在上一篇文章里，介绍了投稿SCI论文时，如何写一个吸引人的标题。主要谈到SCI论文来自纯临床资料，没有任何生物学指标，重点强调了临床科研的重要性。如果有好思路、设计出好课题， 即使没有科研经费，仅仅是利用病历、或收集临床量表资料，也能做出非常精彩的课题，并发表系列高水平SCI文章，这是年轻学者们和医生护士们的一个非常好的努力方向，希望引起大家重视。
本篇文章是上一篇的姊妹篇，主要进一步阐述如何在临床资料的基础上，利用生物学指标，包括外周血中biomarkers和遗传学资料做分析、写文章，并写出吸引人的标题出来，起到画龙点睛的作用。同时谈及如何利用生物学指标，结合临床资料去做科研。请大家在仔细阅读此文的过程中，重点琢磨其中的科研思路，反复思考一下，学习和掌握科研思路才是最宝贵的。
二，生物学指标或基因型研究
我们常常在临床上采用case-control设计，检测某种或某几种精神病人的某项/某些生物学指标，同时与正常组对照，另外检测基因型的研究与此类似。我们相关文章的题目如下：
2.1. 单纯病人组vs 正常组（没有检测临床症状和/或认知）：
这种研究在临床上比较常见，就是纳入一组或几组病人+正常组，然后检测某项/几项生物学指标，比较单纯的case-control 研究，统计分析也比较简单。以我们的文章举例如下：
Altered serum levels of interleukin-3 in first-episode drug-naive and chronic medicated schizophrenia. Schizophrenia Research 2016; 176:196-200
Reduced plasma total antioxidant status in first-episode drug-naive patients with schizophrenia. Progress in Neuropsychopharmacology and Biological Psychiatry 2011；35:1064-1067
Decreased serum BDNF levels in chronic institutionalized schizophrenia on long-term treatment with typical and atypical antipsychotics. Progress in Neuropsychopharmacology and Biological Psychiatry 2009; 33:1508-1512
Increased serum S100B levels in chronic schizophrenic patients on long-term clozapine or typical antipsychotics. Neuroscience Letters 2009; 462:113-117
Increased serum S100B in never-medicated and medicated schizophrenic patients.Journal of Psychiatric Research 2010; 44:1236-1240
The novel oxidative stress marker thioredoxin is increased in first-episode schizophrenic patients. Schizophrenia Research 2009; 113:151-7
Decreased BDNF in serum of patients with chronic schizophrenia on long-term treatment with antipsychotics. Neuroscience Letters 2005; 382:27-32.
Decreased production of interleukin-2 (IL-2), IL-2 secreting cells and CD4+ cells in medication-free patients with schizophrenia. Journal of Psychiatric Research 2002; 36:331-336
Altered interleukin-3 serum levels in drug-naïve and neuroleptic-treated schizophrenic patients. Schizophrenia Research 2008；106:369-370
有三组：精神分裂症首发组+慢性组+对照组
2.2. 病人组分为亚组：
比如精神分裂症吸烟组vs 非吸烟组，自杀组vs 非自杀组，糖尿病组vs 非糖尿病组等，比较亚组之间的某项/些生物学指标。
Reduced serum TNF alpha level in chronic schizophrenia patients with or without tardive dyskinesia. Progress in Neuro-Psychopharmacology and Biological Psychiatry 2014; 54: 259–264
精神分裂症合并TD对非TD之间血清TNF alpha水平差异
Nicotine dependence and serum BDNF levels in male patients with schizophrenia. Psychopharmacology 2010；212:301-307
男性精神分裂症吸烟组与非吸烟组之间BDNF血清水平差异
Antioxidant enzymes and lipid peroxidation in different forms of schizophrenia treated with typical and atypical antipsychotics. Schizophrenia Research 2006; 81:291-300
不同的抗精神病药之间对抗氧化酶和脂质过氧化物的差异影响
Disrupted antioxidant enzyme activity and elevated lipid peroxidation products in schizophrenic patients with tardive dyskinesia. Journal of Clinical Psychiatry 2007; 68:754-760
精神分裂症合并TD对抗氧化酶和脂质过氧化物的影响
Lower serum cytokine levels in smokers than nonsmokers with chronic schizophrenia on long-term treatment with antipsychotics. Psychopharmacology 2008；201: 383-389
精神分裂症吸烟者的细胞 因子血清水平降低，因为用了复数，说明有多个细胞因子
Nicotine dependence, symptoms and oxidative stress in male patients with schizophrenia. Neuropsychopharmacology 2007；32:2020-2024
精神分裂症吸烟对症状和氧化应激指标的影响。这篇文章背后有个很精彩的故事，我在讲课中提到过，大家想起来了吗？
Altered IL-2, IL-6 and IL-8 serum levels in schizophrenia patients with tardive dyskinesia. Schizophrenia Research 2015; 162(1-3):261-268
精神分裂症合并TD 导致三个细胞因子改变。用了altered 这个词，而不是higher/increased 或者是lower/decreased, 说明什么呢？ 说明有高有低
Increased serum S100B levels in chronic schizophrenic patients on long-term clozapine or typical antipsychotics. Neuroscience Letters 2009；462:113-7
与典型抗精神病药相比，氯氮平增加S100B血清水平
Reduced status of plasma total antioxidant capacity in schizophrenia with tardive dyskinesia. Journal of Psychiatric Research 2010；44:1111-2.
2.3. 生物学指标+临床症状/认知功能：
这类研究在临床上也比较常见，就是纳入一组或几组病人+正常组，然后检测某项/几项生物学指标，同时病人还检测了临床症状，和/或者认知功能等。统计分析相对有些复杂。
Extensive white matter abnormalities and clinical symptoms in first episode and drug-naïve schizophrenia: a voxel-based diffusion tensor imaging study. Journal of Clinical Psychiatry 2016;77: 205–211
检测首发从未服药的精神分裂症DTI，同时测查PANSS，分析DTI变化与临床症状关系
Interleukin 18 and cognitive impairment in first episode and drug naïve schizophrenia versus healthy controls. Brain Behavior and Immunity 2013; 32:105-111
首发从未服药的精神分裂症检测血IL-18，同时检测PANSS, 分析IL-18与临床症状关系
Thioredoxin, a novel oxidative stress marker and cognitive performance in chronic and medicated schizophrenia versus healthy controls. Schizophrenia Research 2013;143:301-306
检测慢性精神分裂症硫氧还蛋白，同时测查认知功能, 分析它们之间的关系。因为硫氧还蛋白是在国际精神科第一次报道，比较少见的一个抗氧化蛋白，所以在题目中专门给出说明
Low BDNF is associated with cognitive impairment in chronic patients with schizophrenia. Psychopharmacology 2012；222(2):277-284
此类研究的典型题目：慢性精神分裂症BDNF降低，与认知损伤相关
Elevated plasma superoxide dismutase in first-episode and drug naive patients with schizophrenia: inverse association with positive symptoms. Progress in Neuropsychopharmacology and Biological Psychiatry 2012；36:34-38
此类研究的典型题目：首发未服药精神分裂症血浆SOD升高，与阳性症状相关
Decreased serum TNF-alpha levels in chronic schizophrenia patients on long-term antipsychotics: correlation with psychopathology and cognition. Psychopharmacology 2015;232:165-172
此类研究的典型题目：慢性长期服用抗精神病药的精神分裂症TNF alpha 降低，与临床症状和认知损伤相关
Decreased interleukin-10 serum levels in first-episode drug-naïve schizophrenia: Relationship to psychopathology. Schizophrenia Research 2014;156: 9-14
典型题目：首发未服药精神分裂症血浆IL-10降低，与临床症状相关
Increased interleukin-2 serum levels were associated with psychopathological symptoms and cognitive deficits in treatment-resistant schizophrenia. Schizophrenia Research 2015;169:16-21
典型题目：难治性精神分裂症IL-2 增高，与临床症状和认知损伤相关
Increased S100B serum levels in schizophrenic patients with tardive dyskinesia: Association with dyskinetic movements. Journal of Psychiatric Research 2010; 44: 429–433
精神分裂症TD组的S100B增高，而且与运动障碍症状相关
Low BDNF is associated with cognitive impairments in patients with Parkinson’s disease. Parkinsonism and Related Disorders 2016; 29:66-71
我带的神经内科的博士生，扩展我们的研究到帕金森氏病，从题目看，病人血BDNF降低，认知损伤，两者存在关联
Low BDNF is associated with cognitive deficits in patients with type 2 diabetes.Psychopharmacology 2013; 227(1):93-100
我带的内分泌学科的博士生，扩展我们的研究到糖尿病，从题目看，病人血BDNF降低，认知损伤，两者存在关联。看来不管是精神疾病，还是内科疾病，病人BDNF水平降低在认知功能损伤中起作用
Elevated interleukin-2, interleukin-6 and interleukin-8 serum levels in neuroleptic-free schizophrenia: association with psychopathology. Schizophrenia Research 57:247-258 (2002).
Elevated blood superoxide dismutase in neuroleptic-free schizophrenia: association with positive symptoms. Psychiatry Research 117:85-88 (2003).
Decreased levels of serum brain-derived neurotrophic factor in drug-naïve first-episode schizophrenia: relationship to clinical phenotypes. Psychopharmacology 207:375-80 (2009)
2.4. 病人组vs正常组：单个或多个基因型+临床症状/认知功能：
精神疾病的遗传学研究是研究热点，但随着GWAS等技术的发展，现在单纯的case-control研究很难发表文章了，但与临床症状、认知功能以及一些亚型结合，还能发表文章，尤其是能找到一些好的endophenotype 内表型，能发很好文章。另外如果同时检测了2个以上的基因多态性，需要特别的遗传统计软件，做haplotype分析。
The CCK-A receptor gene possibly associated with positive symptoms of schizophrenia. Molecular Psychiatry 2000；5:239-240
这是我的第一篇SCI文章，很久以前发表的，在英国的蔚军老师指导和帮助下发表，发现CCK受体基因与精神分裂症阳性症状相关
Tumour necrosis factor alpha polymorphism (-1031T/C) is associated with age of onset of schizophrenia. Molecular Psychiatry 2005; 10:897-899
TNF alpha 的这个多态性与发病年龄有关
BDNF polymorphisms are associated with schizophrenia onset and positive symptoms.Schizophrenia Research 2016; 170:41-47
BDNF多态性与精神分裂症发病和阳性症状相关，注意：polymorphisms多态性用了复数，说明不止一个, 统计方法也不一样了
BDNF polymorphisms are associated with cognitive performance in schizophrenia versus healthy controls. Journal of Clinical Psychiatry 2016; 77(8):e1011-e1018
BDNF多态性与精神分裂症认知功能相关。大家看到了吧，与上个题目很像，大家还记得我在公众号里曾经写的一篇文章里提到一个逆袭的故事吗？。本来这两篇文章的内容是放在一篇文章里，投稿Psychoneuroendocrinology，IF=4.7，已经被要求修回了，我以为修稿后应该能顺利被接受的，但未曾想最后竟然被拒稿了，反复思考后，决定拆分为这两篇，最后都被接受了，JCP 的IF=5.5，SR 的IF=4.5，影响因子总分增加一倍多，逆袭成功。
未完待续……
下一篇文章（第三篇）将从：
三，系统之间的交互作用
四，治疗前后临床疗效+生物学指标
等多个方面，继续详细介绍如何写一个好的题目，以及更多的科研思路。
注：本文是继上篇由张向阳教授撰写的《投稿SCI论文，如何写一个吸引人的题目+科研思路》的第二篇，主要谈对于包含生物学指标的文章，如何去写一个吸引人的标题，同时如何利用生物学指标，结合临床资料去做科研。
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