Background The precise clinical features and prognosis of IPNB remain challenging to define. More research is needed to enhance understanding of the disease. Methods The study retrospectively analyzes the clinical data of 123 patients with IPNB from two medical centers during January 2013 and May 2024. The clinicopathological characteristics of IPNB were compared across subgroups. Risk factors for invasive IPNB and survival predictors of IPNB were identified by regression analysis. The prognosis of patients with IPNB was evaluated through survival and recurrence analysis. Result The majority of tumors (51.2 %) were located in the extrahepatic bile ducts, 42.3 % were in the intrahepatic bile ducts, and 6.5 % exhibited diffuse distribution. 23 patients (18.7 %) were diagnosed with low-grade dysplasia, 41 patients (33.3 %) were diagnosed with high-grade dysplasia, and the remaining 59 patients (48.0 %) were diagnosed with invasive carcinomas. Mucin secretion was observed in 33.3 % of cases. Focal bile duct wall thickening and pancreaticobiliary maljunction were identified as independent risk factors for invasive IPNB. The 1-year, 3-year, and 5-year overall survival rates were 97.4 %, 77.2 %, and 70.1 %, respectively. For all IPNB patients, the extrahepatic type and presence of invasive carcinoma were independent predictors of survival. In invasive IPNB, the extrahepatic type, local invasion, and vascular invasion were associated with worse survival. Conclusion The clinicopathological features of IPNB exhibited significant heterogeneity across subgroups. Early diagnosis and timely surgical intervention are critical for optimizing patients’ long-term outcomes.

Background:Due to a lack of early diagnosis methods and effective drugs, pancreatic ductal adenocarcinoma (PDAC) has an extremely poor prognosis. DNA methylation, transcriptome expression and gene copy number variation (CNV) have critical relationships with development and progression of various diseases. The purpose of the study was to screen reliable early diagnostic biomarkers and potential drugs based on integrative multiomics analysis. Methods:We used methylation, transcriptome and CNV profiles to build a diagnostic model for PDAC. The protein expression of three model-related genes were externally validated using PDAC samples. Then, potential therapeutic drugs for PDAC were identified by interaction information related to existing drugs and genes. Results:Four significant differentially methylated regions (DMRs) were selected from 589 common DMRs to build a high-performance diagnostic model for PDAC. Then, four hub genes, PHF12, FXYD3, PRKCB and ZNF582, were obtained. The external validation results showed that PHF12, FXYD3 and PRKCB protein expression levels were all upregulated in tumor tissues compared with adjacent normal tissues (P<0.05). Promising candidate drugs with activity against PDAC were screened and repurposed through gene expression analysis of online datasets. The five drugs, including topotecan, PD-0325901, panobinostat, paclitaxel and 17-AAG, with the highest activity among 27 PDAC cell lines were filtered. Conclusions:Overall, the diagnostic model built based on four significant DMRs could accurately distinguish tumor and normal tissues. The five drug candidates might be repurposed as promising therapeutics for particular PDAC patients.

Background:Hepatocellular carcinoma (HCC) is one of the most common malignant tumors originating from the digestive system. Tertiary lymphoid structures (TLS), non-lymphoid tissues outside of the lymphoid organs, are closely connected to chronic inflammation and tumorigenesis. However, the detailed relationship between TLS and HCC prognosis remained unclear. In this study, we aimed to construct a TLS-related gene signature for predicting the prognosis of HCC patients. Methods:The Cancer Genome Atlas (TCGA) clinical data from 369 HCC tissues and 50 normal liver tissues were utilized to examine the differential expression of TLS-related genes. Based on least absolute shrinkage and selection operator (LASSO) Cox regression analysis, the prognostic model was constructed using the TCGA cohort and validated in the GSE14520 cohort and International Cancer Genome Consortium (ICGC) cohort. The Kaplan-Meier (KM) and receiver operating characteristic (ROC) curves were employed to validate the predictive ability of the prognostic model. Furthermore, Cox regression analysis was applied to identify whether the TLS score could be employed as an independent prognosis factor. A nomogram was developed to predict the survival probability of HCC patients. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were performed for TLS-related genes. Genetic mutation analysis, the CIBERSORT algorithm, and single-sample gene set enrichment analysis (ssGSEA) were used to assess the tumor mutation landscape and immune infiltration. Finally, the role of the TLS score in HCC therapy was investigated. Results:Six genes were included in the construction of our prognostic model (CETP, DNASE1L3, PLAC8, SKAP1, C7, and VNN2), and we validated its accuracy. Survival analysis showed that patients in the high-TLS score group had a significantly better overall survival than those in the low-TLS score group. Univariate, multivariate Cox regression analysis and the establishment of a nomogram indicated that the TLS score could independently function as a potential prognostic marker. A significant association between TLS score and immunity was revealed by an analysis of gene alterations and immune cell infiltration. In addition, two subtypes of the TLS score could accurately predict the effectiveness of sorafenib, transcatheter arterial chemoembolization (TACE), and immunotherapy in HCC patients. Conclusion:In this research, we conducted and validated a prognostic model associated with TLS that may be helpful for predicting clinical outcomes and treatment responsiveness for HCC patients.

目的 探讨紫草素对肝癌Huh-7细胞增殖、迁移和侵袭的影响及其可能的分子机制.方法 实时荧光定量聚合酶链反应(FQ-PCR)检测微小RNA(miR)-637的表达水平;噻唑蓝(MTT)检测Huh-7细胞增殖;Transwell实验检测Huh-7细胞的迁移和侵袭;蛋白质印迹法检测Huh-7细胞中增殖、迁移和侵袭相关蛋白的表达.两组间比较采用t检验,多组件比较采用单因素方差分析,组内间比较采用SNK-q检验.结果 肝癌组织中miR-637表达水平低于癌旁组织(0.43±0.05比1.00±0.11,t=25.840,P＜0.05);1、2、3、4 μg/ml 紫草素组 Huh-7 细胞存活率低于对照组(82.24±7.82、54.15±6.16、43.34±6.35、38.68±5.24 比 100.00±9.69,t=4.279、11.980、14.670、16.700,P＜0.05);2μg/ml 紫草素处理组 Huh-7 细胞的增殖(0.81±0.07 比 1.46±0.18,t=10.097,P＜0.05)、迁移(79.28±8.12 比 137.19±14.36,t=10.531,P＜0.05)和侵袭(48.67±5.32 比102.52±11.25,t=12.982,P＜0.05)能力低于对照组.过表达miR-637组Huh-7细胞的增殖(0.78±0.08 比 1.52±0.13,F=96.865,P＜0.05)、迁移(74.12±8.16 比 134.26±15.69,F=77.227,P＜0.05)和侵袭(74.12±8.16 比 134.26±15.69,F=131.214,P＜0.05)能力低于 miR-NC组.2 μg/ml 紫草素+抗 miR-637 组 Huh-7 细胞增殖(1.27±0.15 比 0.75±0.08,F=65.743,P＜0.05)、迁移(116.28±12.53 比 71.45±7.82,F=58.264,P＜0.05)和侵袭(86.41±9.23 比46.32±4.92,F=113.920,P＜0.05)能力高于2μg/ml紫草素+抗miR-NC组.结论 紫草素可通过上调miR-637抑制Huh-7细胞的增殖、迁移和侵袭.

目的 分析基于案例学习(CBL)教学法联合模拟诊疗以及"WWWWTP"六步问答法在肝胆胰外科临床思维能力教学实践中的应用效果.方法 选取2021年8月至2022年1月在郑州大学第一附属医院实习的50名临床医学本科学生作为研究对象,以随机的方式将其分为实验组和对照组,每组25名.对照组学生采用传统教学方法,实验组学生在传统教学方法的基础上加入CBL联合模拟诊疗以及"WWWWTP"六步问答法.本科室实习期结束后,观察2组学生的临床思维考核评分、实践技能考核评分以及理论知识考核评分.结果 实验组学生的临床思维考核评分、实践技能考核评分以及理论知识考核评分均高于对照组,差异均有统计学意义(t=5.095,P＜0.001;t=5.146,P＜0.001;t=7.115,P＜0.001).结论 CBL教学法联合模拟诊疗以及"WWWWTP"六步问答法可有效提升肝胆胰外科实习学生的临床思维能力.

目的 探讨微小RNA(miRNA,miR)-342-3p靶向性别决定区Y框蛋白6(SOX6)对肝癌细胞增殖、周期和凋亡的影响及其分子机制.方法 选取2021年6月至2022年6月驻马店市中心医院收集的121例原发性肝癌组织和癌旁组织作为研究对象,采用荧光定量聚合酶链反应(PCR)技术分析肝癌组织和癌旁组织miR-342-3p表达水平;采用miRNA对照和miR-342-3p过表达慢病毒感染人肝癌细胞HepG2,构建miRNA对照组和miR-342-3p组细胞,采用细胞计数试剂盒(CCK-8)、克隆形成实验和体外移植瘤实验分析miRNA对照组和miR-342-3p组细胞的增殖;采用流式细胞术分析两组细胞的周期变化;采用膜联蛋白V-异硫氰酸荧光素(Annexin V-FITC)/碘化丙锭(PI)凋亡试剂盒分析两组细胞的凋亡水平;采用生物信息学和双荧光素酶报告基因分析miR-342-3p的靶基因;蛋白质免疫印迹(Western blot)分析蛋白质表达水平.组间计数资料比较采用t检验.结果 肝癌组织中miR-342-3p表达水平(1.23±0.22)明显低于癌旁组织表达水平(0.71±0.14),差异有统计学意义(t=21.710,P＜0.05).miRNA对照组细胞吸光度(A)值(2.02±0.13)明显高于miR-342-3p组(1.61±0.09),差异有统计学意义(t=6.441,P＜0.05).miRNA对照组细胞克隆形成率[(85.92± 4.95)％]明显高于miR-342-3p组[(59.06±4.39)％],差异有统计学意义(t=9.942,P＜0.05).miRNA对照组细胞体内成瘤体积[(690.67±72.49)mm3]明显高于miR-342-3p组[(59.06± 4.39)mm3],差异有统计学意义(t=9.942,P＜0.05).miRNA对照组细胞G0/G1期百分比[(41.33±2.58)％]明显低于 miR-342-3p 组[(58.33±2.93)％],差异有统计学意义(t=10.980,P＜0.05).miRNA 对照组细胞 S 期百分比[(39.17±2.71)％]明显高于 miR-342-3p 组[(28.33± 3.31)％],差异有统计学意义(t=5.911,P＜0.05).miRNA对照组细胞凋亡率[(2.63±0.95)％]明显低于 miR-342-3p 组[(16.33±2.29)％],差异有统计学意义(t=13.510,P＜0.05).SOX6 是miR-342-3p的靶基因.癌旁组织中miR-342-3p靶基因SOX6表达水平(1.01±0.12)明显低于肝癌组织表达水平(2.00±0.14),差异有统计学意义(t=18.924,P＜0.05).miRNA对照组细胞SOX6蛋白表达水平(1.19±0.17)明显高于miR-342-3p组(0.62±0.11),差异有统计学意义(t=6.924,P＜0.05).结论 miR-342-3p在肝癌组织中呈低表达,通过靶向调节SOX6蛋白表达水平促进肝癌细胞的增殖,抑制细胞凋亡水平.

Hepatocellular carcinoma (HCC) remains one of the most fatal malignancies with high morbidity and mortality rates in the world, whose molecular pathogenesis is incompletely understood. As an RNA-binding protein participating in the processing and modification of RNA, KIAA1429 has been proved to be implicated in the pathogenesis of multiple cancers. However, how KIAA1429 functions in alternative splicing is not fully reported. In the current study, multi-omics sequencing data were used to analyze and decipher the molecular functions and the underlying mechanisms of KIAA1429 in HCC samples. RNA sequencing data (RNA-seq) analysis demonstrated that in HCCLM3 cells, alternative splicing (AS) profiles were mediated by KIAA1429. Regulated AS genes (RASGs) by KIAA1429 were enriched in cell cycle and apoptosis-associated pathways. Furthermore, by integrating the RNA immunoprecipitation and sequencing data (RIP-seq) of KIAA1429, we found that KIAA1429-bound transcripts were highly overlapping with RASGs, indicating that KIAA1429 could globally regulate the alternative splicing perhaps by binding to their transcripts in HCCLM3 cells. The overlapping RASGs were also clustered in cell cycle and apoptosis-associated pathways. In particular, we validated the regulated AS events of three genes using clinical specimens from HCC patients, including the exon 6 of BPTF gene and a marker gene of HCC. In summary, our results shed light on the regulatory functions of KIAA1429 in the splicing process of pre-mRNA and provide theoretical basis for the targeted therapy of HCC.

Phthalates (PAEs) are considered endocrine-disrupting chemicals (EDCs), a series of compounds able to disrupt the normal regulation of the human endocrine-system. In the present study, we investigated the roles of four PAEs, butyl benzyl phthalate (BBP), dibutyl phthalate (DBP), dimethyl phthalate (DMP), and diethyl phthalate (DEP), in hepatocellular carcinoma (HCC) cells. We define novel roles for the PAEs on the migration of HCC cells via their enhancing of the interaction between the pregnane X receptor (PXR) and E26 transformation specific sequence 1 (ETS-1). Our results indicate that PAEs induced the transcriptional activation of ETS-1 and PXR. PXR activated by PAEs could bind to ETS-1 directly and enhanced the activity of ETS-1, which resulted in the induction of invasion-related ETS-1 target genes. The "LXXLL" motif in the ETS-1C-terminal was essential for the interaction between PXR and ETS-1 induced by PAEs. Treatment of PAEs promoted the nuclear accumulation of ETS-1 or the recruitment of ETS-1, but not in cells expressing ETS-1 with a mutated LXXLL motif in its downstream gene promoter region, or following transfection of PXR siRNA. Treatment with the PXR antagonist ketoconazole almost completely inhibited the effects of PAEs. Moreover, PAEs enhanced the in vitro or in vivo invasion of HCC cells via PXR/ETS-1. Therefore, our results not only contribute to a better understanding of HCC, but also extended the roles of EDCs regulating human malignancies.

Objective:To investigate the effect of circular RNA 0007841 (circ_0007841) targeting microRNA (miR)-557 on the biological behavior of liver cancer cells MHCC97H.Methods:Liver cancer tissues and paracancerous tissues were collected from 47 patients with liver cancer who underwent surgical treatment in our hospital from January 2017 to December 2018. The relative levels of circ_0007841 and miR-557 were detected using real-time quantitative reverse transcriptase-polymerase chain reaction (RT-qPCR). According to different transfectants, MHCC97H cells were divided into si-NC group, si-circ_0007841 group, pcDNA group, pcDNA-circ_0007841 group, miR-NC group, miR-557 group, si-circ_0007841 + anti-miR-NC group, si-circ_0007841+ anti-miR-557 group. Cell counting kit-8 (CCK-8) assay, clone formation experiment, scratch healing experiment and Transwell experiment were applied to detect the absorbance ( A) value, clonal formation number, scratch healing rate and number of invasive MHCC97H cells. The dual luciferase report experiment verified the targeting relationship between circ_0007841 and miR-557. The independent-sample t test was used for comparison between the two groups, and the One-Way ANOVA and LSD- t test were used for the comparison between multiple groups. Results:The relative level of circ_0007841 (3.87±0.30 vs. 1.00±0.07, t=63.873, P<0.05) was increased, and that of miR-557 (0.34±0.04 vs. 1.00±0.09, P<0.05) was decreased in liver cancer tissues as compared with that in the adjacent tissues. As compared with the si-NC group, the A value (0.59±0.05 vs. 1.08±0.08, t=15.582, P<0.05), clonal formation number [(38.94±3.77) vs. (87.24±6.77, t=18.699, P<0.05), scratch healing rate [(25.21±2.51)% vs. (65.36±5.08)%, t=21.257, P<0.05] and the number of invasive cells [(47.97±4.82) vs. (111.04±9.84), t=17.268, P<0.05] in the si-circ_0007841 group were decreased, and the relative level of miR-557 (2.82±0.21 vs. 10.97±0.06, t=25.412, P<0.05) increased. As compared with the miR-NC group, the A value [(0.66±0.05) vs. (1.06±0.09), t=11.655, P<0.05)], clonal formation number [(46.17±4.02) vs. (46.17±4.02), t=15.098, P<0.05], scratch healing rate [(34.58±3.16)% vs. (68.56±5.81)%, t=15.413, P<0.05] and the number of invasive cells [55.12±5.58) vs. (109.94±11.52), t=12.848, P<0.05] in miR-557 group were decreased. As compared with the pcDNA group, the relative level of miR-557 [(0.36±0.04) vs. (1.00±0.00), t=48.000, P<0.05] in the pcDNA-circ_0007841 group was decreased. The circ_0007841 was directly bound with miR-557. As compared with the si-circ_0007841+ anti-miR-NC group, the A value [(0.89±0.06) vs. (0.56±0.05), t=12.676, P<0.05), clonal formation number [(76.01±6.35) vs. (36.94±3.93), t=15.695, P<0.05], scratch healing rate [(55.63±5.17)% vs. (23.54±2.92)%, t=16.214, P<0.05] and the number of invasive cells [(90.88±7.71) vs. (44.87±4.68), t=15.304, P<0.05] in the si-circ_0007841+ anti-miR-557 group were increased. Conclusion:Circ_0007841 may promote the proliferation, migration and invasion of liver cancer cells by targeting miR-557.

Objective:To explore the effect of phillyrin on the proliferation, migration, invasion and apoptosis of hepatoma cells and its regulatory effect on circ_0054537/miR-409-3p.Methods:Hep3B liver cancer cells were cultured in vitro, and Hep3B cells were treated with phillyrin at different doses (5, 10, 20 μmol/L). Cell counting kit-8 (CCK-8) method was used to detect cell proliferation. Flow cytometry was used to detect the apoptosis rate. Transwell cell test was used to detect cell migration and invasion ability. The expression levels of circ_0054537 and miR-409-3p were detected by real-time quantitative reverse transcriptase-polymerase chain reaction (RT-qPCR) method. The dual luciferase report experiment detected the targeting relationship of circ_0054537 and miR-409-3p. Hep3B cells were transfected with si-circ_0054537, pcDNA-circ_0054537, respectively, and cell proliferation, apoptosis, migration and invasion were detected by the above methods. SPSS 21.0 statistical software was used to analyze the data. The measurement data were expressed as ( Mean± SD) and all accorded with normal distribution. The comparison between the two groups was performed by independent sample t test. The comparison between groups was performed by one-way analysis of variance, with P<0.05 The difference was statistically significant. Results:Phillyrin could significantly reduce cell viability [(1.276±0.110) vs. (1.031±0.090), (0.637±0.050), (0.507±0.040), F=244.841, P<0.05], increased apoptosis rate [(7.34±0.62)% vs. (12.44±1.03)%, (22.86±2.12)%, (28.16±2.71)%, F=244.841, P<0.05], reduce the number of migrating cells [(154.15±12.76) vs. (124.06±10.04), (78.05±7.25), (61.13±5.83)] and the number of invasive cells [(112.04±10.08) vs. (89.43±8.13), (57.11±5.12), (43.08±4.05), F=186.018, 166.514, P<0.05], inhibit the expression of circ_0054537 [(1.00±0.10) vs. (0.40±0.04), t=16.713, P<0.05], promote the expression of miR-409-3p [(1.02±0.11) vs. (3.42±0.31), t=21.889, P<0.05]. Transfection of si-circ_0054537 could significantly inhibit cell viability [(1.264±0.10) vs. (0.686±0.06)], migration [(151.96±11.17) vs. (79.03±7.21)] and invasion ability[(115.28±11.05) vs. (68.14±6.43), t=14.869, 16.457, 11.062, P<0.05], increase the apoptosis rate [(7.26±0.71)% vs. (23.79±2.06)%, t=22.759, P<0.05]. The dual luciferase report experiment confirmed that circ_0054537 could target and bind to miR-409-3p. Transfection of pcDNA-circ_0054537 could significantly reverse the regulatory effect of phillyrin on proliferation, apoptosis, migration, invasion of Hep3B cells. Conclusion:Phillyrin could down-regulate the expression of circ_0054537 and up-regulate the expression of miR-409-3p to inhibit hepatocellular carcinoma cell proliferation, migration, invasion and promote apoptosis.

It has been found that the circular RNA (circRNA) CDR1as is upregulated in cholangiocarcinoma (CCA) tissues. In this study, we tried to explore the roles of CDR1as in CCA. CDR1as was overexpressed or knocked down in human CCA cells to assess the effects of CDR1as on cell behaviors and tumor xenograft growth. In vitro, the CDR1as level was significantly increased in CCA cell lines. The results showed that CDR1as promoted the cell proliferation, migration, invasion, and activation of the AKT3/mTOR pathway in CCA cells. Moreover, miR-641, a predicted target microRNA (miRNA) of CDR1as, could partially reverse the effects of CDR1as on cell behaviors in CCA cells. Furthermore, CDR1as improved tumor xenograft growth, and it could be attenuated by miR-641 in vivo Additionally, CDR1as expression was inversely correlated with miR-641 in CCA cells, and miR-641 could directly bind with CDR1as and its target genes, the AKT3 and mTOR genes. Mechanistically, CDR1as could bind with miR-641 and accelerate miR-641 degradation, which possibly leads to the upregulation of the relative mRNA levels of AKT3 and mTOR in RBE cells. In conclusion, our findings indicated that CDR1as might exert oncogenic properties, at least partially, by regulating miR-641 in CCA. CDR1as and miR-641 could be considered therapeutic targets for CCA.

It is crucial to grasp the characteristics of tumour immune microenvironment to improve effects of immunotherapy. In this study, the immune and stromal scores of 371 cases were calculated for quantitative analysis of immune and stromal cell infiltration in the tumour microenvironment of hepatocellular carcinoma (HCC). The weighted gene co-expression network analysis and protein-protein interaction network were analysed to identify immune microenvironment-related genes. The results showed that patients with high immune scores had a higher 4-year recurrence-free rate. TP53, CTNNB1, and AXIN1 mutations significantly varied with immune scores. In immune score-related modules analysis, Kyoto encyclopaedia of genes and genomes pathways and gene ontology terms were closely related to immune processes, tumorigenesis, and metastasis. Twelve new immune microenvironment-related genes were identified and had significantly positive correlations with seven immune checkpoint genes. In prognostic analysis, eleven immune microenvironment-related genes exhibited high expression, nine of which were validated in the GSE62232 dataset and were significantly associated with a good prognosis. Our findings suggest that calculating immune score and stromal score could help to determine tumour purity and immune cell infiltration in the tumour microenvironment. Nine immune microenvironment-related genes identified in this study had potential as prognostic markers for HCC.

目的 探讨中性粒细胞计数与淋巴细胞计数比(NLR)对胰腺腺癌根治术后患者预后的评估价值.方法 回顾性分析郑州大学第一附属医院肝胆胰外科行胰腺癌根治术的77例患者的临床资料,通过术前的血常规结果计算出NLR值,取NLR中位数2.63为截点将患者分为高NLR和低NLR 2组.比较2组患者术后第1年、第3年的生存率,并分别对其影响因素进行分析.结果 低NLR组第1年、第3年的生存率分别为89.2％、40.5％,均高于高NLR组的65.7％、11.4％,差异有统计学意义(P<0.05);单因素及多因素分析提示NLR为胰腺癌根治术后患者预后的影响因素(P<0.05).结论 外周血高NLR是一个提示胰腺癌预后较差的指标.

Background: Gastric cancer is a common lethal cancer worldwide. We aimed to develop a reliable, individualized, immune-related prognostic signature that can be used to stratify and estimate prognosis in patients with gastric cancer. Methods: This retrospective study analyzed the gene expression profiles of gastric cancer with tumor tissue samples from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) cohorts, which included 676 cases in total. Immune genes from the InnateDB database were selected to develop and validate an immune-related prognostic model for gastric cancer patients. Results: An immune-related gene pair (IRGP) model was constructed that enabled us to stratify patients into high- and low-risk immune risk groups in the training set. Patients with a low risk score had a significantly longer median survival time than those with a high risk score. Further, we compared the predictive accuracy of the IRGP model with clinical characteristics, including TNM, grade, age, and stage. The results showed that the model had the highest mean C-index (0.69) compared with grade (0.55) or stage (0.60) in survival prediction. Then, we constructed a nomogram that integrated the IRGP model with independent clinical characteristics, which showed the best prognostic accuracy compared with other signatures. Conclusion: A clinical-immune signature based on IRGP is a promising prognostic biomarker in gastric cancer. Prospective studies are needed to further validate its accuracy and to test its clinical utility in individualized treatment.

目的 探究原发性肝癌术后复发行经皮射频消融(RFA)后的疗效、生存率及其影响因素.方法 回顾性分析2012年6月至2016年6月郑州大学第一附属医院行手术切除的原发性肝癌术后复发的67例患者临床资料,采用统计软件SPSS 21.0分析,生存曲线采用Kaplan-Meier法绘制,组间比较采用Log-Rank检验,Cox风险比例模型进行预后因素分析.结果 67例术后复发的肝癌患者经皮RFA治疗后1、3、5年总体生存率分别为94％、62％、50％,1、3、5年无瘤总体生存率分别为56％、39％、26％.根据肝癌切除术后复发的肿瘤直径分为小肝癌组(≤3 cm,n=47)和中肝癌组(>3 cm且≤5 cm,n=20),小肝癌组及中肝癌组行经皮RFA治疗后1、3、5年生存率分别为98％、67％、54％及86％、55％、40％,小肝癌组的生存率明显高于中肝癌组(P=0.007).通过Cox模型多因素分析,结果显示复发病灶直径、术后甲胎蛋白(AFP)水平是影响患者经皮RFA后生存时间的危险因素.结论 经皮RFA治疗术后复发性肝癌疗效确切,能以较小的创伤达到治疗的目的,小肝癌及术后AFP低行RFA预后更好.

PURPOSE:tumor-infiltrating immune cells are highly relevant to the progression and prognosis of colorectal cancer (CRC). The aim of this study is to explore the immune cells and immune-related gene expression in tumor microenvironment of CRC.METHODS:CIBERSORT, a deconvolution algorithm, was used to analyze the infiltration of 22 immune cell types in the tumor microenvironment and immune-related gene expression in 404 CRC and 40 adjacent non-tumorous tissues.RESULTS:a wide heterogeneity of immune cells among different paired tissues and in tumor stages was uncovered. M0 macrophages, M1 macrophages and CD4 memory activated T cells were infiltrated significantly more in CRC compared with normal tissues in both TCGA and GEO cohorts. CRC with T1-2 tumor stage showed increased CD4 memory activated T cells compared with T3-4 tumors. M0 macrophages were the highest in stage N1 tumors. Significant immune-related genes were identified to build prognostic models by Cox regression analysis. The concordance index of the prognostic model for TNM stage I-II was 0.69, and 0.71 for stage III-IV. The AUC values for 1-, 3-, and 5-year survivals were 0.674, 0.773, 0.812 for TNM stage I-II, respectively, and 0.764, 0.782, 0.803 for stage III-IV, respectively.CONCLUSION:these results could assist clinicians in selecting targets for immunotherapies and individualize treatment strategies for patients with CRC.

Objective Analysis the date of patients with stage B Primary hepatocellular carcinoma in Barcelona Clinical Liver Classification (BCLC-B),and to explore the value of aspartate transaminase and platelet ratio index (APRI) combined with the indocyanine green retention rate at 15 mins (ICGR15)in evaluating the risk of the posthepatectomy liver failure (PHLF) for BCLC-B.Methods Analysis of clinical data of 216 patients with BCLC-B hepatocellular carcinoma undergoing hepatectomy.The best cut-off point of APRI value was obtained by receiver operating characteristic (ROC) curve.the logistic regression model was used to identify independent predictive indices for PHLF.According to whether Postopeatectomy Liver Failure (PHLF),they were divided into hepatic failure group and non-hepatic failure group.The differences in clinical biochemical parameters,ICGR15 and APRI between the two groups were recorded and analyzed.Results A total of 216 patients were enrolled in this study,among whom 30 (12.9％) had PHLF.he univariate and multivariate analyses showed that APRI and ICGR15 were significantly associated with the prognosis of PHLF patients (P ＜0.01).The ROC curve analysis shows that APRI has a strong ability to predict PHLF (The area under the curve is 0.831,the sensitivity is 93.3％,and the specificity is 65.6％),and the best cut-off point is 0.59.APRI-ICGR15 had a significantly higher area under the receiver operating characteristic curve (AUC)than APRI or ICGR15,and The AUC of APRI and ICGR15 are similar.For patients with BCLC-B stage hepatocellular carcinoma (HCC),when APRI ＜ 0.59 and ICGRI5 ＜ 10％,the incidence of liver failure after hepatectomy is low;when APRI≥0.59 and ICGR15 ＜ 10％,or APRI ＜ 0.59 and ICGR15 ≥ 10％ at that time,the incidence of PHLF is slightly higher.At this time,surgical treatment should be cautious.Liver function should be actively corrected before operation,and active supportive treatment should be given after surgery.When APRI≥0.59 and ICGR15≥10％,the incidence of PHLF is higher.Surgical treatment is not recommended for the time being.Conclusion ICGR15 and APRI are good indicators for evaluating liver reserve function.The combination of the two can better evaluate the risk of postoperative liver failure in patients with BCLC-B HCC.

目的 研究高血糖与胰腺癌脉管瘤栓的形成以及对胰腺癌根治术后预后的影响.方法 回顾性分析99例行胰腺癌根治术患者的病历资料并随访.按入院时空腹血糖是否>7.0 mmol/L分为高血糖组和正常血糖组,比较2组一般资料和预后.结果 2组患者的淋巴结转移、脉管瘤栓、神经浸润比较,差异有统计学意义(P<0.05).其中高血糖组出现脉管瘤栓比例(60.1％)高于正常血糖组(39.4％),差异有统计学意义(P<0.05).高血糖组术后中位生存期(12.3±0.8)个月短于正常血糖组(15.4±2.9)个月,差异有统计学意义(P<0.05).COX分析显示血糖、分化程度、TNM分期、神经浸润、脉管瘤栓是影响预后的独立因素.结论 高血糖对胰腺癌脉管瘤栓的形成有影响,胰腺癌伴高血糖患者行根治术后预后较差.

Background: Immunotherapy, as a very promising treatment, has the potential to change the therapeutic landscape for malignancies. However, due to the complexity of immunotherapy and the heterogeneity of Hepatocellular carcinoma (HCC), it is crucial to grasp the characteristics of the tumour immune microenvironment to improve effects of immunotherapy. Methods: The ESTIMATE (Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data) algorithm was used to calculate the immune and stromal scores for quantitative analysis of immune and stromal cell infiltration in HCC. The weighted gene co-expression network analysis (WGCNA) and protein-protein interaction (PPI) network were analysed to identify immune microenvironment-related genes. Findings: Immune and stromal scores calculated by ESTIMATE closely represented immune cell components in the tumour microenvironment. Patients with high immune scores had a higher 4-year survival rate. TP53, CTNNB1, and AXIN1 mutations significantly varied with immune scores. In immune score-related modules analysis, Kyoto encyclopaedia of genes and genomes (KEGG) pathways and gene ontology (GO) terms were closely related to immune processes, tumorigenesis, and metastasis. Twelve new immune microenvironment-related genes were identified and had significantly positive correlations with seven checkpoint genes. In prognostic analysis, eleven immune microenvironment-related genes exhibited high expression, nine of which were validated in the GSE62232 dataset and were significantly associated with a good prognosis (P<0.05). Interpretation: Calculating immune score and stromal score could help to determine tumour purity and immune cell infiltration in the tumour microenvironment. Nine immune microenvironment-related genes identified in this study had potential as prognostic markers for HCC. Funding Statement: This research received no external funding.Declaration of Interests: The authors have declared that no conflict of interest existsEthics Approval Statement: The data from TCGA, GEO and The Human Protein Atlas were all publicly available and open access, so no approval was needed from the ethics committees.

Background/Aims: This study aims to examine the effect of long noncoding RNA HOST2 (LncRNA HOST2) on epithelial-mesenchymal transition (EMT), proliferation, invasion and migration of hepatocellular carcinoma (HCC) cells via activation of the JAK2-STAT3 signaling pathway. Methods: HCC and para-cancerous tissues were collected from 136 HCC patients. Immunohistochemistry was used to detect the expression of JAK2 and STAT3. HCC SMMC7721 cells were grouped into blank, negative control (NC), HOST2 mimic and HOST2 inhibitor groups. The mRNA and protein expression levels of HOST2, JAK2, STAT3, E-cadherin, vimentin, Snail, Slug, Twist and Zeb1 in tissues and cells were determined by reverse transcription -quantitative polymerase chain reaction (RT-qPCR) and Western blotting, respectively. An MTT assay, scratch test and Transwell assay were applied to measure cell proliferation, migration and invasion, respectively. Results: The levels of JAK2, STAT3 and vimentin were higher in HCC tissues, while the expression of E-cadherin was lower in HCC tissues compared with para-cancerous tissues. The silencing of HOST2 significantly decreased cell proliferation, migration and invasion, reduced the levels of HOST2, JAK2, STAT3 and vimentin, and elevated the expression of E-cadherin. HOST2 silencing also decreased the levels of Snail, Slug and Twist but increased the level of Zeb1 protein, while the opposite findings were observed in the HOST2 mimic group. Conclusion: These results reveal a possible mechanism in HCC in which LncRNA HOST2 may increase EMT and enhance proliferation, invasion and metastasis of HCC cells via activation of the JAK2-STAT3 signaling pathway.