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分享一下我论文被拒的审稿人意见已有11人参与
之前投了一个SCI，昨天接到通知：reject
以下是审稿人意见，貌似只有一位审稿人。
Reviewer's comments on your work have now been received. You will see that he/she is advising against publication of your work. Therefore I must reject it.
For your guidance, I append the reviewer's comments below.
We would like to thank you for submitting your paper to the journal and we are sorry it cannot be published. We look forward to any contributions you might want to make to our journal in the future.
Yours sincerely,
Reviewers' comments:
Reviewer #1: The paper is not acceptable for publication in S&A. A lot of figures, but little information for the S&A community. In its present form it doesn't give sufficient information for a full paper.
我个人觉得这位审稿人比较不负责任，或者没时间仔细看论文就草草reject了事。
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blogAbstract:'Reviewer(s)\' Comments to Author:Reviewer: 1Recommendation: Publish after minor revision.Comments:The manuscript describes very important new findings that deserve rapid publication as Communication to Materials Chemistry. Certainly, the topic (search for novel non-noble metal catalysts for oxygen electroreduction) is of primary importance. Basically, I recommend ',
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{list wl as x}{/list}关注今日：1 | 主题：584719
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【公告】分享你的审稿意见和修稿回复经验
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这个帖子发布于4年零278天前，其中的信息可能已发生改变或有所发展。
为了更好地帮助新手了解投稿、审稿、修稿过程的系列等，特举办本活动——分享你的审稿意见和修稿回复经验。活动要求：有国内外期刊投稿经验的战友，可就既往投稿遇到的困难以及解决方法、审稿意见以及修稿回复等方面内容进行分享、交流。发帖格式：1）研究题目：（建议保留研究疾病和方向，可酌情隐去关键部分）2）审稿意见：（关于主题、语法词法、统计学、增补实验等等任何方面的问题均可，审稿各个阶段均可，鼓励分享SCI审稿意见，鼓励保留原始问题）3）修稿回复：（要求真实，言之有理有据，中英文不限，鼓励SCI回复信并同时附上简要的中文翻译概要，可酌情隐去研究指标或疾病）4）经验总结：（投稿、审稿、修稿、接受、出版等过程的相关总结均可）5）其他方面分享：（可选）加分条件：视中英文论著、问题多少和回复内容质量等情况，按照每篇投稿、修稿相关问题总结加1-5分（我为人人，人人为我。加分从宽哦）每人最多限10分。备注：欢迎“原汁原味”分享，转载亦可但请注明！拒绝抄袭、编造虚假内容。本活动长期有效。本活动细则解释权归属论文版。
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哈哈每次活动我都会抢到沙发，仅凭这点，版主就该额外给小弟加一分，just a joke！开始正题！1）研究题目：xxx versus xxx for early gastric cancer in xxx: A systematic review and meta-analysis2）审稿意见Reviewer #1:1. There are many places where the writing is difficult to understand and the syntax is unclear please be sure to double check the sentence structure as well (&Although the incidence of gastricis declining...&). We have now reviewed and edited our manuscript with the aid of an English-speaking editor. 2. For the inclusion criteria, the authors mention that they included &unpublished high quality trials...& Are these trials that the authors conducted? Ifnot, where do these unpublished trials come from? Why should they be included?Accordingto the Cochrane handbook for systematic review of intervention (version 5.1.0),sources to search should include bibliographic databases, journals, and othernon-bibliographic-database sources, as well as unpublished and ongoing studies.Accordingly, some completed studies are never published. Including data from unpublished studies in a systematic review, when appropriate, is important to minimize the bias of meta-analysis. We thoroughly searched for potentially suitable unpublished trials for our meta-unfortunately,there were none. Hopefully this addresses your concern. 3. The discussion is amajor area of weakness in my opinion. I think it&#39;s important in the discussion towrite about the implications of the research, not simply restate the results.Currently, the discussion is more or less a summary of the results and adds little to the manuscript. We thank you for your suggestion, and have made theadvised changes in the discussion section of the paper.4. There seems tohave been at least one similar meta-analysis published by this journal within the past year on the topic (ref 22). What does the manuscript by Zhang andcolleagues add to the body of literature? Is this manuscript unique because of its focus on early gastric cancer?First, our meta-analysis focuses on patientswith xxxx 17 trials (five RCTs and 12 CCTs), 1665 patients in total. Reference22 focusing on patients with xxxx(usually for patients with advanced gastriccancer) contains 10 trials (one RCT and 9 CCTs), for a total of 1039 patients.Second, Reference 22 focuses on the topic of xxx for gastric cancer, which canbe used for patients with early and advanced gastric cancer. Our manuscript focuses on early gastric cancer, since we propose that xxx is more suitable forearly compared with advanced gastric cancer. The reasons for this are as follows: (1) xx has fewer xxx, affecting prognosis, especially the patients with advanced gastric cancer, who tend to have more l (2)xxhas a longer operative time, and longer exposure to anesthesia and CO2 pneumoperitoneum, which may increase the incidence of postoperative serious complications and mortality rate. (3) the learning curve of xxx for advanced gastric cancer is also an important issue, which might increase operative andCO2 pneumoperitoneum time. If these areas could all be addressed and the authors could clarify what this paper adds to the current body of scientific literature, the manuscript would be strengthened significantly. Thank you for the opportunity to review this manuscript.We have revised the manuscript accordingly.Reviewer #21. Please state units for parameters listed in result section of the abstract. For example,wound length: -12.91 cm.....ect.We have added such information in the results section of the abstract.2. Similarly, in resultsection of the paper, state units (1.64?).We have again added such information in the results section of the abstract.3. Suggest the authorshave the paper review by an English editor.We have done so accordingly with the editorialhelp of xxxxx3）修稿回复：具体的修稿内容见上！附上自己的cover letter：Dear Dr.Melvin:Thank you for theopportunity to resubmit our revised manuscript. We thank you and the reviewersfor your constructive suggestions and comments. Our point-by-point answers tothe reviewers’ comments are below, with amendments highlighted in red.We hope that the revised manuscript is now acceptable forpublication. We look forward to hearing from you.Sincerely <font style="color:#）经验总结：投稿SLEPT(IF:1.227)大约 20天送外审，<font style="color:#个月后修稿意见回来，认真按照意见修稿，同时请了一家公司润色，花了<font style="color:#0欧，有点贵，不过修稿的很认真，重新resubmission以后，<font style="color:#天后接受（<font style="color:#13年<font style="color:#月<font style="color:#日）。总之过程比较顺利。前后一共用了大约5个月的时间。5）其他方面分享：修稿的时候一定要找一个师弟帮忙检查一遍，而且全文的排版，字体什么进来和所投杂志一直，尽量做到即将发表时候的状态，这样杂志社直接接收的可能性更大些！沙发分享经验，望 @ 版主加分从优（小弟准备晋级准中）！！！哈哈论文版又有经典的活动了，大力支持！
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美国临床营养杂志接受的稿子（IF&6），其实下面的意见综合后，编辑给的是拒稿但可以重投，因此我们回复和修改格外重视，大家可以参考一下1）研究题目:
XX intake is associated with lower XX cancer risk: results from a XX of epidemiological studies2）审稿意见/修稿回复：1
Replies to Reviewer #11.1 Major commentsMajor comments #1: In general, the presentation of results from each study should emphasize the various sub-populations, so that the comparisons are meaningful in the context of the soy-lung cancer hypothesis. E.g. results are summarized graphically in one Forest Plot, which gives the overall results for each study - unfortunately, in many cases the populations are quite different, and presenting the results in this way is not optimal. It would be very helpful to the reader to stratify individual study results by gender, smoking status and Asian/non-Asian population and present these separately in the Forest Plot.Answer: Changes have been made as suggested.We agree. Three figures have been plotted to display the results (soy intake and the risk of lung cancer) by gender, smoking status, and study population (shown in Supplemental Figure 1, 2, and 3. page 27-29). Considering the manuscript length, we decide to provide these graphs as online supplemental materials (OSM). And the relevant data can also be available in Table 3 in the text. Major comments #2: Differences in average intake of soy and soy isoflavones between populations are notable, and this is mentioned on page 8 (line 3-4), but only briefly. Would strongly suggest that this is described in more detail, and that the discussion and interpretation of the results should take this into account. For example, in the Discussion, page 10 line 10, there could be some indication as to what level of intake would constitute a &#39;diet rich in soy&#39;, based on the available evidence.
Answer: Relevant data regarding levels of soy or soy isoflavones intake in studies we analyzed have been added in Table 1 (i.e., levels of soy or soy isoflavones consumption in the highest and the lowest category). In addition, comments have been made in Discussion section (line 3-9, page 12), and we only compared the values for soy isoflavones intake between Asian and Western populations, because values for total soy food intake are not available in studies from Western populations.Table I Dose-response assessment in epidemiological studies of soy intake and lung cancer1 (Supplemental data for reviewers only)Study (Reference)RegionDesignFrequencycomparisonOR/RR(95%CI)AmountcomparisonOR/RR(95%CI)Shimazu T 2010 (23)JapanCS
-Soy genistein:9 mg/day17 mg/day26 mg/day48 mg/daySoy genistein:9 mg/day17 mg/day26 mg/day48 mg/dayMen:1(reference)1.09(0.84, 1.41)1.10(0.84, 1.44)0.89(0.67, 1.19)Women:1(reference)0.88(0.58, 1.33)0.85(0.55, 1.30)0.83(0.54, 1.29)Ho SY 2006 (24)ChinaPC-CSSoy product:&1/month1-3/month1-3/week&4/weekSoy product:&1/month1-3/month1-3/week&4/weekM*:1(reference)0.94 (0.66, 1.35) 0.96(0.71, 1.30) 0.76(0.54, 1.05)W*：1(reference)1.00 (0.63, 1.59)0.88 (0.59, 1.31)0.71 (0.46, 1.10)
-Schabath MB 2005 (25)USAHC-CS
-Total soy isoflavones:≤8.2μg/day8.3-38.2μg/day38.3-83.1μg/day≥83.2μg/dayM&W*:1(reference)0.47(0.40, 0.58)0.33(0.27, 0.40)0.39(0.32, 0.48)Seow A 2009 (26)SingaporeCS
-Total soy isoflavones:4.0 mg/1000 kcal/day8.4 mg/1000 kcal/day13.1 mg/1000 kcal/day22.0 mg/1000 kcal/dayW:1(reference)0.97(0.72, 1.3)0.83(0.60, 1.14)0.74(0.53, 1.04)Seow A 2002 (27)SingaporeHC-CS
-Total soy isoflavones:&69.1mg/day69.1-171.6 mg/day&171.6 mg/dayTotal soy isoflavones:&69.1mg/day69.1-171.6 mg/day&171.6 mg/dayW (smokers):1(reference)1.55(0.78, 3.08)1.30(0.64, 2.61)W (never smokers)*:1(reference)0.57(0.38, 0.86)0.56(0.37, 0.85)Wakai K 1999 (29)JapanPC-CSSoy bean:&1/month1-2/month1-2/week or moreSoybean:&1/month1-2/month1-2/week or moreM*:1(reference)0.69(0.41, 1.18)0.63(0.40, 0.98)W:1(reference)1.24(0.48,3.24)1.09(0.49, 2.39)
-Hu J 1997 (31)ChinaHC-CSSoy bean product:&2 Kg/year2-5 Kg/year5-8 Kg/year&8 Kg/yearT:1(reference)1.00(0.60, 1.60)0.90(0.50, 1.70)0.60(0.40, 1.10)--Cutler GJ 2008 (32)USACS--Total soy isoflavones:≤0.13mg/day0.13-0.23mg/day0.23-0.27mg/day0.27-0.51mg/day&0.51 mg/dayW*:1(reference)1.00(0.93, 1.08)0.99(0.92, 1.07)1.00(0.92, 1.07) 0.93(0.86, 1.00)Matsuo K 2008 (33)JapanHC-CSSoy product:&32g/day33-54.6 g/day&54.7 g/dayT*:1(reference)0.79 (0.50, 1.27)0.56 (0.34, 0.93)1 M, W, T, BMI, OR, RR, CI, CS: HC-CS: hospital based case- PC-CS: population based case-control study.* Ptrend&0.05. If not specified, the P-value for trend test is bigger than 0.05.As the referee suggested, it is very meaningful that more recommendations based on the available evidence should be made for the public. For example, based on the epidemiological data, what amount of average soy or soy isoflavones intake is needed for a reduced risk in lung cancer. In order to answer this question, we extracted the dose-response data from included studies (shown in Table I,Supplemental data for reviewers only) and attempted to conduct a dose-response analysis (1. Greenland S, Longnecker MP. Methods for trend estimation from summarized dose-response data, with applications to meta-analysis. Am J Epidemiol 01-9.; 2.Hamling J, Lee P, Weitkunat R, Ambuhl M. Facilitating meta-analyses by deriving relative effect and precision estimates for alternative comparisons from a set of estimates presented by exposure level or disease category. Stat Med -70.). Unfortunately, we failed to summarize those dose-response data due to different methods used to assess and report soy intake across the included studies (Table I). Moreover, because no included study has simultaneously evaluated the three key elements of soy or soy isoflavones intake i.e. frequency, intensity, and duration, or at least two of the three, and the dose-response relationships are not fairly consistent (Table I), it is difficult to determine which levels of soy or soy isoflavones intakes are optimal in lung cancer prevention. This issue was discussed in the revised text (line 11-17, page 13). Major comments #3: The differentiation between fresh and fermented soy food is not very clear (page 12 lines 14ff). I am not sure if I understood this paragraph, but were the two studies (trials?) selected based on the inclusion of fermented foods, and did this mean that the estimates for unfermented soy foods were not included in the analysis? If so, what would the potential impact be on the summary OR? The basis of selection of specific types of soy foods for specific studies would need to be explained in the methods section more clearly.
Answer: Changes have been made as suggested.Fermentation is a processing method for improving nutritional and functional properties of soybeans due to the increased content of small bioactive compounds. The large protein, lipid, and carbohydrate molecules in raw soybean are broken down by enzymatic hydrolysis during fermentation to small molecules such as peptides, amino acids, fatty acids, and sugars, which are responsible for the unique sensory and functional properties of the final products (Kwon DY, Daily JW, Kim HJ, Park S. Antidiabetic effects of fermented soybean products on type 2 diabetes. Nutrition Research.-13.). In addition, human in vivo study showed that fermentation can increase the availability of isoflavones in soy via increasing the urinary isoflavonoid recovery (Hutchins AM, Slavin JL, Lampe JW. Urinary isoflavonoid phytoestrogen and lignan excretion after consumption of fermented and unfermented soy products. J Am Diet Assoc -51.). However, to the best of authors&#39; knowledge, no published data, to date, has compared the effects of fermented soy foods with those of unfermented soy foods on carcinogenesis in animal experiments. Although dietary supplementation with miso shows an inhibitory effect on breast (46), stomach (47), and colon (48) tumorgenesis, there is currently no published study available in a lung model. Therefore our finding (i.e. the different effect on lung cancer was observed between fermented and unfermented soy foods) underscores the need for future studies to clarify the difference between fermented and unfermented soy food in the etiology and prevention of lung cancer, and we rewrote the comments on this issue in discussion section (line 13-23, page 12).Because two studies (28, 29)separated the risk estimates according to the different types of soy foods (i.e. tofu, miso soup, soybean, and soybean curd), and did not report the effect of total soy food or soy product intake, we only selected tofu in overall analysis in our previous version. But in current revised manuscript, the study-specific estimate was recalculated in these two studies (28, 29), via pooling the risk estimates of those various soy types reported in each study, weighted by inverse variance (18) (line 18-21, page 6 and line 11-13, page 8). However, the study-specific OR/RR in overall analysis from other studies we analyzed was based on a wide range of soy foods and can be most representative of the total soy or soy product intake (Table 1-footnote, page 22). 1.2 Minor commentsMinor comments #1: Table 1: The OR/RRs quoted in the table are assumed to be the overall estimates for each study. For Ref 29, the OR quoted is the figure for smokers only (this also applies to Fig 2).Answer: Errors have been corrected in the revised version. Minor comments #2: References in Table 1 are not in accord with the text and reference list. Answer: Errors have been corrected in the revised version. Minor comments #3: Would suggest removing the analysis by specific isoflavones (table 3 and page 12 lines 19-22) because of the limited number of studies that reported results separately for genistein/daidzein/equol.Answer: Changes have been made according to the referee’s suggestion. 2
Replies to Reviewer #22.1 Major commentsMajor comments #1:The authors conducted a meta-analysis on the association of soy and isoflavone intake with risk of lung cancer. They found an inverse association in the overall studies, and inverse association seemed to be restricted to women, never smokers, and Asian populations.This meta-analysis included a study using plasma isoflavone concentration (reference no. 33). All other studies seem to assess dietary intake using questionnaire. Plasma isoflavone concentration is not identical to dietary intake because plasma level reflects not only intake but also absorption and metabolism of isoflavones. In fact the total isoflavone concentration in the plasma study includes equol. The exclusion of the study from main analysis should be considered.Answer: Changes have been made based on this constructive suggestion. Arai Y and colleagues found that the dietary intake of daidzein and genistein after adjustment for total energy intake was significantly correlated with the plasma concentration (r = 0.335 for daidzein and r = 0.429 for genistein) (Arai Y, Uehara M, Sato Y, et al. Comparison of isoflavones among dietary intake, plasma concentration and urinary excretion for accurate estimation of phytoestrogen intake. J Epidemiol -135), suggesting that measurements of plasma concentration of isoflavones (genistein and daidzein) are useful biomarkers of dietary intake. However, whether the plasma equol or the three (i.e., genistein, daidzein, and their metabolite: equol) can reflect the level of total dietary isoflavones intake is unknown. In addition, no evidence shows that almost the entire dietary isoflavones intake in the study by Shimazu T et al (Shimazu T, Inoue M, Sasazuki S, et al. Plasma isoflavones and the risk of lung cancer in women: a nested case-control study in Japan. Cancer Epidemiol Biomarkers Prev -27.) is from soy foods. For the above uncertainties, inclusion of a study by Shimazu T et al, may threat to the validity of research synthesis in our meta-analysis, and we cautiously excluded it in the current version of our manuscript and modified the study selection criteria in Methods section (line 17-19, page 5).2.2 Minor comments:Minor comments #1: Title: Because soy foods are not equal to isoflavones, “Soy intake is…” should be “Soy and isoflavone intake is…”Answer: No change has been made.Our present meta-analysis mainly focused on the relationship between soy food intake and the risk of lung cancer. Although the constituents responsible for the hypothesized anticancer effects of soy have not been definitively identified, soy isoflavones have received the most attention, and considerable evidence suggests that they are the primary soy chemopreventive agents (Messina M, Flickinger B. Hypothesized anticancer effects of soy: evidence points toward isoflavones as the primary anticarcinogens. Pharm Biol –S23). Thus, we also, with interest, tested the effect of soy-derived isoflavones (daidzein and genistein) intake on lung carcinogenesis based on currently available epidemiological studies (refs. 25-27, 32, please see the reference list in the revised version), while other isoflavones (e.g., biochanin A and formononetin) or other dietary isoflavones sources rather than soy in relation to lung cancer was not studied in current analysis. We therefore believe that the title in the text can sufficiently and accurately summarize our work. Minor comments #2: Table 1: The authors used the word “Soy isoflavones”. Foods other than soy may contain isoflavones. Almost all of the isoflavone sources in Asian populations may be soy foods. However, is this the case in non-Asian populations? If not, “Soy isoflavones” should be “Isoflavones”. Also, if available, absolute value of isoflavone intake in the highest category is informative.Answer: Yes, it has been known that isoflavones are found in a number of legumes, grains and vegetables in addition to soy. Although dietary soy is the main contributor to the total isoflavones intake worldwide, no evidence suggests that almost the entire dietary isoflavones sources are soy foods, even in countries with high soy consumption, such as Japan, Singapore, and China (Messina M, Nagata C, Wu AH. Estimated Asian adult soy protein and isoflavone intakes. Nutr Cancer -12). “Soy isoflavones” in current version of our manuscript means the isoflavones ONLY derived from soy foods, and we only included studies if they evaluated the association between soy or soy-derived isoflavones (refs. 25-27, 32) and lung cancer risk (line 13-19, page5).The data as to the amount or the frequency of soy or soy isoflavones intake in two compared categories have been added in the revised version (shown in Table 1). Moreover, some comments have been made in the Discussion section (line 3-10, page 12) regarding this issue. Minor comments #3: Tables 1-3 and figure 1: Please check the references. Page 7, line 17: Judging by Figure 1, reference no. 29 should be no. 30. Answer: The correction has been made according to the referee’s comment. Minor comments #4: Page 9, lines 22-25: Why did the authors exclude these two studies only?Answer: In sensitivity analyses, we recalculated summary effects by excluding one study per iteration to examine the influence of each individual study on the overall RR, and arrayed in order of the point estimate of the remaining 10 studies, with the lowest at the top (Shown in Table II). The data shows that the results across sensitivity analyses are consistent without great fluctuate and are similar to the overall estimate. Considering the space limit, we only reported the lowest and highest pooled estimates (i.e., the variation range) in Result section (line 19-23, page 9).Table II. Sensitivity analysis (Supplemental data for reviewers only)Study excludedReferenceSummary RR (95%CI)Wakai K 1999(29)0.75 (0.62, 0.91)Shimazu T 2010 (23)0.76 (0.63, 0.93)Cutler GJ 2008(32)0.76 (0.62, 0.93)Takezaki T 2001(28)0.76 (0.63, 0.91)Wu-Williams AH 1990(30)0.76 (0.63, 0.92)Seow A 2002(27)0.77 (0.64, 0.93)Ho SY 2006(24)0.78 (0.64, 0.95)Seow A 2009(26)0.78 (0.65, 0.94)Hu J 1997(31)0.79 (0.66, 0.94)Matsuo K 2008(33)0.79 (0.66, 0.94)Schabath MB(25)0.84 (0.75, 0.94)All studies(23-33)0.77 (0.65, 0.92) 4）经验总结：这篇稿子其实先投给Cancer杂志的后被拒稿，虽然分值低，但可能专业不对口。相关的经验可以详见帖子：
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好几年没来dxy赚分了，今天回到论文版，感觉还是那么的熟悉，那么的亲切。也来分享一下我修回的一点经验吧：<font style="color:#）研究题目：Proteomic analysis of *** in mice revealed the protective role of ***2）审稿意见及回复Replies to Reviewer #1Comment 1: For the 2DE based proteome analysis how many gel did you made for each group? What was the reproducibility of 2DE and what was the methods to normalized the data?Answer: Thank you very much for this comment. In the present study three reduplicative gels were run for each group. The reduplicative gels in each group were matched after several rounds of automatic matching process and manual validation using PDQuest software. The reproducibility of the 3 images in each group was good with the match rates between 90-95%. The intensity of each spot was normalized based on total quantity of valid spots on the gels which was executed by PDQuest software automatically. We have added this information to pages 9 and 10.Page 9, line 14 to 15: “Triplicate gels were run for each group to obtain statistical significance for protein differences.”Page 10, lines 11 to 12: “based on total quantity of valid spots on the gels”Comment 2: Normally the cutoff value for differential displayed protein spots is 2 fold increasing or decreasing, why and according to what did the authors use more than 1.5-fold difference value?Answer: The cutoff value used for differential protein spots varies in many studies and 2 fold is the most common used. Meanwhile, a considerable number of proteins with the difference value between 1.5 and 2 fold have also been reported to have important physiological functions (see references 1-6 listed blow). In order to discover as much as possible about the proteins potentially involved in hepatic I/R injury and IPC, we used 1.5-fold as cutoff value for differential displayed protein spots in this study.Comment 3: The title of Table1 is suggested the be changed as “The classification of differential proteins in I/R injury liver with the comparison of sham group”, and for Table 2, “The classification of differential proteins in IPC + I/R liver comparing with I/R group”Answer:Thanks very much for your valuable suggestions! We have made corrections in Table 1 and Table 2.Page 32, line 1: “The classification of differential proteins in I/R injury liver with the comparison of sham group”.Page 33, line 1: “The classification of differential proteins in IPC + I/R liver comparing with I/R group”. Comment 4: In both table, the MV should be replaced by MW (Molecular weight), and for protein identification, the Protein Score is the very important parameter, it is suggested to add the protein score to ensure the accuracy of such identification. Answer: Thanks very much for your comment. We have made corrections in Table 1 (page 32) and Table 2 (page 33).Comment 5: The ATP5B should rewritten as ATP5β. And it is better to add the MS-MS data of ATP5β as usual. The matched peptide should be underlined to complete the data.Answer: Thank you very much for your comment. We have rewritten ATP5B as ATP5β and MS-MS data of ATP5β was added to page 17, page 31 and page 38.Page 17, last line: “The peptide coverage maps and one of MS/MS data was shown in Figure 5.”Page 31, legend for Figure 5.Page 38, Figure 5.Comment 6: If possible, the functional analysis of ATP5β is strongly suggested to confirm its critical role in I/R injury and the enzymatic activity should be measured in this case. The proteome analysis only presented the alteration in protein content or quatitation.Answer: Thank you very much for your comment. ATP5β is the major catalytic subunit of ATP synthase, which produces ATP from ADP in the presence of a proton gradient across the mitochondrial membrane (see reference 7 listed below), and the ATP production is positively correlated with enzymatic activity of ATP5β. Due to the limitation of samples, we only measured hepatic ATP content since ATP is the end product of ATP5β catalysis. Our result showed that change pattern of hepatic ATP content was the same as that of hepatic ATP5β expression. Thus, increased ATP5β expression and the final ATP production indirectly indicated that enzymatic activity of ATP5β was increased in the livers pretreated by IPC. We have added above information to page 18 and page 21.Page 18, line 2: “ATP is the end product of ATP5β catalysis”.Page 18, line 4 to 6: “the change pattern of hepatic ATP content was the same as that of hepatic ATP5β expression”.Page 21, line 15 to 18: “ATP is the end product of ATP5β catalysis, increased ATP5β expression and the final ATP production indirectly indicated that enzymatic activity of ATP5β was increased in the livers pretreated by IPC.”References&#91;1&#93;
White, M.Y., Cordwell, S.J., McCarron, H.C., Prasan, A.M., et al., Proteomics of ischemia/reperfusion injury in rabbit myocardium reveals alterations to proteins of essential functional systems. Proteomics 2005, 5, .&#91;2&#93;
Schumacher, J.A., Crockett, D.K., Elenitoba-Johnson, K.S., Lim, M.S., Proteome-wide changes induced by the Hsp90 inhibitor, geldanamycin in anaplastic large cell lymphoma cells. Proteomics 2007, 7, .&#91;3&#93;
Greenlee, K.J., Corry, D.B., Engler, D.A., Matsunami, R.K., et al., Proteomic identification of in vivo substrates for matrix metalloproteinases 2 and 9 reveals a mechanism for resolution of inflammation. J. Immunol. 2006, 177, .&#91;4&#93;
Bech-Serra, J.J., Santiago-Josefat, B., Esselens, C., Saftig, P., et al., Proteomic identification of desmoglein 2 and activated leukocyte cell adhesion molecule as substrates of ADAM17 and ADAM10 by difference gel electrophoresis. Mol. Cell. Biol. 2006, 26, .&#91;5&#93;
Rao, P.V., Lu, X., Standley, M., Pattee, P., et al., Proteomic identification of urinary biomarkers of diabetic nephropathy.Diabetes Care 2007, 30, 629-637.&#91;6&#93;
van Balkom, B.W., Hoffert, J.D., Chou, C.L., Knepper, M.A., Proteomic analysis of long-term vasopressin action in the inner medullary collecting duct of the Brattleboro rat. Am. J. Physiol. Renal. Physiol. 2004, 286, F216-224.&#91;7&#93;
Vendemiale, G., Guerrieri, F., Grattagliano, I., Didonna, D., et al., Mitochondrial oxidative phosphorylation and intracellular glutathione compartmentation during rat liver regeneration. Hepatology 1995, 21, .Replies to Reviewer #2Comment 1: The study is descriptive, the authors used a few of references in the section of D however, they did not provide sufficient data for mechanism.Answer: Thank you very much for your comment. As we know now, physiological processes are involved by the interaction of many proteins which form a complex network. To figure out this network, proteomics provides us high-throughput information, and may help us to observe the possible proteins involved in the network. In this report, we studied the proteome altered in the livers upon I/R injury and IPC, and concerned on the global alteration of protein expression rather than a certain protein change.Since many information got from omics such as genomics, transcriptomics and proteomics is hard to be explained individually upon current knowledge. Regard to this study, we mainly discussed the role of differential proteins in hepatic I/R injury and IPC by their functional categories. Although we did not provide sufficient data for mechanism, the potential role of ATP5β and other three proteins (BHMT, MUP6 and TTR) in hepatic I/R injury and IPC were discussed in Discussion section. In the revised manuscript, we have added the above information to the Discussion section in order to explain the results of this study more clearly.Comment 2: In the Tables, there are a few proteins that might be involved in I/R mechanism, why the authors just validated ATP5B by western blot. The authors should explain the reasons.Answer: We apologize for the confusion. As we replied in comment 1, in this study, we mainly focused on the global changes in protein expression during hepatic I/R injury and IPC, in order to explore potential proteins that may be involved in the network of these processes. Intriguingly, ATP5β was one of the differentially expressed proteins that may explain ATP preserving effect of IPC, an effect that was observed in recent studies but without detailed explanation (see references 24 and 39 in our manuscript: J Hepatol 2003; 39: 55-61, and Hepatology 2001; 34: ). Therefore, we paid more attention to this protein. Potential roles of the rest proteins in hepatic I/R injury and IPC are under further investigation. We have added the above information to page 17 and page 21.Page 17, line 14 to 19: “Increased expression of hepatic ATP5β may explain ATP preserving effect of IPC, an effect that was observed in recent studies but without detailed explanation. Therefore, we paid more attention to this protein and used Western blot analysis to verify its expression.”Page 21, line 2 to 4: “and potential roles of these proteins in hepatic I/R injury and IPC are under further investigation.”Comment 3: The manuscript would be better, if the author validated the results in human samples.Answer: Thank you very much for your comment. We agree with you that it is very important to investigate whether experimental observations hold true in human studies. At present, IPC has not yet been applied in our clinic for liver surgery and transplantation. Therefore, we could not get corresponding human liver samples to validate our experimental results observed in this study.<font style="color:#）经验总结：一般来讲，审稿人审临床的文章会比较客气，而审基础的文章会比较苛刻，会提很多意见，要求补很多实验。但是不管是临床的、还是基础的文章，修稿的原则是一样的：简单的说，就是想办法把审稿人“伺候”好，把每个意见都有理有节的回复清楚，审稿人问什么，就回复什么；不能逃避问题，不能含糊不清；如果没有做的，或者难以做到的，就直接说明难度，解释清楚即可。一般看审稿人的意见，就能判断出他对这篇文章的总体印象，如果出现以下几个信号，表示接收的可能性是很大的：1、审稿人大段大段写修改意见，就像帮你修稿一样；2、审稿人建议你补充一些直接相关的参考文献；3、审稿人指出文中多处小错误（这说明审稿人对文章还是蛮感兴趣的，能仔仔细细看完；如果印象不好的话，随便写点套话就可以拒稿的）。对于要求补实验的审稿建议，很多站友会觉得不好把握，我的经验是：10分以上：需要补；5-10分：最好要补；3-5分：不一定要补；3分以下：不要补。
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