论文题目：Pharmacokinetic and pharmacodynamic studies on the antivirus effects of A (一种中草药) against virus B （一种病毒）

所投杂志：Life Sciences

投稿结果：这次大修后又经过一次小修，被接受发表

编辑信内容（注：有删节）：

Dear Mr. XXX,

Your manuscript has been examined by the editors and qualified referee . We think the manuscript has merit but requires revision before we can accept it for publication in the Journal. Careful consideration must be given to the points raised in the reviewer comments, which are enclosed below.

If you choose to submit a revision of your manuscript, please incorporate responses to the reviewer comments into the revised paper. A complete rebuttal with no manuscript alterations is usually considered inadequate and may result in lengthy re-review procedures.

A letter detailing your revisions point-by-point must accompany the resubmission.

You will be requested to upload this Response to Reviewers as a separate file in the Attach Files area.

We ask that you resubmit your manuscript within 45 days. After this time, your file will be placed on inactive status and a further submission will be considered a new manuscript.

To submit a revision, go to /lfs/ and log in as an Author. You will see a menu item called Submission Needing Revision. You will find your submission record there.

Yours sincerely,

Joseph J. Bahl, PhD

Editor

Life Sciences

Format Suggestion: Please access the Guide to Authors at our website to check the format of your article. Pay particular attention to our References style.

Reviewers' comments:

Reviewer #1:

XXXXX （略）

Reviewer #2:

XXXXX （略）

Editors note and suggestions: （注：编辑的建议）

Title: Re-write the title to read more smoothly in contemporary English>>>

Pharmacokinetic and pharmacodynamic studies of the antiviral effects of A against virus B.

Abstract: Re-write the abstract to read more smoothly.

A, an alkaloid isolated from C (注：一种中草药), was tested for antiviral activity against virus B. Both in vitro and in vivo assays along with serum pharmacological experiments showed A to have potent antiviral activity. The pharmacokinetic profile of A in Sprague/Dawley rat plasma after oral administration was measured by HPLC. Blood samples taken at selected time points were analyzed to study potential changes in antiviral pharmacodynamics as measured by infectivity of viruses. From the similarity of the serum concentration profiles and antiviral activity profiles it is concluded that A it self, rather than a metabolite, exerted the effect against the virus prior to bioinactivation. The need for effective clinical agents against virus B and these results suggest the possibility of benefit from further experiments with A.

The authors should check to be sure that the terms blood samples, plasma and serum are always used appropriately throughout the abstract and text.

Introduction: some sentences can be made less passive. example 1st paragraph >>>> A appears to be the most important alkaloid isolated from the plant, its structural formula is shown in Fig 1. ... While it produced a general inhibition of antibody production lymphocyte proliferation was stimulated (Xia and Wang, 1997). These pharmacological properties suggest a potential use in the treatment of viral myocarditis against virus B that could be studied in experiments in cell culture and animals.

>>>The authors should check the entire manuscript for spelling errors (example given: in your text alkaloid is incorrectly spelled alkaloid)

>>>The authors should read the guidelines to the authors and not include the first name of the authors being cited in the text. In the reference section the first name should be abbreviated as shown in the guideline to authors (thus the earlier text reference should be (Liu et al., 2003)and the remaining one should be (Chen et al., 2002)

>>>>>The authors instead of directly answering the first complex question of reviewer #1 may include the three questions as future research aim in the discussion section.

>>>>>>Rather than redrawing figure the authors may choose to amend the

wording of the statistical analysis section to state that the result of tables are means +-SEM and for figures are +- SD.

>>>>> reviewer #1 comment number 8 and reviewer # 2 comment 3 might be satisfied by inclusion of a representative photo of cells and heart showing CPE. Remember most readers of the journal have never seen what you are trying to describe.

Because I think that you can deal with all of the points raised I am hoping to see a revised manuscript that you have carefully checked for errors. If you have questions or do not know how to respond to any of the points raised please contact me at bahl@u.arizona.edu Joseph Bahl, PhD Editor 2 Life Sciences

作者回复信原稿：

Dear Dr. Bahl,

I’m （注：正式信函不要简写）very appreciate （注：不适合作为给编辑回信的开始，同时有语法错误）for your comments and suggestions.

I （注：实际上是学生做的）have conducted in vivo antivirus experiments again （注：要表明是应审稿人或编辑建议而作）. Mice were sacrificed on 15 days and 30 days after infection. Death rate, heart weight to body weight ratio (HW/BW), virus titers and pathologic slices （注：用词错误）were calculated（注：用词不当）. Production of mRNA of IL-10, IFN-γand TNF-αwere （注：语法错误）measured by RT-PCR.

I have revised this manuscript and especially paid much attention to your comments and suggestions. I would like to re-submit it to LIFE SCIENCE. Title of manuscript has been changed to “The antivirus effects of A against virus B and its pharmacokinetic behaviour in SD rats serum” to make it more clear and smooth.

Answers to Reviewers’ questions were as follows: （注：可附在给编辑的回复信后）

Reviewer #1:

XXXXX

Reviewer #2:

XXXXX

Editors note and suggestions:

Title: Re-write the title to read more smoothly in contemporary English

Answer: I have rewrite the title to “The antivirus effects of A against virus B and its pharmacokinetic behaviour in SD rats serum” to make it more clear and smooth（注：多处语法错误）.

Abstract: Re-write the abstract to read more smoothly.

Answer: I have revise the abstract carefully to make it more smooth and informative（注：语法错误）.

The authors should check to be sure that the terms blood samples, plasma and serum are always used appropriately throughout the abstract and text.

Answer: I have paid attention to this question and it is clearer （注：不具体）. Introduction:

some sentences can be made less passive.

Answer: I have revise the whole paper to make sentences less passive and obtained help of my colleague proficient in English （注：语法错误，句子不通顺）.

The authors should check the entire manuscript for spelling errors

Answer: I’m very sorry to give you so much trouble for those spelling errors （注：不必道歉，按建议修改即可）. I have carefully corrected them.

The authors should read the guidelines to the authors and not include the first name of the authors being cited in the text. In the reference section the first name should be abbreviated as shown in the guideline to authors (thus the earlier text reference should be (Liu et al., 2003) and the remaining one should be (Chen et al., 2002)

Answer: I changed the style of references.

Rather than redrawing figure the authors may choose to amend the wording of the statistical analysis section to state that the result of tables are means +-SEM and for figures are +- SD.

Answer: （注：作者请编辑公司帮回答）

reviewer #1 comment number 8 and reviewer # 2 comment 3 might be satisfied by inclusion of a representative photo of cells and heart showing CPE. Remember: most readers of the journal have never seen what you are trying to describe.

Answer: Thank you for your suggestions. I have supplemented pictures of cardiac pathologic slices in the paper (Fig2).

I have to apologize for giving you so much trouble because of those misspelling and confusing statements （注：一般不是延误或人为失误，不必轻易道歉，按建议修改即可）. Your comments and suggestions really helped me a lot. I have put great efforts to this review. I wish it can be satisfactory.

If there’s （注：正式信函不要简写）any information I can provide, please don’t hesitate to contact me.

Thank you again for your time and patience. Look forward to hear （注：语法错

误）from you.

Yours Sincerely

Xxxx Xxxx (通讯作者名)

建议修改稿：

Dear Dr. Bahl,

Thanks you very much for your comments and suggestions.

As suggested, we have conducted in vivo antivirus experiments. Mice were sacrificed on 15 days and 30 days after infection with virus B. Mortality, heart weight to body weight ratio (HW/BW), virus titers and pathologic scores were determined. In addition, mRNA expression of IL-10, IFN-γ and TNF-α were measured by RT-PCR.

We have revised the manuscript, according to the comments and suggestions of reviewers and editor, and responded, point by point to, the comments as listed below. Since the paper has been revised significantly throughout the text, we feel it is better not to highlight the amendments in the revised manuscript （正常情况最好表明修改处）.

The revised manuscript has been edited and proofread by a medical editing company in Hong Kong.

I would like to re-submit this revised manuscript to Life Sciences, and hope it is acceptable for publication in the journal.

Looking forward to hearing from you soon.

With kindest regards,

Yours Sincerely

Xxxx Xxxx (通讯作者名)

Replies to Reviewers and Editor

First of all, we thank both reviewers and editor for their positive and constructive comments and suggestions.

Replies to Reviewer #1:

Xxxxx （略）

Replies to Reviewer #2:

Xxxxx （略）

Replies to the Editors note and suggestions:

Title: Re-write the title to read more smoothly in contmeporary English

Answer: I have rewrite the title to “The antivirus effects of Sophoridine against Coxsackievirus B3 and its pharmacokinetics in rats” to make it more clear and read more smoothly.

Abstract: Re-write the abstract to read more smoothly.

Answer: I have rewritten the abstract to make it more informative and read more smoothly.

The authors should check to be sure that the terms blood samples, plasma and serum are always used appropriately throughout the abstract and text.

Answer: I have paid attention to this issue, and they are now used appropriately throughout the abstract and text in the revised manuscript.

Introduction:

some sentences can be made less passive.

Answer: I have revised the whole paper to make sentences less passive with the help of the editing company.

The authors should check the entire manuscript for spelling errors

Answer: This has been done by us as well as the editing company.

The authors should read the guidelines to the authors and not include the first name of the authors being cited in the text. In the reference section the first name should be abbreviated as shown in the guideline to authors (thus the earlier text reference should be (Liu et al., 2003) and the remaining one should be (Chen et al., 2002)

Answer: I have changed the style of references according to the journal.

Rather than redrawing figure the authors may choose to ament the wording of the statistical analysis section to state that the result of tables aremeans +-SEM and for figures are +- SD.

Answer: SD has been used throughout the text, and shown in the Figs. 3 and 4 in the revised manuscript.

reviewer #1 comment number 8 and reviewer # 2 comment 3 might be satified by inclusion of a representative photo of cells and heart showing CPE. Remember: most readers of the journal have never seen what you are trying to describe.

Answer: Thank you very much for the suggestion. I have added pictures of cardiac pathologic changes in the revised manuscript (Fig. 2). 论文题目： Clinical implications of XXXX (一种病理指标) in X cancer

所投杂志：BMC Cancer.

结果：这次大修后被接受发表（同时编辑在接受信中提出课题是否得到伦理委员会同意的问题。作者在论文适当地方加上了有关陈述）

审稿人内容（有删节）：

Reviewer's report

Clinical implications of XXXX (一种病理指标) in X cancer

Version: 1 Date: 12 June 200X

Reviewer: XXXX XXXX (A Japanese Reviewer)

Reviewer's report:

General

-------------------------------------------------------------------------------

Major Compulsory Revisions (that the author must respond to before a decision on publication can be reached)

1. XXXXX.

2. XXXXX.

3. XXXXX.

4) The clinico pathological parameters examined are reported in Table 1. Among the primary tumor characteristics, the Authors consider the diameter, but ignore T stage. Consequently the T parameter is not considered in the multivariate analysis. In other studies, T stage has emerged as an independent factor. The Authors should therefore state the reason for their unusual choice. Nor is the number of metastatic nodes reported in this table. Moreover, for tumor differentiation, the Authors distinguish between two groups (differentiated vs undifferentiated), instead of between the usual 3 categories (G1, G2 and G3). I have never heard of the histological classification used by the Authors (massive, next and diffuse). They might therefore state their reasons for choosing it, providing a reference, if available.

-------------------------------------------------------------------------------

Minor Essential Revisions (such as missing labels on figures, or the wrong use of a term, which the author can be trusted to correct)

XXXXX.

-------------------------------------------------------------------------------

Discretionary Revisions (which the author can choose to ignore)

(None)

What next?: Reject because too small an advance to publish

Level of interest: An article of limited interest

Quality of written English: Needs some language corrections before being published

[b]Statistical review: Yes, but I do not feel adequately qualified to assess the statistics.

作者原答: T stage is considered in the multivariate analysis, and some

modification has been made in tumor differentiation and histological classification.

建议改答： We accept Dr. XXX comment (表明你对审稿人的欣赏和赞同). In the revised version of the manuscript, T stage has been added in the multivariate analysis, and description of tumor differentiation and histological classification has been modified; the histological classification in the original manuscript has been replaced by the generally accepted classification (Page 6, line 15; Table 4) (同意审稿人的建议，并根据其建议进行修改。同时指出在何处做了修改。).

加注：作者原回答与修改后的回答并无本质差别，正文中的修改也是一样的。但作者原回答会给审稿人“不太乐意”或“轻描淡写”的印象。因为审稿人花了122个单词来就此问题发表建议，而作者只用了20个。

修改后的回答，相信一开始就赢得审稿人的好感。你的回答不光是给审稿人看的，杂志编辑也会看（至少审稿人会这么认为），所以，审稿人会有种满足感（国外审稿人没有酬劳，得到作者和编辑的认可是他们审稿最主要的目的）。建议得到认可（当然，这里审稿人的确是正确合理的），而且作者还按其建议对文章进行修改，相信绝大多数审稿人是不会（不好意思）再拒绝修改稿的（所谓伸手不打笑面人）。当然，这篇文章起死回生、二审通过审稿关，关键是杂志编辑手下留情，给了作者再投(Re-submission)的机会。

有时，审稿人的建议得到作者认可，但作者无法按建议修改，尤其补做试验。这种情况将在以后举例说明。论文题目：Misdiagnosis of A (一种先天性疾病) as 某某 tumor: a case report

所投杂志：Neuro-Ophthalmology

投稿结果：大修，结果未知（前途未卜，因为该审稿人建议拒稿，但审稿人给作者机会）

审稿人审稿内容及作者原答和建议改答（有删节）：

Reviewer 2's report

审稿人问题1

The authors try to caution eye specialists and neurosurgeons not to do major orbital surgery on children without doing a dilated fundus examination with an indirect ophthalmoscope. In their case, once the correct diagnosis was made, by properly examining the eye, surgery was not necessary. A thorough pre-operative examination of the eye should be a automatic prerequisite to orbital surgery for poor vision, so I do not think their paper presents a unique idea.

作者原答

Answer: Although correct diagnosis can be made by thorough examinations, doctors are often misleaded by a “wrong” chief complaint（wrong可能表示主诉

症状本身误导，也可能表示病人说错，也可能是收诊医生记录错误）. In our case, the retinal specialist who made a misdiagnosis at first （at first用词不当）, was misleaded by “blurred vision in the left eye over a month” and did not pay enough attention to differentiate a congenital disease from “tumor”（需说明两者关联）. In （On） the other hand, it is also the result of too many patients we have to manage per working day (most large hospital （hospitals）in China is (are) on this occasion) and doctors in outpatient clinic have not much time to perform thorough ophthalmic examination (不应太绝对). So, the clinical misdiagnosis is not complete occasional event. We could learn a lot from this case.

建议改答

Answer: We agree with the referee that correct diagnosis can be made by proper and thorough examinations （首先肯定审稿人的观点to make him/her happy）. However, doctors are often misled by an “atypical”（比wrong要具体且客观）chief complaint, especially when there are too many patients in an outpatients department such as in a Chinese ophthalmic hospital （这句点出误诊原因，下面再逐一解释）. In our case, both the retinal specialist and orbital specialist who made the initial misdiagnosis, were misled by the symptom of “blurred vision in the left eye over a month”, which is characteristic of an “acquired disease”, and thus he did not pay enough attention to differentiate a congenital disease from a “tumor”（指出没有想到先天性疾病的原因1）. On the other hand, like most large hospitals in China, doctors in the Outpatient Department have to manage up to X (number) patients we per working day and thus some may have little time to follow the “good clinical practice” and perform thorough ophthalmic examinations （误诊原因2）. Consequently, the misdiagnosis inevitably occurred. This case report presents the lesion and reiterate the importance of thorough ophthalmic examinations prior to any surgery （这句表明为什么该病例报告值得发表）.

审稿人问题2

They have an interesting case, and a case report reviewing the subject might be of value, but I think they may have to be satisfied that they practiced good medicine and saved a child from an unnecessary operation, but that it did not merit publication.

作者原答

Answer: The initially misdiagnosis was made by our two specialists (one is a retinal specialist and the other orbital) （词句的意义不明）. Moreover, the reasons for the misdiagnosis have been discussed in our case report, which would be useful

for other doctors, especially for residents to avoid the same mistake (说服力比较弱). And （正规书信和论文不宜用And开句）we believe our radiology images in our case will contribute to a better understanding of this condition(说服力比较弱).

建议改答

Answer: We did feel relieved and satisfied when the unnecessary surgery was avoided （正面回应审稿人的肯定意见）. However, the fact that initial misdiagnosis was made by two experienced but busy specialists (one is a retinal specialist and the other orbital), cannot be ignored in our clinical practice （表明我们不能因为我们避免了不必要的手术而自满）. We feel that it would be beneficial to report the case and share our experience or lesion with other doctors, in order to avoid or minimize the same mistake （因此，我们希望发表该病例报告已警示同行）. In addition, we believe that the radiology images from our unique case will contribute to a better understanding of this congenital disease （虽不重要，但也许编辑喜欢）.

加注：

1.该文的特色是一审稿人觉得本病例报告不值得发表，但编辑愿意给作者rebuttal的机会。其实，该审稿人的评语总体来讲是不错的。但令人不解的是，每条评语最后一句得出跟前面截然不同的结论。可能他/她并不是“大牛”，不太能掌握病例报告发表的标准。

2.作者的回答总体还是非常好的，只是语气稍欠委婉，理据说服力需更进一步加强。论文题目：Prophylactic NSAIDs use in post-ERCP pancreatitis

所投杂志：Gut

结果：编辑直接拒稿，作者重新修改并申诉，申诉成功，直接接受。

编辑信内容（有删节）：

GUT/2008/156323

Prophylactic NSAIDs use in post-ERCP pancreatitis

Authors’ names （略）

Dear XXX,

Thank you for submitting this manuscript to Gut, which was discussed at the last Editorial Committee meeting. We are sorry to say that we are unable to accept it for publication, as it did not achieve a high enough priority score to enable it to be published in Gut. We favour letters which add new data and did not feel that you letter did this sufficiently.

Please remember that Gut receives about eight times as many manuscripts as we are able to publish, therefore regrettably it follows that many perfectly adequate papers must be rejected. This decision must be based not only on quality, but also

timeliness and priority against other subject areas.

For more details, please go to:

http://submit-

enter you Author Area and click on the 'Manuscripts with decisions' queue.

We are sorry to disappoint you on this occasion.

With kind regards.

Professor Robin Spiller

Handling Editor

Professor Robin Spiller

Editor

作者申诉信原文：

Dear editors,

Thanks for your kindly help in our previous manuscripts (GUT/2008/156323 and GUT/2008/156711).

The decision of the editorial board was a little disappointed to me. We had discussed the topic again and rewrite the manuscript according to the suggestions of the editorial board. We also invited our friend Harry Hua-Xiang Xia for insightful editing the paper.

Although Elmunzer et al. concluded that rectal administration of NSAIDs is effective in preventing PEP (these results are of significant clinical implications), several issues remain unsolved. For example, do risk factors influence the prophylactic effect? So, we performed a complimentary meta-analysis based on the methodology and the source articles identical to those used by Elmunzer et al. Also, it must emphasized that there were several limitations of the both meta-analyses including small sample sizes (for both subjects and studies), inconsistent definition of PEP, and less representative populations.

We believe the issues raised will improve the quality of the meta-analysis. Thanks for your re-consideration.

On behalf of my co-authors, I am submitting the enclosed material “Rectal Administration of NSAIDs in the Prevention of Post-ERCP Pancreatitis: a Complimentary Meta-analysis” for possible publication in GUT. I have read most of the papers that the journal had published and I believe our research to be in accordance with the style of the JOURNAL.

We have reviewed the final version of the manuscript and approved it for publication. To the best of our knowledge and belief, this manuscript neither has

been published in whole or in part nor is it being considered for publication elsewhere.

We state that there is no conflict of interest and ethical adherence in this study. Best Regards,

Authors’ names and affiliations （略）

作者申诉信建议修改文：

Dear Professor Spiller （在已知编辑姓氏和职称时请不要再泛称editor, 以示尊重）

Thanks for your letter in response to our previous submission of Letter to Editor (GUT/2008/156323) （事实上，编辑并没有帮助，而是回复）.

The decision of the Editorial Board might be because that we did not make it clear that the letter supports the overall conclusion of the Elmunzer et al., but provides additional analysis and points out the weaknesses of the meta-analysis. We further discussed the topic again and have modified the Letter according to your letters. In addition, we also invited Dr. Harry Hua-Xiang Xia, who is an internationally recognized gastroenterologist, to join the authorship team and make comments and edit the manuscript. （这一段非常重要。陈述失望心情于事无补。相反，应说明由作者引起的可能导致论文被拒的原因（很多作者论文被拒后归咎于审稿人或编辑不理解论文的价值），并再次强调论文的价值所在。加上本人为作者也许对论文被接收有一定作用，但关键还是在于强调论文本身的价值。）

We believe the Letter is publishable for the following reasons. First, although Elmunzer et al. concluded that rectal administration of NSAIDs is effective in preventing PEP, which is of significant clinical implications, several issues remain unsolved. For example, do risk factors influence the prophylactic effect? So, we performed a complimentary meta-analysis based on the methodology and the source articles identical to those used by Elmunzer et al. We further revealed that administration of NSAIDs was associated with decreased incidence of PEP in patients with low (RR = 0.29, 95% CI: 0.12-0.71, P = 0.006) and high risks (RR = 0.40, 95% CI: 0.23~0.72, P = 0.002). Second, there were several limitations of the meta-analyses originated from the source articles. These include small sample sizes (for both subjects and studies), inconsistent definition of PEP, and less representative populations. These limitations should be more clearly acknowledged in the paper by Elmunzer et al. （这一段是核心。能否说服编辑在此一博。原信缺乏数据，而且稍欠层次和说服力）。

Therefore, we wish to re-submit the further revised version for your

re-consideration. （原信有三段与本申诉无关，建议删掉）。

With best regards,

Yours sincerely,

Authors’ names and affiliations （略）

加注：

1.该文的特色是编辑委员会觉得本信稿(Letter to Editor)不值得发表，并说明原因，即稿源太多（8倍），本文无新意。但作者坚持认为该信稿有新意，故决定申诉(Appeal)。

2.在看了该信稿并与作者交流后，本人认为值得申诉。并一起讨论修改原文及申诉信。该信稿很快被接受（并成为作者特殊的结婚礼物）。

3.论文写作与发表只有一般规则，没有绝对定律。只要你坚信是有价值的东西（试验结果或心灵火花）都有发表的潜力，关键在于如何准确将价值的东西表达出来。

4. 对待拒稿，要有良好心态。多多检讨课题设计和论文写作中的问题，而不是抱怨审稿人或编辑没有认真阅读你的论文。遇到审稿人对论文有误解时，我常用的一句话是“We are sorry that we did not make it clear”, 或“We are sorry for the misunderstanding due to unclear descriptions in our previous manuscript”而不是“The reviewer doesn’t understand?”或“The reviewer is wrong?.”.等等。在我的回复信中，审稿人从没有“错”。