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关键词： circRNA   代谢重编程   消化系统肿瘤   分子机制   临床转化  

摘要： 消化系统肿瘤的高死亡率与其独特的代谢重编程密切相关,而环状RNA(circular RNA, circRNA)在此过程中的调控作用尚未得到系统阐明。本综述旨在填补这一知识空白,系统构建了circRNA介导的消化系统肿瘤代谢重编程多维调控网络。我们详细阐述了circRNA通过作为竞争性内源RNA(competing endogenous RNA, ceRNA)、编码功能性微肽、与RNA结合蛋白相互作用等核心机制,在糖酵解、谷氨酰胺代谢、脂质代谢和线粒体功能等关键代谢通路中发挥精密调控作用。重点剖析了circRNA在肝细胞癌、胃癌、食管癌和结直肠癌等主要消化系统肿瘤中的特异性调控网络,并探讨其作为诊断生物标志物和治疗靶点的转化潜力。这些研究不仅确立了circRNA作为代谢重编程网络关键节点的理论地位,也为其临床转化奠定了重要基础:circRNA不仅展现出作为高稳定性液体活检标志物的潜力,也为靶向代谢提供了新型治疗思路。尽管在靶向递送和标志物标准化验证方面仍存在挑战,但未来通过开发智能递送系统、推进多中心临床验证,靶向circRNA-代谢轴有望为消化系统肿瘤的精准诊疗提供创新性策略。

关键词： 叶酸   癫痫   妊娠结局   围产期   神经发育   先天性畸形   肿瘤   Meta分析  

摘要： 目的 系统评价叶酸补充对癫痫孕妇妊娠结局的影响。方法 检索PubMed、Embase、Cochrane Library、CNKI、万方、VIP及中国生物医学文献数据库从建库至2025年12月31日的相关文献,对癫痫孕妇补充叶酸的母婴结局进行Meta分析,并对服用抗癫痫发作药物(ASM)的孕妇进行敏感性分析。结果 共纳入17项研究。Meta分析显示,补充叶酸可降低不良神经发育结局[OR=0.38,95% CI(0.20,0.70),P=0.002]与不良围产期结局风险[OR=0.41,95% CI(0.21,0.78),P=0.007],但未减少先天性畸形发生[OR=0.99,95% CI(0.54,1.83),P=0.975],且与后代癌症风险升高相关[OR=2.29,95% CI(1.27,4.13),P=0.006]。在接受ASM治疗的癫痫孕妇中,叶酸补充与神经发育改善相关,而对围产期结局及先天性畸形无显著影响。结论 叶酸补充可能改善癫痫孕妇后代的神经发育,但对围产期结局作用不明确,未能降低先天畸形风险,且可能与后代癌症风险增加有关。未来仍需高质量研究进一步明确其具体影响。

关键词： Contrast-enhanced ultrasound   Differential diagnosis   Microflow imaging   Renal tumors  

摘要： 目的: 探讨多模态血流成像对肾脏小肿瘤(SRMs)的良恶性诊断价值。 方法: 2020年1月至2023年12月在天津医科大学肿瘤医院行手术治疗的肾肿瘤患者170例(病灶172个),肿瘤最大径≤4 cm,术前均行彩色多普勒血流成像(CDFI)、能量多普勒血流成像(PDI)、微视血流成像(MFI)和超声造影(CEUS)检查。由2位超声医师进行血流分级和血管形态评估并进行良恶性诊断。以术后病理诊断为金标准,采用受试者操作特征曲线(R0C)分析比较4种超声检查方法的诊断效能。 结果: 172个病灶中,恶性141个,良性31个。MFI成像模式下,2位独立超声医师评估SRMs血流分级的Kappa值为0.819,血管形态的Kappa值为0.806。MFI对血流分级为2~3级和血管形态为Ⅳ~Ⅴ型病灶的显示率为77.9%(134/172),高于CDFI[36.6%(63/172)]和PDI[43.0%(74/172)],MFI模式下血流分级为2~3级和血管形态为Ⅳ~Ⅴ型可作为恶性SRMs的独立预测因子(P<0.001)。CEUS模式下,恶性SRMs主要表现为快进(75.9%)、快退(70.9%)和高增强(85.1%),而良性SRMs主要表现为慢进(51.6%)、慢退(45.2%)和低增强(45.2%),37.6%的恶性SRMs可见环状增强,良性SRMs均未见环状增强,差异均有统计学意义(P<0.001)。CDFI、PDI、MFI和CEUS诊断恶性SRMs的准确性分别为0.500、0.552、0.855和0.901,灵敏度分别为0.418、0.489、0.887和0.986,特异度分别为0.871、0.839、0.710和0.516,曲线下面积分别为0.645、0.664、0.798和0.751。综合来看,MFI和CEUS对SRMs的诊断效能更为优越。 结论: MFI在检测SRMs的微血流信号时表现出较高的灵敏度,在区分SRMs良恶性方面表现出与CEUS相当的诊断性能,是一种无创、安全、经济、可重复性较好的检查方法。.;Objective: To investigate the diagnostic value of multimodal blood flow imaging in differentiating benign and malignant small renal masses (SRMs). Methods: A total of 170 patients with renal tumors (172 lesions) who underwent surgical treatment at Tianjin Medical University Cancer Institute and Hospital from January 2020 to December 2023 were *** maximum diameter of the tumors was ≤4 cm. All patients received Color Doppler flow imaging (CDFI), Power Doppler imaging (PDI), Microflow imaging (MFI), and Contrast-enhanced ultrasound (CEUS) examinations before surgery. Two sonologists were responsible for grading the blood flow and evaluating the vascular morphology to make a diagnosis of whether the tumors were benign or malignant. Taking the postoperative pathological diagnosis as the gold standard, the receiver operating characteristic (ROC) curve analysis was used to compare the diagnostic efficacy of the four ultrasound examination methods. Results: Among the 172 lesions, 141 were malignant and 31 were benign. In the MFI imaging mode, the Kappa value for the evaluation of SRMs blood flow grading by two indepe

关键词： Annual percentagechange   Incidence   Mortality   Neoplasms   Yunnan  

摘要： 目的: 分析2012—2020年云南省肿瘤登记地区老年人恶性肿瘤发病和死亡水平及变化趋势。 方法: 从云南省肿瘤随访登记系统获取2012—2020年各年份云南省符合要求的登记点的肿瘤登记数据,计算各年度及2012—2020年合计全部恶性肿瘤和主要恶性肿瘤的发病率和死亡率,以2000年中国人口进行标化计算中标率,以Segi′s世界人口进行标化计算世标率。采用Joinpoint 4.9软件计算2012—2020年全部恶性肿瘤和主要恶性肿瘤发病率和死亡率平均年度变化百分比(AAPC)。 结果: 2012—2020年云南省肿瘤登记地区老年人恶性肿瘤发病率为720.10/10万,中标率为708.83/10万,世标率为691.71/10万。其中男性发病率为901.52/10万,女性发病率为550.45/10万。同时期,云南省肿瘤登记地区老年人恶性肿瘤死亡率为538.76/10万,中标率为516.24/10万,世标率为498.32/10万。其中男性死亡率为706.15/10万,女性死亡率为382.24/10万。年龄别发病和死亡分析显示,60~岁组发病率最低(556.23/10万),75~岁组发病率最高(927.82/10万);60~岁组死亡率最低(335.81/10万),80~岁组死亡率最高(855.31/10万)。2012—2020年发病前5位的恶性肿瘤依次为肺癌、结直肠癌、肝癌、前列腺癌和胃癌,死亡前5位的恶性肿瘤依次为肺癌、肝癌、结直肠癌、胃癌和前列腺癌。2012—2020年云南省老年人全部恶性肿瘤发病率无明显上升或下降趋势(AAPC=-0.04,95% CI:-1.23%~1.17%)。主要恶性肿瘤中,肝癌和食管癌的发病率呈上升趋势,AAPC分别为2.07%和7.57%;膀胱癌和胰腺癌的发病率呈下降趋势,AAPC分别为-3.36%和-2.86%。全部恶性肿瘤死亡率亦无明显上升和下降趋势(AAPC=0.09,95% CI:-1.17~1.37)。主要恶性肿瘤中,肝癌和食管癌的死亡率呈上升趋势,AAPC分别为2.73%和8.92%;乳腺癌的死亡率呈下降趋势,AAPC为-7.34%。 结论: 2012—2020年云南省老年人恶性肿瘤发病和死亡水平一直偏高,无明显下降趋势。肺癌多年来一直是云南省老年人恶性肿瘤发病和死亡的主要原因,肝癌、食管癌的发病和死亡形势不容乐观,应引起重视。.;Objective: To analyze the incidence, mortality, and changing trends of malignant tumors among the elderly in tumor registration areas of Yunnan Province from 2012 to 2020. Methods: Tumor registry data from qualified registration sites in Yunnan Province from 2012 to 2020 were obtained from the Yunnan Tumor Follow-up Registration System. The annual and overall (2012-2020) incidence and mortality rates of all and major malignant tumors were calculated. The age-standardized rates were calculated using the 2000 Chinese standard population and Segi's world standard population. Joinpoint 4.9 software was used to calculate the average annual percentage change (AAPC) in the incidence and mortality rates of all and major malignant tumors from 2012 to 2020. Results: From 2012 to 2020, the incidence of malignant tumors among the elderly in tumor registry areas of Yunnan Province was 720.10/100 000, with a Chinese age-standardized rate of 708.83/100 000 and a world age-standardized rate of 691.7

关键词： Cox proportional hazards model   Oncology   Statistics   Survival analysis   Survival curve  

摘要： 生存分析可用于估计患者的生存时间、评价治疗效果及预测预后,在肿瘤临床研究中占有重要地位。然而,生存数据的复杂性和统计方法的适用条件给生存分析的方法选择和结果解读带来挑战。作者系统梳理了生存分析的基本思路与步骤,重点阐述了Kaplan-Meier法、对数秩检验、Cox比例风险模型、加速失效时间模型的适用条件与分析流程。同时,列举了肿瘤临床研究实践中生存分析的常见问题并提出了解决方案,包括:(1)协变量的选择缺乏科学性;(2)进行Cox比例风险模型分析时易忽略比例风险假设的检验;(3)删失数据处理不当;(4)样本量或结局事件数量不足导致研究效能较低;(5)对绝对风险效应关注不足;(6)混淆中位生存时间与中位随访时间;(7)忽略生存分析中的多重比较校正。为开展肿瘤临床研究和撰写研究报告提供参考,以提高肿瘤临床研究质量,推动肿瘤防治工作发展。.;Survival analysis plays a crucial role in clinical oncology by estimating patient survival time, evaluating treatment efficacy, and predicting prognosis. However, the complexity of survival data and the application conditions of statistical methods pose challenges in method selection and result interpretation. This review systematically outlines the fundamental concepts and procedures of survival analysis, with a focus on the application conditions and analytical processes of the Kaplan-Meier method, Log-rank test, Cox proportional hazards model, and the Accelerated Failure Time (AFT) model. Common pitfalls in clinical oncology research are also discussed, including: (1) unscientific selection of covariates;(2) neglecting the assessment of the proportional hazards assumption when applying the Cox proportional hazards model;(3) improper handling of censored data;(4) inadequate sample size or number of events resulting in low statistical power;(5) insufficient attention to absolute risk measures;(6) confusion between median survival time and median follow-up time;and (7) failure to adjust for multiple comparisons. This review aims to provide practical guidance for conducting and reporting survival analysis in oncology research, thereby improving research quality and supporting cancer prevention and treatment efforts.

关键词： Combination therapy   Dendritic cell vaccine   Immune checkpoint   Lung neoplasms   Neoantigen  

摘要： 目的: 探究新抗原树突状细胞(DC)疫苗联合CpG治疗肺癌免疫“冷”肿瘤的新策略。 方法: 对肺癌LLC1细胞进行全外显子组二代测序和RNA测序,利用RNA测序数据鉴定肿瘤特异性非同义突变表达,通过NetMHCpanv 4.0和NetMHCⅡpan 3.2预测新抗原与主要组织相容性复合体分子的结合亲和力,筛选候选新抗原。采用芴甲氧羰基化学合成法合成新抗原LLC1-M01、LLC1-M02、LLC1-M03、LLC1-M04和LLC1-M05。分别在C57BL/6小鼠皮下接种候选新抗原,采用流式细胞术进行新抗原免疫原性鉴定,采用酶联免疫斑点方法检测效应T细胞的γ-干扰素(IFN-γ)分泌。基于多肽制备新抗原DC疫苗。利用流式细胞术和酶联免疫吸附试验(ELISA)测定肿瘤微环境中免疫细胞和细胞因子变化。在肺癌LLC1细胞荷瘤鼠模型分别接种未负载多肽DC疫苗、CpG、LLC1-M02-DC、LLC1-M02-WT-DC和LLC1-M02-DC+CpG,检测肿瘤组织检测CD3+ CD4+和CD3+ CD8+ T细胞百分数、CD3+ T细胞或CD8+ T细胞穿孔素和颗粒酶的表达,观察肿瘤体积和小鼠体重的变化及小鼠的生存时间。 结果: 新抗原LLC1-M01和LLC1-M02诱导的CD3+ IFN-γ+ T细胞百分数分别为(4.80±1.00)%和(13.81±3.00)%,高于无关肽水疱性口炎病毒载体表达的流感病毒核蛋白43~69位氨基酸片段(VSV-NP43-69)的(1.00±0.30)%(均P<0.001)。LLC1-M01诱导的效应脾细胞分泌IFN-γ的能力为(200.00±45.00)斑点形成单位(SFU)/105个细胞,与LLC1-M01-WT[(193.00±42.00)SFU/105个细胞]差异无统计学意义(P=0.753);而LLC1-M02诱导的效应脾细胞分泌IFN-γ的能力为(820.00±200.00)SFU/105个细胞,高于LLC1-M02-WT[(430.00±100.00)SFU/105个细胞;P<0.001]。当效靶比为50∶1时,LLC1-M02-DC诱导的效应T细胞对LLC1细胞的特异性杀伤率为(35.02±8.00)%,高于对MC38细胞和对B16-F10细胞的特异性杀伤率(P<0.001),也高于M02-WT诱导的T细胞对LLC1细胞的特异性杀伤率[(20.01±4.00)%,P<0.001]。与无CpG组相比,CpG组肿瘤组织中CD3+ CD8+、CD3+ 穿孔素+、CD3+ 颗粒酶+、CD8+ 穿孔素+、CD8+ 颗粒酶+ T细胞百分数均增高(均P<0.01),肿瘤坏死因子α、IFN-γ、白细胞介素(IL)-2和IL-12表达下调(均P<0.01),而IL-10和IL-13表达上调(均P<0.01)。荷瘤小鼠治疗实验显示,与未负载多肽DC疫苗组、CpG组和LLC1-M02-WT-DC组相比,LLC1-M02-DC组荷瘤小鼠肿瘤生长明显受到抑制,LLC1-M02-DC+CpG组对肿瘤生长的抑制效应比LLC1-M02-DC组更强(P<0.001),而各组小鼠的体重无明显差异。未负载多肽DC疫苗组、CpG组、LLC1-M02-DC组、LLC1-M02-WT-DC组和LLC1-M02-DC+CpG组荷瘤小鼠的中位生存时间分别为28.0、30.5、55.0、37.5和79.0 d,其中LLC1-M02-DC组荷瘤小鼠的生存时间比LLC1-M02-WT-DC组明显延长(P=0.045),但比LLC1-M02-DC+CpG组明显缩短(P=0.008)。 结论: 小鼠LLC1细胞系中的新抗原LLC1-M02具有强免疫原性,LLC1-M02-DC疫苗与CpG联合可增强对肺癌“冷”肿瘤的抑制作用。.;Objective: To explore a novel strategy for treating immunologically "cold" lung tumors by combining neoantigen-pulsed dendritic cell (DC) vaccines with CpG. Methods: LLC1 cells were analyzed by whole-exome sequencing and RNA sequencing. Tumor-specific nonsynonymous mutations were identified using RNA sequencing data, and candidate neoantigens were screened by predicting their binding affinity to major histocom

关键词： Gastrointestinal pancreatic neuroendocrine neoplasm   Liver metastases   Liver transplantation   Therapeutic  

摘要： Neuroendocrine tumors are rare, low-grade malignant tumors with a gradually increasing incidence rate in recent years, with gastroenteropancreatic neuroendocrine tumors being the most common among them. The majority of gastropancreatic neuroendocrine tumors have already metastasized to the liver at the time of initial diagnosis;therefore, treatment targeting liver metastases is crucial. The most effective treatment for hepatic metastases of gastropancreatic neuroendocrine tumors is surgical resection. However, 60%-70% of patients are ineligible for radical resection due to diffuse liver involvement. Thus, an alternative treatment option offered for these patients is liver transplantation. Liver transplantation is considered an indication for well-differentiated, unresectable hepatic metastases of gastropancreatic neuroendocrine tumors because of the tumor's low invasiveness, slow growth, and the fact that the liver is often the only distant metastasis site. This article reviews the research progress of liver transplantation therapy for hepatic metastases in gastropancreatic neuroendocrine tumors. 2026, Chinese Medical Association

关键词： hepatocellular carcinoma   malignant biological behaviors   membrane protein palmitoylated 6   prognosis  

摘要： 目的: 明确膜棕榈酰化蛋白6(MPP6)在肝细胞癌(HCC)中的表达,分析其表达与HCC患者临床病理特征和预后的关系,探讨其对HCC细胞生物学行为的影响。方法: 选取2017年1月~2019年12月在我院行手术治疗的118例HCC患者肿瘤及癌旁组织标本,收集患者的临床病理资料,随访患者总生存期。采用免疫组化分析MPP6在肿瘤和癌旁组织中的表达水平;采用Cox回归分析MPP6表达水平与HCC患者临床病理特征和患者总生存期的相关性;采用平板克隆、划痕实验、Transwell实验和流式细胞术检测MPP6对HCC细胞Hep3B生物学行为的影响。结果: 与癌旁组织相比,MPP6在HCC组织中高表达(P<0.001);MPP6表达水平与患者肝硬化背景(P=0.028)和基线白蛋白水平(P=0.035)相关;生存分析提示,高表达MPP6患者预后较差(P<0.001);Cox回归分析显示,MPP6表达水平是患者总生存期的独立预测因素(P=0.012,HR:2.335,95% CI:1.502~3.629)。体外敲减MPP6可致Hep3B细胞增殖、迁移及侵袭能力下降(P<0.05),并阻滞细胞周期于G0/G1期(P<0.001)。结论: MPP6在HCC组织中高表达,并与HCC患者重要临床病理特征、不良预后相关;体外敲减MPP6可抑制HCC细胞增殖、迁移和侵袭能力并阻滞细胞周期于G0/G1期。.;OBJECTIVES: To investigate the expression of membrane protein palmitoylated 6 (MPP6) in hepatocellular carcinoma (HCC) and analyze its correlation with clinicopathological features and patient prognosis and its impact on biological behaviors of HCC cells. METHODS: We examined MPP6 expressions using immunohistochemistry in tumor and adjacent tissues from 118 HCC patients undergoing surgeries in our hospital from January, 2017 to December, 2019, and analyzed the correlation of MPP6 expression levels with clinicopathological data and overall survival (OS) of the patients using Cox regression analysis. In human hepatoma Hep3B cells, the effects of lentivirus-mediated MPP6 knockdown on biological behaviors of the cells were evaluated using colony formation assay, wound-healing assay, Transwell assay and flow cytometry. RESULTS: Compared with adjacent tissues, HCC tissues showed significant overexpression of MPP6 (P<0.001), whose expression levels was correlated with liver cirrhosis (P=0.028) and baseline albumin level (P=0.035) of the patients. Survival analysis suggested that HCC patients with a high expression of MPP6 had a worse prognosis (P<0.001);Cox regression analysis indicated that MPP6 expression (P=0.012, HR: 2.335, 95% CI: 1.502-3.629) was an independent predictor of OS of HCC patients following hepatectomy. In Hep3B cells, MPP6 knockdown obviously inhibited cell prolifera

关键词： Eosinophilic sialodochitis   I-induced sialadenitis   Immunoglobulin G4-related sialadenitis   Salivary glands   Tight junction proteins  

摘要： Salivary gland diseases are common disorders in the oral and maxillofacial region, mainly classified into two categories: Tumorous and non-tumorous. Non-tumorous salivary gland diseases include various types such as salivary gland inflammation, Sjogren syndrome, granulomatous diseases, and developmental abnormalities. Some of these diseases are local lesions, while others are closely associated with systemic diseases, often accompanied by impaired salivary secretion function, leading to xerostomia and secondary lesions. Over the past more than 20 years, the Salivary Gland Disease Research Center of Peking University School and Hospital of Stomatology has conducted systematic and in-depth studies focusing on the regulation of salivary secretion function by tight junction proteins, the clinicopathological characteristics, prevention and treatment of novel chronic sialadenitis [including immunoglobulin (Ig) G4-related sialadenitis, 131I-induced sialadenitis, and eosinophilic sialodochitis], stem cells from human exfoliated deciduous teeth-based therapy for Sjogren syndrome, and salivary gland developmental abnormalities. These studies provide important references for the basic research, clinical diagnosis and treatment of related diseases. © 2026 Editorial Department of Journal of Peking University (Health Sciences). All rights reserved.