胰腺干细胞研究中的思考

从干细胞研究发展和胰腺生理病理学研究发展两个方面,横向和纵向两个角度阐述了胰腺干细胞研究的思路,用辩证认识论和普遍联系与对立统一原理分析了胰腺干细胞研究中所面临的问题和挑战,提出应对的策略和方法,并结合胰腺干细胞发展现状,展望其应用前景。     

诱导多能干细胞技术的生命伦理分析

诱导多能干细胞(induced pluripotent stem cells,iPSCs)是通过向分化的体细胞转入特定的外源转录因子进行重编程,从而获得具有自我更新能力和多能性的细胞.iPSCs具有形成体内所有细胞类型的潜能,尤其是能以患者自身体细胞制备iPSCs,可用于特定疾病的治疗,规避了异体移植引发的免疫排斥风险以及伦理和法律冲突等问题,在基础研究和临床应用都有广阔的应用前景.目前,在重编程体细胞为iPSCs的过程中,由于细胞来源不同,所采用的基因组合以及转基因方式各不相同,获得的iPSCs具有潜在的致癌性等安全隐患,导致iPSCs的临床应用面临新的生命伦理挑战.     

Treatment of Patients with Advanced Hepatocellular Carcinoma using Stem Cell Differentiation Stage Factors

Hepatocellular carcinoma (HCC) represents the third leading cause of cancer-related death. Because HCC is multicentric with time, excluding the few transplanted patients, sooner or later it becomes untreatable with loco-regional therapies and, until some years ago, it was not responsive to systemic therapies. In 2005 a randomized trial indicated the efficacy of a product containing stem cell differentiation stage factors (SCDSF) taken from zebrafish embryos during the stage in which the totipotent stem cells are differentiating into the pluripotent adult stem cells. In such a trial the patients, with “intermediate” and “advanced” HCC according to Barcelona Clinic Liver Cancer/American Association for the Study of Liver Diseases (BCLC/AASLD) guidelines, presented benefit in terms of performance status and objective tumoral response, with some cases (2.4%) of complete response, that is, sustained disappearance of the neoplastic areas or blood supply therein, accompanied by normalization of alpha-fetoprotein (AFP) levels (complete response [CR]). A second study reporting the experience of a tertiary referral center on patients with “advanced” stage confirmed the possibility to obtain CR. Out of 38 patients, 5 presented a sustained CR (13.1%). Improvement on PS was obtained in 17 patients (34.6%). No side effects occurred.     

Theoretical accounts of spatial learning: A neurobiological view (commentary on Pearce, 2009)

Theories of learning have historically taken, as their starting point, the assumption that learning processes have universal applicability. This position has been argued on grounds of parsimony, but has received two significant challenges: first, from the observation that some kinds of learning, such as spatial learning, seem to obey different rules from others, and second, that some kinds of learning take place in processing modules that are separate from each other. These challenges arose in the behavioural literature but have since received considerable support from neurobiological studies, particularly single neuron studies of spatial learning, confirming that there are indeed separable (albeit highly intercommunicating) processing modules in the brain, which may not always interact (within or between themselves) according to classic associative principles. On the basis of these neurobiological data, reviewed here, it is argued that rather than assuming universality of associative rules, it is more parsimonious to assume sets of locally operating rules, each specialized for a particular domain. By this view, although almost all learning is associative in one way or another, the behavioural-level characterization of the rules governing learning may vary depending on which neural modules are involved in a given behaviour. Neurobiological studies, in tandem with behavioural studies, can help reveal the nature of these modules and the local rules by which they interact.     

A model of episodic memory: Mental time travel along encoded trajectories using grid cells

The definition of episodic memory includes the concept of mental time travel: the ability to re-experience a previously experienced trajectory through continuous dimensions of space and time, and to recall specific events or stimuli along this trajectory. Lesions of the hippocampus and entorhinal cortex impair human episodic memory function and impair rat performance in tasks that could be solved by retrieval of trajectories. Recent physiological data suggests a novel model for encoding and retrieval of trajectories, and for associating specific stimuli with specific positions along the trajectory. During encoding in the model, external input drives the activity of head direction cells. Entorhinal grid cells integrate the head direction input to update an internal representation of location, and drive hippocampal place cells. Trajectories are encoded by Hebbian modification of excitatory synaptic connections between hippocampal place cells and head direction cells driven by external action. Associations are also formed between hippocampal cells and sensory stimuli. During retrieval, a sensory input cue activates hippocampal cells that drive head direction activity via previously modified synapses. Persistent spiking of head direction cells maintains the direction and speed of the action, updating the activity of entorhinal grid cells that thereby further update place cell activity. Additional cells, termed arc length cells, provide coding of trajectory segments based on the one-dimensional arc length from the context of prior actions or states, overcoming ambiguity where the overlap of trajectory segments causes multiple head directions to be associated with one place. These mechanisms allow retrieval of complex, self-crossing trajectories as continuous curves through space and time.     

脑内移植发展的回顾和展望

脑内移植是神经系统疾病的一种新的治疗措施。它适应临床实践的需要而产生,历经脑内组织移植和脑内干细胞移植两个重要发展阶段,其中脑内干细胞移植的研究主要有神经干细胞移植、胚胎干细胞移植、骨髓和脐血间充质干细胞移植。脑内干细胞移植是目前国内外医学研究的热点,具有广阔的临床应用前景,但也存在许多有待解决的问题,还需要经过一个艰难曲折的探索过程,最终使之成为治疗神经系统疾病的有效方法。它的产生和发展遵循着认识论和辩证法的客观规律,体现了科学认识的实践性、深刻性和创造性。     

Detection of subtype blood cells using deep learning

Deep Learning has already shown power in many application fields, and is accepted by more and more people as a better approach than the traditional machine learning models. In particular, the implementation of deep learning algorithms, especially Convolutional Neural Networks (CNN), brings huge benefits to the medical field, where a huge number of images are to be processed and analyzed. This paper aims to develop a deep learning model to address the blood cell classification problem, which is one of the most challenging problems in blood diagnosis. A CNN-based framework is built to automatically classify the blood cell images into subtypes of the cells. Experiments are conducted on a dataset of 13k images of blood cells with their subtypes, and the results show that our proposed model provide better results in terms of evaluation parameters.     

干细胞纠缠

干细胞生物学的研究目前还处于一个“灰箱”的状态,阻止机制阐明的最大障碍之一可能是因为缺少一个行之有效且又不会改变干细胞自然属性的研究平台。这个平台的中心是要有一个像“薛定谔的猫”那样能即时报告干细胞属性的作用角色。目前,主要有两方面阻碍了干细胞研究的进一步深化,一个是干细胞如何不对称分裂,另一个是干细胞巢的结构组成。其实,在微观世界的许多研究中,如物理学中的量子论,都是因为缺少那只“薛定谔的猫”才使研究的钟摆停在原地不动。     

干细胞技术与肝硬化:共性与个性的新实践

干细胞横向分化(transdifferentiation)的能力,在肝脏再生过程中发挥作用,随着对干细胞的深入研究,干细胞技术为终末期肝病的治疗提供了新思路。本文对干细胞加以分类并综述了各种干细胞研究进展,对干细胞在肝脏疾病细胞治疗上的应用及前景作了总结和展望。     

Bioterrorism, Embryonic Stem Cells, and Frankenstein

The stem cell controversy raises a fundamental question for humankind. Does science have a right to pursue knowledge whatever the cost? Our Enlightenment culture says yes. However, human history and literature are sending warning signals. Ethical issues impact the “knowledge for its own sake” imperative, and must be addressed.     

肿瘤干细胞与肿瘤治疗

肿瘤可看作是由功能异质性的细胞群体所组成的,具有不定增殖能力的异常器官.最近提出的肿瘤干细胞学说认为肿瘤起源于干细胞,肿瘤生长是肿瘤组织中极少量具有特殊细胞表面标志的肿瘤干细胞增殖的结果.因此治疗的关键应是针对肿瘤干细胞,通过靶向肿瘤干细胞及其异常调节的信号转导通路来治疗肿瘤.这对传统的治疗方式提出了巨大挑战,也为有效地根治肿瘤开辟了新的思路.     

到底路有多长--对干细胞移植治疗研究的一点思考

目前干细胞研究的争论主要集中于干细胞研究的过程和方式,诸如干细胞来源以及被提取干细胞的胚胎的权利与地位等伦理问题是争论的焦点所在,而对于研究的最终目的是治病而非克隆人则少有争议.然而在伦理问题等争论相对较小的干细胞应用研究领域,就应用于人的技术层面而言还有很多问题有待解决.安全性(safety)和有效性(efficacy)原则是目前公认的干细胞临床应用研究的基准.干细胞移植治疗最终应用于临床可能还有相当一段路程要走,无论是研究者还是伦理学家以及社会舆论和普通百姓在其中都应当并可以发挥积极的作用.     

干细胞技术应用于口腔医学的希望与困惑

骨髓干细胞、胚胎干细胞已开始应用于口腔医学领域,有关牙髓干细胞、牙周干细胞、牙胚干细胞等研究也取得了一系列重要的进展,为治疗口腔疾病开辟了一个新的途径,但同时也面临着需要进一步探讨的技术和伦理等方面的问题.     

肿瘤干细胞研究的进展及启示

肿瘤干细胞理论认为,肿瘤增长是由肿瘤中具有干细胞特性的细胞分裂增殖引起的。针对性地抑制肿瘤干细胞的增殖,能显著提高肿瘤治愈率。本文用哲学的观点对肿瘤干细胞假说的提出、验证、临床应用进行分析,对于深入认识肿瘤干细胞的本质、探索其分离方法、发现抑制其增殖的有效手段将起到积极作用。     

微流控分析芯片在循环肿瘤细胞检测中的运用

随着人们对于肿瘤性疾病的发生、发展、转移机制的进一步探索,循环肿瘤细胞（CTCs）逐渐进入人们视野,其应用价值日益体现,可用于肿瘤性疾病的早期诊断及治疗效果的监测,尤其是对于早期肿瘤的诊断具有独特优势。其富集技术及检测方法也在发生着日新月异的变化。近年来,微流控分析芯片技术运用于 CTCs 的富集及检测,具有高丰度、高富集度、高活性及不需要对样本进行预处理等优点使得人们聚焦于此技术,本文对微流控分析芯片在 CTCs 检测中的运用做简要综述。     

胚胎干细胞研究进展

胚胎干细胞具有重大的生物学基础研究价值和医学应用价值。关于胚胎干细胞的研究起源自20世纪70年代,目前的研究热点主要集中在胚胎干细胞的基础生物学特性和临床应用上。同时科学家也在想办法克服研究中面临的伦理问题。     

胰岛细胞移植治疗1型糖尿病现状与未来

自2000年加拿大Edmonton报道了7例1型糖尿痛患者施行胰岛细胞移植术成功以来,越来越多的人把注意力投向了胰岛细胞移植的领域。然而,临床移植工作的成功开展还面临两大困难,一方面现有的胰岛细胞来源已经远远不能满足临床移植的需要,另一方面,现有免疫抑制方案造成了很多副作用。近年来,科技工作者正在探索新的途径,寻找新的胰岛来源。特别是包括体外重编程干细胞（iPS）、调节性T细胞和脐血干细胞在内的多种新技术的研究工作取得了许多进展,将为我们提供更多的选择,有可能成为今后的发展方向。本文就胰岛细胞移植治疗1型糖尿病的现状与未来展望进行简要的综述。     

噻唑烷二酮类药物在1型糖尿病治疗中的价值

噻唑烷二酮类药物（TZD）已在2型糖尿病中广泛应用。鉴于TZD具有增加胰岛素敏感性、抗炎症、调节免疫等作用,对它在1型糖尿病中的应用价值亦有探讨,这有助于指导实践和进一步研究。