Trends in the clinical features of amyotrophic lateral sclerosis: A 14-year Chinese cohort study.

BACKGROUND AND PURPOSE: The aim was to determine the transitional patterns in the clinical characteristics, treatments and comorbidities in amyotrophic lateral sclerosis (ALS) patients over the past 14 years using data from a large clinical cohort in mainland China. METHODS: Sporadic ALS patients who visited the Peking University Third Hospital from January 2005 to December 2018 were included in this study. The 14 years were divided into three periods, and changes in the baseline characteristics of the participants were analyzed at 5-year intervals. RESULTS: In total, 3410 patients with sporadic ALS were recruited: 2181 were men and 1229 were women. The proportion of patients with bulbar-onset ALS increased from 13.0% in 2005-2009 to 19.5% in 2015-2018 (p < 0.001). The mean (standard deviation) age at onset increased from 49.5 (11.4) years in 2005-2009 to 53.0 (11.0) years in 2015-2018 (p < 0.001). ALS patients with diabetes or hypertension showed a delay in ALS onset, and the delay was even more apparent when the patients had both comorbidities. The proportion of riluzole users in 2015-2018 was approximately 2.5-fold of that in 2005-2009 (p < 0.001). CONCLUSIONS: In the context of a lack of clinical data on ALS in mainland China, this study evaluated a large cohort of patients diagnosed over a 14-year period. The age at onset and percentage of patients who used riluzole both increased over the study period. Additionally, it was found that patients with comorbidities such as diabetes and hypertension had a delayed age of ALS onset.

BAALC and ERG expression levels at diagnosis have no prognosis impact on acute myeloid leukemia patients undergoing allogeneic hematopoietic stem cell transplantation.

Brain and acute leukemia, cytoplasmic (BAALC) and ETS-related gene (ERG) expression levels are independent prognostic factors for acute myeloid leukemia (AML); however, their prognostic impacts on AML patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) require further investigation. We studied 71 de novo AML patients treated with allo-HSCT and defined low and high expressers according to the median expression levels of BAALC and ERG at diagnosis respectively. High BAALC expression was associated with wild-type NPM1 (P = 0.000) and RUNX1 mutations (P = 0.027). High ERG expression was associated with FLT3-ITD absence (P = 0.003) and wild-type NPM1 (P = 0.001). BAALC and ERG expression levels were significantly correlated with each other (P = 0.001). Survival analyses including Kaplan-Meier curves and univariate and multivariate analysis consistently reported that there were no significant differences for both event-free survival (EFS) and overall survival (OS) (all P > 0.1), between high versus low BAALC and ERG expressers. Our study suggested that despite of their well-known adverse role in prognosis of AML, neither BAALC nor ERG expression levels at diagnosis had effect on survival of AML patients who underwent allo-HSCT.

Cu(II)/Proline-Catalyzed Reductive Coupling of Sulfuryl Chloride and P(O)-H for P-S-C Bond Formation.

A considerably improved method for the Cu-catalyzed coupling of sulfuryl chloride with P(O)-H was described. Using commercially available l-proline as the ligand decreased the precatalyst loading, broadened the substrate scope and greatly promoted the efficiency of the coupling reaction. Moreover, gram-scale preparation, easy-to handle and recyclable catalyst featured this transformation.

Resourceful Treatment of Battery Recycling Wastewater Containing H2SO4 and NiSO4 by Diffusion Dialysis and Electrodialysis.

Facing the increasing demand for batteries worldwide, recycling waste lithium batteries has become one of the important ways to address the problem. However, this process generates a large amount of wastewater which contains high concentration of heavy metals and acids. Deploying lithium battery recycling would cause severe environmental hazards, would pose risks to human health, and would also be a waste of resources. In this paper, a combined process of diffusion dialysis (DD) and electrodialysis (ED) is proposed to separate, recover, and utilize Ni2+ and H2SO4 in the wastewater. In the DD process, the acid recovery rate and Ni2+ rejection rate could reach 75.96% and 97.31%, respectively, with a flow rate of 300 L/h and a W/A flow rate ratio of 1:1. In the ED process, the recovered acid from DD is concentrated from 43.1 g/L to 150.2 g/L H2SO4 by the two-stage ED, which could be used in the front-end procedure of battery recycling process. In conclusion, a promising method for the treatment of battery wastewater which achieved the recycling and utilization of Ni2+ and H2SO4 was proposed and proved to have industrial application prospects.

A correlation and prediction study of the poor prognosis of high-grade aneurysmal subarachnoid hemorrhage from the neutrophil percentage to albumin ratio.

OBJECTIVE: Inflammatory response and nutritional status play crucial roles in patients with aneurysmal subarachnoid hemorrhage (aSAH). This study mainly investigated the correlation between neutrophil percentage to albumin ratio (NPAR) and clinical prognosis in aSAH patients with high-grade Hunt-Hess and its predictive model. METHODS: A retrospective analysis was conducted based on 806 patients with aneurysmal subarachnoid hemorrhage who were admitted to the studied hospital from January 2017 to December 2021. Modified Fisher grade and Hunt-Hess grade were obtained according to their status at admission and hematological parameters within 48 h after hemorrhage. Univariate and multivariate logistic regression analysis were conducted to evaluate the relationship between NPAR and the clinical prognosis of patients with aSAH. And propensity matching analysis of patients with aSAH in the severe group. Receiver operating characteristic (ROC) curve analysis was used to determine the optimal cut-off value of NPAR at admission to predict prognosis and its sensitivity and specificity. The nomogram diagram and Calibration curve were further used to examine the prediction model. RESULTS: According to the mRS score at discharge, 184 (22.83 %) cases were classified as having poor outcomes (mRS > 2). Through multivariate logistic regression analysis, it was found that the Modified Fisher grade at admission, Hunt-Hess grade, eosinophils, neutrophil to lymphocyte ratio (NLR), and NPAR were independent risk factors for poor outcome in patients with aSAH (p < 0.05). The NPAR of aSAH patients with poor outcomes in the high-grade group was significantly higher than that in the low-grade group. The optimal cut-off value for NPAR was 21.90, the area under the ROC curve was 0.780 (95 % CI 0.700 - 0.861, p < 0.001). The Calibration curves show that the predicted probability of the drawn nomogram is overall consistent with the actual probability. (Mean absolute error = 0.031) CONCLUSION: The NPAR value of patients with aSAH at admission is significantly correlated with Hunt-Hess grade in a positive manner, namely, the higher the Hunt-Hess grade, the higher the NPAR value, and the worse the prognosis. Findings indicate that early NPAR value can be used as a feasible biomarker to predict the clinical prognosis of patients with aSAH.

Environmentally specific servant leadership and voluntary pro-environmental behavior in the context of green operations: A serial mediation path.

Green operations of organizations and enhancement of corporate social responsibility hinges upon leaders. This study investigated the influential role performed by environmentally specific servant leadership in provoking voluntary pro-environmental behavior of employees. The findings illuminate a serial chain mediation model that originates as a result of environmentally specific servant leadership and leads toward psychological empowerment, and organizational identity, ultimately leading toward voluntary pro-environmental behavior. Data from the textile sector of Pakistan uncovered that environmentally specific servant leadership prompted the voluntary pro-environmental behavior of employees. Moreover, environmentally specific servant leadership was significantly linked with voluntary pro-environmental behavior through psychological empowerment. The study supports the serial mediation of psychological empowerment and organizational identity in stirring voluntary pro-environmental behavior. An organizational psychological mechanism has been unraveled that can help organizations achieve a high level of sustainability and can serve as a catalyst for organizational green operations.

The Clinical Features of In-Hospital Recurrence in Acute Ischaemic Stroke Patients over Time: A Real-World Observation at a Single Center.

Acute ischaemic stroke (AIS) has a high risk of recurrence, particularly in the early stage. Our study aimed to assess the clinical characteristics and risk factors of in-hospital ischaemic recurrence in AIS patients in different periods. This study was a retrospective, single-center analysis. The patients were divided into two stages based on their admission time. The primary endpoint was recurrent stroke during hospitalization. In total, 978 patients in Stage 1 and 1047 patients in Stage 2 were included in this study. The in-hospital recurrence rate in Stage 1 was 5.9%, while that in Stage 2 was 4.0% (p = 0.046). A recurrence rate reduction mainly occurred in the minor stroke and large-artery atherosclerosis (LAA) stroke patients. Infection was an independent risk factor despite amelioration by antiplatelet therapy (p < 0.001). Diabetes patients also had a higher risk of in-hospital ischaemic recurrence among the minor stroke and large-artery atherosclerosis patients. A positive attitude towards antiplatelet therapy failed to completely halt recurrence of the disease. In conclusion, the rate of in-hospital ischaemic recurrence in AIS patients showed a decreasing trend over time, especially in the minor stroke and large-artery atherosclerosis stroke patients. Infection and diabetes were associated with a higher risk of stroke recurrence.

CT-Visible Convexity Subarachnoid Hemorrhage Predicts Early Recurrence of Lobar Hemorrhage.

Background and Purpose: Convexity subarachnoid hemorrhage (cSAH) may predict an increased recurrence risk in cerebral amyloid angiopathy (CAA)-related intracerebral hemorrhage (ICH) survivors. We aimed to investigate whether cSAH detected on CT was related to early recurrence in patients with ICH related to CAA. Methods: We analyzed data from consecutive lobar ICH patients diagnosed as probable or possible CAA according to the Boston criteria using the method of cohort study. Demographic and clinical data, ICH recurrence at discharge and within 90 days were collected. The association between cSAH detected on CT and early recurrent ICH was analyzed using multivariable logistic regression. Results: A total of 197 cases (74 [66-80] years) were included. cSAH was observed on the baseline CT of 91 patients (46.2%). A total of 5.1% (10/197) and 9.5% (17/179) of patients experienced ICH recurrence within 2 weeks and 90 days, respectively. The presence of cSAH was related to recurrence within 2 weeks (OR = 5.705, 95%CI 1.070-30.412, P = 0.041) after adjusting for hypertension, previous symptomatic ICH and anticoagulant use. The presence of cSAH was related to recurrence within 90 days (OR 5.473, 95%CI 1.425-21.028, P = 0.013) after adjusting for hypertension, previous symptomatic ICH and intraventricular hemorrhage. The similar results were obtained in other models using different methods to select adjusting variables. Conclusion: In patients with lobar ICH related to CAA, 5.1% and 9.5% of them experienced ICH recurrence within 2 weeks and 90 days, respectively. CT-visible cSAH was detected in 46.2% of patients and indicates an increased risk for early recurrent ICH.

Clinical Value and Prognosis of C Reactive Protein to Lymphocyte Ratio in Severe Aneurysmal Subarachnoid Hemorrhage.

Objective: To investigate the relationship between CLR and disease severity and clinical prognosis of aSAH. Methods: The authors retrospectively analyzed the clinical data of 221 patients with aSAH, who were admitted to the intensive care unit from January 2017 to December 2020. The indicators of inflammatory factors in the first blood routine examination within 48 h of bleeding were obtained. The prognosis was evaluated by mRS score at discharge, mRS>2 was a poor outcome. Through the receiver operating characteristic (ROC) curve, the area under the curve was calculated and the predicted values of inflammatory factors (CLR, CRP, WBC, and neutrophils) were compared. Univariate and multivariable logistic regression analyses were used to evaluate the relationship between CLR and the clinical prognosis of patients. ROC curve analysis was performed to determine the optimal cut-off threshold, sensitivity, and specificity of CLR in predicting prognosis at admission. Results: According to the mRS score at discharge, 139 (62.90%) patients were classified with poor outcomes (mRS>2). The inflammatory factor with the best predictive value was CLR, which had an optimal cut-off threshold of 10.81 and an area under the ROC curve of 0.840 (95%CI.788-0.892, P < 0.001). Multivariable Logistic regression analysis showed that the Modified Fisher grade, Hunt-Hess grade, and CLR at admission were independent risk factors for poor outcomes of patients with aSAH (P < 0.05). According to Hunt-Hess grade, patients were divided into a mild group (Hunt-Hess ≤ 3) and a severe group (Hunt-Hess > 3), and the CLR value was significantly higher in severe patients with aSAH than in mild patients. The optimal cut-off threshold of CLR in the severe group was 6.87, and the area under the ROC curve was 0.838 (95% CI.752-0.925, P < 0.001). Conclusions: The CLR value at the admission of patients with aSAH was significantly associated with Hunt-Hess grade, The higher Hunt-Hess grade, the higher the CL R-value, and the worse the prognosis. Early CLR value can be considered as a feasible biomarker to predict the clinical prognosis of patients with aSAH.

Corrigendum: Clinical value and prognosis of C reactive protein to lymphocyte ratio in severe aneurysmal subarachnoid hemorrhage.

[This corrects the article DOI: 10.3389/fneur.2022.868764.].

Risk factors and predictive models of poor prognosis and delayed cerebral ischemia in aneurysmal subarachnoid hemorrhage complicated with hydrocephalus.

Objective: To evaluate the correlation of serum biological markers and related scales to the occurrence of delayed cerebral ischemia and clinical prognosis in patients with aneurysmal subarachnoid hemorrhage (aSAH) complicated with acute hydrocephalus before admission. Methods: The clinical data of 227 patients with pre-admission aSAH complicated with acute hydrocephalus admitted to Henan Provincial People's Hospital from April 2017 to December 2020 were retrospectively analyzed. Patients were grouped according to the presence or absence of delayed cerebral ischemia (DCI) after surgery and the prognosis at 6 months after discharge. Univariate and multivariable logistic regression analysis were performed to analyze the relationship between serum biological indicators combined with aneurysm related clinical score scale and the occurrence and prognosis of delayed cerebral ischemia. ROC curves and nomogram were drawn. Results: Multivariable Logistic regression analysis showed that high Hunt-Hess grade and surgical clipping were independent risk factors for postoperative DCI (P < 0.05). Older age, higher Hunt-Hess grade, higher CRP and neutrophil levels were independent risk factors for poor prognosis at 6 months after surgery (P < 0.05). ROC curve analysis showed that the area under the curve (AUC) of Hunt-Hess grade and surgical method for predicting DCI in patients with aSAH combined with hydrocephalus after surgery were 0.665 and 0.593. The combined AUC of Hunt-Hess grade and surgical method was 0.685, the sensitivity was 64.9%, and the specificity was 64.7%. The AUC of CRP, neutrophil, age and Hunt-Hess grade for predicting poor prognosis in patients with aSAH combined with hydrocephalus at 6 months after surgery were 0.804, 0.735, 0.596, 0.757, respectively. The combined AUC of CRP, neutrophil, age, Hunt-Hess grade was 0.879, the sensitivity was 79%, and the specificity was 84.5%. According to the correction curve, the predicted probability of the nomogram is basically consistent with the actual probability. Conclusion: Hunt-Hess grade and surgical method are independent predictors of postoperative DCI in patients with aSAH complicated with hydrocephalus. "CRP," "neutrophil," "age" and "Hunt-Hess grade" at admission are independent predictors of clinical prognosis in patients with aSAH complicated with hydrocephalus. The combination of the above indicators has high predictive value.

Hypermetabolism associated with worse prognosis of amyotrophic lateral sclerosis.

BACKGROUND AND OBJECTIVE: Exploration of hypermetabolism in amyotrophic lateral sclerosis (ALS) with different ethnicities is needed to understand its metabolic implications for clinical management. We aimed to evaluate the features of hypermetabolism and investigate its association with clinical characteristics and prognosis of ALS in a prospective Chinese cohort. METHODS: This prospective study was conducted at Peking University Third Hospital, China from 2017 to 2020. 343 participants were enrolled initially. After strict screening, 147 matched health controls and 93 patients with ALS were eligible and underwent detailed clinical assessments. Disease severity and progression were evaluated using recognized scales. Metabolic assessments included body composition and metabolic index (MI) [hypermetabolism if MI ≥ 120.0%]. Patients were followed up every 6 months for survival analysis. RESULTS: Compared with controls, hypermetabolism was significantly more prevalent in ALS (p = 0.009). MI was consistently higher in ALS than controls (p = 0.009). Further correlation analysis showed that MI significantly decreased with disease progression, as graded by King's College staging system (p < 0.001). MI was significantly correlated with fat-free mass and fat mass (p = 0.005 and 0.007). Survival analysis showed that hypermetabolism independently indicated a worse prognosis for ALS (HR = 1.020, CI = 1.004-1.036, p = 0.013). CONCLUSION: A significant increase in the prevalence and degree of hypermetabolism was identified in ALS compared with strictly matched controls. Metabolic index, which is significantly associated with disease progression and body composition, is an independent prognostic indicator for a worse survival of ALS.

Exercise Physiology Impairments of Patients With Amyotrophic Lateral Sclerosis: Cardiopulmonary Exercise Testing Findings.

Background and Objective: In amyotrophic lateral sclerosis (ALS), progressive weakness significantly limits the ability to exercise. However, measurements of the impaired exercise function and their practical value to assess disease progression in ALS are scarce. Cardiopulmonary exercise testing (CPET) is a non-invasive accurate method used to comprehensively quantify exercise physiology in a variety of diseases. This study aimed to evaluate the clinical value of CPET and to explore its association with disease severity and prognosis prediction in ALS. Methods: A total of 319 participants were enrolled in this 3-year prospective study. After strict quality control, 109 patients with ALS and 150 age- and sex-matched healthy controls were included with comprehensive clinical assessment and follow-ups. The incremental ramp protocol for symptom-limited CPET was applied in both groups. The exercise physiology during peak effort exercise was systematically measured, including the overall aerobic capacity of exercise (VO2 peak) and the respective capacity of the exercise-involved organs [cardiac response (heart rate peak-HR peak), ventilatory efficiency (VE/VCO2 slope), breathing economy (VE/VO2 peak), and other relevant parameters]. Disease severity and progression were evaluated using recognized scales. Survival was monitored with regular follow-ups every 6 months. Results: Decreased exercise capacity (VO2 peak < 16 ml/kg/min) occurred more frequently in patients with ALS than in controls (44.95% vs. 9.33%, p < 0.01). In patients with ALS, the average VO2 peak (16.16 ± 5.43 ml/kg/min) and HR peak [135 (112-153) bpm] were significantly lower (p < 0.01) than in controls [22.26 ± 7.09 ml/kg/min; 148 (135-164) bpm], but the VE/VCO2 slope was significantly higher [28.05 (25.03-32.16) vs. 26.72 (24.37-29.58); p = 0.03]. In patients with ALS, the VO2 peak and HR peak were significantly correlated with disease severity and progression scores (p < 0.05). Survival analyses revealed the VO2 peak and HR peak as protective indicators while the VE/VO2 peak as a detrimental indicator for the prognostic prediction in ALS (HR = 0.839, p = 0.001; HR = 0.967, p < 0.001; HR = 1.137, p = 0.028, respectively). Conclusion: Our prospective study quantified the significantly decreased exercise capacity in ALS through non-invasive CPET. The impaired VO2 peak and HR peak closely correlated with disease severity and independently predicted a worse prognosis. Our findings identified the clinical value of CPET as an objective indicator of disease progression in ALS.

Warburg effect-promoted exosomal circ_0072083 releasing up-regulates NANGO expression through multiple pathways and enhances temozolomide resistance in glioma.

BACKGROUND: Temozolomide (TMZ) resistance limits its application in glioma. Exosome can carry circular RNAs (circRNAs) to regulate drug resistance via sponging microRNAs (miRNAs). miRNAs can control mRNA expression by regulate the interaction with 3'UTR and methylation. Nanog homeobox (NANOG) is an important biomarker for TMZ resistance. Hitherto, it is unknown about the role of exosomal hsa_circ_0072083 (circ_0072083) in TMZ resistance in glioma, and whether it is associated with NANOG via regulating miRNA sponge and methylation. METHODS: TMZ-resistant (n = 36) and sensitive (n = 33) patients were recruited. The sensitive cells and constructed resistant cells were cultured and exposed to TMZ. circ_0072083, miR-1252-5p, AlkB homolog H5 (ALKBH5) and NANOG levels were examined via quantitative reverse transcription polymerase chain reaction and western blot. The half maximal inhibitory concentration (IC50) of TMZ, cell proliferation, apoptosis, migration and invasion were analyzed via Cell Counting Kit-8, colony formation, flow cytometry, wound healing and transwell assays. The in vivo function was assessed using xenograft model. The N6-methyladenosine (m6A) level was analyzed via methylated RNA immunoprecipitation (MeRIP). Target relationship was investigated via dual-luciferase reporter assay and RNA immunoprecipitation. Warburg effect was investigated via lactate production, glucose uptake and key enzymes expression. Exosome was isolated and confirmed via transmission electron microscopy and specific protein expression. RESULTS: circ_0072083 expression was increased in TMZ-resistant glioma tissues and cells. circ_0072083 knockdown restrained the resistance of resistant cells via decreasing IC50 of TMZ, proliferation, migration, invasion and xenograft tumor growth and increasing apoptosis. circ_0072083 silence reduced NANOG expression via blocking ALKBH5-mediated demethylation. circ_0072083 could regulate NANOG and ALKBH5 via targeting miR-1252-5p to control TMZ resistance. Warburg effect promoted the release of exosomal circ_0072083 in resistant cells. Exosomal circ_0072083 from resistant cells increased the resistance of sensitive cells to TMZ in vitro and xenograft model. Exosomal circ_0072083 level was enhanced in resistant patients, and it had a diagnostic value and indicated a lower overall survival in glioma. CONCLUSION: Exosomal circ_0072083 promoted TMZ resistance via increasing NANOG via regulating miR-1252-5p-mediated degradation and demethylation in glioma.

A Novel Scoring System Based on Preoperative Routine Blood Test in Predicting Prognosis of Atypical Meningioma.

PURPOSE: The aim of this study was to explore the correlation and clinical significance of preoperative fibrinogen and neutrophil-lymphocyte ratio (F-NLR) scoring system with 3-year progression-free survival (PFS) of patients with atypical meningioma. MATERIALS AND METHODS: Clinical, pathological, radiological, and laboratory variables were collected to analyze their correlation with 3-year PFS in the training set with 163 patients. Patients were classified by different F-NLR scores (0, 1, or 2). External validation for the predictive value of F-NLR scoring system was performed in the validation set with 105 patients. RESULTS: Overall, 37.3% (100 of 268) of the enrolled patients were male. The scoring system showed good performance in predicting 3-year PFS (AUC = 0.872, 95%CI = 0.811-0.919, sensitivity = 66.1%, specificity = 93.3%, and Youden index = 0.594). DeLong's test indicated that the AUC of F-NLR scoring system was significantly greater than that of fibrinogen level and NLR (Z = 2.929, P = 0.003; Z = 3.376, P < 0.001). Multivariate Cox analysis revealed that tumor size (HR = 1.39, 95%CI = 1.10-1.76, P = 0.007), tumor location (HR = 3.11, 95%CI = 1.60-6.95, P = 0.001), and F-NLR score (score of 1: HR = 12.78, 95%CI = 3.78-43.08, P < 0.001; score of 2: HR = 44.58, 95%CI = 13.02-152.65, P < 0.001) remained significantly associated with 3-year PFS. The good predictive performance of F-NLR scoring system was also demonstrated in the validation set (AUC = 0.824, 95%CI = 0.738-0.891, sensitivity = 62.5%, specificity = 87.9%, and Youden index = 0.504). CONCLUSION: Our study confirmed the correlation and clinical significance of preoperative F-NLR scoring system with 3-year PFS of patients with atypical meningioma. A prospective and large-scale study is required to validate our findings.

Exosome-mediated transfer of circRNA CircNFIX enhances temozolomide resistance in glioma.

Development of chemotherapy resistance remains a major obstacle for glioma management. Exosome-mediated transfer of circular RNAs (circRNAs) are being found to have relevance to many human cancers, including glioma. The purpose of this study is to explore the effect and underlying mechanism of exosomal circRNA nuclear factor I X (CircNFIX) on temozolomide (TMZ) chemoresistance in glioma. Our results indicated that exosomal CircNFIX was up-regulated in the serum of TMZ-resistant patients and predicted poor prognosis. Exosomal CircNFIX from TMZ-resistant cells conferred TMZ resistance to recipient sensitive cells through the enhancement of cell migration and invasion and the repression of cell apoptosis under TMZ exposure. CircNFIX directly interacted with miR-132 by binding to miR-132. CircNFIX knockdown enhanced TMZ sensitivity in resistant glioma cells by up-regulating miR-132. Additionally, exosomal CircNFIX promoted tumor growth and its depletion enhanced TMZ sensitivity in glioma cells in vivo. Taken together, our study suggests that exosome-mediated transfer of CircNFIX enhances TMZ resistance in glioma at least partially through sponging miR-132, highlighting a potentially prognostic biomarker and therapeutic target for improving the clinical benefits of TMZ treatment in patients with glioma.

Long Non-Coding RNA MEG3 Modifies Cell-Cycle, Migration, Invasion, and Proliferation Through AKAP12 by Sponging miR-29c in Meningioma Cells.

Meningioma (MEN) is a common central nervous system disease. Accumulating evidence indicated that long non-coding RNA maternally expressed gene 3 (MEG3) participated in the progression of MEN. However, the potential mechanisms of MEG3 in altering the aggressive phenotypes of MEN need further exploration. Levels of MEG3, microRNA (miR)-29c, and A-kinase anchor protein 12 (AKAP12) were determined using quantitative real-time Polymerase Chain Reaction (qRT-PCR) assay. Dual-luciferase reporter and RNA immunoprecipitation (RIP) assays were performed to verify the relationship between miR-29c and MEG3 or AKAP12. The protein level of AKAP12 was detected by western blot. Moreover, cell-cycle arrest, migration, invasion, and proliferation were assessed by flow cytometry, wound healing, transwell assays, and CCK-8 assay, respectively. Levels of MEG3 and AKAP12 were downregulated, while miR-29c was effectively increased in MEN tissues and cell line. Mechanically, MEG3 was a sponge of miR-29c to regulate the expression of AKAP12. Functionally, increase of MEG3 diminished cell-cycle, migration, invasion, and proliferation in MEN cells, and reintroduction of miR-29c could eliminate these effects. In addition, AKAP12 depletion overturned the inhibitory effects of miR-29c absence on cell-cycle, migration, invasion, and proliferation in vitro. Also, AKAP12 was co-regulated by MEG3/miR-29c axis. MEG3 mediated the aggressive behaviors of MEN cells via miR-29c/AKAP12 axis, supporting that MEG3 served as a promising biomarker for the diagnosis and treatment of human MEN.

ssExpression level of GAS6-mRNA influences the prognosis of acute myeloid leukemia patients with allogeneic hematopoietic stem cell transplantation.

As high expression level of growth arrest-specific 6 (GAS6) had an adverse effect on prognosis in acute myeloid leukemia (AML) patients, it is interesting to reveal the relationship between GAS6-mRNA level and the survival condition of AML patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT). We screened The Cancer Genome Atlas database and found 71 AML patients with GAS6-mRNA expression and received allo-HSCT treatments. We divided them into two groups based on the median expression of GAS6-mRNA. Patients with GAS6-mRNAhigh (n=36) seemed to have lower bone marrow (BM) blast (P=0.022), lower percentage of type M5 (P=0.034), lower percentage of inv(16)/CBFß-MYH11 karyotype (P=0.020), and lower rate of good risk classification (P=0.005) than the group GAS6-mRNAlow (n= 35). Higher expression level of GAS6-mRNA also brought higher RUNX1 mutations (P=0.003), MLL-PTD mutations (P=0.042), TP53 mutations (P=0.042), and lower NRAS/KRAS mutations (P=0.042). Univariate analyses showed that GAS6-mRNA was unfavorable for overall survival (OS) (P=0.044), as RUNX1 and WT1 also gave negative influences. Multivariate analyses confirmed that GAS6-mRNA cut down the event-free servival (EFS) and OS of AML patients with HSCT (P=0.029, P=0.025). Our study indicated that higher expression of GAS6-mRNA related with adverse effects in AML patients with HSCT treatment.

High expression of dedicator of cytokinesis 1 adversely influences the prognosis of acute myeloid leukemia patients undergoing allogeneic hematopoietic stem cell transplantation.

Background: Overexpression of dedicator of cytokinesis 1 (DOCK1) has been confirmed as an unfavorable prognostic marker in acute myeloid leukemia (AML). Purpose: This study is to explore the clinical implications of DOCK1 on AML patients underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT). Patients and methods: We analyzed 71 de novo AML patients treated with allo-HSCT and divided them into two groups (DOCK1 high vs DOCK1 low) by the median expression level of DOCK1. Results: High DOCK1 expression was associated with older age (P=0.019), wild-type CEBPA (P=0.002), IDH1/2 mutations (P=0.010) and RUNX1 mutation (P=0.005). Univariate analyses showed that DOCK1 high and RUNX1 mutation were associated with shorter OS (P<0.001, P=0.024). Multivariate analysis confirmed the negative effect of high DOCK1 level on overall survival (P=0.010). Conclusion: Our results demonstrate that in AML patients who received allo-HSCT, high DOCK1 expression might have a persistent negative prognostic impact post-transplant.