Nanosecond pulsed electric field (NsPEF) ablation effectively eliminates early-stage hepatocellular carcinoma (HCC) by local ablation and advanced HCC by inducing a remarkable and sustained host immune response. However, this approach is not sufficient to prevent cancer progression, and complementary approaches are necessary for effective immunotherapy. In this study, we evaluated the immunoactivating effects and mechanisms of action of nsPEF ablation and PD-1 blockade on an HCC orthotopic xenograft mouse model. Briefly, 24 C57BL-6J tumor-bearing mice were randomly assigned to three groups: nsPEF ablation group, anti-PD-1 administration group, and untreated control group. Tumor-infiltrating T, B, and NK cell levels and plasma concentrations of Th1 (IL-2, IFN-γ, and TNF-α), Th2 (IL-4, IL-5, IL-6, and IL-10), Th9 (IL-9), and Th17 (IL-17A, IL-17F, IL-21, and IL-22) cytokines were evaluated. Both nsPEF ablation and anti-PD-1 treatment induced immune cell infiltration in local tumors and modulated cytokine levels in the peripheral blood, with distinct changes in the two treatment groups. Based on these findings, both nsPEF ablation and PD-1 antibody administration can trigger a local and systemic immune response in a partially complementary manner, and nsPEF ablation should be considered along with PD-1 blockade for the treatment of HCC.

Background Alveolar echinococcosis (AE) lesion microenvironment (LME) is crucial site where parasite-host interactions happen and of great significance during surgery and obtaining liver samples for basic research. However, little is known about quantification of LME range and its’ metabolic activity regarding different lesion characteristics. Methods A prospective and retrospective analysis of LME from surgical AE patients was performed. Patients (n = 75) received abdominal computed tomography (CT) and position emission tomography/computed tomography using 18F-fluodeoxyglucose (18F-FDG-PET/CT) within 1 week prior to surgery. Semiquantitatively, calcification was clustered with 0%, < 50% and ≥ 50% degrees at lesion periphery; liquefaction was clustered with 0%, < 50%, 50 ~ 75%, ≥75% degrees at lesion center using volumetric ratio. Tumor to background ratio (TBR) of 18F-FDG standard uptake value (SUV, n = 75) was calculated, and range of 18F-FDG uptake area was measured; Multi-site sampling method (MSS, n = 35) was introduced to obtain histological slides to evaluate immune cell infiltrative ranges. Results Altogether six major lesion groups have been identified (A: 0% calcified, 0% liquefied; B: ≥50% calcified, 0% liquefied; C: < 50% calcified, < 50% liquefied; D: ≥50% calcified, < 50% liquefied; E: < 50% calcified, 50 ~ 75% liquefied; F: ≥50% calcified, ≥75% liquefied). Statistically, TBR values respectively were 5.1 ± 1.9, 2.7 ± 1.2, 4.2 ± 1.2, 2.7 ± 0.7, 4.6 ± 1.2, 2.9 ± 1.1 in groups A ~ F, and comparisons showed A > B, A > D, A > F, E > B, E > D, E > F, C > B, C > D, C > F (P < 0.05); LME ranges indicated by PET/CT respectively were 14.9 ± 3.9, 10.6 ± 1.5, 12.3 ± 1.1, 7.8 ± 1.6, 11.1 ± 2.3, 7.0 ± 0.4 mm in groups A ~ F, and comparisons showed A > B, A > D, A > F, A > E, C > B, C > D, C > F, E > D, E > F, B > D, B > F (P < 0.05); LME ranges indicated by MSS respectively were 17.9 ± 4.9, 13.0 ± 2.7, 11.9 ± 2.6, 6.0 ± 2.2, 11.0 ± 4.1, 6.0 ± 2.2 mm in groups A ~ F, and comparisons showed A > C, A > D, A > F, B > D, B > F, C > D, C > F (P < 0.05). Generally, less calcifications indicated higher TBR values and wider LME ranges; and, severer liquefactions indicated smaller LME ranges. Additionally, patients with previous medication history had lower TBR values. Conclusions PET/CT and MSS method showed distinct TBRs and LME ranges for different calcifications and liquefactions. This study would be able to provide references for both surgical resections of lesions and more accurate sample acquisitions for basic research targeted to immunology.

Background Alveolar echinococcosis (AE) is a worldwide zoonosis caused by Echinococcus Multilocularis. AE is a severe chronic parasitic disease that exhibits a tumor-like growth, with the potential for invasion and distant metastasis; however, the molecular mechanism underlying this condition remains unclear. Methods Transcriptome analyses were performed to detect differentially expressed genes (DEGs) in samples from patients with AE with invasion and distant metastasis. The results were further verified by immunohistochemistry. Results A total of 1796 DEGs were identified, including 1742 upregulated and 54 downregulated DEGs. A subsequent functional analysis showed that the significant DEGs were involved in the angiogenesis process. Immunohistochemical analysis confirmed the reliability of the transcriptomic data. Conclusions These results suggest that angiogenesis is a possible mechanism underlying the tumor-like biological behavior observed during E. multilocularis infection. Genes related to this process may play important roles in AE invasion and distant metastasis.

Retraction type (multiple responses allowed):  Unreliable findings   Lab error  Inconsistent data  Analytical error  Biased interpretation   Other:  Irreproducible results  Failure to disclose a major competing interest likely to influence interpretations or recommendations  Unethical research   Fraud   Data fabrication  Fake publication  Other:  Plagiarism  Self plagiarism  Overlap  Redundant publication *  Copyright infringement  Other legal concern:  Editorial reasons   Handling error  Unreliable review(s)  Decision error  Other: ✘ Other: Results of publication (only one response allowed): ✘ are still valid.  were found to be overall invalid.

Background: Alveolar echinococcosis (AE) lesion microenvironment (LME) is crucial site where parasite-host interactions happen and of great significance during surgery and obtaining liver samples for basic research targeting immunology. However, little is known about quantification of LME range and its’ metabolic activity regarding different lesion types.Methods: A prospective analysis of LME from consecutive surgical AE cases with relevant imaging results was performed. Patients (n=39) received abdominal computed tomography (CT) and position emission tomography/computed tomography using 18F-fluodeoxyglucose (18F-FDG-PET/CT) within one week prior to surgery. Tumor to background ratios (TBRs) of standard uptake value (SUV) in PET/CT was calculated for corresponding LME regions. Multi-site sampling method (MSS, n=26) was introduced to obtain histological slides from LME at different levels off the lesion to evaluate immune cell infiltrative ranges quantitatively. At last, data was statistically analyzed from the perspective of different lesion types.Results: Altogether six major lesion categories have been identified based on different morphology and calcification pattern (A: non-calcified uniform density lesion; B: diffuse calcified solid lesion; C: half necrotic and half solid lesion with minor calcification; D: half necrotic and half solid lesion with obvious calcification; E: subtotal necrotic lesion with minor calcification; F: total necrotic lesion with obvious calcification). Statistical significances were resulted from TBRs calculation (A>B, A>D, A>F, B<C, B<E, A+C+E>B+D+F, etc.). Less calcified lesions were evidenced with higher TBRs, however, not much was valuable for necrosis. The 95% CI of LME ranges were (10.0, 12.1) mm and (9.9, 14.0) mm by PET/CT and MSS. And, weak regressions between TBRs and LME ranges indicated by PET/CT or MSS (r2 respectively were 0.2436 and 0.3171) were observed.Conclusions: PET/CT showed distinct TBRs for different lesion types with heterogenic calcification. PET/CT and MSS had similar discoverability for LME ranges, which also varied among different lesion types. Higher activity meant wider LME range within certain limit. This pioneering study would be able to provide references for both surgical removal of lesions and sample acquisitions more accurately for basic research targeted to immunology.