不管你是出口成章，还是下笔成文，在写作文章的时候，我们依旧需要经过细细的斟酌和品味，以便找到更好的表达与修饰。而在SCI写作的过程中也是如此，想要将稿件投递出去，我们需要认真修改润色；投稿之后，面对编辑意见我们也需要认真修改润色。论文讨论部分的重中之重是对研究结果的解读，然而，在这篇论文的讨论部分，只占10%的篇幅。70%的篇幅被用于重申引言部分已经交代的研究背景与合理性，20%篇幅描述研究结果的细节。这是浪费读者时间！如果我写这篇论文，讨论部分会这样安排：首先，简要总结一下核心结果Summary of results:1.comparable rate of EGFR mutation in small biopsy specimens vs. surgically resected specimens;（第一，用小活检样本进行检测，EGFR基因突变总检出率和具体的突变位点，和手术切除标本相当；）2. lower rate of ELM4-ALK fusion in small biopsy specimens vs. surgically resected specimens（第二，用小活检样本进行检测，ALK融合基因检出率只有手术切除标本的40%；）总结完毕，然后给出一个大致的解读，General interpretation: small biopsy specimens are useful in determination of EGFR mutation status (and therefore, useful to guide the use (or non-use of EGFR TKIs), but not useful for ELM4-ALK fusion (and therefore, not useful to guide the choice of targeted therapy。（小活检标本可以用来检测EGFR基因突变，不可以用来检测ALK融合基因。）然后，简单讨论这个结果的临床价值 - 多少以及哪些患者能够从这个新的检测方法中获益。Significance：1. How many and what type of patients could benefit from these results (based on the number of NSCLC patients who are not suitable candidate for surgery? What is the percentage of NSCLC patients who harbor EGFR mutations?）。（首先，每年在全球范围内有多少肺癌患者就诊时已经太晚、不能接受手术治疗；其次，多少比例的肺癌患者携带突变的EGFR基因。）如果你愿意，可以细化一点，描述不同病理类型肺癌和不同种族的具体情况。对结果的临床意义作出一个基本解读以后，有很多事情可以、也应当去讨论。比如：你的发现是否有理论依据支持。有依据的话，你的发现就可信；没有显而易见的依据，你就需要进行解释或者推测，否则你的结果很难让别人相信。具体到这篇论文，作者需要讨论的是，Why I saw what I saw? Why similar rate of EGFR mutation, but lower rate of ELM4-ALK fusion in small biopsy specimens?（为什么小活检标本检测EGFR基因突变，得到的结果和手术标本差不多，而用于检测ALK融合基因，检出率低很多？）这样一个差异，至少有2种可能的原因：Why I saw what I saw? Why similar rate of EGFR mutation, but lower rate of ELM4-ALK fusion in small biopsy specimens?1.Technical issues, for example, the method used to detect ELM4-ALK fusion requires more tissue (than EGFR mutation detection) in order to be reliable.（第一，EGFR基因突变检测方法比较成熟，用小量的样本就能很好地完成。ALK融合基因检测不够成熟，小量样本不行。）2. Higher degree of genetic heterogeneity within a certain subjects (but across different cell populations) with ELM4-ALK fusion than with EGFR?（第二，EGFR基因突变在同一个病人病变的不同部位、不同的肿瘤细胞上异质性，也就是差别较小，所以一小块组织能够较好地代表整个肿瘤。而ALK融合基因在肿瘤不同部位、不同细胞上表达差别较大，所以，用一小块样本检测得到的结果和手术切除标本不一致。）3. Have similar findings been reported for other types of cancer?（到底是怎么回事儿，作者必须去查阅文献，在论文讨论部分给出一个具备说服力的判断。）作者应当讨论的第2个内容是，Limitations. Distinct groups of patients for the 2 types of samples vs. the ability to provide a solid answer to the main question (whether the results of detection are consistent between small biopsy specimens and surgical specimens)，（这个研究本身有什么重大缺陷。）例如，研究设计和基本方法是否能够对研究核心问题给出一个靠谱的答案。这个研究的目的是看：小活检标本检测结果是否和手术标本一致。作者需要给出的答案是 - 两种样本结果是否一致。你需要告诉别人，10个病人，我用A方法检测，阳性的是第1、3、5、7号病人，用B方法检测，阳性的也是这4号病人。仅仅检出率相仿不说明问题。你必须在同一群患者上对比两种检测方法。这是一个重大的缺陷。审稿人不傻，我张科宏能够看到的东西，他们一定能看到。明智的做法是：承认缺陷，然后对这个缺陷背后的障碍给出说明，比如说：准备手术的患者进行穿刺不符合伦理。第3个需要讨论的问题是研究结果的普适性，比如，External validity. Is your sample sufficiently representative of patients with advanced NSCLC? For example, the EGFR mutation rate was 42% in this study (much higher than the general belief of 15%-20% in most previous studies). If the higher rate does NOT reflect technical flaw, what was the cause? Does your patient sample ONLY reflect a sub-section of patients with advanced NSCLC? If yes, what sub-section, and does this limit the application of your findings to the medical practice by other physicians?这个研究中EGFR基因突变的比例为42%。而绝大多数的文献报道中比例为15%20%。显然，你的样本和别人看到的病人基本特征不同。因此，你的研究结果用在别人的患者上不见得好使。你必须说明几个问题。第一，肺癌患者EGFR基因携带率在东方人中高于西方人，我这个研究得到的42%检出率和先前他人在东方人上的研究一致，结果是靠谱的。第二，具体的突变位点在东西方肺癌患者上是否相同，如果基本一致，你的结果就可以推广到西方人中去；如果不一样，你的研究就缺乏普适性。事实上，这个研究中最常见的EGFR基因突变位点，和西方肺癌患者一致。因此，研究结果可以用到西方患者。这一点，作者必须演绎出来。第4个需要讨论的问题，你的研究结果对临床实践的价值是什么，有什么障碍？Clinical relevance/applicability:1.Assuming good scientific validity of this study, are the findings (consistent EGFR mutation status in small biopsy specimens vs. surgically resected specimens) applicable in clinical settings?Answer NO!Reason: “small biopsy specimens” included CT-guide percutaneous lung puncture (50%), bronchoscopy (40%), exfoliated cells from pleural effusion (7%), and lymph node puncture (3%).Question of clinical relevance is: could I use a specific type of the “small biopsy specimens to determine oncogene status of a specific patient? The primary analysis (small biopsy specimens vs. surgically resected specimens) does NOT provide an answer!Solution: a) break “small biopsy specimens” into the 4 types; b) due to small sample size of the exfoliated cells and lymph node puncture, the results regarding these 2 types of specimens are NOT reliable at all! Solution: present ONLY the first 2 types of specimens, andSEPARATELY.2. Assuming that small biopsy specimens could reliably reflect EGFR mutation status, is there any reason that dis-encourage you from conducting such an assay? For example, potential dissemination o