Brain stem cells as the cell of origin in glioma

Glioma incidence rates in the United States are near 20000 new cases per year, with a median survival time of 14.6 mo for high-grade gliomas due to limited therapeutic options. The origins of these tumors and their many subtypes remain a matter of investigation. Evidence from mouse models of glioma and human clinical data have provided clues about the cell types and initiating oncogenic mutations that drive gliomagenesis, a topic we review here. There has been mixed evidence as to whether or not the cells of origin are neural stem cells, progenitor cells or differentiated progeny. Many of the existing murine models target cell populations defined by lineage-specific promoters or employ lineagetracing methods to track the potential cells of origin. Our ability to target specific cell populations will likely increase concurrently with the knowledge gleaned from an understanding of neurogenesis in the adult brain. The cell of origin is one variable in tumorigenesis, as oncogenes or tumor suppressor genes may differentially transform the neuroglial cell types. Knowledge of key driver mutations and susceptible cell types will allow us to understand cancer biology from a developmental standpoint and enable early interventional strategies and biomarker discovery.

Multiple cells of origin in cholangiocarcinoma underlie biological,epidemiological and clinical heterogeneity

Recent histological and molecular characterization of cholangiocarcinoma(CCA) highlights the heterogeneity of this cancer that may emerge at different sites of the biliary tree and with different macroscopic or morphological features.Furthermore,different stem cell niches have been recently described in the liver and biliarytree,suggesting this as the basis of the heterogeneity of intrahepatic(IH)-and extrahepatic(EH)-CCAs,which are two largely different tumors from both biological and epidemiological points of view.The complexity of the organization of the liver stem cell compartments could underlie the CCA clinical-pathological heterogeneity and the criticisms in classifying primitive liver tumors.These recent advances highlight a possible new classification of CCAs based on cells of origin and this responds to the need of generating homogenous diagnostic,prognostic and,hopefully,therapeutic categories of IH-and EH-CCAs.

Spatiotemporal switching signals for cancer stem cell activation in pediatric origins of adulthood cancer:Towards a watch-and-wait lifetime strategy for cancer treatment

Pediatric origin of cancer stem cell hypothesis holds great promise and potential in adult cancer treatment, however; the road to innovation is full of obstacles as there are plenty of questions left unanswered. First, the key question is to characterize the nature of such stem cells (concept). Second, the quantitative imaging of pediatric stem cells should be implemented(technology). Conceptually, pediatric stem cell origins of adult cancer are based on the notion that plasticity in early life developmental programming evolves local environments to cancer. Technologically, such imaging in children is lacking as all imaging is designed for adult patients. We postulate that the need for quantitative imaging to measure space-time changes of plasticity in early life developmental programming in children may trigger research and development of the imaging technology. Such quantitative imaging of pediatric origin of adulthood cancer will help develop a spatiotemporal monitoring system to determine cancer initiation and progression. Clinical validation of such speculative hypothesis-that cancer originates in a pediatric environment-will help implement a wait-andwatch strategy for cancer treatment.

Squamous cell carcinoma metastatic to cervical lymph nodes from unknown primary origin:the impact of chemoradiotherapy

The management of cervical lymph node metastases of squamous cell carcinoma from an unknown primary site is still a therapeutic challenge.We report here our experience in treating these patients with chemoradiotherapy as a curative approach.Data from 40 patients were reviewed.In total,20(50%) patients underwent excisional biopsy.All patients underwent radiotherapy,which was delivered to both sides of the neck and pharyngeal mucosa(extensive field),and concurrent chemotherapy consisting of weekly cisplatin at a dose of 40 mg/m2.The clinical stage of the cervical nodes at presentation was N1 in 25%,N2 in 60%,and N3 in 15%.Most patients(75%) developed at least grade 3 mucositis.Eight patients(20%) had grade 3 xerostomia and 18 patients(45%) required esophageal dilation for stricture.The 5-year overall survival(OS) rate of all patients was 67.5%.The 5-year OS rates of patients with N1,N2,and N3 lesions were 100%,67%,and 41%,respectively(P = 0.046).The 5-year progression-free survival rate was 62.5%.In multivariate analysis,only N stage significantly affected OS(P = 0.022).Emergence of the occult primary was very limited(1 patient only).Our results suggest that extensive irradiation of both sides of the neck and pharyngeal mucosa with concurrent chemotherapy results in a lower emergence of primary tumor.Because the survival of patients with unknown primary is comparable to that of patients with known primary,an attempt at cure should always be made.

Case Report: Fever of Unknown Origin <br/>—An Unusual Presentation for Diffuse Large B-Cell Lymphoma

A 61-year-old male initially presented with fever of unknown origin. He had extensive work-up over two years including an infectious diseases panel, autoimmune studies, and Rheumatology and Hematology evaluations. The patient was initially diagnosed with Adult Still’s disease and underwent an out-patient right nodal fine-needle aspiration that was indeterminate. After continued failure of treatment for Adult Still’s disease, the patient had surgical resection of a right axillary lymph node that yielded the diagnosis of diffuse large B-cell lymphoma. Further work-up revealed Epstein-Barr virus positivity, the possible trigger behind his mutation for diffuse large B-cell lymphoma and its uncommon presentation. The patient met criteria for central nervous system prophylaxis and received multiple administrations throughout his therapy. He ultimately expired following recurrence of his disease at its initial site but without central nervous system involvement. We report an uncommon presentation of a patient with diffuse large B-cell lymphoma. This lymphoma can have numerous, vague presentations requiring a broad differential diagnosis and may lead to multiple evaluations prior to an ultimate diagnosis. We will also discuss the need for central nervous system prophylaxis, how this patient is qualified for prophylaxis, and how central nervous system prophylaxis benefits, harms, or does not affect patients with diffuse large B-cell lymphoma.

In vitro and in vivo cell tracking of chondrocytes of different origin by fluorescent PKH 26 and CMFDA

Tissue engineering techniques for cartilage re-pair to heal defects in joint surfaces is a clinical practice. Harvested autologous chondrocytes are expanded in culture and delivered in a suitable carrier medium back into the patient>s joint de-fect. The defect is then subsequently filled by new cartilage. Whether the cells in the repair tissue originate from the engineered tissue of the host or are derived from the surrounding original cartilage remains a relevant question for the ap-plied therapy. To answer this several methods exist to track cells, such as transfection of cells with LacZ carrying viruses, radio labeling with 111 IN or 51 Cr or fluorescent labeling with FDA. However, these techniques have drawbacks such as they may influence cellular properties, are radioactive and or quickly lose their tracking ability. New fluorescent probes are easier to handle and do not to interfere with cells. PKH 26劌 is a relatively new cell-labeling agent, but few data exist on the application of this dye in chondrocytes in vitro and in vivo. 5-chloromethylfluorescein diacetate - CMFDA (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#168;cell tracker green〔) is an established fluores-cent probe for imaging the dynamic processes of cell proliferation in vitro and in vivo. Likewise, several studies exist on different cell types. However, little data are available for chondro-cytes. The first aim of the study was to evaluate qualitative differences in fluorescence pattern after labeling of articular, auricular and costal chondrocytes. Secondly, we evaluated the influ-ence of labeling with CMFDA on cellular adhe-sion properties. The third aim was to compare the duration of cell labeling of chondrocytes of different origin with established CMFDA as stan-dard and PKH 26潴 for 3 cell generations in vitro and 12 weeks in vivo. We show that chondro-cytes from different origin can be labeled effec-tively with both PKH 26潴 and CMFDA. The PKH 26潴 labeled articular chondrocytes maintained fluorescence longer than CMFDA in vitro and in vivo. A higher percentage of articular chondro-cytes remained stained at 63 days than auricular or costal chondrocytes.

基于手机信令数据的城市居民动态OD矩阵提取方法

现有的城市居民出行调查周期较长,交通小区划分粒度粗糙,导致调查不能及时准确地获取居民出行信息。针对该问题,提出了一种基于手机信令数据的城市居民动态OD矩阵提取方法。首先,针对信令数据中的两种复杂噪声:乒乓切换和漂移数据,提出了基于窗口阈值的检测与等效位置替换方法,以及复杂漂移点的检测和标记处理方法;然后,提出一种改进的ST-DBSCAN聚类方法,引入一种等时化方法将时间信息与空间信息相结合,识别出行过程中的驻留点;最后,基于地理信息系统构建含有道路关键节点的路网,将居民出行OD与路网节点相匹配,有效推导出城市居民动态OD矩阵。实验结果表明:与ST-DBSCAN算法相比,所提改进的ST-DBSCAN算法在聚类效果和识别速度上分别提升了6.10%和5.26%;与统计方法和二阶统计量方法相比,基于改进的ST-DBSCAN算法的动态OD矩阵提取方法在均方误差(MSE)上分别降低了16.98%和21.55%。以北京市为例,运用提出的动态OD矩阵提取方法,能够及时有效地分析城市居民日常与高峰时段的出行特征。

Origin和SigmaPlot拟合细胞存活曲线效果的比较

目的考察Origin和SigmaPlot软件对人食管癌细胞系EC9706照射后细胞存活曲线的拟合效果。方法分别用Origin和SigmaPlot软件的曲线拟合功能对人食管癌细胞系EC9706的细胞存活曲线进行多靶单击模型、线性二次模型的曲线拟合,并比较两种软件的拟合效果。结果两种软件以上述两种数学模型拟合的细胞存活曲线都有意义,其决定系数均大于0.95。结论 Origin和SigmaPlot软件拟合细胞存活曲线的效果高度一致,是放射生物学拟合细胞存活曲线的有效方法。

Origin在太阳能电池基本特性测定实验中的数据处理及分析

本文测试了太阳能电池的输出特性,并利用Origin软件对实验数据进行了计算、绘图和数据拟合,得到较好的实验结果.表明Origin软件为大学物理实验提供了一种简便、适用的实验数据处理方法,提高了实验教学效果.

铝电解槽用铝基打壳锤头的研究与应用

打壳锤头在强磁场、高温环境下工作,受熔盐电解质的腐蚀以及下料口硬质壳面的冲击磨损,打壳锤头逐渐消耗,其中的铁、镉等杂质进入原铝液中影响电解槽原铝品位。本文开展了专用铝基打壳锤头的试验研究及开发,对铝基打壳锤头试样的耐磨、耐热、耐蚀等性能进行研究,找出适宜打壳作业的性能组合,试验数据结果表明,铝合金锤头的耐高温性、硬度、耐磨性及耐蚀性均能达到现场使用要求。实际应用效果表明,使用铝基锤头后电解槽原铝液中的铁含量降低了0.0178%,从根本上解决了铁质打壳锤头消耗磨损造成原铝污染的问题。在25万t/a系列上推广,每年节约成本和因铝品质提升而带来的效益可达132万元,经济效益良好。

MYC蛋白高表达弥漫大B细胞淋巴瘤45例分子特征分析

目的探讨MYC蛋白高表达弥漫大B细胞淋巴瘤(diffuse large B cell lymphoma,DLBCL)的分子特征。方法收集45例DLBCL临床资料。采用免疫组化EnVision法将患者分为MYC蛋白高表达/低表达组。所有样本均行DNA靶向测序,并使用LymphGen在线工具进行分子分型。运用Lymph2Cx法对细胞起源进行测定。采用χ^(2)检验和Fisher精确检验分析MYC蛋白高表达与临床病理参数的相关性。绘制生存曲线并使用Cox单因素、多因素回归分析生存相关因素。结果DLBCL病例分为MYC蛋白高表达组(n=17)和低表达组(n=28),与MYC蛋白低表达组相比,MYC蛋白高表达组PIM1、MYD88、CD79B、CD58和PRDM1的突变率较高(76.5%vs 28.6%,70.6%vs 32.1%,58.8%vs 28.6%,29.4%vs 3.6%,29.4%vs 3.6%,P均<0.05);分子亚型以MCD亚型多见(58.8%vs 10.7%,P=0.001);COO亚型GCB少见(17.6%vs 50.0%,P=0.030)。MYC蛋白高表达患者的总生存期显著缩短(P<0.05);Cox多因素分析显示,年龄是DLBCL的独立预后因素(P<0.05)。结论MYC蛋白高表达多为MCD型和ABC型,常见PIM1、MYD88、CD79B、CD58和PRDM1突变。MYC蛋白高表达的患者预后较差。

Combined hepatocellular cholangiocarcinoma: Controversies to be addressed

Combined hepatocellular cholangiocarcinoma(CHC) accounts for 0.4%-14.2% of primary liver cancer cases and possesses pathological features of both hepatocellular carcinoma and cholangiocarcinoma. Since this disease was first described and classified in 1949, the classification of CHC has continuously evolved. The latest definition and classification of CHC by the World Health Organization is based on the speculation that CHC arises from hepatic progenitor cells. However, there is no evidence demonstrating the common origin of different components of CHC. Furthermore, the definition of CHC subtypes is still ambiguous and the identification of CHC subtype when a single tumor contains many components has remained unresolved. In addition, there is no summary on the newly recognized histopathology features or the contribution of CHC components to prognosis and outcome of this disease. Here we provide a review of the current literature to address these questions.

road to stemness in hepatocellular carcinoma

Carcinogenic process has been proposed to relay on the capacity to induce local tissue damage and proliferative repair. Liver has a great regeneration capacity and currently, most studies point towards the dominant role of hepatocytes in regeneration at all levels of liver damage. The most frequent liver cancer is hepatocellular carcinoma(HCC). Historical findings originally led to the idea that the cell of origin of HCC might be a progenitor cell. However, current linage tracing studies put the progenitor hypothesis of HCC origin into question. In agreement with their dominant role in liver regeneration, mature hepatocytes are emerging as the cell of origin of HCC, although, the specific hepatocyte subpopulation of origin is yet to be determined. The relationship between the cancer cell of origin(CCO) and cancer-propagating cells, known as hepatic cancer stem cell(HCSC) is unknown. It has been challenging to identify the definitive phenotypic marker of HCSC, probably due to the existence of different cancer stem cells(CSC) subpopulations with different functions within HCC. There is a dynamic interconversion among different CSCs, and between CSC and non-CSCs. Because of that, CSC-state is currently defined as a description of a highly adaptable and dynamic intrinsic property of tumor cells, instead of a static subpopulation of a tumor. Altered conditions could trigger the gain of stemness, some of them include: EMT-MET, epigenetics, microenvironment and selective stimulus such as chemotherapy. This CSC heterogeneity and dynamism makes them out reach from therapeutic protocols directed to a single target. A further avenue of research in this line will be to uncover mechanisms that trigger this interconversion of cell populations within tumors and target it.

硅太阳能电池负载特性及Origin软件处理数据的应用研究

分别测量了多晶硅薄膜电池与卤素灯之间距离为50 cm,70 cm,90 cm时输出功率随负载电阻变化之间关系,用origin软件绘制了功率随电阻变化关系和伏安特性曲线,并找到最大功率点,计算出了电池的填充因子（FF）。结果表明距离越小,FF愈大,输出功率愈高。

Research on human glioma stem cells in China

Research on human glioma stem cells began early in the 21^(st) century and since then has become a rapidly growing research field with the number of publications increasing year by year. The research conducted by our diverse group of investigators focused primarily on cell culture techniques, molecular regulation, signaling pathways, cancer treatment, the stem cell microenvironment and the cellular origin and function of glioma stem cells. In particular, we put forward our view that there are inverse or forward transformations among neural stem cells, glial cells and glioma stem cells in glioma tissues under certain conditions. Based on the background of the progress of international research on human glioma stem cells, we aim to share our progress and current findings of human glioma stem cell research in China with colleagues around the world.

Developmental potency of mouse primitive ectoderm cells, embryonic ectoderm cells and primordial germ cells after blastocyst injection

Developmental potency of primitive and embryonic ectoderm cells from 4.50-day to 6.25-day post-coitum (p.c.) mouse embryos and primordial germ cells from 12.50-day p.c.male genital ridges of fetal mice were studied by direct introducing them into 3.50-day p.c.blastocysts.Sixteen (61.5) overt chimaeras out of 26(50%) offsprings were obtained after transfer of 52 blastocysts injected with 4.50-day primitive ectoderm cells;four (16.0%) overt chimaeras were obtained out of 25 (51.0%) offsprings with 4.75-day primitive ectoderm cells from 49 transferred blastocysts.However,no overt chimaera was obtained with either 5.25-day or 6.25-day embryonic ectoderm cells or 12.50-day male primordial germ cells.GPI analysis of mid-gestation conceptuses developed from injected blastocysts showedthat 5.25-day embryonic ectoderm cells could only contributed to yolk sac of conceptus.Results suggested that implantation acts as a trigger for the determination of primitive ectoderm cells,and their developmental potency becomes limited within a short period of time in normal development.

Origin软件在光伏电池伏安特性实验中的应用

介绍在光伏电池伏安特性实验中应用Origin软件处理实验数据的方法。先利用Origin软件的双y轴绘图功能绘制光伏电池的伏安特性曲线和功率曲线,并进行多项式曲线拟合;再利用其寻峰功能读取对应最大功率的最佳输出电压和最佳输出电流数据,然后计算最大输出功率、填充因子等特征参数。应用Origin软件处理实验数据,可以简化数据处理过程,减少人为因素造成的随机性误差。

肺癌小鼠肿瘤组织IL-10的来源及其功能验证

为了解肺癌肿瘤组织白细胞介素-10(interleukin-10,IL-10)的表达和来源,并探究IL-10对肿瘤的作用,采用MSD超敏电化学发光技术检测Lewis肺癌小鼠模型血清中IL-10的水平,使用流式细胞术分析肿瘤组织IL-10的主要来源,再通过CCK-8实验、膜联蛋白V-碘化丙啶(annexin V-PI)凋亡实验、划痕实验,检测IL-10重组蛋白对肺癌细胞增殖、凋亡、迁移的影响。结果表明:Lewis肺癌小鼠血清中IL-10水平较正常小鼠显著升高,肿瘤组织中的IL-10主要由免疫细胞产生。其中,B细胞和髓源性抑制细胞(myeloid-derived suppressor cells, MDSCs)是IL-10的主要来源,IL-10重组蛋白可以显著抑制LLC(小鼠Lewis肺癌细胞:Lewis lung carcinoma line)的增殖和迁移并促进其凋亡。综上可见,IL-10水平与肺癌密切相关,B细胞和MDSCs是产生IL-10的主要来源,IL-10可能通过激活CD8 T细胞或者直接作用于肿瘤细胞而发挥抗肿瘤作用。

骨髓增生异常综合征疾病演变过程中的免疫细胞水平变化研究

目的观察外周血免疫细胞在健康人、骨髓增生异常综合征(myelodysplastic syndromes,MDS)、急性髓系白血病(acute myeloid leukemia,AML)不同人群中的表达差异,并进一步分析其差异与MDS患者国际预后评分系统(international prognostic scoring system,IPSS)评分、原始细胞数目等因素的相关性。方法回顾性分析2012年1月~2022年4月北京中医药大学东直门医院收治的MDS患者55例,并纳入25例健康人、67例AML患者进行对照分析。根据免疫细胞绝对值计数及占淋巴细胞百分比,比较T细胞亚群(CD3^(+)、CD4^(+)、CD8^(+)、CD4^(+)/CD8^(+)、CD3^(+)CD4^(+)CD25^(+)FoxP3^(+))、B细胞(CD19^(+))及NK细(CD3-CD16^(+)CD56^(+))表达差异;并将差异指标与IPSS评分、原始细胞数目进行相关性分析。结果3组免疫指标表达水平存在差异;进一步两两比较结果提示,与健康组比较,MDS组各类免疫细胞计数均偏低(P<0.025),考虑与MDS患者总淋巴细胞计数低于健康组相关。3组Treg细胞、B细胞、T细胞百分比比较,差异有统计学意义;进一步两两比较结果提示,与健康组比较,MDS组T细胞、Treg细胞占比增高,B细胞占比降低,其中T细胞、B细胞占比比较,差异有统计学意义(P<0.025);与MDS组比较,AML组Treg细胞占比增高,B细胞占比降低,差异有统计学意义(P<0.025);Treg细胞占比与IPSS评分、原始细胞数目呈正相关。结论Treg细胞占比在健康人、MDS、AML人群中表达水平整体呈上升趋势,Treg细胞在MDS表达水平中升高可能是评估MDS患者预后及病情进展的重要因素。