Objective: This study aims to identify independent risk factors for ultra-early recurrence in patients with early solitary hepatocellular carcinoma (HCC) and develop an individualized predictive nomogram for ultra-early recurrence. Materials and Methods: A total of 332 patients with early solitary HCC who underwent curative liver resection at our hospital from January 2015 to May 2021 were included in this study. Based on the patients’ recurrence status at 6 months, they were divided into the non-ultra-early recurrence group and the ultra-early recurrence group. Univariate and multivariate Cox regression analyses were used to construct the nomogram, and internal validation of its performance was performed using calibration plots with bootstrapping. Results: Among the 332 patients with early solitary HCC, 39 (11.7%) experienced ultra-early recurrence. Tumor morphology, age > 46 years, AFP > 332.4 ng/mL, GGT > 51.2 U/L, ALP > 126 U/L, PT > 12.8 s, and satellite nodules were identified as independent prognostic factors for ultra-early recurrence in patients with early solitary HCC and were incorporated into the final predictive nomogram. The C-index of the nomogram and bootstrap resampling were 0.842 and 0.815, respectively. The calibration plot demonstrated good agreement between the predicted and observed probabilities of ultra-early recurrence, and DCA indicated the favorable clinical utility of the nomogram. Additionally, AFP > 332.4 ng/mL, AST > 35 U/L, GGT > 51.2 U/L, ALP > 126 U/L, tumor morphology, tumor size, satellite nodules, and intratumoral hemorrhage were identified as risk factors for overall survival in patients with early solitary HCC. Conclusion: Our study establishes a nomogram for predicting the postoperative ultra-early recurrence status in patients with early solitary HCC, which provides valuable supplementary decision-making information for clinical decision-makers and guides the selection of the most appropriate treatment strategy.

Aim: To noninvasively observe dynamic changes in tumor hypoxia in mouse models of human non-small-cell lung cancer (NSCLC) using 18F-fluoromisonidazole PET. Materials & methods: Nude mice with NSCLC H460 and A549 subcutaneous xenografts were coinjected intravenously with 18F-fluoromisonidazole and the hypoxia marker pimonidazole, and observed by serial PET scans. After sacrifice, the tumor distribution of 18F-fluoromisonidazole and pimonidazole was compared by digital autoradiography and microscopy, respectively. Results: The NSCLC hypoxic microenvironment was spatially heterogeneous. Serial PET scans over 48 h revealed an apparent change in the intratumoral distribution of 18F-fluoromisonidazole. Conclusion: The tumor hypoxic microenvironment is spatially and temporally heterogeneous, and hypoxic cancer cells have a shorter life span when growing in vivo. Therefore, the concept of hypoxic resistance and hypoxia-targeting therapy of macroscopic tumors should be revisited.

Background: Differentiated thyroid cancer (DTC) is commonly treated with radioactive iodine (RAI), but resistance to RAI remains a significant clinical challenge. The molecular mechanisms driving dedifferentiation and RAI refractoriness, particularly in BRAF^V600E-mutated tumors, are not fully understood. Methods: RNA sequencing was conducted on BRAF^V600E-mutated DTC and RAIR-DTC tissue samples to identify differentially expressed genes. Gadd45B was identified as significantly downregulated in RAIR-DTC. Functional studies including overexpression and knockdown experiments were performed in thyroid cancer cell lines and xenograft models. Downstream targets, including MAP3K4 and MYCBP, were evaluated through co-immunoprecipitation, luciferase assays, and Western blot. The therapeutic efficacy of recombinant Gadd45B protein in combination with BRAF^V600E and TERT inhibitors was assessed in patient-derived xenograft (PDX) models. Results: Gadd45B overexpression suppressed MAPK pathway activity by interacting with MAP3K4 and downregulated c-MYC stability through competition with MYCBP. These interactions enhanced the expression of iodine-metabolism genes (NIS, TPO, Tg), increased RAI uptake, and reversed tumor dedifferentiation. In vivo, Gadd45B restoration reduced tumor burden and improved RAI uptake. Combined treatment with Gadd45B protein, PLX4720, and BIBR1532 produced synergistic therapeutic effects in PDX models. Conclusions: Gadd45B plays a pivotal role in regulating the differentiation status and RAI sensitivity of BRAF^V600E-mutated thyroid cancer. These findings identify Gadd45B as a promising therapeutic target for restoring RAI responsiveness in RAIR-DTC patients.

Hepatocellular carcinoma (HCC) recurrence following microwave ablation poses a pressing clinical challenge, driven by metabolically adapted residual cells that establish an immunosuppressive tumour microenvironment. Our study identifies the post-ablation upregulation of fumarylacetoacetate hydrolase (FAH) as a crucial "metabolic checkpoint" promoting relapse. Elevated FAH expression results in increased fumarate levels within residual HCC cells, supporting tumour cell survival by enhancing energy metabolism while concurrently impairing CD8⁺ T cell function. Mechanistically, fumarate binds to and stabilises heat shock protein 70 (HSP70), establishing a thermal ablation induced FAH-fumarate-HSP70 axis that drives immunosuppression. To counteract this pivotal axis, we engineered a gallium-based functionalized nanoplatform. This system incorporates a lactate oxidase shell that responds to the lactate-rich tumour microenvironment, enabling the site-specific co-release of Ga³⁺, FAH-silencing plasmids and the glycolysis inhibitor 2-deoxy-D-glucose. Our nanoplatforms disrupt the FAH-fumarate-HSP70 axis to eradicate residual HCC, activate CD8⁺ T cells, and restore immunity, targeting recurrence dysregulation while integrating metabolic blockade with immunomodulation to prevent post-ablation relapse with clinical translation potential.