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<front>
<journal-meta>
<journal-id journal-id-type="publisher-id">Front. Neurol.</journal-id>
<journal-title-group>
<journal-title>Frontiers in Neurology</journal-title>
<abbrev-journal-title abbrev-type="pubmed">Front. Neurol.</abbrev-journal-title>
</journal-title-group>
<issn pub-type="epub">1664-2295</issn>
<publisher>
<publisher-name>Frontiers Media S.A.</publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="doi">10.3389/fneur.2025.1732787</article-id>
<article-version article-version-type="Version of Record" vocab="NISO-RP-8-2008"/>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Systematic Review</subject>
</subj-group>
</article-categories>
<title-group>
<article-title>Efficacy and safety of electroacupuncture for post-stroke depression: a systematic review and meta-analysis</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name>
<surname>Liang</surname>
<given-names>Yue</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
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<surname>Gu</surname>
<given-names>Yujie</given-names>
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<contrib contrib-type="author">
<name>
<surname>Han</surname>
<given-names>Hui</given-names>
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<contrib contrib-type="author">
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<surname>Yin</surname>
<given-names>Huichao</given-names>
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<surname>Gao</surname>
<given-names>Junjun</given-names>
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<surname>Hou</surname>
<given-names>Libo</given-names>
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<surname>Ning</surname>
<given-names>Wenwen</given-names>
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<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
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<contrib contrib-type="author" corresp="yes">
<name>
<surname>Zheng</surname>
<given-names>Zuncheng</given-names>
</name>
<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
<xref ref-type="aff" rid="aff2"><sup>2</sup></xref>
<xref ref-type="aff" rid="aff3"><sup>3</sup></xref>
<xref ref-type="corresp" rid="c001"><sup>&#x002A;</sup></xref>
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<aff id="aff1"><label>1</label><institution>Rehabilitation Centre, Taian Central Hospital</institution>, <city>Taian</city>, <country country="cn">China</country></aff>
<aff id="aff2"><label>2</label><institution>Rehabilitation Centre, Qingdao University Affiliated Taian Central Hospital</institution>, <city>Taian</city>, <country country="cn">China</country></aff>
<aff id="aff3"><label>3</label><institution>Rehabilitation Centre, Taishan Medical and Care Centre</institution>, <city>Taian</city>, <country country="cn">China</country></aff>
<author-notes>
<corresp id="c001"><label>&#x002A;</label>Correspondence: Zuncheng Zheng, <email xlink:href="mailto:zhengzc1965@126.com">zhengzc1965@126.com</email></corresp>
</author-notes>
<pub-date publication-format="electronic" date-type="pub" iso-8601-date="2026-01-12">
<day>12</day>
<month>01</month>
<year>2026</year>
</pub-date>
<pub-date publication-format="electronic" date-type="collection">
<year>2025</year>
</pub-date>
<volume>16</volume>
<elocation-id>1732787</elocation-id>
<history>
<date date-type="received">
<day>26</day>
<month>10</month>
<year>2025</year>
</date>
<date date-type="rev-recd">
<day>22</day>
<month>12</month>
<year>2025</year>
</date>
<date date-type="accepted">
<day>25</day>
<month>12</month>
<year>2025</year>
</date>
</history>
<permissions>
<copyright-statement>Copyright &#x00A9; 2026 Liang, Gu, Han, Yin, Gao, Hou, Ning and Zheng.</copyright-statement>
<copyright-year>2026</copyright-year>
<copyright-holder>Liang, Gu, Han, Yin, Gao, Hou, Ning and Zheng</copyright-holder>
<license>
<ali:license_ref start_date="2026-01-12">https://creativecommons.org/licenses/by/4.0/</ali:license_ref>
<license-p>This is an open-access article distributed under the terms of the <ext-link ext-link-type="uri" xlink:href="https://creativecommons.org/licenses/by/4.0/">Creative Commons Attribution License (CC BY)</ext-link>. The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.</license-p>
</license>
</permissions>
<abstract>
<sec>
<title>Background</title>
<p>Depression is a common comorbid condition in stroke patients, significantly impairing their quality of life. Electroacupuncture (EA) has shown promising effects in treating post-stroke depression (PSD), but integrated evidence remains scarce.</p>
</sec>
<sec>
<title>Objective</title>
<p>To investigate the efficacy of EA in improving PSD and evaluate its clinical effectiveness and safety through systematic review and meta-analysis.</p>
</sec>
<sec>
<title>Methods</title>
<p>We searched eight electronic databases (PubMed, Cochrane Library, Embase, Web of Science, CNKI, VIP Data Platform, Wanfang Data Knowledge Service Platform, and China Biomedical Literature Service System) and manually reviewed reference lists of relevant literature and clinical trial registries for randomized controlled trials (RCTs) of EA for PSD. Eligible studies were screened based on inclusion and exclusion criteria, and relevant data were extracted. Meta-analysis was performed using RevMan 5.4 software.</p>
</sec>
<sec>
<title>Results</title>
<p>A total of 22 studies involving 1,640 patients were included. Meta-analysis results showed that EA improved HAMD (MD&#x202F;=&#x202F;&#x2212;1.71, 95% CI: &#x2212;2.79 to &#x2212;0.63, <italic>I</italic><sup>2</sup> =&#x202F;89%, <italic>p</italic>&#x202F;=&#x202F;0.002), efficacy rate (OR&#x202F;=&#x202F;1.94, 95% CI: 1.43 to 2.64, <italic>I</italic><sup>2</sup> =&#x202F;0%, <italic>p</italic>&#x202F;&#x003C;&#x202F;0.0001), and safety (OR&#x202F;=&#x202F;0.2, 95% CI: 0.12&#x2013;0.34, <italic>I</italic><sup>2</sup> =&#x202F;45%, <italic>p</italic>&#x202F;&#x003C;&#x202F;0.00001). However, it did not show superiority over the control group in terms of the Barthel Index (BI) (MD&#x202F;=&#x202F;4.01, 95% CI: &#x2212;0.26 to 8.27, <italic>I</italic><sup>2</sup> =&#x202F;70%, <italic>p</italic>&#x202F;=&#x202F;0.07) and SDS (MD&#x202F;=&#x202F;&#x2212;3.28, 95%CI: &#x2212;6.78 to 0.21, <italic>I</italic><sup>2</sup> =&#x202F;97%, p&#x202F;=&#x202F;0.07). The GRADE assessment indicates that the evidence level for HAMD is very low, while that for BI is low.</p>
</sec>
<sec>
<title>Conclusion</title>
<p>EA demonstrated superiority over conventional drug therapy in improving HAMD scores, efficacy rates, and safety. However, no significant difference was observed between EA and the control group in improving BI and SDS scores. The pooled results for HAMD scores and SDS showed high heterogeneity, and the study itself exhibited considerable heterogeneity. Furthermore, all included studies were conducted in China, which may introduce regional bias. Future rigorous clinical research is needed to provide high-quality evidence.</p>
</sec>
</abstract>
<kwd-group>
<kwd>depression</kwd>
<kwd>electroacupuncture</kwd>
<kwd>meta-analysis</kwd>
<kwd>stroke</kwd>
<kwd>systematic review</kwd>
</kwd-group>
<funding-group>
<funding-statement>The author(s) declared that financial support was not received for this work and/or its publication.</funding-statement>
</funding-group>
<counts>
<fig-count count="11"/>
<table-count count="3"/>
<equation-count count="0"/>
<ref-count count="44"/>
<page-count count="15"/>
<word-count count="7497"/>
</counts>
<custom-meta-group>
<custom-meta>
<meta-name>section-at-acceptance</meta-name>
<meta-value>Experimental Therapeutics</meta-value>
</custom-meta>
</custom-meta-group>
</article-meta>
</front>
<body>
<sec sec-type="intro" id="sec1">
<label>1</label>
<title>Introduction</title>
<p>Stroke is characterized by high incidence, high disability rates, and high mortality, significantly impacting global health (<xref ref-type="bibr" rid="ref1">1</xref>). Post-stroke depression (PSD), as a common and severe psychiatric complication, adversely affects patients&#x2019; recovery and quality of life (<xref ref-type="bibr" rid="ref2">2</xref>). Data indicates that 25.4% of patients develop PSD within 2 years of stroke onset, yet only 7.8% recognize their depressive symptoms (<xref ref-type="bibr" rid="ref3">3</xref>). These individuals often lack timely or standardized treatment. Despite physical functional improvements, psychological symptoms may worsen, hindering overall recovery.</p>
<p>PSD onset is associated with factors like age, gender, education level, and stroke type. It commonly manifests as persistent low mood, accompanied by cognitive impairment, apathy, anhedonia, fatigue, self-blame, self-harm behaviors, and even suicidal ideation (<xref ref-type="bibr" rid="ref4">4</xref>). PSD exhibits complex interactions with other complications such as anxiety, neurological deficits, and obstructive sleep apnea (<xref ref-type="bibr" rid="ref5">5</xref>), potentially leading to severe functional impairment, reduced quality of life, recurrent stroke, and mortality (<xref ref-type="bibr" rid="ref6">6</xref>, <xref ref-type="bibr" rid="ref7">7</xref>). PSD may involve diverse etiological mechanisms, encompassing biological and psychological hypotheses (<xref ref-type="bibr" rid="ref8">8</xref>). Biological hypotheses include four mechanisms: lesion localization, neurotransmitter, inflammatory cytokine, and genetic polymorphism. The specific location of lesions plays a crucial role in PSD pathogenesis; reduced serotonin and norepinephrine in the brain are associated with PSD; increased cytokines post-stroke may lead to depression; and the short variant genotype of the serotonin transporter gene linkage promoter region shows a significant association with major depressive disorder after stroke (<xref ref-type="bibr" rid="ref9">9</xref>). Psychological hypotheses suggest that social and psychological stressors associated with stroke may be primary contributors to depression. Currently, no definitive evidence supports or refutes purely biological or purely psychosocial mechanisms. It appears to be a psychosocial, multifactorial mental disorder.</p>
<p>Current PSD treatment primarily relies on pharmacotherapy, supplemented by psychotherapy and techniques like transcranial magnetic stimulation (<xref ref-type="bibr" rid="ref10">10</xref>). However, pharmacological interventions exhibit slow onset (typically 4&#x2013;8&#x202F;weeks) and are prone to drug tolerance and adverse reactions (<xref ref-type="bibr" rid="ref11">11</xref>, <xref ref-type="bibr" rid="ref12">12</xref>). This poses challenges for PSD patients&#x2019; recovery. EA is a technique that builds upon traditional acupuncture methods. After obtaining qi sensation at the acupoint, a microcurrent wave (sensing) that responds to the body&#x2019;s bioelectricity is applied through the needle to treat diseases. It is currently widely used in the treatment of PSD and has achieved certain clinical effects. Although clinical evidence demonstrates the good efficacy of EA in treating PSD, the current evidence has not been effectively integrated and has not formed persuasive evidence-based medical evidence.</p>
<p>Therefore, this study conducts a systematic review and meta-analysis of clinical research on EA for PSD to integrate existing evidence, provide reliable guidance for clinical practice, clarify current research limitations, and offer reference for future studies.</p>
</sec>
<sec sec-type="materials|methods" id="sec2">
<label>2</label>
<title>Materials and methods</title>
<p>This study was conducted according to the PRISMA statement and was registered in PROSPERO prior to commencement (Registration Number: CRD420251171897).</p>
<sec id="sec3">
<label>2.1</label>
<title>Data sources and search strategy</title>
<p>This study searched eight databases including PubMed, Cochrane Library, Embase, Web of Science, China Knowledge Infrastructure (CNKI), China Science Journal Database (VIP), Wanfang Database, and China Biomedical Literature Service System (CBM). Publications were limited to English and Chinese languages, with the search cutoff date set at July 21, 2025. Mesh terms were combined with free-text keywords for retrieval, with primary search terms including &#x201C;Electroacupuncture,&#x201D; &#x201C;Stroke,&#x201D; and &#x201C;Depression.&#x201D; The specific search strategy is detailed in <xref ref-type="table" rid="tab1">Table 1</xref> (using PubMed as an example). Search strategies for other databases and the PRISMA 2020 checklist are provided in the <xref rid="SM1" ref-type="supplementary-material">Supplementary material</xref>.</p>
<table-wrap position="float" id="tab1">
<label>Table 1</label>
<caption>
<p>Search strategy (PubMed as an example).</p>
</caption>
<table frame="hsides" rules="groups">
<thead>
<tr>
<th align="left" valign="top">Rank</th>
<th align="center" valign="top">Search term</th>
<th align="center" valign="top">Result</th>
</tr>
</thead>
<tbody>
<tr>
<td align="left" valign="top">#1</td>
<td align="left" valign="top">Electroacupuncture [MeSH]</td>
<td align="center" valign="top">5,658</td>
</tr>
<tr>
<td align="left" valign="top">#2</td>
<td align="left" valign="top">Electroacupuncture OR electro-acupuncture OR electric acupuncture OR Electroneedle OR &#x201C;Electroacupuncture Treatment&#x201D; OR &#x201C;Treatment, Electroacupuncture&#x201D;</td>
<td align="center" valign="top">11,276</td>
</tr>
<tr>
<td align="left" valign="top">#3</td>
<td align="left" valign="top">#1 OR #2</td>
<td align="center" valign="top">11,276</td>
</tr>
<tr>
<td align="left" valign="top">#4</td>
<td align="left" valign="top">Stroke [MeSH]</td>
<td align="center" valign="top">192,769</td>
</tr>
<tr>
<td align="left" valign="top">#5</td>
<td align="left" valign="top">Ischemic stroke [MeSH]</td>
<td align="center" valign="top">18,031</td>
</tr>
<tr>
<td align="left" valign="top">#6</td>
<td align="left" valign="top">Hemorrhagic stroke [MeSH]</td>
<td align="center" valign="top">844</td>
</tr>
<tr>
<td align="left" valign="top">#7</td>
<td align="left" valign="top">Brain infarction [MeSH]</td>
<td align="center" valign="top">45,224</td>
</tr>
<tr>
<td align="left" valign="top">#8</td>
<td align="left" valign="top">Cerebral hemorrhage [MeSH]</td>
<td align="center" valign="top">39,969</td>
</tr>
<tr>
<td align="left" valign="top">#9</td>
<td align="left" valign="top">Cerebrovascular accident OR Cerebrovascular Accidents OR CVA OR Cerebrovascular Apoplexy OR Apoplexy, Cerebrovascular OR Vascular Accident, Brain OR Brain Vascular Accident&#x002A; OR Vascular Accidents, Brain OR Cerebrovascular Stroke&#x002A; OR Stroke, Cerebrovascular OR Strokes, Cerebrovascular OR Apoplexy OR Cerebral Stroke&#x002A; OR Stroke, Cerebral OR Strokes, Cerebral OR Stroke, Acute OR Acute Stroke&#x002A; OR Strokes, Acute OR Cerebrovascular Accident, Acute OR Acute Cerebrovascular Accident&#x002A; OR Cerebrovascular Accidents, Acute</td>
<td align="center" valign="top">505,119</td>
</tr>
<tr>
<td align="left" valign="top">#10</td>
<td align="left" valign="top">#4 OR #5 OR #6 OR #7 OR #8 OR #9</td>
<td align="center" valign="top">531,500</td>
</tr>
<tr>
<td align="left" valign="top">#11</td>
<td align="left" valign="top">Depression [MeSH]</td>
<td align="center" valign="top">282,884</td>
</tr>
<tr>
<td align="left" valign="top">#12</td>
<td align="left" valign="top">Depressive disorder [MeSH]</td>
<td align="center" valign="top">129,269</td>
</tr>
<tr>
<td align="left" valign="top">#13</td>
<td align="left" valign="top">Depressive Symptoms OR Depressive Symptom OR Symptom, Depressive OR Emotional Depression OR Depression, Emotional OR Depressive Disorders OR Disorder&#x002A;, Depressive OR Neurosis, Depressive OR Depressive Neuroses OR Depressive Neurosis OR Neuroses, Depressive OR Depression&#x002A;, Endogenous OR Endogenous Depression&#x002A; OR Depressive Syndrome&#x002A; OR Syndrome&#x002A;, Depressive OR Depression&#x002A;, Neurotic OR Neurotic Depression&#x002A; OR Melancholia&#x002A; OR Unipolar Depression OR Depression&#x002A;, Unipolar OR Unipolar Depressions</td>
<td align="center" valign="top">637,288</td>
</tr>
<tr>
<td align="left" valign="top">#14</td>
<td align="left" valign="top">#11 OR #12 OR #13</td>
<td align="center" valign="top">637,288</td>
</tr>
<tr>
<td align="left" valign="top">#15</td>
<td align="left" valign="top">#3 AND #10 AND #14</td>
<td align="center" valign="top">50</td>
</tr>
</tbody>
</table>
</table-wrap>
</sec>
<sec id="sec4">
<label>2.2</label>
<title>Inclusion and exclusion criteria</title>
<p>Inclusion criteria were established using the PICOS (Population, Intervention, Comparison, Outcome, Study Design) framework. Specific criteria were: (1) P: Participants with a confirmed diagnosis of PSD; (2) I: Treatment group receiving EA therapy; (3) C: Control group receiving conventional medication; (4) O: Using the HAMD as the primary indicator; (5) S: Study design being randomized controlled trials.</p>
<p>Exclusion criteria: (1) Studies with unclear diagnoses or comorbidities affecting outcome assessment; (2) Studies involving concurrent interventions; (3) Studies with non-representative outcome measures; (4) Not randomized controlled trials; (5) Studies lacking full-text access or incomplete data.</p>
</sec>
<sec id="sec5">
<label>2.3</label>
<title>Literature management and data extraction</title>
<p>Two researchers independently screened and extracted data based on inclusion and exclusion criteria. Disagreements were resolved through consultation with a third researcher. The screening process involved: (1) Removing duplicate records using EndNote X9.3 literature management software. (2) Reviewing titles and abstracts to exclude reviews, theses, conference papers, scientific achievements, and other non-relevant literature. (3) Full-text review to determine eligibility.</p>
<p>After literature screening, the following information was extracted: (1) Basic literature information: author details, publication year, etc.; (2) Basic subject information; (3) Intervention method, intervention frequency, and treatment duration; (4) Outcome measures.</p>
</sec>
<sec id="sec6">
<label>2.4</label>
<title>Literature quality assessment</title>
<p>We used the Cochrane Risk of Bias tool (ROB 2.0) to assess the quality of included studies. This tool evaluates five domains: Bias in the randomization process, bias in deviation from the intended intervention, bias in missing outcome data, bias in outcome measurement, and bias in selective reporting of results. The bias in deviation from the intended intervention domain is further subdivided into two scenarios based on research objectives: evaluating the effectiveness of intervention assignment and evaluating the effectiveness of intervention adherence. Each domain contains multiple signal questions. When assessing the risk of bias in RCTs, researchers must make judgments and objectively answer these questions. Signal questions typically offer five response options: Yes (Y), Probably Yes (PY), Probably No (PN), No (N), and No Information (NI).</p>
</sec>
<sec id="sec7">
<label>2.5</label>
<title>Statistical analysis</title>
<p>Following the recommendations of the Cochrane Collaboration and PRISMA guidelines, statistical analyses were conducted using Review Manager 5.4.1, reporting pooled risk ratios (RR) and mean differences (MD) with 95% confidence intervals (CI). Heterogeneity was quantified using the <italic>I</italic><sup>2</sup> statistic. Heterogeneity was defined as low, moderate, or high based on <italic>I</italic><sup>2</sup> values of 25, 50, and 75%, respectively. Publication bias for primary outcomes was visually assessed using funnel plots. The Egger regression test was applied to analyze publication bias.</p>
<p>To more accurately assess the robustness of the analysis results and the inclusion of bias in the studies, we shall employ Stata 18 to conduct sensitivity analyses and Egger&#x2019;s test.</p>
</sec>
</sec>
<sec sec-type="results" id="sec8">
<label>3</label>
<title>Results</title>
<sec id="sec9">
<label>3.1</label>
<title>Search results</title>
<p>A total of 1,106 publications were retrieved from databases. After removing duplicates, 633 publications remained. Further screening based on title and abstract review yielded 27 publications. Full-text review of these 27 publications resulted in 22 eligible publications meeting inclusion criteria, all in Chinese. The specific screening process is illustrated in <xref ref-type="fig" rid="fig1">Figure 1</xref>.</p>
<fig position="float" id="fig1">
<label>Figure 1</label>
<caption>
<p>Literature screening process.</p>
</caption>
<graphic xlink:href="fneur-16-1732787-g001.tif" mimetype="image" mime-subtype="tiff">
<alt-text content-type="machine-generated">Flowchart illustrating the process of study identification through databases and registers, detailing stages of identification, screening, and inclusion. Initially, 1,108 records were identified, with 473 duplicates removed. After screening titles and abstracts, 635 records remained. Exclusions included reviews, protocols, systematic reviews, meta-analyses, animal experiments, irrelevant studies, conference papers, case reports, letters, non-electroacupuncture interventions, and guidelines. A total of 29 full articles were screened, resulting in 22 studies included in the review.</alt-text>
</graphic>
</fig>
</sec>
<sec id="sec10">
<label>3.2</label>
<title>Basic characteristics of included studies</title>
<p>A total of 20 studies were included (<xref ref-type="bibr" rid="ref13 ref14 ref15 ref16 ref17 ref18 ref19 ref20 ref21 ref22 ref23 ref24 ref25 ref26 ref27 ref28 ref29 ref30 ref31 ref32 ref33 ref34">13&#x2013;34</xref>). These comprised 22 individual research projects involving 1,761 patients. All studies were conducted in China across 12 provinces. All studies provided specific diagnostic criteria. The intervention group in each trial received EA. Among the control groups, 18 studies used fluoxetine as the control, two studies used sertraline tablets, one study used Flupentixol and Melitracen Tablets, and one study used sertraline hydrochloride. The intervention periods ranged from 4&#x202F;weeks to 60&#x202F;days across the 22 studies. Detailed information is presented in <xref ref-type="table" rid="tab2">Table 2</xref>.</p>
<table-wrap position="float" id="tab2">
<label>Table 2</label>
<caption>
<p>Basic characteristics of included studies.</p>
</caption>
<table frame="hsides" rules="groups">
<thead>
<tr>
<th align="left" valign="top">No.</th>
<th align="center" valign="top">Author</th>
<th align="center" valign="top">Year</th>
<th align="center" valign="top">Research location</th>
<th align="center" valign="top">Diagnostic criteria</th>
<th align="center" valign="top">Grouping method</th>
<th align="center" valign="top">Blind method</th>
<th align="center" valign="top">Sample size</th>
<th align="center" valign="top">Intervention methods</th>
<th align="center" valign="top">Intervention frequency</th>
<th align="center" valign="top">Course of treatment</th>
<th align="center" valign="top">Outcome</th>
</tr>
</thead>
<tbody>
<tr>
<td align="left" valign="middle">1</td>
<td align="center" valign="middle">Bi et al.</td>
<td align="center" valign="middle">2010</td>
<td align="center" valign="middle">Shandong Province</td>
<td align="center" valign="middle">Yes</td>
<td align="center" valign="middle">Merely mentioned randomly</td>
<td align="center" valign="middle">Double-blind</td>
<td align="center" valign="middle">I:31<break/>C:32</td>
<td align="center" valign="middle">I: Electroacupuncture<break/>C: Fluoxetine</td>
<td align="center" valign="middle">I: 5&#x202F;t/w<break/>C: 20&#x202F;mg/d</td>
<td align="center" valign="middle">I:6 w<break/>C:6 w</td>
<td align="center" valign="middle">HAMD; SDS</td>
</tr>
<tr>
<td align="left" valign="middle">2</td>
<td align="center" valign="middle">Chen</td>
<td align="center" valign="middle">2012</td>
<td align="center" valign="middle">Zhejiang Province</td>
<td align="center" valign="middle">Yes</td>
<td align="center" valign="middle">Merely mentioned randomly</td>
<td align="center" valign="middle">Not mentioned</td>
<td align="center" valign="middle">I:47<break/>C:47</td>
<td align="center" valign="middle">I: Electroacupuncture<break/>C: Fluoxetine</td>
<td align="center" valign="middle">I: 3&#x202F;t/w<break/>C: 20&#x202F;mg/d</td>
<td align="center" valign="middle">I:4 w<break/>C:4 w</td>
<td align="center" valign="middle">HRDS; clinical efficacy rate; comparison of limb function</td>
</tr>
<tr>
<td align="left" valign="middle">3</td>
<td align="center" valign="middle">Chen et al.</td>
<td align="center" valign="middle">2005</td>
<td align="center" valign="middle">Jilin Province</td>
<td align="center" valign="middle">Yes</td>
<td align="center" valign="middle">Computerised random grouping</td>
<td align="center" valign="middle">Not mentioned</td>
<td align="center" valign="middle">I:30<break/>C:30</td>
<td align="center" valign="middle">I: Electroacupuncture<break/>C: Fluoxetine</td>
<td align="center" valign="middle">I: 1&#x202F;t/d<break/>C: 20&#x202F;mg/d</td>
<td align="center" valign="middle">I:4 w<break/>C:4 w</td>
<td align="center" valign="middle">Clinical efficacy rate; SDS; SCAG</td>
</tr>
<tr>
<td align="left" valign="middle">4</td>
<td align="center" valign="middle">Chu et al.</td>
<td align="center" valign="middle">2007</td>
<td align="center" valign="middle">Jilin Province</td>
<td align="center" valign="middle">Yes</td>
<td align="center" valign="middle">Random number table method</td>
<td align="center" valign="middle">Not mentioned</td>
<td align="center" valign="middle">I:36<break/>C:36</td>
<td align="center" valign="middle">I: Electroacupuncture<break/>C: Fluoxetine</td>
<td align="center" valign="middle">I: 5&#x202F;t/w<break/>C: 20&#x202F;mg/d</td>
<td align="center" valign="middle">I:8 w<break/>C:8 w</td>
<td align="center" valign="middle">HAMD; clinical efficacy rate; adverse events</td>
</tr>
<tr>
<td align="left" valign="middle">5</td>
<td align="center" valign="middle">Dai</td>
<td align="center" valign="middle">2009</td>
<td align="center" valign="middle">Hubei Province</td>
<td align="center" valign="middle">Yes</td>
<td align="center" valign="middle">Randomised allocation according to order of presentation</td>
<td align="center" valign="middle">Not mentioned</td>
<td align="center" valign="middle">I:30<break/>C:30</td>
<td align="center" valign="middle">I: Electroacupuncture<break/>C: Flupentixol and Melitracen Tablets</td>
<td align="center" valign="middle">I: 6&#x202F;t/w<break/>C: 21&#x202F;mg/d</td>
<td align="center" valign="middle">I:4 w<break/>C:4 w</td>
<td align="center" valign="middle">HADM; clinical efficacy rate; onset time</td>
</tr>
<tr>
<td align="left" valign="middle">6</td>
<td align="center" valign="middle">Dong et al.</td>
<td align="center" valign="middle">2017</td>
<td align="center" valign="middle">Heilongjiang Province</td>
<td align="center" valign="middle">Yes</td>
<td align="center" valign="middle">Random number table method</td>
<td align="center" valign="middle">Not mentioned</td>
<td align="center" valign="middle">I:50<break/>C:50</td>
<td align="center" valign="middle">I: Electroacupuncture<break/>C: Fluoxetine</td>
<td align="center" valign="middle">I: 1&#x202F;t/d<break/>C: 20&#x202F;mg/d increased to 80&#x202F;mg/d</td>
<td align="center" valign="middle">I:30 d<break/>C:28 d</td>
<td align="center" valign="middle">HAMD; SDS; electroencephalogram changes; 5-HIAA; clinical efficacy rate</td>
</tr>
<tr>
<td align="left" valign="middle">7</td>
<td align="center" valign="middle">Dong et al.</td>
<td align="center" valign="middle">2007</td>
<td align="center" valign="middle">Heilongjiang Province</td>
<td align="center" valign="middle">Yes</td>
<td align="center" valign="middle">Random number table method</td>
<td align="center" valign="middle">Not mentioned</td>
<td align="center" valign="middle">I:38<break/>C:34</td>
<td align="center" valign="middle">I: Electroacupuncture<break/>C: Fluoxetine</td>
<td align="center" valign="middle">I:1&#x202F;t/d<break/>C: 20&#x202F;mg/d</td>
<td align="center" valign="middle">I:30 d<break/>C:28 d</td>
<td align="center" valign="middle">HAMD; SDS; severity index; clinical efficacy rate</td>
</tr>
<tr>
<td align="left" valign="middle">8</td>
<td align="center" valign="middle">Hong et al.</td>
<td align="center" valign="middle">2015</td>
<td align="center" valign="middle">Zhejiang Province</td>
<td align="center" valign="middle">Yes</td>
<td align="center" valign="middle">Random number table method</td>
<td align="center" valign="middle">Not mentioned</td>
<td align="center" valign="middle">I:30<break/>C:30</td>
<td align="center" valign="middle">I: Electroacupuncture<break/>C: Escitalopram Oxalate Tablets</td>
<td align="center" valign="middle">I: 6&#x202F;t/w<break/>C: 20&#x202F;mg/d</td>
<td align="center" valign="middle">I:30 d<break/>C:30 d</td>
<td align="center" valign="middle">HAMD; Barthel; clinical efficacy rate</td>
</tr>
<tr>
<td align="left" valign="middle">9</td>
<td align="center" valign="middle">Huang et al.</td>
<td align="center" valign="middle">2014</td>
<td align="center" valign="middle">Sichuan Province</td>
<td align="center" valign="middle">Yes</td>
<td align="center" valign="middle">Random number table method</td>
<td align="center" valign="middle">Envelope method</td>
<td align="center" valign="middle">I:30<break/>C:30</td>
<td align="center" valign="middle">I: Electroacupuncture<break/>C: Fluoxetine</td>
<td align="center" valign="middle">I: 5&#x202F;t/w<break/>C: 20&#x202F;mg/d</td>
<td align="center" valign="middle">I:6 w<break/>C:6 w</td>
<td align="center" valign="middle">HAMD; Ronneberg Sleep Scale; Clinical efficacy rate; adverse events</td>
</tr>
<tr>
<td align="left" valign="middle">10</td>
<td align="center" valign="middle">Kang et al.</td>
<td align="center" valign="middle">2014</td>
<td align="center" valign="middle">Hebei Province</td>
<td align="center" valign="middle">Yes</td>
<td align="center" valign="middle">Merely mentioned randomly</td>
<td align="center" valign="middle">Not mentioned</td>
<td align="center" valign="middle">I:40<break/>C:40</td>
<td align="center" valign="middle">I: Electroacupuncture<break/>C: Fluoxetine</td>
<td align="center" valign="middle">I: 1&#x202F;t/d<break/>C: 20&#x202F;mg/d</td>
<td align="center" valign="middle">I:4 w<break/>C:4 w</td>
<td align="center" valign="middle">NIHSS; ADL; HAMD</td>
</tr>
<tr>
<td align="left" valign="middle">11</td>
<td align="center" valign="middle">Li et al.</td>
<td align="center" valign="middle">2015</td>
<td align="center" valign="middle">Zhejiang Province</td>
<td align="center" valign="middle">Yes</td>
<td align="center" valign="middle">Computerised random grouping</td>
<td align="center" valign="middle">Not mentioned</td>
<td align="center" valign="middle">I:11<break/>C:10</td>
<td align="center" valign="middle">I: Electroacupuncture<break/>C: Fluoxetine</td>
<td align="center" valign="middle">I: 1&#x202F;t/d<break/>C: 20&#x202F;mg/d</td>
<td align="center" valign="middle">I:8 w<break/>C:8 w</td>
<td align="center" valign="middle">HAMD; r CBF; clinical efficacy rate; ROI radioactive count ratio</td>
</tr>
<tr>
<td align="left" valign="middle">12</td>
<td align="center" valign="middle">Li et al.</td>
<td align="center" valign="middle">2013</td>
<td align="center" valign="middle">Heilongjiang Province</td>
<td align="center" valign="middle">Yes</td>
<td align="center" valign="middle">Randomised allocation according to order of presentation</td>
<td align="center" valign="middle">Not mentioned</td>
<td align="center" valign="middle">I:35<break/>C:35</td>
<td align="center" valign="middle">I: Electroacupuncture<break/>C: Fluoxetine</td>
<td align="center" valign="middle">I: 1&#x202F;t/d<break/>C: 20&#x202F;mg/d</td>
<td align="center" valign="middle">I:4 w<break/>C:4 w</td>
<td align="center" valign="middle">HAMD; MESSS; clinical efficacy rate</td>
</tr>
<tr>
<td align="left" valign="middle">13</td>
<td align="center" valign="middle">Long et al.</td>
<td align="center" valign="middle">2004</td>
<td align="center" valign="middle">Hunan Province</td>
<td align="center" valign="middle">Yes</td>
<td align="center" valign="middle">Merely mentioned randomly</td>
<td align="center" valign="middle">Single-blind</td>
<td align="center" valign="middle">I:36<break/>C:36</td>
<td align="center" valign="middle">I: Electroacupuncture<break/>C: Fluoxetine</td>
<td align="center" valign="middle">I: 6&#x202F;t/w<break/>C: 10-40&#x202F;mg/d</td>
<td align="center" valign="middle">I:4 w<break/>C:4 w</td>
<td align="center" valign="middle">HAMD; CNS; BI; FMA; adverse events</td>
</tr>
<tr>
<td align="left" valign="middle">14</td>
<td align="center" valign="middle">Nie et al.</td>
<td align="center" valign="middle">2010</td>
<td align="center" valign="middle">Guangdong Province</td>
<td align="center" valign="middle">Yes</td>
<td align="center" valign="middle">Random number table method</td>
<td align="center" valign="middle">Not mentioned</td>
<td align="center" valign="middle">I:30<break/>C:30</td>
<td align="center" valign="middle">I: Electroacupuncture<break/>C: Fluoxetine</td>
<td align="center" valign="middle">I: 1&#x202F;t/d<break/>C: 20&#x202F;mg/d</td>
<td align="center" valign="middle">I:60 d<break/>C:60 d</td>
<td align="center" valign="middle">Clinical efficacy rate; HAMD; MESSS; Barthel</td>
</tr>
<tr>
<td align="left" valign="middle">15</td>
<td align="center" valign="middle">Peng et al.</td>
<td align="center" valign="middle">2011</td>
<td align="center" valign="middle">Guangdong Province</td>
<td align="center" valign="middle">Yes</td>
<td align="center" valign="middle">Merely mentioned randomly</td>
<td align="center" valign="middle">Envelope Method</td>
<td align="center" valign="middle">I:58<break/>C:59</td>
<td align="center" valign="middle">I: Electroacupuncture<break/>C: Fluoxetine</td>
<td align="center" valign="middle">I: 6&#x202F;t/w<break/>C: 20&#x202F;mg/d</td>
<td align="center" valign="middle">I:4 w<break/>C:4 w</td>
<td align="center" valign="middle">HRSD; SDS; FIM; adverse events</td>
</tr>
<tr>
<td align="left" valign="middle">16</td>
<td align="center" valign="middle">Wang</td>
<td align="center" valign="middle">2010</td>
<td align="center" valign="middle">Zhejiang Province</td>
<td align="center" valign="middle">Yes</td>
<td align="center" valign="middle">Merely mentioned randomly</td>
<td align="center" valign="middle">Not mentioned</td>
<td align="center" valign="middle">I:40<break/>C:40</td>
<td align="center" valign="middle">I: Electroacupuncture<break/>C: Sertraline hydrochloride</td>
<td align="center" valign="middle">I: 1&#x202F;t/d<break/>C: 50&#x202F;mg/d</td>
<td align="center" valign="middle">I:30 d<break/>C:30 d</td>
<td align="center" valign="middle">HAMD; affected side FMA</td>
</tr>
<tr>
<td align="left" valign="middle">17</td>
<td align="center" valign="middle">Wu et al.</td>
<td align="center" valign="middle">2007</td>
<td align="center" valign="middle">Gansu Province</td>
<td align="center" valign="middle">Yes</td>
<td align="center" valign="middle">Randomised allocation according to order of presentation</td>
<td align="center" valign="middle">Not mentioned</td>
<td align="center" valign="middle">I:32<break/>C:31</td>
<td align="center" valign="middle">I: Electroacupuncture<break/>C: Escitalopram Oxalate Tablets</td>
<td align="center" valign="middle">I: 5&#x202F;t/w<break/>C: 20&#x202F;mg/d</td>
<td align="center" valign="middle">I:6 w<break/>C:6 w</td>
<td align="center" valign="middle">Clinical efficacy rate; HAMD;ADL; adverse events; TESS</td>
</tr>
<tr>
<td align="left" valign="middle">18</td>
<td align="center" valign="middle">Xu et al.</td>
<td align="center" valign="middle">2015</td>
<td align="center" valign="middle">Liaoning Province</td>
<td align="center" valign="middle">Yes</td>
<td align="center" valign="middle">Randomised allocation by treatment method</td>
<td align="center" valign="middle">Not mentioned</td>
<td align="center" valign="middle">I:40<break/>C:40</td>
<td align="center" valign="middle">I: Electroacupuncture<break/>C: Fluoxetine</td>
<td align="center" valign="middle">I: 1&#x202F;t/d<break/>C: 20&#x202F;mg/d</td>
<td align="center" valign="middle">I:6 w<break/>C:6 w</td>
<td align="center" valign="middle">Clinical efficacy rate; HAMD</td>
</tr>
<tr>
<td align="left" valign="middle">19</td>
<td align="center" valign="middle">Zhang et al.</td>
<td align="center" valign="middle">2013</td>
<td align="center" valign="middle">Hubei Province</td>
<td align="center" valign="middle">Yes</td>
<td align="center" valign="middle">Merely mentioned randomly</td>
<td align="center" valign="middle">Not mentioned</td>
<td align="center" valign="middle">I:34<break/>C:27</td>
<td align="center" valign="middle">I: Electroacupuncture<break/>C: Fluoxetine</td>
<td align="center" valign="middle">I: 6&#x202F;t/w<break/>C: 20&#x202F;mg/d</td>
<td align="center" valign="middle">I:6 w<break/>C:6 w</td>
<td align="center" valign="middle">HAMD; SDS</td>
</tr>
<tr>
<td align="left" valign="middle">20</td>
<td align="center" valign="middle">Zhou</td>
<td align="center" valign="middle">2010</td>
<td align="center" valign="middle">Henan Province</td>
<td align="center" valign="middle">Yes</td>
<td align="center" valign="middle">Computerised random grouping</td>
<td align="center" valign="middle">Not mentioned</td>
<td align="center" valign="middle">I:145<break/>C:148</td>
<td align="center" valign="middle">I: Electroacupuncture<break/>C: Fluoxetine</td>
<td align="center" valign="middle">I: 1&#x202F;t/d<break/>C: 20&#x202F;mg/d</td>
<td align="center" valign="middle">I:8 w<break/>C:8 w</td>
<td align="center" valign="middle">HAMD; clinical efficacy rate; adverse events</td>
</tr>
<tr>
<td align="left" valign="middle">21</td>
<td align="center" valign="middle">Zhou</td>
<td align="center" valign="middle">2007</td>
<td align="center" valign="middle">Hunan Province</td>
<td align="center" valign="top">Yes</td>
<td align="center" valign="top">Merely mentioned randomly</td>
<td align="center" valign="top">Not mentioned</td>
<td align="center" valign="top">I:31<break/>C:30</td>
<td align="center" valign="top">I: Electroacupuncture<break/>C: Fluoxetine</td>
<td align="center" valign="top">I: 1&#x202F;t/d<break/>C: 20&#x202F;mg/d</td>
<td align="center" valign="top">I:4 w<break/>C:4 w</td>
<td align="center" valign="top">HAMD; Adverse events; TESS; patient satisfaction rate</td>
</tr>
<tr>
<td align="left" valign="top">22</td>
<td align="center" valign="top">Zhu et al.</td>
<td align="center" valign="top">2012</td>
<td align="center" valign="top">Zhejiang Province</td>
<td align="center" valign="top">Yes</td>
<td align="center" valign="top">Merely mentioned randomly</td>
<td align="center" valign="top">Not mentioned</td>
<td align="center" valign="top">I:32<break/>C:30</td>
<td align="center" valign="top">I: Electroacupuncture<break/>C: Fluoxetine</td>
<td align="center" valign="top">I: 5&#x202F;t/w<break/>C: 20&#x202F;mg/d</td>
<td align="center" valign="top">I:8 w<break/>C:8 w</td>
<td align="center" valign="top">Clinical efficacy rate; HAMD; adverse events</td>
</tr>
</tbody>
</table>
</table-wrap>
</sec>
<sec id="sec11">
<label>3.3</label>
<title>Quality assessment of included studies</title>
<p>The Cochrane Risk of Bias tool (ROB 2.0) was used to assess the risk of bias in the included studies. Six studies used random number tables for allocation, three used computer software, 11 mentioned random allocation only, and two allocated participants based on order of arrival. One study employed an envelope method during randomization to ensure blinding. One study reported achieving double-blinding during the research process, one study reported achieving single-blinding, and the remaining studies mentioned blinding measures. This lack of consistent blinding protocols was the primary factor reducing study quality. Of the 22 studies, one was classified as &#x201C;low risk,&#x201D; one as &#x201C;some concerns,&#x201D; and 20 as &#x201C;high risk.&#x201D; Specific details are shown in <xref ref-type="fig" rid="fig2">Figures 2</xref>, <xref ref-type="fig" rid="fig3">3</xref>.</p>
<fig position="float" id="fig2">
<label>Figure 2</label>
<caption>
<p>Risk of bias summary.</p>
</caption>
<graphic xlink:href="fneur-16-1732787-g002.tif" mimetype="image" mime-subtype="tiff">
<alt-text content-type="machine-generated">A table assessing risk levels in various studies, identified by unique IDs. Columns titled D1 to D5 indicate specific risk factors, and an Overall column summarizes the risk. Symbols represent risk levels: green plus for low risk, yellow exclamation for some concerns, and red minus for high risk. Rows include names and years of studies.</alt-text>
</graphic>
</fig>
<fig position="float" id="fig3">
<label>Figure 3</label>
<caption>
<p>Risk of bias graph.</p>
</caption>
<graphic xlink:href="fneur-16-1732787-g003.tif" mimetype="image" mime-subtype="tiff">
<alt-text content-type="machine-generated">Bar chart showing risk assessment percentages for intention-to-treat aspects. Categories include overall bias, selection, measurement, missing data, deviations, and randomization, color-coded by risk level: low (green), some concerns (yellow), and high (red).</alt-text>
</graphic>
</fig>
</sec>
<sec id="sec12">
<label>3.4</label>
<title>Primary outcome measures</title>
<sec id="sec13">
<label>3.4.1</label>
<title>Hamilton depression scale (HAMD)</title>
<p>Eighteen studies evaluated HAMD scores before and after treatment, involving a total of 1,429 patients: 717 in the experimental group and 712 in the control group. Meta-analysis results indicated that the treatment group demonstrated greater improvement in HAMD scores compared to the control group (MD&#x202F;=&#x202F;&#x2212;1.71, 95% CI: &#x2212;2.79 to &#x2212;0.63, <italic>I<sup>2</sup></italic> =&#x202F;89%, <italic>p</italic>&#x202F;=&#x202F;0.002). See <xref ref-type="fig" rid="fig4">Figure 4</xref> for details.</p>
<fig position="float" id="fig4">
<label>Figure 4</label>
<caption>
<p>HAMD forest plot.</p>
</caption>
<graphic xlink:href="fneur-16-1732787-g004.tif" mimetype="image" mime-subtype="tiff">
<alt-text content-type="machine-generated">Forest plot depicting the mean differences and confidence intervals for various studies comparing experimental and control groups. The plot shows data from multiple studies with corresponding weights and mean differences listed in a table format. The graphical plot on the right visualizes these differences, with a diamond shape representing the overall effect estimate at the bottom. The confidence interval indicates a generally favorable outcome for the experimental group, with significant heterogeneity indicated.</alt-text>
</graphic>
</fig>
</sec>
<sec id="sec14">
<label>3.4.2</label>
<title>Clinical efficacy rate</title>
<p>Fifteen studies evaluated the clinical efficacy rate between the two groups, involving a total of 1,227 patients: 616 in the experimental group and 611 in the control group. Meta-analysis results showed that the experimental group had a higher efficacy rate compared to the control group (OR&#x202F;=&#x202F;1.94, 95% CI: 1.43 to 2.64, <italic>I<sup>2</sup></italic> =&#x202F;0%, <italic>p</italic>&#x202F;&#x003C;&#x202F;0.0001). See <xref ref-type="fig" rid="fig5">Figure 5</xref> for details.</p>
<fig position="float" id="fig5">
<label>Figure 5</label>
<caption>
<p>Clinical efficacy rate forest plot.</p>
</caption>
<graphic xlink:href="fneur-16-1732787-g005.tif" mimetype="image" mime-subtype="tiff">
<alt-text content-type="machine-generated">Forest plot from a meta-analysis showing odds ratios with 95% confidence intervals for various studies comparing experimental and control groups. Each study is represented by a square, with horizontal lines indicating confidence intervals. The diamond at the bottom represents the overall pooled estimate, favoring the experimental group with an odds ratio of 1.94.</alt-text>
</graphic>
</fig>
</sec>
</sec>
<sec id="sec15">
<label>3.5</label>
<title>Secondary outcomes</title>
<sec id="sec16">
<label>3.5.1</label>
<title>BI</title>
<p>Three studies evaluated the BI before and after treatment, involving 192 patients (96 in the experimental group and 96 in the control group). The meta-analysis showed no significant difference between the two groups in improving the Barthel Index (MD&#x202F;=&#x202F;4.01, 95% CI: &#x2212;0.26 to 8.27, <italic>I<sup>2</sup></italic> =&#x202F;70%, <italic>p</italic>&#x202F;=&#x202F;0.07). See <xref ref-type="fig" rid="fig6">Figure 6</xref> for details.</p>
<fig position="float" id="fig6">
<label>Figure 6</label>
<caption>
<p>Barthel forest plot.</p>
</caption>
<graphic xlink:href="fneur-16-1732787-g006.tif" mimetype="image" mime-subtype="tiff">
<alt-text content-type="machine-generated">Forest plot comparing experimental and control groups across three studies. It shows mean differences with 95 percent confidence intervals. The overall effect size is 4.01 with a confidence interval of negative 0.26 to 8.27. Heterogeneity is indicated as Chi-squared equals 6.76, P equals 0.03, and I-squared equals 70 percent.</alt-text>
</graphic>
</fig>
</sec>
<sec id="sec17">
<label>3.5.2</label>
<title>Self-rating depression scale (SDS)</title>
<p>Six studies evaluated SDS before and after treatment, involving 473 patients: 241 in the experimental group and 232 in the control group. Meta-analysis results showed no significant difference between the two groups in improving the Barthel Index (MD&#x202F;=&#x202F;&#x2212;3.28, 95% CI: &#x2212;6.78 to 0.21, <italic>I<sup>2</sup></italic> =&#x202F;97%, p&#x202F;=&#x202F;0.07). See <xref ref-type="fig" rid="fig7">Figure 7</xref> for details.</p>
<fig position="float" id="fig7">
<label>Figure 7</label>
<caption>
<p>SDS forest plot.</p>
</caption>
<graphic xlink:href="fneur-16-1732787-g007.tif" mimetype="image" mime-subtype="tiff">
<alt-text content-type="machine-generated">Forest plot showing a meta-analysis of six studies comparing experimental and control groups. The plot displays mean differences with confidence intervals for each study, with a summary mean difference of -3.28 favoring the experimental group. Heterogeneity indicators include Tau-squared at 18.17, Chi-squared at 14.07, and I-squared at 97%, suggesting high variability. The overall effect test yields a Z-score of 1.84 with a p-value of 0.07. The diagram includes a diamond symbol at the summary mean difference to represent the combined effect.</alt-text>
</graphic>
</fig>
</sec>
<sec id="sec18">
<label>3.5.3</label>
<title>Adverse events</title>
<p>Six studies evaluated adverse events before and after treatment, involving 667 patients (333 in the experimental group and 334 in the control group). Meta-analysis results indicated that the experimental group demonstrated superior safety (OR&#x202F;=&#x202F;0.2, 95% CI: 0.12 to 0.34, <italic>I<sup>2</sup></italic> =&#x202F;45%, <italic>p</italic>&#x202F;&#x003C;&#x202F;0.00001). See <xref ref-type="fig" rid="fig8">Figure 8</xref> for details.</p>
<fig position="float" id="fig8">
<label>Figure 8</label>
<caption>
<p>Adverse events forest plot.</p>
</caption>
<graphic xlink:href="fneur-16-1732787-g008.tif" mimetype="image" mime-subtype="tiff">
<alt-text content-type="machine-generated">Forest plot displaying odds ratios with 95% confidence intervals for six studies comparing experimental and control groups. Odds ratio values range from 0.05 to 0.49, favoring the experimental group. The overall effect is 0.20 with a confidence interval of 0.12 to 0.34. Heterogeneity is moderate with an I-squared of 45%.</alt-text>
</graphic>
</fig>
</sec>
</sec>
<sec id="sec19">
<label>3.6</label>
<title>Bias analysis</title>
<p>We examined potential publication bias by plotting funnel plots, where symmetry indicates no publication bias. <xref ref-type="fig" rid="fig9">Figure 9A</xref> shows the funnel plot for HAMD, and <xref ref-type="fig" rid="fig9">Figure 9B</xref> shows the funnel plot for efficacy rate. As shown in <xref ref-type="fig" rid="fig9">Figure 9A</xref>, most studies cluster around effect sizes close to zero, suggesting consistent overall effect directions (no studies with markedly extreme effects). Observing the symmetry of the &#x201C;funnel&#x201D; reveals a degree of asymmetry in the distribution of study points (particularly in the region with larger standard errors, where points are skewed toward one side). This asymmetry suggests potential publication bias. As shown in <xref ref-type="fig" rid="fig9">Figure 9B</xref>, study points are primarily concentrated in the region where effect sizes are close to 1, indicating that the effect sizes of most studies are consistent in direction. Observing the symmetry of the &#x201C;funnel&#x201D; reveals a pronounced asymmetry in the distribution of research points&#x2014;in regions with larger standard errors (i.e., small-sample studies), the points deviate from the symmetrical funnel shape, exhibiting a distinct &#x201C;gap&#x201D; at the bottom. This asymmetry suggests a higher likelihood of publication bias.</p>
<fig position="float" id="fig9">
<label>Figure 9</label>
<caption>
<p><bold>(A)</bold> HAMD funnel plot. <bold>(B)</bold> Clinical efficacy rate funnel plot.</p>
</caption>
<graphic xlink:href="fneur-16-1732787-g009.tif" mimetype="image" mime-subtype="tiff">
<alt-text content-type="machine-generated">Panel A shows a funnel plot with SE(MD) on the vertical axis and MD on the horizontal axis, with data points clustered around the center line. Panel B displays another funnel plot with SE(log[OR]) on the vertical axis and OR on the horizontal axis, also with data points centered around the middle. Both plots include dashed lines forming a symmetrical funnel shape.</alt-text>
</graphic>
</fig>
<p>To accurately analyse publication bias, we employed the Egger test in Stata 18 to assess the combined effect size of the HAMD. The results indicate that, the Egger test <italic>p</italic>-value for HAMD scores was 0.15, and that for efficacy rate was 0.417, both exceeding the significance level of <italic>&#x03B1;</italic>&#x202F;=&#x202F;0.05. This indicates no significant linear association between effect size and precision for either measure across the included studies. Furthermore, the scatter plot for the Egger test showed symmetrical distribution of individual studies around the regression line, with no evident skewing. These findings indicate that the included studies in this meta-analysis exhibit no statistically significant publication bias, with a low risk of publication bias. The pooled results for the improvement in HAMD scores and the difference in treatment response rates demonstrate good authenticity and reliability. This provides objective and robust evidence-based medical support for evaluating the clinical efficacy of electroacupuncture in treating post-stroke depression. See <xref ref-type="fig" rid="fig10">Figure 10</xref> for details.</p>
<fig position="float" id="fig10">
<label>Figure 10</label>
<caption>
<p><bold>(A)</bold> The Egger test for HAMD. <bold>(B)</bold> The Egger test for efficacy rate.</p>
</caption>
<graphic xlink:href="fneur-16-1732787-g010.tif" mimetype="image" mime-subtype="tiff">
<alt-text content-type="machine-generated">Two Egger's publication bias plots are shown. Plot A has standardized effect on the y-axis and precision on the x-axis, with points scattered above and below the horizontal line. Plot B also depicts standardized effect versus precision, with a more clustered distribution of points. Both plots include fitted regression lines assessing bias presence.</alt-text>
</graphic>
</fig>
</sec>
<sec id="sec20">
<label>3.7</label>
<title>Sensitivity analysis</title>
<p>Observation of the meta-analysis results revealed considerable heterogeneity in the HAMD and SDS scores. We conducted sensitivity analyses on both datasets using Stata 18. The findings indicated varying degrees of stability in the outcomes across different endpoints within this study. The analysis using SDS as the outcome measure included six studies. Upon sequentially excluding individual studies, the pooled effect size estimates fluctuated between &#x2212;1.87 and 0.35. In some instances, the effect size direction reversed and the confidence interval crossed the null line, indicating weak stability in the meta-analysis results for this measure and conclusions susceptible to interference from individual included studies. In contrast, the analysis using HAMD as the outcome measure included 18 studies. After excluding any single study, the pooled effect size consistently remained within the negative range of &#x2212;0.76 to &#x2212;0.43. Furthermore, all confidence intervals remained within the non-negligible threshold, with no reversal in effect size direction. This indicates robust stability and high reliability in the meta-analysis results for this measure. This further substantiates the robustness of the conclusion that electroacupuncture intervention demonstrates superior efficacy to conventional pharmacological interventions in ameliorating depressive symptoms (as measured by HAMD scores) in post-stroke patients, with minimal susceptibility to individual study data biases. See <xref ref-type="fig" rid="fig11">Figures 11A</xref>,<xref ref-type="fig" rid="fig11">B</xref> for details.</p>
<fig position="float" id="fig11">
<label>Figure 11</label>
<caption>
<p><bold>(A)</bold> HAMD sensitivity analysis. <bold>(B)</bold> SDS sensitivity analysis. <bold>(C)</bold> HAMD subgroup analysis forest plot.</p>
</caption>
<graphic xlink:href="fneur-16-1732787-g011.tif" mimetype="image" mime-subtype="tiff">
<alt-text content-type="machine-generated">Panel A shows a forest plot displaying meta-analysis estimates and lower confidence intervals for various studies from 2000 to 2020. Panel B is a sensitivity analysis plot showing the impact of omitting each study on overall estimates and confidence intervals. Panel C presents a forest plot with detailed statistical data comparing interventions, including mean differences, standard deviations, confidence intervals, and overall heterogeneity, divided into interventions not exceeding four weeks and those exceeding four weeks. The plots indicate a general favoring of experimental over control interventions.</alt-text>
</graphic>
</fig>
<p>To further investigate the sources of heterogeneity, we conducted a subgroup analysis of HAMD-related studies according to treatment duration. The subgroup analysis revealed substantial heterogeneity in both studies with treatment durations not exceeding 4 weeks and those exceeding 4 weeks, suggesting that the sources of heterogeneity may be independent of treatment duration. See <xref ref-type="fig" rid="fig11">Figure 11C</xref> for details.</p>
<p>A review of relevant studies revealed inconsistencies between the MDs reported by Huang Shile, Long Haowen, Nie Bin, Xu Guoqing, and Zhu Genying and those from other studies (<xref ref-type="bibr" rid="ref19">19</xref>, <xref ref-type="bibr" rid="ref23">23</xref>, <xref ref-type="bibr" rid="ref24">24</xref>, <xref ref-type="bibr" rid="ref28">28</xref>, <xref ref-type="bibr" rid="ref32">32</xref>). In Huang Shile&#x2019;s study, the disease duration was significantly shorter than in other studies. In Long Haowen&#x2019;s study, the control group received an uncertain dosage of 10&#x2013;40&#x202F;mg/day, which may have contributed to the heterogeneity. Regarding studies involving the Barthel Index, excluding Hong Zhenmei&#x2019;s study yielded <italic>I</italic><sup>2</sup> =&#x202F;0%, <italic>p</italic>&#x202F;=&#x202F;0.1. Reviewing this study revealed that the control group received sertraline tablets, whereas the other two trials used fluoxetine in their control groups, which may explain the heterogeneity.</p>
</sec>
<sec id="sec21">
<label>3.8</label>
<title>Evidence grade assessment</title>
<p>We used the GRADE approach to assess the quality of evidence for this study. The meta-analysis results for HAMD and Barthel Index showed very low and low certainty, while meta-analyses for other indicators demonstrated high certainty. Detailed information is provided in <xref ref-type="table" rid="tab3">Table 3</xref>.</p>
<table-wrap position="float" id="tab3">
<label>Table 3</label>
<caption>
<p>Grade assessment results.</p>
</caption>
<table frame="hsides" rules="groups">
<thead>
<tr>
<th align="left" valign="top" colspan="7">Certainty assessment</th>
<th align="center" valign="top" colspan="2">No. of patients</th>
<th align="center" valign="top" colspan="2">Effect</th>
<th align="center" valign="top" rowspan="2">Certainty</th>
<th align="center" valign="top" rowspan="2">Importance</th>
</tr>
<tr>
<th align="left" valign="top">No. of studies</th>
<th align="center" valign="top">Study design</th>
<th align="center" valign="top">Risk of bias</th>
<th align="center" valign="top">Inconsistency</th>
<th align="center" valign="top">Indirectness</th>
<th align="center" valign="top">Imprecision</th>
<th align="center" valign="top">Other considerations</th>
<th align="center" valign="top">Electroacupuncture</th>
<th align="center" valign="top">Conventional drugs</th>
<th align="center" valign="top">Relative (95% CI)</th>
<th align="center" valign="top">Absolute (95% CI)</th>
</tr>
</thead>
<tbody>
<tr>
<td align="left" valign="middle" colspan="13">HADM</td>
</tr>
<tr>
<td align="left" valign="top">18</td>
<td align="center" valign="top">Randomised trials</td>
<td align="center" valign="top">Very serious<xref ref-type="table-fn" rid="tfn1"><sup>a</sup></xref></td>
<td align="center" valign="top">Not serious<xref ref-type="table-fn" rid="tfn2"><sup>b</sup></xref></td>
<td align="center" valign="top">Not serious</td>
<td align="center" valign="top">Not serious</td>
<td align="center" valign="top">Publication bias strongly suspected</td>
<td align="center" valign="top">717</td>
<td align="center" valign="top">712</td>
<td align="center" valign="top">&#x2014;</td>
<td align="center" valign="top">MD 1.71 lower (2.79 lower to 0.63 lower)</td>
<td align="center" valign="top">&#x2A01;&#x25EF;&#x25EF;&#x25EF; Very low<xref ref-type="table-fn" rid="tfn1"><sup>a</sup></xref><sup>,</sup><xref ref-type="table-fn" rid="tfn2"><sup>b</sup></xref></td>
<td/>
</tr>
<tr>
<td align="left" valign="middle" colspan="13">Efficiency</td>
</tr>
<tr>
<td align="left" valign="top">15</td>
<td align="center" valign="top">Randomised trials</td>
<td align="center" valign="top">Not serious<xref ref-type="table-fn" rid="tfn1"><sup>a</sup></xref></td>
<td align="center" valign="top">Not serious</td>
<td align="center" valign="top">Not serious</td>
<td align="center" valign="top">Not serious</td>
<td align="center" valign="top">None</td>
<td align="center" valign="top">616/1227 (50.2%)</td>
<td align="center" valign="top">611/1227 (49.8%)</td>
<td align="center" valign="top">OR 1.94 (1.43 to 2.64)</td>
<td align="center" valign="top">160 more per 1,000 (from 89 more to 226 more)</td>
<td align="center" valign="top">&#x2A01;&#x2A01;&#x2A01;&#x2A01; High<xref ref-type="table-fn" rid="tfn1"><sup>a</sup></xref></td>
<td/>
</tr>
<tr>
<td align="left" valign="middle" colspan="13">Adverse events</td>
</tr>
<tr>
<td align="left" valign="top">6</td>
<td align="center" valign="top">Randomised trials</td>
<td align="center" valign="top">Not serious</td>
<td align="center" valign="top">Not serious</td>
<td align="center" valign="top">Not serious</td>
<td align="center" valign="top">Not serious</td>
<td align="center" valign="top">None</td>
<td align="center" valign="top">26/333 (7.8%)</td>
<td align="center" valign="top">82/334 (24.6%)</td>
<td align="center" valign="top">OR 0.20 (0.12 to 0.34)</td>
<td align="center" valign="top">184 fewer per 1,000 (from 208 fewer to 146 fewer)</td>
<td align="center" valign="top">&#x2A01;&#x2A01;&#x2A01;&#x2A01; High</td>
<td/>
</tr>
<tr>
<td align="left" valign="middle" colspan="13">SDS</td>
</tr>
<tr>
<td align="left" valign="top">5</td>
<td align="center" valign="top">Randomised trials</td>
<td align="center" valign="top">Not serious</td>
<td align="center" valign="top">Not serious</td>
<td align="center" valign="top">Not serious</td>
<td align="center" valign="top">Not serious</td>
<td align="center" valign="top">None</td>
<td align="center" valign="top">241</td>
<td align="center" valign="top">232</td>
<td align="center" valign="top">&#x2014;</td>
<td align="center" valign="top">MD 3.28 lower (6.78 lower to 0.21 higher)</td>
<td align="center" valign="top">&#x2A01;&#x2A01;&#x2A01;&#x2A01; High</td>
<td/>
</tr>
<tr>
<td align="left" valign="middle" colspan="13">Barthel</td>
</tr>
<tr>
<td align="left" valign="top">3</td>
<td align="center" valign="top">Randomised trials</td>
<td align="center" valign="top">Serious<xref ref-type="table-fn" rid="tfn1"><sup>a</sup></xref></td>
<td align="center" valign="top">Not serious</td>
<td align="center" valign="top">Not serious</td>
<td align="center" valign="top">Not serious</td>
<td align="center" valign="top">Publication bias strongly suspected</td>
<td align="center" valign="top">96</td>
<td align="center" valign="top">96</td>
<td align="center" valign="top">&#x2014;</td>
<td align="center" valign="top">MD 4.01 higher (0.26 lower to 8.27 higher)</td>
<td align="center" valign="top">&#x2A01;&#x2A01;&#x25EF;&#x25EF; Low<xref ref-type="table-fn" rid="tfn1"><sup>a</sup></xref></td>
<td/>
</tr>
</tbody>
</table>
<table-wrap-foot>
<p>CI, confidence interval; MD, mean difference; OR, odds ratio.</p>
<fn id="tfn1">
<label>a</label>
<p>The funnel plot indicates the presence of bias.</p>
</fn>
<fn id="tfn2">
<label>b</label>
<p>The meta-analysis results exhibit heterogeneity.</p>
</fn>
</table-wrap-foot>
</table-wrap>
</sec>
</sec>
<sec sec-type="discussion" id="sec22">
<label>4</label>
<title>Discussion</title>
<p>This systematic review and meta-analysis evaluated the efficacy and safety of EA for treating PSD. Results indicate that EA outperformed conventional drug therapy in improving HAMD scores, increasing treatment response rates, and reducing adverse events. However, no significant differences were observed between EA and drug groups in improving Barthel Index or SDS scores. These findings provide preliminary evidence-based support for incorporating EA into the clinical management of PSD.</p>
<sec id="sec23">
<label>4.1</label>
<title>Potential mechanisms of EA in treating PSD</title>
<sec id="sec24">
<label>4.1.1</label>
<title>Regulation of mitochondrial function</title>
<p>In recent years, multiple studies have confirmed the efficacy of EA for PSD and identified potential mechanisms. Researchers found that EA increases AMPK expression in the prefrontal cortex of PSD rats, thereby improving mitochondrial function and alleviating depressive symptoms in model rats (<xref ref-type="bibr" rid="ref35">35</xref>). In another study, researchers confirmed that EA intervention promotes cannabinoid receptor 1 (CB1R) and mitochondrial expression, restores mitochondrial dysfunction, and consequently improves PSD (<xref ref-type="bibr" rid="ref36">36</xref>).</p>
</sec>
<sec id="sec25">
<label>4.1.2</label>
<title>Regulation of monoamine neurotransmitters and neurotrophic factors</title>
<p>Multiple studies suggest that EA may exert antidepressant effects by modulating serotonin system function. Xu Nenggui and Yao Lulu&#x2019;<italic>s team</italic> published findings in <italic>Translational</italic> Psychiatry indicating that electrical EA stimulation at Baihui and Shenting acupoints significantly enhances 5-HT neural projections from the dorsal raphe nucleus to the prefrontal cortex, restoring functional connectivity in this pathway and thereby improving depressive-like behaviors in PSD mice. Further chemogenetic inhibition experiments demonstrated that the DRN-mPFC 5-HT neural circuit is essential for EA efficacy. When this circuit was specifically suppressed, EA&#x2019;s therapeutic effects were markedly attenuated (<xref ref-type="bibr" rid="ref37">37</xref>). This finding strongly aligns with the significant improvement in HAMD scores observed in the EA group within this meta-analysis, suggesting a distinct neural circuit regulatory mechanism underlies clinical efficacy.</p>
<p>EA may also exert effects by modulating brain-derived neurotrophic factor (BDNF). Researchers have found that EA applied to the Four Gates points promotes hippocampal BDNF and TrkB expression in PSD rats (<xref ref-type="bibr" rid="ref38">38</xref>). Further studies revealed that EA enhances serum and prefrontal cortex BDNF expression in model rats. Additionally, EA was shown to increase tPA and TrkB expression in the prefrontal cortex of PSD rats, proposing that EA improves PSD by regulating the tPA/BDNF/TrkB pathway (<xref ref-type="bibr" rid="ref39">39</xref>).</p>
</sec>
<sec id="sec26">
<label>4.1.3</label>
<title>Regulation of inflammation and ferroptosis</title>
<p>Inflammation is closely associated with PSD. Studies have revealed that EA exerts its effects by regulating inflammation and ferroptosis. Li&#x2032;s research demonstrated that EA reduces inflammatory factor expression in model mice, protects hippocampal neurons, and lowers TLR4, p-p38, p-NF-&#x03BA;B, and NLRP3 levels, validating the mechanism whereby EA acts through the TLR4/p38/NF-&#x03BA;B/NLRP3 pathway (<xref ref-type="bibr" rid="ref40">40</xref>). Recent studies further confirm that EA alleviates hippocampal inflammation and pyroptosis in PSD by downregulating NLRP3 inflammasome activation, suggesting NLRP3 as a potential therapeutic target for PSD (<xref ref-type="bibr" rid="ref41">41</xref>). The association between ferroptosis and depression has been established (<xref ref-type="bibr" rid="ref42">42</xref>), and the mechanism by which EA improves PSD through ferroptosis has been elucidated. Gao&#x2019;s study revealed that EA inhibits ferroptosis in prefrontal cortical neurons to reduce neurological deficits and enhance spontaneous activity and exploratory behavior in rats (<xref ref-type="bibr" rid="ref43">43</xref>).</p>
<p>In summary, current research has confirmed the definite efficacy of EA in treating PSD and identified multiple targets and pathways through which EA exerts its effects, demonstrating systemic and holistic characteristics.</p>
</sec>
</sec>
<sec id="sec27">
<label>4.2</label>
<title>Overview of meta-analysis results</title>
<p>Notably, the pooled results for HAMD scores and SDS in this study exhibited high heterogeneity (<italic>I</italic><sup>2</sup> =&#x202F;89%; <italic>I</italic><sup>2</sup> =&#x202F;97%), indicating significant clinical or methodological differences among studies. Sensitivity analysis revealed that inconsistencies in patient disease duration, drug dosage, and types were likely primary sources of heterogeneity. For example, the shorter disease duration in Huang et al.&#x2019;s (<xref ref-type="bibr" rid="ref19">19</xref>) study and the wider range of drug dosages in the control group of Long et al.&#x2019;s (<xref ref-type="bibr" rid="ref23">23</xref>) study may have impacted the consistency of results. Future studies should standardize intervention protocols and patient stratification to enhance the reliability of findings.</p>
<p>Regarding secondary outcomes, no significant differences were observed between EA and medication in improving the Barthel Index and SDS scores. This may stem from limited sample sizes or varying sensitivities of assessment tools across different dimensions of psychological and functional status. Furthermore, the Barthel Index primarily reflects activities of daily living, whereas the SDS is a self-report scale; its assessment of depression severity may differ from clinician-rated HAMD scores.</p>
<p>Furthermore, all included studies were conducted in China, and most exhibited suboptimal methodological quality, particularly with inadequate implementation of blinding and allocation concealment, potentially introducing implementation and measurement biases. The findings of this study are primarily applicable to the Chinese population and should be applied with caution to other regions or populations. Future research requires more high-quality, multicenter, large-sample randomized controlled trials to enhance the generalizability and strength of evidence.</p>
<p>Furthermore, this study applied more precise inclusion criteria for the experimental group. For the experimental group, the studies included in our analysis featured subjects receiving only EA treatment, while the control groups received only conventional drug therapy. This allows for a more precise analysis of the advantages and limitations of acupuncture compared to conventional therapies. Previous meta-analyses (<xref ref-type="bibr" rid="ref44">44</xref>), however, appear to have applied broader criteria for intervention methods, incorporating studies using various acupuncture techniques such as EA, body acupuncture, auricular acupuncture, and scalp acupuncture. While this approach yielded more comprehensive results, it lacked the necessary precision.</p>
</sec>
</sec>
<sec id="sec28">
<label>5</label>
<title>Limitations</title>
<p>This study has several limitations. First, all included studies originated from China, potentially introducing regional bias and limiting the generalizability of findings. Second, most studies inadequately described specific methods for random sequence generation and allocation concealment, and incomplete blinding may have introduced implementation and measurement biases. Furthermore, the number of studies for certain outcome measures was limited&#x2014;for example, only three studies included the Barthel Index&#x2014;compromising the robustness of results. Finally, funnel plots suggest potential publication bias, particularly with small-sample studies showing a tendency toward positive results, indicating that negative findings may be underreported.</p>
</sec>
<sec sec-type="conclusions" id="sec29">
<label>6</label>
<title>Conclusion</title>
<p>This systematic review of existing clinical trials preliminarily confirms the efficacy of EA in improving core PSD symptoms and its safety profile. Future research should focus on multicenter, large-sample, methodologically rigorous randomized controlled trials to further validate the long-term efficacy and mechanisms of EA, and to explore response variations across different patient subgroups.</p>
</sec>
</body>
<back>
<sec sec-type="data-availability" id="sec30">
<title>Data availability statement</title>
<p>The original contributions presented in the study are included in the article/<xref rid="SM1" ref-type="supplementary-material">Supplementary material</xref>, further inquiries can be directed to the corresponding author.</p>
</sec>
<sec sec-type="author-contributions" id="sec31">
<title>Author contributions</title>
<p>YL: Conceptualization, Formal analysis, Methodology, Writing &#x2013; original draft, Writing &#x2013; review &#x0026; editing. YG: Data curation, Writing &#x2013; original draft, Writing &#x2013; review &#x0026; editing. HH: Data curation, Writing &#x2013; original draft, Writing &#x2013; review &#x0026; editing. HY: Data curation, Software, Writing &#x2013; original draft, Writing &#x2013; review &#x0026; editing. JG: Data curation, Formal analysis, Writing &#x2013; original draft, Writing &#x2013; review &#x0026; editing. LH: Data curation, Formal analysis, Writing &#x2013; original draft, Writing &#x2013; review &#x0026; editing. WN: Data curation, Formal analysis, Software, Writing &#x2013; original draft, Writing &#x2013; review &#x0026; editing. ZZ: Supervision, Writing &#x2013; original draft, Writing &#x2013; review &#x0026; editing.</p>
</sec>
<sec sec-type="COI-statement" id="sec32">
<title>Conflict of interest</title>
<p>The author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.</p>
</sec>
<sec sec-type="ai-statement" id="sec33">
<title>Generative AI statement</title>
<p>The author(s) declared that Generative AI was not used in the creation of this manuscript.</p>
<p>Any alternative text (alt text) provided alongside figures in this article has been generated by Frontiers with the support of artificial intelligence and reasonable efforts have been made to ensure accuracy, including review by the authors wherever possible. If you identify any issues, please contact us.</p>
</sec>
<sec sec-type="disclaimer" id="sec34">
<title>Publisher&#x2019;s note</title>
<p>All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.</p>
</sec>
<sec sec-type="supplementary-material" id="sec35">
<title>Supplementary material</title>
<p>The Supplementary material for this article can be found online at: <ext-link xlink:href="https://www.frontiersin.org/articles/10.3389/fneur.2025.1732787/full#supplementary-material" ext-link-type="uri">https://www.frontiersin.org/articles/10.3389/fneur.2025.1732787/full#supplementary-material</ext-link></p>
<supplementary-material xlink:href="Table_1.DOCX" id="SM1" mimetype="application/vnd.openxmlformats-officedocument.wordprocessingml.document" xmlns:xlink="http://www.w3.org/1999/xlink"/>
<supplementary-material xlink:href="Table_2.DOCX" id="SM2" mimetype="application/vnd.openxmlformats-officedocument.wordprocessingml.document" xmlns:xlink="http://www.w3.org/1999/xlink"/>
</sec>
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<fn-group>
<fn fn-type="custom" custom-type="edited-by" id="fn0001">
<p>Edited by: <ext-link ext-link-type="uri" xlink:href="https://loop.frontiersin.org/people/2250721/overview">Tianye Hu</ext-link>, The First Affiliated Hospital of Jiaxing University, China</p>
</fn>
<fn fn-type="custom" custom-type="reviewed-by" id="fn0002">
<p>Reviewed by: <ext-link ext-link-type="uri" xlink:href="https://loop.frontiersin.org/people/1112422/overview">Hantong Hu</ext-link>, Third Affiliated Hospital of Zhejiang Chinese Medical University, China</p>
<p><ext-link ext-link-type="uri" xlink:href="https://loop.frontiersin.org/people/1368725/overview">Kelin He</ext-link>, Zhejiang Chinese Medical University, China</p>
</fn>
</fn-group>
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</article>