Chongqing Cancer Hospital

Using the fibular flap as a model, this study aims to develop a three-dimensional visualization method for perforator vessels. This method integrates artificial intelligence algorithms, mixed reality technology, and polyetheretherketone (PEEK) fiducial markers to achieve precise localization and three-dimensional rendering of the vessels. The goal is to provide surgeons with an independent, controllable 3D vascular visualization system and to offer a reference for extending this method's application to multidisciplinary fields such as vascular intervention and neurosurgery. The study included three patients undergoing reconstructive surgery with fibular flaps. The technical procedure consisted of: (1) fabricating PEEK fiducial markers and affixing them to the designated flap donor site; (2) performing CT angiography and reconstructing the acquired two-dimensional data into a three-dimensional model incorporating the lower limb and the PEEK markers; (3) developing an artificial intelligence algorithm within the HoloLens 2 head-mounted holographic display to align the virtual 3D PEEK model with the physical markers on the patient, thereby achieving registration between the model and the human body. During surgery, we recorded the number of perforator vessels identified by the system versus the actual number found surgically, the distance between the projected and actual vessel exit points, and the time required for registration. Across the three patients, the system identified a total of five perforator vessels, which matched the surgical findings. The average distance between the localized and actual vessel exit points was 1.7 mm. The total registration time, from system activation to successful alignment, averaged 108 s, with the core registration process itself averaging 16 s. All flaps survived postoperatively with no related complications. In this study, an AI algorithm was developed and integrated into the HoloLens 2, which was able to identify the physical fiducial markers attached to the patient's body surface. Through the registration of these physical markers with their virtual counterparts, alignment between the human tissue and its three-dimensional model was achieved. This technical framework demonstrated potential versatility and adaptability, and may serve as a methodological reference for developing navigation systems in other surgical disciplines. However, its broader applicability requires validation through larger-scale future studies.

Lung cancer is the leading cause of cancer-related death and has the second-highest incidence worldwide. For patients with advanced EGFR-mutated non-small cell lung cancer, EGFR tyrosine kinase inhibitors (EGFR-TKIs) are the preferred treatment option; however, acquired resistance to TKIs is inevitable. Gefitinib and osimertinib, the first-generation and third-generation EGFR-TKI, have shown promising results in patients with EGFR-mutated lung cancer in clinical treatment. Here, we identified that pyruvate dehydrogenase kinase 1 (PDK1) was up-regulated in gefitinib- and osimertinib-resistant cell lines, and PDK1 knockdown rendered cells more sensitive to TKI treatment. PDK1 expression levels were significantly increased in lung, colon, liver, and breast cancer tissues compared with those in normal tissues. Histone demethylase KDM3A was also induced in TKI-resistant cell lines, and demethylated histone H3 lysine 9 to facilitate PDK1 expression to regulate TKI resistance. Further study demonstrated that METTL16 promoted the m6A modification of PDK1 mRNA, and the m6A reader IGF2BP1 directly recognized and enhanced PDK1 mRNA stability. Interestingly, KDM3A also induced METTL16 expression. Moreover, PDK1 inhibitor JX06 rendered cancer cells more sensitive to gefitinib treatment in vivo, and JX06 and gefitinib combination treatments have a synergic effect to inhibit tumor growth. In conclusion, the KDM3A/METTL16/PDK1 axis plays an important role in cancer development and TKI resistance, which may offer new prognostic biomarkers and therapeutic targets for TKI resistance in the future.

Publisher Correction: Early-phase semi-quantitative analysis versus full time-course quantitative modeling of ultrafast dynamic contrast-enhanced MRI for breast cancer diagnosis, molecular subtyping, and treatment response prediction

Introduction: Current guidelines lack consensus on fibrinogen replacement thresholds in critical hemorrhage. This study aims to establish evidence-based supplementation thresholds and optimal targets for ICU patients with major bleeding, providing a framework for individualized coagulation management. Methods: This prospective multicenter cohort study enrolled 197 patients with severe hemorrhage and coagulopathy from 12 tertiary ICUs in China. Standardized systems collected demographics, laboratory parameters, and interventions. Analysis comprised two phases: (1) Restricted cubic spline (RCS) models evaluated nonlinear associations between baseline fibrinogen and outcomes (hemostasis, ICU mortality), identifying a critical threshold at 1.54 g/L; (2) Post-treatment fibrinogen peaks (within 72h) were stratified into subgroups based on prior MIMIC-IV validation: < 1.54 g/L (low-risk), 1.54–2.0 g/L (intermediate), 2.0–2.5 g/L (target), ≥2.5 g/L (high-level). Statistical analyses included Cochran-Armitage test (dose-response), Firth’s regression (small-sample bias correction), and Kruskal-Wallis tests with Benjamini-Hochberg FDR correction (FDR< 0.05; transfusion heterogeneity). Results: We enrolled 197 patients with massive hemorrhage (treatment: n=98; control: n=99). Baseline data showed the treatment group had significantly greater blood loss (1735vs.967 mL, P=0.013), lower fibrinogen (1.49vs.2.04 g/L, P=0.001), and higher APACHE II scores (19.5vs.16.7, P=0.047). Pretreatment fibrinogen showed nonlinear associations with hemostasis and ICU mortality (both Pnon-linear< 0.001), identifying a critical threshold at 1.54 g/L. Post-treatment fibrinogen levels of 2.0-2.5 g/L achieved a hemostasis rate of 75%-80%; higher levels (2.5-3.5 g/L) showed slightly reduced efficacy. Mortality was 35% for levels < 1.5 g/L, significantly decreasing to 15% at 2.0-2.5 g/L, and approaching zero at 2.5-3.5 g/L. Post-treatment levels also showed nonlinear associations with outcomes (both Pnon-linear< 0.001), with a critical threshold at 2.5 g/L. Conclusions: Fibrinogen levels predict outcomes in critically ill patients with massive hemorrhage. Initiation of fibrinogen supplementation is recommended when levels fall below 1.5g/L, targeting 2.0–2.5g/L as the optimal therapeutic window to improve prognosis.

172 Background: Pasritamig is a first-in-class bispecific antibody T-cell engager that simultaneously binds human kallikrein 2 (KLK2) on PC cells and CD3 receptor complexes on T cells. Tolerable safety profile and promising anti-tumor activity was reported for US &amp; EU population. We report results for the Asian mCRPC population from a first-in-human study (NCT04898634) evaluating pasritamig in patients with advanced PC. Methods: The RP2D dose schedule of 3.5mg (step-up dose 1)-18mg (step-up dose 2)-300mg IV Q6W was administered. Pre-medication with dexamethasone (16 mg) was implemented for step-up and first treatment dose. The primary objective was safety. Secondary objectives included preliminary antitumor activity, PK and PD. Results: As of July 4, 2025, 22 Asian patients (17 Chinese, 5 Japanese, median [range] age 69 [52-85] years), with a median of 3 prior therapies (range 2-6; 100.0% ARPI, 95.5% taxane, 22.7% PARPi, 4.5% RLT), received at least 1 pasritamig dose. Fifteen patients had bone and/or lymph node metastasis only while the other 7 patients had visceral metastasis. No DLTs, pasritamig-related deaths or treatment discontinuations were reported. Sixteen (72.7%) patients reported ≥1 treatment-related AE (TRAE), and 8 (36.4%) patients experienced Grade ≥3 TRAE. Most (7/8) Grade ≥ 3 TRAEs were cytopenia (5 lymphopenia, 2 anemia), of which the majority (5/7) already had Grade 2 cytopenia at baseline. The other Grade 3 TRAE was dermatitis, which recovered in 22 days with steroid treatment. Two (9.1%) CRS cases were reported with the severity of Grade 1. No infusion-related reactions or ICANS were observed. The PSA50 response was 50.0% (10/20), including 4 responders with visceral metastases, and confirmed PSA50 was 35.0% (7/20) in the PSA-evaluable population. With a median follow up of 2.7 months, median rPFS was still not reached (95% CI: 1.81, NE) with 68.2% (15/22) patients ongoing. ORR in the patients with measurable disease was 11.1% (1/9), with response at a site of liver metastasis. PK was linear with a mean half-life of 14 days. Biomarker assessment revealed an elevated on-treatment IL-6 level in a patient who had Grade 1 CRS. Increases in on-treatment IFN-γ and CD38+/CD8+ T-cells were observed following pasritamig treatment, indicating peripheral T-cell activation consistent with the proposed MOA. A higher baseline frequency of PD-1+/CD8+ T-cells was noted in PSA50 responders. Conclusions: The safety, efficacy, PK and PD profile of pasritamig in Asia is broadly consistent with the US &amp; EU population reported previously. Longer follow up for efficacy and further quantification of responses in visceral lesions are in progress. These results highlight the potential of pasritamig to fulfill the unmet need for a safe T-cell based therapy for mCRPC and support the inclusion of Asian patients in global phase 3 trials. Clinical trial information: NCT04898634 .

With the rollout of HPV vaccination in China from 2018, the epidemiological distribution of female HPV infections has changed. We aimed to characterize the vaginal microecology (VME), ThinPrep cytologic test (TCT) results, and HPV infection epidemiology among women in Western China and to analyze their correlations to inform cervical cancer screening. We retrospectively analyzed VME, TCT, and HPV results for all women who underwent voluntary screening for gynecological diseases at Chongqing Cancer Hospital in 2023 to assess epidemiological characteristics and correlations among VME, TCT, and HPV infection. VME and TCT results were available for a subset of 1,718 participants who completed all three tests, allowing correlation analyses. Among 8,528 patients, 9.53% were HPV positive. The three most common HPV types were 52, 58, and 16; HPV 18 fell from the previous top three to 10th. Multiple HPV infections occurred in 1.31% of patients, most frequently involving types 52, 58, and 51.The HPV infection rate in the 40-49year-old group (8.07%) was the fifth highest across all age groups, differing markedly from previous studies. In total, 1,718 participants completed VME, TCT, and HPV testing, in which the HPV-positive cases accounted for 6.11%. Patients with bacterial vaginosis and dysbiosis had significantly higher HPV infection rates (P = 0.016 and P = 0.01, respectively) than those with normal flora, whereas patients with vulvovaginal candidiasis (VVC) had significantly lower rates (P = 0.044). Abnormal TCT rates showed a similar pattern: significantly higher in bacterial vaginosis (P = 0.012) and significantly lower in VVC (P = 0.029). The distribution of HPV types and age groups in Western China differs from previous reports. This may be attributable to HPV vaccination and may reflect selection bias related to reduced reproductive health attention among postmenopausal women. VME is differentially associated with cervical HPV infection and TCT findings. The correlation among VME, TCT, and HPV infection warrants further investigation. Not applicable.

Abstract Background: Epigenetic dysregulation, particularly promoter hypermethylation, plays a critical role in the silencing of tumor suppressor genes during cancer progression. Although FXYD1 has been associated with ion transport regulation, its epigenetic regulation and functional significance in breast cancer metastasis remain to be elucidated. Methods: FXYD1 expression was evaluated using public datasets (TCGA, GEO), breast cancer cell lines, and patient-derived tissues. Functional analyses, including proliferation assays, Transwell invasion assays, and murine xenograft metastasis models, were conducted following FXYD1 overexpression or knockdown. Mechanistic studies involved RNA sequencing, co-immunoprecipitation, DNA methylation analysis, ubiquitination assays, and genetic rescue experiments. Results: FXYD1 expression was significantly downregulated in breast cancer tissues compared with adjacent normal tissues (p&amp;lt;0.001, Student's t-test), and low expression was associated with advanced TNM stage and decreased overall survival (HR=1.83, 95% CI 1.2-2.8). Methylation analysis demonstrated that promoter hypermethylation was a critical mechanism underlying FXYD1 silencing. Functional restoration of FXYD1 suppressed tumor proliferation (50% reduction in colony formation, p&amp;lt;0.01), migration (70% decrease in wound healing, p&amp;lt;0.001), and lung metastasis (4-fold reduction in nodules, p&amp;lt;0.005). Mechanistically, FXYD1 facilitated Lysine 63 (K63)-linked polyubiquitination of DDX5 at residue K470 by recruiting the E3 ligase MAEA, leading to proteasomal degradation. This resulted in inhibition of Wnt/β-catenin signaling, as evidenced by reduced nuclear β-catenin (60% decrease) and downstream target expression (c-Myc, Cyclin D1). Rescue experiments confirmed that DDX5 re-expression (1.5-fold increase) or β-catenin stabilization (via CHIR99021) reversed FXYD1-mediated tumor suppression. Conclusions: Our findings establish FXYD1 as a previously unrecognized tumor suppressor that inhibits breast cancer metastasis via the DDX5-β-catenin axis. This study not only clarifies a novel ubiquitination regulatory mechanism but also highlights FXYD1 as a potential therapeutic target for metastasis intervention. Citation Format: P. Wen, G. Wang, F. Qu, Q. Shao, L. Wang, N. Zhang, X. Zeng. Promoter Hypermethylation-Induced Silencing of FXYD1 Drives Breast Cancer Metastasis via DDX5-Mediated Wnt/β-Catenin Pathway Activation [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS2-12-04.