The prognostic and predictive value of plasma D-dimer in children with neuroblastoma: a 7-year retrospective analysis at a single institution.

Purpose: Elevated plasma D-dimer level is a poor prognostic factor for many solid tumors. However, limited research has been conducted on D-dimer in children with neuroblastoma (NB), and its clinical significance remains unclear. The present study investigated the clinical and prognostic significance of D-dimer in pediatric NB patients. Methods: A retrospective analysis of all newly admitted NB patients was conducted from January 2014 to December 2020. Baseline clinicopathological features, preoperative laboratory parameters, and follow-up information were collected. Univariate and multivariate analyses were performed to determine the relationship between D-dimer level, clinical features, and the prognostic value. Results: Among 266 patients, the median value of D-dimer was 2.98 ng/mL, of which 132 patients showed elevated D-dimer levels before surgery (>2.98 ng/mL). Univariate analysis revealed that elevated D-dimer was significantly associated with age, hemoglobin, neutrophil-to-lymphocyte ratio, neuron-specific enolase, 24-hour vanillylmandelic acid, overall survival, and so on (P < 0.05). Patients with elevated D-dimer levels had shorter median overall survival time when compared with normal D-dimer levels (P = 0.01). The prognosis was better in patients with normal D-dimer levels when combined with lower age, ganglioneuroblastoma tumor type, lower stage on International Neuroblastoma Staging System, low-risk group, and without bone metastasis or bone marrow metastasis. The continuous increase of D-dimer level after treatment indicated tumor recurrence or progression. Conclusion: A high D-dimer level is associated with low overall survival, and an elevated D-dimer level after treatment indicates tumor recurrence and progression. D-dimer can be used as one of the evaluation factors for NB treatment or prognosis.

[Feasibility of Preheating at 41 ℃ to Correct Red Blood Cell Parameters in the Presence of High-titer Cold Agglutinins].

Objective To explore the feasibility of preheating in 41 ℃ water bath for 30 minutes to correct the red blood cell parameters in the specimens containing high-titer cold agglutinins(CAs). Methods Two specimens containing high-titer CAs were selected during work,and the parameters of complete blood count at room temperature or after preheating in 37 ℃ or 41 ℃ water bath were compared.The smears were stained,and the distribution of red blood cells was observed with a microscope.Further,74 specimens without CAs were collected for complete blood count,and then the test results at room temperature and after preheating at 41 ℃ were compared. Results At room temperature,the specimens containing high-titer CAs showed significantly reduced red blood cell count(RBC)and hematocrit(HCT),abnormally increased mean corpuscular hemoglobin(MCH)and mean cell hemoglobin concentration(MCHC),abnormal percents of hemoglobin(HGB)and RBC,and aggregation of a large number of red blood cells.After being preheated at 37 ℃ for a certain time,the specimens demonstrated obviously improved parameters while still aggregation of a small number of red blood cells.After being preheated at 41 ℃ for 30 minutes,the specimens showed significantly increased RBC,normal HCT,MCH,and MCHC,and evenly distributed red blood cells.The 74 specimens without CAs showed the comparability was ≥80% between room temperature and preheating at 41 ℃ for 30 minutes or 60 minutes. Conclusion We can preheat the specimens containing high-titer CAs in a water bath at 41 ℃ to obtain accurate red blood cell parameters.

Semi-Supervised Segmentation Framework Based on Spot-Divergence Supervoxelization of Multi-Sensor Fusion Data for Autonomous Forest Machine Applications.

In this paper, a novel semi-supervised segmentation framework based on a spot-divergence supervoxelization of multi-sensor fusion data is proposed for autonomous forest machine (AFMs) applications in complex environments. Given the multi-sensor measuring system, our framework addresses three successive steps: firstly, the relationship of multi-sensor coordinates is jointly calibrated to form higher-dimensional fusion data. Then, spot-divergence supervoxels representing the size-change property are given to produce feature vectors covering comprehensive information of multi-sensors at a time. Finally, the Gaussian density peak clustering is proposed to segment supervoxels into sematic objects in the semi-supervised way, which non-requires parameters preset in manual. It is demonstrated that the proposed framework achieves a balancing act both for supervoxel generation and sematic segmentation. Comparative experiments show that the well performance of segmenting various objects in terms of segmentation accuracy (F-score up to 95.6%) and operation time, which would improve intelligent capability of AFMs.

ZGDHu-1 promotes apoptosis of chronic lymphocytic leukemia cells.

Chronic lymphocytic leukemia (CLL) is a low-grade lymphoid malignancy incurable with conventional modalities of chemotherapy. We aimed to examine the proapoptotic effects of a novel proteasome inhibitor, N,N'-di-(m-methylphenyi)-3,6- dimethyl-1,4-dihydro-1,2,4,5-tetrazine-1,4-dicarboamide (ZGDHu-1), on CLL cells. B lymphocytes were isolated from CLL patients and normal healthy controls, and treated with various concentrations of ZGDHu-1 for different days. CLL cell viability was detected by MTT assay. The apoptosis, mitochondrial membrane potential (∆ψm) and reactive oxidative species (ROS) were examined by flow cytometry. The expression of caspase-3 and Bcl-2/Bax ratio was detected by western blotting. ZGDHu-1 significantly reduced the viability of CLL cells and induced apoptosis in comparison to the control cells (both P<0.05). Normal peripheral B cells were resistant to the apoptosis-inducing effects of ZGDHu-1. Apoptosis induced by ZGDHu-1 was accompanied with generation of ROS, loss of ∆ψm, downregulation of Bcl-2 and increase of caspase-3 cleavage. Results of this study indicate that ZGDHu-1 is a promising specific treatment for CLL in the clinic.

[Apoptosis of human lung carcinoma cell line EBC-1 induced by N, N'-di-(m-methylphenyl)-3,6-dimethyl-1,4-dihydro-1,2,4,5-tetrazine-1,4-dicarboamide and its molecular mechanism].

OBJECTIVE: To study whether N, N'-di-(m-methylphenyi)-3,6-dimethyl-1,4-dihydro-1,2,4,5-tetrazine-1,4-dicarboamide (ZGDHu-1) inhibits proliferation and induces apoptosis in human lung carcinoma cell line EBC-1 cells and its molecular mechanism. METHODS: Different concentrations of ZGDHu-1 and different times of culture were used to treat EBC-1 cells in vitro. The inhibition of proliferation was measured by BrdU-ELISA. Cell apoptosis was detected by Annexin V/PI staining and cellular DNA fragmentation ELISA. Phosphorylated p38MAPK and STAT3 were examined by flow cytometry. The protein expressions of bcl-2, bax, p53, Fas, and caspase-3 were detected by Western blot analysis. RESULTS: ZGDHu-1 inhibited EBC-1 cell proliferation within a certain range of treating times and does, with a 24 h IC(50) of (295 ± 25) ng/ml, 48 h of (112 ± 8) ng/ml and 72 h of (23 ± 2) ng/ml. The EBC-1 cell apoptosis was confirmed by Annexin V/PI labeling and cellular DNA fragmentation ELISA in a dose-related manner. When EBC-1 cells were treated with 50, 200, and 500 ng/ml ZGDHu-1 for 48 h, the expression rates of phosphor-p38MAPK protein were 67.4%, 88.2%, 91.1%, respectively, and that of the control was 10.6%. That of STAT3 protein were 56.5%, 43.6% and 34.6%, respectively, and that of the control was 89.1%. The expression of bax, p53 and Fas protein was significantly increased, that of bcl-2 was not changed, and that of caspase-3 was significantly decreased by the ZGDHu-1 treatment. CONCLUSION: ZGDHu-1 can inhibit proliferation and induce apoptosis in EBC-1 cells. The mitochondrial pathway mediated by Fas may be one of its mechanisms. The apoptosis of EBC-1 cells may associate with up-regulation of phosphor-p38MAPK and down-regulation of phosphor-STAT3 in the cells.

[Effect of macrocalyxin A on HL-60 cells proliferation, differentiation and apoptosis].

OBJECTIVE: To study the effect of macrocalyxin A (MA) on proliferation, differentiation and apoptosis in HL-60 cells and explore its possible mechanisms. METHODS: Different concentration of MA were used to treat HL-60 cells. Proliferation inhibition was analyzed by Trypan blue staining and MTT assay, cell apoptosis by cell morphology, DNA content, cell cycle analysis, Annexin-V/PI and Hoechst 33258 fluorescence staining. The differentiation of HL-60 cells was evaluated by cell morphology, NBT tests and expression of CD11b, CD13, CD14. The expressions of bcl-2, bax, Fas, P53, mitochondrial transmembrane-potential (DeltaPsim) and mitochondrial membrane protein were analyzed by flow cytometry. RESULTS: MA could inhibit HL-60 cells proliferation capacity in a time-and dose-effect, with a 24 h IC50 value of 8.76 microg/ml, 48 h of 7.17 microg/ml and 72 h of 7.14 microg/ml. The HL-60 cells apoptosis was confirmed by cell morphology, sub-G1 phase and Annexin-V/PI labeling in a time and dose dependent manner. The more mature HL-60 cells were a with higher positivity of NBT and expressions of CD11b than those cultured without MA. The expression of bax was increased, while bcl-2, P53, Fas were unchanged on the MA treatment. MA could increase the expression of mitochondrial membrane protein in a dose-dependent manner while the DeltaPsim was reduced. CONCLUSION: MA can inhibit proliferation and induce differentiation and apoptosis of the HL-60 cells. The mechanism may be related with up-regulating bax, opening the mitochondrial permeability transition pore and reducing DeltaPsim.