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Pediatric T-cell acute lymphoblastic leukemia (T-ALL) has historically been associated with a poor prognosis. However, prognostic indicators and methods of treatment used for T-ALL remain controversial. A total of 136 children newly diagnosed with T-ALL between 2005 and 2018 were consecutively enrolled in this study. We assessed the effect of different prognostic factors, such as clinical characteristics, minimal residual disease (MRD), and the role of transplantation in postremission treatment, as the outcomes. Compared with B-ALL patients, patients with T-ALL are generally older, more likely to be male and have a higher white blood cell count. The complete remission (CR) rate was 95.6%, while the 5-year overall survival (OS), event-free survival (EFS), and cumulative incidence of relapse (CIR) were 74.3 ± 3.7%, 71.3 ± 3.9%, and 24.4 ± 3.8%, respectively. In the multivariate analysis, day 33 MRD ≥0.1% and hyperleukocytosis were associated with a significantly worse prognosis in the whole group. Transplantation resulted in a significant survival advantage, compared with chemotherapy, for high-risk (HR) patients (5-year CIR: 15.6 ± 10.2% vs. 55.6 ± 11.7%, P = .029). The prognosis of children with T-ALL was poor, and the MRD on day 33 was found to be an important predictive factor of clinical outcome at our center., Competing Interests: Disclosure The authors have stated that they have no conflicts of interest., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Polycyclic aromatic hydrocarbons (PAHs) are produced during combustion of organic matter, such as during cigarette smoking, and they exist widely in the environment. Exposure to 3,4-benzo[a]pyrene (BaP), as the most widely studied PAHs, relates to many cardiovascular diseases. However, the underlying mechanism of its involvement remains largely unclear. In this study, we developed a myocardial ischemia-reperfusion (I/R) injury mouse model and an oxygen and glucose deprivation-reoxygenation H9C2 cell model to evaluate the effect of BaP in I/R injury. After BaP exposure, the expression of autophagy-related proteins, the abundance of NLRP3 inflammasomes, and the degree of pyroptosis were measured. Our results show that BaP aggravates myocardial pyroptosis in a autophagy-dependent manner. In addition, we found that BaP activates the p53-BNIP3 pathway via the aryl hydrocarbon receptor to decrease autophagosome clearance. Our findings present new insights into the mechanisms underlying cardiotoxicity and reveal that the p53-BNIP3 pathway, which is involved in autophagy regulation, is a potential therapeutic target for BaP-induced myocardial I/R injury. Because PAHs are omnipresent in daily life, the toxic effects of these harmful substances should not be underestimated., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Adolescents (aged 10-17 years) with acute lymphoblastic leukemia (ALL) represent a unique patient population, with a disproportionate survival disadvantage compared with younger patients. We aimed to determine the outcomes and prognostic factors of adolescent patients treated at our institution., Patients and Methods: Between 2005 and 2017, 335 adolescents with ALL were enrolled; clinical characteristics and treatment outcomes were analyzed and compared between adolescents and younger children (1-9 years old, n = 704)., Results: Adolescents were more likely to have high-risk factors such as hyperleukocytosis, a T-cell immunophenotype, BCR-ABL1, and/or poor early treatment responses. Compared with younger children, adolescents had significantly worse 5-year event-free survival (EFS) (73.0% ± 2.5% vs. 82.6% ± 1.5%; P < .001) and overall survival (OS) (77.1% ± 2.3% vs. 87.7% ± 1.3%; P < .001). Furthermore, younger adolescents (10-14 years) tended to have better outcomes compared with those older than 15 years (5-year OS: 79.3% ± 2.5% vs. 68.4% ± 5.7%; P = .042), mainly because of the lower frequencies of toxicities. On multivariate analysis, white blood count ≥ 50 × 10 9 /L and extramedullary involvement at diagnosis were the most powerful prognostic factors for both OS and EFS., Conclusion: The outcomes among adolescent patients were not as good as that of younger children. Further studies are required to define optimal treatment strategies for adolescents, particularly those aged 15 to 17 years., (Copyright © 2021. Published by Elsevier Inc.)

Background: The role of haploidentical hematopoietic stem cell transplantation (haplo-HSCT) for children with intermediate-risk acute myeloid leukemia (IR-AML) in first complete remission has been controversial. The present study compared the effect of chemotherapy with unmanipulated haplo-HSCT as treatment of patients with IR-AML in first complete remission (CR1)., Patients and Methods: We retrospectively analyzed the outcomes of 80 children with IR-AML and compared the effects of chemotherapy (n = 47) with those of haplo-HSCT (n = 33) as treatment in CR1., Results: The 3-year overall survival, event-free survival (EFS), and cumulative incidence of relapse (CIR) was 85.4% ± 4.1%, 73.2% ± 5.0%, and 25.4% ± 4.5%, respectively. Compared with the chemotherapy group, the patients in the haplo-HSCT group had a lower CIR (P = .059) and better EFS (P = .108), but roughly equivalent overall survival (P = .841). Multivariate analysis revealed chemotherapy and minimal residual disease (MRD) of ≥ 10 -3 after induction therapy as independent risk factors affecting CIR and EFS. EFS (P = .045) and CIR (P = .045) differed significantly between the 2 treatment groups in patients with MRD of ≥ 10 -3 after induction therapy., Conclusion: Haplo-HSCT might be a feasible option for children with IR-AML in CR1, especially for patients with MRD of ≥ 10 -3 after induction therapy., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Acute lymphoblastic leukemia (ALL) with t(1;19)/TCF3-PBX1 is a common genotype, and its prognosis has significantly improved owing to risk stratification and intensive treatment. This study aimed to determine the outcomes and prognostic factors of patients with TCF3-PBX1 treated with the modified Berlin-Frankfurt-Münster protocol., Patients and Methods: Between 2005 and 2017, a total of 1051 pediatric patients with ALL were enrolled. TCF3-PBX1 was detected by reverse-transcriptase PCR and/or cytogenetic analysis. Clinical characteristics and treatment outcomes were analyzed and compared in patients with TCF3-PBX1 and with other B-precursor ALL (B-ALL)., Results: TCF3-PBX1 was detected in 64 patients with ALL (6.1%), and all were of B-cell lineage. These patients were more likely to express the pre-B-ALL immunophenotype (P < .001), be in the National Cancer Institute high-risk group (P = .030), and exhibit more rapid disease clearance during induction therapy (P < .001) compared to patients with other B-ALL. However, the outcomes of this genotype were not better than those of other patients with intermediate risk. At a median (range) follow-up of 60.6 (0.8-184.5) months, the estimated 5-year overall survival was 85.2 ± 4.6% versus 88.2 ± 1.8% (P = .500) and 5-year event-free survival was 76.8 ± 5.5% versus 83.0 ± 2.0% (P = .210) for patients with TCF3-PBX1 and those with other B-ALL. After adjusting for other risk factors, reemergent minimal residual disease (MRD) was the most significant poor prognostic indicator for patients with TCF3-PBX1., Conclusion: The overall outcome of patients with TCF3-PBX1 was intermediate at our institution. Sequential MRD measurement is important for this genotype. Thus, more efforts should be made to eradicate reemergent MRD to improve prognosis., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objectives: To assess microstructural alterations in white matter (WM) in amyotrophic lateral sclerosis (ALS) using diffusion tensor imaging (DTI)., Methods: DTI data were collected from 34 subjects (18 patients with ALS and 16 healthy controls). The atlas-based region of interest (ROI) analysis was conducted to assess WM microstructure in ALS by combining intra-voxel metrics, which included fractional anisotropy (FA) and mean diffusivity (MD), and an inter-voxel metric, i.e., local diffusion homogeneity (LDH). Correlation analysis of diffusion values and clinical factors was also performed., Results: ALS group showed a significant FA reduction in bilateral corticospinal tract (CST) as well as right uncinate fasciculus (RUF). The areas with higher MD were situated in right corticospinal tract (RCST), left cingulum hippocampus (LCH), RUF, and right superior longitudinal fasciculus (RSLF). Additionally, ALS patients showed decreased LDH in bilateral anterior thalamic radiation (ATR), bilateral CST and left inferior frontal-occipital fasciculus (LIFOF). Significant correlations were observed between ALSFRS-R (revised ALS Functional Rating Scale) scores or progression rate and FA in bilateral CST, as well as between disease duration and LDH in right CST. Receiver operating characteristic (ROC) analysis revealed the feasibility of employing diffusion metrics along the CST to distinguish two groups (AUC = 0.792-0.868, p < .005 for all)., Conclusions: WM microstructural alteration is a common pathology in ALS, which can be detected by both intra- and inter-voxel diffusion metrics. The extent of abnormalities in several WM tracts such as ATR and LIFOF may be better assessed through the inter-voxel diffusion measurement., (Copyright © 2019. Published by Elsevier B.V.)

Shrimps are the most widely and increasingly cultured crustaceans in land-based ponds in Taiwan. However, few studies have investigated the phthalate contamination of and insecticide residues in shrimp. In this study, we applied a validated method to analyze the phthalate and 18 insecticides residues in shrimp. A total of 46 samples of whiteleg, grass, or giant river shrimp were collected from aquafarms and production areas in Taiwan. We detected 0.02-0.70 mg/kg of di-2-ethylhexyl phthalate (DEHP) in three shrimps; 0.02-0.03 mg/kg of chlorpyrifos in three shrimps, and 0.03 mg/kg of trichlorfon in one shrimp, indicating that 6.52% and 8.70% of the samples contained phthalate and insecticide residues, respectively. Furthermore, the assessed risk was negligible and indicated no immediate health risk associated with shrimp consumption. Continual monitoring of the residues in shrimps is critical for further assessment of possible effects on human health., (Copyright © 2019. Published by Elsevier Ltd.)

A 96-well single-pot protein precipitation, liquid chromatography/tandem mass spectrometry (LC/MS/MS) method has been developed and validated for the determination of muraglitazar, a PPAR alpha/gamma dual agonist, in human plasma. The internal standard, a chemical analogue, was dissolved in acetonitrile containing 0.1% formic acid. The solvent system was also served as a protein precipitation reagent. Human plasma samples (0.1 mL) and the internal standard solution (0.3 mL) were added to a 96-well plate. The plate was vortexed for 1 min and centrifuged for 5 min. Then the supernatant layers were directly injected into the LC/MS/MS system. The chromatographic separation was achieved isocratically on a Phenomenox C18(2) Luna column (2 mm x 50 mm, 5 microm). The mobile phase contained 20/80 (v/v) of water and acetonitrile containing 0.1% formic acid. Detection was by positive ion electrospray tandem mass spectrometry on a Sciex API 3000. The standard curve, which ranged from 1 to 1000 ng/mL, was fitted to a 1/x weighted quadratic regression model. This single-pot approach effectively eliminated three time consuming sample preparation steps: sample transfer, dry-down, and reconstitution before the injection, while it preserved all the benefits of the traditional protein precipitation. By properly adjusting the autosampler needle offset level, only the supernatant was injected, without disturbing the precipitated proteins in the bottom. As a result, the quality of chromatography and column life were not compromised. After more than 600 injections, there was only slightly increase of column back-pressure. The validation results demonstrated that this method was rugged and provide satisfactory precision and accuracy. The method has been successfully applied to analyze human plasma samples in support of a first-in-man study. This method has also been validated in monkey and mouse plasma for the determination of muraglitazar.

A simple, high throughput, direct-injection high-performance liquid chromatography tandem mass spectrometry method (LC/MS/MS) has been developed and validated for the quantitation of pioglitazone in human serum. After mixing the internal standard with a sample, a 10 microl portion of the mixture was directly injected into a high-flow LC/MS/MS system, which included an extraction column, an analytical column and a six-port switching valve. The on-line extraction was achieved on an Oasis HLB column (1 mm x 50 mm, 30 microm) with a 100% aqueous loading mobile phase containing 5 mM ammonium acetate (pH 4.0) at a flow rate of 4 ml/min. The extracted analyte was eluted by a mobile phase which contained 5 mM ammonium acetate and acetonitrile. The analytical column was a Luna C18 column (4.6 mm x 50 mm, 5 microm). Detection was achieved by positive ion electrospray tandem mass spectrometry. The lower limit of quantitation of the method was 9 ng/ml. The standard curve, which ranged from 9 to 1350 ng/ml, was fitted by a weighted (1/x2) quadratic regression model. The validation results demonstrated that this method had satisfactory precision and accuracy across the calibration range. There was no evidence of instability of the analyte in human serum following three freeze-thaw cycles, and samples could be stored for at least 2 weeks at -30 degrees C. This method was used to analyze pioglitazone concentrations in human serum samples from a bioequivalence study of a blinded Actos formulation (encapsulated 15 mg tablet) and an Actos 15 mg tablet. The blinded formulation was shown to be bioequivalent to an Actos 15 mg tablet.