,06-1,32; P = 0,004; intervalo de predicción 0,79-1,75). El análisis de subgrupos mostró que el efecto negativo de la PTL del lado derecho en la OS fue más prominente en la población no asiática (HR 1,47; i.c. del 95% 1,33-1,62) que en la asiática (HR 1,18; i.c. del 95% 1,05-1,32; Pinteracción < 0,01). CONCLUSIÓN: Este estudio demostró que la PTL tiene un papel pronóstico tras la hepatectomía de las CRLM, especialmente respecto a la OS. La adición de la PTL proporcionaría una optimización importante en los modelos actuales de predicción pronóstica de CRLM.


Assuntos
Neoplasias Colorretais/patologia , Hepatectomia/métodos , Neoplasias Hepáticas/secundário , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/cirurgia , Intervalo Livre de Doença , Saúde Global , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/cirurgia , Metástase Neoplásica , Estadiamento de Neoplasias , Prognóstico , Taxa de Sobrevida/tendências
11.
Zhonghua Yi Xue Za Zhi ; 96(28): 2214-9, 2016 Jul 26.
Artigo em Zh | MEDLINE | ID: mdl-27480651

RESUMO

OBJECTIVE: To campare the effect and tolerance beween intensified myeloablative conditioning regime (IMCR) without antithymocyte globulin (ATG) and myeloablative conditioning regime (MCR) for single-unit unrelated umbilical cord blood transplantation (sUCBT) in hematological malignancies. METHODS: The clinical data of 190 patients with hematological malignancies undergoing sUCBT between April 2000 and December 2013 at Department of Hematology, Anhui Provincial Hospital were retrospectively analyzed, of whom 156 received IMCR without ATG (IMCR group), including 79 patient receiving total body irradiation (TBI)/cytosine arabinoside (Ara-C)/cyclophosphamide (CY) regime, 47 receiving fludarabine (Flu)/busulfan (Bu)/CY regime, and 30 receiving Ara-C/Bu/CY regime, and all of the 156 received a combination of cyclosporine A (CsA) and mycophelonate mofetil (MMF) for the prophylaxis of graft-versus-host disease (GVHD); the remaining 34 patients received MCR (MCR group), 30 patients receiving Bu/CY regime, and 4 receiving TBI/CY regime, all using CsA/MMF±ATG or methotrexate (MTX) for the prophylaxis of GVHD. The two groups were compared in disease status at the time of transplantation, characteristics of graft, transplantation effect, and transplantation-related complications. RESULTS: There were no statistically significant differences between the two groups in gender, disease type, human leukocyte antigen match, ABO blood type match, and disease status at the time of transplantation (all P>0.05). The median age and body weight at transplantation in the IMCR group were significantly higher than those in the MCR group (13 years vs 9 years, P=0.003; 44 kg vs 26 kg, P=0.000). The median doses of infused total nucleated cells (×10(7)/kg) and CD34(+) cells (×10(5)/kg) in the IMCR group were significantly lower than in the MCR group (3.87 vs 4.99, P=0.002; 2.00 vs 3.17, P=0.000). The cumulative incidence of myeloid engraftment on the 42th day and platelet engraftment on the 120th day in the IMCR group were remarkably higher than in the MCR group [96.33%(95%CI: 96.27%-96.39%)vs 82.30%(95%CI: 80.67%-83.93%), P=0.000; 86.44%(95%CI: 86.28%-86.60%)vs 51.17%(95%CI: 49.02%-53.32%), P=0.002]. There were no statistically significant differences in the incidences of grade Ⅱ to Ⅳ acute GVHD, grade Ⅲ to Ⅳ acute GVHD, and 2-year chronic GVHD(P=0.482, 0.928, 0.579). The incidence of pre-engraftment syndrome in the IMCR group was higher than in the MCR group(82.70% vs 47.06%, P=0.000). And 180-day transplantation-related mortality (TRM) in the IMCR group was lower than that in the MCR group [20.50%(95%CI: 20.28%-20.71%)vs 42.20% (95%CI: 41.32%-45.09%), P=0.004]. Up to October 2015, with a median follow-up of 44.2(22.7-188.9)months, the estimated 3-year overall survival and disease-free survival in the IMCR group were both significantly higher than those in the MCR group (62.90% vs 34.10%, P=0.000; 58.60% vs 34.10%, P=0.001). CONCLUSION: IMCR without ATG may improve the engraftment without increasing complications, reduce early transplantation-related mortality, and improve survival.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Bussulfano/administração & dosagem , Transplante de Células-Tronco de Sangue do Cordão Umbilical/métodos , Ciclofosfamida/administração & dosagem , Neoplasias Hematológicas/cirurgia , Neoplasias Hematológicas/terapia , Condicionamento Pré-Transplante/métodos , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bussulfano/uso terapêutico , China/epidemiologia , Ciclofosfamida/uso terapêutico , Ciclofosfamida/toxicidade , Ciclosporina , Citarabina/administração & dosagem , Citarabina/uso terapêutico , Intervalo Livre de Doença , Feminino , Sangue Fetal/citologia , Doença Enxerto-Hospedeiro/prevenção & controle , Antígenos HLA , Transplante de Células-Tronco Hematopoéticas , Humanos , Incidência , Masculino , Estudos Retrospectivos , Resultado do Tratamento , Vidarabina/análogos & derivados , Irradiação Corporal Total
12.
Genet Mol Res ; 14(3): 7463-8, 2015 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-26214425

RESUMO

To study the role of boswellic acid in reducing asthma phenotype severity and the relationship between the expression of pSTAT6 and GATA3, thirty-six mice were randomly divided into normal control group, asthma group, and boswellic acid group (treatment group). The asthma model was established through an intraperitoneal injection of sensitization liquid (0.15 mL aluminum hydroxide gel at 88.67 mg/mL and 0.05 mg ovalbumin). pSTAT6 and GATA3 expression levels in peripheral blood were detected by reverse transcription-polymerase chain reaction and Western blot analysis. pSTAT6 and GATA3 gene expressions in the asthmatic group were significantly higher than in the normal control group; they were markedly lower in the treatment group than the asthma group, and there was no significant difference when compared with the normal control group. The pSTAT6 expressions in the asthma, control and treatment groups were 2.256 ± 0.125, 0.524 ± 0.210, and 0.897 ± 0.134 at gray level, respectively. The GATA3 expressions in the asthma, control, and treatment groups were 3.521 ± 0.631, 0.435 ± 0.136, and 0.743 ± 0.149 at gray level, respectively. pSTAT6 and GATA3 expression levels were similar in the treatment and control groups. GATA3 expression had a positive correlation with pSTAT6 expression. Boswellic acid may improve asthma symptoms by inhibiting pSTAT6 expression, which consequently reduces GATA3 expression.


Assuntos
Asma/tratamento farmacológico , Asma/patologia , Regulação para Baixo/efeitos dos fármacos , Fator de Transcrição GATA3/genética , Fator de Transcrição STAT6/antagonistas & inibidores , Triterpenos/uso terapêutico , Animais , Asma/genética , Fator de Transcrição GATA3/metabolismo , Masculino , Camundongos Endogâmicos BALB C , Fenótipo , Fosforilação/efeitos dos fármacos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Fator de Transcrição STAT6/genética , Fator de Transcrição STAT6/metabolismo , Triterpenos/farmacologia
13.
Genet Mol Res ; 14(1): 574-84, 2015 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-25729993

RESUMO

In previous studies, we first isolated one different protein ß-1,3-glucanase using two-dimensional electrophoresis and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry from normal wheat (Triticum aestivum L.) and chemical hybridization agent-induced male sterility (CIMS) wheat. In this experiment, ß-1,3-glucanase activity and the expression of a callose deposition-related gene, UDP-glucose phosphorylase (UGPase), were determinate in normal, CIMS, and genetic male sterility (GS) wheat. ß-1,3-glucanase activity was significantly different between the fertile and sterile lines during callose synthesis and degradation, but there was no difference between CIMS and GS wheat. The UGPase gene of callose deposition was highly expressed in the meiophase and sharply decreased in the tetrad stage. However, the expression of the UGPase gene was significantly different between the fertile and sterile lines. These data indicated that ß-1,3-glucanase activity and the expression of the UGPase gene play important roles in the male sterility of wheat. Consequently, pollen mother cells (PMCs) might degenerate at the early meiosis stage, and differences in UGPase gene expression and ß-1,3-glucanase activity might eventually result in complete pollen collapse. In addition, the critical period of anther abortion might be the meiosis stage to the tetrad stage rather than what we previously thought, the mononuclear period.


Assuntos
Regulação da Expressão Gênica de Plantas , Glucana 1,3-beta-Glucosidase/metabolismo , Glucanos/metabolismo , Infertilidade das Plantas/genética , Triticum/enzimologia , Triticum/genética , DNA Complementar/genética , Eletroforese em Gel Bidimensional , Regulação Enzimológica da Expressão Gênica , Genes de Plantas , Nucleotidiltransferases/metabolismo , Proteínas de Plantas , Pólen/metabolismo , Pólen/ultraestrutura , RNA Ribossômico 18S/genética , Triticum/ultraestrutura
14.
Eur Rev Med Pharmacol Sci ; 28(4): 1456-1463, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38436179

RESUMO

OBJECTIVE: We aimed to explore the effectiveness of the modified tubularized incised plate urethroplasty (Snodgrass Technique) in hypospadias surgery. PATIENTS AND METHODS: A study was conducted on 50 pediatric patients with hypospadias treated in our hospital from May 2020 to May 2023. The patients were divided into two groups based on the condition of their urethral plate; 22 patients were included in the study group and 28 patients were included in the control group. The control group underwent the traditional Snodgrass technique, while the study group received the modified Snodgrass technique. The two groups were compared in terms of treatment efficacy, preoperative and postoperative 6-month Hypospadias Objective Scoring Evaluation (HOSE) scores, surgical data, and postoperative complications. RESULTS: The operation time for the study group was longer than that of the control group, and the intraoperative blood loss was less, but the differences were not statistically significant (p > 0.05). The success rate of surgery in the study group was 95.45% (21/22), compared to 71.43% (20/28) in the control group, showing a statistically significant difference (p < 0.05). The maximum urinary flow rate at 3 and 6 months postoperatively was significantly higher in the study group than in the control group (p < 0.05). The time to maximum flow (TQmax) and post-void residual (PVR) at 3 and 6 months postoperatively were significantly lower in the study group (p < 0.05). A total of 3 patients in the cohort developed urethral fistulas, all between 0.10 cm x 0.10 cm and 0.15 cm x 0.15 cm in size. By instructing the patients to apply pressure to the fistula during urination, all fistulas closed between 3 and 6 months postoperatively. The incidence of postoperative complications was 4.55% in the study group and 28.57% in the control group, a difference that was statistically significant (p < 0.05). CONCLUSIONS: The modified Snodgrass technique shows significant therapeutic effectiveness in hypospadias surgery, substantially increasing the success rate and reducing postoperative complications in pediatric patients, making it suitable for widespread application.


Assuntos
Fístula , Hipospadia , Masculino , Humanos , Criança , Hipospadia/cirurgia , Perda Sanguínea Cirúrgica , Hospitais , Complicações Pós-Operatórias
15.
Artigo em Inglês | MEDLINE | ID: mdl-37787059

RESUMO

This paper proposes an optimized Long Short-Term Memory (LSTM+) model for predicting cumulative confirmed cases of COVID-19 in Germany, the UK, Italy, and Japan. The LSTM+ model incorporates two key optimizations: (1) fine-adjustment of parameters and (2) a 're-prediction' process that utilizes the latest prediction results from the previous iteration. The performance of the LSTM+ model is evaluated and compared with that of Backpropagation (BP) and traditional LSTM models. The results demonstrate that the LSTM+ model significantly outperforms both BP and LSTM models, achieving a Mean Absolute Percentage Error (MAPE) of less than 0.6%. Additionally, two illustrative examples employing the LSTM+ model further validate its general applicability and practical performance for predicting cumulative confirmed COVID-19 cases.

16.
Genet Mol Res ; 10(4): 2987-95, 2011 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-22180032

RESUMO

The hypoxic-ischemic encephalopathy caused by peripartum asphyxia is a serious disease in newborn infants, and effective therapies need to be developed to reduce injury-related disorders. We evaluated the effects of NEP1-40 and fasudil on Nogo-A expression in neonatal hypoxic-ischemic brain damage (HIBD) rats. Seven-day-old Wistar rats were randomly divided into control, HIBD, NEP1-40, and fasudil groups. NEP1-40 and fasudil groups were injected intraperitoneally with these compounds. Rat brains at 6, 24, 72 h, and 7 days after HIBD were collected to determine histopathological damage and the expression levels of Nogo-A. Histopathological damage was reduced in NEP1-40 and fasudil groups compared with the untreated HIBD group. The expression of Nogo-A in the HIBD group was significantly higher than that in control, NEP1-40 and fasudil groups at the same times. Compared with the fasudil group, the expression levels of Nogo-A were significantly reduced in the NEP1-40 group. We conclude that NPE1-40 and fasudil have potential for neuroprotective effects in the neonatal rat HIBD model, mediated by inhibiting Nogo-A/ Rho pathways.


Assuntos
1-(5-Isoquinolinasulfonil)-2-Metilpiperazina/análogos & derivados , Encéfalo/efeitos dos fármacos , Hipóxia-Isquemia Encefálica/prevenção & controle , Proteínas da Mielina/biossíntese , Proteínas da Mielina/uso terapêutico , Fármacos Neuroprotetores/uso terapêutico , Fragmentos de Peptídeos/uso terapêutico , 1-(5-Isoquinolinasulfonil)-2-Metilpiperazina/administração & dosagem , 1-(5-Isoquinolinasulfonil)-2-Metilpiperazina/uso terapêutico , Animais , Animais Recém-Nascidos , Encéfalo/metabolismo , Encéfalo/patologia , Artérias Carótidas/efeitos dos fármacos , Artérias Carótidas/metabolismo , Artérias Carótidas/patologia , Feminino , Expressão Gênica/efeitos dos fármacos , Hipóxia-Isquemia Encefálica/genética , Hipóxia-Isquemia Encefálica/metabolismo , Hipóxia-Isquemia Encefálica/patologia , Imuno-Histoquímica , Hibridização In Situ , Injeções Intraperitoneais , Ligadura/métodos , Masculino , Proteínas da Mielina/administração & dosagem , Proteínas da Mielina/genética , Neurônios/citologia , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Fármacos Neuroprotetores/administração & dosagem , Proteínas Nogo , Fragmentos de Peptídeos/administração & dosagem , Ratos , Ratos Wistar
17.
Zhonghua Xue Ye Xue Za Zhi ; 41(6): 490-494, 2020 Jun 14.
Artigo em Zh | MEDLINE | ID: mdl-32654463

RESUMO

Objective: This study aimed to examine the safety and efficacy of CD19 chimeric antigen receptor T cell (CD19 CAR-T) therapy in relapsed/refractory Philadelphia chromosome-positive acute B-precursor lymphoblastic leukemia (R/R Ph(+) B-ALL) . Methods: The clinical data of 14 patients with R/R Ph(+) B-ALL treated with CD19 CAR-T cell therapy from November 2016 to April 2019 were retrospectively analyzed. Results: Among the 14 patients in this study, 7 were male and 7 were female, with a median age of 33 (7-66) years old. The efficacy was evaluated on the 28th day following CAR-T cells infusion; the overall response rate was 100.0% (14/14) , the complete response (CR) rate was 92.9% (13/14) , and the partial response (PR) rate was 7.1% (1/14) . After CAR-T cells infusion,12 cases (85.7%) developed cytokine release syndrome (CRS) : 1 case of grade 1 CRS, 4 cases of grade 2 CRS, 6 cases of grade 3 CRS, and 1 case of grade 4 CRS. Moreover, one case developed CAR T-cell-related encephalopathy syndrome (CRES) ; 14 cases had Ⅲ-Ⅳ hematological toxicity; and 13 CR cases had B cell dysplasia. These adverse reactions were all controllable. The median follow-up time was 441 (182-923) d. The median overall survival (OS) and progression-free survival (PFS) were 515 [95% confidence interval (CI) 287-743] days and 207 (95% CI 123-301) days, respectively. Conclusion: CD19 CAR-T cell therapy is safe and effective for R/R Ph(+) B-ALL treatment. However, the long-term efficacy needs to be further improved.


Assuntos
Cromossomo Filadélfia , Leucemia-Linfoma Linfoblástico de Células Precursoras , Adolescente , Adulto , Idoso , Antígenos CD19 , Criança , Feminino , Humanos , Imunoterapia Adotiva , Masculino , Pessoa de Meia-Idade , Receptores de Antígenos de Linfócitos T , Estudos Retrospectivos , Linfócitos T , Adulto Jovem
18.
Zhonghua Xue Ye Xue Za Zhi ; 41(9): 756-761, 2020 Sep 14.
Artigo em Zh | MEDLINE | ID: mdl-33113608

RESUMO

Objective: This study aims to evaluate the prognostic effect of peripheral blood cells in multiple myeloma (MM) patients treated with bortezomib. Methods: The clinical data of 155 newly diagnosed MM patients in two blood disease treatment centers from January 2014 to December 2016 were retrospectively studied. All patients received bortezomib as the first-line treatment. The results of the peripheral blood cell counts, including absolute neutrophil count, absolute monocyte count (AMC) , hemoglobin level, mean corpuscular volume (MCV) , and platelet count, and other clinical features were analyzed. Results: AMC (>0.6×10(9)/L) , MCV (>99.1 fl) , and platelet count (<150×10(9)/L) significantly affected patients' PFS and OS. The above three factors were assigned 1 point, respectively, to form the blood cell score. The analysis showed that 64 cases (41.3% ) had a score of 0, 57 cases (36.8% ) had 1, 32 cases (20.6% ) had 2, and 2 cases (1.3% ) had 3. The median PFS of the four groups were 42.8 m, 26.5 m, 15.8 m, and 6.4 m, respectively (P<0.001) . The median OS were NR, 48.2 m, 31.1 m, and 31.4 m, respectively (P=0.001) . Multivariate analysis suggested that the blood cell score (2-3 vs 0-1) and the proportion of marrow plasma cells (>30% ) were independent prognostic factors for PFS (HR=1.95 and 1.76, respectively) , while age (>65y vs ≤65y) , R-ISS stage (3 vs 1-2) , and blood cell score (2-3 vs 0-1) were independent prognostic factors for OS (HR=2.08, 2.13 and 2.12, respectively) . Conclusion: As an easy-to-access biomarker, the blood cell score can be used to evaluate the prognosis of newly diagnosed MM patients in the era of new drugs, but it is still necessary to expand the cases and make further confirmation in the prospective study.


Assuntos
Bortezomib/uso terapêutico , Mieloma Múltiplo , Células Sanguíneas , Intervalo Livre de Doença , Humanos , Mieloma Múltiplo/tratamento farmacológico , Prognóstico , Estudos Retrospectivos
20.
Zhonghua Er Ke Za Zhi ; 56(7): 505-510, 2018 Jul 02.
Artigo em Zh | MEDLINE | ID: mdl-29996183

RESUMO

Objective: To investigate the impact of early antibiotics treatment on intestinal microbiota in preterm infants. Methods: The cohort study was performed from January 2015 to June 2015 in Neonatal Intensive Care Unit of Peking University Third Hospital. A total of 33 preterm infants were enrolled, among whom 25 were antibiotics-exposure group, and 8 were non-exposure group. Serial stool samples were collected on the first day, 14th and 30th days of life and analyzed by high-throughput sequencing. In exposure group, intestinal microbiota was also analyzed at 8 months to 1 year of age. Categorical variables were analyzed with χ(2) test, and continuous variables were analyzed with t test or non-parametric test. Results:Proteobacteria was the most prominent flora after birth in all cases (exposure group 69.6%, non-exposure group 83.7%) . In exposure group, at the phylum level, Proteobacteria was the dominant bacteria within the first 30 days, followed by Firmicutes after 30 days of life. At the genus level, Escherichia was the most abundant genera within 30 days after birth, while Veillonella became dominant after 8 months to 1 year of life. In non-exposure group, at the phylum level, Proteobacteria was the dominant phylum within the first 30 days. At the genus level, Actinobacteria (37.5%) was the dominant genus after birth, followed by Escherichia within the first month. Intestinal bacterial abundance and diversity were lower in exposure group, which was most significant on 30th day of life (shannon index 2.6 vs.3.4, ACE index 563.9 vs.591.6) . The influence of single antibiotics was less significant than combined treatment (shannon index 2.7 vs.2.5, ACE index 727.3 vs.492.9) . At the genus level, compared to non-exposure group, there were significant decrease of Escherichia (9.3% vs. 54.3%, Z=-2.830, P=0.005), Klebsiella (0.03% vs.12.4%,Z=-2.240, P=0.025), and Clostridium (0.2% vs. 4.8%, Z=-2.979, P=0.003) in exposure group on 14 days of life. Bifidobacterium (0.1% vs.2.0%, Z=-2.349, P=0.019) in cases treated with combined antibiotics was lower than that treated with antibiotic monotherapy on 30 days of life. Conclusions: Early application of combined antibiotics impacts on the intestinal microbiome of preterm infants significantly. The infants who have received antibiotic after birth have lower quantity and diversity of Clostridium, Lactobacillus, Bacteroides and Bifidobacterium.


Assuntos
Antibacterianos , Microbioma Gastrointestinal , Recém-Nascido Prematuro , Antibacterianos/farmacologia , Estudos de Coortes , Microbioma Gastrointestinal/efeitos dos fármacos , Humanos , Recém-Nascido , RNA Ribossômico 16S
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