Deciphering intratumoral heterogeneity of hepatocellular carcinoma with microvascular invasion with radiogenomic analysis.

BACKGROUND AND AIMS: The recurrence and metastasis of hepatocellular carcinoma (HCC) are mainly caused by microvascular invasion (MVI). Our study aimed to uncover the cellular atlas of MVI+ HCC and investigate the underlying immune infiltration patterns with radiomics features. METHODS: Three MVI positive HCC and three MVI negative HCC samples were collected for single-cell RNA-seq analysis. 26 MVI positive HCC and 30 MVI negative HCC tissues were underwent bulk RNA-seq analysis. For radiomics analysis, radiomics features score (Radscore) were built using preoperative contrast MRI for MVI prediction and overall survival prediction. We deciphered the metabolism profiles of MVI+ HCC using scMetabolism and scFEA. The correlation of Radscore with the level of APOE+ macrophages and iCAFs was identified. Whole Exome Sequencing (WES) was applied to distinguish intrahepatic metastasis (IM) and multicentric occurrence (MO). Transcriptome profiles were compared between IM and MO. RESULTS: Elevated levels of APOE+ macrophages and iCAFs were detected in MVI+ HCC. There was a strong correlation between the infiltration of APOE+ macrophages and iCAFs, as confirmed by immunofluorescent staining. MVI positive tumors exhibited increased lipid metabolism, which was attributed to the increased presence of APOE+ macrophages. APOE+ macrophages and iCAFs were also found in high levels in IM, as opposed to MO. The difference of infiltration level and Radscore between two nodules in IM was relatively small. Furthermore, we developed Radscore for predicting MVI and HCC prognostication that were also able to predict the level of infiltration of APOE+ macrophages and iCAFs. CONCLUSION: This study demonstrated the interactions of cell subpopulations and distinct metabolism profiles in MVI+ HCC. Besides, MVI prediction Radscore and MVI prognostic Radscore were highly correlated with the infiltration of APOE+ macrophages and iCAFs, which helped to understand the biological significance of radiomics and optimize treatment strategy for MVI+ HCC.

Prediction of vaginal birth after cesarean delivery in Southeast China: a retrospective cohort study.

BACKGROUND: We aimed to develop and validate a nomogram for effective prediction of vaginal birth after cesarean (VBAC) and guide future clinical application. METHODS: We retrospectively analyzed data from hospitalized pregnant women who underwent trial of labor after cesarean (TOLAC), at the Fujian Provincial Maternity and Children's Hospital, between October 2015 and October 2017. Briefly, we included singleton pregnant women, at a gestational age above 37 weeks who underwent a primary cesarean section, in the study. We then extracted their sociodemographic data and clinical characteristics, and randomly divided the samples into training and validation sets. We employed the least absolute shrinkage and selection operator (LASSO) regression to select variables and construct VBAC success rate in the training set. Thereafter, we validated the nomogram using the concordance index (C-index), decision curve analysis (DCA), and calibration curves. Finally, we adopted the Grobman's model to perform comparisons with published VBAC prediction models. RESULTS: Among the 708 pregnant women included according to inclusion criteria, 586 (82.77%) patients were successfully for VBAC. Multivariate logistic regression models revealed that maternal height (OR, 1.11; 95% CI, 1.04 to 1.19), maternal BMI at delivery (OR, 0.89; 95% CI, 0.79 to 1.00), fundal height (OR, 0.71; 95% CI, 0.58 to 0.88), cervix Bishop score (OR, 3.27; 95% CI, 2.49 to 4.45), maternal age at delivery (OR, 0.90; 95% CI, 0.82 to 0.98), gestational age (OR, 0.33; 95% CI, 0.17 to 0.62) and history of vaginal delivery (OR, 2.92; 95% CI, 1.42 to 6.48) were independently associated with successful VBAC. The constructed predictive model showed better discrimination than that from the Grobman's model in the validation series (c-index 0.906 VS 0.694, respectively). On the other hand, decision curve analysis revealed that the new model had better clinical net benefits than the Grobman's model. CONCLUSIONS: VBAC will aid in reducing the rate of cesarean sections in China. In clinical practice, the TOLAC prediction model will help improve VBAC's success rate, owing to its contribution to reducing secondary cesarean section.