Objective: The effects and molecular mechanisms of micheliolide on cytokine expression in myeloproliferative neoplasm cell lines were explored based on the signal transducer and activator of transcription 3 (STAT3)/nuclear factor-kappa B (NF-κB) signaling pathways. Methods: The UKE-1 and SET-2 cell lines were investigated, and micheliolide concentrations were screened using the CCK-8 assay. The UKE-1 and SET-2 cells were divided into the control and micheliolide-treated groups at concentrations of 2.5, 5.0, and 10.0 μmol/L. Each group received 1 mL of micheliolide solution at final concentrations of 2.5, 5.0, and 10.0 μmol/L, respectively, whereas the control group only received an equal volume of culture medium. The inhibition rates of interleukin-1β(IL-1β), tumor necrosis factor-α (TNF-α), and chemokine ligand 2 (CCL2) mRNA expression in cells from each group were detected using real-time fluorescent PCR (RT-PCR). Western blotting was used to measure STAT3 and phosphorylated STAT3 (p-STAT3) protein expression levels in cells from each group. Reversal experiments with reduced glutathione and dithiothreitol were performed using UKE-1 cells, which were divided into the control group, micheliolide, micheliolide + glutathione, micheliolide + dithiothreitol, and glutathione + dithiothreitol groups. Western blotting was used to detect the STAT3 and p-STAT3 protein expression levels in the cells of each group. UKE-1 cells were stimulated with TNF-α (5 μg/L) to replicate a pathological model of excessive cytokine secretion. Subsequently, UKE-1 cells were divided into the control, model, and three micheliolide-treated groups at concentrations of 2.5, 5.0, and 10.0 μmol/L. RT-PCR was used to measure the indicators above. An enzyme-linked immunosorbent assay (ELISA) was used to detect the CCL2 content in the cell culture media of each group. Western blotting was performed to assess the protein expression levels of STAT3, p-STAT3, and proteins related to the NF-κB signaling pathway. Results: Compared with the control group, the proliferation inhibition rates of UKE-1 cells at 24, 48, and 72 h increased in the micheliolide-treated groups at concentrations of 2.5, 5.0, 10.0, and 20.0 μmol/L. Similarly, the proliferation inhibition rates of SET-2 at 48 and 72 h increased in the micheliolide-treated groups at concentrations of 5.0, 10.0, and 20.0 μmol/L (P<0.05). Concentrations of 2.5, 5.0, and 10.0 μmol/L were selected for further studies to exclude the potential influence of high micheliolide concentrations on subsequent result owing to reduced cell numbers. Compared with the control group, the inhibition rates of TNF-α mRNA expression in UKE-1 and SET-2 cells increased in the micheliolide-treated groups at concentrations of 2.5, 5.0, and 10.0 μmol/L. Similarly, the inhibition rates of IL-1β mRNA expression in UKE-1 and SET-2 cells also increased in the micheliolide-treated groups at concentrations of 5.0 and 10.0 μmol/L. Additionally, the inhibition rate of CCL2 mRNA expression in UKE-1 and SET-2 cells increased in the micheliolide-treated group at a concentration of 10 μmol/L (P<0.05). Compared with the model group, the inhibition rates of TNF-α, IL-1β, and CCL2 mRNA expression in UKE-1 cells increased in the micheliolide-treated groups at concentrations of 2.5, 5.0, and 10.0 μmol/L after stimulation with TNF-α (P<0.05). ELISA showed that compared with the control group, the CCL2 content in UKE-1 cells increased in the model group. Compared with the model group, the CCL2 content in UKE-1 cells decreased in the micheliolide-treated groups at concentrations of 2.5, 5.0, and 10.0 μmol/L (P<0.05). Western blotting showed that compared with the control group, the p-STAT3 protein expression levels in UKE-1 and SET-2 cells were downregulated in the micheliolide-treated groups at concentrations of 5.0 and 10.0 μmol/L, and the protein expression level of STAT3 in SET-2 was also downregulated (P<0.05). Compared with the control group, the p-STAT3 expression level in UKE-1 cells decreased in the micheliolide group in the reductive glutathione and dithiothreitol reversal experiments. Compared with the micheliolide group, the p-STAT3 protein expression levels in UKE-1 cells increased in the micheliolide + dithiothreitol and micheliolide + glutathione groups (P<0.05). Compared with the control group, the model group showed increased p-STAT3, p-IκKα/β, p-IκBα, and p-NF-κB p65 protein expression and decreased IκBα protein expression after stimulation with TNF-α. Compared with the model group, the micheliolide-treated groups showed decreased p-IκKα/β, p-IκBα, p-STAT3, and p-NF-κB p65 protein expression at concentrations of 2.5, 5.0, and 10.0 μmol/L, whereas the micheliolide-treated groups showed increased IκBα protein expression at concentrations of 5.0 and 10.0 μmol/L (P<0.05). Conclusion Micheliolide potently suppresses IL-1β, TNF-α, and CCL2 mRNA expression in UKE-1 and SET-2 cells, as well as CCL2 secretion by UKE-1 cells, which may be associated with STAT3 phosphorylation suppression and NF-κB signaling pathway activation.

The level of urinary albumin is a critical indicator for the early diagnosis and management of chronic kidney disease (CKD). However, existing methods for detecting albumin are not conducive to point-of-care testing due to the complexity of reagent addition and incubation processes. This study presents a smartphone-integrated handheld automated biochemical analyzer (sHABA) designed for point-of-care testing of urinary albumin. The sHABA features a pre-loaded, disposable reagent cassette with reagents for the albumin assay arranged in the order of their addition within a hose. The smartphone-integrated analyzer can drive the reagents following a preset program, to enable automatic sequential addition. The sHABA has a detection limit for albumin of 5.9 mg/L and a linear detection range from 7 to 450 mg/L. The consistency of albumin level detection in 931 urine samples using sHABA with clinical tests indicates good sensitivity (95.78%) and specificity (90.16%). This research advances the field by providing an automated detection method for albumin in a portable device, allowing even untrained individuals to monitor CKD in real time at the patient's bedside. In the context of promoting tiered diagnosis and treatment, the sHABA has the potential to become an essential tool for the early diagnosis and comprehensive management of CKD and other chronic conditions.

Objective To analyze the risk factors and effective predictive indicators for postpartum hemor-rhage(PPH)in pregnant women with severe pre-eclampsia(sPE)in singleton pregnancies.The findings will serve as a valuable reference for the clinical prevention and management of PPH in these patients.Methods A retrospective analysis was conducted on 932 pregnant women with sPE at two tertiary hospitals in Guangzhou from January 1,2016,to December 31,2022.Among these,95 cases were complicated by PPH.A comparative analysis was performed between the sPE group and the sPE with PPH group.Results(1)The incidence of assisted reproductive technology,intrapartum blood loss,placental abruption,elevated D-dimer levels,increased monocyte counts,and higher SIRI levels were significantly higher in the PPH group,whereas platelet counts were significantly lower(P<0.05).(2)The results indicated that intrapartum blood loss,D-dimer levels,and platelet counts were inde-pendently associated with PPH in pregnant women with sPE.(3)The area under the curve(AUC)for intrapartum blood loss,D-dimer,and platelet counts were 0.805,0.717,and 0.571,respectively.The optimal cutoff value for D-dimer was determined to be 2.295 μg/mL.The combined AUC for intrapartum blood loss and D-dimer was 0.859.(4)Intrapartum blood loss values were significantly higher in the PPH group for both vaginal delivery and cesarean section(P<0.001).The corresponding optimal cutoff values were 285 mL and 375 mL,respectively.Conclusions Intrapartum haemorrhage,D-dimer levels,and platelet count were identified as independent risk factors for PPH in pregnant women with sPE.Specifically,pregnant women with sPE who experienced blood loss exceeding 285 mL during vaginal delivery or 375 mL during caesarean section,along with a D-dimer level greater than 2.295 μg/mL,demonstrated an increased likelihood of developing PPH.Therefore,it is crucial to enhance clinical monitoring of these relevant indicators in high-risk populations.

Clonal hematopoiesis of indeterminate potential (CHIP) and clonal cytopenias of undetermined significance (CCUS) are included in both fifth edition of the World Health Organization classification (WHO 2022) and International Consensus Classification (ICC). Recently three models were developed for prediction of myeloid neoplasms risk and clinical trials are initiated to investigate potential treatments for CHIP and CCUS. Challenges in diagnosis and therapeutic intervention of CHIP and CCUS were discussed.

Systemic mastocytosis (SM) with an associated myelodysplastic/myeloproliferative neoplasm (MDS/MPN) is a rare subtype of myeloid neoplasms. Avapritinib, a potent and selective inhibitor of KIT D816V, is approved for treating advanced systemic mastocytosis (AdvSM). We report a case of a patient with SM and an associated MDS/MPN treated with avapritinib. The patient achieved sustained complete remission (CR) of SM, with persistent molecular negativity for the KIT D816V mutation, but ultimately succumbed to disease progression to chronic myelomonocytic leukemia (CMML). Although avapritinib, a novel targeted therapy, has significantly improved outcomes for SM, the efficacy of treatment for the associated hematologic neoplasm in patients with SM-AHN may be the primary determinant of long-term overall survival and progression-free survival. This report includes a review of relevant literature to provide insights into the clinical diagnosis and management of this rare entity.

To enhance the understanding of familial erythrocytosis type 2 (ECYT2) resulting from compound heterozygous mutations in the VHL gene.Methods:We conducted a retrospective analysis of the case data from a patient with ECYT2 to investigate its pathogenesis, clinical features, diagnosis and treatment options, as well as prognosis, while also reviewing the relevant literature.Results:A 31-year-old man was admitted to the hospital due to facial and hand flushing that had persisted for 29 years. Whole exome sequencing revealed compound heterozygous mutations in VHL p.P81L and p.N90T. Both of his parents were found to carry only one of these heterozygous mutations, yet they exhibited normal phenotypes. Based on the patient's hematological tests, a clear diagnosis of ECYT2 was established. Following treatment with erythrocytapheresis and daily administration of aspirin at a dosage of 100 mg, the patient experienced relief from dizziness and headaches associated with blood hyperviscosity, without any thrombotic or bleeding complications during this period.Conclusions:ECYT2 is a rare group of autosomal recessive genetic disorders. This case of ECYT2, resulting from compound heterozygous mutations in the VHL gene, represents the first report in China. Clinically, it is characterized by elevated red cell mass, normal or increased serum erythropoietin levels, and normal hemoglobin oxygen affinity levels. These factors contribute to thrombotic and bleeding complications that can lead to early mortality.

Objective:To compare the clinical and laboratory characteristics and survival between Chinese and Western patients with myelodysplastic neoplasms (MDS) .Methods:Clinical and laboratory data were collected from 1,464 primary adult patients diagnosed with MDS at the Institute of Hematology & Blood Diseases Hospital from August 2016 to June 2024. Collected data were retrospectively analyzed and compared with 2,191 patients from the International Working Group for the Prognosis of Myelodysplastic Syndromes (IWG-PM) .Results:Chinese patients were significantly younger (median age: 56 years vs. 72 years, P<0.001) and experienced more severe hematopenia ( P<0.001) compared with patients from the IWG-PM. Further, Chinese patients exhibited a higher percentage of isolated del (20q), +8, and complex karyotypes as well as a lower percentage of normal karyotypes, del (5q), and -Y ( P<0.001). Higher U2AF1, NRAS, and NPM1 mutation rates and lower ASXL1, SF3B1, and RUNX1 mutation rates were observed in Chinese patients than in participants from the IWG-PM ( P<0.05). No significant difference in overall survival (OS) was found between the two groups (median OS: 48 [95% CI: 40 - 56]months, vs. 45[95% CI: 40 - 49] months; P=0.449). Among participants aged ≤45 years, Chinese patients demonstrated more trisomy 8 ( P=0.070) and U2AF1 mutation ( P<0.001) and higher 4-year OS rate compared with those from the IWG-PM (75.5% vs. 62.1%, P=0.001). Among participants aged ≥70 years, Chinese patients exhibited more complex karyotypes but fewer del (5q) as well as more NPM1 but less SF3B1 and TET2 compared with those from the IWG-PM ( P<0.05). Chinese patients demonstrated shorter survival (median OS: 20 [95% CI: 13 - 27] months vs. 37 [95% CI: 32 - 42] months, P<0.001) . Conclusion:Chinese and Western MDS patients differ in age of onset, clinical features, and cytogenetic or molecular genetic abnormalities, with significant differences persisting in age-matched groups. Although the OS is similar, disparities exist in survival for younger and older patients between the two populations.

Objective:To investigate the association between pre- and post-treatment gene mutation profiles and clinical outcomes (treatment response and prognosis) in patients with myelodysplastic syndromes with excess blasts (MDS-EB) receiving hypomethylating agent (HMA) monotherapy.Methods:The clinical characteristics, treatment efficacy, and survival outcomes of 69 treatment-naive patients with MDS-EB who underwent next-generation sequencing (NGS) before treatment and completed at least 4 cycles of HMA monotherapy at the Institute of Hematology & Blood Diseases Hospital, CAMS & PUMC, between June 2016 and September 2023, were retrospectively analyzed.Results:① The cohort comprised 47 males and 22 females with a median age of 62 years (range: 41-80). Thirty-nine patients were classified as MDS-EB1 and 30 as MDS-EB2. The median number of treatment cycles was 6 (range: 4-35). The median follow-up duration was 22 months (range: 5-72), and the median overall survival (OS) was 32 months (95% CI: 27-43). ② The presence of DTA (DNMT3A, TET2, or ASXL1) mutations, signaling pathway mutations, transcription factor mutations, or splicing factor mutations before HMA treatment showed no significant association with the best response within 4 treatment cycles, duration of response (DOR), or OS. TP53 mutation status was significantly associated with DOR and shorter OS. The median DOR was 3 months (95% CI: 1-10) for patients with biallelic TP53 mutations, 10 months (95% CI: 3-34) for those with monoallelic TP53 mutations, and 16 months (95% CI: 8-27) in patients without TP53 mutations ( P=0.032). The median OS was 16 months (95% CI: 7-38), 15 months (95% CI: 6-40), and 35 months (95% CI: 14-91), respectively ( P<0.001). ③ Neither the Revised International Prognostic Scoring System (IPSS-R) nor the Molecular International Prognostic Scoring System (IPSS-M) could predict the best response within 4 treatment cycles or DOR in patients receiving HMA therapy. ④ Among patients without TP53 mutations, the median OS was 55 months (95% CI: 9-106) for the major clone significant clearance group ( n=14) and 31 months (95% CI: 16-184) for the major clone non-significant clearance group ( n=10) ( P=0.013). For patients who responded to HMA treatment and had significant major clone clearance, the 3-year OS rate reached (77.8±13.9) %. Conclusion:For MDS-EB patients receiving HMA monotherapy, single gene mutations, IPSS-R, and IPSS-M could not effectively predict treatment outcomes before therapy. However, for patients without TP53 mutations, monitoring the degree of major clone clearance by NGS during treatment may predict the long-term efficacy in MDS patients receiving HMA therapy.

Objective:To analyze the clinical characteristics, therapeutic responses, and survival outcomes of patients with lymphocytic variant hypereosinophilic syndrome (L-HES) .Methods:We retrospectively reviewed clinical data from 16 consecutive patients diagnosed with L-HES at the Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences, between July 2019 and October 2024. A control group of 65 patients with idiopathic hypereosinophilic syndrome (iHES), diagnosed during the same period, was used for comparison. Clinical and laboratory characteristics, therapeutic responses, and survival outcomes were compared between the two groups.Results:The most frequently involved organs at presentation in patients with L-HES were the skin (75.0%), gastrointestinal tract (25.0%), respiratory tract (18.8%), lymph nodes (18.8%), heart (12.5%), and spleen (6.3%). Compared with iHES patients, patients with L-HES had a significantly higher incidence of skin involvement ( P=0.016), with no statistically significant differences observed in the involvement of other organs. No statistically significant differences were found in complete blood count parameters between the two groups. Multiparameter flow cytometry revealed that the median percentage of CD3 -CD4 + T cells in the peripheral blood of patients with L-HES was 4.08% ( IQR: 1.64%-32.78%), with a median absolute count of 0.10 (0.05-0.55) ×10 9/L. Serum immunoglobulin E (IgE) levels were significantly higher in the L-HES group than in the iHES group ( P<0.001). Clonal rearrangement of T-cell receptor genes was detected in 75.0% of patients with L-HES. After diagnosis, 14 patients with L-HES received glucocorticoids as first-line therapy, yielding an overall response rate of 92.9%. During glucocorticoid tapering, 11 patients experienced recurrent eosinophilia or worsening of clinical symptoms. Three patients received interferon-alpha as a second-line therapy, with two achieving complete remission. After a median follow-up of 16 months ( IQR: 8-28 months), one patient died of cardiac insufficiency 8 months after diagnosis, and no cases of lymphoma transformation were observed. The 2-year overall survival rate was (91.7±8.0) %, which did not significantly differ from that of the iHES group (96.2±2.6) % ( P=0.746) . Conclusions:Patients with L-HES generally have a favorable prognosis and are often characterized by skin involvement and significantly elevated serum IgE levels at diagnosis. They typically respond well to glucocorticoid therapy, although relapse is common during dose tapering. Interferon-alpha may serve as an effective second-line therapeutic option.

Objective:To identify the prognostic value of the Revised 15-item Myelodysplastic Syndrome-specific frailty scale (FS-15) in Chinese patients with myelodysplastic syndromes (MDS) .Methods:This retrospective study analyzed 812 patients with newly diagnosed MDS admitted to the Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences, and Peking Union Medical College from August 2016 to June 2023. Patients were assessed using the FS-15 and subsequently categorized into frail and non-frail groups. Clinical and laboratory characteristics, as well as overall survival (OS), were compared between these groups.Results:① The median patient age was 55 years ( IQR 45–64), with a median follow-up of 22.5 months (95% CI: 20.2–24.9) and a median OS of 43.3 months (95% CI: 36.8–49.8). The median FS-15 score was 0.42, with a cutoff value of 0.44. Male patients demonstrated higher median FS-15 scores than female patients (0.42 vs 0.38, P=0.006). In both the Revised International Prognostic Scoring System (IPSS-R; P=0.001) and Molecular International Prognostic Scoring System (IPSS-M; P=0.014) stratifications, FS-15 scores were significantly higher in the very high-risk group compared with the very low-risk group. ② The median OS was 54.7 months (95% CI: 47.5–NA) and 31.5 months (95% CI: 22.9–41.0) in the nonfrail ( n=452) and frail groups ( n=360), respectively ( P<0.001). The 3-year OS rates were (63.2 ± 3.2) % and (46.4 ± 3.6) % for the non-frail and frail groups, with 5-year OS rates of (49.9 ± 4.7) % and (32.0 ± 4.3) %, respectively ( P<0.001). ③Subgroup analysis revealed that nonfrail patients demonstrated significantly higher 3-year OS rates than frail patients in both the IPSS-M low-risk and very high-risk groups (all P<0.05). Similarly, nonfrail patients demonstrated superior 3-year OS rates compared with frail patients in the IPSS-R very low-risk, low-risk, and high-risk groups (all P<0.05). ④Among patients receiving hypomethylating agent therapy, the overall response rate was significantly higher in the non-frail group than in the frail group (86.7% vs 64.6%, P=0.007). Moreover, the frail group experienced higher rates of treatment-related adverse events, including febrile neutropenia (67.1% vs 47.4%, P=0.016) and liver function abnormalities (30.0% vs 14.5%, P=0.023), compared with the non-frail group. Conclusion:The FS-15 frailty score is a feasible and effective tool for assessing frailty in patients newly diagnosed with MDS in China and serves as a valuable prognostic indicator.