PONE-D-19-18282

Physiological impact of nanoporous acupuncture needles: laser Doppler perfusion imaging in healthy volunteers

PLOS ONE

Dear Dr Koh-Woon Kim,

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.

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Thank you for your submission to this journal.

Please find the reviewers comments. Please address each of these points and indicate clearly your response to each and where it can be found in the revised manuscript.

I would like to see more defence of the design. Specifically, 1) the choice of a randomised crossover trial and it be clearly marked on the results tables the data from each group before and after the cross-over 2) defence of the choice of the blinding question to participants 3) consideration in the discussion as to the statistical power of the study (for a large, medium or small effect) and whether the study is powered to find the change that occurred.

One reviewer is quite critical about the choice of one acupuncture point and healthy volunteers therefore please defend these choices heavily in your revised paper.

The other reviewer has made comment about some of your procedural choices and possible effects on microcirculation - please consider these carefully.

I look forward to seeing your revised paper and hope you find the reviewers comments constructively helpful.

Leica

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We would appreciate receiving your revised manuscript by Nov 08 2019 11:59PM. When you are 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.

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We look forward to receiving your revised manuscript.

Kind regards,

Leica S. Claydon-Mueller

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: Partly

Reviewer #2: No

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

Reviewer #1: I Don't Know

Reviewer #2: N/A

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

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Reviewer #1: No

Reviewer #2: Yes

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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: I thought the authors present an excellent piece of research on nanoporous acupuncture needles - there's definitely novelty and implications for use in clinical practice. However, I reckon this manuscript needs minor to major revisions with regard to (I) English language for clarity and style consistent with the standards of scientific / academic rigour (II) inadequate reporting of data from which inferences were drawn.

I have tried to highlight some of the points

Lines 36-37 & 108-109: "In a randomized, controlled crossover trial" - is this a randomised crossover laboratory study?

Line 43: "consequently" - or subsequently?

Lines 91-95: consider rephrasing the sentence - it appears too long and difficult to comprehend.

Line 101: "led to the enhanced therapeutic effect of acupuncture" - therapeutic effect appears vague, is it increased flow of blood in the microcirculation, pain-relief? consider for clarity?

Line 117: "Participants" - I think they are still volunteers at this stage. Once they enroll after signing consent, they become participants.

Lines 117-121: I was wondering what is the reason for your eligibility criteria? Some references might help

Lines 122-125: Consider rephrasing the sentence - unclear

Line 129: consider deleting "trial"

Line 133 & 152-156: "received PA on the left leg and, after 30 minutes of rest, received OA on the right leg" - I think I get the sense of it but some readers might find it difficult to follow - for e.g., was Doppler imaging done during these 30 mins? I think it would be easier to follow if there's a graph showing sequence of events

Lines 141-145: "history of alcohol ingestion, smoking, and medication" - I appreciate the information collected, think these could potentially have affected blood microcirculation? If these were not controlled, I'd consider making a note of it in the limitations section.

Line 155: "consequently" or subsequently?

Line 166: could cleaning with alcohol have altered blood microcirculation?

Lines commencing 359: "study`" single inverted comma might have inadvertently been put?

Other points

1. Statistical analysis seem to have been performed appropriately however reporting data tables might be useful.

2. Other information missing such as was constraint randomisation used? What are the p values in Tables 2 & 3

3. Although the authors have provided conclusion in the abstract, I think it is missing from the main text.

Reviewer #2: This study is a physiological assessment of one new kind of acupuncture (nanoporous acupuncture) compared with traditional acupuncture. Although, the study is innovative, the design of the study is not rigorous. Firstly, the choose of healthy people is not enough since most of the subjects who seek acupuncture treatment is not healthy. Secondly, only one acupoint-ST36 for the assessment is not consistent with the real situation. Usually, we will use more than 10 acupoints per treatment and their blood flow may interact with each other. Thirdly, the effectiveness of this kind of acupuncture is totally unknown and the underlying mechanism of acupuncture is complex and only test blood flow is too far from the traditional acupuncture.

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Reviewer #1: Yes: Gourav Banerjee, PhD

Reviewer #2: No

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PONE-D-19-18282R1

Physiological impact of nanoporous acupuncture needles: laser Doppler perfusion imaging in healthy volunteers

PLOS ONE

Dear Dr Koh-Woon Kim,

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.

Thank you for your very clear and appropriate responses to my comments and the reviewers.

I have one final suggestion in relation to blinding. Please could some consideration be made, not only about the participants, but the assessors and statistician blinding. For example, did the statistician know which groups received what stimulation when performing the analysis?

Thank you very much.

We would appreciate receiving your revised manuscript by 5 November 2019. When you are 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.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter.

To enhance the reproducibility of your results, we recommend that if applicable you deposit your laboratory protocols in protocols.io, where a protocol can be assigned its own identifier (DOI) such that it can be cited independently in the future. For instructions see: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols

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). This letter should be uploaded as separate file and labeled 'Response to Reviewers'.
• A marked-up copy of your manuscript that highlights changes made to the original version. This file should be uploaded as separate file and labeled 'Revised Manuscript with Track Changes'.
• An unmarked version of your revised paper without tracked changes. This file should be uploaded as separate file and labeled 'Manuscript'.

Please note while forming your response, if your article is accepted, you may have the opportunity to make the peer review history publicly available. The record will include editor decision letters (with reviews) and your responses to reviewer comments. If eligible, we will contact you to opt in or out.

We look forward to receiving your revised manuscript.

Kind regards,

Dr. Leica S. Claydon-Mueller

Academic Editor

PLOS ONE

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

[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 to be viewed.]

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 us at figures@plos.org. Please note that Supporting Information files do not need this step.

Physiological impact of nanoporous acupuncture needles: laser Doppler perfusion imaging in healthy volunteers

PONE-D-19-18282R2

Dear Dr. Koh-Woon Kim,

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

Within one week, you will receive an e-mail containing information on the amendments required prior to publication. When all required modifications have been addressed, you will receive a formal acceptance letter and your manuscript will proceed to our production department and be scheduled for publication.

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With kind regards,

Leica S. Claydon-Mueller

Academic Editor

PLOS ONE