Paroxysmal nocturnal hemoglobinuria (PNH) is a rare chronic bone marrow failure condition characterized by complement-mediated hemolytic anemia and thrombosis. While its initial clinical description occurred in 1882, somatic mutations in PIGA were discovered in the 1990s. With an improved understanding of PNH biology, a focused effort on complement inhibitors led to the discovery of eculizumab, a C5 inhibitor initially approved by the US Food and Drug Administration in 2007. Terminal complement pathway inhibition reduced intravascular hemolysis, anemia, and thrombosis. Further advancements in drug development for PNH have included improved pharmacokinetics with ravulizumab in 2018 and the introduction of proximal complement inhibitors such as pegcetacoplan (2021), iptacopan (2023), danicopan (2024), and crovalimab (2024) to enhance patient outcomes. With these new proximal and distal complement inhibitors in the treatment landscape, it is timely for clinicians to review the evolving landscape of PNH treatments and patient selection.

Objective: Interferon-regulatory factor 2 (IRF2) and inositol polyphosphate 4-phosphatase B (INPP4B) are indispensable for differentiating immune T-cells, but the regulatory principle of the IRF2-INPP4B signaling channel in the apoptosis of acute myeloid leukemia (AML) cells remains unclear. This work investigates the function and regulatory principle of IRF2-INPP4B signaling in the progression of AML.
Materials and Methods: CD4+ T-cells were extracted from peripheral blood and characterized via flow cytometry. Flow cytometry was used to estimate apoptosis in the HL60 AML cell line and determine the Th1/Th2 cell ratio. Quantitative real-time polymerase chain reaction was used to measure IRF2 mRNA. Western blotting was performed to evaluate the protein levels of IRF2, INPP4B, JAK2, p-JAK2, STAT3, p-STAT3, and caspase 3. Interleukin-4 and interferon gamma concentrations were determined using enzyme-linked immunoadsorption assay kits.
Results: We discovered that levels of IRF2 and INPP4B were high in AML-derived CD4+ T-cells. Furthermore, CD4+ T-cells encouraged HL60 cell apoptosis. Downregulation of IRF2 encouraged HL60 cell apoptosis via alterations in the Th1/Th2 ratio while the overexpression of IRF2 stimulated the JAK2-STAT3 signaling channel and downregulated caspase 3.
Conclusion: We revealed that IRF2-INPP4B signaling in CD4+ T-cells stimulated the JAK2-STAT3 signaling channel and downregulated caspase 3, reducing AML cell apoptosis and aggravating AML progression. This work highlights an important regulatory principle concerning AML progression, as the IRF2-INPP4B pathway might impact the JAK2-STAT3 signaling channel. The findings contribute to our knowledge of the complicated interplay of these pathways in AML.

Objective: Acute myeloid leukemia (AML) highly lethal hematological malignancy that is difficult to treat. This study aimed to clarify the molecular mechanisms of miR-379-5p in AML progression.
Materials and Methods: Quantitative real-time polymerase chain reaction was utilized to evaluate miR-379-5p expression levels in AML patients and a control group. A receiver operating characteristic curve was created to assess the clinical predictive value of miR-379-5p in AML, while cell experiments used the CCK-8 assay, flow cytometry, and transwell chambers. Potential target genes of miR-379-5p were predicted by employing online bioinformatics tools, followed by validation using a dual luciferase reporter assay.
Results: miR-379-5p expression was significantly decreased in AML patients and had clinical predictive value for the disease. In AML cell lines, miR-379-5p was downregulated; conversely, the upregulation of miR-379-5p inhibited proliferation, migration, and invasion while promoting apoptosis. Notably, YBX1 was a potential target gene of miR-379-5p and its upregulation reduced the effects of miR-379-5p on AML cell behavior.
Conclusion: miR-379-5p has potential as a biomarker for AML by regulating cell proliferation and apoptosis through the targeting of YBX1.

Objective: Leucine-rich alpha-2-glycoprotein 1 (LRG1) is a novel mediator involved in abnormal angiogenesis. We aimed to investigate circulating LRG1 levels and their relationship with proangiogenic mediators in sickle cell disease (SCD).
Materials and Methods: A total of 50 patients with SCD, with 25 in steady-state condition (SCD-SS) and 25 in periods of painful vasoocclusive crisis (SCD-VOC), and 25 healthy controls were included in the study. Demographical and clinical data were collected from hospital records. Serum LRG1, vascular endothelial growth factor A (VEGFA), and hypoxia-inducible factor 1-alpha (HIF1A) levels were measured by enzyme-linked immunosorbent assay (ELISA), and C-reactive protein (CRP) was measured by the nephelometric method. Routine biochemical parameters were assessed using an autoanalyzer. Multinomial logistic regression was used to analyze ELISA parameters, and receiver operating characteristic (ROC) curves were constructed to determine the optimal cut-off point for HIF1A to predict VOCs in SCD patients.
Results: LRG1 and VEGFA levels were significantly higher in SCD patients than controls (p<0.001), with no difference between the SCD-SS and SCD-VOC groups. HIF1A, CRP, and lactate dehydrogenase levels differed significantly across all groups, being highest in the SCDVOC group (p<0.001). After adjusting for age and sex, LRG1, HIF1A, and VEGFA remained elevated in the SCD groups. HIF1A correlated with CRP (r=0.351, p=0.024), but LRG1 showed no correlation with proangiogenic mediators in the SCD-VOC group. The area under the ROC curve was calculated as 0.694 (95% confidence interval: 0.542- 0.845, p=0.021) and the optimal cut-off point was 494.5 pg/mL for HIF1A in predicting vaso-occlusive crises in patients with SCD.
Conclusion: Circulating LRG1 levels may reflect neutrophil activation and contribute to the cross-talk between proangiogenic mediators released in SCD.

Objective: Deep vein thrombosis (DVT) is a vascular disorder with an incidence rate of about 0.1%. Endothelial progenitor cells (EPCs) are precursor cells of endothelial cells and contribute to vascular repair and regeneration. Circular RNA (circRNA) has become a new focus of research as circRNAs are involved in various biological processes including the progression of DVT. This study explored the upregulation of hsa_circRNA_092488 in DVT patients.
Materials and Methods: The expression of hsa_circRNA_092488 was evaluated in venous blood samples obtained from DVT patients (n=42) and healthy controls (n=42). Gain- and loss-of-function studies of hsa_circRNA_092488 were carried out. The expression levels of related RNAs and proteins were examined by quantitative real-time reverse-transcription polymerase chain reaction, western blotting and immunofluorescence assays. The proliferation, migration, cell cycle progression, and apoptosis of transfected cells were measured by CCK-8 assay, transwell assay, and flow cytometry. The association of hsa_circRNA_092488 and NOD-like receptor protein 3 (NLRP3) in EPCs was revealed using RNA pull-down analysis. Furthermore, the stability of NLRP3 mRNA was examined in transfected EPCs.
Results: Upregulation of hsa_circRNA_092488 was detected in blood samples from DVT patients and it had the ability to suppress the proliferation and migration of EPCs, induce cell cycle arrest from the S to the G0/G1 phase, and trigger cellular apoptosis. Furthermore, NLRP3 was identified as the potential downstream target molecule of hsa_circRNA_092488 and it could exert its regulatory functions by activating the NLRP3/nuclear factor (NF)-κB signaling pathway. Overexpression of hsa_circRNA_092488 in cells notably elevated the protein expression of caspase-1, interleukin-1β, P-NF-κB-p65/NF- κB-p65, and P-IκBα/IκBα, while knockdown of hsa_circRNA_092488 significantly reduced the levels of those proteins in EPCs.
Conclusion: hsa_circRNA_092488/NLRP3/NF-κB signaling could be a novel therapeutic candidate for the treatment of DVT.

Objective: This study comprehensively compares the efficacy, safety, and tolerability of two commonly used intravenous iron preparations, ferric carboxymaltose (FCM) and iron sucrose (IS), in adult patients with iron-deficiency anemia (IDA).
Materials and Methods: A systematic literature search was conducted across the PubMed, Ovid MEDLINE, Web of Science, and Cochrane Library databases up to January 1, 2024, to identify randomized controlled trials directly comparing FCM and IS treatments in adult patients with IDA. The primary outcome of interest was change in hemoglobin (Hb) levels during follow-up. Meta-analyses were conducted with inverse variance random effects models.
Results: Fourteen trials were included in the study, with a total of 4757 patients. FCM resulted in a non-significant increase in Hb levels (mean difference [MD]: 0.45 g/dL, 95% confidence interval [CI]: 0.08 to 0.83, p=0.02) and ferritin levels (MD: 37.32 ng/mL, 95% CI: 18.98 to 55.65, p<0.01) compared to IS. FCM was associated with a higher risk of hypersensitivity reactions compared to IS (relative risk [RR]: 2.97, 95% CI: 1.35 to 6.52, p<0.01) but showed no significant difference in severe adverse events (RR: 1.03, 95% CI: 0.88 to 1.21, p=0.70) and had a non-significant increased risk of hypophosphatemia (RR: 2.84, 95% CI: 0.89 to 9.06, p=0.08).
Conclusion: Ten studies showed some concerns of risk of bias (RoB) and four studies had a high RoB for the change in Hb levels during follow-up. The lack of standardized definitions for hypersensitivity reactions and variability in dosing protocols and follow-up durations across studies may affect the generalizability of our safety findings.

This study evaluated the demographic data, clinical characteristics, treatment approaches, and treatment responses of 43 patients with primary cutaneous CD30+ lymphoproliferative disorders. Lymphomatoid papulosis (LyP) was characterized by predominantly papular (94.1%) and generalized (70.6%) lesions, while primary cutaneous anaplastic large-cell lymphoma (pcALCL) presented with tumoral (77.8%) and solitary (77.8%) lesions (p<0.001). Common treatments for LyP included methotrexate (response rate: 78.5%), topical corticosteroids (response rate: 83.3%), and phototherapy (response rate: 85.8%), but relapse rates were high. In pcALCL, complete remission was achieved with all treatments, with no relapses after brentuximab vedotin (BV). Secondary malignancies were noted in 20.6% of LyP cases. Both LyP and pcALCL had a 100% 5-year disease-specific survival rate, although two LyP patients (5.9%) died of secondary malignancies. In conclusion, LyP and pcALCL are both indolent lymphomas, with LyP being more prone to relapse. BV is effective for resistant pcALCL. LyP patients need long-term monitoring due to the risk of secondary malignancies.