Objectives To investigate to investigate the role of circ_0000075 levels and its regulatory mechanism in patients with acute myeloid leukemia (AML).Methods A total of 115 patients with AML and 60 patients with non-haematological tumors (control group) were included. Bone marrow fluid was collected, and the patients were followed-up for a 5-year postoperative prognosis. RT-qPCR was used to detect the expression of circ_0000075 and miR-218-5p, Kaplan-Meier curves recorded for prognostic survival, and multivariate Cox regression analysis to assess factors affecting patient mortality. Cell proliferation was assessed using the Cell Counting Kit-8 (CCK-8), and Transwell assays were performed to study cell migration and invasion. A dual-luciferase reporter assay verified the interaction between the interaction between circ_0000075 and miR-218-5p.Results High levels of circ_0000075 were present in AML patients and correlated with their pathological features. AML patients with high circ_0000075 expression had lower survival rates, and circ_0000075 was predicted to be a risk factor for poor prognosis in AML patients. circ_0000075 levels were elevated in AML cells compared to normal cells, and silencing circ_0000075 attenuated cancer cell proliferation, migration, and invasion. miR-218-5p has abundant circ_0000075 binding sites, and its expression is markedly suppressed in cancer tissues. A dual-luciferase reporter assay demonstrated a targeting relationship between circ_0000075 and miR-218-5p. Response experiments suggested that the use of miRNA inhibitors promoted AML cell function.Conclusion circ_0000075 is a risk factor for poor prognosis in AML patients. Silenced circ_0000075 blocks the function of tumor cells mainly by promoting miR-218-5p expression.

The optimal timing for systematic re-excision following the unplanned excision (UE) of soft tissue sarcomas (STS) remains controversial. This study evaluated the impact of delayed versus immediate re-excision on overall survival (OS), progression-free survival (PFS), and local recurrence-free survival (LRFS). We retrospectively analysed patients who underwent re-excision for primary STS following UE between August 2011 and February 2019. Patients with metastasis at presentation or a follow-up of less than two years were excluded. The cohort was stratified into an early re-excision (RE) group (≤ 3 months from initial UE) and a late RE group (> 3 months). The LRFS, PFS, OS, and the extent of excision were assessed. A total of 104 patients met the inclusion criteria of this study, including 74 cases in the early RE group and 30 cases in the late RE group. At a mean follow-up of 61.0 ± 20.5 months, the 5-year OS was 86.5

Background Mesenchymal stem cell (MSC)-derived endothelial-like cells exhibit enhanced angiogenic potential compared with undifferentiated MSCs. However, the role of N6-methyladenosine (m6A) RNA modification in MSC endothelial differentiation remains unclear. Methods Human bone marrow-derived MSCs were isolated and induced toward an endothelial phenotype using cytokine-enriched medium. Endothelial differentiation was evaluated using flow cytometry, western blotting, immunofluorescence staining, tube formation assays, and Dil-Ac-LDL uptake assays. MeRIP-seq and RNA-seq were performed to profile transcriptome-wide m6A methylation and gene expression changes. Bioinformatics analyses, including GO enrichment, KEGG pathway analysis, and protein–protein interaction (PPI) network construction, were conducted to identify key regulatory genes and pathways. Results Following induction, MSCs exhibited endothelial characteristics, including increased expression of CD31 and CD34, enhanced tube formation ability, and increased Dil-Ac-LDL uptake. Transcriptome-wide analysis identified 16,355 differentially methylated peaks and 2,732 differentially expressed genes, including 1,204 differentially methylated and expressed genes (DMEGs). Functional enrichment analysis revealed that DMEGs were mainly associated with extracellular matrix organization, endothelial differentiation, and cell adhesion. PPI network analysis identified a highly interconnected module, and integrin family genes (ITGA1, ITGAV, ITGA11, ITGB5) and ADAMTS2 were identified as key hub genes. Conclusions This study provides a transcriptome-wide landscape of m6A methylation during endothelial differentiation of BM-MSCs and identifies key regulatory pathways and hub genes potentially involved in this process. These findings suggest that m6A-mediated epitranscriptomic regulation plays an important role in MSC endothelial differentiation and angiogenesis.

ABSTRACT Background GATA binding protein 2 (GATA2) plays a crucial role in the differentiation, proliferation, and maintenance of hematopoietic stem cells (HSCs). GATA2 mutations have been identified in acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), but the impact of somatic GATA2 mutations on prognosis remains controversial, especially on patients who undergo allogeneic hematopoietic stem cell transplantation (allo‐HSCT). Objectives The aim of this retrospective case–control study was to explore the prognostic significance of somatic GATA2 mutations in MDS/AML patients who underwent allo‐HSCT. Study Design Propensity score matching (PSM) analysis was used to match patients with wild‐type GATA2 as the control group (ratio 1:3). A total of 14 patients with somatic GATA2 mutations and 39 patients with wild‐type GATA2 were enrolled. Results The baseline characteristics were comparable between the two groups. However, patients with GATA2 mutations had a higher frequency of WT1 mutations and relapse rate (p = 0.036 and p = 0.008, respectively). Compared to patients with wild‐type GATA2, patients with GATA2 mutations had shorter progression‐free survival (PFS) and overall survival (OS), and post‐transplant PFS (p < 0.001, p = 0.030, and p = 0.004, respectively). Subgroup analysis showed that the PFS, OS, post‐transplant PFS, and OS of patients with GATA2 non‐zinc finger domain 1 (non‐ZF1) mutations (p < 0.001, p = 0.004, p < 0.001, and p = 0.049, respectively), but not those of patients with somatic GATA2 ZF1 mutations, were shorter than that of patients with wild‐type GATA2. Moreover, somatic GATA2 mutations and WBC count ≥ 20.86 × 109/L were independent adverse prognostic factors for PFS (p = 0.005 and p = 0.020, respectively). Relapse before transplantation was an independent adverse prognostic factor for OS (p = 0.009). Conclusions Our preliminary study revealed that somatic GATA2 mutations, especially non‐ZF1 mutations, may be associated with unfavorable outcomes in patients with MDS/AML, even for patients who underwent allo‐HSCT.

Objectives: Respiratory motion degrades the quantitative accuracy and test-retest (TRT) reliability of fluorine-18 fluorodeoxyglucose ([18F] FDG) positron emission tomography (PET)/computed tomography (CT) in lung cancer. This study investigated whether a deep-learning-based respiratory motion correction (RMC) method improves the TRT reliability and image quality of [18F] FDG PET tumor quantification compared with non-motion-corrected (NMC) reconstructions. Methods: Thirty-one patients with primary lung cancer underwent three PET acquisitions: whole body free breathing (Scan1), thoracic free breathing (Scan2), and thoracic controlled breathing (ScanCB). Each dataset was reconstructed with and without RMC. Visual assessments of liver motion artifacts, lesion clarity, and PET-CT co-registration were scored. Lung tumors were segmented to derive standardized uptake value max (SUVmax), SUVmean, metabolic tumor volume (MTV), PET-derived lesion length (PLL), and total lesion glycolysis (TLG). Visual image scores and TRT reliability of tumor quantification were compared using Kruskal-Wallis one-way analysis of variance and intraclass correlation coefficients (ICCs). Results: RMC reconstructions achieved higher visual scores of lesion clarity and PET-CT co-registration across all lung lobes and significantly reduced liver motion artifacts compared with NMC reconstructions. Differences in SUVmax, SUVmean, PLL, MTV, and TLG between Scan2 and ScanCB were significantly smaller with RMC than with NMC. ICCs for SUVmax, SUVmean, MTV, and TLG were higher between scans with RMC than NMC reconstructions, indicating improved TRT reliability. Conclusions: The deep-learning-based RMC method improved the image quality and TRT reproducibility of [18F] FDG PET/CT quantification in lung cancer, supporting its potential for routine adoption in therapy-response assessments.

To describe imaging features of 18F-FDG positron emission tomography/computed tomography (PET/CT) of polymyalgia rheumatica (PMR) and evaluate their ability to distinguish PMR in elderly patients presenting with myalgia. Ninety-three elderly patients (male 29, female 64, age 66.3 ± 8.7 years) with myalgia underwent 18F-FDG PET/CT for suspected PMR. Based on final clinical diagnosis, clinical data of PMR patients and other subjects were compared. Diagnostic efficacy of 2012 EULAR/ACR classification criteria was assessed. PET/CT findings were reviewed to define PMR-related metabolic patterns. An imaging score algorithm was developed to discriminate PMR from rheumatoid arthritis (RA), the most common alternative diagnosis. The score algorithm’s diagnostic performance was validated in the cohort. Based on final clinical diagnosis, 44 (47.3

BACKGROUND:Immunoglobulin G4 (IgG4) is the least abundant IgG subclass and has distinctive structural and functional properties, including Fab-arm exchange and limited activation of antibody-dependent effector mechanisms. These features contribute to its generally non-inflammatory and tolerogenic profile. However, the role of IgG4 in rheumatoid arthritis (RA) remains incompletely understood. OBJECTIVE:This review aims to summarize and critically evaluate the biological characteristics of IgG4, its clinical significance in RA, and the potential therapeutic implications of IgG4-mediated immune responses. EVIDENCE:Elevated serum IgG4 levels have been reported in a subset of patients with RA and have been associated with disease activity, inflammatory markers, autoantibody levels, and treatment response in some studies. IgG4 autoantibodies, including antinuclear IgG4 antibodies, have also been detected in autoimmune diseases and may influence complement activation and proinflammatory cytokine production. However, findings remain heterogeneous, and current evidence is insufficient to establish IgG4 as an independent diagnostic or prognostic biomarker in routine RA care. CONCLUSION:IgG4 may have a complex, context-dependent role in RA, potentially reflecting both immune dysregulation and compensatory anti-inflammatory responses. Further research is needed to clarify its pathogenic mechanisms, clinical utility, and potential as a therapeutic target.

Background The nectin cell adhesion molecule 4 (NECTIN4) has been implicated in tumor progression and immune evasion, yet its role and translational targeted imaging potential in lung cancer remain unclear. Therefore, this study aims to elucidate the significance of NECTIN4 by integrating multi-omics analyses, and to evaluate the diagnostic efficacy of the NECTIN4-targeted PET/CT imaging in lung cancer. Methods Transcriptomic and proteomic datasets from The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), Gene Expression Omnibus (GEO) and other bioinformatic tools were used to characterize NECTIN4 expression, genomic alterations, epigenetic regulation, and prognostic relevance in lung cancer. Subsequently, in a prospective clinical cohort study involving 20 patients with suspected primary lung cancer, paired PET/CT imaging using Ga-68-N188 and F-18-FDG was conducted. Diagnostic performances were assessed by quantitatively comparing the tumor-to-blood pool ratio between malignant and inflammatory lesions. Results Bioinformatics analyses indicated that NECTIN4 was significantly upregulated across multiple cancer types and correlated with genomic instability and poor prognosis in non-small cell lung cancer (NSCLC). NECTIN4 expression was positively associated with DNA methyltransferases and RNA modifications, suggesting that it may be regulated by epigenetic and post-transcriptional. As for NECTIN4-targeted imaging, Ga-6(8)-N188 PET/CT exhibited superior specificity (100% vs. 50%) and comparable sensitivity (87.5% vs. 93.8%) to & sup1;F-8-FDG PET/CT in differentiating malignant from inflammatory lung lesions, but with lower sensitivity (42.2% vs. 100.0%) for detecting lymph node metastases and fewer identified distant metastatic lesions (21 vs. 51). Conclusion Integrated bioinformatics analyses prove that overexpression of NECTIN4 is associated with occurrence and progression of lung cancer. Further preliminary clinical translation study suggests the potential of NECTIN4-targeted radiotracer Ga-6(8)-N188 to aid in the differential diagnosis of lung cancer, highlighting a promising clinical application warrants further validation.

ObjectiveTo highlight the diagnostic value of the ferritin-LDH-IL-10 triad and image-guided targeted biopsy in intravascular large B-cell lymphoma (IVLBCL) presenting as fever of unknown origin (FUO), with a review of relevant literature.MethodsWe present a case of a 60-year-old woman with a 10-month history of cough, progressive fever, and weight loss. We retrospectively analyzed her clinical course, laboratory profile, imaging findings, and histopathological results, and reviewed the relevant literature on IVLBCL diagnosis.ResultsExtensive initial investigations including multiple biopsies (bone marrow, colon, skin) and imaging were nondiagnostic. Persistent extreme hyperferritinemia (peak >15,000 ng/mL), markedly elevated LDH (735 U/L), and strikingly high IL-10 (>600 pg./mL) formed a diagnostic triad raising suspicion for IVLBCL. Re-review of PET-CT identified a subtle pulmonary FDG-avid focus (SUVmax 3.0), guiding video-assisted thoracoscopic wedge resection. Histopathology confirmed IVLBCL with CD20 + tumor cells within vascular lumina. The patient subsequently met criteria for secondary hemophagocytic lymphohistiocytosis. R-CHOP immunochemotherapy achieved rapid symptom resolution and complete metabolic response on follow-up PET-CT.ConclusionThe triad of extreme hyperferritinemia, elevated LDH, and markedly increased IL-10 may serve as a useful diagnostic clue to raise suspicion for IVLBCL in FUO patients, though its interpretation is confounded by secondary HLH and requires prospective validation. When random biopsies fail, multidisciplinary re-evaluation of PET-CT to identify subtle targets for image-guided biopsy is essential for definitive diagnosis. Early recognition of this triad and adoption of a hypothesis-driven biopsy strategy can significantly improve diagnostic outcomes in this elusive lymphoma.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the only curative option for chronic myelomonocytic leukemia (CMML), yet the population benefit from HSCT and the optimal timing of HSCT remain controversial. Current guidelines, largely based on older CPSS criteria and retrospective data, may not reflect recent advances in transplant techniques and molecular stratification systems. This multicenter retrospective analysis included 389 adult CMML patients from 14 Chinese centers (2015-2023), aiming to reassess the survival benefit of allo-HSCT in a large multicenter cohort within the molecular era. Among all patients, 145 (37.3%) underwent allo-HSCT, including 68.3% from haploidentical donors. Risk stratification was performed using CPSS, MDAPS, CPSS-mol, and MMM systems. Landmark analysis set at day 148 (median transplant interval) was used to assess the effect of time-dependent covariates on long-term survival. The entire cohort had 1-, 3-, and 5-year overall survival (OS) rates of 82.7%, 55.5%, and 46.1%, respectively. In patients ≤70 years, allo-HSCT was associated with significantly improved 3-year OS in CPSS intermediate-1 (63.4% vs. 45.4%, p = 0.038) and intermediate-2 (60.2% vs. 38.7%, p = 0.049), MDAPS intermediate-1 (69.5% vs. 47.4%, p = 0.004), intermediate-2 (60.6% vs. 30.4%, p = 0.029), and high-risk (51.4% vs. 45.0%, p = 0.022), CPSS-mol intermediate-2 (59.8% vs. 39.0%, p = 0.046), and MMM high-risk groups (65.5% vs. 10.5%, p < 0.001). Landmark analysis confirmed sustained benefit in these subgroups. Haploidentical HSCT yielded outcomes comparable to matched donors. Multivariable analysis identified HSCT as an independent favorable factor for survival (HR = 0.619, p = 0.031). These findings advocate expanding transplant eligibility through integration of molecular stratification and modern HSCT platforms, particularly haploidentical protocols.

Objective This study was conducted to evaluate the predictive value of endoscopic measurements of cardia opening diameter and sliding hernia length for diagnosing gastroesophageal reflux disease. Methods A total of 233 patients with typical gastroesophageal reflux disease symptoms who underwent endoscopy and esophageal pH-impedance monitoring between September 2017 and September 2023 were enrolled in this study. Cardia opening diameter and sliding hernia length were measured during endoscopy under adequate gastric insufflation. Using esophageal pH-impedance monitoring as the gold standard (with acid exposure time >4% as the diagnostic criterion for gastroesophageal reflux disease), the correlation between cardia opening diameter/sliding hernia length and gastroesophageal reflux disease-related parameters was analyzed. A nomogram prediction model was subsequently developed. Results The optimal cutoff values for predicting pathological acid reflux were cardia opening diameter >2 cm and sliding hernia length >1 cm (area under the receiver operating characteristic curve = 0.648 for both). Compared with patients with a cardia opening diameter ≤2 cm, those with a cardia opening diameter >2 cm had significantly higher acid exposure time (6.8% vs. 2.5%), DeMeester score (25.7 vs. 10.9), and number of reflux episodes (108 vs. 59) (all p < 0.001). Similarly, sliding hernia length >1 cm was associated with more severe reflux parameters ( p < 0.05) and was more prevalent in males (72.4% vs. 43.6%). Univariate and multivariate logistic regression analyses demonstrated that a nomogram incorporating age, body mass index, and sliding hernia length exhibited good predictive performance (area under the curve = 0.739). Conclusion Endoscopically assessed cardia opening diameter and sliding hernia length are useful functional predictors of gastroesophageal reflux disease. The integrated prediction model may serve as a valuable diagnostic aid, especially in primary care or resource-limited settings.

The diagnosis of infectious diseases is often a challenging problem faced by clinicians, especially in the case of complex infections manifested as fever of unknown origin or inflammation of unknown origin (FUO/IUO). Currently, 18F-fluorodeoxyglucose (FDG) Positron emission tomography/Computed tomography (PET/CT) has been increasingly used in the inflammatory diseases. This study aimed to explore the diagnostic and therapeutic value of FDG PET/CT for infectious diseases in patients with FUO/IUO. A retrospective analysis was conducted on the clinical and imaging data of 156 consecutive hospitalized patients who underwent FDG PET/CT examination due to the etiological diagnosis of FUO/IUO and were ultimately diagnosed with infectious diseases. The analysis included general clinical characteristics and pathogenic distribution among patients. FDG PET/CT imaging results were evaluated, encompassing overall lesion detection rates in the cohort, detection efficacy for infectious foci caused by different types of pathogens, and FDG uptake patterns in lesions. The correlation between FDG PET/CT findings and serum inflammatory markers was assessed. Additionally, the impact of FDG PET/CT results on clinical diagnosis and treatment was evaluated through clinical questionnaires. Among the 156 patients with infectious diseases, 82 cases (52.6

PURPOSE:Hydration of patients before the PET/CT examination may lead to non-specific FDG accumulation in the intestine. This study aims to explore the influence of isotonic saline and hypotonic water on physiologic intestinal 18F-FDG uptake in PET/CT imaging. METHODS:185 patients were included, 82 patients were randomized to receive oral administration of isotonic saline and 103 patients received oral administration of hypotonic water before examination. About 32 patients in the isotonic group and 19 patients in hypotonic group underwent repeated PET/CT with pre-administration of hypotonic water, and the intra-individual comparative analysis was performed for the first and second examinations. Segmental uptake patterns were documented and volumetric regions of interest were delineated. The SUVmax of intestinal segment and the SUVmean of liver were recorded. RESULTS:No significant differences existed in baseline characteristics between the two groups. The isotonic group demonstrated lower physiological uptake incidence and target-to-background ratio (TBR) in all segments except jejunum and ascending colon (p < 0.05). Physiological uptake incidence in jejunum showed no intergroup difference, whereas the TBR of isotonic group showed lower tendency. Notably, the isotonic group exhibited higher physiological uptake incidence (p < 0.001) in the ascending colon, though no significant difference existed in TBR between two groups. These results were similar in intra-individual comparative analysis of the first and second examinations. Moreover, constipation was positively associated with FDG uptake in the ileum, diarrhea was positively associated with FDG uptake in the transverse colon, ascending colon and rectum. Bone tumors and gynecological tumors were positively correlated with FDG uptake in the ascending colon and transverse colon. BMI was negatively correlated with FDG uptake in the duodenum, ileum, jejunum, and sigmoid colon. CONCLUSION:Pre-administration of isotonic saline resulted in lower physiologic 18F-FDG uptake in different intestine segments (except ascending colon), which is helpful for accurate assessment of gastrointestinal diseases.

The nectin cell adhesion molecule 4 (NECTIN4) has been implicated in tumor progression and immune evasion, yet its role and translational targeted imaging potential in lung cancer remain unclear. Therefore, this study aims to elucidate the significance of NECTIN4 by integrating multi-omics analyses, and to evaluate the diagnostic efficacy of the NECTIN4-targeted PET/CT imaging in lung cancer. Transcriptomic and proteomic datasets from The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), Gene Expression Omnibus (GEO) and other bioinformatic tools were used to characterize NECTIN4 expression, genomic alterations, epigenetic regulation, and prognostic relevance in lung cancer. Subsequently, in a prospective clinical cohort study involving 20 patients with suspected primary lung cancer, paired PET/CT imaging using 68Ga-N188 and 18F-FDG was conducted. Diagnostic performances were assessed by quantitatively comparing the tumor-to-blood pool ratio between malignant and inflammatory lesions. Bioinformatics analyses indicated that NECTIN4 was significantly upregulated across multiple cancer types and correlated with genomic instability and poor prognosis in non-small cell lung cancer (NSCLC). NECTIN4 expression was positively associated with DNA methyltransferases and RNA modifications, suggesting that it may be regulated by epigenetic and post-transcriptional. As for NECTIN4-targeted imaging, ⁶⁸Ga-N188 PET/CT exhibited superior specificity (100

OBJECTIVE:Clinical data on incorporating selinexor into conditioning regimens before allogeneic hematopoietic stem cell transplantation (allo-HSCT) remain limited. We evaluated the feasibility and safety of selinexor-containing conditioning in patients with high-risk myeloid malignancies. METHODS:This retrospective single-center case series included 12 consecutive patients receiving selinexor-containing conditioning before allo-HSCT. Toxicities, engraftment, graft-versus-host disease (GVHD), relapse, non-relapse mortality (NRM), and survival were descriptively evaluated. PFS and OS were estimated using Kaplan-Meier methods; competing-risk methods were used for relapse, NRM, and GVHD; and follow-up was estimated using reverse Kaplan-Meier. RESULTS:All patients completed planned selinexor administration, with manageable toxicity and no unexpected organ toxicity. Neutrophil engraftment was achieved in all evaluable patients and platelet engraftment in the majority. Median follow-up was 42 months (95% CI, 25-42 months). Median PFS and OS were 9.0 months (95% CI, 2.0-25 months) and 10.0 months (95% CI, 2-30 months), respectively. At 12 months, the cumulative incidences of relapse and NRM were both 33.3% (95% CI, 10.3%-58.8%). Day + 100 overall aGVHD incidence was 41.7% (95% CI, 15.2%-66.5%), and 12-month overall cGVHD incidence was 25.0% (95% CI, 6.0%-50.5%). CONCLUSION:In this single-center retrospective experience, incorporation of selinexor into conditioning regimens prior to allo-HSCT was feasible and associated with manageable toxicity in in selected patients with high-risk myeloid malignancies. Given the small sample size and absence of a comparator cohort, these findings should be interpreted cautiously. Prospective studies are warranted to further define the role of selinexor in the transplant setting.

As one of the most common cancers worldwide, lymphoma requires reliable tools to assess treatment response. The Deauville score (DS) is a widely used PET/CT-based standard for this purpose and plays a central role in clinical decision-making and research. In many regions, DS is embedded in clinical workflows and directly influences treatment adjustment. However, DS assessment remains reader-dependent, as it requires complex longitudinal interpretation of prior and current PET/CT findings, leading to limited interobserver agreement and challenges for large-scale application. Here, we introduce a large language model (LLM)-based framework that leverages longitudinal PET/CT reports to perform structured, stepwise reasoning for automated Deauville scoring. In a multicentre dataset of 6,009 lymphoma cases from three hospitals, the model achieved 85.8% accuracy for six-class classification across internal and external cohorts, outperforming human readers and state-of-the-art baselines, with the greatest advantage observed in cases with low inter-reader agreement. These findings suggest that LLM-based approaches can provide a practical strategy for addressing complex imaging-derived clinical assessment tasks through structured semantic reasoning, enabling more standardized and scalable lymphoma response assessment.

Objective: To investigate the relationship between cardiovascular risk factors and the progression of motor and non-motor symptoms in Parkinson's disease (PD). Methods: We used data from the Parkinson's Progression Markers Initiative (PPMI) cohort with a follow-up duration of >5 years. Baseline assessments included genetic analysis, brain MRI, cardiovascular risk factors, and overall cardiovascular disease (CVD) risk. Motor symptoms and non-motor symptoms of PD were evaluated using the Movement Disorders Society revised Unified Parkinson's Disease Rating Scale (MDS-UPDRS) and sub-scores, Hoehn-Yahr stage, and Montreal Cognitive Assessment (MoCA). Statistical analyses comprised univariate and multivariate linear regression and stratified analysis. Results: A total of 169 newly diagnosed PD patients and 78 healthy controls (HCs) were included. At baseline, no significant differences in cardiovascular risk factors or overall CVD risk were observed between PD patients and HCs. Hypertension (β = 6.748, p = 0.040) and hyperlipidemia (β = 8.316, p = 0.005) were associated with faster motor progression. ApoE genotype was correlated with motor progression (β = 7.593, p = 0.007). PD patients with a moderate-to-low CVD risk (<20%) had milder axial motor symptoms (3.0 [IQR, 4.0] vs. 4.0 [IQR, 5.0], p = 0.048) and lower MDS-UPDRS Part I total scores (7.0 [IQR, 6.25] vs. 9.0 [IQR, 7.0], p = 0.039) at last follow-up compared to high-CVD-risk (≥20%) patients. Overall CVD risk was negatively correlated with total MoCA score at last follow-up (β = -0.208, p< 0.001). Conclusions: Cardiovascular risk factors accelerate the progression of motor and non-motor symptoms in PD, suggesting that management of modifiable CVD risk factors may represent a promising target to delay the progression of PD.

While variant TP53 is an adverse prognosis factor in myelodysplastic syndromes (MDS)/acute myeloid leukemia (AML), current clinical prognosis and variation feature analysis of TP53 alterations remain limited. We evaluated 333 MDS/AML patients with TP53 mutations, single nucleotide polymorphisms (SNPs), and wild-type TP53 to characterize clinical features and identify prognostic factors using next-generation sequencing (NGS) data. Interpretation requires caution due to sample size limitations, particularly in subgroup analyses. Multivariate analysis identified age, gender, cytogenetic risk, transplantation, white blood cell (WBC) count, TP53 status, and TP53 variant allele frequency (VAF) > 40

OBJECTIVE:To develop and validate an ovarian cancer risk assessment tool for first-degree relatives of patients in the Chinese population. METHODS:A bidirectional multicenter cohort was established, including 529 probands and 3141 first-degree relatives. Cancer incidence was analyzed using the standardized incidence ratio (SIR). Significant variables were identified through Cox regression analyses and visualized via a nomogram. Model performance was evaluated using the C-index, with first-degree relatives stratified into high- and low-risk groups based on a 10 % cancer risk threshold. RESULTS:Among 1596 first-degree female relatives, 57 ovarian cancer cases were identified, demonstrating a significant increase in SIR (SIR = 9.19; 95 % CI, 7.03-11.83; p < 0.001). In 980 relatives with germline mutations, elevated SIRs were observed for ovarian cancer (SIR = 23.33; 95 % CI, 16.51-32.09; p < 0.001) and breast cancer (SIR = 3.56; 95 % CI, 2.46-5.00; p < 0.001). Cox regression analyses identified key risk factors, including the proband's age of onset, tumor histology, gene mutation status, family history of breast cancer, and relationship to the proband. The nomogram demonstrated good predictive accuracy, with C-indices of 0.75 (training set), 0.75 (internal validation), and 0.71 (external validation). Calibration plots and Kaplan-Meier curves confirmed strong agreement and significant differences between high- and low-risk groups (cut-off value = 2.1). CONCLUSIONS:This study develops and preliminarily validates a risk assessment tool for first-degree relatives of ovarian cancer patients in China, utilizing accessible clinical and familial data to enable early identification of high-risk individuals.