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1.
Blood Purif ; 53(2): 138-150, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37903464

RESUMO

INTRODUCTION: This study aimed to evaluate whether the addition of a hemoadsorption (HA) cartridge, HA-380, in the cardiopulmonary bypass (CPB) circuit in acute type A aortic dissection (ATAAD) surgery reduced inflammatory cytokine levels and decreased postoperative complications. METHODS: A retrospective observational cohort study was conducted between March 1, 2021, and February 28, 2022. Patients with ATAAD undergoing emergent total arch replacement surgery were divided into the control (CON) and HA groups on the basis of the addition of the HA-380 cartridge in the CPB circuit. RESULTS: Overall, 121 patients met the eligibility criteria; 2 patients in each group who died within the first postoperative week were excluded. Further, 57 and 60 patients in the CON and HA groups, respectively, were included in the pooled analysis. The major perioperative data, baseline values of interleukin-6 (IL-6) and C-reactive protein, and therapeutic interventions were similar in the two groups (all, p > 0.05). The serum IL-6 levels increased more rapidly in the CON group than those in the HA group postoperatively (205.73 ± 174.72 vs. 146.13 ± 64.15 pg/mL, p = 0.020). The HA group had a lower incidence of postoperative acute kidney injury (AKI) and severe acute respiratory distress syndrome than the CON group (25.4 vs. 44.6%, p = 0.032 and 18.3 vs. 35.1%, p = 0.040, respectively). Logistic regression analyses showed that HA may be a protective factor against postoperative AKI. The incidence of bleeding, delirium, and stroke as well as the lengths of intensive care unit and hospital stay in both groups were similar (all, p > 0.05). CONCLUSIONS: The use of HA-380 in the CPB circuit may attenuate inflammatory response and reduce major complications following ATAAD surgery. HA may be associated with lower rate of postoperative AKI.


Assuntos
Injúria Renal Aguda , Dissecção Aórtica , Humanos , Estudos Retrospectivos , Interleucina-6 , Dissecção Aórtica/cirurgia , Citocinas , Complicações Pós-Operatórias/terapia , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/terapia , Fatores de Risco
2.
Heart Surg Forum ; 26(1): E043-E047, 2023 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-36856510

RESUMO

BACKGROUND: Acute type A aortic dissection complicated by limb malperfusion presents a risk of mortality to the patients. Debates exist regarding management, whether focused on reperfusion first or immediate repair. Here, we aimed to describe our experience with the management of acute type A aortic dissection (ATAAD) complicated by limb malperfusion. METHODS: From January 1, 2020 to December 31, 2021, 22 consecutive patients were admitted to Xiamen Cardiovascular Hospital, due to acute type A aortic dissection complicated by limb malperfusion. All perioperative variables were recorded and analyzed. Limb malperfusion was diagnosed, according to the clinical symptoms, computed tomography angiography, and laboratory test. We adopted the clinical categories of acute limb ischemia to stratify severity of limb ischemia. Surgery strategies are as follows: Reperfusion first followed by central repair, immediate central repair, and immediate central repair followed by stenting. RESULTS: There were 21 males and one female with an average of 53.3±11.7 years. Management strategies were as follows: immediate central repair using total arch replacement with frozen elephant trunk in 15 patients, endovascular stenting followed by central repair in four patients, and endovascular stenting after central repair in two patients. The average extracorporeal circulation time was 258.8 ± 70.5 min; the average aortic cross-clamp time was 177.9 ± 54.2 min; and the average circulatory arrest time was 45.5 ± 13.1 min. The early mortality rate was 13.6% (3/22). Two patients left the hospital voluntarily, due to cerebral infarction and bleeding. One patient underwent fasciotomy for osteofascial compartment syndrome and uneventfully was discharged. Six patients underwent continuous renal replacement therapy and hemoperfusion. CONCLUSION: Central repair is safe and feasible for ATAAD complicated with limb malperfusion. For serious limb malperfusion, endovascular stenting followed by central repair is a good choice with continuous renal replacement therapy (CRRT) and hemoperfusion. Hospital mortality rate is high in cases with multiple organ malperfusion.


Assuntos
Dissecção Aórtica , Terapia de Substituição Renal Contínua , Masculino , Humanos , Feminino , Angiografia , Infarto Cerebral , Angiografia por Tomografia Computadorizada
3.
Cancer Invest ; 39(10): 819-825, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34325590

RESUMO

Glioma is a common central nervous system tumors in children. CMYC has a range of functions that are disrupted in various tumor cells, and may contribute to the occurrence and development of glioma. Two CMYC single nucleotide polymorphisms (rs4645943C>T and rs2070583 A>G) were genotyped in 190 cases and 248 controls from Wenzhou and Guangzhou hospitals. After adjusting for age and sex, odds ratio and 95% confidence interval values were calculated by logistic regression to evaluate the correlation between CMYC gene polymorphisms and glioma risk; no significant associations were detected. These results require future validation in a larger sample cohort.


Assuntos
Neoplasias Encefálicas/genética , Genes myc , Predisposição Genética para Doença , Glioma/genética , Polimorfismo de Nucleotídeo Único , Adolescente , Neoplasias Encefálicas/etiologia , Criança , Pré-Escolar , Feminino , Glioma/etiologia , Humanos , Lactente , Modelos Logísticos , Masculino
4.
Clin Lab ; 67(6)2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-34107624

RESUMO

BACKGROUND: Isochromosome 11q in patients with acute myeloid leukemia is rarely reported, and little is known about its main features. METHODS: The presence of isochromosome 11q was identified in four patients (three adults and one child) from screening 441 patients with an acute myeloid leukemia diagnosis between 2009 and 2018 by using R-banding and fluorescence in situ hybridization. RESULTS: The child, patient 1 with unreported isochromosome (partial 11q isochromosome), accompanied with t(1;11) translocation, initially achieved remission after receiving chemotherapy. However, 4 months later this patient experienced a relapse. While multiple treatments were tried, it had no effect and the patient survived for 16 months. The remaining patients with isochromosome 11q exhibited numerical/structural chromosomal abnormal-ities involving myelodysplastic syndrome-related chromosomes 5, 7, 8, and 20. In patients 2 and 3, we found a derivative chromosome 21. Patient 3 was newly diagnosed with acute myeloid leukemia and was treated with many chemotherapy protocols, unfortunately with no effect. The patient then received traditional Chinese medicine and survived for 10 months, although she still has not achieved complete remission. Patients 2 and 4 received chemotherapy but experienced rapid disease progression and died within 2 months. CONCLUSIONS: In summary, patients with isochromosome 11q/partial 11q isochromosome have a poorer prognosis, especially for isochromosome 11q. Furthermore, these chromosome aberrations may be risk factors for the presence of isochromosome 11q or myelodysplastic syndrome-related genes, both of them may be associated with a failure to respond to treatment and poor outcomes. Hence, these discoveries may lay a foundation to study mechanisms and explore treatments.


Assuntos
Isocromossomos , Leucemia Mieloide Aguda , Adulto , Criança , Aberrações Cromossômicas , Feminino , Humanos , Hibridização in Situ Fluorescente , Isocromossomos/genética , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Prognóstico
5.
Crit Care ; 24(1): 306, 2020 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-32513206

RESUMO

BACKGROUND: Early and rapid identification of Pseudomonas aeruginosa (P. aeruginosa) in patients with suspected ventilator-associated pneumonia (VAP) provides theoretical clinical advantages in therapeutic optimization strategies. METHODS: The P. aeruginosa-multiple cross displacement amplification (PA-MCDA) assay was conducted at an isothermal temperature during the amplification stage, and products were visually detected by color changes. The entire process was completed within 1 h. A total of 77 strains, including P. aeruginosa species and various other species of non-P. aeruginosa, were used to evaluate PA-MCDA assays. Bronchoalveolar lavage fluid (BALF) of suspected VAP patients was examined by the MCDA assay. RESULTS: The MCDA assay exhibited a 100% analytical specificity in detecting PA from all 77 strains, and the limit of detection was as low as 100 fg DNA per reaction. A temperature of 65 °C was recommended as standard during the amplification stage. The agreement between PA-MCDA and bacteria culture was 91.18% (κ = 0.787; p = 0.000) in the identification of P. aeruginosa in BALF from suspected VAP. The PA-MCDA assay showed values of 92.31%, 90.78%, 77.41%, and 97.18% for sensitivity, specificity, positive predictive value, and negative predictive value, respectively. PA-MCDA had a higher detective rate of P. aeruginosa than bacteria culture in patients with antipseudomonal therapy. CONCLUSIONS: The instrument-free platform of the MCDA assay makes it a simple, rapid, and applicable procedure for "on-site" diagnosis and point-of-care testing for the presence of P. aeruginosa without the need for specific bacterial culture.


Assuntos
Técnicas e Procedimentos Diagnósticos/normas , Pneumonia Associada à Ventilação Mecânica/etiologia , Pneumonia Associada à Ventilação Mecânica/microbiologia , Líquido da Lavagem Broncoalveolar/microbiologia , Técnicas e Procedimentos Diagnósticos/instrumentação , Técnicas e Procedimentos Diagnósticos/estatística & dados numéricos , Humanos , Pseudomonas aeruginosa/patogenicidade , Fatores de Tempo
6.
Org Biomol Chem ; 15(17): 3580-3584, 2017 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-28177033

RESUMO

A cascade biocatalysis system involving asymmetric hydroxylation and diastereoselective oxidation was developed using Rhodococcus equi ZMU-LK19, which gave chiral 2-substituted-1,2,3,4-tetrahydroquinoline-4-ols (2) (up to 57% isolated yield, 99 : 1 dr, and >99% ee) and chiral 2-substituted-2,3-dihydroquinolin-4(1H)-ones (3) (up to 25% isolated yield, and >99% ee) from (±)-2-substituted-tetrahydroquinolines (1). In addition, a possible mechanism for this cascade biocatalysis was tentatively proposed.


Assuntos
Quinolinas/química , Quinolinas/síntese química , Rhodococcus equi/metabolismo , Biocatálise , Técnicas de Química Sintética , Hidroxilação , Oxirredução , Estereoisomerismo
7.
Med Sci Monit ; 22: 4967-4973, 2016 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-27987364

RESUMO

BACKGROUND The aim of this study was to investigate the association of the polymorphism of folylpolyglutamate synthetase (FPGS) with the dynamic plasma concentration of methotrexate (MTX) in pediatric patients with acute lymphocytic leukemia (ALL), as well as the prognosis. MATERIAL AND METHODS 57 ALL patients and 31 age and sex-matched children (control) were included in this study. Polymerase chain reaction-restriction fragment length polymorphism was performed for the analysis of the genotype of FPGS rs1544105 and high-performance liquid chromatography for measurement of MTX plasma concentration after 24-h and 44-h treatment. Overall survival was analyzed by Kaplan-Meier method. RESULTS No differences were observed between patients and controls regarding the distribution frequency of genotype and alleles of rs1544105. Patients carrying AA genotype had a significantly higher plasma concentration of MTX after 24 h than those carrying GG or GA (P<0.05) and no differences were found after 44 h. Kaplan-Meier survival analysis showed a longer median survival time in patients with AA than other genotypes with significant difference in overall survival. CONCLUSIONS Polymorphism of FPGS rs1544105 might be used as an effective approach for prediction of the treatment outcome of MTX.


Assuntos
Metotrexato/administração & dosagem , Peptídeo Sintases/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/enzimologia , Alelos , Antimetabólitos Antineoplásicos/administração & dosagem , Antimetabólitos Antineoplásicos/efeitos adversos , Antimetabólitos Antineoplásicos/sangue , Criança , Pré-Escolar , Feminino , Frequência do Gene , Humanos , Masculino , Metotrexato/efeitos adversos , Metotrexato/sangue , Peptídeo Sintases/metabolismo , Polimorfismo de Nucleotídeo Único , Leucemia-Linfoma Linfoblástico de Células Precursoras/sangue , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Prognóstico
8.
J Mol Histol ; 55(1): 37-50, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38165568

RESUMO

Acute myeloid leukemia (AML) is a hematologic disease associated with genetic abnormalities. This study aimed to explore the role of leucine-rich repeat-containing protein 1 (LRRC1) in the malignant activities of AML and to reveal the molecular mechanism related to microtubule actin cross-linking factor 1 (MACF1). GEPIA database was used to analyze the expression of LRRC1 in bone marrow tissues of AML patients and the correlation between LRRC1 expression and survival analysis. LRRC1 was knocked down to assess the change of AML cell proliferation, cell cycle and apoptosis using CCK-8 assay and flow cytometry. Besides, the contents of extracellular acidification and oxygen consumption rates were measured to evaluate the glycolysis. Additionally, the interaction between LRRC1 and MACF1 predicted by MEM database and was verified by co-immunoprecipitation (Co-IP) assay. Then, MACF1 was overexpressed to conduct the rescue experiments. Expression of proteins in ß-catenin/c-Myc signaling was detected by western blot. Finally, AML xenograft mouse model was established to observe the impacts of LRRC1 silencing on the tumor development. Notably upregulated LRRC1 expression was observed in bone marrow tissues of AML patients and AML cells, and patients with the higher LRRC1 expression displayed the lower overall survival. LRRC1 depletion promoted cell cycle arrest and apoptosis and inhibited the glycolysis. Co-IP confirmed the interaction between LRRC1 and MACF1. MACF1 upregulation relieved the impacts of LRRC1 knockdown on the malignant activities of AML cells. Moreover, LRRC1 silencing inhibited the development of xenograft tumor growth of HL-60 cells in nude mice, suppressed MACF1 expression and inactivated the ß-catenin/c-Myc signaling. Collectively, LRRC1 knockdown suppressed proliferation, glycolysis and promoted apoptosis in AML cells by downregulating MACF1 expression to inactivate ß-catenin/c-Myc signaling.


Assuntos
Proteínas de Transporte , Leucemia Mieloide Aguda , Proteínas de Membrana , MicroRNAs , Humanos , Animais , Camundongos , Transdução de Sinais , Actinas/metabolismo , beta Catenina/genética , beta Catenina/metabolismo , Proteínas Proto-Oncogênicas c-myc/genética , Proteínas Proto-Oncogênicas c-myc/metabolismo , Cateninas/metabolismo , Camundongos Nus , Apoptose/genética , Proliferação de Células/genética , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/patologia , Microtúbulos/metabolismo , Microtúbulos/patologia , Linhagem Celular Tumoral , MicroRNAs/genética , Proteínas dos Microfilamentos/metabolismo
9.
J Cancer ; 15(4): 1067-1076, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38230206

RESUMO

Background: Glioblastoma (GBM) is a type of central nervous system malignancy. In our study, we determined the effect of NCDN in GBM patients through The Cancer Genome Atlas (TCGA) data analysis, and studied the effects of NCDN on GBM cell function to estimate its potential as a therapeutic target. Methods: Gene expression profiles of glioblastoma cohort were acquired from TCGA database and analyzed to look for central genes that may serve as GBM therapeutic targets. Then the cell function of NCDN in glioblastoma cell was explored through in vitro cell experiments. Results: Through gene ontology (GO) analysis, weighted gene co-expression network analysis (WGCNA), and survival analysis, we identified three key genes (NCDN, PAK1 and SPRYD3) associated with poor prognosis in glioblastoma. In vitro experiments showed impaired cell migration, apoptosis, and cell cycle arrest in NCDN knockdown cells. Conclusion: NCDN affects the progress and prognosis of glioblastoma by promoting cell migration and inhibiting apoptosis.

10.
Artigo em Inglês | MEDLINE | ID: mdl-38218532

RESUMO

BACKGROUND: The mortality of acute type A aortic dissection (ATAAD) with malperfusion syndrome (MPS) is high. However, the management strategy remains controversial. We aimed to evaluate the strategy for MPS at our institution. METHODS: Among 724 patients with ATAAD, 167 patients with MPS were treated with immediate central repair (first stage) or an optimized strategy (second stage). In the second stage, the optimized strategy used was based on 6-hour threshold from symptom onset. For MPS with symptom onset within 6 hours, immediate central repair was performed, followed by endovascular reperfusion if malperfusion persisted. With symptom onset beyond 6 hours, individualized delayed central repair was performed. We compared outcomes between the first and second stages. RESULTS: The in-hospital mortality of ATAAD was significantly decreased when the optimized strategy was used (4.3% in the second stage vs 12.5% in the first stage; P < .01). In the second stage, the in-hospital mortality for MPS was decreased (10.2% vs 33.9%; P < .01). Moreover, the in-hospital mortality for MPS with symptom onset within 6 hours and beyond 6 hours decreased from 24% to 7.5% and from 41.2% to 11.8%, respectively. The operative mortality of MPS in the second stage was comparable to that in patients without MPS (4.0% vs 2.4%; P > .05). CONCLUSIONS: The optimized strategy significantly improved the outcomes of MPS. The 6-hour threshold from symptom onset could be very useful in determining the timing of central repair. For patients with MPS symptom onset within 6 hours, immediate central repair is reasonable; for those with symptom onset beyond 6 hours, individualized delayed central repair should be considered.

11.
J Mol Neurosci ; 72(6): 1334-1344, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35322376

RESUMO

The aim of this study was to analyze the efficacy and underlying mechanism of adipose-derived mesenchymal stem cell exosome (ADSC-exosomes)-mediated protection on methotrexate (MTX)-induced neuronal damage. We established a H2O2-induced oxidative stress model in vitro, as well as an MTX-induced neuronal damage rat model in vivo. We analyzed the effects of ADSC-exosomes on neuronal damage and Nrf2-ARE signaling pathway in rats and related mechanisms. The morphological and functional recovery of rat hippocampal neurons by ADSC-exosomes was examined by Nissl staining and modified neurological severity score (mNSS) score. The activation of Nrf2-ARE pathway effectively inhibited H2O2-induced oxidative stress. ADSC-exosomes treatment restored the activity of hippocampal neuronal cells, reduced ROS production, and inhibited hippocampal neuronal cells apoptosis. In in vivo experiments, ADSC-exosomes ameliorates MTX-induced hippocampal neuron damage by triggering Nrf2-ARE pathway, decreasing IL-6, IFN-, and TNF-a levels and TUNEL positive cells in hippocampus, and repairing hippocampal neuronal cell damage. ADSC-exosomes ameliorated MTX-induced neuronal damage and suppressed oxidative stress induced by neuronal damage through the activation of Nrf2-ARE signaling pathway.


Assuntos
Elementos de Resposta Antioxidante , Exossomos , Células-Tronco Mesenquimais , Fator 2 Relacionado a NF-E2 , Neurônios , Estresse Oxidativo , Animais , Exossomos/efeitos dos fármacos , Exossomos/metabolismo , Peróxido de Hidrogênio/metabolismo , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/metabolismo , Metotrexato/toxicidade , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Ratos
12.
Int J Hematol ; 116(1): 146-151, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35181851

RESUMO

Cases of pediatric acute myeloid leukemia (AML) with complex karyotypes including chromosome 5 abnormalities are rare and have a very poor prognosis. Management of AML with monosomy 5/del(5q) has been inconsistent. We treated three adolescents with this AML subtype using combined low-dose cytarabine and mitoxantrone, concurrently with decitabine and G-CSF, for remission induction. Decitabine was also included in the conditioning regimen before hematopoietic cell transplantation (HCT). All three patients achieved complete remission after treatment with this combination therapy. The treatment was well tolerated, and the patients are alive and free of disease at 3.6, 3.2, and 3.0 years after HCT, respectively.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Cariótipo Anormal , Adolescente , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Criança , Aberrações Cromossômicas , Deleção Cromossômica , Citarabina , Decitabina , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Indução de Remissão
13.
Guang Pu Xue Yu Guang Pu Fen Xi ; 31(2): 362-5, 2011 Feb.
Artigo em Zh | MEDLINE | ID: mdl-21510381

RESUMO

The Kennard/Stone(K/S) algorithm is adopted to select the transfer set samples in the near infrared analysis calibration transfer by calculating the Euclidean distance of the spectrum of the samples. In order to get a best expression of the comparability of the samples and select the best samples for calibration transfer, piecewise direct standardization (PDS) algorithm was investigated for resolving calibration transfer of near-infrared spectra of mixed amine, then the Euclidean distance and the Mahalanobis distance were applied to calculate the comparability of the spectra of the samples and the standard error of prediction (SEP) was used to evaluate them. The combination of spectral difference and property difference was introduced to estimate the effect of individual spectral difference and property difference. The experimental results showed that the Mahalanobis distance was better than the Euclidean distance in PDS and the combination of spectral difference and property difference was more effective in expressing the comparability of the samples.

14.
Front Oncol ; 11: 762653, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34868978

RESUMO

Most randomized trials for acute promyelocytic leukemia (APL) have investigated highly selected patients under idealized conditions, and the findings need to be validated in the real world. We conducted a population-based study of all APL patients in Zhejiang Province, China, with a total population of 82 million people, to assess the generalization of all-trans retinoic acid (ATRA) and arsenic as front-line treatment. The outcomes of APL patients were also analyzed. Between January 2015 and December 2019, 1,233 eligible patients were included in the final analysis. The rate of ATRA and arsenic as front-line treatment increased steadily from 66.2% in 2015 to 83.3% in 2019, with no difference among the size of the center (≥5 or <5 patients per year, p = 0.12) or age (≥60 or <60 years, p = 0.35). The early death (ED) rate, defined as death within 30 days after diagnosis, was 8.2%, and the 3-year overall survival (OS) was 87.9% in the whole patient population. Age (≥60 years) and white blood cell count (>10 × 109/L) were independent risk factors for ED and OS in the multivariate analysis. This population-based study showed that ATRA and arsenic as front-line treatment are widely used under real-world conditions and yield a low ED rate and a high survival rate, which mimic the results from clinical trials, thereby supporting the wider application of APL guidelines in the future.

15.
Int J Clin Exp Pathol ; 13(3): 347-356, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32269672

RESUMO

The purpose of the study was to analyze the clinical characteristics and the course of diagnosis and therapy of asparaginase-associated pancreatitis (AAP) in childhood, improve the ability of diagnosis and treatment, and evaluate ULK2 gene polymorphism as a predictive factor for AAP. Data of 12 patients with childhood AAP were reviewed. Sanger sequencing of ULK2 gene was performed in AAP group (n=12) and control group (n=146). The main symptoms of AAP were abdominal pain and vomiting. Generally, the levels of amylase and lipase in the serum peaked within 72 h. Abdominal ultrasonography was performed in 11 patients; seven patients exhibited findings of pancreatic enlargement. Computed tomography was performed in 9 patients. Five patients exhibited findings of pancreatic enlargement and peri-pancreatic exudation. All patients were managed by fasting at the early stage, and seven patients underwent placement of a nasojejunal tube to receive enteral nutrition. One patient underwent endoscopic retrograde cholangiopancreatography (revealing dilation of the pancreatic duct) and endoscopic retrograde pancreatic drainage. Another patient developed signs of shock and received continuous renal replacement. There were no deaths caused by AAP. Therefore, early identification of patients at risk of AAP is of great importance. In addition, repeated elevation in the levels of pancreatic enzymes is indicative of complications. Sanger sequencing analysis of ULK2 gene showed that there was a significant difference of EXON1: -493C>T and EXON1: -308C>G between the AAP group and control group (P<0.0001). Thus, ULK2 gene polymorphism may be associated with the development of AAP. However, more validation of this finding is needed.

16.
Front Pharmacol ; 11: 571747, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33364947

RESUMO

Objective: This study evaluated the pharmacokinetics, safety, and bioequivalence (BE) of two formulations of rasagiline tablets in healthy Chinese subjects under fasting and fed conditions. Methods: An open, randomized, single-dose, double-cycle, two-sequence, self-crossover pharmacokinetic study in healthy Chinese subjects under fasting and high-fat postprandial conditions was performed. A total of 108 healthy subjects (36 in the fasting group and 72 in the postprandial group) were recruited. In each cycle of the study under both conditions, subjects received a single oral dose of 1 mg of a test or reference preparation of rasagiline tablets (1 mg each). A washout period of 3 days was observed. Blood samples were obtained up to 10 h post-intake. Primary endpoints were the BE of major pharmacokinetic parameters (AUC0-t and AUC0-∞) and the maximum observed serum concentration (Cmax). Secondary endpoints were safety parameters. Results: The 90% confidence interval (CI) of the geometric mean ratio (GMR) of the test drug vs. the reference drug for rasagiline was 94.16-105.35% for the AUC0-t under fasting conditions and 99.88-107.07% under postprandial conditions. The 90% CIs for the AUC0-∞ were 93.55-105.01% and 99.59-107.05% under fasting and postprandial conditions, respectively. The 90% CIs for the Cmax were 88.26-108.46% and 89.54-118.23% under fasting and postprandial conditions, respectively. The 90% CIs for the test/reference AUC ratio and Cmax ratio were within the acceptable range (0.80-1.25) for BE. In this BE study, there were no serious adverse events (AEs). Conclusion: BE between the test and the reference products was established in both fasting and postprandial conditions. The two formulations of rasagiline showed good tolerability and a similar safety profile. Clinical Trial Registration: chinaDrugtrials.org.cn, identifier CTR20181466.

17.
Biosci Rep ; 40(2)2020 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-32083300

RESUMO

Wilms tumor is the most common pediatric malignancy in the kidney. The miR34b/c is a downstream target gene of the transcription factor p53. The important role of TP53 mutations, the methylation of miR34b/c, and the interaction between these two molecules in tumorigenesis have been well documented. Due to the biological connection between p53 and miR34b/c, in the present study, we investigated the association between polymorphisms in these two molecules and Wilms tumor susceptibility through genotyping two important functional polymorphisms (miR34b/c rs4938723 T>C and TP53 rs1042522 C>G) in 183 cases and 603 controls. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) derived from the logistic regression analysis were used to assess the correlation of miR34b/c rs4938723 and TP53 rs1042522 polymorphisms with Wilms tumor risk. Our results indicated that the association of miR34b/c rs4938723 and TP53 rs1042522 polymorphisms with Wilms tumor susceptibility was not statistically significant. Stratified analysis by age, gender, and clinical stage, as well as combined effect analysis were also performed, yet, no significant association was found. In conclusion, our study indicated a lack of association between the two selected polymorphisms and Wilms tumor susceptibility. Our findings need to be verified in studies with larger sample size in the future.


Assuntos
Biomarcadores Tumorais/genética , MicroRNAs/genética , Polimorfismo de Nucleotídeo Único , Proteína Supressora de Tumor p53/genética , Tumor de Wilms/genética , Estudos de Casos e Controles , China , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Lactente , Masculino , Fenótipo , Medição de Risco , Fatores de Risco , Tumor de Wilms/diagnóstico
18.
Zhonghua Nan Ke Xue ; 15(11): 994-1000, 2009 Nov.
Artigo em Zh | MEDLINE | ID: mdl-20218311

RESUMO

OBJECTIVE: Clinical studies have shown decreased levels of sexual hormones, particularly testosterone deficiency, in men with chronic heart failure (CHF). The authors aimed to investigate the effect of testosterone on cardiac function and the possible mechanism of androgen protecting the heart in male rats. METHODS: Forty-three male SD rats were randomly divided into 3 groups: right heart failure (RHF, n = 15), physiologic testosterone treatment (TT, n = 15) and control (n = 13). The RHF group was given intraperitoneal injection of monocrotaline at 60 mg/kg to make RHF models; the TT group was injected with testosterone at 5 mg/kg 3 days after monocrotaline administration; and the control group received equal volume of saline. The CD34+ cells in the peripheral blood of each rat were counted by flow cytometry. The levels of serum testosterone and tumor necrosis factor alpha (TNF-alpha) were measured by chemiluminescence immunoassay and enzyme linked immunosorbent assay, respectively. The hearts, lungs and livers of all the surviving rats were excised at 6 weeks for pathological and immunohistochemical examinations. RESULTS: The level of serum testosterone was gradually decreased, while that of TNF-alpha obviously increased in the RHF group. After testosterone treatment, the TT group showed a remarkable improvement of cardiac performance and a significant decrease in the level of serum TNF-alpha as compared with the RHF group. Statistically significant differences were observed neither in the CD34+ cell count in the peripheral blood nor in the CD34+ expression of the myocardial cells between the TT and RHF groups. CONCLUSION: Physiological supplementation of testosterone can improve the cardiac function of RHF male rats, probably through its inhibition of TNF-alpha rather than by autologous mobilization of bone marrow stem cells.


Assuntos
Insuficiência Cardíaca/tratamento farmacológico , Testosterona/uso terapêutico , Animais , Insuficiência Cardíaca/metabolismo , Masculino , Ratos , Ratos Sprague-Dawley , Testosterona/sangue , Fator de Necrose Tumoral alfa/sangue
19.
Nanoscale ; 11(45): 21740-21747, 2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31720643

RESUMO

In this paper, we present a new method for reducing the subthreshold swing (SS) of ionic-modulated oxide field-effect transistors (FETs) below 60 mV per decade. The electrical performances of ion gel-gated In-Sn-O FETs with and without a nano-thick Al2O3 charge trapping layer are compared and studied. A significant SS reduction in the In-Sn-O FETs is observed when naturally oxidized Al2O3 and an ion gel are used as the gate stacking dielectric layer. The back sweep SS reaches as low as ∼27 mV per decade and extends over three orders of magnitude in drain current. A theoretical explanation for these results based on energy band diagrams is presented. The proposed devices described here have the potential to open up new avenues for further development of low power electronics, as well as for energy efficient memristive devices and synaptic electronics.

20.
J Neurosurg ; : 1-7, 2019 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-31323632

RESUMO

OBJECTIVE: Increased intracranial pressure (ICP) results in enlarged optic nerve sheath diameter (ONSD). In this study the authors aimed to assess the association of ONSD and ICP in severe traumatic brain injury (TBI) after decompressive craniotomy (DC). METHODS: ONSDs were measured by ocular ultrasonography in 40 healthy control adults. ICPs were monitored invasively with a microsensor at 6 hours and 24 hours after DC operation in 35 TBI patients. ONSDs were measured at the same time in these patients. Patients were assigned to 3 groups according to ICP levels, including normal (ICP ≤ 13 mm Hg), mildly elevated (ICP = 14-22 mm Hg), and severely elevated (ICP > 22 mm Hg) groups. ONSDs were compared between healthy control adults and TBI cases with DC. Then, the association of ONSD with ICP was analyzed using Pearson's correlation coefficient, linear regression analysis, and receiver operator characteristic curves. RESULTS: Seventy ICP measurements were obtained among 35 TBI patients after DC, including 25, 27, and 18 measurements in the normal, mildly elevated, and severely elevated ICP groups, respectively. Mean ONSDs were 4.09 ± 0.38 mm in the control group and 4.92 ± 0.37, 5.77 ± 0.41, and 6.52 ± 0.44 mm in the normal, mildly elevated, and severely elevated ICP groups, respectively (p < 0.001). A significant linear correlation was found between ONSD and ICP (r = 0.771, p < 0.0001). Enlarged ONSD was a robust predictor of elevated ICP. With an ONSD cutoff of 5.48 mm (ICP > 13 mm Hg), sensitivity and specificity were 91.1% and 88.0%, respectively; a cutoff of 5.83 mm (ICP > 22 mm Hg) yielded sensitivity and specificity of 94.4% and 81.0%, respectively. CONCLUSIONS: Ultrasonographic ONSD is strongly correlated with invasive ICP measurements and may serve as a sensitive and noninvasive method for detecting elevated ICP in TBI patients after DC.

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