Methylated SEPT9 combined with AFP and PIVKA-II is effective for the detection of HCC in high-risk population.

BACKGROUND: The methylation SEPT9 (mSEPT9) appeared to be effective for hepatocellular carcinoma (HCC) detection. However, its performance in high-risk population has not been validated. We designed a pilot study and aimed to investigate the performance of mSEPT9, AFP, PIVKA-II and their combination in hepatic cirrhosis (HC) population. METHODS: A training cohort was established including 103 HCC and 114 HC patients. 10 ml blood was collected from each patient with K2EDTA tubes, and 3-4 ml plasma was extracted for subsequent tests. The performance of mSEPT9, AFP, PIVKA-II and their combination was optimized by the training cohort. Test performance was prospectively validated with a validation cohort, including 51 HCC and 121 HC patients. RESULTS: At the optimal thresholds in the training cohort, the sensitivity, specificity and area under curve (AUC) was 72.82%, 89.47%, 0.84, and 48.57%, 89.92%, 0.79, and 63.64%, 95.95%, 0.79 for mSEPT9, AFP and PIVKA-II, respectively. The combined test significantly increased the sensitivity to 84.47% (P < 0.05) at the specificity of 86.84% with an AUC of 0.91. Stage-dependent performance was observed with all single markers and their combination in plasma marker levels, positive detection rate (PDR) and AUC. Moderate correlation was found between mSEPT9 and AFP plasma levels (r = 0.527, P < 0.0001). Good complementarity was found between any two of the three markers, providing optimal sensitivity in HCC detection when used in combination. Subsequent validation achieved a sensitivity, specificity and AUC of 65.31%, 92.86%, 0.80, and 44.24%, 89.26%, 0.75, and 62.22%, 95.27%, 0.78 for mSEPT9, AFP and PIVKA-II, respectively. The combined test yielded a significantly increased sensitivity of 84.00% (P < 0.05) at 85.57% specificity, with an AUC at 0.89. CONCLUSIONS: The performance was optimal by the combination of mSEPT9, AFP, PIVKA-II compared with any single marker, and the combination may be effective for HCC opportunistic screening in HC population.

Unraveling the Heterogeneity of CD8+ T-Cell Subsets in Liver Cirrhosis: Implications for Disease Progression.

Background/Aims: : Liver cirrhosis involves chronic inflammation and progressive fibrosis. Among various immune cells, CD8+ T cells are considered a major contributor to hepatic inflammation and fibrosis. However, the exact molecular pathways governing CD8+ T-cell-mediated effects in cirrhosis remain unclear. Methods: : This study analyzed transcriptomic and single-cell sequencing data to elucidate CD8+ T-cell heterogeneity and implications in cirrhosis. Results: : Weighted gene co-expression analysis of bulk RNA-seq data revealed an association between cirrhosis severity and activated T-cell markers like HLA and chemokine genes. Furthermore, single-cell profiling uncovered eight CD8+ T-cell subtypes, notably, effector memory (Tem) and exhausted (Tex) T cells. Tex cells, defined by PDCD1, LAG3, and CXCL13 expression, were increased in cirrhosis, while Tem cells were decreased. Lineage tracing and differential analysis highlighted CXCL13+ Tex cells as a terminal, exhausted subtype of cells with roles in PD-1 signaling, glycolysis, and T-cell regulation. CXCL13+ Tex cells displayed T-cell exhaustion markers like PDCD1, HAVCR2, TIGIT, and TNFRSF9. Functional analysis implicated potential roles of these cells in immunosuppression. Finally, a CXCL13+ Tex-cell gene signature was found that correlated with cirrhosis severity and poorer prognosis of liver cancer. Conclusions: : In summary, this comprehensive study defines specialized CD8+ T-cell subpopulations in cirrhosis, with CXCL13+ Tex cells displaying an exhausted phenotype associated with immune dysregulation and advanced disease. Key genes and pathways regulating these cells present potential therapeutic targets.

Experimental Study on Injection and Plugging Effect of Core-Shell Polymer Microspheres: Take Bohai Oil Reservoir as an Example.

To meet the technical requirements of deep fluid diversion in Bohai oilfield, the swelling property, plugging effect, transport characteristics of polymer microspheres, and fluid diversion effect in heterogeneous cores are studied in this paper. There are two kinds of polymer microspheres including core-shell microspheres and traditional microspheres. The instruments used in this study include a biomicroscope, a metallurgical microscope, a scanning electron microscope, and core displacement experimental devices. The results of microscopes indicated that the core-shell microspheres were successfully synthesized, and the microspheres had good hydration expansion effect. The expanded microspheres could attract each other through the electrostatic force of anions and cations to achieve the purpose of coalescence. Compared with traditional microspheres (initial particle size is 3.8 µm), the initial particle size of the synthesized core-shell microspheres is close to 3.3 µm, but the particle size distribution is more concentrated, so the injection performance is close to that of traditional microspheres (initial particle size is 3.8 µm). After 8 days of hydration expansion, although the expansion multiple is small, it can coalesce and enhance the plugging effect, which can adapt to a wider range of permeability, ranging from 200 × 10-3 to 3000 × 10-3 µm2 (200 × 10-3-1500 × 10-3 µm2 for traditional microspheres). Under the same conditions (heterogeneous core), compared with the traditional microspheres, the core-shell microspheres have the characteristics of coalescence. Therefore, its fluid diversion effect is better, and the oil recovery is increased by 5.5%. Nevertheless, there is the "end effect" during the injection process, which weakens the steering effect of deep liquid flow. The results show that the "end effect" can be effectively reduced by alternate injection of microspheres and water. Meanwhile, the effect of deep fluid diversion is improved, and the increase of oil recovery is increased by 2.06%.