This paper focuses on the elective surgical scheduling problem with multi-resource constraints, including material resources, such as operating rooms (ORs) and non-operating room (NOR) beds, and human resources (i.e., surgeons, anesthesiologists, and nurses). The objective of multi-resource constrained elective surgical scheduling (MESS) is to simultaneously minimize the average recovery completion time for all patients, the average overtime for medical staffs, and the total medical cost. This problem can be formulated as a mixed integer linear multi-objective optimization model, and the honey badger algorithm based on the Nash equilibrium (HBA-NE) is developed for the MESS. Experimental studies were carried out to test the performance of the proposed approach, and the performance of the proposed surgical scheduling scheme was validated. Finally, to narrow the gap between the optimal surgical scheduling solution and actual hospital operations, digital twin (DT) technology is adopted to build a physical-virtual hospital surgery simulation model. The experimental results show that by introducing a digital twin, the physical and virtual spaces of the smart hospital can be integrated to visually simulate and verify surgical processes.

Background: This study sought to review colorectal cancer liver metastasis (CRLM) patients at multiple centers to analyze the factors affecting the success of conversion therapy in patients whose CRLM was initially evaluated as potentially resectable, to explore the effect of different treatment approaches on patient survival, and to provide a scientific reference for clinical treatment of CRLM. Methods: Fifty patients whose CRLM was initially evaluated as potentially resectable at 3 large Chinese general hospitals were enrolled in this retrospective study. Statistical analyses were carried out on the general data and pathological characteristic data to examine the clinical efficacy of the treatment approaches. The factors affecting the success of conversion therapy were analyzed by logistic regression. Additionally, follow-up appointments were conducted to examine survival, and survival curves were plotted using the Kaplan-Meier estimator. The effect of different clinical and pathological characteristics on CRLM patients was analyzed. Results: Seventeen patients achieved no evidence of disease (NED) status through surgical resection/ablation after undergoing conversion therapy. The multifactor analysis demonstrated that the number of liver metastases was the primary risk factor affecting the efficacy of conversion therapy (P<0.05). Survival analysis results showed statistically significant difference in overall survival (OS) between the NED group and the inconspicuous/progressive group (P<0.0001). Also, there was a statistically significant difference in the progression-free survival (PFS) between the NED group and the inconspicuous/progressive group (P<0.0001). Patients in the surgical resection group had better OS and PFS than those in the ablation group (P<0.0001 and P<0.01, respectively). The monofactor analysis demonstrated that the number and maximum diameter of liver metastases, serum Carcino-Embryonic Antigen (CEA) level, and BRAF V600E mutation status were factors affecting the OS of CRLM patients (P<0.05), of which BRAF V600E mutation was the primary determinant (P<0.05). Conclusions: Among the patients whose CRLM was initially evaluated as unresectable, those who underwent surgical resection of the primary lesions and liver metastases after receiving conversion therapy had the best prognosis. Thus, a thorough evaluation should be conducted to determine the effect of and survival factors affecting conversion therapy in the treatment of liver metastases.

To study the expression of RUNX3 in colorectal adenocarcinoma tissues and its correlation with microvessel density (MVD), and investigate the clinical pathological prognostic significance of RUNX3 and MVD in patients with colorectal cancer. The expression value of RUNX3 and MVD in 70 specimens' colorectal adenocarcinoma tissues were detected by immunohistochemistry staining technique. The correlation between their expression and the clinicopathologic features was also investigated. The expression value of RUNX3 and the positive rates of RUNX3 in colorectal adenocarcinoma tissues were 3.25 ± 1.14 and 25.71% (18/70). The expression value of MVD in colorectal adenocarcinoma tissues was 13.14 ± 3.23. Expression of RUNX3 and MVD value were correlated with CEA, serosal invasion, liver metastasis, lymph node metastasis, and TNM stage (P < 0.01). The expression value of RUNX3 had negative correlations with that of MVD. The high expression of RUNX3 could inhibit tumor microvascular generation in order to have negative control response on invasion and distant metastasis.

Objective. To investigate the effect of Runt‐associated transcription factor 3 (RUNX3) on the invasion and metastasis of human colon cancer HT‐29 cells and to preliminarily explore the mechanism of its anticancer effect. Methods. The RUNX3 plasmid vector was transfected into human colon cancer HT‐29 cells by liposome‐mediated transfection, while the empty vector and the blank group were used as the control group. After Geneticin (G418) screening, HT‐29 cells with stable expression of RUNX3 gene were obtained. The expressions of mRNA and proteins of RUNX3 and metalloproteinases (MMP)‐2/9 were detected by reverse transcription‐polymerase chain reaction (RT‐PCR) and western blot. Cell proliferation was determined by MTT assay. The effect of RUNX3 on invasion and metastasis of HT‐29 cells was evaluated by scratch injury assay, Transwell chamber, and Matrigel invasion model. Results. RUNX3 was expressed stably in HT‐29 cells after transfection. The expressions of RUNX3 mRNA and proteins in the experimental group were significantly higher than those in the blank/empty vector groups. Meanwhile, the expressions of MMP‐2/9 mRNA and proteins in the observation group were significantly lower than those in the blank group and the empty vector group. The proliferation and migration ability in the experimental group was significantly lower than blank/empty vector groups from the third day. Transwell chamber experiment and Matrigel invasion assay showed that the number of Transwell cells was decreased significantly than blank/empty vector groups, but no difference was found between the blank group and the empty vector group. Conclusion. RUNX3 can inhibit the invasion and metastasis of human colon cancer HT‐29 cells, and the mechanism may be related to decreased expression of MMP‐2 and MMP‐9.

Background: The incidence of colorectal cancer is high and on the rise. The genetic and protein expressions of RUNT-associated transcription factor 3 (RUNX3) and human epidermal growth factor receptor 2 (HER2) in colorectal cancer (CRC) and adjacent normal tissues were detected to preliminarily explore their correlation and clinical significance. Methods: CRC specimens excised during general surgery were selected for localization and quantitative analysis of protein and gene expression by SP (Streptavidin-peroxidase conjugated method) immunohistochemical staining, reverse transcription-polymerase chain reaction (RT-qPCR) and western blot. Combined with the patients’ data, the relationship between the expression of the two genes and tumor characteristics was analyzed. Log-rank test was used to analyze the correlation between the two proteins and survival prognosis of CRC patients. The expression of RUNX3 in RKO and HCT-116 was knocked down, and the relative expression of HER2 in the two cell lines was detected. Results: Immunohistochemical, RT-qPCR and Western blot results showed that the positive expression rate of RUNX3 in CRC was lower than in the normal group, and HER2 in CRC was higher than in the normal group. The positive expression of the two proteins correlated with the pT and pN stages of CRC. A significant negative correlation between the expression of the two genes in CRC. Follow-up results showed that the number of Runx3-positive patients was higher than negative ones, while HER2 positive were fewer than negative ones. In vitro experiments showed that RUNX3 protein and gene expression decreased, HER2 protein and gene expression increased in RUNX3 knockdown RKO and HCT-116 cells, respectively (P<0.05). Conclusions: The expression of RUNX3 and HER2 in CRC is related to the occurrence and development of CRC, and the two genes have a negative regulating effect.

Background: LncRNA cancer susceptibility candidate 9 (CASC9) is up-regulated in various cancers. In this study, we explored the role of CASC9 in colon cancer (CC). Methods: The level of CASC9 in CC tissues, adjacent normal tissues, intestinal epithelial cells (HIEC) and CC cell lines was evaluated by qRT-PCR. HCT116 and SW480 CC cells were transfected with siCASC9. The cell growth and cell proliferation makers (Ki-67 and PCNA) were detected by CCK-8, colony formation and western blotting, respectively. The cell apoptosis and cell cycle were determined by flow cytometry. MicroRNA sponged by CASC9 was predicted by starBase and verified by dual-luciferase reporter assay. Further analyses were performed to investigate the role of CASC9 sponging the microRNA in CC cells by transfection or co-transfection of siCASC9 and miR-145-5p inhibitor. Results: LncRNA CASC9 was high-expressed in CC cells and tissues, especially in CC at advanced TNM stages. In HCT116 and SW480 cells, knockdown of CASC9 suppressed cell proliferation, promoted cell apoptosis and arrested cell cycle at G0/G1 phase. Furthermore, CASC9 was observed to sponge and regulate the expression of miR-145-5p, which was down-regulated in CC tissues. Moreover, increased cell proliferation and decreased cell apoptosis and arrested cell cycle caused by miR-145-5p inhibitor were abrogated by the knockdown of CASC9. Conclusions: LncRNA CASC9 is an oncogene in CC cells through sponging miR-145-5p. The findings in the current study provide a new understanding on CASC9 in CC.