白血病的靶向治疗:前世和今生

白血病是一类具有异质性的造血系统恶性肿瘤。世界上第一例白血病的报道始于近200年前,而白血病的治疗亦有近百年的历史。在急性早幼粒细胞和慢性髓系白血病治疗的探索之路上,维甲酸、砷剂以及酪氨酸激酶抑制剂的出现均为白血病靶向治疗史上成功范例。急性髓系白血病(AML)是成人白血病最常见的类型,过去40多年来其标准治疗方案几乎没有进展。近年来涌现的靶向新药给AML的治疗带来了新的希望。本文简述白血病的发现及治疗史,重点介绍急性早幼粒细胞白血病和慢性粒细胞白血病靶向治疗的成功过去,以及近年来AML靶向治疗的进展。     

导言:急性髓细胞白血病诊治的优化选择

正急性白血病(Acute leukemia,AL)是发生于造血干细胞的克隆性恶变,导致大量白血病细胞无限制地分裂增殖,不能发生程序性凋亡,从而导致骨髓及外周血中大量白血病细胞积聚,进一步抑制正常造血细胞的发生及发育,而呈现贫血、出血、严重感染等临床表现,及全身脏器的广泛浸润,比如浸润至肝、脾、淋巴结等组织器官。按照造血干细胞细胞系别发生恶变的不同,白血病分为急性淋巴细胞白血病和急性髓细胞白血病(Acute myelogenous leukemia,AML)。     

白血病诱导分化治疗中的生态自然观

诱导分化是一种治疗白血病的新方法,它通过促使分化不完全的肿瘤细胞分化成熟,使恶性转为良性.临床应用全反式维甲酸(ATRA)和三氧化二砷(As2O3)诱导急性早幼粒细胞性白血病取得了较高的完全缓解率,毒副作用也较低.诱导分化治疗策略突破了将杀灭肿瘤细胞作为治疗肿瘤的惟一方法的思维局限,谋求在与白血病细胞的和谐中获得人类的健康,是生态自然观应用于医疗实践的成功范例.     

混合表型急性白血病的预后评估及治疗选择

混合表型急性白血病(MPAL)是指在免疫学检测中,可见具有不同表型的两群以上白血病细胞,或者一种白血病细胞表达两种以上细胞的表面标志。MPAL发病率低,相关研究少,整体预后差,目前对于MPAL没有统一明确的治疗方案,因此治疗选择难度大。本文对MPAL的诊断流程、预后评估及治疗选择予以综述。     

大剂量阿糖胞苷治疗急性髓细胞白血病疗效及不良反应观察

为探讨大剂量阿糖胞苷(Ara-c)用于急性髓细胞白血病(AML)完全缓解后巩固强化治疗的疗效及不良反应,本文分析5例AML患者,在治疗前完善细胞遗传学及分子生物学检查,经诱导治疗达到完全缓解(CR)后,即给予大剂量Ara-c(Ara-c 3g/m2,12小时1次,共6次)单药强化治疗共3疗程,每次化疗前均进行骨髓穿刺、分子生物学检查等判断治疗效果,观察15例次的治疗效果及不良反应。之后所有患者均持续完全缓解,并且早期达到分子生物学缓解,所有患者均出现明显的骨髓抑制及不同程度的感染、消化道反应等,但均安全度过,不影响进一步治疗。本研究提示大剂量Ara-c作为AML缓解后的巩固强化治疗方案,疗效确切、分子生物学缓解率高、安全性好。     

缺血性心肌病性冠心病概述

随着世界人口老龄化,老年疾病尤其是心血管病的病死率随年龄而增加.有人认为40岁以后明显上升,60岁以上每增加10岁,心血管病的病死率则增加1倍左右.近年来随着冠心病介入诊疗技术的快速发展,急性心肌梗死或者心绞痛的患者通过介入得以存活,从而心肌缺血性冠心病患者较前明显增加,本文从缺血性心肌病性冠心病危险因素、发病机制、临床表现、诊断治疗、预后等方面详细阐述缺血性心肌病性冠心病的防治策略.     

老年粗隆间骨折内固定与关节置换术的治疗策略分析

股骨粗隆间骨折临床常见,多发于老年人.手术治疗方法很多,主要分为髓内、髓外的内固定治疗及人工关节置换等.然而,目前没有统一的标准采指导如何选择手术方式.虽然绝大多数的手术治疗方法都能取得较好的效果,但出现问题的病例也较为多见.本文通过文献复习,对近年来的老年粗隆间骨折内固定治疗与关节置换的治疗策略进行分析,为临床治疗提供参考.     

成人复发难治性急性髓系白血病治疗进展

复发急性髓系白血病(AML)患者的预后差,约半数以上复发患者存在耐药难治,其治疗面临着诸多挑战和难题。对于复发后获得再次完全缓解的患者,异基因造血干细胞移植(alloHSCT)是最有效的治疗方式之一,但移植相关死亡率(TRM)和复发率(CIR)均很高,从而部分抵消了移植带来的益处。因此,allo-HSCT对于部分患者并不适合,亟待寻找新的治疗手段。近几年,随着我们对AML发病机制认识的加深。新药物新疗法层出不穷,极大改善了复发难治性AML的预后。多个小分子靶向药物和免疫疗法目前正处于临床试验阶段,初步试验结果鼓舞人心。虽然新疗法治疗相关副作用越来越少,疗效越来越好,但allo-HSCT是治愈复发难治性AML的唯一途径。     

白血病需要综合治疗

通过分析目前白血病单一治疗方法学中的利与弊,可以得到一些重要的启示和思考,这些启示引导我们要用综合的手段去治疗白血病,并最终攻克白血病这一顽疾.     

老年高血压患者降压治疗中的低血压原因分析及对策

老年高血压患者降压治疗中可能并发低血压,原因为假性高血压、体位性低血压,餐后低血压,季节变化、伴随疾病和不适当用药引起的低血压.低血压可导致心脑肾等重要脏器灌注不足,甚至发生脑卒中、心肌梗死等严重并发症.因此,及时发现老年高血压患者治疗中的低血压,给予相应治疗已显得十分重要.     

Maladjustment in statistical minorities within ethnically unbalanced classrooms

Ascertained if being a member of a statistical minority influences children's adjustment in school, as measured by the AML, a teacher-administered adjustment rating scale. Teachers from a southwest school district evaluated elementary students on aggressive, acting-out behaviors, moody-internalized behaviors, and learning difficulties. Analyses conducted on 376 students revealed significant effects of statistical minority status on certain dimensions of adjustment ratings for both Hispanic and Anglo students. Hispanic students in the statistical minority received poorer ratings on the moodiness dimension of the AML than nonminority Hispanic students. Anglo students in the statistical minority received poorer ratings on the aggression dimension of the AML than nonminority Anglo students. These results were interpreted in terms of cultural differences in coping with statistical minority status. Traits commonly exhibited within a culture may intensify and be perceived as maladaptive when stress resulting from being a minority occurs. Implications of the finding that statistical minority status within the school environment influences adjustment are discussed.     

The criminalization of money laundering and terrorism in global contexts: a hybrid solution

What obligations do global actors have to prevent terrorism? Is consent required to create an international obligation, or does the correctness of its goals ground its legitimacy? In this paper, I consider these questions with respect to a subset of international law often overlooked: anti-money laundering and combating the financing of terrorism (AML/CFT). AML/CFT comprises peaceful response to violence and terrorism, making it a significant component of international justice and diplomacy. First, I present the current legal framework for AML/CFT institutions and identify two conflicting sources of justification: objective value and consent. The fix for this problem, I argue, does not come from either component alone. Objective value cannot provide the sole source of justification because it cannot settle the choice between multiple competing norms that would achieve the same objective goods were we to follow them (‘the choice problem’). Consent cannot provide the sole source of justification (‘the constraint problem’) for two reasons: some contracts that people agree to are morally abhorrent and others are morally required but people do not agree to them. But objective value and consent can be combined consistently, and I articulate this hybrid as a sound basis for evaluating and reforming AML/CFT laws and institutions.     

膀胱癌治疗方法的最优选择

膀胱癌的治疗比较复杂,治疗方法多种多样,根据不同的病理及临床过程恰当的选用不同的治疗方法,以期治疗的个体化和最优化.从哲学的角度来观察和分析膀胱癌的治疗方法,以便为临床实践和进一步的研究提供思路.     

Relativized common knowledge for dynamic epistemic logic

Relativized common knowledge is a generalization of common knowledge proposed for public announcement logic by treating knowledge update as relativization. Among other things relativized common knowledge, unlike standard common knowledge, allows reduction axioms for the public announcement operators. Public announcement logic can be seen as one of the simplest special cases of action model logic (AML). However, so far no notion of relativized common knowledge has been proposed for AML in general. That is what we do in this paper. We propose a notion of action model relativized common knowledge for action model logic, and study expressive power and complete axiomatizations of resulting logics. Along the way we fill some gaps in existing expressivity results for standard relativized common knowledge.     

How many notions of necessity?

Evans distinguishes between superficial necessity and deep necessity in his analysis of the contingent a priori. The distinction between these two notions of necessity is formalized by Davies and Humberstone through the addition of the operator Fixedly to Actuality Modal Logic (AML, S5A), where deep necessity is represented by the combination Fixedly Actually. Wehmeier’s Subjunctive Modal Logic (SML) provides an extension of the expressive capacity of ordinary modal predicate logic alternative to AML. I add Fixedly to SML and show that in the system SML with Fixedly the distinction between deep and superficial necessity disappears. I conclude that the existence of the distinction between deep and superficial necessity, as well as the existence of the contingent a priori, cannot be asserted independently of the choice of background logic.     

药物性肝损伤的临床处置策略

本文讨论了药物性肝损伤治疗的相关临床问题,概括出以下几点：（1）可预知性与不可预知性肝毒性药物的临床处置方法,强调治疗的关键是停止肝毒性药物的使用以及停药的具体指征;（2）支持治疗不应被忽视,以及如何实施;（3）解毒药物的概念和种类;（4）保肝药物应用中存在的问题,主要是不按药理机理选择和多重用药,介绍了保肝药的不同机理和代表药物,阐述不要多种保肝药联合的基本原则;（5）根据肝损伤临床类型选择不同的治疗方案,肝细胞损伤以保肝药物治疗为主,胆汁淤积以利胆治疗为主,对重症肝损伤者应人工肝支持治疗,必要时进行肝移植.     

对脊柱结核诊疗策略的思考

脊柱结核是临床常见病,其诊疗策略主要包括正确的诊断思路、合适的治疗选择。尤其重视非典型性脊柱结核的诊断,治疗方面要重视药物治疗、营养支持、休息制动等手段。对于需要手术治疗的患者,需个体化选择最适合的术式,且应完整理解并客观评估新技术的应用。     

Abstract: Evaluation of Test Statistics for Robust Structural Equation Modeling With Nonnormal Missing Data

Traditional structural equation modeling (SEM) techniques have trouble dealing with incomplete and/or nonnormal data that are often encountered in practice. Yuan and Zhang (2011a) developed a two-stage procedure for SEM to handle nonnormal missing data and proposed four test statistics for overall model evaluation. Although these statistics have been shown to work well with complete data, their performance for incomplete data has not been investigated in the context of robust statistics.

Focusing on a linear growth curve model, a systematic simulation study is conducted to evaluate the accuracy of the parameter estimates and the performance of five test statistics including the naive statistic derived from normal distribution based maximum likelihood (ML), the Satorra-Bentler scaled chi-square statistic (RML), the mean- and variance-adjusted chi-square statistic (AML), Yuan-Bentler residual-based test statistic (CRADF), and Yuan-Bentler residual-based F statistic (RF). Data are generated and analyzed in R using the package rsem (Yuan & Zhang, 2011b).

Based on the simulation study, we can observe the following: (a) The traditional normal distribution-based method cannot yield accurate parameter estimates for nonnormal data, whereas the robust method obtains much more accurate model parameter estimates for nonnormal data and performs almost as well as the normal distribution based method for normal distributed data. (b) With the increase of sample size, or the decrease of missing rate or the number of outliers, the parameter estimates are less biased and the empirical distributions of test statistics are closer to their nominal distributions. (c) The ML test statistic does not work well for nonnormal or missing data. (d) For nonnormal complete data, CRADF and RF work relatively better than RML and AML. (e) For missing completely at random (MCAR) missing data, in almost all the cases, RML and AML work better than CRADF and RF. (f) For nonnormal missing at random (MAR) missing data, CRADF and RF work better than AML. (g) The performance of the robust method does not seem to be influenced by the symmetry of outliers.     

Psychological aspects of myelomeningocele—a longitudinal study

The possibilities of treatment of the congenital neurological disease myelomeningocele have improved since the 1960s. The patients who survive often suffer from severe motor and mental handicaps, and it has been discussed whether a selection should be made of those children who should be treated or whether all children should be treated. Here we present results of a longitudinal study of 56 children, who were all treated and still continue active treatment. The results show that mental retardation was not greater than in groups of children selected for treatment according to a criterion. There was no difference between the sexes. Mean IQ was 90, 75% attended normal school, and only 33% received remedial instruction, primarily because of difficulties with emptying the bladder.     

Suicidality and its relationship to treatment outcome in depressed adolescents

This study investigates the impact of suicidality on treatment outcome in 107 depressed adolescents who participated in a clinical trial, and received either cognitive-behavioral (CBT), systemic-behavioral-family (SBFT), or non-directive-supportive therapy (NST). Suicidal depressed adolescents had a higher dropout rate and were more likely to be depressed at the end of treatment, in large part due to the particularly poor response of suicidal patients to NST. The relationship between suicidality and treatment response was mediated by severity of depression and hopelessness at intake. Hopelessness should be specifically targeted early in treatment. Suicidal depressed adolescents should not receive NST but a specific treatment like CBT.