【经验】历时半年，经历7个杂志，处女作SCI终于接受!

如题：历时半年，经历7个杂志，处女作SCI终于接受。
分数不高，杂志一般，也来献献丑，给大家交流讨论，分享我的经验教训，包括审稿人意见、我的回信统统都端出来了。希望对您有那么一点点帮助和启发，也预祝正在投SCI的同仁们早日如愿。
不论对你有用否，看在我忙碌半天的望你多投投票，也希望斑竹给俺加加分，毕竟园子里好多帖子都要积分哦。
【第一个杂志】：TOXSCI（Toxicological Sciences）
【投稿理由】：自己课题与“毒理学”密切相关，这个杂志在毒理学中还算是比较有分量的，第一个投嘛，我等俗人也想“中大奖”。
【投稿日期】：2009年2月3日
【被拒日期】：2009年2月21日
【理由】：After carefully reading your paper, I have concluded that the focus of this paper does not match that of Toxicological Sciences, and I think the paper is better suited for another journal.（没有具体的原因）
【经验与教训】：没有具体的原因，我也不知道怎么改？？晕啊，准备改投其他杂志。

【第二个杂志】：BBRC（Biochemical and Biophysical Research Communications）
【投稿理由】：审稿周期短，看看自己的文章能否“意外”中奖，第一个投SCI，忐忑不安，不想等待太长时间；
【投稿日期】：2009年2月21日
【被拒日期】：2009年2月23日
【理由】：Comments:
1)  The English is not clear and concise.
2)  Avoid typo error such as, "upregrulated".
3)  In English we do not use plural noun as adjective. E.g., "threshold cycles (Ct) values".
【心理想法】：“审稿真的很快也”，英文看来真的很差！不过再投其它杂志，看看是内容如何？

【第三个杂志】：EHP（Environmental Health Perspectives）
【投稿理由】：既然TOXSCI毒理学方面的杂志不要，看看环境方面的的杂志
【投稿日期】：2009年2月23日
【被拒日期】：2009年2月26日
【理由】：Based on the recommendation of the consulting editors, a decision has been made to not seek an outside review for this particular manuscript. The advisory board suggest you try submitting your paper to Toxicology and Applied Pharmacology or Toxicology.
【心理想法】：这个杂志叫我投毒理学方面的，看来自己的文章写的有点“两不像”，咋办呢？

【第四个杂志】：TOXLET（Toxicology Letters）
【投稿理由】：再投投毒理学方面的杂志，看看！说不准，这个杂志会接受哦
【投稿日期】：2009年2月28日
【被拒日期】：2009年4月20日
【理由】：Reviewers' comments on your work have now been received. You will see that they are advising against publication of your work. Therefore I must reject it.
Reviewers' comments:

Reviewer #1: There is considerable interest in the possibility that prenatal exposure to certain chemicals, especially certain endocrine disruptors such as phthalates, might alter“***************” and thus cause later disease or disorders. This study has attempted (poorly) to address this “***************”to DEHP in utero. The authors claim that this exposure alters “***************” and expression of “***************” in offspring and that this may be related to cryptorchidism. Unfortunately, the study has several fundamental flaws which render the results largely uninterpretable. This is categorically not the way to address the important question in the first sentence. Specific points are:
1.  The authors claim their results are related to cryptorchidism, yet do not compare scrotal versus cryptorchid testes (see also point 2). So I am at a loss to understand why cryptorchidism is mentioned and how they can claim to relate “***************” to such a discrete event. Surely the aim would be to investigate “***************” of genes known to be related to testis descent?
2.  How was cryptorchidism defined? “***************”. Why was this dose chosen and why the mouse, as both seem completely inappropriate if the objective was to evaluate gene methyaltion changes in relation to cryptorchidism. As the inguinal canal remains patent in rodents, they can ascend their testes into the abdomen at times of stress and this has to be taken into account when making the assessment of cryptorchidism. For example, by ensuring that testes cannot be manoeuvred into the scrotum by palpation - if they can, the testes are probably scrotal. Testis position can be confirmed by testis weight, which will be greatly reduced in later puberty and in adulthood due to gross germ cell loss if testes are cryptorchid. Authors need to provide the testis weight data.
3.  If there has been massive germ cell loss due to cryptorchidism, then this means that testes from control and DEHP (cryptorchid testes) is not comparing like with like (somatic cells grossly over-represented in cryptorchid testes), meaning that no straightforward conclusions are possible. But were authors comparing normal versus cryptorchid testes?
4.  No data is actually shown for “***************”, so no conclusions can be made. For “***************” expression, how do the authors explain the age effects? For how many animals and litters was this determined (it looks like N=3, which is about 4-fold too small for any Taqman in my experience). Were testes scrotal or cryptorchid (see above)? In M&M, only mRNA isolation from fetal testes is mentioned, but no data is shown for fetal testes and no mention is made of postnatal testes.

【经验与教训】：查文献，尽量文章的补充立论依据。mRNA水平看来不合符英文要求，补充实验，加紧时间补蛋白水平（wb）

【第五个杂志】：JRD（Journal of Reproduction and Development）
【投稿理由】：一边补实验，一边另投他刊，看能不能（侥幸）被其他杂志接受
【投稿日期】：2009年4月28日
【被拒日期】：2009年5月30日
【理由】：The editor agrees with the comments of reviewers that while this paper is of merit because of a new method showing a change of “***************” in the rat testis, it lacks direct evidence, such as data concerning to “***************” of the specific genes, to indicate the relationship of “***************” and cryptorchidism. Therefore, the manuscript is required complete rewrite adding new data.
<Reviewers' comments>
Reviewer #1:

This paper is a good trial to relate “***************”. The results include the examination of “***************” and the expression of “***************”. I have a comment and question.

Major comments:
The weak point is that this report did not include any data concerning to “***************” of the specific genes. Assay of “***************” changes may be not sensitive for considering whether the changes were related with the occurrence of “***************”. DEHP has been reported to alter the expression of many genes as described in Discussions. If possible, I recommend authors check the “***************” status of these genes. The increased expression of “***************” induced by DEHP is very interesting, but it should be considered carefully. Does authors have any hypotheses that can explain the phenomenon?

Minor comments:
In the Fig.1, there was no asterisk in 10, 40, and 60d, but there were significant differences in the text (Page 8, Line 13). In the line 9 of page 8, "Fig. 1" may be "Fig. 1A and B". In the line 13, "(Fig. 1C)" should be at the end of the sentence.

Reviewer #2:

This manuscript proposes to “***************” by treatment of DEHP.

DEHP has been shown to display antiandorogen activity, and perinatal administration of DEHP inhibits fetal testicular production. It is generally accepted that the role of testosterone in normal testicular descent centers on the final, inguinoscrotal phase, and it is disorders of descent that account for most cases of cryptorchidism. Furthermore, a role of Insulin-like factor 3 in development of the gubernaculum and in the transabdominal phase of testicular descent. What purpose of this manuscript is?
This reviewer thinks that this paper demonstrates a new method showing a change of “***************” in the rat testis, but these results could not reveal the relationship of “***************” and cryptorchidism.
The author should rewrite this manuscript.

Introduction
As described above, the authors should rewrite “Introduction” and “Discussion”.

Materials and Methods
1. p5,3lines3-5 : DEHP was administerd to mice from GD12.5 to PND 3 as a described previous paper (Gray et al., 2000). But, Gray et al. used rats. Why the authors administered DEHP to mice the same period?
2. p5, lines 11- : What is 5mdC? What are dC,dG,dT snd dA in Fig.2?

Results
1. p9, lines 2-3 : “ but the -------------- PND 20” is not correct.

【经验与教训】：现在才发现，当初没看到“rewrite”，以为被拒，就再也没理了。

【第六个杂志】：BBRC（Biochemical and Biophysical Research Communications）
【投稿理由】：从2月到现在，请人改了“英文语法”，感觉逻辑强多了，但是讨论还是不足，总觉得很泛泛，不深入。但自己也不知道怎么改，投投杂志，说不定审稿人能给我很好的意见。虽说这个做法有点不地道，有点卑微，但作为没有国际友人，也没有“牛人”相助的我，也算下下之策吧。
【投稿日期】：2009年6月1日
【被拒日期】：2009年6月8日
【理由】：After a careful review of your manuscript, I am afraid that we are not able to accept it for publication in BBRC. As you know, this is a rapid communication journal and not all submissions, regardless of their merit, are suitable for this format. Our standards are increasingly high, and in fact, approximately 80% of submissions do not meet our criteria. In this case, we have found that your manuscript represents a good beginning, but the amount of new information at this stage of the work does not warrant the rapid advance publication provided by this journal.

(Comments)
The authors investigated the effect of maternal exposure to DEHP on the “***************” in the testes of the fetuses. It was found that DEHP administration to pregnant rats increased “***************” and elevated “***************” expression in the testes of the fetuses. The authors propose that changes in “***************” play an important role in abnormal testicular function caused by DEHP.
Effect of DEHP on “***************” in animal tissues has been reported before. This paper confirms the effect of DEHP on the “***************” in the testes of fetal animals, and suggests its correlation with the testicular dysgenesis syndrome. However, this study is apparently in the beginning stage. Some more study is needed to confirm the physiological significance of the observations. Alterations in “***************” must be examined in other tissues of the fetuses. The molecular mechanism of the DEHP-induced stimulation of the expression of “***************” must be studied. The amount of DEHP administered to the female animals seems to be too high compared with the concentration of DEHP in the polluted environment. The dose effect of DEHP on “***************” must be examined. We regret to conclude that the amount of new information at this stage of the work does not warrant the rapid publication of this paper in BBRC.

I am sorry to convey this negative decision; I know it is a disappointment. However, I thank you for the opportunity to see your work, and I hope you will consider submitting future manuscripts to BBRC.
【经验与教训】：研究深度不高，创新性不强。针对意见，逐一修改，再改投其他杂志

【第七个杂志】：BCPT (Basic & Clinical Pharmacology & Toxicology)
【投稿理由】：毒理学，基础，临床。既然自己条件所限，做的不深，也不很创新。打打擦边球，投个沾边，但都不是非常专业的杂志吧。
【投稿日期】：2009年6月8日
【revised日期】：2009年7月9日
【理由】：The manuscript has now been evaluated by two external experts in the field as well as by the editor. A number of points of criticism were raised during the evaluation and I therefore regret to inform you that the manuscript is not acceptable for publication in its present form. If you feel that you can adequately address the criticisms outlined in the reviewers' reports, I would be willing to reconsider a thoroughly
revised manuscript.
Review:
Date of review:2009-07-06
Comments to authors:
The paper by Wu et al deals with the impact of prenatal exposure to Di-2-(ethylhexyl) phthalate (DEHP) on “***************” and “***************” expression in testes of foetal mice. The find,in exposed animals, a more than 10% relative increase in the “***************” and also a rise in the expression of some of the “***************”.
This is a straight forward paper dealing with an issue which is interesting and relevant from a biological and environmental point of view – the effect of prenatal phthalate exposure on male gonadal functiom. The study design looks to be OK and the interpretation of data and conclusions are proper and well balanced in relation to the findings made by the authors. The manuscript is well written

I have only a few minor comments of rather “cosmetic” character:

1)  The authors should be more clear in the Methods part of the paper
with describing the tissue (=testes) used for “***************”studies and for “***************” expression assay;
2)  Furthermore, the number of animals used for testing should be given – both for the controls and for the exposed group;
3)  Was any dose-response experiment done?
4)  Were both testes from the same animal tested? In such case, are those data treated as independent experiments?

Review:
Date of review:2009-07-07
Comments to authors:
This manuscript by Wu et al reports the effects of maternal DEHP treatment on the “***************” status in the male embryo. The authors found a 0.5% increase in global “***************” using HPLC. They have also found an increase in the mRNA levels of “***************” in DEHP treated testis.

This article provides very minimal information. A list of concerns is
provided below.

Specific points:

1. Experimental design issue: First line of page 5: Maternal exposure to DEHP was initiated at GD12.5 which is rather late in rat since the sex differentiation process, known to be targeted by DEHP in vivo, initiates prior to that.

2. Page 5, first line of the HPLC description: it is mentioned that high molecular weight genomic was extracted using… “***************” from what? Whole embryo? Fetal testis?

3. The global increase in the “***************” status observed in DEHP treated animals seems very small (from 3.35 to 3.82% = 0.47%). Are there evidence in the literature that this type of increase is known to have effects on gene expression? This must be discussed.

4. The increase in mRNA levels for the “***************” cannot be extrapolated to indicate an increase in protein levels or activity. The authors should therefore determine “***************” activity in testis extracts from DEHP treated animals.

5. Page 10, lines 4-6: “It is well known that DEHP…..” If it is well
known, some references must be provided.

6. Page 10, lines 10-11: “(3) whether “***************” and “***************”participate in mice in TDS”. The authors have not examined that. Must be removed.

7. Page 10, lines 18-20: “In contrast to a study…” The authors do not
provide any explanation for this discrepancy. This important difference
should be discussed.

8. The Discussion section is not in depth and sounds more like an
Introduction. There are also repetitive sections.

【经验与教训】：针对问题，查文献，认真修改。具体如下：
Dear Editor and Reviewers:
Thank you very much for your letter and the comments from the referees about our paper (Manuscript title: “***************”). Overall the comments have been fair, encouraging and constructive, and we have learned much from it.
I am sure that the reference list is organized correctly, that figures and tables are on separate sheets. Furthermore, the relevant regulations had been made in the original manuscript according to the comments of reviewers, and the major revised portions were marked in red bold. We also responded point by point to each reviewer comments as listed below, along with a clear indication of the location of the revision.
Hope these will make it more acceptable for publication.
List of Major Changes:
1) Methods of HPLC and “***************” assay are clearer.
2) Added protein levels of “***************”.
3) Discussion had been rewritten.
Response to Reviewer 1:
Thanks for your comments on our paper. We have resubmitted our paper according to your good advice:
1) In method parts, we described the the tissue (testes) used for “***************” studies and for “***************” expression assay more clearly.
2) Number of animals in each group was given.
3) Absorption, metabolism, and distribution of DEHP is almost linear up to 750mg/kg when given in oil, therefore, solubility is not exceeded and the doses employed. We also see effects at much lower doses. We use large doses to ensure a high incidence of malformations are induced to study in our model rather than the smaller doses used to determine noael’s and impact risk assessment. Thanks for your advice. Next, we will also study whether changes of “***************”and “***************” expression exist at low doses.
4) Both testes from the same animal were tested: one was used for studied level of “***************”, the other was used for “***************” expression.

Response to Reviewer 2:
We very much appreciate your careful reading of our manuscript and valuable suggestions. After carefully studying your comments and advice, we have made corresponding changes to the paper.
1) As you known, standard teratology studies using exposure on gestation days (GD) 6-15 had shown effects on development only associated with toxicity to the dam and in general high (approximately 1g/kg/day) exposure levels (Field et al., 1993; Ema et al., 1993; Hellwig et al., 1997; Waterman et al., 1999). Interestingly, these standard teratological investigations did not expose pregnant dams through the window required for reproductive development (GD12-19). Research is showing first that there is a sensitive time window for phthalate exposure, approximately between embryonic Days 12 and 19 (Barlow et al., 2003). Secondly, some of the earliest detectable events involve altered gene expression specifically of Leydig cell products (including INSL3), though since all three major testicular cell types (Leydig cells, Sertoli cells and germ cells) are mutually interacting at this time (O'Shaughnessy et al., 2006; Hu GX, et al., 2009; Hutchison GR et al.,2008; and Kasahara E, et al., 2002).
2) Genomic DNA from Fetal testis was used for “***************” studied by “***************”.
3) Through absolute increase in the “***************” status observed in DEHP treated animals seems very small (from 3.35 to 3.82% = 0.47%), but a more than 10% relative increase in the global “*********”. Kun-Lin reported that Murine cerebral endothelial cell treated with Amyloid-β, the relative folds of the “***************” was reduced to 0.6663 ± 0.0201.
4) Added protein levels of “***************”.
5) Page 10, lines 4-6: “It is well known that DEHP…..”, we had detected this sentence.
6) Page 10, lines 10-11: “(3) whether “***************” and “***************” participate in mice in TDS”. The sentence had been moved.
7) Page 10, lines 18-20: “In contrast to a study…”. We had added discussion about that.
8) Discussion had been rewritten.

Reference:
Barlow NJ, et al. Quantitative changes in gene expression in fetal rat testes following exposure to di(n-butyl) phthalate. Toxicol Sci, 2003, 73(2):431-441.
Ema M, et al. Teratogenic evaluation of di-n-butyl phthalate in rats. Toxicol Lett, 1993, 69(2):197-203.
Field EA, et al. Developmental toxicity evaluation of diethyl and dimethyl phthalate in rats. Teratology, 1993, 48(1):33-44.
Hellwig J, et al. Differential prenatal toxicity of branched phthalate esters in rats. Food Chem Toxicol, 1997, 35(5):501-512.
Hu GX, et al. Phthalate-induced testicular dysgenesis syndrome: Leydig cell influence. Trends Endocrinol Metab, 2009,20(3):139-145.
Hutchison GR et al. Sertoli cell development and function in an animal model of testicular dysgenesis syndrome. Biol Reprod, 2008, 78(2):352-360.
Kasahara E, et al. Role of oxidative stress in germ cell apoptosis induced by di(2-ethylhexyl)phthalate. Biochem J, 2002, 365(Pt 3):849-856.
Kun-Lin chen, et al. The epigenetic effects of amyloid-β1–40 on global DNA and neprilysin genes in murine cerebral endothelial cells. Biochem Biophys Res Commun, 2009, 378(1):57-61.
O'Shaughnessy PJ, et al. The foetal Leydig cell-- differentiation, function and regulation. Int J Androl, 2006, 29(1):90-95.
Waterman SJ, et al. Developmental toxicity of di-isodecyl and di-isononyl phthalates in rats. Reprod Toxicol, 1999, 13(2):131-136.
Thank you, again!
I look forward to hearing from you.
Yours sincerely
【再次revised日期】：2009年8月14日
【理由】：Thank you very much for submitting the above manuscript to Basic &Clinical Pharmacology & Toxicology. It has been reviewed by two external
experts in the field as well as by the editor. Your manuscript is
pertinent and of interest but the reviewers have raised some points of
criticism that need to be addressed before your manuscript can be
accepted for publication, these are detailed in the reviewers' reports.
【理由】：Review:
Date of review:2009-08-13
Comments to authors:
The manuscript has been revised acording to the suggestions given and I do not have more unresolved points of criticism.

Review:
Date of review:2009-08-04
Comments to authors:
The authors have significantly improved the manuscript. I have two
concerns:

1. page 11, line 6: "In contrast to our results, Pogribny observed that
exposure to DEHP had no effect on the “***************”" No explanation is provided for this discrepancy. This was an original comment to which the authors have not responded.

2. The authors have now added expression of “***************” at the protein levels. They indicate that protein levels are increased in DEHP-treated animals (Results and Discussion sections). Figure 3A however shows the complete opposite: a potent reduction of “***************” levels in DEHP-treated animals. This issue must be resolved.
【心理】：要命啊：第一个问题第一次修回时怎么会忘记了哈？第二个错误就大了：居然把WB条带标注时：实验组和正常值正好弄反了。幸亏审稿人还比较慈祥，没有把文章毙掉。查文献，找依据，认真补充分析自己文章和别人的差异；向编辑和审稿人说明自己不小心标注错误了。具体如下：
Dear Editor and Reviewers:
We very much appreciate your help and valuable suggestions for our paper (Manuscript title: “***************”).
I am sure our paper is followed according to rules for organization of manuscripts, and the major revised portions were marked in red bold.
Hope these will make it more acceptable for publication.
List of Major Changes:
1) Added explanation about the differnt results between Pogribny’s and ours: We can speculate on 2 possible explanations. It is possible that animals were exposed to DEHP at different time Periods. In Pogribny’s research, rats were exposed to DEHP at 12 weeks of age, but our animals were exposed to DEHP in utero. The developing embryo and fetus are highly sensitive to their environments. More important, “***************” occurs early in the development of primordial germ cells in the mouse. This “***************” is completed by GD 13 to 14 in both male and female germ cells (Monk et al., 1987; Reik et al., 2001; Surani, 1998); and re”*********” takes place several days later, at GD15 to GD16 (Brandeis et al., 1993; Coffigny et al., 1999; Kafri et al., 1992). So in this period, “***************” and “***************” are more easily altered by DEHP. It is also possible that animals were exposed to DEHP at different doses. Compared to 500 mg/kg/day, 1.2% DEHP in dietary exposure is too low to have any appreciable effect on the “***************”.)
2) Corrected Figure 3A. I am very sorry about the error in Figure 3A. Lane 1 refers to DEHP-exposed, and lane 2 refers to control. Thank you very much for your help, and I hope you can give me a chance to correct it.
Reference:
Brandeis, M., Kafri, T., Ariel, M., Chaillet, J.R., McCarrey, J., Razin, A., and Cedar, H. (1993). The ontogeny of allele-specific “*********” associated with imprinted genes in the mouse. EMBO J 12, 3669-3677.
Coffigny, H., Bourgeois, C., Ricoul, M., Bernardino, J., Vilain, A., Niveleau, A., Malfoy, B., and Dutrillaux, B. (1999). Alterations of DNA “*********” patterns in germ cells and Sertoli cells from developing mouse testis. Cytogenet Cell Genet 87, 175-181.
Kafri, T., Ariel, M., Brandeis, M., Shemer, R., Urven, L., McCarrey, J., Cedar, H., and Razin, A. (1992). Developmental pattern of gene-specific DNA “*********” in the mouse embryo and germ line. Genes Dev 6, 705-714.
Monk, M., Boubelik, M., and Lehnert, S. (1987). Temporal and regional changes in DNA “*********” in the embryonic, extraembryonic and germ cell lineages during mouse embryo development. Development 99, 371-382.
Reik, W., Dean, W., and Walter, J. (2001). Epigenetic reprogramming in mammalian development. Science 293, 1089-1093.
Surani, M.A. (1998). Imprinting and the initiation of gene silencing in the germ line. Cell 93, 309-312.

Thank you, again!
I look forward to hearing from you.

Yours sincerely
【接受日期】：2009年8月17日
Dear Dr **
It is a pleasure to inform you that the above manuscript is acceptable
for publication。
【总的感觉】：（1）文章写好后，最后请相关专业的专家看看，毕竟我们自己只考虑到很小的一方面；
（2）针对审稿专家的意见，好好查文献，找依据，充实文章的理论基础；
（3）及时补做实验，如果是标书课题，不要局限于标书，与时俱进；
（4）只要不灰心，总有杂志会相中你的文章，杂志社也是“青菜萝卜各有所爱”，相信付出就有回报，你一定能发SCI.

【ps】：很多同仁可能误解了，以为我一直在乱投。其实只有前面几个杂志是“撞”。
每次投出去后，我会根据前面审稿人意见反复修改。经过一次一次地修改，每次都有进步。现在电脑上的版本就有十几个。
我想说：正是自己不懈努力的修改，才最终被接受。