专家述评
腺苷至肌苷RNA编辑(AIRE)是指转录前体RNA在腺苷酸脱氨酶的作用下,某些位点的腺苷发生脱氨反应转变成肌苷的过程,在碱基配对时,肌苷被识别作鸟苷,导致转录组重编写。随着高通量测序技术的不断进步,大量异常的AIRE被发现可导致氨基酸编码改变、RNA剪切异常以及microRNA-mRNA重定向等过程,从而参与肿瘤的发生发展。绝大部分的AIRE位点均位于基因非编码区,解析它们的生物学功能仍存在一定的挑战。本综述旨在描述AIRE的生物学机制和AIRE位点在不同肿瘤发生发展作用的进展,为AIRE与肿瘤的研究提供思路。
Adenosine-to-inosine RNA editing(AIRE)is catalysed by adenosine deaminases acting on RNA(ADARs),which converts adenosine to inosine in nascent RNA.Since inosine is recognized as guanosine in post-transcriptional process,AIRE is functionally approximate to an A-to-G mutation and results in transcriptome recoding.With the continuous advancement of high-throughput sequencing technology,a large number of abnormal AIRE events have been found to exert different biological mechanisms such as amino acid changes,RNA splicing abnormalities and microRNA-mRNA redirection,which plays an important role in the development of human tumorigenesis.Most of AIRE sites are located in non-coding region,which brings challenges in analyzing their biological functions.This review aims to describe the biological mechanisms of AIRE and the relationship between AIRE sites and the development of different tumor types,providing ideas for the study of AIRE and tumors.
专家述评
药物治疗抵抗在临床实践中成为肿瘤治疗失败的主因。最近的研究指出,肿瘤细胞的耐药性可能源于其内部高度的细胞异质性,而这种异质性的基础则是肿瘤可塑性。肿瘤细胞可塑性可能引发一系列反应,包括对治疗的耐药性发展、免疫系统逃逸以及对周围组织和血管系统的侵袭和转移等。本文简要介绍肿瘤细胞可塑性的表现形式以及其在药物治疗抵抗的非遗传适应性机制与靶向治疗新策略。
Drug therapy resistance has emerged as a primary cause of treatment failure in cancer management.Recent research indicates that the resistance of tumor cells may stem from their high degree of intracellular heterogeneity,with the underlying basis being tumor plasticity.Tumor cell plasticity can trigger a cascade of responses,including the development of resistance to treatment,evasion of the immune system,and invasion and metastasis into surrounding tissues and the vascular system.This article provides a brief overview of the manifestations of tumor cell plasticity and its non-genetic adaptive mechanisms in drug therapy resistance,along with novel strategies for targeted treatment.
论著
目的 分析神经系统副肿瘤综合征(PNS)的临床特点以提高对该病的早期诊断和治疗效果。方法 回顾性分析惠州市第一人民医院和惠州市中心人民医院神经内科2019年10月—2022年10月收治的21例PNS患者的临床表现、实验室检查结果和治疗效果,并作文献回顾。结果 21例患者中出现了10种副肿瘤综合征,其中经典综合征占比28.6%(6/21),最多见的是边缘叶脑炎;20例在血液或脑脊液中发现检测到抗神经元抗体,非特征性抗体阳性率最高(12/20),其中以半定量脑组织切片TBA检测阳性率最高(7/20);有特征性抗体的8例以抗Yo抗体阳性率最高(6/8)。21例患者均随访至2023年3月,8例发现原发肿瘤,其中4例在神经系统病变之后。69.25%(9/13)的患者使用糖皮质激素治疗和(或)丙种球蛋白治疗有效。结论 21例PNS患者中以非经典综合征占比较多,经典与非经典副肿瘤综合征均应进行肿瘤筛查,未发现肿瘤者应密切随访。非特征性抗体阳性率最高,提示PNS可能仍有许多相关抗体未明确,临床工作中也应对非特征性抗体阳性予以重视。
Objective To analyze the clinical features of paraneoplastic neurological syndrome(PNS)to improve the early diagnosis and treatment of this disease. Methods The clinical manifestations,laboratory results and treatment effects of 21 patients with PNS admitted to Huizhou First People's Hospital and Huizhou Central People's Hospital from October 2019 to October 2022 were retrospectively analyzed,and literature review was performed. Results There were 10 paraneoplastic syndromes in 21 patients,of which classical syndrome accounted for 28.6%(6/21),the most common was limbic lobe encephalitis.Anti-neuronal antibodies were detected in blood or cerebrospinal fluid in 20 cases,with the highest positive rate of non-characteristic antibodies(12/20),among which the positive rate of TBA detection by semi-quantitative brain tissue sections was the highest(7/20);Eight cases with characteristic antibodies had the highest positive rate of anti-Yo antibody(6/8).All 21 patients have been followed up so far,and 8 cases have found primary tumors,4 of which were after neurological lesions.There was 69.25%(9/13)of patients responded to hormone therapy or(and)gamma globulin therapy. Conclusions Non-classical syndrome accounts for more patients with PNS,and both classical and non-classical paraneoplastic syndromes should be screened for tumors,and those who have not found tumors should be closely followed.The positive rate of non-characteristic antibodies is the highest,indicating that there may still be many related antibodies in PNS that are not clear,and the positive of non-characteristic antibodies should also be paid attention to in clinical work.
专家述评
在过去的几十年中,随着RNA生物学的深入研究,越来越多的证据表明,非编码RNA(ncRNA)对包括癌症在内的多种疾病进展起着关键作用,同时在作为生物标志物和治疗靶点方面表现出了巨大的潜力。在全球范围内,消化道(GI)肿瘤是肿瘤相关死亡的主要原因,目前消化道肿瘤晚期患者的生存率依然很低。既往大量研究报道了ncRNA中,特别是长链非编码RNA(lncRNA)在消化道肿瘤发生发展中发挥重要作用。本文将着重阐述lncRNA在消化道肿瘤分子生物学中的作用,旨在为深入理解lncRNA在消化道肿瘤发生发展机制以及临床转化应用提供新的思路和线索。
In recent decades,an increasing body of evidence has pointed to the pivotal roles of non-coding RNAs(ncRNAs),particularly long non-coding RNAs(lncRNAs),in the development of various diseases,including cancer.Meanwhile,ncRNAs have been shown great potential as biomarker and therapeutic target.Gastrointestinal(GI)cancers are a leading cause of cancer-related mortality globally and the survival rate of advanced GI cancer patients is still very low.Extensive research has underscored the significant involvement of lncRNAs in the initiation and progression of GI cancers.This review aims to offer a comprehensive overview of lncRNAs,shedding light on their roles in the molecular biology of GI cancers.By synthesizing previous studies,this review seeks to provide new insights into the mechanisms underlying lncRNAs' contribution to GI cancer development and their potential clinical applications.
论著
目的 探讨与分析核磁弥散成像(DWI)及表观弥散系数(ADC)值在肝内非肿瘤性病变诊断与鉴别诊断中的价值。方法 选择2020年8月—2023年5月厦门大学附属第一医院收治的120例肝脏占位性病变患者为研究对象,所有患者均给予常规MRI与DWI,记录图像质量、信号特征,计算ADC值,评价诊断效能。结果 120例患者中,病理诊断为肝内非肿瘤性病变70例(非肿瘤组:肝脓肿32例、肝囊肿28例、肝炎性假瘤10例),肝内肿瘤性病变50例(肿瘤组:肝血管瘤38例,肝癌12例)。非肿瘤组与肿瘤组的图像质量优良率分别为94.29%(66/70)与88.00%(44/50),组间比较差异无统计学意义(χ2=1.509,P>0.05)。非肿瘤组的磁共振信号特征多为高信号(62.86%),肿瘤组多为低信号(60.00%),两组比较差异有统计学意义(χ2=45.691,P<0.05)。在b值为400 s/mm2和800 s/mm2条件下,非肿瘤组的ADC值(0.84±0.17、0.77±0.14)均低于肿瘤组(1.29±0.24、1.19±0.34),差异有统计学意义(t=12.029、9.302,P<0.05)。DWI判断为肝内非肿瘤性病变68例,DWI在肝内非肿瘤性病变的鉴别诊断灵敏度与特异度分别为95.71%(67/70)和98.00%(49/50),ROC曲线显示DWI在肝内非肿瘤性病变的诊断曲线下面积为0.895。结论 DWI在肝内非肿瘤性病变中的图像显示质量高,可通过信号特征与ADC判断病灶状况,对鉴别肝内非肿瘤性病变具有较高的诊断效能。
Objective To investigate and analyze the value of diffusion weighted imaging(DWI)and apparent diffusion coefficient(ADC)in the diagnosis and differential diagnosis of non neoplastic liver lesions.Methods A total of 120 patients with liver focal lesions admitted to the First Affiliated Hospital of Xiamen University from August 2020 to may 2023 were selected.All patients were given conventional MRI and DWI,the image quality and signal characteristics were recorded,the ADC value was calculated,and the diagnostic efficiency was evaluated.Results Among the 120 patients,70 cases were pathologically diagnosed as non neoplastic lesions(non tumor group,32 cases of liver abscess,28 cases of liver cyst,10 cases of hepatitis pseudotumor),and 50 cases were neoplastic lesions(tumor group,38 cases of hepatic hemangioma,12 cases of liver cancer).The excellent and good image quality rates of non tumor group and tumor group were 94.29%(66/70)and 88.00%(44/50),respectively,and there was no significant difference between the two groups(χ2=1.509,P>0.05).The MRI signal characteristics of non tumor group were mostly high signal(62.86%),while the tumor group were mostly low signal(60.00%),and the difference between the two groups was statistically significant(χ2=45.691,P<0.05).When the b value was 400 s/mm2 and 800 s/mm2,the ADC value of non tumor group(0.84±0.17,0.77±0.14)was significantly lower than that of tumor group.The difference was statistically significant(t=12.029,9.302,P<0.05).Sixty-eight patients were diagnosed as non neoplastic lesions by DWI.The sensitivity and specificity of DWI in the differential diagnosis of non neoplastic lesions were 95.71%(67/70)and 98.00%(49/50),respectively.The ROC curve shows that the area under the diagnostic curve of DWI for non tumor lesions in the liver was 0.895.Conclusion sDWI has high image quality in the diagnosis of non neoplastic lesions in the liver.Doctors can judge the status of lesions by signal characteristics and ADC,which has high diagnostic efficiency in the identification of non neoplastic lesions in the liver.
论著
目的 探讨多原发恶性肿瘤(MPMN)的临床特点,提高该类型肿瘤的认识,为临床诊断及治疗提供一定的经验。方法 分析2021年12月广州市第一人民医院呼吸与危重症学科二区收治的1例乳腺、甲状腺及肺三重多原发恶性肿瘤的临床特点及诊治经过,并结合相关文献进行回顾分析。结果 该例首患乳腺导管内癌并予手术切除,9年后再同时患肺癌及甲状腺癌,最终确诊为三重多原发恶性肿瘤。结论 通过对多原发恶性肿瘤的临床特点的分析研究,可一定程度提高临床医生对MPMN的认知以及早期临床鉴别的能力,亦为肿瘤患者早期诊断、早期治疗提供更好的时机,改善患者生活质量。
Objective To explore the clinical characteristics of multiple primary malignant neoplasms (MPMN), to improve the understanding of this type of tumors, and to provide some experience for clinical diagnosis and treatment. Methods The clinical characteristics, diagnosis and treatment of a case with triple MPMN of breast, thyroid and lung treated in the Respiratory and Critical Care Department (Area 2) of Guangzhou First People's Hospital in December 2021 were analyzed retrospectively. Results The breast intraductal carcinoma was the first tumor of that case and had been resected, and 9 years later, lung cancer and thyroid cancer occured at the same time, which were diagnosed as triple MPMN. Conclusions The analysis and study of the clinical characteristics of MPMN can improve the clinicians' cognition and the ability of early clinical differentiation, and provide a better opportunity for early diagnosis and early treatment of tumor patients, and improve their quality of life.
专家综述
N6-甲基腺苷(N6-methyladenosine, m6A)修饰是真核生物信使 RNA中最丰富的表观遗传修饰,其失调会导致mRNA异常生物学行为如翻译和降解紊乱,从而调控肿瘤发生发展。近期研究表明m6A在免疫调控过程中可发挥重要作用,其不仅可调节免疫细胞的活化,还在肿瘤微环境中免疫应答发挥重要调控作用,从而影响免疫治疗效果。越来越多的证据表明m6A修饰可能是肿瘤免疫治疗的重要潜在干预靶点。本文阐述了免疫细胞中m6A修饰调控及其在肿瘤免疫微环境中相关调节作用,并进一步探讨了靶向m6A调控蛋白在肿瘤免疫治疗中的干预策略及潜在治疗价值。
N6-methyladenosine (m6A) modification is the most abundant epigenetic modification in eukaryotic messenger RNA (messenger RNA). Its dysregulation drives abnormal transcription and translation processes, which promotes the occurrence and development of tumors. Studies have shown that m6A modification can regulate the activation of immune cells and their infiltration into the tumor microenvironment (TME), which may affect the efficiency of immunotherapy. Therefore, m6A modification may be a potential target for tumor immunotherapy. This paper describes the modification of m6A in immune cells and the antitumor immune response associated with TME, and explores the potential therapeutic value of targeting m6A regulators in tumor immunotherapy.
论著
目的 学习母细胞性浆细胞样树突细胞肿瘤(BPDCN)的临床病理及免疫表型特征,总结该少见肿瘤的病理诊断经验。方法 回顾分析2例BPDCN患者临床资料,通过苏木素-伊红(HE)染色分析肿瘤组织及细胞形态,通过免疫组织化学染色分析肿瘤免疫表型,通过流式细胞学检测骨髓有无肿瘤侵犯,并结合文献分析。结果 本报道中1例为97岁女性,临床以皮肤瘀斑结节为首发症状,肿瘤细胞真皮内弥漫浸润,不侵犯表皮,细胞中等大小,核形不规则,核仁不明显。另1例为69岁男性,临床以淋巴结肿大为首发症状,淋巴结结构完全破坏,肿瘤细胞弥漫浸润,细胞呈中等大小的母细胞样,核仁明显。2例免疫表型均表达CD123、CD4、CD56、TDT,不表达B系、T系淋巴细胞及髓系标志物,肿瘤均累及骨髓。结论 BPDCN是一种罕见的淋巴造血肿瘤,临床常以皮肤病变或淋巴结肿大为首发症状,临床过程具高度侵袭性,通常伴有骨髓侵犯。该肿瘤需与具有母细胞形态的淋巴系肿瘤和白血病相鉴别,诊断需结合临床信息、HE形态及免疫组化结果综合判断。
Objective To summarize the diagnostic experiences of blastic plasmacytoid dendritic cell neoplasm (BPDCN) based on the study of its clinicopathological features and immunophenotypes. Methods The clinical data of 2 patients with BPDCN were collected, the structure alteration and cell morphology were observed by HE staining, the immunophenotype of tumor cells were studied by immunohistochemistry staining and flow cytometry was adopted to confirm the bone marrow involvement. Results Two patients, one of whom was a 97 year-old female, presented with cutaneous ecchymosis nodules as the first symptom. The epidermis, but not the dermal, was diffusedly infiltrated by tumor cells, which were medium-sized with irregular nuclei without prominent nucleoli. The other case was a 69 year-old male with lymph node enlargement as the first symptom. The skin was normal, but the lymph nodes were invasively destroyed by tumor cells, which were medium-sized blast-like with prominent nucleoli. The immunophenotypes of the two patients were both positive for CD123, CD4, CD56 and TDT, but negative for B, T lymphocyte derived and myeloid origin markers, both of which involved bone marrow. Conclusions BPDCN is a rare form of hematological neoplasm, skin symptoms or lymph node enlargement may be presented as the initial symptom, the clinical course were highly aggressive with high frequency of bone marrow involvement. The blastic-like lymphoma and leukemia entities should be considered into account for differential diagnose. The precise diagnosis of BPDCN should be established by integrating histomorphology, immunophenotype and clinical presentation information comprehensively.
专家综述
肿瘤相关巨噬细胞(TAMs)是肿瘤微环境中最丰富的免疫细胞之一,M2-TAMs在肿瘤发生、发展、转移和治疗过程中发挥重要作用,被认为是肿瘤治疗中的重要靶点。已有的研究表明,通过将促肿瘤的M2-TAMs重编程为促炎的M1-TAMs可实现抑制肿瘤生长和转移。本综述在介绍TAMs与肿瘤治疗相关背景的基础上,重点关注纳米药物重编程TAMs增强抗肿瘤的研究进展。本文将从TAMs靶向递送各种活性物质进行重编程TAMs和纳米药物介导的异常肿瘤微环境调节的间接重编程TAMs两种方式,综述近年来基于纳米药物递送系统的调控策略及典型例子。
Tumor associated macrophages(TAMs)is one of the most abundant immune cells in the tumor microenvironment.M2-TAMs play an important role in tumor genesis,progression,metastasis and treatment,and is additionally a very important target in tumor therapy.Previous studies have shown that inhibition of tumor growth and metastasis can be achieved by reprogramming M2-TAMs to M1-TAMs.On the basis,this review focuses on the analysis progress of nano-drug reprogramming TAMs to boost anti-tumor.In this paper,we reviewed two methods of reprogramming TAMs for targeted delivery of various active substances and indirect reprogramming TAMs for abnormal tumor microenvironment regulation mediated by nanomedicine.The regulatory strategies and typical samples of nanomedicine delivery systems in recent years were summarized.
论著
目的 探讨桥小脑角肿瘤微创切除术中应用神经内镜对其功能恢复及预后的影响,以便临床寻找出更有效的治疗方案,进而改善患者预后。方法 本次研究对象为赣州市人民医院2017年6月—2022年1月收治的82例桥小脑角肿瘤患者,用随机数字表法将其分为对照组(41例)和实验组(41例)。对照组患者给予常规显微手术治疗,实验组患者给予神经内镜辅助常规显微手术治疗,2组患者均于术后观察8周。比较2组患者肿瘤全切率,手术时间、住院时间及住院费用,术前及术后2、4、8周格拉斯哥预后量表(GOS)评分,以及术后8周内并发症发生情况。结果 肿瘤全切率:实验组患者术后8周(90.24%)与对照组(73.17%)相比,处于更高水平;手术时间、住院时间:实验组患者与对照组相比,处于更短水平;GOS评分:术前至术后2周,2组患者评分均呈下降趋势,术后2周至8周,2组患者评分呈升高趋势,其中实验组术后2、4、8周与对照组相比,处于更高水平,差异有统计学意义(P<0.05);并发症总发生率:术后8周内,实验组患者(4.88%)与对照组(17.07%)相比,差异无统计学意义(P>0.05)。结论 桥小脑角肿瘤微创切除术中应用神经内镜,可有效缓解患者的临床症状,优化手术相关指标,减轻神经功能受损,提高肿瘤全切率,改善预后,且安全性高。
Objective To investigate the effect of neuroendoscope on functional recovery and prognosis of patients with cerebellopontine angle tumor after microinvasive resection,so as to find out more effective treatment and improve the prognosis of patients.Methods The subjects were 82 patients with cerebellopontine angle tumors admitted to Ganzhou People's Hospital from June 2017 to January 2022.They were divided into control group(n = 41)and experimental group(n = 41)by random number table method.Patients in the control group were treated with conventional microsurgery,while patients in the experimental group were treated with neuroendoscope assisted conventional microsurgery.All patients were observed for 8 weeks after operation.The total tumor resection rate,operation time,hospitalization time,hospitalization expense,Glasgow Outcome Scale(GOS)score before and 2,4,8 weeks after operation,and complications within 8 weeks after operation were compared between the two groups.Results Compared with the control group(73.17%),the patients in the experimental group had a higher resection removal rate of tumor after 8 weeks of operation(90.24%).Patients in the experimental group had a shorter operation time and hospital stay than those in the control group.From pre-operation to 2 weeks after operation,the GOS scores of patients in both groups showed a downward trend,and from 2 weeks to 8 weeks after operation,the scores of patients in both groups showed an upward trend,and the patients in the experimental group were at a higher level than those in the control group at 2,4,8 weeks after operation,the difference were statistically significant(P < 0.05).Within 8 weeks after surgery,there was no significant difference in total incidence of complications between the experimental group(4.88%)and the control group(17.07%,P > 0.05).Conclusions The application of neuroendoscope in the minimally invasive surgery of cerebellopontine angle tumor can effectively relieve the clinical symptoms of patients,optimize the operation-related indexes,reduce the damage of nerve function,increase the total resection rate of tumor,improve the prognosis,and with high safety.