Efficacy of acupuncture in the treatment of post-stroke depression: A study protocol of a randomized controlled trial

Menghan Li; Dawei Ran; Xinming Yang; Yu Wang; Qian Zhu; Xiaoli Song; Lei Shi; Yuzheng Du

doi:10.1371/journal.pone.0303162

Peer Review History

Original SubmissionOctober 10, 2023
12 Dec 2023 Decision Letter - Yung-Hsiang Chen, Editor PONE-D-23-31081Efficacy of Acupuncture in the Treatment of Post-stroke Depression: A Study Protocol of a Randomized Controlled Trial PLOS ONE Dear Dr. YANG, 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 Jan 26 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. 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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 If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.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: Thank you for submitting the following manuscript to PLOS ONE. Please revise the manuscript according to the reviewers' comments and upload the revised file. [Note: HTML markup is below. Please do not edit.] Reviewers' comments: Reviewer's Responses to Questions Comments to the Author 1. Does the manuscript provide a valid rationale for the proposed study, with clearly identified and justified research questions? The research question outlined is expected to address a valid academic problem or topic and contribute to the base of knowledge in the field. Reviewer #1: Yes Reviewer #2: Yes ******** 2. Is the protocol technically sound and planned in a manner that will lead to a meaningful outcome and allow testing the stated hypotheses? The manuscript should describe the methods in sufficient detail to prevent undisclosed flexibility in the experimental procedure or analysis pipeline, including sufficient outcome-neutral conditions (e.g. necessary controls, absence of floor or ceiling effects) to test the proposed hypotheses and a statistical power analysis where applicable. As there may be aspects of the methodology and analysis which can only be refined once the work is undertaken, authors should outline potential assumptions and explicitly describe what aspects of the proposed analyses, if any, are exploratory. Reviewer #1: Yes Reviewer #2: Yes ****** 3. Is the methodology feasible and described in sufficient detail to allow the work to be replicable? Descriptions of methods and materials in the protocol should be reported in sufficient detail for another researcher to reproduce all experiments and analyses. The protocol should describe the appropriate controls, sample size calculations, and replication needed to ensure that the data are robust and reproducible. Reviewer #1: Yes Reviewer #2: Yes ****** 4. Have the authors described where all data underlying the findings will be made available when the study is complete? The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception, at the time of publication. 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: No ****** 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 and, if applicable, provide comments about issues authors must address before this protocol can be accepted for publication. You may also include additional comments for the author, including concerns about research or publication ethics. You may also provide optional suggestions and comments to authors that they might find helpful in planning their study. (Please upload your review as an attachment if it exceeds 20,000 characters) Reviewer #1: There are minor English errors throughout the proposed protocol. Introduction: Stroke increases the risk of PSD, which is also a negative factor in stroke recovery Since PSD is defined as “post stroke depression” stroke does not increase the risk of PSD, it is a required factor to have PSD. This needs to be re-written. Methods: tense should be changed to consistently be future tense: For example: One group received XNKQ acupuncture mainly, and escitalopram was taken… This should be re-written as One group WILL receive XNKQ acupuncture mainly, and escitalopram will be taken…. This tense issue remains throughout this section. Adverse event report Suppose severe adverse events appear in the experiment. In that case, the researcher must take immediate measures to protect the safety… This needs to be written without the “suppose” and adverse events happen to subjects not “appear in the experiment.” Please re-write this section. Reviewer #2: Dear editors The following is my opinion, and the purpose of this trial is to demonstrate the efficacy of acupuncture in PSD. Patients six months after stroke were selected for this study. Depression is one of the most important sequelae of stroke, and PSD often appears within 3 months of stroke. The golden rehabilitation period for stroke is 3-6 months after stroke, and post-stroke depression will reduce the patient's willingness to do rehabilitation, slow down the recovery from stroke, and even miss the opportunity of the golden rehabilitation period for stroke. Acupuncture for depression is a proven treatment that can be recommended. The study was not completed, and there were no experimental results in the text. The number of people who actually participated in and dropped out of the trial, adverse reactions, etc. Ask questions about the design of the study are as follows. 1 Will the patients in the study lose the best opportunity for treatment after six months of stroke? 2 Inclusion criteria 4 on page 5, Select subjects The HAMD score of 8 to 17 with mild depression. Will the HAMD score be less sensitive to changes in the severity of depression in mild cases, and will it affect the outcome analysis? 3 Depending on your design, Acupuncturists and subjects cannot communicate with each other. If a patient has adverse effects after needling, such as persistent soreness or difficulty withdrawing needles, will the patient withdraw from the trial, or will there be other treatments? 4 Are the acupuncture points fixed or can they be adjusted, and will the subjects receive acupuncture and electroacupuncture at the same time? 5 Isn't the medication necessarily the same for different subjects? 6 Table 2 shows the acupuncture points of both the experimental group and the control group, please color distinguish them in Table 2 to avoid confusion. 7 According to the text, the acupuncture of the control group did not administer "De Qi". 8 XingnaoKaiqiao (XNKQ) acupuncture is usually used in patients who are unconscious in the acute phase of stroke, where techniques such as Sparrow-pecking acupuncture techniques in Shuigou (DU26) on the upper lip can cause extreme pain and tears and are subjects with depression in remission of stroke too irritated. ****** 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: Yes: Jennifer Brett 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/. 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Revision 1
14 Feb 2024 Author Response Dear reviewers, We deeply appreciate your review work. Thank you for raising constructive questions about this study, which can make it more scientific. We have also deeply reflected on and made revisions. The following are responses to the questions raised by two reviewers. If you have any questions, please criticize and contact us. Answers to Reviewer 1's Questions: Q: There are minor English errors throughout the proposed protocol. Introduction: Stroke increases the risk of PSD, which is also a negative factor in stroke recovery Since PSD is defined as “post stroke depression” stroke does not increase the risk of PSD, it is a required factor to have PSD. This needs to be re-written. Methods: tense should be changed to consistently be future tense: For example: One group received XNKQ acupuncture mainly, and escitalopram was taken… This should be re-written as One group WILL receive XNKQ acupuncture mainly, and escitalopram will be taken…. This tense issue remains throughout this section. Adverse event report Suppose severe adverse events appear in the experiment. In that case, the researcher must take immediate measures to protect the safety… This needs to be written without the “suppose” and adverse events happen to subjects not “appear in the experiment.” Please re-write this section. Re: Thank you for your careful guidance. We regret the presentation errors, grammatical and tense errors in the manuscript, and have revised and proofread the manuscript in its entirety, including deleting the relevant content in the introduction section regarding the relationship between stroke and PSD. The tense in the Methods section has been changed to future tense. The Adverse Event Report section has been rewritten. Answers to Reviewer 2's Questions: 1. Will the patients in the study lose the best opportunity for treatment after six months of stroke? Re: Thank you for your concern in the long-term treatment of stroke in the patients who will be involved in this study. The timing of stroke rehabilitation is critical, and there are statistics that 8 to 12 weeks after stroke is a period of rapid recovery from physical dysfunction in patients. If early rehabilitation can be carried out as early as six months after the onset of the disease, the survival rate of patients will increase to over 90% [1]. It can be confirmed that there are still opportunities for treatment even after six months. Taking into account the actual clinical efficacy and the patient's own needs for treatment, after a six-month stroke prognosis and rehabilitation, in addition to the basic medication that will continue to be taken under the supervision of the physician, the treatment will continue to have acupuncture outpatient treatment by the responsible physician. It is certain that this study will not delay the clinical treatment available to any subjects. [1] Shao Limin. Evaluation of the effect of medical and nursing joint health education intervention on nursing extension service for patients discharged from hospital with cerebral infarction[J]. Modern practical medicine,2018,30(07):968-969. 2. Inclusion criteria 4 on page 5, Select subjects The HAMD score of 8 to 17 with mild depression. Will the HAMD score be less sensitive to changes in the severity of depression in mild cases, and will it affect the outcome analysis? Re: With regard to the choice of depression scales, we believe that the HAMD is necessary, the HAMD scale is the "gold standard" for the diagnosis and assessment of depression, and the scores of the 17-item HAMD were derived from the ratings according to the conversion method described by Endicott [1], and in the conclusions of the study by Zimmerman [2] et al. patients with mild depression had significantly lower HAMD scores than those with moderate depression, and those with moderate depression had significantly lower HAMD scores than those with major depression. The HAMD threshold that maximized the sum of sensitivity and specificity was 17 in the comparison of mild and moderate depression, and 24 in the comparison of moderate and severe depression, thus suggesting that HAMD is sensitive in mild depression. In addition, Helmreich [3] et al. compared the Inventory of Depressive Symptomatology(IDS-C) and HAMD scales concerning sensitivity to changes in antidepressant treatment, and although mild depression was more sensitive on the PSDIDS-C subscale, the subscales did not cover all aspects of depression and the benefit ratios, and the IDS-C scales themselves are less frequently used in diagnostic assessment of PSD, so we still selected the classical scale HAMD. [1] Endicott J, Cohen J, Nee J, Fleiss J, Sarantakos S. Hamilton Depression Rating Scale: Extracted From Regular and Change Versions of the Schedule for Affective Disorders and Schizophrenia. Arch Gen Psychiatry. 1981;38(1):98–103. doi:10.1001/archpsyc.1981.01780260100011 [2] Zimmerman M, Martinez JH, Young D, Chelminski I, Dalrymple K. Severity classification on the Hamilton Depression Rating Scale. J Affect Disord. 2013;150(2):384-388. doi:10.1016/j.jad.2013.04.028 [3] Helmreich, I., Wagner, S., Mergl, R. et al. Sensitivity to changes during antidepressant treatment: a comparison of unidimensional subscales of the Inventory of Depressive Symptomatology (IDS-C) and the Hamilton Depression Rating Scale (HAMD) in patients with mild major, minor or subsyndromal depression. Eur Arch Psychiatry Clin Neurosci 262, 291–304 (2012). https://doi.org/10.1007/s00406-011-0263-x 3. Depending on your design, Acupuncturists and subjects cannot communicate with each other. If a patient has adverse effects after needling, such as persistent soreness or difficulty withdrawing needles, will the patient withdraw from the trial, or will there be other treatments? Re: The scope of the inability to communicate in the design of this manuscript refers to the inability to communicate between the subjects and the acupuncturists about the plan, and the subject's inability to communicate with other subjects, for which we have rewritten in the revised manuscript due to inappropriate language, rewritten in the 2.4 Blinding section. If subjects experience adverse reactions after acupuncture, such as persistent soreness or difficulty in removing the needle, we can refer to the additional content on the treatment of adverse reactions in section 2.7 Safety Evaluation and Adverse Events 4. Are the acupuncture points fixed or can they be adjusted, and will the subjects receive acupuncture and electroacupuncture at the same time? Re: Once the study is underway, all acupuncture points will be fixed, including those in the antidepressant acupuncture group and those in the control group, while subjects in the antidepressant acupuncture group will receive both "XNKQ" acupuncture and electroacupuncture. 5. Isn't the medication necessarily the same for different subjects? Re: In Section 2.5 Interventions and Comparison, we set out the need for physicians responsible for treating high-risk underlying conditions for stroke to provide basic symptomatic treatment in response to the patient's symptoms.Basic therapeutic drugs are not necessarily the same for different subjects, however, the principle of medication is consistent across subjects, for example, all will be taking antiplatelet drugs and lipid-lowering drugs, and there will also be for hypertension, diabetes, etc. There may also be a superimposition of different types of underlying diseases. In several studies [1-3] on the use of acupuncture in the treatment of post-stroke-related disorders, both control and experimental groups were given conventional treatments, including symptomatic treatments such as infection prevention, vasodilatation, and anticoagulation, which suggests that receiving different symptomatic primary treatments does not have a significant impact on the existing treatment protocols or on the subjects themselves. [1] Chu Jiaxin,Peng Fei, Li Jiaojiao et al. Clinical effect of waking up the brain and opening up the mind acupuncture combined with repetitive transcranial magnetic stimulation in the treatment of post-stroke thalamic pain[J]. Chinese Medicine Herald,2023,20(32): 88-92.DOI:10.20047/j.issn1673-7210.2023.32.19. [2] Yang Daohai,Miao Yongjuan,Xu Shasha et al. Effects of waking up the brain and opening up the mind acupuncture method on the morphology of oropharynx and sleep breathing parameters in patients with obstructive sleep apnoea syndrome after stroke[J]. Shanghai Journal of Acupuncture and Moxibustion,2023,42(06):565-569.DOI:10.13460/j.issn.1005-0957.2023.06.0565. [3] Yu Zhuoting,Chen Yangfu,Xu MiMi. Analysis of therapeutic effect of waking up the brain and opening up the mind in treating patients with hemiplegia after stroke by acupuncture[J]. Liaoning Journal of Chinese Medicine,2023,50(09):192-195.DOI:10.13192/j.issn.1000-1719.2023.09.051. 6. Table 2 shows the acupuncture points of both the experimental group and the control group, please color distinguish them in Table 2 to avoid confusion. Re: The lack of clarity in the grouping of acupuncture points in Table 2 is an omission, and to show the grouping of the points, we have added a description of the grouping of acupoints in Table 2, =Acupoints in the Antidepressant acupuncture group. =Acupoints in the Control group 7. According to the text, the acupuncture of the control group did not administer "De Qi". Re: Thank you for your careful monitoring of the requirement of "De Qi" as an important step in the practice of acupuncture, we have added the following sentence to section 2.5.1 of the manuscript “The acupuncture method is used to “De Qi” before the acupuncture is performed” , and to add an explanation of "De Qi" in section 2.5.2. 8. XingnaoKaiqiao (XNKQ) acupuncture is usually used in patients who are unconscious in the acute phase of stroke, where techniques such as Sparrow-pecking acupuncture techniques in Shuigou (DU26) on the upper lip can cause extreme pain and tears and are subjects with depression in remission of stroke too irritated. Re: Shuigou(DU 26)is from "Zhen Jiu Jia Yi Jing", belonging to the DuMai, in the face of the human middle groove of the upper 1/3 and the middle 1/3 point of the intersection. In a study by Zhang [1], specific acupuncture points of the "XNKQ" acupuncture method combined with medication for the treatment of PSD improved the patients' depression and ability to perform daily life and reduced the corresponding inflammatory response. Huang [2] et al. also found the effect of acupuncture at Shuigou on the function of limbs and intracranial haemodynamics of patients recovering from a stroke, in their study, when patients recovering from stroke were treated with acupuncture at Shuigou acupoint and Baihui combined with acupuncture at the foot transporting sensory area, the levels of NT-3 and NGF increased, indicating that the treatment of patients recovering from stroke with acupuncture at Shuigou acupoint and Baihui combined with acupuncture at the foot transporting sensory area was able to improve the patients' neurological function. intracranial haemodynamics. Yan [3] found the Shuigou point to be a high-frequency point in a study on the matching pattern of acupoints selected for acupuncture treatment of post-stroke depression. In addition, in a recent study by Li [4] et al, high-level evidence was provided that the "XNKQ" acupuncture method is effective in the treatment of post-stroke motor aphasia, which is a long-term prognosis. [1] Zhang Chuanwen, Min Xirui. Effects of waking up the brain and opening up the orifices acupuncture combined with wuling capsule in treating post-stroke depression on autophagy-related protein levels[J]. Shanghai Journal of Acupuncture and Moxibustion,2023,42(02):121-126.DOI:10.13460/j.issn.1005-0957.2023.02.0121. [2] Huang Shiwei,LI Gui Ying,Yang Liang. Effects of acupuncture Shuigou and Baihui points combined with foot transporting sensory zone on limb function and intracranial haemodynamics in patients recovering from stroke[J]. New Chinese Medicine,2022,54(21):178-182.DOI:10.13457/j.cnki.jncm.2022.21.040. [3] Yan KH,Ren RX,Fan WT et al. Analysis of the pattern of acupuncture point selection and matching in the treatment of post-stroke depression by acupuncture[J]. Journal of Integrated Cardiovascular and Cerebrovascular Diseases of Chinese and Western Medicine,2023,21(03):421-425. [4] Li B, Deng S, Zhuo B, et al. Effect of Acupuncture vs Sham Acupuncture on Patients With Poststroke Motor Aphasia: A Randomized Clinical Trial. JAMA Netw Open. 2024;7(1):e2352580. Published 2024 Jan 2. doi:10.1001/jamanetworkopen.2023.52580 Attachments Attachment Submitted filename: Response to Reviewers(2).docx* https://doi.org/10.1371/journal.pone.0303162.r002
28 Feb 2024 Decision Letter - Yung-Hsiang Chen, Editor PONE-D-23-31081R1Efficacy of Acupuncture in the Treatment of Post-stroke Depression: A Study Protocol of a Randomized Controlled TrialPLOS ONE Dear Dr. YANG, 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 submitting the following manuscript to PLOS ONE. Please revise the manuscript according to the reviewers' comments and upload the revised file. ============================== Please submit your revised manuscript by Apr 13 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, Yung-Hsiang Chen, Ph.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: Thank you for submitting the following manuscript to PLOS ONE. Please revise the manuscript according to the reviewers' comments and upload the revised file. [Note: HTML markup is below. Please do not edit.] Reviewers' comments: Reviewer's Responses to Questions Comments to the Author 1. Does the manuscript provide a valid rationale for the proposed study, with clearly identified and justified research questions? The research question outlined is expected to address a valid academic problem or topic and contribute to the base of knowledge in the field. Reviewer #1: Yes Reviewer #2: Yes ******** 2. Is the protocol technically sound and planned in a manner that will lead to a meaningful outcome and allow testing the stated hypotheses? The manuscript should describe the methods in sufficient detail to prevent undisclosed flexibility in the experimental procedure or analysis pipeline, including sufficient outcome-neutral conditions (e.g. necessary controls, absence of floor or ceiling effects) to test the proposed hypotheses and a statistical power analysis where applicable. As there may be aspects of the methodology and analysis which can only be refined once the work is undertaken, authors should outline potential assumptions and explicitly describe what aspects of the proposed analyses, if any, are exploratory. Reviewer #1: Yes Reviewer #2: Yes ****** 3. Is the methodology feasible and described in sufficient detail to allow the work to be replicable? Descriptions of methods and materials in the protocol should be reported in sufficient detail for another researcher to reproduce all experiments and analyses. The protocol should describe the appropriate controls, sample size calculations, and replication needed to ensure that the data are robust and reproducible. Reviewer #1: Yes Reviewer #2: Yes ****** 4. Have the authors described where all data underlying the findings will be made available when the study is complete? The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception, at the time of publication. 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 and, if applicable, provide comments about issues authors must address before this protocol can be accepted for publication. You may also include additional comments for the author, including concerns about research or publication ethics. You may also provide optional suggestions and comments to authors that they might find helpful in planning their study. (Please upload your review as an attachment if it exceeds 20,000 characters) Reviewer #1: Acupoint identification and naming issues remain in sections 2.5.1 and 2.5.2 In 2.5.1: Shuigou (DU26) is said to be needled bilaterally. DU26 has only one location on the midline. Are two needles to be placed? In 2.5.2 use of the acupoint names is inconsistent with Table 2. In the table the Du Mai points are labeled Du 16 and Du 20. In 2.5.2, acupoint names use “GV” rather than DU: “Baihui (GV20)… Fengfu (GV16)” Please change all to “DU” in 2.5.2. Reviewer #2: The author answered the previous question and can accept its correction. Question 2 asked earlier Inclusion criteria 4 Select subjects The HAMD score of 8 to 17 with mild depression. It may affect the difference, resulting in little difference between the two groups, but it will also need to be verified by clinical trials. ****** 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". 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Revision 2
8 Apr 2024 Author Response Dear reviewers, We deeply appreciate your review work. Thank you for raising constructive questions about this study. We have also deeply reflected on and made revisions. The following are responses to the questions raised by two reviewers. If you have any questions, please criticize and contact us. Answers to Reviewer 1's Questions: Q: Acupoint identification and naming issues remain in sections 2.5.1 and 2.5.2. In 2.5.1: Shuigou (DU26) is said to be needled bilaterally. DU26 has only one location on the midline. Are two needles to be placed? In 2.5.2 use of the acupoint names is inconsistent with Table 2. In the table the Du Mai points are labeled Du 16 and Du 20. In 2.5.2, acupoint names use “GV” rather than DU: “Baihui (GV20)… Fengfu (GV16)” Please change all to “DU” in 2.5.2. Re: Thank you for your careful guidance. We apologize for these errors and have now standardized the descriptions of acupoints in 2.5.1, 2.5.2 and Table 2, with Baihui being standardized as DU20, Yintang as EX-HN3 and Fengfu as DU16. The standardization of the terminology and names of the locations is very important and will be taken care of in future studies. We will be careful in future studies. Answers to Reviewer 2's Questions: Q: The author answered the previous question and can accept its correction. Question 2 asked earlier Inclusion criteria 4 Select subjects The HAMD score of 8 to 17 with mild depression. It may affect the difference, resulting in little difference between the two groups, but it will also need to be verified by clinical trials. Re: Thank you very much for raising this thought-provoking question. In fact, when designing the experiment, we mainly wanted to observe the effect of acupuncture therapy on mild depression after stroke. If we include patients with scores above 17 and severe depression, medication intervention is necessary, and the existing research protocol does not comply with clinical guidelines and ethical requirements. However, the comparison with drug efficacy is not the problem that our research aims to solve. We aim to explore the significance of acupuncture intervention in patients with mild depression after stroke based on the anti-inflammatory mechanism of acupuncture. The comparison of drug efficacy may be the plan for the next step of research. Of course, the question you raised is also a reality, so we have read a lot of related research. We found that a published study also used the same inclusion criteria for HAMD segments[1]. And they also obtained statistically significant results. Moreover, sample size is also a factor that affects the statistical significance of the results. This study used 35 patients in each group, while our study sample consisted of 42 patients in each group. So we believe that this setting is reasonable. If, as you mentioned, the research results do not show significant differences, we will carefully analyze the reasons and discuss them, which also provides an opportunity for future research. [1] Sun Q, Xu H, Zhang W, Zhou Y, Lv Y. Behavioral Activation Therapy for Subthreshold Depression in Stroke Patients: An Exploratory Randomized Controlled Trial. Neuropsychiatr Dis Treat. 2022 Nov 29;18:2795-2805. doi: 10.2147/NDT.S392403. Attachments Attachment Submitted filename: Response to Reviewers.docx https://doi.org/10.1371/journal.pone.0303162.r004
22 Apr 2024 Decision Letter - Yung-Hsiang Chen, Editor Efficacy of Acupuncture in the Treatment of Post-stroke Depression: A Study Protocol of a Randomized Controlled Trial PONE-D-23-31081R2 Dear Dr. Yang, 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. Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication. An invoice will be generated when your article is formally accepted. Please note, if your institution has a publishing partnership with PLOS and your article meets the relevant criteria, all or part of your publication costs will be covered. 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Reviewers' comments: Reviewer's Responses to Questions Comments to the Author 1. Does the manuscript provide a valid rationale for the proposed study, with clearly identified and justified research questions? The research question outlined is expected to address a valid academic problem or topic and contribute to the base of knowledge in the field. Reviewer #1: Yes ******** 2. Is the protocol technically sound and planned in a manner that will lead to a meaningful outcome and allow testing the stated hypotheses? The manuscript should describe the methods in sufficient detail to prevent undisclosed flexibility in the experimental procedure or analysis pipeline, including sufficient outcome-neutral conditions (e.g. necessary controls, absence of floor or ceiling effects) to test the proposed hypotheses and a statistical power analysis where applicable. As there may be aspects of the methodology and analysis which can only be refined once the work is undertaken, authors should outline potential assumptions and explicitly describe what aspects of the proposed analyses, if any, are exploratory. Reviewer #1: Yes ****** 3. Is the methodology feasible and described in sufficient detail to allow the work to be replicable? Descriptions of methods and materials in the protocol should be reported in sufficient detail for another researcher to reproduce all experiments and analyses. The protocol should describe the appropriate controls, sample size calculations, and replication needed to ensure that the data are robust and reproducible. Reviewer #1: Yes ****** 4. Have the authors described where all data underlying the findings will be made available when the study is complete? The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception, at the time of publication. 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 ****** 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 ****** 6. Review Comments to the Author Please use the space provided to explain your answers to the questions above and, if applicable, provide comments about issues authors must address before this protocol can be accepted for publication. You may also include additional comments for the author, including concerns about research or publication ethics. You may also provide optional suggestions and comments to authors that they might find helpful in planning their study. (Please upload your review as an attachment if it exceeds 20,000 characters) Reviewer #1: The updated submission has addressed all concerns previously identified by this reviewer. No additional corrections needed. ****** 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. 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Formally Accepted
3 May 2024 Acceptance Letter - Yung-Hsiang Chen, Editor PONE-D-23-31081R2 PLOS ONE Dear Dr. Yang, I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now being handed over to our production team. At this stage, our production department will prepare your paper for publication. This includes ensuring the following: * All references, tables, and figures are properly cited * All relevant supporting information is included in the manuscript submission, * There are no issues that prevent the paper from being properly typeset If revisions are needed, the production department will contact you directly to resolve them. If no revisions are needed, you will receive an email when the publication date has been set. At this time, we do not offer pre-publication proofs to authors during production of the accepted work. Please keep in mind that we are working through a large volume of accepted articles, so please give us a few weeks to review your paper and let you know the next and final steps. Lastly, if your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org. If we can help with anything else, please email us at customercare@plos.org. Thank you for submitting your work to PLOS ONE and supporting open access. Kind regards, PLOS ONE Editorial Office Staff on behalf of Dr. Yung-Hsiang Chen Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0303162.r006

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