单细胞测序技术在膀胱癌研究中的应用进展

膀胱癌是泌尿系统最常见的恶性肿瘤之一, 其复杂的肿瘤微环境和极高的肿瘤内异质性, 导致膀胱癌早期诊断困难及治疗效果欠佳。新兴的单细胞测序技术是一项对单细胞进行基因组、转录组、代谢组及表观遗传学测序, 进而识别细胞间精细差异的强大技术, 对于揭示肿瘤内异质性及探讨肿瘤微环境中细胞间的复杂关系具有独特优势。本文中, 我们总结了单细胞测序技术在膀胱癌肿瘤内异质性、肿瘤微环境、治疗耐药性及治疗靶点等方面的研究, 以期为膀胱癌的诊疗及研究提供新的思路。     

单细胞测序技术及其在结直肠癌中的研究进展

结肠直肠癌(CRC)是全球第三常见及第二位肿瘤致死癌症疾病, 由于基因突变的发生及肿瘤转移等事件造成CRC的预后不良。单细胞测序技术可以在单细胞水平上进行基因组、转录组、表观遗传学的高通量测序分析, 在肿瘤免疫微环境分析、肿瘤异质性检测、肿瘤转移机制探究及循环肿瘤细胞(CTCs)监测等有着特殊的技术优势。本文简要介绍了单细胞测序的技术流程及数据处理并回顾目前单细胞测序在CRC应用进展, 从而为了解CRC发生及肿瘤进展过程中的肿瘤内异质性、深入理解CTCs的应用与寻找新的药物作用靶点提供参考。     

单细胞测序技术在膀胱癌研究中的应用

单细胞测序技术是在单细胞水平上, 对基因组、转录组、表观组进行高通量测序分析的一项新技术。目前, 单细胞测序技术已广泛应用于膀胱癌的研究, 通过识别不同的细胞亚群、免疫微环境, 开辟了解膀胱细微肿瘤生物学的新途径, 并且单细胞测序技术有望通过识别和使用新的生物标志物和靶向治疗, 对膀胱癌的诊断和治疗做出重要改变。本文总结单细胞测序技术在膀胱癌的异质性细胞亚群、发生发展规律、免疫微环境和耐药性等方面中最新的研究应用进展。     

单细胞转录组测序技术在骨关节炎中的研究进展

骨关节炎是一种常见的以软骨细胞退变、软骨下骨重构以及滑膜炎症为主要特征的慢性退行性骨关节疾病,目前病因及分子发病机制尚不明确。单细胞转录组测序可以对全转录组在单细胞水平进行扩增与测序,可以解决普通细胞测序技术不能精确到细胞类型的问题,用于细胞异质性发现及微量样品的转录组分析,可以在分子水平上研究骨关节炎的发病机制和病理分期,发现新的治疗靶点,为骨关节炎的早期诊断和治疗提供新的理论依据。本文就单细胞转录组测序技术及在骨关节炎领域的研究进展进行概述。     

单细胞测序技术在骨关节疾病方面的应用

在关节疾病的发病机制的研究上,目前最常针对的对象还是骨、软骨及滑膜组织,以及从这些组织的整个病理改变的方向去探索可能的发病过程及发病机制,所以存在很多局限性和不准确性,比如忽略了疾病组织内部的单个细胞的异质性在疾病当中所发挥的作用。单细胞测序技术(single-cell sequencing)是在单个细胞水平上对基因组、转录组及表观基因组进行测序的技术,能够从组织样本中获得不同细胞间的异质性信息和对珍贵微量样本进行测序,从而更深层次地反映生命规律与本质,本文就单细胞测序技术的基本方法及在关节疾病方面的应用进行概述。     

单细胞测序和空间转录组技术在肝病研究中的应用进展

新兴的单细胞测序技术联合空间转录组技术,可以从细胞层面分析细胞的基因组、转录组和空间信息,这有助于人们探究细胞的基因表达水平和三维重建,了解细胞间的联系,进而促进探讨疾病的发生和发展机制。近年来,单细胞测序和空间转录组技术的联合运用已促进细胞和多种疾病研究,其在肝脏生理和疾病方面已取得部分成果。本文综述了单细胞测序和空...     

单细胞测序法研究肿瘤异质性

对于肿瘤领域的研究工作者及临床医生来说,肿瘤异质性是一个长久以来所关注的热点问题。所谓肿瘤异质性,即是指肿瘤细胞具有不同表型和功能。目前解释肿瘤异质性机制的理论包括肿瘤进化理论（clonal evolution,CE）以及肿瘤干细胞（cancer stem cell,CSC）理论。前者强调的是肿瘤细胞具有突变的生物学特性,从而导致肿瘤的发生及发展。而后者则强调肿瘤干细胞的分化,使其发展成为具有不同功能的肿瘤细胞,稳定肿瘤的内环境。从种种迹象表明,两种理论相互共存,促进了肿瘤的发牛发展。近年来,单细胞测序（single cell sequencing,SCS）作为一种最新开展的研究方法已应用到了肿瘤异质性研究领域,并具有良好的临床应用前景。它的开展可极大程度地辅助早期小病灶肿瘤的发现、循环肿瘤细胞（circulating tumour cells,CTCs）的监测以及晚期肿瘤药物耐药的判断,从而提高肿瘤的早期诊断、个体化治疗的效果以及预后等方面。     

胰腺癌蛋白质肿瘤标志物的研究进展

胰腺癌是一种常见的消化系统恶性肿瘤,病死率极高,近年来其发病率有明显上升的趋势.由于胰腺癌解剖位置深在、早期症状隐匿、确诊率低,大多数临床确诊的胰腺癌患者已处于中晚期,失去了手术治疗的机会,预后极差.因此,提高胰腺癌的早期诊断率非常重要.肿瘤标志物对于肿瘤早期发现和筛查是一个重要的方法,若能找到并筛选出一种或一组胰腺癌肿瘤标志物,将有助于提高胰腺癌早期诊断率,改善预后.同时,由于肿瘤标志物相关研究技术的突飞猛进,当今的研究重点已经开始从基因水平过渡到蛋白质水平进行整体水平的研究.本文就近年来胰腺癌蛋白质肿瘤标志物的研究进展作一综述.     

胰腺神经内分泌肿瘤临床前研究进展

胰腺神经内分泌肿瘤（pNEN）是相对罕见的胰岛细胞起源的肿瘤，在组织病理学、生物学行为、临床表现等方面异质性显著。近年来，研究的推广和认识的加深推动着国内外专家共识、临床指南的快速更新。然而，pNEN发病率低、异质性高的特点使其临床前研究工作在肿瘤学领域处于相对落后地位。多中心、跨区域乃至国际化合作既是保证研究罕见病样本量的重要模式，也为对比分析不同遗传背景pNEN的特征搭建平台。随着研究数据的快速积累，逐级细化研究亚型将有助于系统、全面地认识pNEN的群体异质性。此外，利用单细胞测序等前沿技术手段从细胞水平阐述pNEN的个体异质性可能会带来突破性的进展。     

三阴性乳腺癌精准治疗研究进展

随着近年来组学技术的蓬勃发展,基因组、转录组、代谢组、蛋白修饰组、单细胞转录组、空间转录组等技术的广泛应用深化了对于三阴性乳腺癌（TNBC）多维度异质性的解析,而基础研究的深入探索使得靶向其中一些关键信号通路以实施精准治疗成为可能。近期临床研究发现富有前景的治疗新手段,针对肿瘤内在靶点以及微环境特点为早、晚期TNBC患者提供治疗机会。基于TNBC的内在特点以及治疗现状,本文笔者从TNBC内部异质性和治疗方式两方面进行探讨其精准治疗进展。     

胰岛素瘤定位及手术方式选择

胰岛素瘤属功能性胰腺神经内分泌肿瘤，由于肿瘤过度分泌胰岛素导致反复发作的低血糖症，症状显著，危害性大，通常临床上持积极干预观点。定位诊断和外科治疗是胰岛素瘤诊治过程中面临的两个关键问题。定位诊断方面，传统影像学检查手段有了新进步，分子成像等新技术方法不断出现。外科治疗方面，随着微创技术的不断推广，手术方案的选择、术式利弊的权衡及术中操作的要点也成为业内学者讨论的热点问题。     

《中国胰腺神经内分泌肿瘤诊疗指南（2020）》解读

胰腺神经内分泌肿瘤的临床决策路径复杂、诊疗难度较大，病人管理依赖多学科协调参与。为此，中华医学会外科学分会胰腺外科学组联合多领域专家，基于循证医学证据及我国现阶段医疗特点，联合制定了《中国胰腺神经内分泌肿瘤诊疗指南（2020）》，以进一步改进中国胰腺神经内分泌肿瘤病人的诊疗流程。该指南的推荐多基于临床证据充分、专家共识度高的观点。在学习现有指南的同时，应积极开展针对胰腺神经内分泌肿瘤的临床和基础研究，共同推动疾病标准化诊疗体系的建立。     

CA19-9��Ӱ��ѧ����������ٰ���������еļ�ֵ

??Clinical value of serum CA19-9 in the diagnosis of suspected pancreatic cancer by imaging methods WANG Wei-lin*, WU Ze-hui, ZHU Feng, et al. Department of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital of Medical School of Zhejiang University, Hangzhou310003, China
Corresponding author: ZHENG Shu-sen, E-mail:shusenzheng@zju.edu.cn
Abstract Objective To explore the clinical value of the combination of serum tumor marker CA19-9 and imaging methods (computed tomography and magnetic resonance imaging) in the diagnosis of pancreatic cancer. Methods The clinical data of 267 patients with suspected pancreatic cancer by imaging methods admitted from January 2010 to February 2012 in Department of Hepatobiliary and Pancreatic Surgery, First Affiliated Hospital of Medical School of Zhejiang University were analyzed retrospectively. Results In all 267 patients, 225 (83.0%) and 42 (17.0%) patients were diagnosed as pancreatic cancer and non-pancreatic cancer respectively. In the pancreatic cancer group, serum CA19-9 was elevated in 173 (76.9%) patients. Eighty-five patients with suspected pancreatic cancer by imaging methods had normal CA19-9 value. Among them, 52 (61.2%) patients were finally diagnosed as pancreatic cancer on pathology, and 33 (38.8%) patients as non-pancreatic cancer. One hundred and eighty-two patients with suspected pancreatic cancer by imaging methods had elevated CA19-9 value. Among them, 173 patients were finally diagnosed as pancreatic cancer on pathology and 9 patients as non-pancreatic cancer. Conclusion Serum tumor marker CA19-9 may provide valuable clues for the diagnosis of pancreatic cancer which is suspected by imaging methods. As to CA19-9 negative patients, in whom pancreatic cancer is suspected by imaging methods, much more attention should be paid to the possibility of false positive results of imaging methods. Pancreas puncture before surgery is recommended to confirm the diagnosis and exclude the possibility of chronic pancreatitis, pancreatic neuroendocrine tumors and solid-pseudopapillary tumor, etc. As to patients with elevated CA19-9 and imaging methods suspected pancreatic cancer, operation is recommended.     

胃癌分子生物学研究现状

随着对胃癌发病分子机制的深入研究,发现胃癌的进展与一系列分子水平的变化有关,包括相关基因的突变、非编码RNA表达失调、信号通路的调节异常、肿瘤微环境改变及胃癌干细胞分化异常等,使分子靶向治疗在抗肿瘤治疗中逐渐显示出良好的应用.但由于胃癌具有较高的肿瘤异质性,导致其缺乏稳定高效的治疗选择性及可靠的用来预测病人预后和治疗反...     

��ѧ����������ʱ���ֲ���չ�����ٰ��Ĵ���

??Management of locally advanced pancreatic cancer in the era of multidisciplinary diagnosis and treatment BAI Xue-li, MA Tao, LIANG Ting-bo. Department of Hepatobiliary and Pancreatic Surgery, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China
Corresponding author: LIANG Ting-bo. E-mail: liangtingbo
@zju.edu.cn
Abstract Radical resection of pancreatic cancer offers the best chance for prolonged survival. Pancreatic resections are not eligible in most cases of pancreatic cancer owing to locally advanced stage or distal organ metastasis. Surgery-oriented multidisciplinary diagnosis and treatment for locally advanced pancreatic cancer (LAPC) may downgrade the tumor to be potentially resectable by offering individualized optimal therapies. Such multidisciplinary management includes adequate imaging evaluation, and pathological diagnosis, neoadjuvant chemo-(radio) therapies, subsequent surgery, and adjuvant therapies. It has been proven to be efficient in managing LAPC. In the article, the authors reviewed recent progress and made some comments on multidisciplinary management of LAPC based on our experience.     

Ӧ�ö�������������θ������غ��ת�����ٰ������о�

??Next-generation sequencing assistants in diagnosis of testicular metastatic adenocarcinoma after gastric cancer surgery CAO Yan-shuo*, SUN Li, SHEN Lin. *Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education of China), Department of GI Oncology, Peking University Cancer Hospital& Institute, Beijing 100142, China
Corresponding author: SHEN Lin, E-mail: linshenpku@163.com
Abstract Objective To investigate the role of next-generation sequencing technique in the diagnosis and treatment of cancer. Methods Using traditional pathologic diagnosis and next-generation sequencing and molecular evolutionary genetics analysis (MEGA) in a patient who was diagnosed of testicular metastatic adenocarcinoma 7 years after the radical surgery of gastric cancer. Results Pathologists make the conclusion that testicular tumor is the metastasis from gastric cancer, while the results of sequencing indicates that there may be other potential original tumor instead of gastric cancer from 7 years ago. Conclusion New gene detection technique has challenged the conclusion of traditional histopathology, and there is necessity to accumulate more data in future research to better apply this technique in clinical practice.     

�ΰ����󸴷��������Ƽ��ٴ�����ѧ����

??Mechanism of recurrent hepatocellular carcinoma and clinicopathological significance CONG Wen-ming, WU Meng-chao. Eastern Hepatobiliary Surgery Hospital, the Second Military Medical University, Shanghai 200438, China
Corresponding author: CONG Wen-ming, E-mail: wmcong@smmu.edu.cn
Abstract Based on molecular pathology, recurrent HCC (RHCC) can be divided into two types: one is monocentric (monoclonal) origin presenting postoperative residual recurrence, and the other is multicentric (multiclonal) origin, meaning a second primary tumor, which can be further divided into six subtypes with concomitant clonal types. However, according to the field cancerization hypothesis, there also exists the possibility of the so called “second field tumor”, which leads to a more complex mechanism and patterns of RHCC. Because correct determination of the clonal origin of RHCC may have actual reference value for personalized therapy, more attention should be paid to establish molecular clonal techniques suitable for pathological lab and to explore the clinical pathway in the diagnosis and treatment of RHCC based on their clonal classifications.     

��Һ����̸��չ�����ٰ��ĺ�������

??Individualized treatment of advanced pancreatic carcinoma with special reference to liquid biopsy LOU Wen-hui*??LIU Xiao-yu. *Department of General Surgery??Zhongshan Hospital??Fudan University??Shanghai 200032??China
Corresponding author??LOU Wen-hui??E-mail??lou.wenhui@
zs-hospital.sh.cn
Abstract The advantage of liquid biopsy in pancreatic cancer lies in minimal invasive, repeatable, and coherent to pathological diagnosis. Circulating tumor cells (CTCs) and Circulating cell-free DNA (cfDNA) are the major parts of liquid biopsy, there will be good perspertive in the personalized therapy of pancreatic cancer. Standardized technique, reasonable interpretation of the result will be the fundation of liquid biopsy in pancreatic cancer. Dynamically monitoring the change of CTC and cfDNA will provide clue for discovering new markers of recurrence and metastasis, as weill as new target of treatment.     

多学科联合诊疗时代局部进展期胰腺癌的处理

根治性切除是延长胰腺癌病人生存期的最有效手段,但大部分胰腺癌在初诊时即为局部进展期或伴有远处转移而无法行手术切除。以外科为中心的多学科综合治疗协作组联合诊治,通过制定规范化、连续性的最优诊疗方案有望使局部进展期胰腺癌降期,从而获得根治性切除的机会。这套系统性的诊疗方案包括充分的影像学评估、准确的病理学诊断、个体化的新辅助治疗、手术及术后的辅助治疗,实践证明其对局部进展期胰腺癌的效果斐然。     

�������Լ���άĸϸ������Ϻ�����

??Hepatic inflammatory myofibroblastic tumor WU Gang, CHEN Xu-chun. Department of Hepatobiliary, Faculty Working Office of General Surgery, the First Hospital of China Medical University, Shenyang 110001, China
Corresponding author: WU Gang, E-mail: WGZWL@hotmail.com
Abstract Hepatic inflammatory myofibroblastic tumor (HIMT) is a relatively rare benign liver tumors characterized by chronic infiltration of inflammatory cells and areas of fibrosis. HIMTs are difficult to diagnose because of the absence of specific symptoms or of characteristic hematological or radiological findings. Reports of HIMTs have a growing trend with recent advances in imaging technology. But there are still some difficulties in the diagnosis. Most cases can be diagnosed only through pathology after operation.