有次审稿，一个审稿人给的意见是增加两篇参考文献（估计也就是审稿人自己的文章啦），结果作者在回复中写到，making a reference is not charity！看到之后我当时就笑喷了，可以想象审稿人得被噎成什么样。正如大家所想的那样，这篇稿子理所当然的被拒了，虽然后来经编辑调解改成了major revision，但毕竟耽误的是作者自己的时间不是？
写答复信的唯一目的是让编辑和审稿人一目了然的知道我们做了哪些修改。因此，所有的格式和写法都要围绕这一目的。一般来说可以把答复信分成三部分，即List of Actions, Responses to Editor, Responses to Reviewers。第一部分List of Actions的作用是简明扼要的列出所有修改的条目，让编辑和审稿人在第一时间对修改量有个概念，同时它还充当着修改目录的作用，详见下面的例子。剩下的两部分是分别对编辑和审稿人所做的答复，格式可以一样，按照“意见”－“argue”（如果有的话）－“修改”这样逐条进行。清楚醒目起见，可以用不同字体分别标出，比如“意见”用italic，“argue”正常字体，“修改”用bold。
LOA1: The revised manuscript is double spaced.
LOA2: A discussion on novelty of this work and a comparison with A and B have been added in page 3.
LOA3: A paragraph has been added in page 5 to further explain the algorithm ***.
LOA4: Explanations of the legend of Figure 3 have been added in page 7.
LOA5: Figure 2 has been enlarged.
LOA6: All typos have been removed.
We have double spaced the text throughout the revised manuscript, see LOA1.
Thank you for pointing this out. A and B’s research groups have done blablablabla. However, the focus of our work is on blablablabla, which is very different from A and B’s work, and this is also the major contribution of our work. We have added the following discussion on this issue in our revised manuscript, see LOA2.
We have added the following discussion to further explain algorithm ***, see LOA3.
We have added the following explanations of the legend of Figure 3, see LOA3.
We have enlarged Figure 2, see LOA 4.
We have removed all typos, see LOA5.
2，绝大部分实验是不要真追加的，除非你受到启发，而想该投另外高档杂志----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。
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.
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.
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.
1. The reviewer’s comment: ......
The authors’ Answer: .....
2. The reviewer’s comment: ......
The authors’ Answer: .....
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.
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 fig1Cplease 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.
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 figure1Aand 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 fig1Cwas 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.
http://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 inspontaneous 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.
1.The spelling and syntax errors have been checked and corrected.
2.Since the results in figure1Aand B were obtained from two separated and parallel experiments, it is not fitness to combine two figures.
Reply to the comments on JBMR-A-05-0172
Reference #10 is missing from the Introduction but used much later in the manuscript. Should these be in order used in manuscript?
The missing reference has been added into the revised manuscript.
What is the sample size for all tests performed?
The sample size for drug release and PCL degradation tests was 3.0×3.0 cm2, with a thickness of about0.1mmand a weight of about 40mg. This dada have been added into the revised manuscript.
Figure 7. There is no scientific evidence presented in the TEM figure to convince this reviewer of sub-jets. This statement on Page 9 cannot be made without clear evidence during the jet formation/separation. Figure 7 is just a large fiber and small fiber fused together, no other conclusion than this can be made.
Necessary change in the statements has been made in the revised manuscript. as well as in the referred figure accordingly.
Table 3: Need standard deviation for all values reported not just for a select few.Equation after Table 3 not necessary. Just reference method used.
Page 11: "faster weight loss" What was the sample size? Where is the statistical analysis of this data? This reviewer does not see a significant difference in any of the data presented, thus weight loss would be considered equivalent.
Although not too much difference was seen, the conclusion that “the GS/PCL membrane exhibited a relatively faster weight loss compared with the RT/PCL membrane” was indeed applicable through “one-way analysis of variance (ANOVA)” analysis. Following the reviewer’s comment, a new sub-section has been added to the manuscript. to address the statistical analysis for the data.
Page 12: What is the sample size for release data? Looks like results based on a sample size of one? Need stand deviations on the data presented in Figure 11. Why wasn t release
performed and compared for all electrospun conditions investigated otherwise?
Three repeated tests were performed for each set of measurements and the resulting data were averaged. As stated in the revised manuscript, each sample had a square area of 3?3cm2 with a slightly different thickness.Standard deviations have been added to the data shown in Fig. 11.The present manuscript. aimed to show that medical drugs can be encapsulated in ultrafine fibers through a co-axial electrospinning process. The drug release data intended to show that the encapsulation was successful. We did not consider any specific application in this preliminary paper, and in fact the two drugs were just chosen as model illustration. As such, there seemed not necessary to perform. release experiments for all of the membranes electrospun with different conditions (i.e. the core concentrations)
Table 3: Yang s or Young s Modulus (page 10 says Young s).
Figure 11: What is the % release, not just concentration. Why just this small sample of release data? Where is the release data for the other conditions?
Unfortunately, we did not measure the amount of the shell material in obtaining the composite nanofibers. Namely, the flow rate of the shell solution during the electrospinning was not accurately controlled using an injecting pump. Hence the % release was not applicable. Please refer to the previous reply related to Page 12 and Figure 11 for the remaining comments.We acknowledge the reviewer’s comments and suggestions very much, which are valuable in improving the quality of our manuscript.
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Subject: Clinical Chemistry -- Manuscript. Decision
RE: Clinical Chemistry MS ID# CLINCHEM/2002/036332
Your manuscript. has been examined by two expert reviewers. Please visit http://submit.clinchem.org to view their comments. For the reasons detailed in these comments, we cannot accept this manuscript. for publication in Clinical Chemistry in this form. Also, your Reference 28 is not formatted properly. Our Information for Authors will offer assistance with journal style; it can be found athttp://www.aacc.org/ccj/infoauth.stmWe would consider a revised version that takes these criticisms into account. If you should resubmit the paper I would also ask that you have several English speaking colleagues proof the paper for grammar and composition. Additionally, be sure to provide a detailed point-by-point response to the comments of the reviewers. Failure to do so will delay consideration of the revised manuscript.Prior to publication we require copyright releases signed by all authors. Our Authors Assurances and Assignment of Copyright form. can be downloaded from http://www.aacc.org/ccj/auth_assure02.pdf. Please note that all authors must sign both sections of the form. (a signature on the lower section means that all conflicts of interest have been disclosed even if there are none). Send the completed form. to us by FAX (434-979-7599).
P.S. You will find your revised manuscript. can be uploaded in your "Submit a Revision" queue at http://submit.clinchem.org. Please do not begin the submission of your revised manuscript. until you are ready to submit the entire manuscript. A checklist regarding requirements for submission can be found athttp://www.aacc.org/ccj/manuscript_check02.pdf. Figures must be uploaded as Image Files in .tif or .eps files at 600 DPI. Alternatively, you may use PowerPoint software for figures but fonts must be embedded and only one image per slide, one slide per file. When uploading the revised version, please be sure to include in the "Response to Reviews" field a point-by-point list of all changes made, or your rebuttal, in response to each of the reviewers?
P.P.S. Please note that if your manuscript. has color figures, the authors are expected to bear the cost of printing them, except in the case of invited papers. The charges for these figures are $1500 for the first color figure or part of a figure, and $500 for each additional color figure or part of a figure. Authors will be billed for color publication costs unless they request that their figures be printed in black and white.
1）实验的有效性和深度（at least for a few substances of major importance
detection limits, cut-off values and specificity should have been studied. Also the description of the assay principle is not quite clear）
2）语言问题（The English text would have to be substantially improved）
3）核心的技术问题（A cut-off value is given for MOL but the dimension is missing. In the discussion various anecdotic reports are given for which no data are presented under results.） 重新验证讨论。
Your revised manuscript. has been examined by the original two reviewers, plus a recommended third reviewer with special expertise in this area. Please visit http://submit.clinchem.org to retrieve their comments. The three reviewers find merit in the work, but have numerous constructive suggestions（别害怕，其实就是几个小问题）. Please consider these suggestions carefully and prepare an improved version that addresses these concerns. I have also noted that there are several color figures included in the paper, which seem to be useful only in color. Please be aware that (should your paper be accepted for publication) authors are expected to pay the costs for publication of color figures. The charge for the first color figure is $1500; subsequent figures, or parts of figures, are $500 each. Of course, if you wish to submit alternate figures in black and white (or grayscale), you may do so.
P.S. You will find your revised manuscript. can be uploaded in your "Submit a Revision" queue at http://submit.clinchem.org. A checklist of requirements for submission can be found at http://www.aacc.org/ccj/manuscript_check02.pdf. When uploading the revised version, please be sure to include in the "Response to Reviews" field a point-by-point list of all changes made, or your rebuttal, in response to each of the reviewer suggestions. Also, please submit copyright releases for all authors. Our Authors Assurances and Assignment of Copyright form. can be downloaded from http://www.aacc.org/ccj/auth_assure02.pdf. Please note that all authors must sign both sections of the form. Send the completed form. to us by FAX (434-979-7599).P.P.S. For figures, please submit .tif files that have a minimum resolution of 600 DPI; the width and height of the Pixels should be about 4200 x 4200. Alternatively, you may use PowerPoint for figures, but each .ppt file may contain only one slide and fonts must be embedded.
Thank you for your revised manuscript. It is acceptable and will be processed for publication. Please note that I edited the paper to remove all text related to Figure 6. The structures of the drugs are available to anyone who wants to look them up. Thus this figure will not be in the proofs that you receive.
If page proofs are returned promptly, your paper is scheduled to appear in the Oct issue.之前电子版会先在网上发布Papers in press are posted online 2-6 weeks before the issue date. Issues are scheduled to be mailed to subscribers and appear on the Internet before the first day of the issue month. The electronic version (http://www.clinchem.org) is published at Stanford University s HighWire Press, where your article will be linked electronically to and from PubMed and directly to and from over 340 other journals that are on-line at Stanford.当然还要转移版权Prior to publication we require copyright releases signed by all authors. Our Authors Assurances and Assignment of Copyright form. can be downloaded from http://www.aacc.org/ccj/auth_assure02.pdf. Please note that all authors must sign both sections of the form. (a signature on the lower section means that all conflicts of interest have been disclosed even if there are none).
Thank you for this contribution.
Thank you very much for giving me an opportunity to revise the above manuscript.
According to the reviewers comments, we have revised the manuscript to provided our explanation.
Furthermore, we revised the paper according to your suggestion.
1) The length of abstract is 194 words, and the word of the main text is 2550.
2) The layout and format guidelines have been followed.
3) The changes to the paper have been highlighted underlined as well as including detailed responses to the reviewers comments.
I hope you are satisfied with the revised version, however, if there is more question, we are willing to revise it again.