Peer Review History

Original SubmissionJanuary 3, 2024
Decision Letter - Antoine Naem, Editor

PONE-D-23-42513Pelvic neural injuries and acute voiding changes in rat models of radical hysterectomyPLOS ONE

Dear Dr. Wang,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

The methodology and results of the manuscript require additional clarifications and explanations. The reviewers comments must be addressed suitably.

Please submit your revised manuscript by Jun 28 2024 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

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If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols.

We look forward to receiving your revised manuscript.

Kind regards,

Antoine Naem, M.D.

Academic Editor

PLOS ONE

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Partly

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2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

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3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

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4. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

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5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: It is an interesting work, the authors spend a remarkable effort to obtain their results, the result was well presented, some remarques required a major revision

In abstract

Add a brief explanation to compare the various terms of types A, B1, C1 and C2.

Add (using immunohistochemistry) in methodology

It is better to use passive tense rather using (We established …..)

In introduction

Line 49: Add a paragraph to compare the various terms of types A, B1, C1 and C2

Line 54: Add a paragraph to explain the normal anatomy of pelvic plexus in human and to justify the use of rat model with references

The paragraph between lines 59 and 61 need a suitable reference

Line 62: (Not only did we show the structural) needs lingual revision, native speaker revision is demanded.

In results

It is not clear whether the loose of rats in B1 and C1 was related to the operation complication? Please clarify.

Line 98: Adding schematic drawing to explain the different types of procedure with location of nerves will help to explain.

Line 171: Adding samples of images of 2:5 and 2.6 procedures could help to explain

Line 195: Add more information about the primary and secondary antibodies and the action of Pgp9.5. with reference>

In discussion:

The clinical application according to the results of this work was not obvious, is it the standardizing of the model or the application in surgical technique in human.

Reviewer #2: The author describes the establishment of a new animal model mimicking neurogenic bladder dysfunction induced by pelvic nerve injury following radical hysterectomy. The new rat model was characterized by the severity of bladder dysfunction being graded by surgical radicality, which is interesting. However, this manuscript still has some points to be resolved, as follows:

Major

1) Several surgical procedures have been developed to create a stratified neurogenic bladder in rats mimicking UAB followed by total hysterectomy. How should the author decide what millimeters of tissue from cervices should be dissected in each rat model?

2) The author mentioned that residual urine was measured by pressing the lower abdomen (P.9, line 167). Is this reliably reproducible?

3) All C2N and C2 rats exhibited NVCs in the CMGs despite being subjected to severe pelvic nerve injury by wider resection. Why? Discuss the issue (P.12, line 240).

Minor

1) how do you evaluate QOL of rat? ( P.12, line 237)

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Reviewer #1: No

Reviewer #2: No

**********

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While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

Revision 1

Reviewer #1: It is an interesting work, the authors spend a remarkable effort to obtain their results, the result was well presented, some remarques required a major revision

In abstract

Add a brief explanation to compare the various terms of types A, B1, C1 and C2.

Add (using immunohistochemistry) in methodology.

It is better to use passive tense rather using (We established …..)

In introduction

Line 49: Add a paragraph to compare the various terms of types A, B1, C1 and C2.

Line 54: Add a paragraph to explain the normal anatomy of pelvic plexus in human and to justify the use of rat model with references.

The paragraph between lines 59 and 61 need a suitable reference.

Line 62: (Not only did we show the structural) needs lingual revision, native speaker revision is demanded.

Response: Thank you for your valuable advice. We have revised the manuscript according to the reviewer’s suggestion.

In results

It is not clear whether the loose of rats in B1 and C1 was related to the operation complication? Please clarify.

Response: Thank you for your valuable advice. We have added this information in the section of “Experimental design”: Besides, one rat in type B1 group and two rats in type C1 group died 2 to 3 days after operation due to operation complication, and additional rats were supplemented.

Line 98: Adding schematic drawing to explain the different types of procedure with location of nerves will help to explain.

Line 171: Adding samples of images of 2.5 and 2.6 procedures could help to explain.

Line 195: Add more information about the primary and secondary antibodies and the action of Pgp9.5. with reference>

Response: The reviewer’s comment is well appreciated. We have revised the manuscript, figure 1 and figure 3 according to the advices.

In discussion:

The clinical application according to the results of this work was not obvious, is it the standardizing of the model or the application in surgical technique in human.

Response: The reviewer’s comment is well appreciated. We have added some comments on this topic at the end of the first paragraph in the discussion section.

Reviewer #2: The author describes the establishment of a new animal model mimicking neurogenic bladder dysfunction induced by pelvic nerve injury following radical hysterectomy. The new rat model was characterized by the severity of bladder dysfunction being graded by surgical radicality, which is interesting. However, this manuscript still has some points to be resolved, as follows:

Major

1) Several surgical procedures have been developed to create a stratified neurogenic bladder in rats mimicking UAB followed by total hysterectomy. How should the author decide what millimeters of tissue from cervices should be dissected in each rat model?

Response: The reviewer’s comment is well appreciated. The average vaginal length of women is approximately 10 cm, and the length of vaginal resection of 0~10mm, at least 10mm, and 15-20mm in human RH of types A, B and C RH respectively1. The average vaginal length of adult SD rats is approximately 15 mm; accordingly, the length of vaginal resection we used is minimal, 1-2mm, 2-3mm and 3mm for types A, B, C1 and C2 RH in this study.

2) The author mentioned that residual urine was measured by pressing the lower abdomen (P.9, line 167). Is this reliably reproducible?

Response: The reviewer’s comment is well appreciated. A more accurate method of measuring residual urine is bladder intubation after anesthesia, which is rarely used. Abdominal compression is a simple, noninvasive method that is comparable to ultrasound measurements in accuracy2, although it may result in a small amount of urine remaining in the bladder. Our data from the same animal at different time points also showed the stability of the measured values.

3) All C2N and C2 rats exhibited NVCs in the CMGs despite being subjected to severe pelvic nerve injury by wider resection. Why? Discuss the issue (P.12, line 240).

Response: The reviewer’s comment is well appreciated. In fact, frequent nonvoiding contraction is not a real contraction but the characteristic of instable detrusor after severe urinary retention and neurogenic bladder. We have added this context in the manuscript: “The loss of neural innervation would impair the sensation, autonomic dilation and contraction of bladder, caused urinary retention and instable detrusor with overactive bladder, characterized by overflow incontinence and NVCs.”

Minor

1) how do you evaluate QOL of rat? ( P.12, line 237)

Response: The reviewer’s comment is well appreciated. The “Quality of life” referred to the voiding habit and pattern reflected by spotting test. Thus, we changed “quality of life” to “voiding habit” for accuracy.

References

1. Querleu D, Morrow CP. Classification of radical hysterectomy. Lancet Oncol. Mar 2008;9(3):297-303. doi:10.1016/S1470-2045(08)70074-3

2. Sartori AM, Schwab ME, Kessler TM. Ultrasound: A Valuable Translational Tool to Measure Postvoid Residual in Awake Rats? Eur Urol Focus. Sep 15 2020;6(5):916-921. doi:10.1016/j.euf.2019.11.016

Attachments
Attachment
Submitted filename: PONE response 20240714WYP.docx
Decision Letter - Antoine Naem, Editor

PONE-D-23-42513R1Pelvic neural injuries and acute voiding changes in rat models of radical hysterectomyPLOS ONE

Dear Dr. Wang,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

Please submit your revised manuscript by Oct 31 2024 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

  • A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.
  • A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.
  • An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.
If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols.

We look forward to receiving your revised manuscript.

Kind regards,

Antoine Naem, M.D.

Academic Editor

PLOS ONE

Journal Requirements:

Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

Additional Editor Comments:

Please address the reviewer’s comment regarding the voiding dysfunction in the Type A group.

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: All comments have been addressed

Reviewer #2: All comments have been addressed

**********

2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: the authors responded to reviewers comments and preformed the demanded modifications in the manuscript

Reviewer #2: The manuscript has now been revised accordingly. However, the following issues remain to be discussed:

In the Discussion section, the authors described “ our findings revealed some clues of neurological damage and voiding dysfunction in type A and B1 RHs,,, “ (line 310). In contrast, there were no significant differences in voiding functional parameters between the sham and type A groups (Fig.3 and 4). The authors cannot conclude that even a type A RH procedure causes voiding dysfunction. Please answer.

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7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

Reviewer #2: No

**********

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

Revision 2

The reviewer’s comment is well appreciated. We have revised the manuscript as “our findings revealed some clues of neurological damage and voiding dysfunction in type B1 RH, as manifested by decreased mean area of urine spots and leakage point pressure, and increased collagen volume fraction in affected rats”.

Attachments
Attachment
Submitted filename: PONE response 20240917WYP.docx
Decision Letter - Antoine Naem, Editor

Pelvic neural injuries and acute voiding changes in rat models of radical hysterectomy

PONE-D-23-42513R2

Dear Dr. Wang,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

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Kind regards,

Antoine Naem, M.D.

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Formally Accepted
Acceptance Letter - Antoine Naem, Editor

PONE-D-23-42513R2

PLOS ONE

Dear Dr. Wang,

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Kind regards,

PLOS ONE Editorial Office Staff

on behalf of

Dr. Antoine Naem

Academic Editor

PLOS ONE

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