Forkhead transcription factor FoxO3a has been reported to have ambiguous functions and distinct mechanisms in various solid tumors, including glioblastoma (GBM). Although a preliminary analysis of a small sample of patients indicated that FoxO3a aberrations in glioma might be related to aggressive clinical behavior, the clinical significance of FoxO3a in glioblastoma remains unclear. We investigated the expression of FoxO3a in a cohort of 91 glioblastoma specimens and analyzed the correlations of protein expression with patient prognosis. Furthermore, the functional impact of FoxO3a on GBM progression and the underlying mechanisms of FoxO3a regulation were explored in a series of in vitro and in vivo assays. FoxO3a expression was elevated in glioblastoma tissues, and high nuclear FoxO3a expression in human GBM tissues was associated with poor prognosis. Moreover, knockdown of FoxO3a significantly reduced the colony formation and invasion ability of GBM cells, whereas overexpression of FoxO3a promoted the colony formation and invasion ability. The results of in vivo GBM models further confirmed that FoxO3a knockdown inhibited GBM progression. More, the pro-oncogenic effects of FoxO3a in GBM were mediated by the activation of c-Myc, microtubule-associated protein 1 light chain 3 beta (LC3B) and Beclin1 in a mixed-lineage leukemia 2 (MLL2)-dependent manner. These findings suggest that high FoxO3a expression is associated with glioblastoma progression and that FoxO3a independently indicates poor prognosis in patients. FoxO3a might be a novel prognostic biomarker or a potential therapeutic target in glioblastoma.
BackgroundAcinetobacter baumannii is an important nosocomial pathogen which shows a high level of mortality risk. Several papers have reported biofilm formation as a well-known pathogenic mechanism in A. baumannii infections and exceptional antibiotic resistance. The study aims to explore the potential relationships between biofilm-related genes and antimicrobial resistance.Material/MethodsSamples from 122 patients with lower respiratory tract infections of A. baumannii were collected at Fujian Longyan First Hospital from January 2013 to September 2014. A. baumannii was isolated from sputum specimens. Biofilm-related genes including abaI, csuE, ompA, and bla-PER1 were analyzed by PCR. The minimum inhibitory concentration method was used to determine the sensitivity of each strain to antibiotics.ResultsThe clinical manifestations of A. baumannii-induced lower respiratory tract infections lacked specificity. Infected patients were most commonly admitted to intensive care units (54.9%) and frequently had chronic obstructive pulmonary disease (27.0%). The detection rates of abaI and csuE were both 59.8%, and those of ompA and bla-PER1 were 100% and 0%, respectively. After genetic testing, antimicrobial resistance to amikacin, ampicillin/sulbactam, and 14 other types of antimicrobials was higher in abaI- and csuE-positive strains than in abaI- and csuE-negative strains (P<0.05).ConclusionsThe findings of our study suggest that abaI- and csuE-positive Acinetobacter baumannii strains are associated with a higher incidence of antibiotic resistance in 14 types of antimicrobials.
Hematosepsis is a systemic inflammatory response syndrome (SIRS) with suspected or confirmed infection, which is the most common infectious disease in clinical neonatal intensive care unit. As the rapid development of neonatal hematosepsis caused by various basic diseases, the mortality rate is high, and there are some sequelae.We report the lasted study to date with 96 cases from Fujian Longyan First Hospital between 2013 and 2015. The aim of our study is to explore the value of soluble cluster of differentiation 14 subtype (sCD14-ST) in whole blood for differential diagnosis of neonatal hematosepsis at an early stage, and used in evaluation of the severity about sepsis combined with acute physiology and chronic health evaluation II (APACHE-II) score, procalcitonin (PCT), C reactive protein (CRP), and leukocyte (WBC).In our cohort, all cases met the diagnostic criteria for hematosepsis specific for newborns. We selected 42 neonates with hematosepsis, 54 neonates with nonhematosepsis, 44 noninfectious SIRS neonates, and 53 healthy neonatal controls. Which were determined the sCD14-ST, PCT, CRP, and WBC of all samples before treatment. Then assign the APACHE-II score for the all samples before and after treatment.The study shows, sCD14-ST levels were significantly higher in hematosepsis than nonhematosepsis group (t = −2.112, P = .041). Meanwhile, sCD14-ST levels were significantly higher in neonatal hematosepsis than in noninfectious SIRS group and controls (χ2 = 57.812, 68.944, P < .01). However, sCD14-ST in hematosepsis group was positively correlated with APACHE-II score (R-value = 0.415, P < .01). During treatment, the sCD14-ST level was decreased obviously along with APACHE-II score, PCT, CRP, and WBC (χ2 = 35.019, 78.399, 52.363, 25.912, 7.252, all P values <.01). The area under the curve (AUC) of sCD14-ST was 0.942. The differences in ROCAUC of sCD14-ST compared with PCT, CRP, and WBC were statistically significant (Z = −6.034, −4.474, −5.722, all P values <.01). The sensitivity and specificity of sCD14-ST were 95.2% and 84.9%, respectively.sCD14-ST could be a blood biomarker for early identification and disease valuation in newborns hematosepsis infection; and its diagnostic value is superior to other laboratory indexes.
This study aimed to investigate the etiology and risk factors of neonatal sepsis. A retrospective analysis was conducted on 192 patients with sepsis from August 2013 to March 2015. One hundred and six healthy neonates were used as the control group. Logistic regression was used to analyze the risk factors and ROC curve analysis performed in laboratory which indicated a significant correlation. The results of univariate analysis showed that postnatal age, body weight, and parity were significantly related to neonatal sepsis (P < 0.5). Logistic regression analysis demonstrated that postnatal age and parity are independent risk factors for neonatal sepsis (OR were 1.176 and 0.692, resp., P < 0.001). The maximum area underneath the curve (ROCAUC) of soluble CD14 (sCD14-ST), which was the most indicative biomarker of sepsis diagnostically, was 0.953 with sensitivity and specificity of 93.8% and 84.9%, respectively. Escherichia coli, Staphylococcus aureus, and Streptococcus agalactiae were the main bacterial strains causing neonatal sepsis, while postnatal age was an independent risk factor for the onset of disease. sCD14-ST could be a potential useful diagnostic marker for pediatric sepsis.
Objective: To investigate the associations between b 1 -adrenergic receptor (ADRB1) and cytochrome P450 2D6 (CYP2D6) gene polymorphisms and b-blocker treatment outcomes in patients with hypertension. Methods: Chinese patients with essential hypertension were treated with the b-blocker metoprolol and followed up for 12 weeks. xTAG Õ liquid-chip technology was used for CYP2D6 100 C > T and ADRB1 1165G > C genotyping. Associations between gene polymorphisms and antihypertensive therapy outcomes were assessed by generalized linear model fitting. A decrease of ! 10 mmHg in systolic blood pressure indicated an effective treatment outcome. Results: A total of 93 patients were included in the study. Mutant allele frequencies of 61.29% and 58.60% were obtained for ADRB1 and CYP2D6, respectively. There was no significant interaction between the effects of ADRB1 and CYP2D6 gene polymorphisms on treatment outcome. Patients homozygous for the mutant ADRB1 genotype (CC) had better treatment outcomes than those heterozygous for the mutation (GC). Interestingly, b-blocker treatment duration was an independent factor associated with treatment outcome. Conclusions: The ADRB1 1165G > C gene polymorphism and b-blocker treatment duration are independent factors associated with b-blocker treatment outcome. These findings suggest that the selection of antihypertensive therapy should take into consideration the patient's genotype.
The results demonstrate that Gly/Gly polymorphism in Arg389Gly ADRB1 was an independent risk factor together with high fasting plasma glucose, smoking and high triglyceride; moreover, the patients who carried the Gly389Gly genotype had a significantly improved metoprolol antihypertensive effect than those with ADRB1.
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