BACKGROUND AND AIMS:The atherogenic index of plasma (AIP), a novel biomarker reflecting atherosclerosis burden, has been associated with an increased risk of metabolic dysfunction-associated steatotic liver disease (MASLD). However, the impact of long-term AIP trajectory patterns on MASLD development remains unclear. METHODS:This retrospective longitudinal study enrolled 13,211 adults who received serial health screenings between January 2017 and November 2024. AIP was derived using the formula: log (triglycerides/HDL-C). MASLD incidence among AIP subgroups was compared via Kaplan-Meier analysis. Restricted cubic splines evaluated potential nonlinear associations between AIP and MASLD risk. Latent class trajectory modeling was used to identify distinct AIP trajectory patterns over time. RESULTS:Over a median follow-up of 2173 days, 2744 cases of MASLD progression were documented. A 1-SD rise in AIP corresponded to a 184% increased MASLD risk. Quartile-based analyses yielded consistent findings. Trajectory modeling stratified participants into low-stable, medium-stable, and high-stable groups. Compared with the low-stable group, the medium-stable and high-stable groups exhibited significantly increased risks of MASLD, with hazard ratios (HRs) of 2.75 (95% CI: 2.43-3.11) and 4.76(95% CI: 4.14-5.47), respectively. CONCLUSIONS:Both elevated baseline AIP levels and sustained high-stable AIP trajectories were strongly associated with an increased risk of MASLD progression. Continuous monitoring of AIP may enable early risk stratification and inform targeted preventive strategies.

Despite advances with JAK and ROCK inhibitors, durable responses in chronic GVHD (cGVHD) remain challenging. For patients with advanced, multi-refractory disease, simultaneously targeting multiple pathways may be necessary. Building on preclinical synergy between JAK and ROCK inhibition, we evaluated the combination of belumosudil and ruxolitinib in a multicenter, retrospective study of 57 ruxolitinib-refractory cGVHD patients. The cohort had high-risk features, with 63.2% having severe NIH-grade disease and 66.7% receiving ≥ 5 prior lines of therapy.The primary endpoint was the 3-month overall response rate (ORR). At a median follow-up of 170 days, the ORR was 59.6%, with a best overall response of 75.4%. Notably, in patients with lung involvement (63.2%), 83.3% achieved symptom-based responses, versus 3.7% FEV1 improvement. The 12-month failure-free survival rate was 94.5%, and 86.4% of patients achieved a corticosteroid reduction. The regimen demonstrated a favorable safety profile, with only 5.3% grade ≥ 3 pneumonia and no treatment-related discontinuations or severe hematologic toxicities.These results confirm the clinically meaningful efficacy and safety of dual JAK/ROCK inhibition in this heavily pretreated population. These findings support the mechanistic rationale for concurrent pathway inhibition and warrant prospective validation in randomized controlled trials.

Atherosclerosis is driven by metabolic dysregulation and endothelial dysfunction; however, the precise molecular mechanisms underlying its pathogenesis remain incompletely elucidated. Fibrinogen-like protein 1 (FGL1) is a well-established hepatokine with critical roles in regulating tumorigenesis and metabolic dysfunction, while its involvement in atherogenesis remains unclear. Our clinical and preclinical studies revealed elevated plasma FGL1 levels in atherosclerotic patients and mice, correlating with arterial stenosis severity. Prolonged high-fat diet exposure specifically upregulated hepatic FGL1 expression. Hepatic FGL1 overexpression accelerated atherosclerosis, while liver-specific knockdown reduced plaque burden. Exogenous administration of FGL1 accelerated endothelial injury and atherosclerosis progression. Mechanistically, liver-derived FGL1 accumulates in vascular endothelium through fibrinogen C-terminal domain Trp225-mediated binding to integrin β1's vWFA domain. This interaction promotes the conformational change of integrin β1 and the formation of integrin β1/ILK1 complex, co-activating FAK/ERK and Smad signaling to drive transcriptional reprogramming of endothelial cells. Therapeutic interventions targeting FGL1–integrin β1 axis by integrin β1 blocking antibody, FGL1-neutralizing antibody, or RGD peptide effectively attenuated endothelial injury and atherogenic progression in murine models. These findings establish hepatic FGL1 as a novel endocrine regulator of vascular pathophysiology, highlighting the FGL1–integrin β1 axis as a promising therapeutic target for endothelial protection and atherosclerosis management.

BACKGROUND:Risks and benefits of intravenous recombinant tissue plasminogen activator (rt-PA) remain unclear among elderly patients with acute ischaemic stroke (AIS). This study investigated 1-year clinical outcomes of intravenous rt-PA treatment in Chinese patients aged >80 years with AIS. METHODS:This retrospective multicentre study included patients with AIS aged >80 years from the Computer-based Online Database of Acute Stroke Patients for Stroke Management Quality Evaluation stroke registry platform between January 2017 and March 2020 who arrived at the hospital within 4.5 hours of symptom onset. Patients who received intravenous rt-PA were propensity score-matched (1:1) by baseline characteristics with those who did not receive reperfusion therapy. The primary outcome was modified Rankin scale (mRS) score 0-1 at 1 year; secondary outcomes were any intracranial haemorrhage (ICH) and all-cause mortality during hospitalisation, mRS 0-2, mRS score distribution and all-cause mortality at 1 year. RESULTS:The analysis included 1560 propensity score-matched elderly patients (intravenous rt-PA, n=780; non-reperfusion, n=780). At 1 year, the intravenous rt-PA group had a higher proportion of patients with mRS 0-1 (27.7% vs 23.8%; OR 1.87, 95% CI 1.35 to 2.59, p<0.001), mRS 0-2 (37.3% vs 33.7%; OR 2.02, 95% CI 1.48 to 2.75, p<0.001) and an overall shift towards better outcomes than placebo (mRS mean±SD score: 3.5±2.4 vs 3.7±2.3; OR 0.77, 95% CI 0.64 to 0.93, p=0.007). No significant differences were observed in any ICH and all-cause mortality during hospitalisation and at 1 year. CONCLUSIONS:This study provided real-world evidence for a positive benefit-risk profile of intravenous rt-PA in Chinese patients with AIS aged >80 years. TRIAL REGISTRATION NUMBER:NCT05401149.

BACKGROUND:The optimal regimens for older adults with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) before allogeneic hematopoietic stem cell transplantation (allo-HSCT) remain uncertain. METHODS:The authors conducted a multicenter phase 2 trial to evaluate the novel venetoclax, fludarabine, and melphalan (VFM) regimen in patients with AML or MDS aged 50 years and older. The VFM regimen consisted of venetoclax (400 mg daily on days -8 to -2), fludarabine (30 mg/m2 daily on days -7 to - 3), and melphalan (120-140 mg/m2 daily on day -2). RESULTS:Sixty patients (median age, 58 years; age range, 51-66 years) received the novel VFM conditioning regimen. The 2-year disease-free survival (DFS) rate was 75.0% (95% confidence interval [CI], 64.8%-86.8%), which was the primary end point. Two-year rates of overall survival, graft-versus-host disease (GVHD)-free and recurrence-free survival, nonrelapse mortality, and relapse were 78.3% (95% CI, 68.6%-89.5%), 61.6% (95% CI, 50.5%-75.3%), 13.3% (95% CI, 6.1%-23.3%), and 11.7% (95% CI, 5.1%-21.3%), respectively. Treatment-related grade 2-3 nonhematologic adverse events occurred in 58% of patients, with no grade 4-5 nonhematologic toxicities. The cumulative incidence of grade 2-4 and grade 3-4 acute GVHD at day 100 was 5.0% (95% CI, 1.3%-12.7%) and 1.7% (95% CI, 0.1%-7.9%), respectively. The 2-year cumulative incidence of moderate-to-severe chronic GVHD was 16.7% (95% CI, 8.5%-27.3%). CONCLUSIONS:These findings support the feasibility of incorporating venetoclax into a fludarabine and melphalan conditioning regimen in older adults with AML/MDS. Notably, the low rates of GVHD and relapse associated with this venetoclax-based conditioning regimen support further study of this platform [ClinicalTrials.gov Identifier: NCT05084027].

BACKGROUND:Acute myeloid leukemia with NUP98 rearrangements (NUP98r) is associated with poor prognosis, and while allo-HSCT remains the primary curative approach, its efficacy in NUP98r patients is still uncertain. The prognostic impact of NUP98 fusion partners, accompanying genetic alterations, and NUP98r dynamics is unclear. METHODS:We retrospectively analyzed 56 adult patients with NUP98r AML undergoing allo-HSCT across multiple centers. Primary outcomes included overall survival (OS), disease-free survival (DFS), and cumulative incidence of relapse (CIR). RESULTS:The most common NUP98r were NUP98::HOXA9 and NUP98::NSD1. With a median follow-up of 755 days, the 2-year CIR, DFS, and OS rates were 28.4%, 69.8%, and 73.0%. Pre-transplant NUP98r status demonstrated no significant association with outcomes in complete remission patients, while nonremission status correlated with higher CIR and reduced survival. NUP98r positivity at 1 month post-HSCT predicted higher 2-year CIR (60.0% versus 21.5%, P = .013), reduced DFS (40.0% versus 78.5%, P = .008) and OS (40.0% versus 84.5%, P = .003). Outcomes worsened at 3 and 6 months, with 100% CIR in the NUP98r positive at 6 months. Multivariable analysis confirmed 1-month post-HSCT NUP98r positivity as an independent predictor of relapse and mortality, whereas pre-transplant NUP98r status lacked prognostic significance. CONCLUSIONS:Patients with detectable NUP98r post-HSCT showed higher relapse risk and mortality, indicating the necessity for early molecular surveillance and early intervention trials in this high-risk subgroup.

BackgroundObesity has become a global health concern, particularly in relation to abdominal fat which is associated with various diseases. The connection between Helicobacter pylori (H. pylori) and obesity is still debated, with limited research on the link between H. pylori and visceral fat. This study aimed to examine the correlation between H. pylori infection and visceral fat area (VFA) among participants.MethodsA total of 18,076 individuals participated in this study, undergoing assessments of VFA, physical parameter measurements, and serum examinations. Bioelectrical impedance was used to analyze VFA, with the triglyceride-glucose (TyG) index indicating levels of insulin resistance (IR) in the population. Multiple linear regression analysis was utilized to determine the factors influencing VFA, while a generalized additive model was employed to assess potential non-linear associations between the TyG index and VFA.ResultsH. pylori was recognized as a contributing factor to VFA exclusively within diabetic populations. In these populations, a significant nonlinear relationship existed between the TyG index and VFA. Furthermore, mediation analysis indicated that the TyG index acted as a mediator in the relationship between H. pylori and VFA.ConclusionH. pylori is closely associated with VFA in individuals with diabetes, with IR serving as a mediating factor in the relationship between H. pylori and VFA.

Introduction Transplant-associated thrombotic microangiopathy (TA-TMA) represents a critical complication in hematopoietic stem cell transplantation (HSCT) with substantial morbidity and mortality risks. Current diagnostic and prognostic approaches rely predominantly on individual laboratory parameters and clinical criteria and lack comprehensive predictive models that integrate multiple inflammatory and hemolytic biomarkers. The heterogeneous clinical presentation, variable treatment responses, and complex pathophysiology of TA-TMA necessitate more sophisticated AI-driven risk stratification approaches. We investigated whether an unsupervised machine learning model, by incorporating pre- and early post-transplant inflammatory and endothelial injury signatures, could stratify patients into distinct subgroups to predict clinical outcomes, particularly mortality, more accurately than conventional methods. Methods This nationwide, multicenter, retrospective cohort study enrolled adult patients who underwent allogeneic HSCT and were subsequently diagnosed with TA-TMA across multiple transplant centers from January 2015 to December 2023. Patient data were retrospectively reviewed and classified according to the 2023 international harmonized diagnostic criteria. The primary cohort comprised 847 patients from our center, with external validation performed in 238 patients from independent centers. We developed STRATOS (STRAtification Tool for TA-TMA OutcomeS), an unsupervised quantitative model integrating eight laboratory biomarkers capturing hemolysis, thrombosis, and complement activation: soluble C5b-9 (sC5b-9), schistocyte ratio, LDH, platelet count, hemoglobin, serum creatinine, haptoglobin, and total bilirubin. The model utilized t-distributed stochastic neighbor embedding (t-SNE) for dimensionality reduction and K-means clustering for patient stratification. The primary endpoint for prognostic evaluation was 1-year non-relapse mortality (NRM). Results Among the 847 patients in the primary cohort (median age, 45 years; 58% male), the median onset of TA-TMA was day +57 post-transplantation. Baseline characteristics at diagnosis revealed a median platelet count of 28×10⁹/L, LDH level of 445 U/L, and schistocyte percentage of 2.1%. t-SNE dimensionality reduction and K-means clustering identified three distinct phenotypic clusters with significantly different mortality risks. Cluster 1 (Severe Endothelial Injury, n=189), characterized by extremely high sC5b-9 levels, marked elevation in LDH, and severe thrombocytopenia, represented the highest-risk patients with the poorest prognosis. Cluster 0 (Hemolytic-Dominant, n=312), defined by pronounced hemolytic markers but moderate complement activation, represented the intermediate-risk group. Cluster 2 (Compensated, n=346), exhibiting relatively preserved hemoglobin and only mild-to-moderate abnormalities in biomarkers, had the best prognosis. In the validation cohort, the risk stratification derived from STRATOS demonstrated excellent performance, achieving an area under the curve (AUC) of 0.87 for predicting 1-year NRM. This significantly outperformed assessment based on individual markers (LDH alone: AUC, 0.64; platelet count: AUC, 0.59; p<0.001). Feature importance analysis revealed that sC5b-9 was the most discriminative biomarker for separating the clusters (variability contribution: 0.91), followed by the schistocyte ratio (0.83) and LDH level (0.70). Conclusions This nationwide, multicenter study establishes and validates the first AI-driven biomarker signature for prognostic risk stratification in patients with established TA-TMA. Compared with conventional approaches, STRATOS provides superior prognostic accuracy for mortality by identifying three distinct phenotypic clusters with disparate outcomes. Future prospective validation studies are warranted to establish guidelines for the real-time clinical integration of this stratification tool.

Allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative strategy for patients with chronic myelomonocytic leukemia (CMML). However, few reports have investigated the outcomes of patients receiving haploidentical HSCT. To this end, we included 117 patients with haploidentical donors (HID) and 75 patients with matched related donors (MRD) from 28 centers across China to explore the prognostic impact of different transplantation modalities. We found no significant difference between these two groups in terms of event-free survival (EFS, p = .211), overall survival (OS, p = .503), cumulative incidence of relapse (CIR, p = .076) or non-relapse mortality (NRM, p = .794). The predominance of peripheral blood (PB) graft source over bone marrow and PB since 2020 may have contributed to the worse outcomes in the MRD group. Moreover, CMML-specific prognostic scoring system (CPSS) lower-risk patients benefited more from the HID modality with superior EFS (p = .006). Multivariate analysis indicated that advanced age (p = .013), anemia at diagnosis (p = .010), and donor relationship (parent-to-child, p = .013) were independently associated with worse EFS in the HID group. Our data suggested that HID was comparable to MRD in CMML. However, under certain conditions, such as CPSS lower-risk ones, HID was preferred.

Allogeneic haematopoietic stem cell transplantation (allo-HSCT) is increasingly used in older patients, but non-relapse mortality (NRM) remains a major concern. The Endothelial Activation and Stress Index (EASIX) has shown prognostic value for transplant outcomes, yet its utility in elderly patients remains unexplored. This study included 164 patients aged ≥60 years undergoing haploidentical HSCT across 12 centres in China (2016-2023). Serial EASIX scores were calculated at eight timepoints throughout the peri-transplant period. Longitudinal log2-EASIX patterns were analysed using group-based trajectory modelling (GBTM). The results indicated that elevated pretransplant log2-EASIX (log2-EASIX-PRE) significantly correlated with inferior overall survival (OS: HR = 1.25, 95% CI 1.07-1.47, p = 0.005), increased NRM (HR = 1.32, 95% CI 1.08-1.62, p = 0.007) and higher incidence of severe infections (HR = 3.73, 95% CI 1.77-7.89, p < 0.001). The optimal EASIX-PRE cut-off was 4.25, with patients exceeding this threshold showing worse 2-year outcomes (OS: 24.3% vs. 59.3%, p < 0.001; NRM: 54.3% vs. 24.5%, p = 0.001). GBTM revealed two distinct trajectory patterns: patients in the log2-EASIX Spiking group experienced significantly higher NRM compared to the log2-EASIX Smooth group (HR = 4.58, 95% CI 1.72-12.2, p = 0.002). These findings establish pretransplant EASIX as a clinically actionable biomarker in elderly allo-HSCT recipients, with dynamic monitoring enabling early risk stratification for personalised interventions.

BACKGROUND:The longer-term benefits of intravenous recombinant tissue plasminogen activator (IV rt-PA) in Chinese acute ischemic stroke (AIS) patients remain lacking. We aimed to evaluate the 1-year clinical outcomes after IV rt-PA for Chinese AIS patients in a real-world setting. METHODS:Based on a prospective multicenter stroke registry in China, we analyzed the data of patients with AIS (aged ≥ 18 years) who arrived at hospital within 4.5 h of symptom onset. Participants were from 80 stroke centers in China between January 2017 and March 2020. IV rt-PA-treated patients were propensity score-matched (1:1) by baseline characteristics with non-reperfusion patients. Primary outcome was 1-year all-cause mortality. Secondary outcomes included 1-year functional outcomes. RESULTS:Participants were mostly male (59.9%), with a mean age of 70.2 years. One-year all-cause mortality was similar between the two groups (11.1% vs. 12.2%; HR, 0.90 [95% CI: 0.78-1.05], p = 0.183). At 1 year, the IV rt-PA group had a higher proportion of functional independence (modified Rankin Scale [mRS] 0-2: 70.9% vs. 66.4%; OR, 1.25 [95% CI, 1.12-1.39]) and favorable outcome (mRS 0-1: 59.5% vs. 54.6%; OR, 1.23 [95% CI, 1.11-1.36]) compared to the non-reperfusion group (both p < 0.001). A lower proportion of severe disability/death was also observed in the IV rt-PA group versus the non-reperfusion group (mRS 5-6: 15.9% vs. 20.3%; OR, 0.73 [95% CI, 0.64-0.83]) (all p < 0.001). CONCLUSIONS:IV rt-PA treatment in Chinese AIS patients eligible for thrombolysis was associated with improved 1-year functional outcomes despite having similar mortality to those who did not receive any reperfusion treatments. TRIAL REGISTRATION:This study is registered on https://clinicaltrials.gov; Unique identifier: NCT0539533.

Autoimmune hemolytic anemia (AIHA) following allogeneic hematopoietic stem cell transplantation (allo-HSCT) is often refractory and relapsing, leading to increased mortality post-HSCT. We retrospectively analyzed the cases of patients with transfusion-dependent β-thalassemia (TDT) who underwent allo-HSCT to study their clinical features, the occurrence of AIHA post-HSCT, and treatment response and to explore the possible pathogenesis of AIHA. A total of 113 patients were registered in the study, out of whom 14 developed AIHA following allo-HSCT, resulting in a cumulative incidence of 12.4

Background:The systemic inflammation response index (SIRI) has emerged as a promising inflammatory biomarker linked to the onset and progression of cardiovascular disease (CVD). However, the association between initial and long-term trajectories of the SIRI index and carotid atherosclerosis (CAS) progression remains unexplored. Methods:This longitudinal retrospective cohort study encompassed 11,623 adults undergoing multiple general health checks at Taizhou Hospital of Zhejiang Province from January 2017 to September 2024. SIRI values were derived using the formula: neutrophil count × monocyte count/lymphocyte count. To assess SIRI trends over time, latent class trajectory modeling was utilized. Hazard ratios (HRs) and 95% confidence intervals (CIs) for both the initial and trajectories of the SIRI index were determined through univariate and multivariate Cox proportional hazards analyses. Restricted cubic splines evaluated potential nonlinear associations between SIRI and CAS risk. Results:Over a median follow-up of 2,043 days, 2,460 individuals experienced progression of CAS. After adjusting for conventional CVD risk factors, a 1-standard deviation (SD) rise in SIRI was linked to a 12% elevated risk of CAS progression (HR = 1.121, 95% CI 1.035-1.213). Comparable findings were noted when SIRI was stratified into quartiles. Participants were classified into three trajectory groups: low-stable, middle-stable, and high-stable. Following multivariate adjustments, the high-stable group exhibited a 1.166-fold increased risk of CAS progression (95% CI 1.021-1.333). Conclusions:Elevated initial SIRI levels and a high-stable trajectory were associated with an increased risk of CAS progression. Tracking SIRI trends over time may help identify individuals at heightened risk, enabling more focused prevention and treatment strategies.

Background Chronic graft-versus-host disease (cGVHD) remains a leading cause of non-relapse mortality post-allogeneic hematopoietic stem cell transplantation (allo-HSCT), with 30-50% of patients developing steroid-refractory disease. Despite advances with JAK inhibitors (ruxolitinib) and ROCK2 inhibitors (belumosudil) in cGVHD, long-lasting responses remain uncommon, a significant number of patients need next immunosuppressive therapies. Refractory cases demand personalized, multi-targeted approaches. Preclinical data suggest synergistic effects through dual JAK/ROCK pathway inhibition, potentially addressing fibrotic and Th17-mediated resistance mechanisms. While clinical data on this specific combination are limited, whether the combined belumosudil and ruxolitinib improves efficacy without safety concerns. Methods We conducted a retrospective multicenter study to investigate the safety and efficacy of belumosudil and ruxolitinib combination in the treatment of ruxolitinib refractory cGVHD. Eligibility required progression or suboptimal response after ≥3 months of ruxolitinib, more than 2 prior lines of treatment. Primary endpoints was 3 months overall response rate (ORR). Best of response (BOR), Failure-free survival (FFS), adverse events (AEs), change in Lee Symptom Scale (LSS) summary score, duration of response (DOR) and change in CS dose were secondary end points. Results A total of 42 patients at median 42 (17-68) years were enrolled, 61.9% (n=26/42) had severe NIH-grade cGVHD, and 61.9% (n=26/42) had ≥4 organs involved. The cohort was heavily pretreated, with 52.4% (n=22/42) having received ≥5 prior lines of therapy (LOTs). Lung involvement occurred in 57.1% (n=24/42) (23.8% with lung score 3). The median time from transplantation to cGVHD diagnosis was 217 days (68-743). Median time from ruxolitinib initiation to combination therapy was 303 days (69–2471). At median follow-up of 178 days (57–577), ORR was 54.8% (n=23/42) (95%CI 39.8–67.0), with BOR reaching 76.2% (n=32/42) (95%CI 60.0–87.1). Patients achieved responses at a median of 48 days (21-112) after starting combination treatment. Subgroup analyses revealed that ORR was 53.9% (n=14/26) in severe cGVHD and 63.6% (n=14/22) in ≥5 prior LOTs. Lung cGVHD showed 87.5% (PR:58.3%; CR:29.2%) symptom-based ORR and 12.5% (PR:12.5%) FEV1%-based ORR. Ocular cGVHD demonstrated higher sensitivity to therapy (ORR 45.5% [18.2% CR + 27.3% PR]) than joint/fascia disease (36.0% ORR [12.0% CR + 24.0% PR]). FFS was 92.5% (82.3–100.0) at 12 months. CS doses were reduced in 90% of patients (median reduction 70.8%). The safety analysis revealed leukocytopenia as the most common hematologic adverse event, occurring in 7.2% of patients (n=3/42). Infectious complications included pneumonia in 14.3% of cases (n=6/42), with grade ≥3 events observed in 4.8% (n=2/42). Notably, no treatment-related discontinuations or grade ≥4 hematologic toxicities were reported. The combination was well tolerated with preserved immune reconstitution and improved LSS. Clinically meaningful improvement (≥7-point reduction) in LSS summary scores was achieved by 19.1% of patients (8/42) at 3 months. Responders demonstrated significantly greater LSS improvement compared to non-responders. Conclusion The belumosudil and ruxolitinib combination demonstrated clinically meaningful efficacy in ruxolitinib-refractory cGVHD. High response rates (ORR 54.8%, best ORR 76.2%), durable disease control (12-month FFS 92.5%), and significant CS reduction (median 70.8% dose decrease) were achieved without severe toxicity (grade ≥3 infections: 4.8%; no treatment discontinuations). These findings support the mechanistic rationale for concurrent JAK/ROCK inhibition and warrant prospective validation.

BackgroundHepatocellular carcinoma (HCC) is a common cancer that is increasingly becoming a global health problem and a major public health concern. In order to improve patient outcomes, additional biomarkers and targets must be explored. Ubiquitination-related genes (URGs), as tumor regulators, exhibit multiple functions in tumor development. Our objective was to examine the influence of URGs on the prognosis of patients with HCC.MethodsBy utilizing unsupervised cluster analysis, we were able to identify URGs in the database and create a risk score profile for predicting the prognosis of patients with HCC. The model's clinical application was explored using subject operating characteristic curves, survival analysis, and correlation analysis. We additionally examined the variances in clinical traits, immune infiltration, somatic genetic alterations, and responsiveness to treatment among high- and low-risk populations identified by the prognostic model. Scores for immune cell infiltration and immune-related pathway activity were determined by performing ssGSEA enrichment analysis. Additionally, to investigate potential mechanisms, we utilized GO, KEGG and GSVA analyses.ResultsWe developed a risk scoring model that relies on genes associated with ubiquitination. As the risk score increased, the malignancy and prognosis of the tumor worsened. The high-risk and low-risk groups exhibited notable disparities in relation to the immune microenvironment, genes associated with immune checkpoints, sensitivity to drugs, and response to immunotherapy.ConclusionThe utilization of a risk model that relies on genes associated with ubiquitination can serve as a biomarker to assess the prognosis of patients with HCC, and aid in the selection of suitable therapeutic agents.

Patients with TP53-mutated myelodysplastic neoplasms (MDS) have unfavorable prognoses; the benefit of cytoreductive treatment before hematopoietic stem cell transplantation (HSCT) is debated. We retrospectively analyzed 284 MDS patients undergoing allogeneic HSCT; among which 49 had TP53 mutation, with 38 receiving cytoreduction and 11 treated exclusively with best supportive care (BSC) before transplantation. Regardless of TP53 allelic state, patients with mutated-TP53 had a lower overall survival rate and higher relapse rate than those with wild-type TP53 (P < 0.001, P = 0.002, respectively). Among the TP53-mutated cohort, the 2-year overall survival rate in the cytoreduction group was comparable to that in the BSC group (34.6% vs. 45.5%, P = 0.53), and no other prognostic benefit was observed as well (all P < 0.05). Moreover, no prognostic difference was found among the chemotherapy subgroup, hypomethylating agent subgroup, and BSC subgroup (all P > 0.05). Patients in the pre-HSCT measurable residual disease (MRD) negative subgroup, pre-HSCT MRD-positive subgroup, and BSC subgroup exhibited similar prognoses (all P > 0.05). Multivariate analyses showed that pre-HSCT cytoreduction was not associated with post-transplant survival (all P > 0.05). In conclusion, TP53-mutated MDS patients have poor post-HSCT outcomes; compared to BSC, pre-HSCT cytoreduction doesn’t improve prognosis, even in those with MRD negative before transplantation.

Membranous nephropathy (MN) is a rare complication that can occur after allogeneic hematopoietic stem cell transplantation (allo-HSCT). MN patients may develop nephrotic syndrome or even kidney failure, which greatly affects their quality of life and prognosis. However, current knowledge regarding MN after allo-HSCT is limited. Thus, a multicenter nested case‒control study was conducted. Patients who had been diagnosed with MN after allo-HSCT were retrospectively identified at 8 HSCT centers. A total of 51 patients with MN after allo-HSCT were included. The median age of MN patients after allo-HSCT was 38 years, and the median duration from HSCT to MN was 18 months. The use of HLA-matched donors (P = 0.0102) and peripheral blood as the graft source (P = 0.0060) were identified as independent predisposing risk factors for the onset of MN after allo-HSCT. Compared to those in the control group, the incidence of extensive chronic graft-versus-host disease was greater in the MN patients (P = 0.0002). A total of 31 patients developed nephrotic syndrome. Patients receiving combination treatments of corticosteroids and immunosuppressants appeared to have better outcomes. In conclusion, MN is a rare but occasionally severe complication following HSCT and may require active treatment.