Biomedical subjects

Kun Li

Publications and source records attributed to Kun Li.

6 recordsLinked to original sources

PubMed2026

Distal versus proximal radial access for diagnostic cerebral angiography: comparative outcomes and learning curve analysis.

BACKGROUND AND PURPOSE: Distal transradial access (dTRA) is an alternative to proximal transradial access (pTRA) for neuroangiography, but comparative real-world data and evidence on its early learning curve remain limited. We compared procedural performance and access-site complications between dTRA and pTRA and evaluated the early learning curve of dTRA. METHODS: We retrospectively analyzed 470 diagnostic cerebral angiography procedures, representing 421 unique patients, performed via radial access at a single center between January 2025 and February 2026, including 237 dTRA and 233 pTRA procedures. Baseline characteristics, including age, sex, body mass index (BMI) category, aortic arch type, and antiplatelet/anticoagulant use, procedural performance, and clinically assessed access-site events were compared between groups. Radial artery occlusion (RAO) was assessed by postoperative bedside pulse examination and confirmed with Doppler ultrasound when clinical findings were uncertain. Multivariable logistic regression was used to evaluate predictors of RAO, persistent bleeding or repeated compression, hand edema, and a composite access-site event endpoint. Because repeated procedures occurred in a subset of patients and event counts were limited, first-procedure sensitivity analysis and analyses of infrequent outcomes were interpreted cautiously. The dTRA learning process was assessed in the first 100 dTRA cases performed by a single operator using multivariable regression, cumulative sum (CUSUM) analysis, segmented trend analysis, and phase-based comparisons. RESULTS: Baseline characteristics were comparable between groups, including age, male sex, BMI category, aortic arch type, and antiplatelet/anticoagulant use. Compared with pTRA, dTRA was associated with more puncture attempts (3.0 [2.0-4.0] vs 2.0 [1.0-3.0], P < 0.001), longer puncture time (2.0 [1.0-5.0] vs 2.0 [1.0-3.0] min, P = 0.003), lower first-pass success (19.4% vs 35.2%, P < 0.001), and a higher crossover rate (11.4% vs 6.0%, P = 0.037). However, dTRA was associated with a lower clinically assessed RAO rate (2.5% vs 7.7%, P = 0.011). On multivariable analysis, pTRA was independently associated with higher odds of RAO (OR 3.27, 95% CI 1.26-8.49, P = 0.015) and the composite access-site event endpoint (OR 3.12, 95% CI 1.55-6.28, P = 0.001). Similar findings were observed in a sensitivity analysis restricted to the first procedure per patient. In the first 100 dTRA cases, cumulative dTRA experience was independently associated with shorter total procedure time (beta = -0.074 min/case, P = 0.009), while CUSUM and moving-average analyses suggested that the major learning effect occurred within approximately the first 10-15 cases. CONCLUSIONS: In this retrospective single-operator cohort, dTRA was associated with lower clinically assessed RAO than pTRA despite greater access difficulty. The early learning effect was mainly reflected in shorter total procedure time. These findings support the feasibility of dTRA but should be interpreted cautiously given the study's observational design and limited anatomical data.

Humans↗

PubMed2026

Pan-cancer analysis identifies KANSL2 as a cell-cycle-associated regulator of tumor progression and immunity in liver hepatocellular carcinoma.

KANSL2, a core component of the NSL histone acetyltransferase complex, has been implicated in tumorigenesis. However, its pan-cancer relevance and functional role in liver hepatocellular carcinoma (LIHC) remain unclear. Multi-omics data from TCGA, GEO, and HPA were integrated to systematically evaluate KANSL2 expression, clinical significance, genomic alterations, and immune associations across cancers. Functional enrichment, immune infiltration analyses, and single-cell transcriptomics were performed. In vitro assays were conducted to validate the biological effects of KANSL2 in LIHC cells. KANSL2 is broadly upregulated across cancers and exhibits strong diagnostic performance. Elevated KANSL2 expression correlates with unfavorable prognosis, particularly in LIHC. Mechanistically, KANSL2 and its co-expressed genes are enriched in cell-cycle progression. KANSL2 expression is also closely associated with immune infiltration and immunoregulatory signaling within the tumor microenvironment, with single-cell data indicating preferential expression in proliferative T-cell subsets. Functional experiments demonstrate that KANSL2 silencing suppresses proliferation, migration, and invasion, and induces G2/M phase arrest in LIHC cells. Notably, its effects on apoptosis are limited, suggesting that KANSL2 primarily drives tumor progression through cell-cycle-dependent mechanisms. This study identifies KANSL2 as a key regulator of tumor progression and immune remodeling in LIHC. By promoting malignancy predominantly via cell-cycle control, KANSL2 represents a promising biomarker for diagnosis and prognosis, and a potential therapeutic target.

Carcinoma, Hepatocellular↗

PubMed2026

Changes of DNA methylation and gene expression profile in placental villi and chorioamniotic membranes under preeclampsia.

BACKGROUND: Preeclampsia (PE) is a serious pregnancy complication with elusive pathogenesis. Although epigenetic dysregulation is implicated, its layer-specific placental roles are poorly defined. This study aimed to identify shared and layer-specific epigenetic alterations in PE by profiling DNA methylation and gene expression in placental villi (PV) and chorioamniotic membranes (CAM). RESEARCH DESIGN AND METHODS: PV and CAM samples were collected from 7 normal and 8 PE pregnancies, and three public DNA methylation datasets (GSE98224, GSE44667, GSE75196) were integrated. Differentially methylated genes (DMGs) and differentially expressed genes (DEGs) were identified based on whole-genome methylation and transcriptome sequencing. Layer-specific and shared gene sets were identified by cross-analysis, with functional annotation using Gene Ontology (GO). RESULTS: EM-seq revealed a hypermethylation-dominant, tissue-specific methylation landscape in PE placentas. Cross-tissue comparison identified shared DMGs between the two layers, including nine key genes consistently altered in public datasets. Integrated analysis in PV further identified 22 co-dysregulated genes, enriched in thermoregulation, maternal-fetal immunity, signal transduction, and cell differentiation. CONCLUSIONS: This study elucidates the shared and layer-specific dysregulation of gene networks at methylomic and transcriptomic levels in PE placenta. Comparing PV and CAM highlights placental epigenetic heterogeneity and dysfunction, offering novel clues for mechanistic research and layer-targeted therapies.

Humans↗

PubMed2026

[State Changes and Stability Grading of Driver Genes in Non-small Cell Lung Cancer Based on Repeated NGS Testing].

BACKGROUND: Next-generation sequencing (NGS)-based driver gene testing has become a routine component of molecular subtyping and precision therapy for non-small cell lung cancer (NSCLC). Dynamic genomic monitoring facilitates early detection of resistance-related molecular alterations and informs timely therapeutic adjustments. However, standardized criteria for evaluating the stability of serial NGS testing are currently lacking, and the applicability of NGS using formalin-fixed paraffin-embedded (FFPE) specimens for dynamic monitoring remains poorly defined. This study aims to establish a stability grading system for driver gene status alterations based on repeated NGS testing, and to provide evidence-based support for clinical repeat biopsy strategies. METHODS: Data from 1232 patients with NSCLC who underwent two or more NGS tests on FFPE tissue specimens at Beijing Chest Hospital between June 2019 and April 2026 were collected retrospectively. Patients with an interval of ≥4 months between the initial and last tests were included to ensure the representativeness of temporal analysis, resulting in a main analysis cohort of 942 patients. The Kappa consistency test was used to evaluate the state stability of nine core driver genes [epidermal growth factor receptor (EGFR), Kirsten rat sarcoma viral oncogene homolog (KRAS), anaplastic lymphoma kinase (ALK), ROS proto-oncogene 1, receptor tyrosine kinase (ROS1), mesenchymal‑epithelial transition factor (MET), rearranged during transfection (RET), v-raf murine sarcoma viral oncogene homolog B1 (BRAF), erb‑b2 receptor tyrosine kinase 2 (ERBB2), and phosphatidylinositol‑4,5‑bisphosphate 3‑kinase catalytic subunit alpha (PIK3CA)] and to construct a five‑level grading system. Paired variant allele frequency (VAF) differences were compared using the Wilcoxon signed‑rank test. Independent influencing factors for mutation accumulation were identified by binary Logistic regression. RESULTS: The state stability of the nine genes was classified into five levels: EGFR showed high stability (Kappa=0.838), ROS1/ALK/KRAS good stability, BRAF/PIK3CA/RET moderate stability, and ERBB2 low stability, and MET showed high instability. MET exhibited the highest rate of state change (9.3%) with a raw observed agreement of 90.7%. Its Kappa value (0.172) was influenced by the low prevalence (3.7%) compression effect and should therefore be interpreted alongside the observed agreement (90.7%) and the prevalence-adjusted and bias-adjusted Kappa (PABAK). The VAF of PIK3CA increased significantly (P=0.005). T790M positivity increased from 5.8% to 10.8%, and 30 new C797S mutations were detected at the last test (13 with T790M, 17 without). The overall rate of new driver gene variants in the main cohort was 18.0%. Binary Logistic regression showed that a lower number of initial mutated genes was the only independent predictor of new variants [odds ratio (OR)=0.399, P<0.001], while sex and detection interval showed no independent association. CONCLUSIONS: A five level stability grading system for state changes of driver genes in NSCLC based on repeated NGS testing has been established. MET showed the most frequent state changes, which should be interpreted in conjunction with the prevalence effect. The VAF increase of PIK3CA is an observational finding, and its clinical significance requires further prospective validation. A lower initial mutation burden may reflect tumor clonal complexity and was associated with a higher likelihood of subsequent acquisition of new variants. FFPE based NGS is applicable for repeated testing at clinical treatment decision nodes.

Humans↗

PubMed2025

Cholesterol Metabolism-related Characteristics Predict Therapeutic Response and Survival in Esophageal Cancer.

INTRODUCTION: Cholesterol homeostasis has been identified as an essential downstream pathway of mutations in TP53. Esophageal cancer is one of the most prevalent malignancies exhibiting the mutation. OBJECTIVES: To explore the significance of cholesterol metabolism-related characteristics in tumor phenotype and treatment outcomes of esophageal cancer. METHODS: We established a cholesterol metabolism-related gene set (CMGs) and performed Lasso-Cox analysis to identify prognostic signatures. Nomogram-based risk scores and clinical stages afterwards were constructed and evaluated. We simultaneously identified two metabolic subtypes based on the distinct features of the CMGs. We annotated the functional and pathway characteristics of differentially expressed genes between the clusters and compared the differences in clinical and immune characteristics. Finally, we assessed the prognostic value of signatures in the GSE53625 and two clinical cohorts using whole-exon sequencing and multiplex immunofluorescence. RESULTS: Our study identified five cholesterol prognosis-related genes (CRGs) that demonstrated superior prognostic efficacy in the training set compared to clinical staging, validated in independent public databases and two clinical cohorts. According to the different expression patterns of the signatures, patients were divided into two subtypes. The C1 group demonstrated poorer overall survival, response to immunotherapy, and downregulation of the p53 pathway. In the immune correlation analysis, we found that the risk score based on 5-signature model was significantly positively correlated with the abundance of suppressive immune cells and the immune checkpoints. Finally, we explored the impact of expression and genomic polymorphism of the signatures on the prognosis at the pan-cancer level. CONCLUSIONS: Our findings underscore the distinct expression patterns of CRGs in esophageal cancer. These signatures are efficient to serve as prognostic indicators and assess the effectiveness of immunotherapy. They may also represent promising targets in other TP53 mutant malignancies.

Humans↗

PubMed2024

Comparative genomic landscape of lower-grade glioma and glioblastoma.

Biomarkers for classifying and grading gliomas have been extensively explored, whereas populations in public databases were mostly Western/European. Based on public databases cannot accurately represent Chinese population. To identify molecular characteristics associated with clinical outcomes of lower-grade glioma (LGG) and glioblastoma (GBM) in the Chinese population, we performed whole-exome sequencing (WES) in 16 LGG and 35 GBM tumor tissues. TP53 (36/51), TERT (31/51), ATRX (16/51), EFGLAM (14/51), and IDH1 (13/51) were the most common genes harboring mutations. IDH1 mutation (c.G395A; p.R132H) was significantly enriched in LGG, whereas PCDHGA10 mutation (c.A265G; p.I89V) in GBM. IDH1-wildtype and PCDHGA10 mutation were significantly related to poor prognosis. IDH1 is an important biomarker in gliomas, whereas PCDHGA10 mutation has not been reported to correlate with gliomas. Different copy number variations (CNVs) and oncogenic signaling pathways were identified between LGG and GBM. Differential genomic landscapes between LGG and GBM were revealed in the Chinese population, and PCDHGA10, for the first time, was identified as the prognostic factor of gliomas. Our results might provide a basis for molecular classification and identification of diagnostic biomarkers and even potential therapeutic targets for gliomas.

Humans↗