Refining risk stratification in paediatric B-acute lymphoblastic leukaemia: Combining IKZF1plus and Day 15 MRD positivity.

This study investigates the potential utility of IKZF1 deletion as an additional high-risk marker for paediatric acute lymphoblastic leukaemia (ALL). The prognostic impact of IKZF1 status, in conjunction with minimal/measurable residual disease (MRD), was evaluated within the MRD-guided TPOG-ALL-2013 protocol using 412 newly diagnosed B-ALL patients aged 1-18. IKZF1 status was determined using multiplex ligation-dependent probe amplification. IKZF1 deletions, when co-occurring with CDKN2A, CDKN2B, PAX5 or PAR1 region deletions in the absence of ERG deletions, were termed IKZF1plus. Both IKZF1 deletion (14.6%) and IKZF1plus (7.8%) independently predicted poorer outcomes in B-ALL. IKZF1plus was observed in 4.1% of Philadelphia-negative ALL, with a significantly lower 5-year event-free survival (53.9%) compared to IKZF1 deletion alone (83.8%) and wild-type IKZF1 (91.3%) (p < 0.0001). Among patients with Day 15 MRD ≥0.01%, provisional high-risk patients with IKZF1plus exhibited the worst outcomes in event-free survival (42.0%), relapse-free survival (48.0%) and overall survival (72.7%) compared to other groups (p < 0.0001). Integration of IKZF1plus and positive Day 15 MRD identified a subgroup of Philadelphia-negative B-ALL with a 50% risk of relapse. This study highlights the importance of assessing IKZF1plus alongside Day 15 MRD positivity to identify patients at increased risk of adverse outcomes, potentially minimizing overtreatment.

Harnessing the Transcriptional Signatures of CAR-T-Cells and Leukemia/Lymphoma Using Single-Cell Sequencing Technologies.

Chimeric antigen receptor (CAR)-T-cell therapy has greatly improved outcomes for patients with relapsed or refractory hematological malignancies. However, challenges such as treatment resistance, relapse, and severe toxicity still hinder its widespread clinical application. Traditional transcriptome analysis has provided limited insights into the complex transcriptional landscape of both leukemia cells and engineered CAR-T-cells, as well as their interactions within the tumor microenvironment. However, with the advent of single-cell sequencing techniques, a paradigm shift has occurred, providing robust tools to unravel the complexities of these factors. These techniques enable an unbiased analysis of cellular heterogeneity and molecular patterns. These insights are invaluable for precise receptor design, guiding gene-based T-cell modification, and optimizing manufacturing conditions. Consequently, this review utilizes modern single-cell sequencing techniques to clarify the transcriptional intricacies of leukemia cells and CAR-Ts. The aim of this manuscript is to discuss the potential mechanisms that contribute to the clinical failures of CAR-T immunotherapy. We examine the biological characteristics of CAR-Ts, the mechanisms that govern clinical responses, and the intricacies of adverse events. By exploring these aspects, we hope to gain a deeper understanding of CAR-T therapy, which will ultimately lead to improved clinical outcomes and broader therapeutic applications.

Prediction of miRNA­mRNA network regulating the migration ability of cytarabine­resistant HL60 cells.

Cytarabine is an important medicine for acute myeloid leukemia (AML) treatment, however, drug resistance hinders the treatment of AML. Although microRNA (miRNA or miR) alteration is one of the well-recognized mechanisms underlying drug resistance in AML, few studies have investigated the role and function of miRNAs in the development of cytarabine resistance. In the present study, total RNA was isolated from parental HL60 and cytarabine-resistant HL60 (R-HL60) cells. Subsequently, miRNAs and mRNAs were detected using small RNA sequencing and gene expression array, respectively. Differentially expressed mRNAs (DEMs) and differentially expressed genes (DEGs) with more than two-fold changes between HL60 and R-HL60 cells were screened out. Negatively associated miRNA-mRNA pairs were selected as candidate miRNA-mRNA target pairs according to the miRDB, Targetscan or miRTar databases. Functional enrichment analysis of DEGs included in the candidate miRNA-mRNA pairs was performed. The results indicated that 10 DEGs (CCL2, SOX9, SLC8A1, ICAM1, CXCL10, SIPR2, FGFR1, OVOL2, MITF and CARD10) were simultaneously involved in seven Gene Ontology pathways related to the regulation of migration ability, namely the 'regulation of cell migration', 'regulation of locomotion', 'regulation of cellular component movement', 'cell migration', 'locomotion', 'cell motility', and 'localization of cell'. DEMs predicted to negatively regulate the aforementioned 10 DEGs were paired with DEGs into 16 candidate miRNA-mRNA pairs related to the regulation of migration ability. In addition, migration assays revealed that the migration ability of R-HL60 cells was greater than that of HL60 cells. These findings provide a new perspective for the treatment of cytarabine-resistant AML and advance our understanding of altered migration ability underlying cytarabine resistance development, specifically related to miRNAs.

Pineal/germ cell tumors and pineal parenchymal tumors.

INTRODUCTION: Pineal region tumors (PRTs) are tumors arising from the pineal gland and the paraspinal structures. These tumors are rare and heterogeneous that account for 2.8-10.1% and 0.6-3.2% of tumors in children and in all ages, respectively. Almost all types and subtypes of CNS tumors may be diagnosed in this region. These tumors come from cells of the pineal gland (pinealocytes and neuroglial cells), ectopic primordial germ cells (PGC), and cells from adjacent structures. Hence, PRTs are consisted of pineal parenchyma tumors (PPTs), germ cell tumors (GCTs), neuroepithelial tumors (NETs), other miscellaneous types of tumors, cystic tumors (epidermoid, dermoid), and pineal cyst in addition. The symptoms of PRTs correlate to the increased intracranial cranial pressure due to obstructive hydrocephalus and dorsal midbrain compression. The diagnostic imaging studies are mainly MRI of brain (with and without gadolinium) along with a sagittal view of whole spine. Serum and/or CSF AFP/ß-HCG helps to identify GCTs. The treatment of PRTs is consisted of the selection of surgical biopsy/resection, handling of hydrocephalus, neoadjuvant and/or adjuvant therapy according to age, tumor location, histopathological/molecular classification, grading of tumors, staging, and threshold value of markers (for GCTs) in addition. METHODS: In this article, we review the following focus points: 1. Background of pineal region tumors. 2. Pineal GCTs and evolution of management. 3. Molecular study for GCTs and pineal parenchymal tumors. 4. Review of surgical approaches to the pineal region. 5. Contribution of endoscopy. 6. Adjuvant therapy (chemotherapy, radiotherapy, and combination). 7. RESULTS: In all ages, the leading three types of PRTs in western countries were PPTs (22.7-34.8%), GCTs (27.3-34.4%), and NETs (17.2-28%). In children and young adults, the leading PRTs were invariably in the order of GCTs (40-80.5%), PPTs (7.6-21.6%), NETs (2.4-37.5%). Surgical biopsy/resection of PRTs is important for precision diagnosis and therapy. Safe resection with acceptable low mortality and morbidity was achieved after 1970s because of the advancement of surgical approaches, CSF shunt and valve system, microscopic and endoscopic surgery. Following histopathological diagnosis and classification of types and subtypes of PRTs, in PPTs, through molecular profiling, four molecular groups of pineoblastoma (PB) and their oncogenic driver were identified. Hence, molecular stratified precision therapy can be achieved. CONCLUSION: Modern endoscopic and microsurgical approaches help to achieve precise histopathological diagnosis and molecular classification of different types and subtypes of pineal region tumors for risk-stratified optimal, effective, and protective therapy. In the future, molecular analysis of biospecimen (CSF and blood) along with AI radiomics on tumor imaging integrating clinical and bioinformation may help for personalized and risk-stratified management of patients with pineal region tumors.

Feasibility and Toxicity of Interval-Compressed Chemotherapy in Asian Children and Young Adults with Sarcoma.

Twelve Asian patients with sarcoma received interval-compressed (ic-) chemotherapy scheduled every 14 days with a regimen of vincristine (2 mg/m2), doxorubicin (75 mg/m2), and cyclophosphamide (1200-2200 mg/m2) (VDC) alternating with a regimen of ifosfamide (9000 mg/m2) and etoposide (500 mg/m2) (IE), with filgrastim (5-10 mcg/kg/day) between cycles. Carboplatin (800 mg/m2) was added for CIC-rearranged sarcoma. The patients were treated with 129 cycles of ic-VDC/IE with a median interval of 19 days (interquartile range [IQR], 15-24 days. Median nadirs (IQR) were neutrophil count, 134 (30-396) × 106/L at day 11 (10-12), recovery by day 15 (14-17) and platelet count, 35 (23-83) × 109/L at day 11 (10-13), recovery by day 17 (14-21). Fever and bacteremia were observed in 36% and 8% of cycles, respectively. The diagnoses were Ewing sarcoma (6), rhabdomyosarcoma (3), myoepithelial carcinoma (1), malignant peripheral nerve sheath tumor (1), and CIC-DUX4 Sarcoma (1). Seven of the nine patients with measurable tumors responded (one CR and six PR). Interval-compressed chemotherapy is feasible in the treatment of Asian children and young adults with sarcomas.

Clinical Predictors and Prediction Models for rFVIII-Fc Half Life in Real-World People with Severe Hemophilia A.

The half life of recombinant factor VIII-Fc (rFVIII-Fc) for people with hemophilia A (PwHA) varies greatly. Understanding the factors influencing the variation and assessment of rFVIII-Fc half life is important for personalized treatment. Eighty-five severe-type PwHA with rFVIII-Fc treatment receiving an evaluation of half life by the Web-Accessible Population Pharmacokinetic (PK) Service-Hemophilia during 2019-2021 were retrospectively enrolled. The 50-patient PK profiles before 2021 were used for analysis and developing prediction models of half life, and the 35-patient PK profiles in 2021 were used for external validation. The patients in the development cohort were aged 8-64, with a median rFVIII-Fc half life of 20.75 h (range, 8.25-41.5 h). By multivariate linear regression analysis, we found two, four, and five predictors of rFVIII-Fc half life for the blood groups non-O, O patients, and overall patients, respectively, including baseline VWF:Ag, BMI, VWF:activity/VWF:Ag ratio, body weight, O blood group, inhibitor history, HCV infection, and hematocrit. The three prediction equations of rFVIII-Fc half life (T) were respectively developed as T for non-O group patients = -0.81 + 0.63 × (BMI, kg/m2) + 6.07 × (baseline VWF:Ag, IU/mL), T for O group patients = -0.68 + 13.30 × (baseline VWF:Ag, IU/mL) + 0.27 × (BW, kg) - 1.17 × (BMI, kg/m2) + 16.02 × (VWF:activity/VWF:Ag ratio), and T for overall patients = -1.76 + 7.24 × (baseline VWF:Ag, IU/mL) - 3.84 × (Inhibitor history) + 2.99 × (HCV infection) - 2.83 × (O blood group) + 0.30 × (Hct, %), which explained 51.97%, 75.17%, and 66.38% of the half life variability, respectively. For external validation, there was a significant correlation between the predicted and observed half lives in the validation cohort. The median half life deviation was +1.53 h, +1.28 h, and +1.79 h for the equations of non-O group, O group, and overall group patients, respectively. In total, eight predictors influencing rFVIII-Fc half life were identified. Prediction equations of rFVIII-Fc half life were developed for the non-O and O blood groups and overall PwHA with a good degree of external validation. The equations could be applied to patients aged 8-64 without the need for PK blood sampling and clinically valuable for personalized therapy.

Aryl hydrocarbon receptor-kynurenine axis promotes oncogenic activity in BCP-ALL.

B-cell precursor acute lymphoblastic leukemia (BCP-ALL), the most common childhood cancer, originates from lymphoid precursor cells in bone marrow committed to the B-cell lineage. Environmental factors and genetic abnormalities disturb the normal maturation of these precursor cells, promoting the formation of leukemia cells and suppressing normal hematopoiesis. The underlying mechanisms of progression are unclear, but BCP-ALL incidence seems to be increasing in parallel with the adoption of modern lifestyles. This study hypothesized that air pollution and haze are risk factors for BCP-ALL progression. The current study revealed that indeno(1,2,3-cd)pyrene (IP), a major component of polycyclic aromatic hydrocarbons (PAHs) in air, promotes oncogenic activities (proliferation, transformation, and disease relapse) in vitro and in vivo. Mechanistically, IP treatment activated the aryl hydrocarbon receptor (AHR)-indoleamine-2,3-dioxygenase (IDOs) axis, thereby enhancing tryptophan metabolism and kynurenine (KYN) level and consequent promoting the KYN-AHR feedback loop. IP treatment decreased the time to disease relapse and increased the BCP-ALL cell count in an orthotopic xenograft mouse model. Additionally, in 50 clinical BCP-ALL samples, AHR and IDO were co-expressed in a disease-specific manner at mRNA and protein levels, while their mRNA levels showed a significant correlation with disease-free survival duration. These results indicated that PAH/IP exposure promotes BCP-ALL disease progression.

Surgical treatment confers prognostic significance in pediatric malignant mediastinal germ cell tumors.

BACKGROUND: Primary malignant mediastinal germ cell tumors (GCTs) are rare pediatric tumors that have a poorer prognosis compared to GCTs occurring elsewhere in the body. The current study aimed to assess the prognostic factors and treatment outcomes of children with primary malignant mediastinal GCT in Taiwan. METHODS: The authors retrospectively reviewed children 0-18 years old who were newly diagnosed with primary malignant mediastinal GCT between January 1, 2005 and December 31, 2019 and were registered in the Taiwan Pediatric Oncology Group patient registry. The impact of presenting characteristics, including sex, age, tumor stage, histology subtype, surgical treatment, and chemotherapy regimens of the patients were analyzed. RESULTS: This study enrolled 52 children with malignant mediastinal GCT who had a median age of 16.0 (range, 6.0-17.9) years at diagnosis. The most common histological subtypes were mixed GCTs (n = 20) and yolk sac tumors (n = 15). Advanced disease stage and choriocarcinoma histology subtype were associated inferior outcomes. Children who received surgical treatment exhibited better outcomes compared to those who did not (5-year overall survival, 78% vs. 7%, p < .001). After comparing patients who received first-line cisplatin- and carboplatin-based chemotherapy, no difference in treatment outcomes was observed. Multivariate analysis showed that surgical management was the only independent predictor for superior OS. CONCLUSIONS: Surgical treatment is recommended for mediastinal GCT. Cisplatin-based chemotherapy was not superior to carboplatin-based chemotherapy as first-line treatment and may be avoided due to toxicity concerns.

Decisional conflicts, anxiety, and perceptions of shared decision-making in cancer treatment trajectory among adolescents with cancer: A longitudinal study.

PURPOSE: To examine the trajectory of decisional conflict and anxiety experienced by adolescents after the cancer diagnosis, and explore their perceptions on participation in shared decision-making (SDM). DESIGN: This longitudinal study used incorporated data from questionnaires and interviews. METHODS: Participants recruited from an academic hospital in southern Taiwan ranged in age from 13 to 20 years with a cancer diagnosis within 1 month and received cancer treatment. Each participant completed questionnaires on decisional conflict and anxiety at diagnosis, 1, 3, and 6 months later. Individual interviews were to gain an in-depth understanding of SDM. FINDINGS: Total scores on decisional conflict changed significantly over time (F = 2.98, p = 0.039); the scores at 1 month were higher than 3 months (t = 2.18, p = 0.04) and 6 months (t = 2.97, p = 0.008). Participants perceived significantly different levels of values clarify (F = 9.49, p < 0.01) and support (F = 8.46, p < 0.01) over time. Only 27.3% of participants were anxiety-free. No significant differences were found in anxiety over time. The perception of SDM was a situational involvement. CONCLUSIONS: Decisional conflict changed over time. Participants experienced greater decisional conflict at 4-8 weeks after diagnosis and their anxiety did not decrease over time. The different levels of participation in SDM during their treatment trajectory were found. CLINICAL RELEVANCE: Participants experienced the highest decisional conflict during diagnosis, and highlighted how their roles in healthcare discussions varied from direct participation to indirect involvement. Further research is needed to develop an SDM model which accommodates different levels of needs and implements timely support.

Diagnostic value of endometrial volume and flow parameters under 3D ultrasound acquisition in combination with serum CA125 in endometrial lesions.

OBJECTIVE: This study aims to discuss the differential diagnosis value of endometrial volume and flow parameters in combination with serum carbohydrate antigen 125 (CA125) in endometrial benign and malignant lesions. MATERIALS AND METHODS: The data of 250 patients with endometrial lesions were retrospectively analyzed. Carbohydrate antigen 125 (CA125) was determined before the operation. The morphology, hemodynamics, volume and flow parameters of the endometrium were measured by transvaginal three-dimensional-power Doppler angiography (3D-PDA). The endometrial volume (EV), 3D-PDA vascular index (VI), flow index (FI) and vascularization flow index (VFI) were calculated using the virtual organ computer-aided analysis software (VOCAL). RESULTS: According to the pathological results, 202 patients (80.8%) had benign endometrial lesions and 48 patients (19.2%) had endometrial cancer (EC). The endometrium of EC patients was thicker (15.64 ± 7.26 mm vs. 9.24 ± 5.06 mm, P < 0.001), the endometrial volume was larger (9.23 ± 4.08 ml vs. 2.26 ± 3.42 ml, P < 0.001), and the flow parameters VI, FI and VFI were higher, when compared to those of benign lesions (P < 0.001). The area under the receiver operating characteristic curve (AUROCC) of VI receptors was 0.86, while the AUC of endometrial thickness (ET) was only 0.66. Therefore, the best variable for distinguishing benign and malignant endometrial lesions was VI. The level of CA125 in the EC group significantly increased (40.57 ± 17.45 vs. 17.87 ± 7.64, P < 0.001), and the level of CA125 increased (P < 0.05) with the increase in clinical grade, degree of tumor differentiation, and pelvic lymph node metastasis (P < 0.05). However, the difference in myometrial invasion was not statistically significant (P > 0.05). CONCLUSION: Transvaginal 3D-PDA can clearly show the morphological and hemodynamic characteristics of endometrial lesions, and assist in the detection of EC in combination with serum CA125. This may have important clinical application value.

Low Expression of IL-15 and NKT in Tumor Microenvironment Predicts Poor Outcome of MYCN-Non-Amplified Neuroblastoma.

Immune tumor microenvironment (TME) in neuroblastoma (NBL) contributes to tumor behavior and treatment response. T cells and natural killer (NK) cells have been shown to play important roles in the neuroblastoma TME. However, few reports address the clinical relevance of natural killer T cells (NKTs) and interleukin-15 (IL-15), one of the crucial cytokines controlling the activation and expansion of NK/NKT cells, in NBL. In this study, we examined NKT immunoscores and IL-15 expression in both MYCN-amplified and MYCN-non-amplified NBL to correlate with clinical outcomes such as event-free survival (EFS) and overall survival (OS). From Gene Expression Omnibus (GEO) datasets GSE45480 (n = 643) and GSE49711 (n = 493), we found that NKT immunoscore and IL-15 expression were both significantly lower in MYCN-amplified NBL, and similar results were observed using our clinical NBL samples (n = 53). Moreover, NBL patients (GEO dataset GSE49711 and our clinical samples) with both lower NKT immunoscore and IL-15 expression exhibited decreased EFS and OS regardless of MYCN gene amplification status. Multivariate analysis further showed that the combination of low NKT immunoscore and low IL-15 expression level was an independent prognostic factor for poor EFS and OS in our NBL patients. These findings provide the rationale for the development of strategy to incorporate IL-15 and NKT cell therapy into the treatment regimen for neuroblastoma.

High B3GALT5 expression confers poor clinical outcome and contributes to tumor progression and metastasis in breast cancer.

BACKGROUND: Existence of breast cancer stem cells (BCSCs) is implicated in disease relapse, metastasis, and resistance of treatment. ß1,3-Galactosyltransferase 5 (B3GALT5) has been shown to be a pro-survival marker for BCSCs. However, little is known about the prognostic significance of B3GALT5 in breast cancer. METHODS: Paired tissues (tumor part and adjacent non-tumor part) from a cohort of 202 women with breast cancer were used to determine the expression levels of B3GALT5 mRNA by qRT-PCR. Kaplan-Meier and multivariable Cox proportional hazard models were used to assess survival differences in terms of relapse-free survival (RFS) and overall survival (OS). Both breast cancer cells and cancer stem cells (BCSCs) were used to see the in vitro effects of knockdown or overexpression of B3GALT5 on cell migration, invasion, and epithelial-to-mesenchymal transition (EMT). A patient-derived xenograft (PDX) model was used to see the in vivo effects of knockdown of B3GALT5 in BCSCs on tumor growth and metastasis. RESULTS: Higher expression of B3GALT5 in 202 breast cancer tissues, especially in adjacent non-tumor tissue, correlated with poor clinical outcomes including shorter OS and RFS in all patients, especially those with early stage breast cancer. In vitro studies showed B3GALT5 could enhance cell migration, invasion, mammosphere formation, and EMT. Of note, B3GALT5 upregulated the expression of ß-catenin and EMT activator zinc finger E-box binding homeobox 1 (ZEB1) pathway in BCSCs. In vivo studies showed B3GALT5 expression in BCSCs is critical for not only tumor growth but also lymph node and lung metastasis in PDX mice. CONCLUSION: Our results demonstrated the value of B3GALT5 as a prognostic marker of breast cancer, especially among the early stage patients, and its crucial roles in regulating EMT, cell migration, and stemness thereby promoting breast cancer progression.

Daily self-care practices influence exit-site condition in patients having peritoneal dialysis: A multicenter cross-sectional survey.

AIMS: To investigate practice patterns in exit-site care and identify the risk factors for exit-site infection. DESIGN: A quantitative cross-sectional design. METHODS: Data were collected in 12 peritoneal dialysis (PD) centres in 2018. Daily exit-site care practice patterns and exit-site status of patients receiving PD were assessed through interviews and questionnaires. RESULTS/FINDINGS: Most of the 1,204 patients adhered with the protocols about main aspects of exit-site care, such as cleansing agents selection, frequency of cleansing, catheter fixation, and following the catheter protective measures. However, their adherence levels on hand hygiene, mask wearing, observing exit site, examining secretion, and communicating with PD staff were rather low. Eighty-four patients' exit sites were evaluated as problematic exit site (PES). And 186 patients had catheter-related infection (CRI) history. After multivariable logistic regression analysis, diabetes (OR = 1.631), traction bleeding history (OR = 2.697), antibiotic agents use (OR = 2.460), compliance on mask wearing (OR = 0.794), and observing exit site (OR = 0.806) were influencing factors of CRI history. Traction bleeding history (OR = 2.436), CRI history (OR = 10.280), and effective communication (OR = 0.808) with PD staff were influencing factors for PES. CONCLUSIONS: The adherence levels on different aspects of exit-site care were varied in patients having PD. Their self-care behaviours did correlate with the exit-site status. IMPACT: The adherence level of patients' exit-site care practice needs attention of medical staff. Further studies about the optimal procedure in exit-site care were warranted.

Healthcare Failure Mode and Effect Analysis (HFMEA) as an Effective Mechanism in Preventing Infection Caused by Accompanying Caregivers During COVID-19-Experience of a City Medical Center in Taiwan.

BACKGROUND AND OBJECTIVES: In response to the COVID-19 pandemic outbreak and to ensure the safety of epidemic prevention in the hospital, the hospital has established mitigation strategies in advance including risk assessment and effect analysis to control hospital visitors and accompanying persons. The study aims to assess the effectiveness of mitigation strategies implemented to effectively prevent the invasion and spread of the virus. METHOD: Conduct a status analysis in accordance with the Healthcare Failure Mode and Effect Analysis (HFMEA) 4-step model, construct a response workflow, confirm the failure mode and potential causes, perform hazard matrix analysis and decision tree analysis, and formulate risk control management measures. RESULTS: For the 4 main processes and 9 subprocesses of the accompanying carers and contract caregivers entering the hospital, 26 potential failure modes and 42 potential causes of failure were analyzed. Following implementing improvement measures including strategies targeting the accompanying person, mitigation workflow failure rates decreased from 42 to 13 items, the pass rate for the maximum body temperature cutoff increased from 53.1% to 90.8%, and the compliance rate of hand washing increased from 89.5% to 100%. CONCLUSION: The HFMEA model can effectively implement preventive risk assessment and workflow management of high-risk medical procedures. The model can adjudicate the health of hospital visitors during the epidemic/pandemic, provide epidemic/pandemic education training and preventive measure health education guidance for hospital visits, and improve their epidemic prevention cognition. When combined, these strategies can prevent nosocomial infection to achieve the best anti-epidemic effect.

[Adsorption Effect and Mechanism of Aqueous Arsenic on FeMnNi-LDHs].

Removing As(Ⅲ)from water steadily and efficiently is still a challenging global issue. In this study, novel FeMnNi-LDHs were prepared by a co-precipitation method using Fe, Mn, and Ni as lamellar cations, and the structure were characterized by XRD, TEM, FT-IR, and XPS techniques, and the adsorption performance and mechanism of As(Ⅲ)was explored. The results showed that FeMnNi-LDHs have typical characteristic peaks of layered double hydroxides, with sharp peaks and high crystallinity. The TEM images also show obvious layered structures. The adsorption kinetics of As(Ⅲ)on FeMnNi-LDHs agree with the quasi second-order kinetic model, and the isotherm adsorption curve agrees with the Freundlich isotherm equation. The maximum adsorption capacity at 45℃ was 240.86 mg·g-1, which is significantly higher than other similar layered double hydroxides. Acidity had little effect on the adsorption performance of As(Ⅲ), and it had a good adsorption effect in the range of pH 2-9. The coexistence of PO43- and CO32- ions in water showed adverse effects on the As(Ⅲ) adsorption capacity, and NO3-, Cd2+, and Pb2+ had less influence. The adsorption mechanism of FeMnNi-LDHs for As(Ⅲ) includes ion exchange, oxidation, and coordination complexation, in which Mn plays a major role in the oxidation process of As(Ⅲ). The prepared FeMnNi-LDHs exhibited good application potential in the adsorption of As(Ⅲ) from water and toxicity control.

Plasma levels of IL-1ß and IL-37 in patients with severe haemophilia.

OBJECTIVE: Haemophilia A and B are disorders caused by the lack of clotting factors VIII and IX, respectively. Repeated bleeding into the same joint leads to haemophilic arthropathy (HA). Interleukin (IL)-1ß is responsible for the pro-inflammatory response and IL-37 is induced by IL-1ß stimuli to have an anti-inflammatory response and prevent uncontrolled inflammation and tissue damage. Our objective was to investigate plasma levels of IL-1ß and IL-37 in patients with severe haemophilia with different severities of HA. METHODS: Peripheral blood samples were collected from 14 patients with severe haemophilia A and 6 with severe haemophilia B, and 18 healthy individuals. Plasma levels of IL-1ß and IL-37 were detected by immunoassay, and severity of HA was evaluated using the Pettersson scoring system. Plasma levels of IL-1ß and IL-37 were analysed in patients with severe haemophilia grouped by Pettersson score and in healthy individuals. RESULTS: Plasma levels of IL-1ß and IL-37 were significantly higher in patients with severe haemophilia compared with healthy individuals and significantly lower in those with moderate to severe HA than in those with no or mild HA. CONCLUSIONS: Plasma levels of IL-1ß and IL-37 may be useful to track HA progression in patients with severe haemophilia.

Determinants of Workplace Bullying Types and Their Relationship With Depression Among Female Nurses.

BACKGROUND: Workplace bullying is commonly experienced by nurses worldwide. PURPOSE: This study was conducted to examine the determinants of different types of workplace bullying and their relationship to depression in female nurses. METHODS: A cross-sectional correlational study was employed, and 484 female nurses from a large medical center in southern Taiwan completed the questionnaire. Data were analyzed using logistic regression analysis. RESULTS: Being unmarried and working in medical/surgical units were found to be the major determinants of work-related bullying, whereas being unmarried was found to be the single determinant of person-related and physical-intimidation bullying. Moreover, work-related and person-related bullying were both found to be significant determinants of depression. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: Nursing administrators should establish workplace-bullying prevention and management strategies by setting reasonable and equal workloads for nurses, assigning tasks equitably, and building depression-related support and consultation groups.

SOX17, ß-catenin and CyclinD1 expression in the endometrioid adenocarcinoma and influence of 5-AZA on expression.

The present study discusses the expression and effect of the SOX17 gene in endometrioid adenocarcinoma. MTT assay is performed to determine the growth inhibition ratio of the DNA methyltransferase inhibitor 5-AZA for endometrial carcinoma cells, and the real-time fluorescence quantification PCR (qRT-PCR) was used to detect the mRNA expression of SOX17, ß-catenin, and CyclinD1 in endometrial carcinoma tissues before and after using 5-AZA to treat the endometrial carcinoma cell line. There were 30 cases on endometrioid adenocarcinoma tissues and 10 cases on normal endometrial tissues. The results revealed that the expression of SOX17 in endometrioid adenocarcinoma tissues was downregulated (P < 0.05), the expression of ß-catenin and CyclinD1 was upregulated (P < 0.05), and the expression of SOX17, CyclinD1, and ß-catenin was negatively correlated (r = -0.353, P > 0.05; R = -0.463, P < 0.05). The higher the histological grade and FIGO staging were, the lower the expression level of SOX17 was (P < 0.05). After HEC1A cells were treated by 5-AZA, the cell growth inhibition was most obvious (IC50 = 12.033) at 72 h, as determined by MTT assay. After cell treatment by 5-AZA, the genetic expression of SOX17 significantly increased, when compared with that before treatment (P < 0.05), while the genetic expression of ß-catenin and CyclinD1 significantly declined (P < 0.05). These results indicate that the expression level of SOX17 in endometrioid adenocarcinoma declined, and the upregulated expression level of SOX17 in cells inhibited the growth of tumor cells.

A cross-sectional follow-up study of physical morbidities, neurocognitive function, and attention problems in post-treatment childhood acute lymphoblastic leukemia survivors.

Acute lymphoblastic leukemia (ALL) is the most common childhood cancer. While ALL therapies are highly effective, western studies have shown excesses late life effects of therapies in survivors. In this survey, we recruited subjects being diagnosed as ALL before the age of 18-year-old and had been in complete continuous remission for at least 3 years. Subjects were arranged to receive three cognitive tests (Wechsler intelligence test, Conners' continuous performance test, and Wisconsin card sorting test). Standardized questionnaires were used to inquiry about attention problem in real life context. Treatment outcome were compared between the standard risk and high/very high risk groups. Final survivors were 42 subjects (26 males, 16 females) with median current age of 17.8 years. Subjects were diagnosed to be with ALL at a median age of 4.8 years. The median survival time (from discontinuation of ALL treatment to the study date) was 8.4 years. Results indicated that 17 subjects (40.5%) had chronic physical conditions in need of clinical management and six subjects (14.3%) had mental condition. For the performance-based cognitive outcome, the average full scale intelligence quotient was 91.7 ± 13.8. Ten percent of the subjects had problem in test of attention, 20% had problem in test of impulsivity and 42.8% of the subject had problems in executive function. When judged from real life contexts, 19 subjects (42%) were with obvious attention problems. Group comparison between standard risk vs high/very high risk patients revealed no difference in neurocognitive outcomes. We hope that this information may benefit the implementation of follow-up program for Taiwanese pediatric leukemia survivors.

Clinical Features and Genotypes of Patients with Hemoglobin H Disease in Taiwan.

BACKGROUND: The genetic background of patients with hemoglobin (Hb) H disease in Taiwan has been investigated; however, the clinical features and treatment outcomes were not reported. OBJECTIVE: To analyze the clinical features and genotypes of patients with HbH who reside in Taiwan. METHODS: We conducted a retrospective analysis of the clinical and molecular characteristics of 38 patients with HbH disease who were undergoing treatment at Kaohsiung Medical University Hospital, Taiwan. RESULTS: Initial Hb levels were lower and the numbers of patients requiring iron-chelation therapy were higher in the nondeletional HbH group than in the deletional HbH group (P <.05). Compared with the healthy population, the patients with HbH disease exhibited short body length, low body weight, and low body mass index (BMI). CONCLUSIONS: Patients with nondeletional HbH disease had lower Hb levels and a higher requirement for splenectomy and iron-chelation therapy than did those with deletional HbH disease. Also, growth status was compromised in patients with HbH disease.