1.所有问题必须逐条回答。
2.尽量满足意见中需要补充的实验。
3.满足不了的也不要回避，说明不能做的合理理由。
4.审稿人推荐的文献一定要引用，并讨论透彻。
以下是本人对审稿人意见的回复一例，仅供参考。
续两点经验：
1. 最重要的是逐条回答，即使你答不了，也要老实交代；不要太狡猾，以至于耽误事；
2. 绝大部分实验是不要真追加的，除非你受到启发，而想改投另外高档杂志----因为你既然已经写成文章，从逻辑上肯定是一个完整的 “story” 了。
以上指国际杂志修稿。国内杂志太多，以至于稿源吃紧，基本没有退稿，所以你怎么修都是接受。
我的文章水平都不高，主要是没有明显的创新性，也很苦恼。但是除了开始几篇投在国内杂志外，其他都在国际杂志（也都是SCI）发表。以我了解的情况，我单位其他同志给国内杂志投稿，退稿的极少，只有一次被《某某科学进展》拒绝。究其原因，除了我上面说的，另外可能是我单位写稿子还是比较严肃，导师把关也比较严的缘故。
自我感觉总结（不一定对）：
1）国内杂志审稿极慢（少数除外），但现在也有加快趋势；
2）国内杂志编辑人员认真负责的人不多，稿子寄去后，少则几个月，多则一年多没有任何消息；
3）国内杂志要求修改的稿子，如果你自己不修，他最后也给你发；
4）国外杂志要求补充实验的，我均以解释而过关，原因见少帖）。还因为：很少杂志编辑把你的修改稿再寄给当初审稿人的，除非审稿人特别请求。编辑不一定懂你的东西，他只是看到你认真修改，回答疑问了，也就接受了（当然高档杂志可能不是这样，我的经验只限定一般杂志（影响因子1-5）。
欢迎大家批评指正。
我常用的回复格式:
Dear reviewer:
I am very grateful to your comments for the manuscript. According with your advice, we amended the relevant part in manuscript. Some of your questions were answered below.
1）
2）
....
引用审稿人推荐的文献的确是很重要的，要想办法和自己的文章有机地结合起来。
至于实验大部分都可以不用补做，关键是你要让审稿人明白你的文章的重点是什么，这个实验对你要强调的重点内容不是很必要，或者你现在所用的方法已经可以达到目的就行了。
最后要注意，审稿人也会犯错误，不仅仅是笔误也有专业知识上的错误，因为编辑找的审稿人未必是你这个领域的专家。只要自己是正确的就要坚持。在回复中委婉地表达一下你的意见，不过要注意商讨语气哦！
我得回复格式是这样的：
Dear Professor xx:
Thank you very much for your letter dated xxx xx xxxx, and the referees’ reports. Based on your comment and request, we have made extensive modification on the original manuscript. Here, we attached revised manuscript in the formats of both PDF and MS word, for your approval. A document answering every question from the referees was also summarized and enclosed.
A revised manuscript with the correction sections red marked was attached as the supplemental material and for easy check/editing purpose.
Should you have any questions, please contact us without hesitate.
然后再附上Q/A，基本上嘱条回答，写的越多越好（老师语）。结果修改一次就接收了：）
我的回复，请老外帮忙修改了
Dear Editor:
Thank you for your kind letter of “......” on November **, 2005. We revised the manuscript in accordance with the reviewers’ comments, and carefully proof-read the manuscript to minimize typographical, grammatical, and bibliographical errors.
Here below is our description on revision according to the reviewers’ comments.
Part A (Reviewer 1)
1. The reviewer’s comment: ......
The authors’ Answer: .....
2. The reviewer’s comment: ......
The authors’ Answer: .....
...
...
Part B (Reviewer 2)
1. The reviewer’s comment: ......
The authors’ Answer: .....
2. The reviewer’s comment: ......
The authors’ Answer: .....
...
...
Many grammatical or typographical errors have been revised.
All the lines and pages indicated above are in the revised manuscript.
Thank you and all the reviewers for the kind advice.
Sincerely yours,
***
一个回复的例子(已接收)
Major comments:
1. The authors need to strengthen their results by including MMP secretion, and tran-matrigel migration by a positive control progenitor cell population i.e. enriched human CD34 cells obtained from mobilized PBL, since this is a more clinically relevant source of CD34 cells which has also been shown to secrete both MMP-9 and MMP-2 (ref. 11). CD34 enriched cells from steady state peripheral blood which also secrete MMPs are also of interest.
2. In fig 1C please specify which cell line represents MMP-negative cells. This needs to be clarified, as well as a better explanation of the method of the protocol.
3. The ELISA results are represented as "fold increase" compared to control. Instead, we suggest that standards should be used and results should be presented as absolute concentrations and only then can these results be compared to those of the zymography.
4. When discussing the results, the authors should distinguish clearly between spontaneous migration vs chemotactic migration. Furthermore, the high spontaneous migration obtained with cord blood CD34 cells should be compared to mobilized PBL CD34 enriched cells and discussed.
5. The authors claim that the clonogenic assay was performed to determine the optimum concentration for inhibition of MMP activity by phenanthroline and anti MMP-9 mAb, however they should clarify that this assay can only determine the toxicity of the inhibitors and not their optimal inhibitory concentrations.
Minor comments:
1. There are many spelling and syntax errors, especially in the results and discussion, which need correction.
a. Of special importance, is the percent inhibition of migration, which is described as percent of migration. i.e. pg 7:"Migration of CB CD34 was reduced to 73.3%?" Instead should read "Migration of CB CD34 was reduced by 73.3%?"
b. The degree symbol needs to be added to the numbers in Materials and methods.
2. It would be preferable to combine figure 1A and B, in order to confirm the reliability of fig. 1B by a positive control (HT1080).
Answer to referee 1 comment:
1. Mobilized peripheral blood is a more clinical source of CD34+ cells, so it is necessary to compare the MMP-9 secretion and trans-migration ability of CB CD34+ cells with that of mobilized PB CD34+ cells. However, we couldn't obtain enough mobilized PB to separate PB CD34+ cells and determine the MMP-9 secretion and migration ability, so we couldn’t complement the study on PB CD34+ cells in this paper. Results obtained by Janowska-Wieczorek et al found that mobilized CD34+ cells in peripheral blood express MMP-9. Furthermore, Domenech’s study showed that MMP-9 secretion is involved in G-CSF induced HPC mobilization. Their conclusions have been added in the discussion. In our present study, our central conclusion from our data is that freshly isolated CD34+ stem/progenitor cells obtained from CB produce MMP-9.
2. MMP-9 negative cell used in fig 1C was Jurkat cell. In zymographic analysis, MMP-9 was not detected in the medium conditioned by Jurkat cell. To exclude that the contaminating cells may play a role in the observed MMP-9 production, we screened the media conditioned by different proportion of CB mononuclear cells with MMP-9 negative cells by zymography. This result may be confusion. Actually, only by detecting the medium conditioned by 2X105 CB mononuclear cells (MNC)/ml (since the purities of CD34+ cell are more than 90%), it could exclude the MNC role. In the revised manuscript, we only detected MMP-9 activity and antigen level in the medium conditioned by 2X105 CB mononuclear cells (MNC)/ml. There is no MMP-9 secretion be detected in the medium conditioned by 2X105 CB MNC/ml. It excluded the possibility that the MMP-9 activity in CB CD34+ cells conditioned medium is due to the contamination by MNC.
3.In this revised paper, we have detected the MMP-9 antigen levels by using commercial specific ELISA kits (R&D System, sensitivity, 0.156ng/ml). Recombinant MMP-9 from R&D System was used as a standard. The results are expressed in the absolute concentration. The absolute concentration result has been added in the paper. As shown in Fig2, MMP-9 levels were detectable in both CB CD34+ cell conditioned medium and BM CD34+ cell conditioned medium. However, MMP-9 level was significantly higher in CB CD34+ cell conditioned medium than in BM CD34+ cell conditioned medium (0.406±0.133ng/ml versus 0.195±0.023ng/ml). Although gelatinolytic activity was not detected in media conditioned by CD34+ cells from BM, sensitivity of ELISA favors the detection of MMP-9 antigen in the BM CD34+.
4. In our study, to establish the direct link between MMP-9 and CB CD34+ cells migration, we only determined the role of MMP-9 in spontaneous migration of CB CD34+ cells, but not in chemotactic migration. Actually, regulation of hematopoietic stem cell migration, homing and anchorage of repopulation cells to the bone marrow involves a complex interplay between adhesion molecules, chemokines, cytokines and proteolytic enzymes. Results obtained by the groups of Voermans reveal that not only the spontaneous migration but also the SDF-1 induced migration of CB CD34+ cells is greatly increased in comparison to CD34+ cells from BM and peripheral blood.
5. CD34+ cells we obtained in each cord blood sample were very limited. It is not enough to screen the inhibitors concentrations to select the optimal inhibitory concentrations. In the blocking experiments, based on the concentrations used by others and the manufacturer's recommendation, we then determined the inhibitors concentrations by excluding the toxicity of the inhibitors in that concentration, which was determined by clonogenic assay.
Minor comments:
1.The spelling and syntax errors have been checked and corrected.
2.Since the results in figure 1A and B were obtained from two separated and parallel experiments, it is not fitness to combine two figures.
