Advances in application of hypoxia-preconditioned mesenchymal stem cell-derived exosomes.

Mesenchymal stem cells (MSCs) primarily secrete physiologically functional exosomes via paracrine effects that act on various adjacent and distant cells, thus exerting their therapeutic effects. In recent years, hypoxic preconditioning, as a novel MSC culture mode, has emerged as a research hotspot. Many previous studies have shown the role and underlying regulatory mechanisms of hypoxic preconditioning in various diseases, which has provided sufficient reference materials for the MSC research field. Therefore, this review summarizes the progress in application of hypoxia-preconditioned MSC-derived exosomes that substantially increases and improves the biological activity of specific molecules, such as microRNA.

Integrating chemokines and machine learning algorithms for diagnosis and bleeding assessment in primary immune thrombocytopenia: A prospective cohort study.

Primary immune thrombocytopenia (ITP) is an autoimmune bleeding disorder, and chemokines have been shown to be dysregulated in autoimmune disorders. We conducted a prospective analysis to identify potential chemokines that could enhance the diagnostic accuracy and bleeding evaluation in ITP patients. In the discovery cohort, a Luminex-based assay was employed to quantify concentrations of plasma multiple chemokines. These levels were subjected to comparative analysis using a cohort of 60 ITP patients and 17 patients with thrombocytopenia other than ITP (non-ITP). Additionally, comparative evaluation was conducted between a subgroup of 12 ITP patients characterised by bleeding episodes (ITP-B, as defined by an ITP-2016 bleeding grade ≥2) and 33 ITP patients without bleeding episodes (ITP-NB, as defined by an ITP-2016 bleeding grade ≤1). Machine learning algorithms further identified CCL20, interleukin-2, CCL26, CCL25, and CXCL1 as promising indicators for accurate diagnosis of ITP and CCL21, CXCL8, CXCL10, CCL8, CCL3, and CCL15 as biomarkers for assessing bleeding risk in ITP patients. The results were confirmed using enzyme-linked immunosorbent assays in a validation cohort (43 ITP patients and 19 non-ITP patients). Overall, the findings suggest that specific chemokines show promise as potential biomarkers for diagnosis and bleeding evaluation in ITP patients.

Targeted Delivery of Nanoparticles to Blood Vessels for the Treatment of Atherosclerosis.

Atherosclerosis is a common form of cardiovascular disease, which is one of the most prevalent causes of death worldwide, particularly among older individuals. Surgery is the mainstay of treatment for severe stenotic lesions, though the rate of restenosis remains relatively high. Current medication therapy for atherosclerosis has limited efficacy in reversing the formation of atherosclerotic plaques. The search for new drug treatment options is imminent. Some potent medications have shown surprising therapeutic benefits in inhibiting inflammation and endothelial proliferation in plaques. Unfortunately, their use is restricted due to notable dose-dependent systemic side effects or degradation. Nevertheless, with advances in nanotechnology, an increasing number of nano-related medical applications are emerging, such as nano-drug delivery, nano-imaging, nanorobots, and so forth, which allow for restrictions on the use of novel atherosclerotic drugs to be lifted. This paper reviews new perspectives on the targeted delivery of nanoparticles to blood vessels for the treatment of atherosclerosis in both systemic and local drug delivery. In systemic drug delivery, nanoparticles inhibit drug degradation and reduce systemic toxicity through passive and active pathways. To further enhance the precise release of drugs, the localized delivery of nanoparticles can also be accomplished through blood vessel wall injection or using endovascular interventional devices coated with nanoparticles. Overall, nanotechnology holds boundless potential for the diagnosis and treatment of atherosclerotic diseases in the future.

Surgical removal of an inferior vena cava filter in the duodenum: A rare case report and literature review.

Background: Inferior vena cava filters are typically retrieved using endovascular procedures. However, in cases where complications related to the filter arise or when endovascular retrieval becomes challenging, open surgery could be considered. Case presentation: A 65-year-old woman underwent inferior vena cava filter placement surgery for progressive venous thrombosis embolism (VTE). Following an unsuccessful endovascular retrieval attempt at an external hospital two months later, she experienced abdominal pain and was transferred to our facility for further treatment. Examination revealed that she was encountered a complication where the inferior vena cava filter penetrated both the vena cava and the duodenum post-implantation. But fortunately, the patient's blood test results were within normal range. Ultimately, our institution successfully removed the filter through open surgery and the patient was discharged without any complications. Conclusions: This case, along with our literature review, illustrates the viability and safety of duodenal-penetrated filter removal via open surgery, resulting in favorable outcomes and a promising prognosis for the patient.

Multi-omics differences in the bone marrow between essential thrombocythemia and prefibrotic primary myelofibrosis.

Essential thrombocythemia (ET) and prefibrotic primary myelofibrosis (pre-PMF) are Philadelphia chromosome-negative myeloproliferative neoplasms. These conditions share overlapping clinical presentations; however, their prognoses differ significantly. Current morphological diagnostic methods lack reliability in subtype differentiation, underlining the need for improved diagnostics. The aim of this study was to investigate the multi-omics alterations in bone marrow biopsies of patients with ET and pre-PMF to improve our understanding of the nuanced diagnostic characteristics of both diseases. We performed proteomic analysis with 4D direct data-independent acquisition and microbiome analysis with 2bRAD-M sequencing technology to identify differential protein and microbe levels between untreated patients with ET and pre-PMF. Laboratory and multi-omics differences were observed between ET and pre-PMF, encompassing diverse pathways, such as lipid metabolism and immune response. The pre-PMF group showed an increased neutrophil-to-lymphocyte ratio and decreased high-density lipoprotein and cholesterol levels. Protein analysis revealed significantly higher CXCR2, CXCR4, and MX1 levels in pre-PMF, while APOC3, APOA4, FABP4, C5, and CFB levels were elevated in ET, with diagnostic accuracy indicated by AUC values ranging from 0.786 to 0.881. Microbiome assessment identified increased levels of Mycobacterium, Xanthobacter, and L1I39 in pre-PMF, whereas Sphingomonas, Brevibacillus, and Pseudomonas_E were significantly decreased, with AUCs for these genera ranging from 0.833 to 0.929. Our study provides preliminary insights into the proteomic and microbiome variations in the bone marrow of patients with ET and pre-PMF, identifying specific proteins and bacterial genera that warrant further investigation as potential diagnostic indicators. These observations contribute to our evolving understanding of the multi-omics variations and possible mechanisms underlying ET and pre-PMF.

Corilagin relieves atherosclerosis via the toll-like receptor 4 signaling pathway in vascular smooth muscle cells.

INTRODUCTION: Corilagin possesses a diverse range of pharmacologic bioactivities. However, the specific protective effects and mechanisms of action of corilagin in the context of atherosclerosis remain unclear. In this study, we investigated the impact of corilagin on the toll-like receptor (TLR)4 signaling pathway in a mouse vascular smooth muscle cell line (MOVAS) stimulated by oxidized low-density lipoprotein (ox-LDL). Additionally, we examined the effects of corilagin in Sprague-Dawley rats experiencing atherosclerosis. METHODS: The cytotoxicity of corilagin was assessed using the CCK8 assay. MOVAS cells, pre-incubated with ox-LDL, underwent treatment with varying concentrations of corilagin. TLR4 expression was modulated by either downregulation through small interfering (si)RNA or upregulation via lentivirus transfection. Molecular expression within the TLR4 signaling pathway was analyzed using real-time polymerase chain reaction (PCR) and Western blotting. The proliferation capacity of MOVAS cells was determined through cell counting. In a rat model, atherosclerosis was induced in femoral arteries using an improved guidewire injury method, and TLR4 expression in plaque areas was assessed using immunofluorescence. Pathological changes were examined through hematoxylin and eosin staining, as well as Oil-Red-O staining. RESULTS: Corilagin demonstrated inhibitory effects on the TLR4 signaling pathway in MOVAS cells pre-stimulated with ox-LDL, consequently impeding the proliferative impact of ox-LDL. The modulation of TLR4 expression, either through downregulation or upregulation, similarly influenced the expression of downstream molecules. In an in vivo context, corilagin exhibited the ability to suppress TLR4 and MyD88 expression in the plaque lesion areas of rat femoral arteries, thereby alleviating the formation of atherosclerotic plaques. CONCLUSION: Corilagin can inhibit the TLR4 signaling pathway in VSMCs, possibly by downregulating TLR4 expression and, consequently, relieving atherosclerosis.

Improvement in Measures of Quality of Life and Symptoms of Anxiety and Depression in Patients with Severe Alopecia Areata Achieving Sustained Scalp Hair Regrowth with Baricitinib.

INTRODUCTION: Alopecia areata (AA) is an autoimmune disease associated with high rates of emotional and psychosocial distress. The analysis reported here describes the evolution of measures assessing health-related quality of life (HRQoL) and symptoms of anxiety and depression up to week 104 in patients who achieved sustained scalp hair regrowth during treatment with baricitinib in the BRAVE-AA phase III trials. METHODS: This post-hoc analysis included data from the double-blind, parallel-group, randomized, placebo-controlled phase III trials BRAVE-AA1 (ClinicalTrials.gov number: NCT03570749) and BRAVE-AA2 (ClinicalTrials.gov number: NCT03899259). Adults with severe AA (defined as a Severity of Alopecia Tool [SALT] score ≥ 50) randomized to baricitinib 4 mg or baricitinib 2 mg at baseline who achieved SALT score ≤ 20 by week 36 and maintained SALT score ≤ 20 through week 104 on the same dose of baricitinib were included in this analysis of integrated data. Scalp hair regrowth (SALT score) and improvements in Skindex-16 AA Scale and Hospital Anxiety and Depression Scale (HADS) domain scores were analyzed over the 104-week period using descriptive statistics. RESULTS: In total, 131 patients (88 on baricitinib 4 mg and 43 on baricitinib 2 mg) were included in this analysis. Across the two groups, the mean age (standard deviation) was 37.2 years (12.7), and 84 (64.1%) patients were female. The interquartile range) for time to achieve a SALT score ≤ 20 for patients treated with baricitinib 4 mg and baricitinib 2 mg was 13.1 and 19.6 weeks, respectively. By week 104, 91% (baricitinib 2 mg) and 96% (baricitinib 4 mg) of patients had achieved a SALT score ≤ 10 on baricitinib treatment. In both groups, progressive improvements in the Skindex-16 AA and HADS domain scores were observed up to week 104. CONCLUSION: This analysis of adults with severe AA treated with baricitinib revealed that achievement of sustained clinically meaningful scalp hair regrowth (SALT score ≤ 20) was associated with improvements in both measures of HRQoL and symptoms of anxiety and depression up to week 104.

Detection of Intrinsically Disordered Peptides by Biological Nanopore.

Intrinsically disordered protein regions (IDPRs) are pivotal in regulation of transcription and facilitation of signal transduction. Because of their multiple conformational states of structure, characterizing the highly flexible structures of IDPRs becomes challenging. Herein, we employed the wild-type (WT) aerolysin nanopore as a real-time biosensor for identification and monitoring of long peptides containing IDPRs. This sensor successfully identified three intrinsically disordered peptides, with the lengths up to 43 amino acids, by distinguishing the unique signatures of blockade current and duration time. The analysis of the binding constant revealed that interactions between the nanopore and peptides are critical for peptide translocation, which suggests that mechanisms beyond mere volume exclusion. Furthermore, we were able to compare the conformational stabilities of various IDPRs by examining the detailed current traces of blockade events. Our approach can detect the conformational changes of IDPR in a confined nanopore space. These insights broaden the understanding of peptide structural changes. The nanopore biosensor showed the potential to study the conformations change of IDPRs, IDPRs transmembrane interactions, and protein drug discovery.

A Novel Anti-CD38 Monoclonal Antibody for Treating Immune Thrombocytopenia.

BACKGROUND: Immune thrombocytopenia (ITP) is an autoimmune disease characterized by autoantibody-mediated platelet destruction. Treatment with CM313, a novel anti-CD38 monoclonal antibody, can result in targeted clearance of CD38-positive cells, including plasma cells. METHODS: We conducted a phase 1-2, open-label study to evaluate the safety and efficacy of CM313 in adult patients with ITP. CM313 was administered intravenously at a dose of 16 mg per kilogram of body weight every week for 8 weeks, followed by a 16-week follow-up period. The primary outcomes were adverse events and documentation of two or more consecutive platelet counts of at least 50×109 per liter within 8 weeks after the first dose of CM313. The status of peripheral-blood immune cells in patients and changes in the mononuclear phagocytic system in passive mouse models of ITP receiving anti-CD38 therapy were monitored. RESULTS: Of the 22 patients included in the study, 21 (95%) had two consecutive platelet counts of at least 50×109 per liter during the treatment period, with a median cumulative response duration of 23 weeks (interquartile range, 17 to 24). The median time to the first platelet count of at least 50×109 per liter was 1 week (range, 1 to 3). The most common adverse events that occurred during the study were infusion-related reaction (in 32% of the patients) and upper respiratory tract infection (in 32%). After CD38-targeted therapy, the percentage of CD56dimCD16+ natural killer cells, the expression of CD32b on monocytes in peripheral blood, and the number of macrophages in the spleen of the passive mouse models of ITP all decreased. CONCLUSIONS: In this study, anti-CD38 targeted therapy rapidly boosted platelet levels by inhibiting antibody-dependent cell-mediated cytotoxicity on platelets, maintained long-term efficacy by clearing plasma cells, and was associated with mainly low-grade toxic effects. (Funded by the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences and others; ClinicalTrials.gov number, NCT05694767).

Suppressed thermal transport in silicon nanoribbons by inhomogeneous strain.

Nanoscale structures can produce extreme strain that enables unprecedented material properties, such as tailored electronic bandgap1-5, elevated superconducting temperature6,7 and enhanced electrocatalytic activity8,9. While uniform strains are known to elicit limited effects on heat flow10-15, the impact of inhomogeneous strains has remained elusive owing to the coexistence of interfaces16-20 and defects21-23. Here we address this gap by introducing inhomogeneous strain through bending individual silicon nanoribbons on a custom-fabricated microdevice and measuring its effect on thermal transport while characterizing the strain-dependent vibrational spectra with sub-nanometre resolution. Our results show that a strain gradient of 0.112% per nanometre could lead to a drastic thermal conductivity reduction of 34 ± 5%, in clear contrast to the nearly constant values measured under uniform strains10,12,14,15. We further map the local lattice vibrational spectra using electron energy-loss spectroscopy, which reveals phonon peak shifts of several millielectron-volts along the strain gradient. This unique phonon spectra broadening effect intensifies phonon scattering and substantially impedes thermal transport, as evidenced by first-principles calculations. Our work uncovers a crucial piece of the long-standing puzzle of lattice dynamics under inhomogeneous strain, which is absent under uniform strain and eludes conventional understanding.

Single-Digit Nanobubble Sensing via Nanopore Technology.

Nanobubbles play an important role in diverse fields, including engineering, medicine, and agriculture. Understanding the characteristics of individual nanobubbles is essential for comprehending fluid dynamics behaviors and advancing nanoscale science across various fields. Here, we report a strategy based on nanopore sensors for characterizing single-digit nanobubbles. We investigated the sizes and diffusion coefficients of nanobubbles at different voltages. Additionally, the finite element simulation and molecular dynamics simulation were introduced to account for counterion concentration variation around nanobubbles in the nanopore. In particular, the differences in stability and surface charge density of nanobubbles under various solution environments have been studied by the ion-stabilized model and the DLVO theory. Additionally, a straightforward method to mitigate nanobubble generation in the bulk for reducing current noise in nanopore sensing was suggested. The results hold significant implications for enhancing the understanding of individual nanobubble characterizations, especially in the nanofluid field.

Geometrically Scalable Iontronic Memristors: Employing Bipolar Polyelectrolyte Gels for Neuromorphic Systems.

Iontronics that are capable of mimicking the functionality of biological systems within an artificial fluidic network have long been pursued for biomedical applications and ion-based intelligence systems. Here, we report on facile and robust realization of iontronic bipolar memristors featuring a three-layer polyelectrolyte gel structure. Significant memristive hysteresis of ion currents was successfully accomplished, and the memory time proved geometrically scalable from 200 to 4000 s. These characteristics were enabled by the ion concentration polarization-induced rectification ratio within the polyelectrolyte gels. The memristors exhibited memory dynamics akin to those observed in unipolar devices, while the bipolar structure notably enabled prolonged memory time and enhanced the ion conductance switching ratio with mesoscale (10-1000 µm) geometry precision. These properties endow the devices with the capability of effective neuromorphic processing with pulse-based input voltage signals. Owing to their simple fabrication process and superior memristive performance, the presented iontronic bipolar memristors are versatile and can be easily integrated into small-scale iontronic circuits, thereby facilitating advanced neuromorphic computing functionalities.

Baricitinib Improvement Across Regions in Atopic Dermatitis Patients with Baseline Body Surface Area up to 40% and Severe Itch.

INTRODUCTION: Patients with moderate-to-severe atopic dermatitis (AD) who are most likely to respond to the Janus kinase (JAK) 1/2 inhibitor baricitinib (BARI) are known to have an impacted body surface area (BSA) ≤ 40% and severe itch (numerical rating scale [NRS] ≥ 7], collectively termed 'BARI itch-dominant' patients. Our objective is to build on our previous work by providing a body region-specific, clinical characterization of the BARI itch-dominant patient at baseline and their response to BARI 4 mg. METHODS: BREEZE-AD7 was a phase 3 trial in adults with moderate-to-severe AD receiving placebo or 2 mg or 4 mg BARI in combination with topical corticosteroids. Assessing only data from BARI itch-dominant patients, we summarized the baseline characteristics and conducted body region-specific analyses on Eczema Area and Severity Index (EASI) data in order to report the response to placebo versus BARI 4 mg within this patient subtype. RESULTS: BARI 4 mg was highly effective across all body regions; at week 16, 75% improvement was seen in EASI scores (EASI75), and response rates with BARI 4 mg (head/neck, 58.3%; trunk, 69.2%; upper extremities, 61.5%; lower extremities, 87.5%) all exceeded those with placebo (head/neck: 37.5%; trunk, 40.6%; upper extremities, 18.8%; lower extremities, 40.6%) as well as the overall EASI75 rates of the intent-to-treat (ITT) population (BARI, 48.0%; placebo, 23.0%). At baseline, most BARI itch-dominant patients presented with involvement of all regions (mean regional BSA 22.7%-40.3%), highest in the head and neck, mean EASI region scores of 15.7-24.0, and considerably severe sign ratings (mean EASI sub-scores: 1.4-2.3, out of 3), especially for erythema. CONCLUSION: BARI itch-dominant patients exhibit AD involvement across all body regions and considerable sign severity, especially erythema. In response to BARI 4 mg, EASI quickly improved across regions, substantially more so in this subtype than in the ITT population.

Corilagin alleviates atherosclerosis by inhibiting NLRP3 inflammasome activation via the Olfr2 signaling pathway in vitro and in vivo.

Introduction: Atherosclerosis, a leading cause of global cardiovascular mortality, is characterized by chronic inflammation. Central to this process is the NOD-like receptor pyrin domain containing 3 (NLRP3) inflammasome, which significantly influences atherosclerotic progression. Recent research has identified that the olfactory receptor 2 (Olfr2) in vascular macrophages is instrumental in driving atherosclerosis through NLRP3- dependent IL-1 production. Methods: To investigate the effects of Corilagin, noted for its anti-inflammatory attributes, on atherosclerotic development and the Olfr2 signaling pathway, our study employed an atherosclerosis model in ApoE-/- mice, fed a high-fat, high-cholesterol diet, alongside cellular models in Ana-1 cells and mouse bone marrow-derived macrophages, stimulated with lipopolysaccharides and oxidized low-density lipoprotein. Results: The vivo and vitro experiments indicated that Corilagin could effectively reduce serum lipid levels, alleviate aortic pathological changes, and decrease intimal lipid deposition. Additionally, as results showed, Corilagin was able to cut down expressions of molecules associated with the Olfr2 signaling pathway. Discussion: Our findings indicated that Corilagin effectively inhibited NLRP3 inflammasome activation, consequently diminishing inflammation, macrophage polarization, and pyroptosis in the mouse aorta and cellular models via the Olfr2 pathway. This suggests a novel therapeutic mechanism of Corilagin in the treatment of atherosclerosis.

Efficacy and safety of human umbilical cord-derived mesenchymal stem cells in the treatment of refractory immune thrombocytopenia: a prospective, single arm, phase I trial.

Patients with refractory immune thrombocytopenia (ITP) frequently encounter substantial bleeding risks and demonstrate limited responsiveness to existing therapies. Umbilical cord-derived mesenchymal stem cells (UC-MSCs) present a promising alternative, capitalizing on their low immunogenicity and potent immunomodulatory effects for treating diverse autoimmune disorders. This prospective phase I trial enrolled eighteen eligible patients to explore the safety and efficacy of UC-MSCs in treating refractory ITP. The research design included administering UC-MSCs at escalating doses of 0.5 × 106 cells/kg, 1.0 × 106 cells/kg, and 2.0 × 106 cells/kg weekly for four consecutive weeks across three cohorts during the dose-escalation phase, followed by a dose of 2.0 × 106 cells/kg weekly for the dose-expansion phase. Adverse events, platelet counts, and changes in peripheral blood immunity were monitored and recorded throughout the administration and follow-up period. Ultimately, 12 (with an addition of three patients in the 2.0 × 106 cells/kg group due to dose-limiting toxicity) and six patients were enrolled in the dose-escalation and dose-expansion phase, respectively. Thirteen patients (13/18, 72.2%) experienced one or more treatment emergent adverse events. Serious adverse events occurred in four patients (4/18, 22.2%), including gastrointestinal hemorrhage (2/4), profuse menstruation (1/4), and acute myocardial infarction (1/4). The response rates were 41.7% in the dose-escalation phase (5/12, two received 1.0 × 106 cells/kg per week, and three received 2.0 × 106 cells/kg per week) and 50.0% (3/6) in the dose-expansion phase. The overall response rate was 44.4% (8/18) among all enrolled patients. To sum up, UC-MSCs are effective and well tolerated in treating refractory ITP (ClinicalTrials.gov ID: NCT04014166).

Metabolomics profile and machine learning prediction of treatment responses in immune thrombocytopenia: A prospective cohort study.

Immune thrombocytopenia (ITP) is an autoimmune disease characterized by antibody-mediated platelet destruction and impaired platelet production. The mechanisms underlying ITP and biomarkers predicting the response of drug treatments are elusive. We performed a metabolomic profiling of bone marrow biopsy samples collected from ITP patients admission in a prospective study of the National Longitudinal Cohort of Hematological Diseases. Machine learning algorithms were conducted to discover novel biomarkers to predict ITP patient treatment responses. From the bone marrow biopsies of 91 ITP patients, we quantified a total of 4494 metabolites, including 1456 metabolites in the positive mode and 3038 metabolites in the negative mode. Metabolic patterns varied significantly between groups of newly diagnosed and chronic ITP, with a total of 876 differential metabolites involved in 181 unique metabolic pathways. Enrichment factors and p-values revealed the top metabolically enriched pathways to be sphingolipid metabolism, the sphingolipid signalling pathway, ubiquinone and other terpenoid-quinone biosynthesis, thiamine metabolism, tryptophan metabolism and cofactors biosynthesis, the phospholipase D signalling pathway and the phosphatidylinositol signalling system. Based on patient responses to five treatment options, we screened several metabolites using the Boruta algorithm and ranked their importance using the random forest algorithm. Lipids and their metabolism, including long-chain fatty acids, oxidized lipids, glycerophospholipids, phosphatidylcholine and phosphatidylethanolamine biosynthesis, helped differentiate drug treatment responses. In conclusion, this study revealed metabolic alterations associated with ITP in bone marrow supernatants and a potential biomarker predicting the response to ITP.

Proteomics landscape and machine learning prediction of long-term response to splenectomy in primary immune thrombocytopenia.

This study aimed to identify key proteomic analytes correlated with response to splenectomy in primary immune thrombocytopenia (ITP). Thirty-four patients were retrospectively collected in the training cohort and 26 were prospectively enrolled as validation cohort. Bone marrow biopsy samples of all participants were collected prior to the splenectomy. A total of 12 modules of proteins were identified by weighted gene co-expression network analysis (WGCNA) method in the developed cohort. The tan module positively correlated with megakaryocyte counts before splenectomy (r = 0.38, p = 0.027), and time to peak platelet level after splenectomy (r = 0.47, p = 0.005). The blue module significantly correlated with response to splenectomy (r = 0.37, p = 0.0031). KEGG pathways analysis found that the PI3K-Akt signalling pathway was predominantly enriched in the tan module, while ribosomal and spliceosome pathways were enriched in the blue module. Machine learning algorithm identified the optimal combination of biomarkers from the blue module in the training cohort, and importantly, cofilin-1 (CFL1) was independently confirmed in the validation cohort. The C-index of CFL1 was >0.7 in both cohorts. Our results highlight the use of bone marrow proteomics analysis for deriving key analytes that predict the response to splenectomy, warranting further exploration of plasma proteomics in this patient population.