Establishing and Externally Validating a Hemoglobin, Albumin, Lymphocyte, and Platelet (HALP) Score-Based Nomogram for Predicting Early Recurrence in BCLC Stage 0/A Hepatocellular Carcinoma Patients After Radical Liver Resection: A Multi-Center Study.

Purpose: Early recurrence (ER) is associated with poor prognosis in hepatocellular carcinoma (HCC). In this study, we developed and externally validated a nomogram based on the hemoglobin, albumin, lymphocytes, and platelets (HALP) score to predict ER for patients with BCLC stage 0/A HCC who underwent radical liver resection. Patients and Methods: A total of 808 BCLC stage 0/A HCC patients from six hospitals were included in this study, and they were assigned to a training cohort (n = 500) and an external validation cohort (n = 308). We used univariate and multivariate Cox regression analysis to identify the independent risk factors for disease-free survival (DFS). We also established and externally validated a nomogram based on these risk predictors. The nomogram was evaluated using the area under the receiver operating characteristic curve (AUC), the concordance index (C-index), the calibration curve, decision curve analysis (DCA), and Kaplan‒Meier analysis. Results: Multivariate COX regression showed that HBV DNA ≥10,000 IU/mL (P < 0.001), HALP score ≤38.20 (P < 0.001), tumor size (P = 0.003), clinically significant portal hypertension (P = 0.001), Edmondson-Steiner grade (III-IV) (P = 0.007), satellite nodules (P < 0.001), and MVI (P = 0.001) were independent risk factors for post-operative tumor recurrence. The AUC of our nomogram for predicting the 2-year and 5-year DFS was 0.756 and 0.750, respectively, in the training cohort and 0.764 and 0.705, respectively, in the external validation cohort. We divided the patients into low-, intermediate- and high-risk groups according to the risk score calculated by the nomogram. There were statistically significant differences in the DFS and overall survival (OS) among the three groups of patients (P < 0.001). Conclusion: We developed and externally validated a new nomogram, which is accurate and can predict ER in BCLC stage 0/A HCC patients after curative liver resection.

Metabolically engineered Escherichia coli for biotechnological production of four-carbon 1,4-dicarboxylic acids.

Confronted with inescapable exhaustion of the earth's fossil energy resources, the bio-based process to produce industrial chemicals is receiving significant interest. Biotechnological production of four-carbon 1,4-dicarboxylic acids (C4 diacids) from renewable plant biomass is a promising and attractive alternative to conventional chemistry routes. Although the C4 diacids pathway is well characterized and microorganisms able to convert biomass to these acids have been isolated and described, much still has to be done to make this process economically feasible. Metabolically engineered Escherichia coli has been developed as a biocatalyst to provide new processes for the biosynthesis of many valuable chemicals. However, E. coli does not naturally produce C4 diacids in large quantities. Rational strain development by metabolic engineering based on efficient genetic tools and detailed knowledge of metabolic pathways are crucial to successful production of these compounds. This review summarizes recent efforts and experiences devoted to metabolic engineering of the industrial model bacteria E. coli that led to efficient recombinant biocatalysts for the production of C4 diacids, including succinate, fumarate, malate, oxaloacetate, and aspartate, as well as the key limitations and challenges. Continued advancements in metabolic engineering will help to improve the titers, yields, and productivities of the C4 diacids discussed here.