Objective To develop a transcriptional signature of gemcitabine(GEM)resistance using patient-derived organoids(PDOs)from cholangiocarcinoma and to validate its biological consistency and predictive rele-vance.Methods Transcriptomic profiles and drug sensitivity data from four PDOs were collected and analyzed through Hallmark pathway enrichment and pre-ranked GSEA in order to construct a 23-gene resistance signature.The associated pathway patterns were validated in TCGA-CHOL and GSE236894 cohorts,while correlations with drug response metrics were assessed with CCLE and PharmacoDB,complemented by experimental validation in cell models.Results GEM resistance was primarily enriched in cell cycle and E2F target pathways.The 23-gene signature was positively correlated with AUC in PDOs and significantly associated with proliferation markers(e.g.,TOP2A,MKI67)and cell cycle activity in independent cohorts.Database analyses further demonstrated a significant positive correlation between the signature score and GEM AAC_recomputed(ρ=0.149,P＜0.001),with higher scores which indicated a stronger resistance.Experimental findings confirmed that signature-related genes remained expressed in re-sistant cells but were suppressed in sensitive cells.Conclusions This signature provides a robust and biologically in-terpretable indicator of GEM resistance in cholangiocarcinoma,with strong generalizability across datasets.
Objective To explore the factors affecting the numerical accuracy of flash glucose monitoring (FGM) system in patients after pancreatic surgery. Methods A retrospective analysis was conducted on 279 adult patients who underwent elective pancreatic surgery at Peking Union Medical College Hospital from March 2024 to March 2025. Finally, 255 cases were included. All patients wore FGM sensors on the dorsum of the left upper arm one day before surgery, and received point-of-care (POC) capillary blood glucose measurements at least twice postoperatively. The reference blood glucose values were contemporaneous POC blood glucose readings. Paired matching was performed by taking the time points of POC blood glucose detection as benchmarks, and retrieving the closest FGM readings in the Gplus system for pairing. The mean absolute difference of paired blood glucose values was calculated for each subject. LASSO regression was used for variable selection, and Bootstrap resampling was applied to evaluate the occurrence frequency of screened variables. Multiple linear regression analysis was adopted to investigate the correlation between relevant variables and the mean difference of paired blood glucose values. Results The median mean difference between FGM readings and POC blood glucose values was 1.2 mmol/L. Multiple linear regression analysis revealed that maximum postoperative blood glucose (β=0.082, 95% CI: 0.055-0.108, P＜0.001), intraoperative crystalloid infusion (per 1L increment, β=0.124, 95% CI: 0.054-0.194, P＜0.001), jaundice (β=0.215, 95% CI: 0.019-0.412, P＜0.05) and age (per decade increase, β=0.091, 95% CI: 0.031-0.150, P＜0.05) were linearly correlated with the natural logarithm of the mean paired blood glucose difference(Radj2=0.245). Conclusions Age, jaundice, intraoperative crystalloid infusion volume and maximum postoperative blood glucose are independent influencing factors for postoperative FGM accuracy. Elevations of these indicators are linearly correlated with greater FGM deviation.
Objective To explore the potential synergistic roles of AU-rich elements(AREs)and their binding proteins(AREBPs)in post-transcriptional regulation and the translation process.Methods A customized algorithm was utilized to extract the core ARE motifs within the 3′UTR regions across human and mouse genomes.The binding sites of AREBPs were identified by integrating data from the Postar3 database,public CLIP-seq data-sets from GEO.Independently constructed CLIP-seq database and PrismNet deep learning predictions.Fisher's exact test was applied to calculate the enrichment degree(odds ratio)of specific AREBPs in tissue-specific genes.The co-expression patterns between AREBPs and target genes were analyzed by combining the GTEx database and tis-sue-specific developmental RNA-seq datasets(e.g.,kidney development dataset GSE100859).Results A com-prehensive genome-wide map of conserved 3′UTR AREs in humans and mice was successfully generated.Specific AREBPs exhibited significant binding enrichment(P＜0.05)in tissue-specific genes associated with muscle,brain,kidney and heart.Expression profiling analysis revealed that during tissue development(such as kidney development),genes containing AREs showed significantly different expression patterns compared to those without AREs.Conclu-sions AREs and their binding proteins play a highly specific function in kidney development,genes containing AREs showed significantly different expression patterns as compared to those without AREs.Conclusions AREs and their binding proteins play a highly specific role in post-transcriptional regulation across different tissues.This study provides a crucial bioinformatics evidence for understanding the RNA regulatory mechanisms underlying tissue de-velopment and homeostasis maintenance.
Objective To investigate the clinical characteristics, diagnostic process, surgical treatment and peri-operative management of retroperitoneal dedifferentiated liposarcoma (DDLPS) and to improve awareness of this type of rare giant tumor while providing a reference for future clinical diagnosis and treatment. Methods A case of a 57-year-old male patient admitted to the Department of Urology, Peking Union Medical College Hospital in September 2025. The patient′s electronic medical records were retrospectively reviewed, including outpatient and inpatient records, laboratory and radiology results, and treatments during hospitalization. Results Physical examination revealed a giant palpable mass in the left abdomen. Radiology imaging showed significant displacements of the spleen, pancreas, left kidney, and left adrenal gland by the tumor and a compressed left ureter, resulting in upper urinary tract hydronephrosis. After en bloc resection, the tumor measured up to 45 cm in maximum diameter and weighed approximately 12.5 kg. Pathological fluorescence in situ hybridization (FISH) demonstrated amplification of murine double minute 2 (MDM2), supporting the diagnosis of DDLPS. The patient recovered uneventfully after surgery, was discharged on postoperative day 11, and remained in generally good condition at the 1-month follow-up. Conclusions The case demonstrated complex imaging features, since DDLPS with polymorphic calcification is relatively rare. For retroperitoneal masses of this size, diagnosis should be established based on a combination of imaging findings, pathological examination, and MDM2 amplification testing. Adequate preoperative assessment and complete surgical resection are also essential for relieving compression-related symptoms and improving prognosis.
Autoimmune hepatitis(AIH)is a chronic,inflammatory liver disease mediated by the immune system.Due to a breakdown in immune tolerance to liver autoantigens,multiple immune cells become activated and release abundant inflammatory factors.These autoantigens and inflammatory factors act upon cell surface receptors,activa-ting multiple signaling pathways,including NF-κB,AMPK,PI3K/Akt,JAK/STAT,and MAPK,which induce or exacerbate immune-mediated liver injury.This occurs through the modulation of various processes in immune cells(such as dendritic cells,macrophages,and T cells),including energy metabolism,autophagy,apoptosis,and re-ceptor expression.
