Objectives To determine whether icaritin (ICA) enhances imatinib (IM) activity in Philadelphia chromosome-positive B-cell acute lymphoblastic leukemia (Ph+ B-ALL) cells and the role of PI3K/AKT signaling in this process.Methods SUP-B15 and TOM-1 cells underwent 48-hour single-agent concentration-response testing and complete 7 × 7 ICA × IM matrix analysis using the zero interaction potency (ZIP) model. Apoptosis, mitochondrial membrane potential andPI3K/AKT/FOXO1 signaling were assessed. SUP-B15 rescue experiments included the PI3K-activating peptide 740Y-P alone and with ICA + IM.Results In SUP-B15 cells, the fitted IM and ICA IC50 values were 8.707 μM and 36.70 μM , respectively. ZIP scores indicated a reproducible but borderline/modest positive interaction. In TOM-1 cells, the fitted IM and ICA IC50 values were 13.32 μM and 44.31 μM , with ZIP scores consistently within the additive range. ICA + IM produced the highest mean apoptotic fraction in both models. In SUP-B15 cells, combined treatment was associated with mitochondrial depolarization, reduced PI3K/AKT/FOXO1 phosphorylation, and increased nuclear FOXO1, BIM, and p27. 740Y-P partially reversed these effects. TOM-1 reproduced several responses, although P-AKT/AKT was not further reduced relative to either monotherapy.Discussion ICA enhanced IM activity in both Ph+ B-ALL cell models, but the interaction classification was model-dependent. Partial pharmacological rescue supports PI3K/AKT involvement without establishing pathway exclusivity, a direct ICA target, or reversal of established IM resistance.Conclusion ICA enhances IM activity in the two Ph+ B-ALL cell models examined. Replicate-level ZIP analysis supports a borderline/modest positive interaction in SUP-B15 and an additive interaction in TOM-1. Further validation in resistant models, primary cells, normal hematopoietic cells, and in vivo systems is required before translational inference.
Objectives Hetrombopag is an oral nonpeptide thrombopoietin receptor agonist approved only in China. We critically appraised evidence across approved and investigational indications, compared it with other thrombopoietin receptor agonists, and assessed clinically relevant safety and risk management.Methods PubMed/MEDLINE, the Cochrane Library, ClinicalTrials.gov, CNKI, and Wanfang were searched from inception through 18 October 2026, with citation tracing and regulatory/guideline review. Evidence was ranked by design and publication status.Results A Chinese phase III adult immune thrombocytopenia trial reported week-8 platelet responses of 58.9% and 64.3% with two starting doses versus 5.9% with placebo. In refractory severe aplastic anemia, a single-arm phase II study reported week-18 hematologic response in at least one lineage of 41.8% (95% confidence interval 28.7–55.9). Randomized trials also underpin 2026 Chinese approvals for chronic immune thrombocytopenia in patients aged at least 6 years and adult solid-tumor treatment-induced thrombocytopenia; however, the pivotal phase III solid-tumor report remained a conference abstract and international validation was pending. No randomized head-to-head trial establishes superiority over eltrombopag, avatrombopag, or romiplostim. Safety data identify hepatic laboratory abnormalities, rare thrombosis and marrow fibrosis in adult immune thrombocytopenia, and clonal evolution in severe aplastic anemia.Discussion Endpoint heterogeneity, sponsor involvement, abstract-only evidence, and limited multiethnic data constrain cross-trial inference. Food markedly reduces exposure; cyclosporine interaction data are reassuring but imprecise.Conclusion Use should follow local labels and disease guidelines, target clinically meaningful outcomes rather than platelet normalization, and include indication-specific hepatic, thrombotic, marrow, and discontinuation surveillance.
Introduction Immune mediated thrombotic thrombocytopenic purpura is a life threatening autoimmune thrombotic microangiopathy caused by severe ADAMTS13 deficiency due to inhibitory autoantibodies. Despite plasma exchange, corticosteroids, rituximab, and caplacizumab, some patients develop refractory disease or persistent and relapsing ADAMTS13 deficiency.Objectives To summarize the mechanistic rationale, clinical efficacy, safety, and potential therapeutic role of daratumumab in refractory or frequently relapsing immune mediated thrombotic thrombocytopenic purpura.Methods A structured narrative review was conducted across five major bibliographic databases, PubMed, EMBASE, the Cochrane Library, China National Knowledge Infrastructure (CNKI), and Web of Science, from database inception through September 13, 2026. Searches of major hematology journal databases were also performed. Case reports, case series, registry analyses, multicenter cohort studies, and conference abstracts describing the use of daratumumab in acquired immune-mediated thrombotic thrombocytopenic purpura (iTTP) were included. Clinical setting, treatment regimen, ADAMTS13 response, time to response, relapse, and adverse events were extracted and qualitatively synthesized. Because reports differ in populations, endpoints, concomitant therapy, and possible patient overlap, findings were synthesized qualitatively without a pooled response estimate.Results Six key clinical reports involving more than 40 patients were identified. Most patients had received multiple previous therapies, including plasma exchange, corticosteroids, rituximab, and caplacizumab. Daratumumab was administered intravenously at 16 mg/kg or subcutaneously at 1,800 mg, usually weekly for two to six doses. Across the available reports, ADAMTS13 recovery was observed in a substantial proportion of treated patients, although reported response rates varied according to the populations studied and the thresholds used to define response. Recovery commonly occurred within several weeks. Multicenter reports also described sustained remission in a proportion of responders, although biochemical relapse remained frequent during follow-up. Adverse events were generally manageable, with predominantly mild infusion reactions and infrequent serious infections. Other individualized treatment strategies described after rituximab failure or intolerance include bortezomib, optimized or alternative anti-CD20 therapy, ciclosporin, azathioprine, and mycophenolate.Conclusion Daratumumab is a promising plasma cell directed therapy for rituximab refractory or frequently relapsing immune mediated thrombotic thrombocytopenic purpura. Prospective studies are required to define its role within treatment algorithms.
Objective To report a case child of Pacak-Zhuang syndrome with EPAS1 p.Pro531Leu somatic variant in a child and to summarize the clinical characteristics, diagnosis, treatment methods, and prognosis of this syndrome based on a literature review.Methods A retrospective analysis was conducted on the clinical data of a child girl with Pacak-Zhuang syndrome admitted to Hebei Children’s Hospital in July 2019. Using the search terms ‘Pacak-Zhuang syndrome’, ‘EPAS1’, ‘HIF-2α’, ‘HIF-2A’, and ‘Polycythemia-paraganglioma syndrome’, relevant literature was retrieved from PubMed and Web of Science. The clinical manifestations, diagnostic methods, treatment plans, and outcomes of patients with this syndrome were analyzed.Results A 4-year-old girl had recurrent hypertension, polycythemia and renal hilar masses. Diagnosis was confirmed by imaging, biochemical detection and paraffin tissue genetic testing. She received three operations for paragangliomas; pathology showed CgA(+), Syn(+), NSE(+) and Ki‑67 ≤5%. Follow-up revealed tumor recurrence, but the condition improved with oral temozolomide. Combined with 10 retrieved articles, 18 patients (4 males,14 females, mean age 25 years) were analyzed. Polycythemia was the cardinal manifestation. All patients received surgery, and 10 suffered uncontrolled tumor recurrence.Conclusion Pacak-Zhuang syndrome is a rare disorder involving the neuroendocrine and hematopoietic systems, often initially presenting with ‘polycythemia’. Most cases are sporadic, with no apparent familial inheritance or history of other neuroendocrine tumors. When encountering pediatric patients with unexplained hypertension accompanied by polycythemia symptoms, the possibility of this syndrome should be considered, and further imaging studies and genetic testing are required for definitive diagnosis.
Background While previous studies have reported conflicting linear or U-shaped associations between vitamin D and anemia, evidence regarding the specific dose-response relationship in middle-aged and older adults remains limited. This study aimed to identify the threshold effect of serum 25-hydroxyvitamin D [25(OH)D] on anemia risk in U.S. adults aged ≥ 45 years.Methods We conducted a cross-sectional analysis using data from the National Health and Nutrition Examination Survey (NHANES) 2007–2018. A total of 9,306 participants were included. Anemia was defined according to WHO hemoglobin thresholds. Survey-weighted multivariate logistic regression and restricted cubic spline (RCS) models, together with segmented regression, were used to assess the association and identify inflection points.Results The prevalence of anemia was 13.3%. In the fully adjusted survey-weighted model, higher serum 25(OH)D levels were independently associated with a lower risk of anemia. RCS analysis revealed a significant non-linear association (P for non-linearity < 0.001), identifying a threshold of 64.57 nmol/L (bootstrap 95% CI: 64.45–64.69). Below this threshold, each 1 nmol/L increment in serum 25(OH)D was associated with approximately 2% lower odds of anemia (OR = 0.98, 95% CI: 0.97–0.99, P < 0.001); at or above this threshold, the association plateaued, with no significant further effect on anemia risk (OR = 1.00, 95% CI: 1.00–1.01, P = 0.64).Conclusion In U.S. adults aged ≥ 45 years, the protective association between serum 25(OH)D and anemia appears to exhibit a threshold around 64.57 nmol/L, below which lower levels were associated with progressively higher anemia risk. These findings are hypothesis-generating and merit confirmation in prospective and interventional studies.
