Surgery has passed through an intuitive and an empirical era and has now entered its modern phase characterized by everincreasing certainty in surgical practice.1 The enormous progress in biomedicine, the rise of evidence-based medicine, and the consensus on the need for humanistic patient care in the 21 st century have laid a foundation for a new surgical paradigm. This surgical paradigm featuring high-certainty clinical practice would enable simultaneous optimization of therapeutic effectiveness, surgical safety, and minimal invasiveness. We argued for the necessity of a paradigm shift in liver surgery, and advocated "precision liver resection" as a surgical concept for the first time in 2006, 2,3 and later extended the concept of "precision liver resection" to "precision liver surgery." 4,5 This concept is widely applicable within various surgical fields and is embraced by both the Chinese and international community. In this review, we advocate the new paradigm of "precision surgery" and attempt to establish its theoretical and technological framework by examining the evolution of surgery, the advances in surgical science and technology, and the health care needs within modern society. "Precision" does not just refer to the accuracy of operative manipulation, some idealized procedure, or a particular advanced technology, 6,7 "Precision" as we define it is a new approach to surgery and its derived system of theories and technologies covering all the elements of surgical practice, including preoperative evaluation, clinical decision making, surgical planning, operative manipulation, and perioperative management. 3 Emergence of Precision SurgerySurgery, as a direct and profound exploration of the human body, has always been a symphony of science and art. In this everlasting symphony, the surgical paradigm has evolved Keywords ► precision surgery ► liver surgery ► certainty ► multiobjective optimization AbstractContinuous theoretical and technological progress in the face of increasing expectations for quality health care has transformed the surgical paradigm. The authors systematically review these historical trends and propose the novel paradigm of "precision surgery," featuring certainty-based practice to ensure the best result for each patient with multiobjective optimization of therapeutic effectiveness, surgical safety, and minimal invasiveness. The main characteristics of precision surgery may be summarized as determinacy, predictability, controllability, integration, standardization, and individualization. The strategy of precision in liver surgery is to seek a balance of maximizing the removal of the target lesion, while maximizing the functional liver remnant and minimizing surgical invasiveness. In this article, the authors demonstrate the application of precision approaches in specific settings in complex liver surgery. They propose that the concept of precision surgery should be considered for wider application in liver surgery and other fields as a step toward the ultimate goal of perfect surgery.

The molecular regulation of growth of hepatocellular carcinoma (HCC) is yet to be fully clarified. Here we found a significantly higher ratio of phosphorylated β-catenin (phos-β-cat) to β-catenin (β-cat) as an indicator of an activated Wnt signaling, with significantly higher levels of c-myc and transcription factor activating protein-4 (AP-4) and a significantly lower level of p21 in the resected HCC, compared to the paired adjacent healthy hepatic tissue from the patients. Moreover, strong correlations were detected between phos-β-cat/β-cat ratio and c-myc level, between c-myc and AP-4 levels, and between AP-4 and p21 levels. These data support the presence of a Wnt/c-myc/AP-4/p21 regulation cascade in HCC as has been reported in colorectal cancer. To prove it, we overexpressed c-myc in two HCC lines, which significantly increased AP-4 level, inhibited p21 level, and then increased cell growth. Meanwhile, c-myc inhibition in these two HCC lines significantly decreased AP-4 level, increased p21 level, and then decreased cell growth. Moreover, AP-4 inhibition in c-myc-overexpressing HCC lines abolished the inhibitory effect on p21 and abolished the increase in cell growth. In line with these findings, overexpression of AP-4 in these two HCC lines significantly decreased p21 level, and then increased cell growth, while AP-4 inhibition significantly increased p21 level, and then decreased cell growth. Our results on HCC are thus consistent with the model detected in colorectal carcinoma, suggesting that Wnt signaling activated c-myc may increase HCC growth through direct inhibitory effect of AP-4 on p21. Our study thus highlights AP-4 as a novel therapeutic target for HCC.

Liver fibrosis is a common pathological feature of end-stage liver disease and has no effective treatment. MicroRNAs (miRNAs) have been found to modulate gene expression in liver disease. But the potential role of miRNA in hepatic fibrosis is still unclear. The objective of this research is to study the potential mechanism and biological function of miR-183-5p in liver fibrosis. In this study, we used high-throughput sequencing to find that miR-183-5p is upregulated in human fibrotic liver tissues. In addition, miR-183-5p was upregulated both in rat liver fibrosis tissue induced by bile-duct ligation (BDL) and activated LX-2 cells (human hepatic stellate cell line) according to the result of quantitative real-time PCR (RT-qPCR). Moreover, the inhibition of miR-183-5p alleviated liver fibrosis, decreased the fibrotic biomarker levels in vitro and in vivo, and led toLX-2 cell proliferation inhibition and, apoptosis induction. The result of dual-luciferase assay revealed that miR-183-5p suppressed fork head box protein O1 (FOXO1) expression by binding to its 3′UTR directly. Next, we used lentivirus to overexpress FOXO1 in LX-2 cells, and we found that overexpression of FOXO1 reversed the promotion of miR-183-5p on liver fibrosis, reducing the fibrotic biomarker levels inLX-2 cells, inhibitingLX-2 cell proliferation, and promoting apoptosis. Furthermore, overexpression of FOXO1 prevented the activation of the transforming growth factor (TGF)-β signaling pathway in TGF-β1-induced LX-2 cells according to the result of western blotting. In conclusion, the findings showed thatmiR-183-5p might act as a key regulator of liver fibrosis, and miR-183-5p could promote cholestatic liver fibrosis by inhibiting FOXO1 expression through the TGF-β signaling pathway. Thus, inhibition of miR-183-5pmay be a new way to prevent and improve liver fibrosis.

Background Bile duct obstruction-induced liver fibrosis is mainly caused by cholestatic liver injury which stimulates liver cell inflammation and damages the liver structure, causing liver fibrosis. The differentially expressed microRNAs and the potential target genes and signal pathways that are involved in bile duct obstruction-induced liver fibrosis remain unclear. We examined the differential expression of microRNAs and the target genes in the liver tissues of patients with liver fibrosis. Methods High-throughput sequencing was used to detect the total microRNAs and identify the differentially expressed microRNAs. The topGO software was used to perform the Gene Ontology (GO) function enrichment analysis. The KOBAS software was used to analyze the associated biochemical metabolic pathways and signal transduction pathways. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot analyses were conducted to detect the expression of miR-1295b-3p, alpha smooth muscle actin (α-SMA), Bcl-2, caspase-3, Bax, and β-arrestin1 (ARRB1). Cell viability and apoptosis were detected by the Cell Counting Kit 8 (CCK-8) assay and flow cytometry. The targeting relationship between ARRB1 and miR-1295b-3p was verified using luciferase reporter assays. Results A total of 44 microRNAs were found to be differentially expressed, including 18 upregulated and 26 downregulated microRNAs. Five downregulated microRNAs, including miR-483-3p, miR-5589-3p, miR-1271-5p, miR-1295b-3p, and miR-7977. GO functional enrichment analysis of the target genes revealed the molecular functions, cellular location, and biological processes involved. Kyoto Encyclopedia of Genes and Genomes (KEGG) signal pathway analysis showed that the target genes are mainly involved in metabolic pathways. In addition, the results of qRT-PCR revealed that miR-1295b-3p was downregulated in human fibrotic liver tissues and TGF-β1-activated LX-2 cells (human hepatic stellate cell line). Overexpression of miR-1295b-3p alleviated liver fibrosis, decreased the α-SMA levels, and inhibited proliferation and enhanced apoptosis in LX-2 cells. Dual-luciferase assays revealed that miR-1295b-3p suppressed ARRB1 expression by binding directly to its 3' untranslated region (UTR). Conclusions This study identified the differentially expressed microRNAs in bile duct obstruction-induced liver fibrosis and revealed the potential target genes and signal pathways involved. Overexpression of miR-1295b-3p alleviated liver fibrosis, however, the specific targeting mechanisms warrant further clarification. Therefore, overexpressing miR-1295b-3p may be a potential treatment method for liver fibrosis.