ABSTRACT
AbstractObjective: To identify the expression and methylation patterns of lncRNA CASC15 in bone marrow (BM) samples of acute myeloid leukemia (AML) patients, and further explore its clinical significance.@*METHODS@#Eighty-two de novo AML patients and 18 healthy donors were included in the study. Meanwhile, seven public datasets from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) were included to confirm the expression and methylation data of CASC15. Receiver operating characteristic (ROC) curve analysis was applied to determine the discriminative capacity of CASC15 expression to identify AML. The patients were divided into CASC15high group and CASC15low group by X-tile method, and the prognostic value of CASC15 was identified by Kaplan-Meier method and univariate and multivariate Cox regression analysis.@*RESULTS@#The expression level of CASC15 was significantly decreased in BM cells of AML patients compared with healthy donors (P<0.001). ROC curve analysis suggested that CASC15 expression might be a potential biomarker to discriminate AML from controls. The expression of CASC15 was high at the early stage of hematopoiesis, and reached a peak at the stage of multipotent progenitors differentiation, then decreased rapidly, and was at a range of low level fluctuations in the subsequent process. Among FAB subtypes, CASC15 expression in M0 was significantly higher than that in M1-M7. Clinically, CASC15low patients were more likely to have NPM1 mutations than CASC15high patients (P=0.048), while CASC15high patients had a significantly higher frequency of IDH1 and RUNX1 mutations (P=0.021 and 0.014, respectively). Moreover, CASC15low group had a shorter overall survival (OS) in patients with NPM1 mutations. Furthermore, multivariate analysis confirmed that CASC15 expression was a significant independent risk factor for OS in NPM1 mutated AML patients. In addition, CASC15 methylation level in BM samples of AML patients was significantly decreased compared with healthy donors. Patients with CASC15 high methylation had poor OS and disease-free survival.@*CONCLUSION@#The expression of CASC15 is decreased in AML, and low CASC15 expression may predict adverse prognosis in AML patients with NPM1 mutations. Moreover, CASC15 methylation level in AML is significantly decreased, and high CASC15 methylation may predict poor prognosis in AML.
Subject(s)
Humans , Leukemia, Myeloid, Acute/metabolism , Mutation , Nuclear Proteins/genetics , Nucleophosmin/genetics , Prognosis , RNA, Long Noncoding/geneticsABSTRACT
OBJECTIVE@#To describe and assess the repair technique and perioperative management for cerebrospinal fluid (CSF) leak resulting from extensive anterior skull base fracture via extradural anterior skull base approach.@*METHODS@#This was a retrospective review conducted at the Department of Neurosurgery of the Shanghai Tenth People's Hospital from January 2015 to April 2020. Patients with traumatic CSF rhinorrhea resulting from extensive anterior skull base fracture treated surgically via extended extradural anterior skull base approach were included in this study. The data of medical and radiological records, surgical approaches, repair techniques, peritoperative management, surgical outcome and postoperative follow-up were analyzed. Surgical repair techniques were tailored to the condition of associated injuries of the scalp, bony and dura injuries and associated intracranial lesions. Patients were followed up for the outcome of CSF leak and surgical complications. Data were presented as frequency and percent.@*RESULTS@#Thirty-five patients were included in this series. The patients' mean age was 33 years (range 11-71 years). Eight patients were treated surgically within 2 weeks; while the other 27 patients, with prolonged or recurrent CSF rhinorrhea, received the repair surgery at 17 days to 10 years after the initial trauma. The mean overall length of follow-up was 23 months (range 3-65 months). All the patients suffered from frontobasal multiple fractures. The basic repair tenet was to achieve watertight seal of the dura. The frontal pericranial flap alone was used in 20 patients, combined with temporalis muscle and/or its facia in 10 patients. Free fascia lata graft was used instead in the rest 5 patients. No CSF leak was found in all the patients at discharge. There was no surgical mortality in this series. Bilateral anosmia was the most common complication. At follow-up, no recurrent CSF leak or meningitis occurred. No patients developed mucoceles, epidural abscess or osteomyelitis. One patient ultimately required ventriculoperitoneal shunt because of progressive hydrocephalus.@*CONCLUSION@#Traumatic CSF rhinorrhea associated with extensive anterior skull base fractures often requires aggressive treatment via extended intracranial extradural approach. Vascularized tissue flaps are ideal grafts for cranial base reconstruction, either alone or in combination with temporalis muscle and its fascia---fascia lata sometimes can be opted as free autologous graft. The approach is usually reserved for patients with traumatic CSF rhinorrhea in complex frontobasal injuries.
ABSTRACT
OBJECTIVE@#LncRNA ITGB2-AS1 has been found to play important roles in the occurrence and development of human solid tumors. However, its role in hematological diseases, especially acute myeloid leukemia (AML), remains unclear. The aim of this study was to identify the expression pattern of ITGB2-AS1 in AML patients and to further explore its clinical significance.@*METHODS@#ITGB2-AS1 expression was analyzed in public datasets (including TCGA and GSE63270) and further validated in a cohort of 109 AML patients by real-time quantitative PCR (RT-qPCR).@*RESULTS@#The level of ITGB2-AS1 was up-regulated among two independent cohorts (TCGA, P<0.05; GSE63270, P<0.05), which was confirmed by the data from 109 AML patients enrolled in this study (P<0.05). Clinically, high ITGB2-AS1 expression was associated with older age (P=0.023) and lower complete remission (CR) rate (P=0.005). Multivariate analysis identified that high ITGB2-AS1 expression was an independent prognostic factor not only for CR rate (P=0.027) but also for overall survival (OS) time (P=0.011), and ITGB2-AS1 was positively correlated with ITGB2 expression in both TCGA (r=0.74, P<0.001) and clinical data detected in this study (r=0.881, P<0.001). High ITGB2 expression was also associated with older age (P=0.02) and lower CR rate (P=0.020). Moreover, high ITGB2 expression predicted worse OS (P=0.028).@*CONCLUSION@#ITGB2-AS1 is overexpressed in AML and predicts poor prognosis in AML patients.
Subject(s)
Aged , Humans , Leukemia, Myeloid, Acute/genetics , Prognosis , RNA, Long Noncoding/geneticsABSTRACT
The optimum medium for Lactobacillus M7 was systematically studied with SAS system. Firstly, the prime factors affecting lactic acid yield were selected by means of Plackett-Burman design; secondly, the pnme facias were optimized by response rurface analysis. Under the optimum level determined, the yield is increased by 15%.