BACKGROUND:With the continuous increase in morbidity among older adults and the rapid progression of population aging, the demand for healthcare services and older adults care services has grown rapidly. However, the traditional model characterized by the separation of healthcare and older adults care has become increasingly inadequate in meeting the diverse and expanding needs of the aging population. Therefore, promoting the coordinated development of healthcare services and older adults care services has emerged as an urgent and critical issue. METHOD:Based on panel data from 31 provinces (including municipalities and autonomous regions) in China from 2014 to 2023, this study employs the entropy method, the coupling coordination degree model, and the geographic detector model to analyze the level of coordinated development and its key influencing factors between community-level healthcare services and older adults care services at the provincial scale. Specifically, the entropy method is used to determine indicator weights, the coupling coordination degree model is applied to evaluate the coordination level, and the geographic detector model is utilized to identify the main influencing factors. RESULTS:(1)The coupling coordination level between community healthcare services and older adults care services in China shows an overall upward trend, although the growth rate is uneven, exhibiting a dynamic evolution characterized by "rapid development-gradual slowdown-bottoming out and rebound-fluctuating advancement."(2)Significant spatial disparities are observed in the coupling coordination level, gradually forming a diversified spatial pattern in which coastal regions take the lead, inland regions rise rapidly, and remote regions demonstrate substantial development potential.(3)The coupling coordination development of community healthcare services and older adults care services in China is jointly influenced by infrastructure, workforce, and service capacity. Among these factors, the number of healthcare institutions, the number of technical staff, the number of outpatient visits, the number of older adults care institutions, the number of certified social workers, and the number of community-based daytime care recipients play a dominant promoting role. CONCLUSION:Based on the findings, this study recommends implementing dynamic regulatory strategies aligned with different development stages, formulating region-specific policies that account for spatial heterogeneity, and adopting targeted interventions focusing on key influencing factors, in order to systematically promote the high-quality coordinated development of healthcare services and older adults care services in China.

Background:Relapsed and refractory multiple myeloma (RRMM) is generally associated with a poor prognosis. Objectives:This real-world study aims to evaluate the efficacy and safety of the carfilzomib-pomalidomide-dexamethasone (KPd) regimen in patients with RRMM. Design:A multicenter, retrospective study was conducted in four centers in China. Methods:RRMM patients who received at least 1 cycle of KPd across four centers were retrospectively included and stratified by prior lines of treatment, survival outcomes and safety profile were analyzed. Results:A total of 82 patients were enrolled. Based on the lines of treatment (LOT) at KPd initiation, patients were stratified into second-line (2L, n=39), third-line (3L, n=26), and fourth-line or beyond (4L+, n=17) groups. Among 72 response-evaluable patients, the overall response rate (ORR) was 69.4%, with ORRs of 79.4%, 73.9%, and 40.0% in the 2L, 3L, and 4L+ groups, respectively. After a median follow-up of 10.8 months, the median progression-free survival (mPFS) for the entire cohort was 22.5 months, while the median overall survival (mOS) was not reached (NR). The mPFS was NR, 22.5, and 10.1 months (P=0.178), and the mOS was NR, NR, and 11.6 months (P=0.019) for patients receiving KPd in the 2L, 3L, and 4L+ settings, respectively. Multivariable analysis identified elevated lactate dehydrogenase (LDH) level (HR=3.489, 95% CI: 1.557-7.823) and LOT ≥4 (HR=2.791, 95% CI: 1.086-7.177) as independent predictors of inferior PFS (P<0.05), while LOT ≥4 (HR=3.917, 95% CI: 1.258-12.200) was also associated with worse OS (P=0.019). Grade ≥3 adverse events (AEs) occurred in 12.8%, 50.0%, and 47.1% of patients in the 2L, 3L, and 4L+ groups, respectively. Conclusion:The KPd regimen demonstrated favorable clinical efficacy and manageable toxicity in RRMM, particularly in those with early-line relapse.

Cytochrome P4501B1 (CYP1B1), overexpressed in solid tumours but minimally in healthy tissues, is a promising anticancer target linked to chemoresistance. While CYP1B1 inhibitors can restore drug efficacy, most suffer from limited scaffold diversity and poor selectivity against other CYPs. We identified 2-(2-phenylethyl) chromones as a novel scaffold for anti-CYP1B1 activity and synthesised 24 derivatives with varied ring A/B substituents and established the SAR. Three compounds (CX-6, CX-9, CX-22) showed nanomolar anti-CYP1B1 activity and exceptional selectivity (SI > 230). In CYP1B1-overexpressing cells, the water-soluble and non-cytotoxic CX-9 (solubility > 100 μM) dose-dependently reversed docetaxel resistance, achieving efficacy at 50 μM comparable to 20 μM of the CYP1B1 inhibitor α-naphthoflavone (ANF). Molecular docking revealed similar binding modes for CX-9 and ANF in CYP1B1's active site. This work hints 2-(2-phenylethyl) chromones as a natural-derived scaffold for promising CYP1B1 inhibitor development.

Background: Although multiple pomalidomide-based combinations are active in relapsed and/or refractory multiple myeloma (RRMM), comparative data to guide regimen selection remain limited. Methods: A total of 230 patients with RRMM from 12 centers in China who received pomalidomide-based regimens were included in this retrospective analysis. Overall response rate (ORR) and progression-free survival (PFS) were compared across regimens incorporating bortezomib or ixazomib (V/IPD), carfilzomib (KPD), or daratumumab (DPD), and multivariable analyses were performed to identify prognostic factors. Results: The overall ORR was 73.9%, with rates of 63%, 79%, and 85% in the V/IPD (n = 66), KPD (n = 69), and DPD (n = 95) cohorts, respectively. ORR differed significantly between V/IPD and DPD (p = 0.0165), driven by a higher proportion of ≥VGPR in the DPD group. The median PFS for the entire cohort was 17.4 months (95% CI: 13.7-20.1), compared with 15.4 months (95% CI: 12.8-20.5), 14.2 months (95% CI: 6.9-not estimable), and 19.2 months (95% CI: 15.1-24.9) for V/IPD, KPD, and DPD, respectively, without significant differences. In multivariable analysis, DPD was associated with improved ORR (HR 4.83, p < 0.001) but not with PFS. R-ISS stage III predicted inferior response (HR 0.35, p = 0.04), whereas ≥3 prior lines of therapy correlated with shorter PFS (HR 1.77, p = 0.012). Adverse events were predominantly hematologic, with limited grade 3-4 toxicity and no treatment-related mortality. Conclusions: This multicenter real-world analysis clarifies the relative positioning of commonly used pomalidomide-based regimens in RRMM and underscores the importance of treatment timing and disease stage in optimizing outcomes.

Ruxolitinib is first-line therapy for intermediate/high-risk myelofibrosis (MF), but ∼50% of patients discontinue within 1 year due to loss of efficacy or intolerance. Four JAK inhibitors (gecacitinib, fedratinib, pacritinib, momelotinib) are approved for ruxolitinib-pretreated MF, with no head-to-head trials comparing their efficacy and safety. This study used matching-adjusted indirect comparison (MAIC) to compare these four agents, aiming to provide evidence-based insights for treatment decision-making in ruxolitinib-resistant or intolerant MF. Individual patient data (IPD) of gecacitinib (100 mg BID; ZGJAK006/ZGJAK017, n = 78) and published data of comparators (fedratinib: JAKARTA-2/FREEDOM2; pacritinib: PAC203; momelotinib: SIMPLIFY-2/MOMENTUM) were analyzed. Eight baseline characteristics were matched. Efficacy outcomes (week-24 SVR35, TSS50, transfusion independence [TI]) were reported as odds ratios (ORs); safety as risk differences (RDs). Gecacitinib showed superior SVR35 versus fedratinib (JAKARTA-2: OR = 3.96, 95% CI = 1.37-11.39, P = 0.0108), pacritinib (PAC203: OR = 6.10, 95% CI = 1.54-24.23, P = 0.0101), and momelotinib (SIMPLIFY-2: OR = 8.65, 95% CI = 1.86-40.31, P = 0.0060), and superior TSS50 versus pacritinib (OR = 7.62 95% CI = 1.84-31.51, P = 0.0050) and momelotinib (MOMENTUM: OR = 7.52, 95% CI = 1.63-34.61, P = 0.0096). Numerically, gecacitinib had better TI. It also had significantly lower incidences of diarrhea, nausea, and AE-related treatment discontinuation. Hematologic AE profiles of gecacitinib varied by comparator cohort. Gecacitinib showed favorable efficacy and tolerability signals versus several comparators, suggesting it may be a valuable second-line option.

Utilization of novel Bruton tyrosine kinase inhibitors (BTKi) has become common for treating CLL/SLL patients, yet limited evidence exists on the clinical characteristics and outcomes following BTKi therapy discontinuation in China. This multicenter retrospective study analyzed 37 CLL/SLL patients in China who discontinued BTKi therapy. The mean age at discontinuation was 62.67 years, with the majority being male (67.57%). Most patients (62.16%) were relapsed/refractory (R/R) CLL/SLL patients prior to BTKi treatment, and 37.84% were treatment-naïve patients. Treatment-naïve patients were significantly younger than R/R patients (56.93 vs. 66.16 years, p = 0.005). Discontinuation reasons included resistance (48.65%), intolerance (32.43%), and other factors (18.92%). The most frequently used regimen among the post-BTKi first subsequent therapies was the anti-CD20 antibody combination therapy (52.90%). The overall disease control rate during BTKi treatment was 78.13%. The median progression-free survival (PFS) for BTKi therapy was 19.09 months, 19.09 months for treatment-naïve patients, and 14.39 months for R/R patients. The minimum median PFS was observed in patients with resistance (7.86 months). After BTKi discontinuation, median PFS was shorter: 8.87 months for first subsequent therapy and 5.32 months for second subsequent therapy. No significant difference was observed in overall survival. These findings illustrate the impact of prior treatment and discontinuation reasons on subsequent outcomes.

Transvaginal natural orifice transluminal endoscopic surgery (v-NOTES) offers several unique advantages including reduced postoperative pain and improved cosmetic outcomes. This study aimed to evaluate the effectiveness of v-NOTES in the treatment of tubal pregnancy, with a focus on patient outcomes and cost-effectiveness. A retrospective analysis was conducted on 40 cases of tubal pregnancy treated surgically between December 1, 2020 and May 31, 2022. Patients were divided into 2 groups: the v-NOTES group (n = 20), who underwent transvaginal natural orifice transluminal endoscopic surgery, and the control group (n = 20), who underwent laparoscopic single-site surgery (LESS). Key variables including age, body mass index, operative time, intraoperative blood loss, postoperative pain, recovery time, and total costs were evaluated and compared between the 2 groups. Operative time and intraoperative blood loss were comparable between the 2 groups, patients in the v-NOTES group reported significantly lower postoperative pain scores and shorter hospital stays ( P < .05). Additionally, the time return to normal activity was markedly shorter in the v-NOTES group compared to the LESS group (16 hours vs 25 hours, respectively). Both procedures demonstrated similar safety profiles; but v-NOTES was associated with a faster recovery and higher patient satisfaction. V-NOTES is a safe and effective minimally invasive surgical option for tubal pregnancy, providing enhanced recovery and improved patient experience compared to LESS.

Background: Acute leukemia is the most common hematological malignancy, mainly including acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). Nucleophosmin 1 mutations (mNPM1) occur in 20%-30% of AML patients. Patients with mNPM1 have a 5-year survival rate of ~50%, with a median overall survival (OS) of 6.1-7.3 months in relapsed/refractory (R/R) patients. The gene rearrangement of the lysine methyltransferase 2A (KMT2Ar) occurs in ~10% of acute leukemia patients. Patients with a KMT2A rearrangement have a 5-year survival rate of ~20%-25%, with a median OS 2.4-6 months in R/R patients. Menin is a scaffolding protein that interacts with aberrant NPM1 or KMT2A to upregulate the HOXA/MEIS1 pathway, resulting in leukemogenesis. Menin inhibitors are a new class of targeted therapy that inhibit the interaction of menin and KMT2A, thus allowing differentiation of blasts. Zefamenib is a potent small molecule inhibitor targeting menin. In mouse studies, zefamenib has been shown to significantly reduce the tumor burden and reduce the proliferation of leukemia cell in peripheral blood, bone marrow, and spleen. Zefamenib has also demonstrated anti-leukemia efficacy and safety in relapsed/refractory acute leukemia patients in a phase 1 dose escalation/dose optimization study; results were presented at ASH in 2024. Of the 28 patients with mNMP1 or KMT2Ar treated with the RP2D of 600 mg BID, the overall response rate and CR/CRh rate was 89.3% and 57.1%, respectively. No patient had a dose-limiting toxicity, and the toxicity profile was acceptable with 2 pts with grade 1 QT prolongation and 2 pts with grade 2 differentiation syndrome. This study is currently enrolling in the phase 2 portion and is designed to evaluate the efficacy, safety, pharmacokinetics (PK), and efficacy of zefamenib in Chinese patients with relapsed/refractory acute leukemia. Study Design and Methods: This study (NCT06052813) is a phase 2, multicenter, open-label study of zefamenib monotherapy in Chinese patients with relapsed/refractory acute leukemias who have either a KMT2A or or an NPM1 gene mutation. Key eligibility criteria include patients diagnosed with relapsed/refractory acute leukemia (including AML, ALL, and mixed lineage leukemia, excluding acute promyelocytic leukemia) according to the World Health Organization 2022 criteria, bone marrow morphological changes (blasts/immature cells ≥5%), confirmed NPM1 gene mutation or KMT2A or NUP98 rearrangement, and meet one of the following four conditions: (i) primary refractory disease; (ii) first relapse and duration of first response ≤12 months; (iii) relapsed/refractory disease after 2 or more lines of therapy; (iv) relapse after allogeneic hematopoietic stem cell transplantation. Zefamenib will be administered twice daily for 28-day treatment cycles until disease progression/recurrence, intolerable toxicity, loss to follow-up, withdrawal of informed consent, death, or the investigator's judgment to terminate the study drug, whichever occurs first. The primary objective of the phase 2 dose expansion phase is to evaluate the efficacy of zefamenib in 30-48 patients using the RP2D dose obtained in phase 1. The patients will be divided into 3 cohorts (10-16 patients per cohort): (A) patients with AML with NPM1 mutations; (B) patients with AML with KMT2A rearrangements; and (C) other patients, including patients with relapsed/refractory ALL or mixed lineage leukemia with KMT2A rearrangement; patients with AML with NUP98 rearrangement; patients with AML or ALL with other types of gene alterations that meet protocol requirements. The primary endpoint for the phase 2 dose expansion phase CRc (CR+CRh+CRi). Key secondary endpoints include CR, CR+CRh, objective response rate, MRD negative remission rate, duration of response, duration of CR+CRh, duration of CRc, EFS, OS, cumulative relapse rate, cumulative mortality, safety, and pharmacokinetics. Based on the phase 1 results of this study, a global phase 2 study assessing the efficacy and safety of zefamenib monotherapy in acute leukemias with NUP98r, HOXA9r, or mNPM1 will be started in Q2 2026.

Background This study aims to examine the level of coupled and coordinated development between China's digital economy and older adult care services, analyzing their spatiotemporal evolution characteristics and key influencing factors, with the goal of providing feasible recommendations and scientific bases for the development of the digital economy and older adult care services in China.Methods This study uses publicly available panel data from China for the years 2015-2022. It employs the entropy method to measure the weights of various indicators in the digital economy and older adult care services. The study analyzes the level of coordinated development between the two using the coupling coordination degree model, and measures the main driving factors using the geographical detector model.Results (1) The overall level of coupling and coordinated development between China's digital economy and older adult care services shows an upward trend, but the growth rate is uneven, exhibiting an "M-shaped" pattern, with rapid growth followed by gradual slowdown, a bottoming-out rebound, and then a continuous decline. (2) There are significant spatial differences in the coupling and coordinated development of China's digital economy and older adult care services. Coastal areas are developing rapidly, inland areas have great potential, while peripheral areas are relatively lagging behind. Additionally, neighboring regions show regional linkage dynamics. (3) The main factors driving the coupling and coordinated development of China's digital economy and older adult care services include enterprise website ownership, technological contract turnover, the proportion of information technology service income, the building area of older adult care institutions, daily in-house visits, and the number of professional technical personnel.Conclusion To achieve coordinated development between the digital economy and older adult care services, efforts should focus on policy, market, technology, and talent. The government should support technological innovation and new service models, while tailoring strategies to regional market demands. Additionally, accelerating the industrialization of innovations and promoting intelligent upgrades in older adult care services are crucial. Finally, more investment is needed to cultivate composite talents in both the government and older adult care institutions.

Introduction Despite recent advances in treating myelofibrosis (MF)-associated splenomegaly and symptoms, disease- and treatment-associated cytopenias remain challenging.Gecacitinib (GCA), a JAK and ACVR1 dual inhibitor, demonstrated spleen, symptom, and anemia benefits in intermediate- and high-risk MF. A matching-adjusted indirect comparison of GCA versus ruxolitinb (presented on 2025 EHA congress; PS1839) reported GCA offered a trend of higher splenic benefits and was associated with significantly less grade 3/4 anemia and neutropenia compared with ruxolitinib (RUX). To evaluate the efficacy and safety of GCA in patients with MF and thrombocytopenia (platelet counts <100 × 109/L), we conducted a post-hoc analyses with pooled data sets from 4 clinical studies: ZGJAK016 (phase 3; GCA versus hydroxyurea; JAK inhibitor naïve), ZGJAK002 (phase 2; GCA optimal dosing frequency exploration; JAK inhibitor naïve), ZGJAK006 (phase 2; GCA single arm; intolerant to RUX), and ZGJAK017 (phase 2; GCA single arm; refractory or relapsed to RUX). Methods Detailed study designs for these studies have been published. In the ZGJAK016 study, patients received randomized treatment for 24 weeks (main study period); thereafter, patients who didn't achieved a 35% reduction in spleen volume from baseline (SVR35) at week 24 could receive open-label GCA 100 mg BID for an extension period, whereas patients who achieved a SVR35 could continue receiving the initially assigned treatment. In the other 3 studies, patients received open-label GCA at different doses (100 mg BID, 150 mg QD and 100 mg QD) for 24 weeks (main study period) and then could continue in the extension period. The primary endpoint of these study was 24-week rate of SVR35. The key secondary endpoints included 24-week rate of total symptom score reduction by 50% or more (TSS50), improvement in anemia at week 24 (including the conversion rate of baseline transfusion-dependence to independence, proportion of non-transfusion-dependent patients with baseline hemoglobin ≤100 g/L achieving an increase of ≥20 g/L, and reduction in red blood cell transfusion frequency or unit by ≥50%). Data were pooled from patients with platelet counts <100 × 109/L at baseline who received at least one dose of GCA, with enrollment dates from 2019 to 2022. Only 1 patient in the hydroxyurea group from ZGJAK016 had platelet counts <100 × 109/L, thereby being excluded. These post hoc, exploratory, efficacy and safety analyses are descriptive. Results A total of 24 of 273 patients (9%) received GCA in ZGJAK016 (n=1), ZGJAK002 (n=3), ZGJAK006 (n=12) and ZGJAK017 (n=8) had baseline platelet counts <100 × 109/L (moderate thrombocytopenia) and only 1 patient (6%) had baseline platelet counts <50 × 109/L (severe thrombocytopenia). Of the 24 patients, 19 patients received 100 mg BID as initial dose (JAKi-naïve, n=4; RUX-intolerant, n=7; RUX-refractory/relapsed, n=8), 4 and 1 received 150 mg QD and 100 mg QD (all were RUX-intolerant). The SVR35 rate at week 24 were 75%, 42% and 25% in the JAKi-naïve, RUX-intolerant and RUX-refractory/relapsed patients. The TSS50 rate at week 24 were 50%, 33% and 50%, respectively. The proportion of non-transfusion-dependent patients with baseline hemoglobin ≤100 g/L achieving a ≥20 g/L increase in hemoglobin level by week 24 were numerically higher in the JAKi-naïve patients (67%, 50% and 50%). Mean platelet counts either increased or were maintained from baseline levels over the 24-week main period. Overall, 79% of 24 patients completed the main study period. Half of the patients had dose suspension or reduction due to adverse events and 3 patients with lower starting dose had a dose increase to 100 mg BID (2 in the main period and 1 in the extension period). After study termination, 8 patients continued to take GCA for compassionate use. As of the data cutoff (25 June 2025), 4 patients were receiving GCA, with all remaining on therapy for >4 years. A median duration of treatment was 17.4 months (range, 0.5-69.4 months). The most common (occurring in ≥10% of patients) treatment-emergent adverse events during the initial 24-week treatment were generally consistent with those reported in the overall population. One exception was a higher incidence of thrombocytopenia (Any grade: 67%; Grade ≥3: 46%), however most were manageable and only 2 led to discontinuation. Conclusions GCA represents a safe and effective treatment option for MF patients with moderate thrombocytopenia.

Large granular lymphocyte leukemia (LGLL) is a rare lymphoproliferative disorder where somatic STAT3 mutation is common. Although LGLL has been described as an underlying condition associated with pure red cell aplasia (PRCA), the clinical characteristics and therapeutic response of LGLL − associated PRCA are largely unclear. We evaluated a set of 81 patients with LGLL − associated PRCA. Comparative analysis was performed on the clinical characteristics, responses to immunosuppressive therapy, and survival outcomes in patients with STAT3 mutation. Among the 81 LGLL − associated PRCA patients, 21 cases (26

Cancer cells evade immune detection through checkpoint molecules like PD-L1 and PD-L2 which suppress T-cell activation. While PD-L1 is well-studied, the role of PD-L2 remains unclear. Pyruvate kinase M2 (PKM2), a metabolic enzyme, influences immune checkpoint regulation, but its role in PD-L1 and PD-L2 modulation is not well defined. Here, we investigate the role of pyruvate kinase M2 (PKM2) in modulating the immune checkpoint molecules PD-L1 and PD-L2 via GATA3 in cancer cells, with insights from both human and mouse models. We find that PKM2 enhances PD-L1 expression while inhibiting PD-L2, a dual regulatory mechanism that facilitates immune evasion. Knockdown and overexpression experiments revealed GATA3 as a key mediator. PKM2 knockout reduced GATA3 level, leading to decreased PD-L1 and increased PD-L2 expression. Chromatin immunoprecipitation (ChIP)-qPCR demonstrates that GATA3 functions as a direct transcription factor capable of binding to the promoters of PD-L1 and PD-L2. In silico analyses of 81 esophageal squamous cell carcinoma (ESCC) cases from the TCGA database demonstrate that PKM2 mRNA is unrelated to PD-L1 and PD-L2 expression but is negatively correlated with CD8 + T-cell infiltration in ESCC. To further validate these findings, we establish a xenograft model using immune-competent C57/BL6N mice, where knockdown of PKM2 results in significant downregulation of both PD-L1 and PD-L2 expression. Collectively, these findings underscore the divergent roles of PKM2 in regulating immune checkpoint expression in human and mouse cancer models and suggest that targeting the PKM2-GATA3 axis could enhance cancer immunotherapy by fine-tuning PD-L1 and PD-L2 levels.

Introduction Patient-controlled intravenous analgesia (PCIA) and patient-controlled epidural analgesia (PCEA) constitute two major advances in pain management after major abdominal surgery. However, the role of PCIA or PCEA has not been particularly studied in elderly patients with gastric cancer. The aim of this study is to make a comparison between PCIA and PCEA in terms of their performance on short-term outcomes in elderly patients undergoing laparoscopic-assisted gastrectomy. Methods This single-center, retrospective study included 254 elderly patients (≥70 y) who underwent laparoscopic radical gastrectomy for gastric cancer. Patients received either general anesthesia combined with epidural anesthesia followed by PCEA (PCEA group, n = 123) or general anesthesia alone followed by PCIA (PCIA group, n = 131). The primary endpoint was pain intensity-tested using a 100-mm visual analog scale on postoperative days 1, 2, and 3. Demographics, comorbidities, perioperative data, postoperative short-term outcomes, and analgesia-related side effects were also assessed. Results The visual analog scale scores at rest were lower in the PCEA group compared to the PCIA group on postoperative day 1, 2, and 3 (27.8 ± 13.9 versus 33.1 ± 15.0, P = 0.004; 25.2 ± 11.3 versus 30.1 ± 14.3, P = 0.002; 16.9 ± 7.1 versus 20.9 ± 9.5, P < 0.001, respectively). The postoperative hospital stay was shorter in the PCEA group than in the PCIA group (11 versus 12 d, P = 0.018). The times to postoperative first flatus, semifluid diet, independent ambulation, and tracheal extubation after surgery in the PCEA group were significantly shorter than in the PCIA group. Overall morbidity, mortality, hospital readmission rate, and reoperation rate were not significantly different between the two groups. Regarding side-effects related to analgesia, there were no significant differences in terms of the rates of postoperative nausea and vomiting, urinary retention, or oxygen saturation <90% between the two groups. However, PCEA was associated with a higher incidence of postoperative hypotension compared to PCIA (10.6% versus 3.8%, P = 0.036). Conclusions In elderly patients undergoing laparoscopic radical gastrectomy, epidural anesthesia and analgesia may convey superior pain relief, faster restoration of gastrointestinal motility, and shorter hospitalization.

Introduction Gecacitinib (GCA), a JAK and ACVR1 dual inhibitor, demonstrated spleen, symptom, and anemia benefits in myelofibrosis (MF) patients. To investigate ferritin dynamics and factors predicting anemia response in MF patients treated with gecacitinib, we conducted a post-hoc analysis with data from a phase 2 ZGJAK006 study. Methods This study enrolled ruxolitinib-intolerant patients with MF. The detailed study design has been published. This exploratory post-hoc analysis included patients with red blood cell (RBC) transfusions within 3 months before enrollment or baseline hemoglobin ≤100 g/L. Patients missing baseline ferritin data were excluded. Anemia response assessment was assessed using the following criteria: 1) Transfusion-dependent patients becoming transfusion-independent within the first 24 weeks ; 2) non-transfusion-dependent patients with baseline hemoglobin of ≤100 g/L demonstrating a hemoglobin increase of ≥20 g/L starting within the first 24 weeks and sustained for ≥12 weeks; and 3) a ≥50% reduction in RBC transfusion frequency or units within the first 24 weeks for patients who had received transfusions within 3 months before study entry. The primary endpoint was 24-week rate of a ≥35% reduction in spleen volume from baseline (SVR35). The key secondary endpoints included 24-week rate of total symptom score reduction by 50% or more (TSS50). To explore factors potentially influencing anemia response, the least absolute shrinkage and selection operator (LASSO) and multivariate logistic regression were used. Variables considered included age, sex, DIPSS assessment, MF subtype, JAK2 V617F mutation status, baseline TSS, transfusion status, spleen volume, hemoglobin levels, and ferritin levels, time from diagnosis to initiation of gecacitinib, and prior ruxolitinib exposure. Results A total of 40 patients were included. The median baseline ferritin level was 735.9 ng/mL (range 49.8 to 5669.3), with 28 patients (70.0%) exhibiting levels above normal and 14 (35.0%) exceeding 1000 ng/ml. Baseline ferritin was higher in the 19 patients who received RBC transfusion within 3 months prior to enrollment compared to those who did not (median 286.3 ng/ml [range 49.8 to 2765.4] vs 1534.9 ng/ml [range 180.9 to 5669.3]; P = 0.0001). Median baseline hemoglobin was 77.5 g/L (range 45.0 to 104.0). Most patients (39/40) initiated gecacitinib at 100 mg BID; one patient started at 150 mg QD and escalated to 100 mg BID on day 16. By week 24, 19 patients (47.5%) achieved an anemia response. Among 20 patients who were transfusion-free within 3 months pre-study, responders had numerically lower baseline ferritin versus non-responders (median 241.4 [range 49.8 to 1224.0] ng/mL vs 339.5 [range 130.1 to 2765.4] ng/mL). Conversely, in previously transfused patients, responders exhibited numerically higher baseline ferritin (median 1664.7 ng/mL [range 398.6 to 5669.3] vs 1331.3 ng/mL [range 180.9 to 5585.5]). LASSO regression analysis identified 5 baseline predictor variables, including MF subtype, transfusion status, HGB levels, JAK2 mutation status and spleen volume. Multivariate logistic regression confirmed an association between anemia response and the presence of JAK2 mutation only (P = 0.0208). Patients achieving anemia response showed decreasing median ferritin levels from week 6 through week 48, with a median change of -109.5 ng/ml (IQR -240.3 to 106.2) and -321.2 ng/ml (IQR -422.9 to 19.0) from baseline to weeks 24 and 48, respectively. Platelet counts demonstrated a modest increasing trend in anemia responders. The SVR35 rate at week 24 was 57.9% (11/19) in anemia responders versus 19.0% (4/21) in non-responders (P = 0.0211). The TSS50 rate at week 24 was 63.2% (12/19) in responders and 42.9% (9/21) in non-responders (P = 0.2248). As of June 25, 2025, 18 patients (12 responders and 6 non-responders) remained on gecacitinib. The median treatment duration was 3.8 years (range 0.3 to 5.0) for responders and 1.5 years (range 0.0 to 4.3) for non-responders (P = 0.0039). Conclusions In our study, JAK2 mutation was significantly associated with anemia response to gecacitinib in ruxolitinib-intolerant MF patients. Ferritin decreased rapidly in patients achieving anemia response. Anemia responders showed significantly higher spleen response and longer treatment duration, with numerically higher symptom response.

Minimally invasive esophagectomy (MIE) has shown potential benefits in reducing postoperative complications and improving recovery for patients with esophageal squamous cell carcinoma (ESCC). This study aims to assess the effects of MIE on preoperative and postoperative quality of life and functional outcomes in ESCC patients. Clinical data from 57 ESCC patients who underwent MIE were retrospectively analyzed. Baseline characteristics, including age, gender, BMI, TNM stage, smoking history, alcohol consumption, comorbidities, tumor location, differentiation, and lymph node metastasis, were collected. Postoperative quality of life scores, nutritional status, and functional outcomes were assessed. Paired t-tests and chi-square tests were used to compare preoperative and postoperative variables, while correlation analysis was conducted to evaluate associations between functional outcomes and quality of life. A total of 57 patients (41 males, 16 females; mean age: 67.61 ± 7.72 years) who underwent MIE were analyzed. Postoperative evaluation demonstrated significant improvements in quality of life scores across multiple dimensions, including physical symptoms (P = 0.006), emotional management (P = 0.013), role function (P = 0.013), cognitive function (P = 0.042), and social function (P = 0.021). Additionally, nutritional status improved postoperatively, with higher albumin levels (4.12 ± 0.34 g/dL vs. 3.78 ± 0.25 g/dL, P < 0.001) and reduced weight loss (1.98 ± 1.02 kg vs. 2.44 ± 1.12 kg, P = 0.026). Functional outcomes also showed significant improvements, including decreased dysphagia scores (3.45 ± 1.56 vs. 4.04 ± 0.31, P = 0.008), while cardiac physical activity and respiratory function remained stable (P > 0.05). Correlation analysis indicated significant associations between specific functional outcomes and quality of life (P < 0.05). MIE improves quality of life, nutritional status, and functional outcomes in patients with esophageal squamous cell carcinoma, highlighting its potential benefits in postoperative recovery and patient well-being. Not applicable.

Background Paroxysmal nocturnal haemoglobinuria (PNH) is an acquired clonal haematopoietic stem cell disorder. Immune escape is crucial in PNH, and our previous studies revealed that natural killer (NK) cells potential participate in the immune escape of PNH. This study aimed to investigate the subtypes and functional changes of NK cells in PNH patients.Methods We analysed CD59+ and CD59- bone marrow mononuclear cells using single-cell RNA sequencing (scRNA-seq). The results were validated through flow cytometry and co-culture experiments.Results We classified NK cells into seven subtypes by scRNA-seq, and found significant differences in the distribution of subtypes in CD59+ and CD59- NK cell of PNH patients. Compared with controls, the proportion of active and adaptive NK cells was higher in CD59+ NK cells. Conversely, the proportion of CD56bright NK cells and terminal NK cells was elevated in CD59- NK cells. Additionally, the proportion of mature NK cells decreased in both the CD59+ and CD59- groups. Gene ontology and Kyoto Encyclopedia of Genes and Genomes analysis revealed impaired function of CD59- NK cells, whereas CD59+ NK cells showed minimal change. Furthermore, similar results were verified by flow cytometry and co-culture in vivo and in vitro. And the proportion of NK cells was closely related to the proportion of CD8+ T cells and the clinical indicators of disease.Conclusions The quantity and function of NK cells in PNH patients are insufficient, in which CD59- NK cells have functional defects, whereas CD59+ NK cells were mainly activated and potential involved in immune escape by regulation of T cells.

This was a multicenter, randomized, registrational phase 2 study to assess efficacy and safety of olverembatinib vs. BAT in pts with CML-CP resistant and/or intolerant to three TKIs (imatinib [I]), dasatinib [D], nilotinib [N]) in China. This report updates an oral presentation at the 2023 American Society of Hematology Annual Meeting (data cutoff date of October 17, 2023), with median (range) follow-up 21.40 (0.6-54.7) months in the olverembatinib and 2.91 (0-48.9) months in the BAT arm. Eligible CP-CML pts were adults resistant or intolerant to three TKIs and in ECOG PS 0-2 with adequate organ function. Pts were randomized 2:1 to olverembatinib (40 mg QOD) or the BAT arm: TKIs (I, D, or N), interferon, hydroxyurea, and/or homoharringtonine by investigator choice. The primary endpoint was event-free survival (EFS), including time from randomization to CML progression; all-cause mortality; relapse; treatment failure; loss of complete hematologic response; and treatment intolerance as per investigator and study sponsor. Efficacy was analyzed in the intention-to-treat (ITT) efficacy population and safety in pts receiving ≥1 dose of olverembatinib. As of January 13, 2025, a total of 144 pts (96, olverembatinib; 48, BAT) were enrolled (69.4% male), with a median (range) age of 49.0 (18-77) years. Pts without the T315I mutation included a somewhat lower proportion of males (68/105; 64.8%) and had the same median age. A total of 129/144 pts (89.6%) were previously treated with ≥ 3 TKIs (I, D, N), including all 105 (100.0%) of those without the T315I mutation. Sixty-six (45.8%) of all pts (27/105; 25.7% of those without the T315I mutation) had ≥1 BCR::ABL1 mutation and 39 (27.1%) BCR::ABL1T315I. A total of 96 (66.7%) of all pts discontinued therapies (54 [56.3%] olverembatinib, 42 [91.3%] BAT) due to disease progression/treatment failure, adverse event (AE), consent withdrawal, poor compliance, or death. Median EFS was significantly longer with olverembatinib (vs. BAT) in pts without T315I mutations: 11.96 (95% CI 8.28-22.11) vs. 3.14 (95% CI, 2.53-12.98) (P = 0.0159; HR, 0.550; 95% CI, 0.335-0.901). Median EFS was also significantly longer in the olverembatinib (vs. BAT) group in all pts: 21.22 (95% CI, 10.15-not reached [NR]) months vs. 2.86 (95% CI 2.53-4.73) months (P < .0001; HR, 0.355; 95% CI, 0.230-0.549). In pts without T315I mutations, estimated EFS at 6, 12, and 24 months was 68.5% (95% CI, 55.5%-78.4%), 49.7% (95% CI, 36.7%-61.5%), and 36.9% (95% CI, 24.7%-49.1%), respectively, in the olverembatinib arm and 41.2% (24.8%-56.9%), 35.3% (19.9%-51.0%), and 22.9% (10.5%-38.1%) in the BAT arm. In the olverembatinib arm in all pts, respective data were 73.0% (95% CI, 62.5%-81.0%), 58.7% (95% CI, 47.5%-68.2%), and 47.0% (95% CI, 35.9%-57.2%). In the BAT group, it was 32.6% (95% CI, 19.7%-46.2%), 26.1% (14.5%-39.3%), and 16.9% (7.7%-29.2%), respectively. Median OS was not reached in both treatment groups (P = 0.21 in those without the T315I mutation and P = 0.17 in all patients). In pts without T315I mutations who were treated with olverembatinib, 32 of 39 (82.1%) achieved complete hematologic response (CHR); 16 of 62 (25.8%) complete cytogenetic response (CCyR); and 10 of 62 (16.1%) major molecular response (MMR). Among those without T315I mutations treated with BAT, these data were 8/16 (50.0%) CHR; 6/29 (20.7%) CCyR; and 3/29 (10.3%) MMR. In the ITT efficacy group, 51 of 60 (85.0%) of all evaluable patients treated with olverembatinib achieved CHR; 33/88 (37.5%), CCyR; and 26/88 (29.5%) MMR. In the BAT group, these values were 8/23 (34.8%) for CHR; 7/37 (18.9%), CCyR; and 3/37 (8.1%) MMR. In the safety population, 85/96 (88.5%) of all pts receiving olverembatinib (60/69; 87.0% in the non-T315I mutation group) and 31/46 (67.4%) BAT (27/35; 77.1% non-T315I) experienced grade ≥ 3 AEs. In all pts and those without T315I mutations, frequent any-grade TEAEs in pts treated with olverembatinib included thrombocytopenia, leukopenia, neutropenia, and CPK increased. Serious AEs (SAEs) (>15%) included thrombocytopenia and leukopenia. This study represents the largest population of pts with CML-CP resistant to or intolerant of both 1G and 2G TKIs, who have now been monitored for up to 4 years. Olverembatinib was more efficacious and better tolerated than BAT in treating these pts (including those without T315I mutations). Internal study (CT.gov) numbers: HQP1351CC203 (NCT04126681).

Introduction To evaluate treatment continuation of gecacitinib in myelofibrosis (MF) patients after ruxolitinib failure, we conducted a post-hoc analysis of pooled data from two phase 2 single-arm studies: ZGJAK006 (ruxolitinib-intolerant MF) and ZGJAK017 (ruxolitinib-refractory/relapsed MF). Methods Study designs were previously published. This analysis included 84 patients (ZGJAK006: n=50; ZGJAK017: n=34) with long-term follow-up for treatment continuation. Results Among the 84 patients, the median age was 60 years (range 25–75), with 50 males (59.5%). Disease subtypes included primary MF (n=70), post-polycythemia vera MF (n=7), and post-essential thrombocythemia MF (n=7). Molecular profiling showed JAK2V617F mutations (n=56), CALR mutations (n=20; Type 1: n=10, Type 2: n=7, uncommon: n=3), MPL mutations (n=6), and triple-negative (n=3). Baseline hematologic parameters included a median hemoglobin level of 87 g/L (range 44–149) and median platelet count of 136×10⁹/L (range 48–951). The median time from initial diagnosis was 24.2 months (range 2.7–352.1), with a median prior ruxolitinib treatment duration of 14.1 months (range 1.5–90.5). Seventy-eight patients started gecacitinib at 100 mg BID, 4 at 150 mg QD, and 1 each at 200 mg QD and 100 mg QD. Thirty-nine patients (46.4%) entered a compassionate use program after study completion. As of June 25, 2025, with a median follow-up of 3.8 years, 31 patients (36.9%) remained on gecacitinib. The median treatment duration was 22.4 months (range 0.1–60.3) for the entire cohort; 23.0 months (range 0.1–53.0) for patients starting at 100 mg BID; 23.0 months (range 0.1–60.3) for ruxolitinib-intolerant patients; and 18.3 months (range 3.2-47.0) for ruxolitinib-refractory/relapsed patients. Additionally, regression analysis demonstrated that treatment duration was significantly positively correlated with the percentage reduction in spleen volume from baseline at week 24. ConclusionsGecacitinib demonstrates durable treatment continuation (median >18 months across subgroups) in MF patients after ruxolitinib failure. These long-term data support its viability as a therapeutic option for ruxolitinib-intolerant or refractory/relapsed MF patients.

ABSTRACT Backgrounds Mitoxantrone hydrochloride liposome (Lipo‐MIT) has shown clinical benefits in various tumors. However, there is no prospective study evaluating its effectiveness and safety in relapsed/refractory multiple myeloma (RRMM). A phase I trial of bortezomib, Lipo‐MIT, and dexamethasone (VMitD) with the primary endpoints being safety and efficacy was performed. Methods Twenty subjects were enrolled this study, and the dose of Lipo‐MIT was designed to be 12, 16, and 20 mg/m2 at Day 1 combined with bortezomib and dexamethasone. Results The most common grade 3/4 non‐hematologic adverse event was pneumonia (20%). The most frequently observed grade 3/4 hematologic toxicity included thrombocytopenia (70%), neutropenia (55%), lymphopenia (30%), and anemia (10%). Fifteen subjects received at least one efficacy evaluation, including 60% (9/15) with a very good partial response (VGPR) or better, resulting in an overall response rate (ORR) of 86.7% (13/15). Conclusions This is the first report about the novel triplet regimen VMitD, including Lipo‐MIT for RRMM, which was well tolerated and demonstrated efficacy. Further studies are required to assess the outcomes more accurately and to evaluate its effectiveness in comparison to other salvage regimens containing proteasome inhibitors and anthracyclines. Trial Registration: ClinicalTrials.gov identifier: NCT05052970