Jinjie Yu

Purpose This study aimed to develop and validate a radiomics nomogram that integrates multi-parametric MRI and clinical factors for the preoperative prediction of parametrial invasion (PMI) in early-stage cervical cancer (ECC). Materials and methods A total of 363 patients with ECC (FIGO stages IB–IIA) were divided into training, internal validation, and external validation cohorts. All patients underwent T2WI, DWI, and T1c scans before radical hysterectomy. Radiomics features were extracted from T2WI, DWI, and T1c images, and selected using the max-relevance and min-redundancy (mRMR) method and the least absolute shrinkage and selection operator (LASSO). Radiomics signatures were then derived from these selected features. An MRI model was built using the radiomics signatures to evaluate their performance in distinguishing patients with PMI. A radiomics nomogram was constructed based on the optimal radiomics signature, pre-procedure hematocrit levels, and CA-125 levels. The discrimination performance of the nomogram was subsequently evaluated. Results For the MRI model, the radiomics signatures yielded AUCs of 0.834 (95% CI: 0.7275–0.9399) and 0.800 (95% CI: 0.6902–0.9105) in the internal and external validation cohorts, respectively. The radiomics nomogram, which integrated the radiomics signatures from T2WI, DWI, and T1c, along with hematocrit and CA-125 levels, showed excellent discrimination between PMI and non-PMI groups. The nomogram achieved an AUC of 0.827 (95% CI: 0.7116–0.9430) in the internal validation cohort and 0.806 (95% CI: 0.6997–0.9114) in the external validation cohort. The specificity and sensitivity were 0.866 and 0.762, respectively, in the internal validation cohort, and 0.875 and 0.583 in the external validation cohort. Conclusions The developed radiomics nomogram provides a non-invasive and reliable tool for preoperative PMI prediction in ECC. By facilitating more accurate risk stratification, it has the potential to inform personalized therapeutic planning.

Bacillus Calmette–Guérin (BCG) is the only widely used prophylactic tuberculosis (TB) vaccine that can prevent severe TB in infants. However, it provides poor protection in adults, and therefore, there is ongoing research into new TB vaccines and immunization strategies with more durable immune effects. The recombinant BCG and BCG prime-protein booster are two important vaccine strategies that have recently been developed based on BCG and could improve immune responses. In this study, three immune strategies based on four protective antigens, namely, ESAT-6, CFP-10, nPPE18, and nPstS1, were applied to construct recombinant rBCG-EPCP009, EPCP009 subunit protein, and BCG prime-EPCP009 booster vaccine candidates. The short- and long-term immune effects after vaccination in Balb/c mice were evaluated based on humoral immunity, cellular immunity, and the ability of spleen cells to inhibit in vitro mycobacterial growth. At 8 and 12 weeks after the initial immunization, splenocytes from mice inoculated with the BCG prime-EPCP009 protein booster secreted higher levels of PPD- and EPCP009-specific IFN-γ, IL-2, TNF-α, IL-17, GM-CSF, and IL-12 and had a higher IFN-γ⁺CD4⁺ TEM:IL-2⁺CD8⁺ TCM cell ratio than splenocytes from mice inoculated with the rBCG-EPCP009 and EPCP009 proteins. In addition, the EPCPE009-specific IgG2a/IgG1 ratio was slightly higher in the BCG prime-EPCP009 protein booster group than in the other two groups. The in vitro mycobacterial inhibition assay showed that the splenocytes of mice from the BCG prime-EPCP009 protein booster group exhibited stronger inhibition of Mycobacterium tuberculosis (M. tuberculosis) growth than the splenocytes of mice from the other two groups. These results indicate that the BCG prime-EPCP009 protein booster exhibited superior immunogenicity and M. tuberculosis growth inhibition to the parental BCG, rBCG-EPCP009, and EPCP009 proteins under in vitro conditions. Thus, the BCG prime-EPCP009 protein booster may be important for the development of a more effective adult TB vaccine.

Tuberculosis (TB) remains a serious global health problem. Despite the widespread use of the Mycobacterium bovis bacillus Calmette-Guerin (BCG) vaccine, the primary factor for the TB pandemic and deaths is adult TB, which mainly result from endogenous reactivation of latent Mycobacterium tuberculosis (MTB) infection. Improved new TB vaccines with eligible safety and long-lasting protective efficacy remains a crucial step toward the prevention and control of TB. In this study, five immunodominant antigens, including three early secreted antigens and two latency associated antigens, were used to construct a single recombinant fusion protein (Epera013f) and a protein mixture (Epera013m). When formulated with aluminum adjuvant, the two subunit vaccines Epera013m and Epera013f were administered to BALB/c mice. The humoral immune responses, cellular responses and MTB growth inhibiting capacity elicited after Epera013m and Epera013f immunization were analyzed. In the present study, we demonstrated that both the Epera013f and Epera013m were capable of inducing a considerable immune response and protective efficacy against H37Rv infection compared with BCG groups. In addition, Epera013f generated a more comprehensive and balanced immune status, including Th1, Th2 and innate immune response, over Epera013f and BCG. The multistage antigen complex Epera013f possesses considerable immunogenicity and protective efficacy against MTB infection ex vivo indicating its potential and promising applications in further TB vaccine development.