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The prognosis of Intrahepatic cholangiocarcinoma (ICC) patients who did not undergo lymphadenectomy is difficult to assess. This study aims to have a dynamic evaluation on the postoperative survival of ICC patients by calculating conditional survival. Relevant data were from patients treated in 12 large-scale hospitals from December 2011 to December 2017. The influence of relevant clinical baseline data on the prognosis of ICC patients was analyzed by Cox regression. Conditional survival (CS) is a method that may predict the prognostic probability dynamically. For a patient with x years of survival, the 1-year CS (CS1) may be calculated as CS1= OS(x + 1)/OS(x). A total of 361 patients who met the criteria were included in the study. Conditional survival (CS) means that the patients' prognosis varies with survival time, meanwhile, relevant factors affecting the prognosis have a time-varying effect. The probability of survival assessed by CS1 increased year by year and the 1,2,3-year survival improved from 68.4% to 87.8%, while the postoperative actuarial OS decreased from 69.4% at 1 years to 36.9% at 3 years. In terms of CS, the estimated survival for ICC varies with the increase of survival time after excision. Patients who live longer were likely to live longer. At the same time, with the passage of time, the role of the original adverse factors of the tumor would gradually decrease. Conditional survival allows a more accurate assessment of ICC patients who did not undergo lymphadenectomy. [ABSTRACT FROM AUTHOR]

China's cultural classics have high artistic and ideological values in the world, which implies China's historical heritage and the inheritance of the cultural situation of the Chinese nation for thousands of years. At present, with the rapid development of China's economy, especially in the development environment of cultural globalization, China's traditional cultural classics have attracted worldwide attention along with historical and cultural treasures. In fact, other countries need to translate cultural classics out of their love for China's cultural classics or academic research. However, there are a large number of cultural classics in China. According to relevant data, there are approximately 35,000 kinds of cultural classics, out of which only 0.2% are translated into foreign languages. In order to make China's excellent cultural classics known to the world and let more people in other countries understand Chinese culture, this paper studies the translation of cultural classics through in-depth learning. Firstly, this paper introduces the basic concept of deep learning and proposes an algorithm that deeply studies the convolution layer and pool layer. Secondly, the algorithm establishes a deep learning model that calculates and counts the text information of ancient books through explicit intertextuality. Thirdly, the model carries out automatic text translation and lists the analysis process of cultural classics translation based on intertextuality, so as to study cultural classics translation. The obtained results can promote the development of cultural classics translation in China. For the translation of complex cultural classics, the effects of the three models are tested experimentally, of which the sequence model (seq) is the best. This model is fast and simple to extract the text of literary classics. [ABSTRACT FROM AUTHOR]

Background: The clinical value of lymph-node dissection (LND) for intrahepatic carcinoma (ICC) patients with clinically negative lymph node metastasis (LNM) remains unclear; hence we conducted a multi-center study to explore it. Methods: Patients who were diagnosed ICC with clinically negative LNM and underwent hepatectomy with or without LND from December 2012 to December 2015 were retrospectively collected from 12 hepatobiliary centers in China. Overall survival (OS) was analyzed using the Kaplan–Meier method, and then subgroup analysis was conducted stratified by variables related to the prognosis. Results: A total of 380 patients were eligible including 106 (27.9%) in the LND group and 274 (72.1%) in the non-LND group. Median OS in the LND group was slightly longer than that in the non-LND group (24.0 vs. 18.0 months, P = 0.30), but a significant difference was observed between the two groups (24.0 vs. 14.0 months, P = 0.02) after a well-designed 1:1 propensity score matching without increased severe complications. And, LND was identified to be one of the independent risk factors of OS (HR = 0.66, 95%CI = 0.46–0.95, P = 0.025). Subgroup analysis in the matched cohort showed that patients could benefit more from LND if they were male, age <60 years, had no HBV infection, with ECOG score <2, CEA ≤5 ug/L, blood loss ≤400 ml, transfusion, major hepatectomy, resection margin ≥1 cm, tumor size >5 cm, single tumor, mass-forming, no satellite, no MVI, and no perineural invasion (all P < 0.05). Furthermore, only patients with pathologically confirmed positive LNM were found to benefit from postoperative adjuvant therapy (P < 0.001). Conclusion: With the current data, we concluded that LND would benefit the selected ICC patients with clinically negative LNM and might guide the postoperative management. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the impact of resection margin on recurrence pattern and survival for hepatocellular carcinoma (HCC) with narrow margin resection, with the aim to guide postoperative treatment. Materials and Methods: Two hundred forty HCC patients after curative hepatectomy between 2014 and 2016 were reviewed retrospectively. The cases were divided into narrow-margin (width of resection margin <1cm, n=106) and wide-margin (width of resection margin ≥1cm, n=134) groups based on the width of resection margin. Recurrence pattern, recurrence-free survival (RFS), and overall survival (OS) were compared between the above two groups. An additional cohort of nine cases with positive margin plus post-operative stereotactic body radiotherapy (SBRT) was also analyzed for the recurrence pattern. Results: Postoperative recurrence was found in 128 (53.3%) patients. The recurrence rate was significantly higher in narrow-margin group than that in wide-margin group (P=0.001), especially for the pattern of marginal recurrence (20.8 vs. 4.5%, P=0.003). The 1-, 2-, 3-year RFS rates for the narrow-margin and wide-margin groups were 55.8, 43.9, 36.9, and 78.7, 67.9, 60.2%, respectively, with significant difference between the two groups (P<0.001). Patients with narrow margin showed a tendency of decreased OS than those with wide margin (P<0.001). As comparison, the nine cases with positive margin treated with postoperative SBRT showed low recurrence rate and no marginal recurrence was found. Conclusion: Patients with narrow resection margin were associated with higher recurrence rate and worse survival than those with wide resection margin. These patients may benefit from adjuvant local treatment, such as radiotherapy. [ABSTRACT FROM AUTHOR]

The tumor microenvironment (TME) has attracted attention owing to its essential role in tumor initiation, progression, and metastasis. With the emergence of immunotherapies for various cancers, and their high efficacy, an understanding of the TME in gastric cancer (GC) is critical. The aim of this study was to investigate the effect of various components within the GC TME, and to identify mechanisms that exhibit potential as therapeutic targets. The ESTIMATE algorithm was used to quantify immune and stromal components in GC samples, whose clinicopathological significance and relationship with predicted outcomes were explored. Low tumor mutational burden and high M2 macrophage infiltration, which are considered immune suppressive characteristics and may be responsible for unfavorable prognoses in GC, were observed in the high stromal group (HR = 1.585; 95% CI, 1.112–2.259; P = 0.009). Furthermore, weighted correlation network, differential expression, and univariate Cox analyses were used, along with machine learning methods (LASSO and SVM-RFE), to reveal genome-wide immune phenotypic correlations. Eight stromal-relevant genes cluster (FSTL1, RAB31, FBN1, ANTXR1, LRRC32, CTSK, COL5A2 , and ENG) were identified as adverse prognostic factors in GC. Finally, using a combination of TIMER database and single-sample gene set enrichment analyses, we found that the identified genes potentially contribute to macrophage recruitment and polarization of tumor-associated macrophages. These findings provide a different perspective into the immune microenvironment and indicate potential prognostic and therapeutic targets for GC immunotherapies. [ABSTRACT FROM AUTHOR]

Background and Aims: The prognosis of intrahepatic cholangiocarcinoma (ICC) after radical resection is far from satisfactory; however, the clinical value of adjuvant therapy (AT) remains controversial. This multicenter study aimed to evaluate the clinical value of AT and identify potential patients who would be benefited from AT. Methods: Data from ICC patients who underwent radical resection were retrospectively collected from 12 hepatobiliary centers in China between December 2012 and December 2015. Patients were divided into AT and non‐AT groups based on whether AT was administered or not. Overall survival (OS) and disease‐free survival (DFS) were analyzed using the Kaplan‐Meier method before and after 1:2 propensity score matching (PSM). Subgroup analyses were conducted based on the established staging systems. Results: A total of 412 patients were enrolled in this study, and 77 patients (18.9%) received AT, including 32 (7.8%) patients who received transarterial chemoembolization (TACE), 21 (5.1%) patients who received chemotherapy, 10 (2.4%) patients who received radiotherapy, and 14 (3.4%) patients who received adjuvant chemoradiotherapy. The median OS and DFS were both longer in the AT group than in the non‐AT group (43.0 months vs 21.0 months, P =.015; 16.0 months vs 11.0 months, P =.045, respectively), and the advantage of AT was confirmed for both the OS and DFS (P =.023; P =.046, respectively) after 1:2 PSM. Furthermore, based on the established nomogram, only "middle‐risk" patients receiving AT cherished a longer median OS (43.0 months vs 20.0 months, P =.033). In subgroup analyses that were stratified by different AT strategies, patients receiving postoperative chemotherapy had a longer median OS (37.0 months vs 21.0 months, P =.039), while patients receiving postoperative TACE had a longer median DFS (50.0 months vs 11.0 months, P =.007). Conclusion: With the current data, we conclude that AT benefits ICC patients following radical resection, especially those "middle‐risk" patients, as evaluated by the established nomogram. However, exactly which patients are the most suitable for AT requires further study and validation. [ABSTRACT FROM AUTHOR]

Background. In China, the cases of liver transplantation (LT) from donation after citizens' death have rose year by year since the citizen-based voluntary organ donor system was initiated in 2010. The objective of our research was to investigate the early postoperative and late long-term outcomes of LT from donation after brain death (DBD) and donation after circulatory death (DCD) according to the current organ donation system in China. Methods. Sixty-two consecutive cases of LT from donation after citizens' death performed in our hospital between February 2012 and June 2017 were examined retrospectively for short- and long-term outcomes. These included 35 DCD LT and 27 DBD LT. Result. Subsequent median follow-up time of 19 months and 1- and 3-year graft survival rates were comparative between the DBD group and the DCD group (81.5% and 66.7% versus 67.1% and 59.7%; P=0.550), as were patient survival rates (85.2% and 68.7% versus 72.2% and 63.9%; P=0.358). The duration of ICU stay of recipients was significantly shorter in the DBD group, in comparison with that of the DCD group (1 versus 3 days, P=0.001). Severe complication incidence (≥grade III) after transplantation was identical among the DBD and DCD groups (48.1% versus 60%, P=0.352). There was no significant difference in postoperative mortality between the DBD and DCD groups (3 of 27 cases versus 5 of 35 cases). Twenty-one grafts (33.8%) were lost and 18 recipients (29.0%) were dead till the time of follow-up. Malignancy recurrence was the most prevalent reason for patient death (38.8%). There was no significant difference in incidence of biliary stenosis between the DBD and DCD groups (5 of 27 cases versus 6 of 35 cases, P=0.846). Conclusion. Although the sample size was small to some extent, this single-center study first reported that LT from DCD donors showed similar short- and long-term outcomes with DBD donors and justified the widespread implementation of voluntary citizen-based deceased organ donation in China. However, the results should be verified with a multicenter larger study. [ABSTRACT FROM AUTHOR]

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The identification of circulating tumor cells (CTCs) relies on epithelial tumor cell markers. In the present study, we aimed to determine whether cell-surface vimentin could be a biomarker to isolate CTCs in pancreatic ductal adenocarcinoma (PDAC). Vimentin was identified as highly expressed on the surface of mesenchymal-phenotype pancreatic tumor cells. Vimentin+ CTCs were detected in 76% of patients with PDAC (76/100) using CTCs enriched via a microfluidic assay. A cut-off value of two vimentin+ CTCs distinguished patients with PDAC from healthy individuals. Combined vimentin+ CTCs and Carbohydrate antigen 19-9 provided favorable diagnostic potency, with an area under the curve of 0.968. Vimentin+ CTCs counts correlated with the change in tumor burden for patients undergoing resection. Significantly reduced CTC counts were observed after chemotherapy in subjects that responded to treatment. Preoperatively higher CTCs counts correlated with shortened recurrence-free survival. Taken together, vimentin+ CTCs could be a reliable biomarker in pancreatic cancer. The enrichment of mesenchymal CTCs complements the strategy of capturing epithelial CTCs, allowing a more thorough interrogation of the biology and clinical significance of CTCs in PDAC. [ABSTRACT FROM AUTHOR]

BACKGROUND RNA N6-methyladenosine (m6A) methylation, the most abundant and prominent form of epigenetic modification, is involved in hepatocellular carcinoma (HCC) initiation and progression. However, the role of m6A methylation in HCC tumor microenvironment (TME) formation is unexplored. This study aimed to reveal the TME features of HCC patients with distinct m⁶A expression patterns and establish a prognostic model based on m⁶A signatures for HCC cohorts. MATERIAL AND METHODS We classified the m⁶A methylation patterns in 365 HCC samples based on 21 m6A modulators using a consensus clustering algorithm. Single-sample gene set enrichment analysis algorithm was used to quantify the abundance of immune cell infiltration. Gene set variation analysis revealed the biological characteristics between the m⁶A modification patterns. The m6A-based prognostic model was constructed using a training set with least absolute shrinkage and selection operator regression and validated in internal and external datasets. RESULTS Two distinct m⁶A modification patterns exhibiting different TME immune-infiltrating characteristics, heterogeneity, and prognostic variations were identified in the HCC cohort. After depicting the immune landscape of TME in HCC, we found patients with high LRPPRC m⁶A modulator expression had depletion of T cells, cytotoxic cells, dendritic cells, and cytolytic activity response. A high m⁶A score, characterized by suppression of immunity, indicated an immune-excluded TME phenotype, with poor survival. A nomogram was developed to facilitate HCC clinical decision making. CONCLUSIONS Our results highlight the nonnegligible role of m6A methylation in TME formation and reveal a potential clinical application of the m⁶A-associated prognostic model for patients with HCC.

Background: Pancreatic cancer (PC) is among the most aggressive types of cancer. Hypoxia has been identified as a key risk factor for cancer progression. The forkhead box (FOX) proteins are multidirectional transcriptional factors that are strongly implicated in malignancies. However, whether FOXO3a, a member of the FOX protein family, is involved in the pro-oncogenic functions of hypoxia in PC has remained largely unelucidated. In this study, we attempted to clarify the role of FOXO3a in metastasis under hypoxic conditions and its underlying mechanism., Methods: MTT and flow cytometry assays were performed to detect the cell proliferation and cell cycle distribution respectively. Transwell assays were used to determine the potential of cell migration and invasion. qPCR and western blot assays were used to assess the expression of mRNA and protein. Immunofluorescence assay was performed to evaluate the cellular localization of FOXO3a. FOXO3a overexpression plasmid was constructed to perform the rescue experiment., Results: Our data indicated that PANC-1 and SW1990 cells represented enhanced cell migration and invasion abilities under hypoxia, while no statistical differences in cell proliferation and cell cycle distribution were observed. Hypoxia upregulated the messenger RNA (mRNA) and protein expressions of HIF-1α, FOXO3a, and the key epithelial-mesenchymal transition (EMT)-related (EMT) molecules N-cadherin and vimentin, as well as the phosphorylation of FOXO3a. Interestingly, hypoxia promoted the extranuclear localization of FOXO3a. Overexpression of FOXO3a not only significantly decreased the invasion, migration, and EMT of PC cell lines, but also reversed hypoxia-induced extranuclear localization. Finally, FOXO3a might act as a tumor suppressor in PC by inhibiting the ERK signaling pathway by inducing DUSP6 expression, and the ERK activator fisetin could effectively attenuate the inhibitory role of FOXO3a on ERK., Conclusions: Taken together, our results identified that hypoxia-induced extranuclear localization of FOXO3a promoted cell migration and invasion of human PC by modulating the DUSP6/ERK pathway., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://dx.doi.org/10.21037/jgo-21-359). The authors have no conflicts of interest to declare., (2021 Journal of Gastrointestinal Oncology. All rights reserved.)

Purpose: To explore the clinical efficacy and safety of Licartin combined with transcatheter hepatic arterial chemoembolization (TACE) in the treatment of middle-advanced primary liver cancer., Methods: The clinical data of 112 patients with middle-advanced primary liver cancer treated in our hospital from March 2015 to March 2017 were collected. Fifty-six patients underwent TACE combined with Licartin (Licartin+TACE group), while the remaining 56 patients were treated with TACE alone (TACE group). The short-term efficacy, peripheral hemogram, liver function, alpha fetoprotein (AFP) level, count of circulating tumor cells (CTCs) and cluster of differentiation (CD)147 phenotype before and after treatment were assessed in both groups, the incidence of adverse reactions was compared, and the postoperative survival and disease development were recorded during follow-up., Results: At 2 weeks after treatment, the levels of ALT and AST were significantly higher in Licartin + TACE group than those in TACE group (p<0.05). After treatment, the white blood cell count (WBC) and platelet count (PLT) obviously declined in both groups, and they were obviously lower in Licartin + TACE group than those in TACE group (p<0.05). After treatment, the count of CTCs evidently declined in both groups compared with that before treatment (p<0.05), and it was evidently lower in Licartin + TACE group than in TACE group (p<0.001). All patients were followed up for 3-36 months. In Licartin + TACE group and TACE group, the mean overall survival (OS) was 13.1±3.6 months and 11.3±2.8 months, respectively, and the mean progression-free survival (PFS) was 7.9±1.4 months and 6.1±1.2 months, respectively. At the end of follow-up, the Kaplan-Meier survival curves were plotted and log-rank test found that the OS rate was remarkably superior in Licartin + TACE group to that in TACE group (p=0.047), but the PFS rate had no statistically significant difference between the two groups (p=0.372)., Conclusions: Licartin combined with TACE has better efficacy than TACE alone in the treatment of middle-advanced primary liver cancer, with tolerable adverse reactions, which prolongs patients' survival time.

BACKGROUND Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive gastrointestinal tumors and has an extremely high mortality rate. Recent studies indicate that alternative splicing (AS), a common post-transcriptional process, has important roles in tumor biological behaviors and may provide novel immunotherapeutic targets. This study systematically analyzes AS profiles in PDAC and reveals their potential regulatory effects on cancer immune response. MATERIAL AND METHODS AS event, RNA sequencing, and splicing factor (SF) data were extracted from SpliceSeq, The Cancer Genome Atlas, and SpliceAid2, respectively. Overall survival (OS)-associated AS events and SFs were identified with univariate analysis. The LASSO method and multivariate Cox regression analysis were used to construct predictive signatures for the prediction of patient prognosis. The proportions of immune cells within PDAC samples were evaluated using the CIBERSORT algorithm. The correlations among AS events, SFs, and immune cell proportions were calculated using Spearman correlation analysis. Consensus clustering and immune classification were performed on the PDAC cohort. RESULTS A total of 4812 OS-related AS events from 3341 parent genes were identified, and 8 AS-based predictive models were constructed for PDAC. An OS-related SF-AS regulatory network was constructed. The AS events regulated by ELAVL4 exhibited strong correlations with CD8 T cells and regulatory T cells. In addition, AS-based clusters demonstrated distinct OS outcomes and immune features. CONCLUSIONS AS-based predictive models with high accuracy were constructed to facilitate prognosis prediction and treatment of PDAC. An SF-AS regulatory network was constructed, revealing the potential relationships among SF, AS, and immune response.

We aimed to explore the application of circulating cell-free DNA (cfDNA) profiling in monitoring tumor burden in patients with pancreatic ductal adenocarcinoma (PDAC). Thirty-eight patients with advanced PDAC receiving first-line FOLFIRINOX chemotherapy were prospectively enrolled. Next-generation sequencing for a panel of 560 genes covering a wide range of cancer-related loci was performed to profile cfDNA. In total, 25 patients (65.8%) had at least one common driver gene alterations ( KRAS, TP53, SMAD4, CDKN2A ) detected within cfDNA. In contrast, no above tumor-related recurrent mutations were found in plasma from 13 healthy individuals. Concordant alterations in plasma cfDNA and tumor tissue DNA was confirmed in two of three patients with available tissues. Further analysis showed that mutant allele fraction (MAF) for altered loci in cfDNA correlated with tumor stage, metastatic burden, and overall survival. Serial blood samples were collected from 17 patients after chemotherapy. We found that allele fraction for specific altered loci declined in chemotherapy-responding subjects. For cases who were resistant to this therapeutic regimen, increased ctDNA MAF was observed at the time of disease progression. Meanwhile, the dynamics of total cfDNA concentration correlated with tumor burden following chemotherapy. Collectively, we provide evidence that pretreatment ctDNA level correlates with tumor burden in PDAC, and serial cfDNA analysis is a robust tool for monitoring cancer response to chemotherapy., (©2018 American Association for Cancer Research.)

The prognostic biomarkers and potential therapy targets are urgently needed in hepatocellular carcinoma (HCC). In this article, we report the expression of TUBA1C was significantly increased in HCC on mRNA and protein level, and this finding was further validated in another two independent datasets. Survival analysis was also implemented on these three datasets, and TUBA1C high expression group was detected to have relative shorter survival time. Furthermore, the metastatic ability is increased along with TUBA1C abundance, according to protein abundance evaluation of normal-tumor-portal vein tumor thrombus pairs, and mRNA comparison between metastasis-averse HCC and metastasis-incline HCC. Correlation analysis was implemented and TUBA1C expression was shown to be significantly associated with recurrence, embolus, and AFP level. Proliferation and migration assays following knock down of TUBA1C in two cell lines, HCCLM3 and PLC, revealed that down-regulation of TUBA1C significantly reduces proliferation and migration in HCC cells. in vivo study also showed the similar results. Gene Set Enrichment Analysis (GSEA) comparing the TUBA1C-low and TUBA1C-high group indicates that KEGG pathways including "cell cycle", "DNA replication", and "proteasome" were significantly enriched in TUBA1C-high group. In conclusion, prognostic biomarker and oncogene TUBA1C promotes migration and proliferation of hepatocellular carcinoma cells, probability via cell cycle signaling pathway., Competing Interests: CONFLICTS OF INTEREST The authors declare that they have no conflicts of interest.