PURPOSE:Ginsenoside (Rg3) is an important small-molecule with anti-tumor and immune-enhancing properties, mainly used in clinical adjuvant chemotherapy for hepatocellular carcinoma (HCC). In this study, we explored the active targets and mechanisms of action of Rg3 in HCC to provide new basic data for clinical pharmaceutical research. METHODS:HepG-2 cells were treated with a concentration gradient of Rg3, cell activity was detected using the CCK-8 assay, and the IC50 was calculated. Flow cytometry was used to detect the apoptosis-inducing effect and the cyclic distribution of the drug in the cells. An enzyme-linked immunosorbent assay (ELISA) kit was used to detect lactic acid (LC) and glucose (GLU) contents after cell treatment. High-throughput data analysis was performed to explore HCC-associated glycolytic genes, analyze the correlation between biomarkers and clinical data, and confirm the gene-binding targets using a luciferase assay. Quantitative real-time polymerase chain reaction (qRT-PCR) and western blot (WB) were utilized to assess gene and protein expression in clinical samples and cell subgroups. The reliability of the cellular experiments was verified in vivo in transplanted mouse tumors. RESULTS:Rg3 at a concentration gradient inhibited LC and GLU secretion and induced apoptosis to inhibit cell proliferation. High-throughput data analysis revealed six biomarkers, among which miR-139-5p was highly expressed in tumor tissues and cells. Immunofluorescence experiments revealed targeted binding to aurora kinase A (AURKA). By targeting miR-139-5p, Rg3 inhibited tumor proliferation to reverse AURKA expression. Rg3 induced apoptosis, reduced the expression levels of AURKA, GLUT1, and GLUT4 and increased the expression of P53. miRNA-inhibit and Overexpression of Aurora Kinase A (OE-AURKA) were combined to stimulate the expression of P53 proteins, which significantly reversed the glycolytic activation of miRNA-inhibit and OE-AURKA and induced apoptosis. In vivo, Rg3 inhibited apoptosis and the expression of glycolytic proteins by targeting miR-139-5p, consistent with the in vitro results. CONCLUSION:Rg3 inhibits the proliferation of HepG-2 cells and explores a novel mechanism by which the miR-139-5p/AURKA axis suppresses aerobic glycolysis in HCC.

Department of HPB surgery, the second affiliated hospital of Kunming Medical University, Kunming, Yunnan, China Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article. Published online ■ ■ *Corresponding author. Address: Department of HPB surgery The second affiliated hospital of Kunming Medical University 374 Burma Road, Kunming, Yunnan,China, 650101 Fax:86 87165351281 Phone: 86 13888990023. E-mail address: [email protected] (X. Wei). This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms. http://creativecommons.org/licenses/by-nc-sa/4.0/

目的 研究胰头癌病人接受根治性胰十二指肠切除术后"教科书式结局"(textbook outcome,TO)的预后及影响TO的危险因素分析.方法 回顾性分析2016年1月至2018年12月昆明医科大学第二附属医院收治的92例接受根治性胰十二指肠切除的胰头癌病人临床病理资料.采用t检验、x2检验及Fisher精确概率法进行统计学分析,logistic回归分析影响TO的独立危险因素,Kaplan-Meier法绘制TO与非TO病人的生存曲线.结果 92例病人中达到TO有20例(21.7％),非TO有72例(78.3％).一般病例资料显示,术前高总胆红素、高糖类抗原(CA)19-9、高TNM分期、术中出血量≥400 mL、手术时间延长的病人更难达到TO,差异均有统计学意义(均P＜0.05).logistic回归分析显示,影响TO的独立危险因素为:手术时间[OR=1.023,95％CI(1.006,1.041)],出血量≥400 mL[OR=5.317,95％CI(1.346,21.002),高 TNM分期[OR=4.766,95％CI(1.191,19.067)],均P＜0.05.Kaplan-Meier生存曲线显示,TO组第1、3年总生存率分别为91.5％、32.4％,非TO组第1年、3年总生存率分别为25.6％、13.7％,差异均有统计学意义(均P＜0.05).结论 根据胰十二指肠切除术后是否达到TO,可有效预测胰头癌病人的预后情况,手术时间短、术中出血量少、低TNM分期的病人更容易达到TO.

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Long non-coding RNAs (lncRNAs) feature prominently in pancreatic carcinoma progression. The present study aimed to clarify the biological functions, clinical significance and underlying mechanism of lncRNA CTBP1 antisense RNA 2 (CTBP1-AS2) in pancreatic carcinoma. Reverse transcription-quantitative PCR was performed to assess the expression levels of CTBP1-AS2, microRNA (miR)-141-3p and ubiquitin-specific protease 22 (USP22) mRNA in pancreatic carcinoma tissues and cell lines. Western blotting was used to examine USP22 protein expression in pancreatic carcinoma cell lines. Loss-of-function experiments were used to analyze the regulatory effects of CTBP1-AS2 on proliferation, apoptosis, migration and invasion of pancreatic carcinoma cells. Dual-luciferase reporter assay was used to examine the binding relationship between CTBP1-AS2 and miR-141-3p, as well as between miR-141-3p and USP22. It was demonstrated that CTBP1-AS2 expression was markedly increased in pancreatic carcinoma tissues and cell lines. High CTBP1-AS2 expression was associated with advanced clinical stage and lymph node metastasis of patients. Functional experiments confirmed that knocking down CTBP1-AS2 significantly inhibited pancreatic carcinoma cell proliferation, migration and invasion, and promoted cell apoptosis. In terms of mechanism, it was found that CTBP1-AS2 adsorbed miR-141-3p as a molecular sponge to upregulate the expression level of USP22. In conclusion, lncRNA CTBP1-AS2 may be involved in pancreatic carcinoma progression by regulating miR-141-3p and USP22 expressions; in addition, CTBP1-AS2 may be a diagnostic biomarker and treatment target for pancreatic carcinoma.

背景与目的:腹腔镜胆总管探查术(LCBDE)以"创伤小、恢复快"的临床优势成为临床治疗胆总管结石的主要手段,甚至是一线推荐方案.但LCBDE后是否需引流胆汁及不同胆汁引流方式的选择仍存在诸多争议,如传统的LCBDE+胆道外引流管(T管)引流适应证的探讨、单纯一期缝合(PDC)是否导致高术后并发症发生率、胆道内引流是否优于外引流等.针对以上问题,本文采取回顾性研究,比较T管、胆道内引流管(双J管)与PDC在LCBDE中的临床应用,并就其相应适应证进行探讨.方法:回顾性收集2015年3月—2018年5月昆明医科大学第二附属医院363例行LCBDE患者的临床资料,根据治疗方式不同分为T管组(128例)、双J管组(115例)和PDC组(120例).比较三组术前一般资料(性别、肝功能、胆总管直径、结石直径);围手术期相关资料(手术时间、住院时间、住院费用)及术后并发症(胆源性胰腺炎、胆汁漏、胆管狭窄、引流管脱落、残余结石)发生率等.结果:三组患者术前一般资料差异无统计学意义(均P＞0.05).PDC组平均手术时间(75.5 min)明显短于T管组(98.5 min)与双J管组(90.5 min),PDC组与双J管组的平均住院时间(4.8 d与5.4 d)均少于T管组(7.8 d),PDC组与双J管组平均住院费用(18 489元与20 157元)均低于T管组(24 034元),差异均有统计学意义(均P＜0.05).三组术后总并发症发生率差异无统计学意义(P--0.521);PDC组胆汁漏发生率(3.3％)高于另两组(均P＜0.05),且患者均为多发胆管结石(＞1枚),其中3例结石嵌顿于Oddi括约肌,2例胆管直径＜10mm;双J管组术后胆源性胰腺炎发生率(4.3％)明显高于另两组(均P＜0.05),其中2例患者由于结石嵌顿致十二指肠乳头水肿,2例十二指肠乳头旁憩室,1例乳头炎性狭窄.结论:虽然PDC在住院时间及住院花费方面有优势,但术后并发症发生率较高,T管引流与双J管引流也有各自优势与适应证.是否需要引流及引流方式的选择,应根据患者经济情况,结合术前检查,术中腹腔镜及胆道镜对胆道情况的评估进行综合判断,"个体化"选择,以期尽量减少术后并发症,提高患者满意度.

目的 探讨腹腔镜胆总管探查术放置新型自脱落支架并一期缝合的临床应用价值.方法 选择本院2019年1月至2020年12月胆总管结石病例共98例为研究对象,根据手术方式分为两组,观察组51例放置新型自脱落支架并一期缝合,对照组47例行T管引流.比较两组的一般资料、手术时间、术中出血量、胆道引流管放置时间、腹腔引流管拔出时间、肛门排气时间、住院时长、住院费用和并发症.结果 观察组一般资料、手术时长(122.84±6.47)min、术中出血量(25.14±3.97)mL、肛门排气时间(2.86±0.72)d与对照组一般资料、手术时长(120.57±9.98)min、术中出血量(24.21±2.30)mL、肛门排气时间(3.12±0.82)d差异无统计学意义(P>0.05);观察组胆道引流管放置时间(14.45±2.90)d、腹腔引流管放置时间(3.33±0.77)d、住院时长(4.80±0.80)d、住院费用(11954.47±1098.00)元、并发症(1例,2.0％)低于对照组胆道引流管放置时间(31.47±1.84)d、腹腔引流管放置时间(6.12±0.85)d、住院时长(7.17±0.70)d、住院费用(13419.64±1470.90)元、并发症(7例,14.9％),差异有统计学意义(P<0.05).结论 在严格掌握手术适应证的基础上,腹腔镜下胆总管探查术放置新型自脱落支架较T管能减少带管时间、缩短腹腔引流管放置时间、缩短住院时间、降低住院费用、减少并发症的发生,是一种安全可行的引流方式.

探索PBL联合情景模拟教学在MBBS留学生肝胆外科实习中的应用效果,以提高MBBS留学生肝胆外科实习效果.

目的 探讨负载肝癌抗原树突状细胞(dendritic cell,DC)联合细胞因子诱导杀伤细胞(cytokine-induced killer,CIK)对肝细胞性肝癌(hepatocellular carcinoma,HCC)微环境的影响.方法 采用手术切除HCC组织制备HCC抗原,采集健康志愿者单个核细胞,诱导并分离出DC,CIK,按是否加入HCC抗原及共培养将细胞分为DC、Ag-Dc、CIK、Ag-DC-CIK四组,流式细胞仪测定各组细胞表型后,ELISA检测IL-6、IL-10及IFN-γ水平;免疫细胞化学SP法检测血管内皮生长因子(vascular endothelial growth factor,VEGF)的表达;RT-PCR检测基质金属蛋白酶(matrix metalloproteinase,MMP)-2,MMP-3,MMP-9mRNA表达水平.结果 负载抗原后DC组CD80及CD86表达阳性率,Ag-DC-CIK组CD3+CD56+、CD8+CD56+双阳性细胞均显著升高(P<0.05);Ag-DC-CIK组IL-6及IFN-γ浓度显著低于其余各组;而IL-10浓度最高(P<0.05);Ag-DC-CIK组VEGF及MMP-2、MMP-3、MMP-9mRNA表达水平均显著下降(P<0.05).结论 在DC负载自身抗原的基础上,与CIK共培养,可显著增强DC及CIK活性,有效降低HePG2微环境中血管形成,炎症反应及纤维化相关因子表达.

Background: Pancreatic colloid carcinoma is a rare pancreatic cancer, which is a subtype of pancreatic ductal adenocarcinoma. Case: a 71-year-old woman with a tumor of about 1.9x1.3cm in size located in the neck and body of the pancreas without invasion of surrounding organs. The patient underwent body and tail pancreatectomy, and the pathology revealed an intraductal papillary mucinous tumor of the pancreas with associated infiltrating colloid carcinoma. The patient recovered well after surgical treatment. Conclusion:  Pancreatic colloid carcinoma is a malignant tumor, but it has a lower degree of malignancy and a better prognosis compared with pancreatic ductal adenocarcinoma. Currently, radical surgical resection is the main treatment principle.

目的 研究对比经皮经肝胆囊穿刺引流(PTGD)续贯腹腔镜胆囊切除术(LC)与一期行LC治疗黄色肉芽肿性胆囊炎(XGC)的安全性和临床疗效差异.方法 回顾性分析2018年9月至2020年9月该院收治的36例XGC患者临床资料,根据不同的治疗方式分为PTGD组(n=21)和LC组(n=15).其中PTGD组首先行PTGD,3个月后行LC;LC组则入院后一期行LC.观察两组患者围术期资料及手术时间、术中出血量、中转开腹率、手术并发症发生率.结果 PTGD组手术时间、术中出血量低于LC组(P＜0.05).PTGD组21例均完成PTGD续贯LC,无中转开腹,而LC组有6例(40.0％)中转开腹,发生率显著高于PTGD组(P＜0.05).PTGD组腹部切口感染、胆管损伤发生率显著低于LC组(P＜0.05);但两组术后胆漏、腹壁皮下气肿发生率差异无统计学意义(P＞0.05).结论 PTGD续贯LC是一种安全有效治疗XGC的方式.

目的 通过为1例直肠癌同时性肝转移患者制定个性化综合治疗方案,探讨多学科团队(MDT)在直肠癌肝转移(CRLM)患者诊治中的作用.方法 2015年3月20日就诊于普外科的1例CRLM患者男性,54岁,在MDT(肝胆外科,胃肠外科,肿瘤科,放射科,影像科,病理科)病例讨论模式下对患者治疗全程不同时期进行全面评估和制定治疗方案.结果 经过MDT多次病例讨论及转化治疗后,患者直肠原发病灶及肝转移灶和复发灶接受两次手术及放化疗、靶向、局部射频等综合治疗,迄至2019年4月患者最终达到无瘤生存状态,实现生存获益.结论 MDT诊疗模式在直肠癌肝转移治疗中可提供个体化最佳方案,确保患者获得最佳治疗.

目的 探讨精准肝切除联合TACE对肝癌患者免疫监视的影响.方法 收集2016年6月至2018年9月昆明医科大学第二附属医院行精准肝切除术+TACE治疗的65例肝癌患者资料,比较手术前后及TACE治疗前后外周血CD4+、CD8+、CD4+/CD8+、IL-10及IFN-γ水平.结果 精准肝切除术后7 d,CD4+、CD4+/CD8+、IL-10及IFN-γ水平均较术前明显下降(P<0.05);术后14 d,T细胞亚群和细胞因子均恢复至术前水平.TACE治疗后7d,CD4+、CD4+/CD8+与术前相比显著上升(P<0.05);IL-10水平较治疗前降低,IFN-γ水平较治疗前升高,差异均有统计学意义(P<0.05).结论 精准肝切除术后短期内(14 d)免疫功能可得到恢复,联合TACE可促进肝癌患者免疫监视,对患者的肿瘤免疫具有正向作用,符合多学科治疗策略.

Objective: To investigate clinical efficacy of percutaneous transhepatic endoscopy (PTES) combined with different lithotripsy methods for precision treatment of complicated hepatolithiasis and summarize relevant experiences. Methods: The clinical data of 49 patients with complicated hepatolithiasis undergoing PTES plus holmium laser lithotripsy or electrohydraulic lithotripsy were retrospectively analyzed. Results: The surgical successful rate was 93.9％ (46/49). The average operative time was (107.5±8.9) min and blood loss was (43.6±10.4) mL. The incidence of residual stones was 8.7％ (4/46) and complications occurred 18 times. The short- and long-term recurrence rate was 6.5％ and 13.6％, respectively. Conclusion: PTES combined with different lithotripsy methods shows favorable efficacy in precision treatment of complicated hepatolithiasis. This method is recommended as the first choice of options for patients with no lobar atrophy, and the stones confined to one segment or one lobe of the liver as well as those without tolerance to an open surgery due to repeated biliary operation history.

Objective:To compare the influences between precise and conventional hepatectomy on changes of T lymphocyte subsets in liver cancer patients.Methods:Forty-seven liver cancer patients were randomly divided into two groups,and underwent precise hepatectomy (precise hepatectomy group,26 cases) and conventional hepatectomy (conventional hepatectomy group,21 cases) respectively.The main clinical variables,and the pre-and postoperative CD3+,CD4+ and CD8+ levels as well as CD4+/CD8+ between the two groups were compared.Results:In precise hepatectomy group compared with conventional hepatectomy group,the operative time was prolonged,but the amount of blood loss,length of hospital stay and incidence of postoperative bile leakage and intra-abdominal hemorrhage were all reduced (all P＜0.05);the postoperative changes in liver function parameters in precise hepatectomy group were superior to those in conventional hepatectomy group (all P＜0.05).At postoperative day (POD) 7,the values of CD3+,CD4+ and CD4+/CD8+ were significantly decreased in both groups compared with their preoperative levels,but the decreasing degrees of them in precise hepatectomy group were significantly less than those in conventional hepatectomy group (all P＜0.05),and the CD8+ values were slightly increased in both groups compared with their preoperative levels (both P＞0.05);at POD 14 the values of all these T lymphocyte subsets in both groups returned to their preoperative levels.Conclusion:Precise hepatectomy is superior to conventional hepatectomy in protection of immune function,which thereby benefits the recovery of liver function in liver cancer patients.