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<front>
<journal-meta>
<journal-id journal-id-type="publisher-id">Front. Public Health</journal-id>
<journal-title>Frontiers in Public Health</journal-title>
<abbrev-journal-title abbrev-type="pubmed">Front. Public Health</abbrev-journal-title>
<issn pub-type="epub">2296-2565</issn>
<publisher>
<publisher-name>Frontiers Media S.A.</publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="doi">10.3389/fpubh.2022.842096</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Public Health</subject>
<subj-group>
<subject>Systematic Review</subject>
</subj-group>
</subj-group>
</article-categories>
<title-group>
<article-title>Reliability of the Evidence to Guide Decision-Making in Acupuncture for Functional Dyspepsia</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name><surname>Huang</surname> <given-names>Jinke</given-names></name>
<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
<xref ref-type="author-notes" rid="fn002"><sup>&#x02020;</sup></xref>
<uri xlink:href="http://loop.frontiersin.org/people/929370/overview"/>
</contrib>
<contrib contrib-type="author">
<name><surname>Liu</surname> <given-names>Jiali</given-names></name>
<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
<xref ref-type="author-notes" rid="fn002"><sup>&#x02020;</sup></xref>
</contrib>
<contrib contrib-type="author">
<name><surname>Liu</surname> <given-names>Zhihong</given-names></name>
<xref ref-type="aff" rid="aff2"><sup>2</sup></xref>
</contrib>
<contrib contrib-type="author">
<name><surname>Ma</surname> <given-names>Jing</given-names></name>
<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
<uri xlink:href="http://loop.frontiersin.org/people/1476733/overview"/>
</contrib>
<contrib contrib-type="author">
<name><surname>Ma</surname> <given-names>Jinxin</given-names></name>
<xref ref-type="aff" rid="aff2"><sup>2</sup></xref>
</contrib>
<contrib contrib-type="author">
<name><surname>Lv</surname> <given-names>Mi</given-names></name>
<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
</contrib>
<contrib contrib-type="author" corresp="yes">
<name><surname>Wang</surname> <given-names>Fengyun</given-names></name>
<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
<xref ref-type="corresp" rid="c001"><sup>&#x0002A;</sup></xref>
<uri xlink:href="http://loop.frontiersin.org/people/1665452/overview"/>
</contrib>
<contrib contrib-type="author" corresp="yes">
<name><surname>Tang</surname> <given-names>Xudong</given-names></name>
<xref ref-type="aff" rid="aff3"><sup>3</sup></xref>
<xref ref-type="corresp" rid="c002"><sup>&#x0002A;</sup></xref>
<uri xlink:href="http://loop.frontiersin.org/people/1246994/overview"/>
</contrib>
</contrib-group>
<aff id="aff1"><sup>1</sup><institution>Department of Gastroenterology, Xiyuan Hospital, China Academy of Chinese Medical Sciences</institution>, <addr-line>Beijing</addr-line>, <country>China</country></aff>
<aff id="aff2"><sup>2</sup><institution>Department of Gastroenterology, Peking University Traditional Chinese Medicine Clinical Medical School (Xiyuan)</institution>, <addr-line>Beijing</addr-line>, <country>China</country></aff>
<aff id="aff3"><sup>3</sup><institution>China Academy of Chinese Medical Sciences</institution>, <addr-line>Beijing</addr-line>, <country>China</country></aff>
<author-notes>
<fn fn-type="edited-by"><p>Edited by: Kevin Lu, University of South Carolina, United States</p></fn>
<fn fn-type="edited-by"><p>Reviewed by: Seok-Jae Ko, Kyung Hee University, South Korea; Shen Guoming, Anhui University of Chinese Medicine, China</p></fn>
<corresp id="c001">&#x0002A;Correspondence: Fengyun Wang <email>wfy811&#x00040;163.com</email></corresp>
<corresp id="c002">Xudong Tang <email>txdly&#x00040;sina.com</email></corresp>
<fn fn-type="other" id="fn001"><p>This article was submitted to Public Health Policy, a section of the journal Frontiers in Public Health</p></fn>
<fn fn-type="equal" id="fn002"><p>&#x02020;These authors have contributed equally to this work</p></fn></author-notes>
<pub-date pub-type="epub">
<day>01</day>
<month>04</month>
<year>2022</year>
</pub-date>
<pub-date pub-type="collection">
<year>2022</year>
</pub-date>
<volume>10</volume>
<elocation-id>842096</elocation-id>
<history>
<date date-type="received">
<day>23</day>
<month>12</month>
<year>2021</year>
</date>
<date date-type="accepted">
<day>21</day>
<month>02</month>
<year>2022</year>
</date>
</history>
<permissions>
<copyright-statement>Copyright &#x000A9; 2022 Huang, Liu, Liu, Ma, Ma, Lv, Wang and Tang.</copyright-statement>
<copyright-year>2022</copyright-year>
<copyright-holder>Huang, Liu, Liu, Ma, Ma, Lv, Wang and Tang</copyright-holder>
<license xlink:href="http://creativecommons.org/licenses/by/4.0/"><p>This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). 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.</p></license> </permissions>
<abstract>
<sec>
<title>Background and Aims</title>
<p>There has been a significant increase in the number of systematic reviews (SRs)/meta-analyses (MAs) investigating the effects of acupuncture for functional dyspepsia (FD). To systematically collate, appraise, and synthesize the current evidence, we carried out an umbrella review of SRs/MAs.</p></sec>
<sec>
<title>Methods</title>
<p>Systemic reviews/meta-analyses on acupuncture for FD were collected by searching major medical databases. The included studies were evaluated in terms of methodological quality, reporting quality, and evidence quality using the criteria from the Assessment of Multiple Systematic Reviews 2 (AMSTAR-2) tool, the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement, and the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) system, respectively.</p></sec>
<sec>
<title>Results</title>
<p>Ten SRs/MAs were analyzed for this study. The methodological quality, reporting quality, and evidence quality of the included SRs/MAs were generally unsatisfactory. Lack of protocol registration, no list of excluded trials, or lack of a comprehensive search strategy were the main limitations. No high-quality evidence was found to support the effects of acupuncture for FD; the qualitative data synthesis relied on low quality trials with small sample sizes and was the main factor for evidence degradation.</p></sec>
<sec>
<title>Conclusions</title>
<p>Acupuncture seems to have a promising efficacy in the treatment of FD. It provides a new and prospective therapeutic method for FD. Although the quality of the included SRs/MAs was generally low and defects were frequent, this umbrella review highlights areas where improvement in methodology is required.</p></sec></abstract>
<kwd-group>
<kwd>reliability</kwd>
<kwd>evidence</kwd>
<kwd>decision-making</kwd>
<kwd>acupuncture</kwd>
<kwd>functional dyspepsia</kwd>
</kwd-group>
<counts>
<fig-count count="3"/>
<table-count count="4"/>
<equation-count count="0"/>
<ref-count count="24"/>
<page-count count="9"/>
<word-count count="4675"/>
</counts>
</article-meta>
</front>
<body>
<sec sec-type="intro" id="s1">
<title>Introduction</title>
<p>Functional dyspepsia (FD) is a functional gastrointestinal disease marked chiefly by early satiation, postprandial fullness, epigastric pain, and epigastric burning (<xref ref-type="bibr" rid="B1">1</xref>). The annual prevalence of FD is 9&#x02013;10%, with 15% of patients having frequent (&#x0003E;3 attacks per week) and chronic (&#x0003E;3 months per year) symptoms (<xref ref-type="bibr" rid="B2">2</xref>). As a result of continuous medical treatment and continuous drug use, indigestion symptoms create a huge socio-economic burden and have a negative impact on the quality of life (<xref ref-type="bibr" rid="B3">3</xref>, <xref ref-type="bibr" rid="B4">4</xref>). It is reported that the total yearly direct cost of presentation and treatment is $805 per patient, yet the economic losses of FD on patients are much higher in combination with the indirect costs caused by resignation or reduced productivity (<xref ref-type="bibr" rid="B4">4</xref>). Abnormal gastric motility (delayed gastric emptying), impaired gastric adaptability to food, and visceral hypersensitivity (gastric hyperdistention sensitivity and acid hypersensitivity) are usually considered to be the main pathophysiological mechanisms of FD (<xref ref-type="bibr" rid="B5">5</xref>). Current pharmacological options include antidepressants, antacids, anxiolytics, prokinetics, and <italic>Helicobacter pylori</italic> eradication (<xref ref-type="bibr" rid="B6">6</xref>). However, none of the available therapies are effective in the majority of patients (<xref ref-type="bibr" rid="B6">6</xref>).</p>
<p>Acupuncture has been widely used to treat functional gastrointestinal disorders including FD. A literature search yielded that an increasing number of systematic reviews (SRs)/meta-analyses (MAs) regarding this topic have been conducted. However, not all SRs/MAs can provide reliable evidence, and low-quality SRs/MAs may instead mislead decision-makers (<xref ref-type="bibr" rid="B7">7</xref>). Furthermore, in an attempt to ensure validity of evidence and improve the quality of SRs/MAs, the measurement tools like the Assessment of Multiple Systematic Reviews 2 (AMSTAR-2) (<xref ref-type="bibr" rid="B8">8</xref>), the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) (<xref ref-type="bibr" rid="B9">9</xref>), and the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) (<xref ref-type="bibr" rid="B10">10</xref>) were published in 2007, 2009, and 2004, respectively. An umbrella review is defined as an evidence-based medicine approach to the systematic review of all SRs/MAs on the same topic. Conducting an umbrella review helps to integrate the evidence more comprehensively, thereby providing higher quality evidence for clinicians. Hence, to systematically collate, evaluate, and synthesize current evidence on acupuncture for FD, we conducted this study.</p></sec>
<sec sec-type="methods" id="s2">
<title>Methods</title>
<p>The protocol of this study was registrated in PROSPERO registry (CRD42021262020), and the methodology was performed following the criteria of the Cochrane Handbook.</p>
<sec>
<title>Criteria for Considering Studies</title>
<p>The criteria for selection were as follows: (a) SRs/MAs of only enrolled randomized controlled trials (RCTs), (b) subjects were diagnosed with FD according to the Rome diagnostic criteria, (c) interventions applied to the experimental group included acupuncture alone or in combination with conventional medicine (CM), while interventions applied to the control included sham acupuncture or CM, (d) reporting at least one prespecified outcome: symptom score (SS), nepean dyspepsia index (NDI), main frequency of electrogastrogram (MF-EGG), gastric half-emptying time (GHET), plasma motilin level (PML), and effective rate (ER). The exclusion criteria were as follows: (a) repeated publications, (b) graduate dissertation, (c) lack of further data, and (d) conference abstracts.</p></sec>
<sec>
<title>Search Strategy</title>
<p>Systematic reviews/Meta-analysis of acupuncture on FD were systematically searched in the following databases from their inception till August 2021: the Cochrane Library, PubMed, Web of Science, Embase, Chinese Biomedical Database, Chinese VIP information, and Wanfang Data. Functional dyspepsia, acupuncture, and systematic review were used as key search terms. A strategy for using PubMed search is shown in <xref ref-type="table" rid="T1">Table 1</xref>.</p>
<table-wrap position="float" id="T1">
<label>Table 1</label>
<caption><p>Detailed retrieval strategy for PubMed.</p></caption>
<table frame="hsides" rules="groups">
<thead><tr>
<th valign="top" align="left"><bold>Query</bold></th>
<th valign="top" align="left"><bold>Search term</bold></th>
</tr>
</thead>
<tbody>
<tr>
<td valign="top" align="left">&#x00023;1</td>
<td valign="top" align="left">Dyspepsia[Mesh]</td>
</tr>
<tr>
<td valign="top" align="left">&#x00023;2</td>
<td valign="top" align="left">Dyspepsia&#x0002A;[Title/Abstract] OR Functional dyspepsia&#x0002A; [Title/Abstract] OR Indigestion&#x0002A; [Title/Abstract] OR non-ulcer dyspepsia&#x0002A; [Title/Abstract]</td>
</tr>
<tr>
<td valign="top" align="left">&#x00023;3</td>
<td valign="top" align="left">&#x00023;1 OR &#x00023;2</td>
</tr>
<tr>
<td valign="top" align="left">&#x00023;4</td>
<td valign="top" align="left">Acupuncture [Mesh]</td>
</tr>
<tr>
<td valign="top" align="left">&#x00023;5</td>
<td valign="top" align="left">Acupuncture [Title/Abstract] OR pharmacoacupuncture[Title/Abstract] OR acupotomy[Title/Abstract] OR acupotomies[Title/Abstract] OR pharmacopuncture[Title/Abstract] OR needle[Title/Abstract] OR needling[Title/Abstract] OR dry-needling[Title/Abstract] OR body-acupuncture[Title/Abstract] OR electroacupuncture[Title/Abstract] OR electro-acupuncture[Title/Abstract] OR auricular acupuncture[Title/Abstract] OR warm needle[Title/Abstract]</td>
</tr>
<tr>
<td valign="top" align="left">&#x00023;6</td>
<td valign="top" align="left">&#x00023;4 OR &#x00023;5</td>
</tr>
<tr>
<td valign="top" align="left">&#x00023;7</td>
<td valign="top" align="left">Meta-Analysis as Topic [Mesh]</td>
</tr>
<tr>
<td valign="top" align="left">&#x00023;8</td>
<td valign="top" align="left">Systematic review[Title/Abstract] OR Meta-Analysis[Title/Abstract] OR meta analysis[Title/Abstract] OR meta-analyses[Title/Abstract] OR metaanalysis[Title/Abstract]</td>
</tr>
<tr>
<td valign="top" align="left">&#x00023;9</td>
<td valign="top" align="left">&#x00023;7 OR &#x00023;8</td>
</tr>
<tr>
<td valign="top" align="left">&#x00023;10</td>
<td valign="top" align="left">&#x00023;3 AND &#x00023;6 AND &#x00023;9</td>
</tr>
</tbody>
</table>
</table-wrap></sec>
<sec>
<title>Literature Screening and Data Extraction</title>
<p>Literature selection and data extraction were conducted by two independent reviewers. For literature selection, titles and abstracts were screened first, and the full texts of potential literature were read for further evaluation. From the articles included, the following data were extracted: first author, publication year, sample size, interventions, outcomes, and main results. Disagreements were settled <italic>via</italic> discussion and consensus.</p></sec>
<sec>
<title>Quality Assessment</title>
<p>Methodological quality, reporting quality, and evidence quality of the enrolled studies were evaluated by two independent reviewers using the AMSTAR-2 tool, the PRISMA statement, and the GRADE system, respectively. The AMSTAR-2 consisted of 16 items, and the methodological quality was ranked as high, moderate, low, or critically low (<xref ref-type="bibr" rid="B8">8</xref>). The PRISMA statement consisted of 27 items, with each of the 16 items given a rating of yes, no, or partly yes (<xref ref-type="bibr" rid="B9">9</xref>). Evidence quality with GRADE was considered from five aspects (risk of bias, inconsistency, indirectness, imprecision, and publication bias) and given a rating of high to critically low (<xref ref-type="bibr" rid="B10">10</xref>). Disagreements were settled <italic>via</italic> discussion and consensus.</p></sec></sec>
<sec sec-type="results" id="s3">
<title>Results</title>
<sec>
<title>Literature Screening</title>
<p>The literature search yielded 193 citations, of which 55 duplicates were removed. After screening the title and abstract, 121 citations were excluded and the remaining 17 were further evaluated through full-text reading. Finally, 10 SRs/MAs (<xref ref-type="bibr" rid="B11">11</xref>&#x02013;<xref ref-type="bibr" rid="B20">20</xref>) met the inclusion criteria (<xref ref-type="fig" rid="F1">Figure 1</xref>).</p>
<fig id="F1" position="float">
<label>Figure 1</label>
<caption><p>Literature screening flowchart.</p></caption>
<graphic mimetype="image" mime-subtype="tiff" xlink:href="fpubh-10-842096-g0001.tif"/>
</fig></sec>
<sec>
<title>Characteristics of the Primary Studies</title>
<p>Then, SRs/MAs published from 2014 to 2021 were included. The interventions applied to the experimental groups were acupuncture alone or in combination with CM, while those administered to the control groups were CM or sham acupuncture. More details are presented in <xref ref-type="table" rid="T2">Table 2</xref>.</p>
<table-wrap position="float" id="T2">
<label>Table 2</label>
<caption><p>A description of the characteristics.</p></caption>
<table frame="hsides" rules="groups">
<thead><tr>
<th valign="top" align="left"><bold>References</bold></th>
<th valign="top" align="left"><bold>Country</bold></th>
<th valign="top" align="left"><bold>Trials (subjects)</bold></th>
<th valign="top" align="left"><bold>Experimental intervention</bold></th>
<th valign="top" align="left"><bold>Control intervention</bold></th>
<th valign="top" align="left"><bold>Quality assessment</bold></th>
<th valign="top" align="left"><bold>Meta-analyses</bold></th>
<th valign="top" align="left"><bold>Results summary</bold></th>
</tr>
</thead>
<tbody>
<tr>
<td valign="top" align="left">Han (<xref ref-type="bibr" rid="B11">11</xref>)</td>
<td valign="top" align="left">China</td>
<td valign="top" align="left">10(1,202)</td>
<td valign="top" align="left">AT</td>
<td valign="top" align="left">Sham AT, CM</td>
<td valign="top" align="left">Cochrane criteria</td>
<td valign="top" align="left">Yes</td>
<td valign="top" align="left">Regarding the improvement in the symptoms of FD, the effect of acupuncture was superior to the sham-acupuncture group or the western medication group.</td>
</tr>
<tr>
<td valign="top" align="left">Mao (<xref ref-type="bibr" rid="B12">12</xref>)</td>
<td valign="top" align="left">China</td>
<td valign="top" align="left">7(853)</td>
<td valign="top" align="left">AT</td>
<td valign="top" align="left">Sham AT, CM</td>
<td valign="top" align="left">Cochrane criteria</td>
<td valign="top" align="left">Yes</td>
<td valign="top" align="left">Acupuncture was more effective than placebo in treating FD, while it was comparable to CM.</td>
</tr>
<tr>
<td valign="top" align="left">Yuan (<xref ref-type="bibr" rid="B13">13</xref>)</td>
<td valign="top" align="left">China</td>
<td valign="top" align="left">31(2,571)</td>
<td valign="top" align="left">AT</td>
<td valign="top" align="left">CM</td>
<td valign="top" align="left">Cochrane criteria</td>
<td valign="top" align="left">Yes</td>
<td valign="top" align="left">Compared with CM, acupuncture can significantly improve the effective rate, functional dyspeptic symptoms and motilin levels.</td>
</tr>
<tr>
<td valign="top" align="left">Zhou (<xref ref-type="bibr" rid="B14">14</xref>)</td>
<td valign="top" align="left">China</td>
<td valign="top" align="left">24(3,097)</td>
<td valign="top" align="left">AT, AT&#x0002B;CM</td>
<td valign="top" align="left">Sham AT, CM</td>
<td valign="top" align="left">Cochrane criteria</td>
<td valign="top" align="left">Yes</td>
<td valign="top" align="left">Acupuncture can effectively alleviate the symptoms of FD and improve the quality of life of patients.</td>
</tr>
<tr>
<td valign="top" align="left">Pang (<xref ref-type="bibr" rid="B15">15</xref>)</td>
<td valign="top" align="left">China</td>
<td valign="top" align="left">16(1,436)</td>
<td valign="top" align="left">AT</td>
<td valign="top" align="left">Sham AT, CM</td>
<td valign="top" align="left">Cochrane criteria</td>
<td valign="top" align="left">Yes</td>
<td valign="top" align="left">Acupuncture was superior to sham acupuncture and CM in improving symptoms and quality of life in FD patients.</td>
</tr>
<tr>
<td valign="top" align="left">Kim (<xref ref-type="bibr" rid="B16">16</xref>)</td>
<td valign="top" align="left">Korea</td>
<td valign="top" align="left">20(1,423)</td>
<td valign="top" align="left">AT, AT&#x0002B;CM</td>
<td valign="top" align="left">Sham AT, CM</td>
<td valign="top" align="left">Cochrane criteria</td>
<td valign="top" align="left">Yes</td>
<td valign="top" align="left">Acupuncture was superior to sham acupuncture and CM in improving symptoms and quality of life in FD patients.</td>
</tr>
<tr>
<td valign="top" align="left">Lan (<xref ref-type="bibr" rid="B17">17</xref>)</td>
<td valign="top" align="left">China</td>
<td valign="top" align="left">7(542)</td>
<td valign="top" align="left">AT</td>
<td valign="top" align="left">Sham AT, CM</td>
<td valign="top" align="left">Cochrane criteria</td>
<td valign="top" align="left">Yes</td>
<td valign="top" align="left">Whether acupuncture was more effective or safer than other treatments for the treatment of FD remains inconclusive.</td>
</tr>
<tr>
<td valign="top" align="left">Peng (<xref ref-type="bibr" rid="B18">18</xref>)</td>
<td valign="top" align="left">China</td>
<td valign="top" align="left">7(1,044)</td>
<td valign="top" align="left">AT</td>
<td valign="top" align="left">CM</td>
<td valign="top" align="left">Cochrane criteria</td>
<td valign="top" align="left">Yes</td>
<td valign="top" align="left">The therapeutic effect of acupuncture on FD was equivalent to that of CM.</td>
</tr>
<tr>
<td valign="top" align="left">Jin (<xref ref-type="bibr" rid="B19">19</xref>)</td>
<td valign="top" align="left">China</td>
<td valign="top" align="left">20(1,301)</td>
<td valign="top" align="left">AT</td>
<td valign="top" align="left">CM</td>
<td valign="top" align="left">Jadad</td>
<td valign="top" align="left">Yes</td>
<td valign="top" align="left">Acupuncture was more effective than CM in the treatment of FD, and had a lower risk of adverse events.</td>
</tr>
<tr>
<td valign="top" align="left">Wu (<xref ref-type="bibr" rid="B20">20</xref>)</td>
<td valign="top" align="left">China</td>
<td valign="top" align="left">16(1,088)</td>
<td valign="top" align="left">AT</td>
<td valign="top" align="left">CM</td>
<td valign="top" align="left">Jadad</td>
<td valign="top" align="left">Yes</td>
<td valign="top" align="left">Acupuncture was more effective than CM in the treatment of FD, and had a lower risk of adverse events.</td>
</tr>
</tbody>
</table>
</table-wrap></sec>
<sec>
<title>Methodological Quality</title>
<p>According to the AMSTAR-2, only one Cochrane SR/MA presented high level of methodological quality, while the other SRs/MAs presented critically low levels of methodological quality. Lack of protocol registration, no list of excluded trials, or lack of a comprehensive search strategy were the main limitations of the included SRs/MAs (<xref ref-type="fig" rid="F2">Figures 2</xref>, <xref ref-type="fig" rid="F3">3</xref>).</p>
<fig id="F2" position="float">
<label>Figure 2</label>
<caption><p>Summary of the Assessment of Multiple Systematic Reviews 2 (AMSTAR-2).</p></caption>
<graphic mimetype="image" mime-subtype="tiff" xlink:href="fpubh-10-842096-g0002.tif"/>
</fig>
<fig id="F3" position="float">
<label>Figure 3</label>
<caption><p>Graphical representation of the AMSTAR-2.</p></caption>
<graphic mimetype="image" mime-subtype="tiff" xlink:href="fpubh-10-842096-g0003.tif"/>
</fig></sec>
<sec>
<title>Reporting Quality</title>
<p>According to the PRISMA statement, only one Cochrane SR/MA fully reported information on the 27 items, while the other SRs/MAs missed serious information in item Q5 (protocol and registration), Q8 (search), and Q27 (funding). More details are shown in <xref ref-type="table" rid="T3">Table 3</xref>.</p>
<table-wrap position="float" id="T3">
<label>Table 3</label>
<caption><p>Result of the PRISMA checklist.</p></caption>
<table frame="hsides" rules="groups">
<thead><tr>
<th valign="top" align="left"><bold>Section/Topic</bold></th>
<th valign="top" align="left"><bold>Items</bold></th>
<th valign="top" align="left"><bold>(<xref ref-type="bibr" rid="B11">11</xref>)</bold></th>
<th valign="top" align="left"><bold>(<xref ref-type="bibr" rid="B12">12</xref>)</bold></th>
<th valign="top" align="left"><bold>(<xref ref-type="bibr" rid="B13">13</xref>)</bold></th>
<th valign="top" align="left"><bold>(<xref ref-type="bibr" rid="B14">14</xref>)</bold></th>
<th valign="top" align="left"><bold>(<xref ref-type="bibr" rid="B15">15</xref>)</bold></th>
<th valign="top" align="left"><bold>(<xref ref-type="bibr" rid="B16">16</xref>)</bold></th>
<th valign="top" align="left"><bold>(<xref ref-type="bibr" rid="B17">17</xref>)</bold></th>
<th valign="top" align="left"><bold>(<xref ref-type="bibr" rid="B18">18</xref>)</bold></th>
<th valign="top" align="left"><bold>(<xref ref-type="bibr" rid="B19">19</xref>)</bold></th>
<th valign="top" align="left"><bold>(<xref ref-type="bibr" rid="B20">20</xref>)</bold></th>
<th valign="top" align="left"><bold>Compliance<break/> (%)</bold></th>
</tr>
</thead>
<tbody>
<tr>
<td valign="top" align="left">Title</td>
<td valign="top" align="left">Q1. Title</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">100%</td>
</tr>
<tr>
<td valign="top" align="left">Abstract</td>
<td valign="top" align="left">Q2. Structured summary</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">100%</td>
</tr>
<tr>
<td valign="top" align="left">Introduction</td>
<td valign="top" align="left">Q3. Rationale</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">100%</td>
</tr>
<tr>
<td/>
<td valign="top" align="left">Q4. Objectives</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">100%</td>
</tr>
<tr>
<td valign="top" align="left">Methods</td>
<td valign="top" align="left">Q5. Protocol and registration</td>
<td valign="top" align="left">N</td>
<td valign="top" align="left">N</td>
<td valign="top" align="left">N</td>
<td valign="top" align="left">N</td>
<td valign="top" align="left">N</td>
<td valign="top" align="left">N</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">N</td>
<td valign="top" align="left">N</td>
<td valign="top" align="left">N</td>
<td valign="top" align="left">10%</td>
</tr>
<tr>
<td/>
<td valign="top" align="left">Q6. Eligibility criteria</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">100%</td>
</tr>
<tr>
<td/>
<td valign="top" align="left">Q7. Information sources</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">100%</td>
</tr>
<tr>
<td/>
<td valign="top" align="left">Q8. Search</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">PY</td>
<td valign="top" align="left">PY</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">PY</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">PY</td>
<td valign="top" align="left">PY</td>
<td valign="top" align="left">PY</td>
<td valign="top" align="left">40%</td>
</tr>
<tr>
<td/>
<td valign="top" align="left">Q9. Study selection</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">100%</td>
</tr>
<tr>
<td/>
<td valign="top" align="left">Q10. Data collection process</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">100%</td>
</tr>
<tr>
<td/>
<td valign="top" align="left">Q11. Data items</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">100%</td>
</tr>
<tr>
<td/>
<td valign="top" align="left">Q12. Risk of bias in individual studies</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">100%</td>
</tr>
<tr>
<td/>
<td valign="top" align="left">Q13. Summary measures</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">100%</td>
</tr>
<tr>
<td/>
<td valign="top" align="left">Q14. Synthesis of results</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">100%</td>
</tr>
<tr>
<td/>
<td valign="top" align="left">Q15. Risk of bias across studies</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">100%</td>
</tr>
<tr>
<td/>
<td valign="top" align="left">Q16. Additional analyses</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">100%</td>
</tr>
<tr>
<td valign="top" align="left">Results</td>
<td valign="top" align="left">Q17. Study selection</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">100%</td>
</tr>
<tr>
<td/>
<td valign="top" align="left">Q18. Study characteristics</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">100%</td>
</tr>
<tr>
<td/>
<td valign="top" align="left">Q19. Risk of bias within studies</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">100%</td>
</tr>
<tr>
<td/>
<td valign="top" align="left">Q20. Results of individual studies</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">100%</td>
</tr>
<tr>
<td/>
<td valign="top" align="left">Q21. Synthesis of results</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">100%</td>
</tr>
<tr>
<td/>
<td valign="top" align="left">Q22. Risk of bias across studies</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">100%</td>
</tr>
<tr>
<td/>
<td valign="top" align="left">Q23. Additional analysis</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">100%</td>
</tr>
<tr>
<td valign="top" align="left">Discussion</td>
<td valign="top" align="left">Q24. Summary of evidence</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">100%</td>
</tr>
<tr>
<td/>
<td valign="top" align="left">Q25. Limitations</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">100%</td>
</tr>
<tr>
<td/>
<td valign="top" align="left">Q26. Conclusions</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">100%</td>
</tr>
<tr>
<td valign="top" align="left">Funding</td>
<td valign="top" align="left">Q27. Funding</td>
<td valign="top" align="left">N</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">N</td>
<td valign="top" align="left">80%</td>
</tr>
</tbody>
</table>
</table-wrap></sec>
<sec>
<title>Evidence Quality</title>
<p>With the GRADE system, the evidence quality of all concerned outcome indicators ranged from &#x0201C;critically low&#x0201D; to &#x0201C;moderate&#x0201D; due to the risk of bias, inconsistency, imprecision, and publication bias. Furthermore, upgrading factors such as large effect and evidence of dose-response gradient were not applicable to the included outcome indicators. More details are shown in <xref ref-type="table" rid="T4">Table 4</xref>.</p>
<table-wrap position="float" id="T4">
<label>Table 4</label>
<caption><p>Results of evidence quality.</p></caption>
<table frame="hsides" rules="groups">
<thead><tr>
<th valign="top" align="left"><bold>References</bold></th>
<th valign="top" align="left"><bold>Treatments</bold></th>
<th valign="top" align="left"><bold>Outcomes</bold></th>
<th valign="top" align="left"><bold>Limitations</bold></th>
<th valign="top" align="left"><bold>Inconsistency</bold></th>
<th valign="top" align="left"><bold>Indirectness</bold></th>
<th valign="top" align="left"><bold>Imprecision</bold></th>
<th valign="top" align="left"><bold>Publication bias</bold></th>
<th valign="top" align="left"><bold>Relative effect (95% CI)</bold></th>
<th valign="top" align="left"><bold>Quality</bold></th>
</tr>
</thead>
<tbody>
<tr>
<td valign="top" align="left">Han (<xref ref-type="bibr" rid="B11">11</xref>)</td>
<td valign="top" align="left">AT vs. Sham AT</td>
<td valign="top" align="left">SS</td>
<td valign="top" align="left">&#x02212;1</td>
<td valign="top" align="left">0</td>
<td valign="top" align="left">0</td>
<td valign="top" align="left">&#x02212;1</td>
<td valign="top" align="left">&#x02212;1</td>
<td valign="top" align="left">SMD &#x02212;3.03 (&#x02212;3.56, &#x02212;2.50)</td>
<td valign="top" align="left">CL</td>
</tr>
<tr>
<td/>
<td/>
<td valign="top" align="left">ER</td>
<td valign="top" align="left">&#x02212;1</td>
<td valign="top" align="left">0</td>
<td valign="top" align="left">0</td>
<td valign="top" align="left">&#x02212;1</td>
<td valign="top" align="left">&#x02212;1</td>
<td valign="top" align="left">OR 5.09 (3.30, 7.86)</td>
<td valign="top" align="left">CL</td>
</tr>
<tr>
<td/>
<td/>
<td valign="top" align="left">MF-ECG</td>
<td valign="top" align="left">&#x02212;1</td>
<td valign="top" align="left">0</td>
<td valign="top" align="left">0</td>
<td valign="top" align="left">&#x02212;1</td>
<td valign="top" align="left">&#x02212;1</td>
<td valign="top" align="left">MD &#x02212;14.36 (&#x02212;18.31, &#x02212;10.41)</td>
<td valign="top" align="left">CL</td>
</tr>
<tr>
<td/>
<td valign="top" align="left">AT vs. CM</td>
<td valign="top" align="left">SS</td>
<td valign="top" align="left">&#x02212;1</td>
<td valign="top" align="left">0</td>
<td valign="top" align="left">0</td>
<td valign="top" align="left">&#x02212;1</td>
<td valign="top" align="left">&#x02212;1</td>
<td valign="top" align="left">MD &#x02212;3.03 (&#x02212;3.56, &#x02212;2.50)</td>
<td valign="top" align="left">CL</td>
</tr>
<tr>
<td/>
<td/>
<td valign="top" align="left">ER</td>
<td valign="top" align="left">&#x02212;1</td>
<td valign="top" align="left">0</td>
<td valign="top" align="left">0</td>
<td valign="top" align="left">&#x02212;1</td>
<td valign="top" align="left">&#x02212;1</td>
<td valign="top" align="left">OR 1.33 (0.70, 2.52)</td>
<td valign="top" align="left">CL</td>
</tr>
<tr>
<td/>
<td/>
<td valign="top" align="left">MF-ECG</td>
<td valign="top" align="left">&#x02212;1</td>
<td valign="top" align="left">0</td>
<td valign="top" align="left">0</td>
<td valign="top" align="left">&#x02212;1</td>
<td valign="top" align="left">&#x02212;1</td>
<td valign="top" align="left">MD 0.01 (&#x02212;0.03, 0.01)</td>
<td valign="top" align="left">CL</td>
</tr>
<tr>
<td/>
<td/>
<td valign="top" align="left">PML</td>
<td valign="top" align="left">&#x02212;1</td>
<td valign="top" align="left">0</td>
<td valign="top" align="left">0</td>
<td valign="top" align="left">&#x02212;1</td>
<td valign="top" align="left">&#x02212;1</td>
<td valign="top" align="left">SMD &#x02212;0.06 (&#x02212;0.23, 0.11)</td>
<td valign="top" align="left">CL</td>
</tr>
<tr>
<td/>
<td/>
<td valign="top" align="left">GHMT</td>
<td valign="top" align="left">&#x02212;1</td>
<td valign="top" align="left">0</td>
<td valign="top" align="left">0</td>
<td valign="top" align="left">&#x02212;1</td>
<td valign="top" align="left">&#x02212;1</td>
<td valign="top" align="left">MD 0.23 (&#x02212;1.94, 2.40)</td>
<td valign="top" align="left">CL</td>
</tr>
<tr>
<td valign="top" align="left">Mao (<xref ref-type="bibr" rid="B12">12</xref>)</td>
<td valign="top" align="left">AT vs. Sham AT</td>
<td valign="top" align="left">SS</td>
<td valign="top" align="left">&#x02212;1</td>
<td valign="top" align="left">0</td>
<td valign="top" align="left">0</td>
<td valign="top" align="left">&#x02212;1</td>
<td valign="top" align="left">&#x02212;1</td>
<td valign="top" align="left">MD &#x02212;3.44 (&#x02212;4.21, &#x02212;2.67)</td>
<td valign="top" align="left">CL</td>
</tr>
<tr>
<td/>
<td/>
<td valign="top" align="left">MF-ECG</td>
<td valign="top" align="left">&#x02212;1</td>
<td valign="top" align="left">&#x02212;1</td>
<td valign="top" align="left">0</td>
<td valign="top" align="left">&#x02212;1</td>
<td valign="top" align="left">&#x02212;1</td>
<td valign="top" align="left">SMD &#x02212;0.69 (&#x02212;3.02, 4.40)</td>
<td valign="top" align="left">CL</td>
</tr>
<tr>
<td/>
<td valign="top" align="left">AT vs. CM</td>
<td valign="top" align="left">SS</td>
<td valign="top" align="left">&#x02212;1</td>
<td valign="top" align="left">&#x02212;1</td>
<td valign="top" align="left">0</td>
<td valign="top" align="left">0</td>
<td valign="top" align="left">&#x02212;1</td>
<td valign="top" align="left">SMD &#x02212;0.18 (&#x02212;0.51, 0.16)</td>
<td valign="top" align="left">CL</td>
</tr>
<tr>
<td/>
<td/>
<td valign="top" align="left">ER</td>
<td valign="top" align="left">&#x02212;1</td>
<td valign="top" align="left">0</td>
<td valign="top" align="left">0</td>
<td valign="top" align="left">0</td>
<td valign="top" align="left">0</td>
<td valign="top" align="left">RR 1.04 (0.96,1.13)</td>
<td valign="top" align="left">M</td>
</tr>
<tr>
<td/>
<td/>
<td valign="top" align="left">PML</td>
<td valign="top" align="left">&#x02212;1</td>
<td valign="top" align="left">0</td>
<td valign="top" align="left">0</td>
<td valign="top" align="left">0</td>
<td valign="top" align="left">0</td>
<td valign="top" align="left">SMD 0.93 (&#x02212;0.30, 1.55)</td>
<td valign="top" align="left">M</td>
</tr>
<tr>
<td/>
<td/>
<td valign="top" align="left">GHMT</td>
<td valign="top" align="left">&#x02212;1</td>
<td valign="top" align="left">0</td>
<td valign="top" align="left">0</td>
<td valign="top" align="left">&#x02212;1</td>
<td valign="top" align="left">&#x02212;1</td>
<td valign="top" align="left">SMD 0.02 (&#x02212;0.16, 0.20)</td>
<td valign="top" align="left">CL</td>
</tr>
<tr>
<td valign="top" align="left">Yuan (<xref ref-type="bibr" rid="B13">13</xref>)</td>
<td valign="top" align="left">AT vs. CM</td>
<td valign="top" align="left">ER</td>
<td valign="top" align="left">&#x02212;1</td>
<td valign="top" align="left">0</td>
<td valign="top" align="left">0</td>
<td valign="top" align="left">0</td>
<td valign="top" align="left">&#x02212;1</td>
<td valign="top" align="left">OR 3.00 (2.33, 3.87)</td>
<td valign="top" align="left">L</td>
</tr>
<tr>
<td/>
<td/>
<td valign="top" align="left">SS</td>
<td valign="top" align="left">&#x02212;1</td>
<td valign="top" align="left">&#x02212;1</td>
<td valign="top" align="left">0</td>
<td valign="top" align="left">0</td>
<td valign="top" align="left">0</td>
<td valign="top" align="left">WMD &#x02212;1.21 (&#x02212;2.13, &#x02212;0.30)</td>
<td valign="top" align="left">L</td>
</tr>
<tr>
<td/>
<td/>
<td valign="top" align="left">PML</td>
<td valign="top" align="left">&#x02212;1</td>
<td valign="top" align="left">0</td>
<td valign="top" align="left">0</td>
<td valign="top" align="left">0</td>
<td valign="top" align="left">0</td>
<td valign="top" align="left">WMD 13.99 (0.45, 27.54)</td>
<td valign="top" align="left">M</td>
</tr>
<tr>
<td valign="top" align="left">Zhou (<xref ref-type="bibr" rid="B14">14</xref>)</td>
<td valign="top" align="left">AT vs. Sham AT</td>
<td valign="top" align="left">SS</td>
<td valign="top" align="left">&#x02212;1</td>
<td valign="top" align="left">&#x02212;1</td>
<td valign="top" align="left">0</td>
<td valign="top" align="left">0</td>
<td valign="top" align="left">0</td>
<td valign="top" align="left">SMD &#x02212;1.23 (&#x02212;2.00,&#x02212;0.47)</td>
<td valign="top" align="left">L</td>
</tr>
<tr>
<td/>
<td valign="top" align="left">AT vs. CM</td>
<td valign="top" align="left">SS</td>
<td valign="top" align="left">&#x02212;1</td>
<td valign="top" align="left">&#x02212;1</td>
<td valign="top" align="left">0</td>
<td valign="top" align="left">0</td>
<td valign="top" align="left">0</td>
<td valign="top" align="left">SMD &#x02212;0.30 (&#x02212;0.77,0.16)</td>
<td valign="top" align="left">L</td>
</tr>
<tr>
<td/>
<td/>
<td valign="top" align="left">PML</td>
<td valign="top" align="left">&#x02212;1</td>
<td valign="top" align="left">&#x02212;1</td>
<td valign="top" align="left">0</td>
<td valign="top" align="left">0</td>
<td valign="top" align="left">0</td>
<td valign="top" align="left">SMD 0.67 (&#x02212;0.07,1.42)</td>
<td valign="top" align="left">L</td>
</tr>
<tr>
<td valign="top" align="left">Pang (<xref ref-type="bibr" rid="B15">15</xref>)</td>
<td valign="top" align="left">AT vs. Sham AT</td>
<td valign="top" align="left">NDI</td>
<td valign="top" align="left">&#x02212;1</td>
<td valign="top" align="left">&#x02212;1</td>
<td valign="top" align="left">0</td>
<td valign="top" align="left">&#x02212;1</td>
<td valign="top" align="left">&#x02212;1</td>
<td valign="top" align="left">MD 20.91 (6.55,35.26)</td>
<td valign="top" align="left">CL</td>
</tr>
<tr>
<td valign="top" align="left">Kim (<xref ref-type="bibr" rid="B16">16</xref>)</td>
<td valign="top" align="left">AT vs. Sham AT</td>
<td valign="top" align="left">SS</td>
<td valign="top" align="left">&#x02212;1</td>
<td valign="top" align="left">0</td>
<td valign="top" align="left">0</td>
<td valign="top" align="left">&#x02212;1</td>
<td valign="top" align="left">&#x02212;1</td>
<td valign="top" align="left">MD 0.54 (0.18, 0.90)</td>
<td valign="top" align="left">CL</td>
</tr>
<tr>
<td/>
<td/>
<td valign="top" align="left">ER</td>
<td valign="top" align="left">&#x02212;1</td>
<td valign="top" align="left">&#x02212;1</td>
<td valign="top" align="left">0</td>
<td valign="top" align="left">&#x02212;1</td>
<td valign="top" align="left">&#x02212;1</td>
<td valign="top" align="left">RR 2.66 (1.85, 3.82)</td>
<td valign="top" align="left">CL</td>
</tr>
<tr>
<td/>
<td valign="top" align="left">AT vs. CM</td>
<td valign="top" align="left">SS</td>
<td valign="top" align="left">&#x02212;1</td>
<td valign="top" align="left">&#x02212;1</td>
<td valign="top" align="left">0</td>
<td valign="top" align="left">0</td>
<td valign="top" align="left">0</td>
<td valign="top" align="left">MD 0.54 (0.33,0.76)</td>
<td valign="top" align="left">L</td>
</tr>
<tr>
<td/>
<td/>
<td valign="top" align="left">ER</td>
<td valign="top" align="left">&#x02212;1</td>
<td valign="top" align="left">&#x02212;1</td>
<td valign="top" align="left">0</td>
<td valign="top" align="left">&#x02212;1</td>
<td valign="top" align="left">&#x02212;1</td>
<td valign="top" align="left">RR 1.18 (1.09, 1.27)</td>
<td valign="top" align="left">CL</td>
</tr>
<tr>
<td valign="top" align="left">Lan (<xref ref-type="bibr" rid="B17">17</xref>)</td>
<td valign="top" align="left">AT vs. CM</td>
<td valign="top" align="left">ER</td>
<td valign="top" align="left">&#x02212;1</td>
<td valign="top" align="left">0</td>
<td valign="top" align="left">0</td>
<td valign="top" align="left">&#x02212;1</td>
<td valign="top" align="left">&#x02212;1</td>
<td valign="top" align="left">RR 1.02 (0.91,1.16)</td>
<td valign="top" align="left">CL</td>
</tr>
<tr>
<td valign="top" align="left">Peng (<xref ref-type="bibr" rid="B18">18</xref>)</td>
<td valign="top" align="left">AT vs. CM</td>
<td valign="top" align="left">ER</td>
<td valign="top" align="left">&#x02212;1</td>
<td valign="top" align="left">0</td>
<td valign="top" align="left">0</td>
<td valign="top" align="left">0</td>
<td valign="top" align="left">0</td>
<td valign="top" align="left">RR 1.17 (1.10,1.24)</td>
<td valign="top" align="left">M</td>
</tr>
<tr>
<td valign="top" align="left">Jin (<xref ref-type="bibr" rid="B19">19</xref>)</td>
<td valign="top" align="left">AT vs. CM</td>
<td valign="top" align="left">ER</td>
<td valign="top" align="left">&#x02212;1</td>
<td valign="top" align="left">&#x02212;1</td>
<td valign="top" align="left">0</td>
<td valign="top" align="left">0</td>
<td valign="top" align="left">0</td>
<td valign="top" align="left">RR 1.21 (1.15,1.27)</td>
<td valign="top" align="left">L</td>
</tr>
<tr>
<td/>
<td/>
<td valign="top" align="left">SS</td>
<td valign="top" align="left">&#x02212;1</td>
<td valign="top" align="left">&#x02212;1</td>
<td valign="top" align="left">0</td>
<td valign="top" align="left">&#x02212;1</td>
<td valign="top" align="left">&#x02212;1</td>
<td valign="top" align="left">MD &#x02212;2.10 (&#x02212;3.61,&#x02212;0.59)</td>
<td valign="top" align="left">CL</td>
</tr>
<tr>
<td/>
<td/>
<td valign="top" align="left">NDI</td>
<td valign="top" align="left">&#x02212;1</td>
<td valign="top" align="left">0</td>
<td valign="top" align="left">0</td>
<td valign="top" align="left">&#x02212;1</td>
<td valign="top" align="left">&#x02212;1</td>
<td valign="top" align="left">MD 9.94 (7.93,11.94)</td>
<td valign="top" align="left">CL</td>
</tr>
<tr>
<td valign="top" align="left">Wu (<xref ref-type="bibr" rid="B20">20</xref>)</td>
<td valign="top" align="left">AT vs. CM</td>
<td valign="top" align="left">ER</td>
<td valign="top" align="left">&#x02212;1</td>
<td valign="top" align="left">0</td>
<td valign="top" align="left">0</td>
<td valign="top" align="left">0</td>
<td valign="top" align="left">0</td>
<td valign="top" align="left">RR 1.18 (1.11,1.24)</td>
<td valign="top" align="left">M</td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<fn id="TN1"><p><italic>SS, symptom score; ER, effective rate; MF-EGG, main frequency of electrogastrogram; PML, plasma motilin level; GHMT, gastric half-emptying time; NDI, nepean dyspepsia index. CL, critically low; L, Low; M, moderate</italic>.</p></fn>
</table-wrap-foot>
</table-wrap></sec>
<sec>
<title>Meta-Analyses Outcomes of Intervention</title>
<sec>
<title>Acupuncture vs. Sham Acupuncture</title>
<p>Five studies (<xref ref-type="bibr" rid="B11">11</xref>, <xref ref-type="bibr" rid="B12">12</xref>, <xref ref-type="bibr" rid="B14">14</xref>&#x02013;<xref ref-type="bibr" rid="B16">16</xref>) compared the effects of acupuncture with sham acupuncture. Three studies (<xref ref-type="bibr" rid="B11">11</xref>, <xref ref-type="bibr" rid="B12">12</xref>, <xref ref-type="bibr" rid="B14">14</xref>, <xref ref-type="bibr" rid="B16">16</xref>) reported significant improvements in SSs in the acupuncture group compared to the sham acupuncture. Two studies reported ERs (<xref ref-type="bibr" rid="B11">11</xref>, <xref ref-type="bibr" rid="B16">16</xref>), and the meta-analysis results revealed that the acupuncture group was significantly superior to the sham acupuncture group. The MF- EGG was reported in two studies (<xref ref-type="bibr" rid="B11">11</xref>, <xref ref-type="bibr" rid="B12">12</xref>). One study (<xref ref-type="bibr" rid="B11">11</xref>) showed that the acupuncture group was significantly superior to the sham group, while the other (<xref ref-type="bibr" rid="B12">12</xref>) reported no significant difference between these two groups. Furthermore, it was reported that acupuncture was superior to sham acupuncture in NDI (<xref ref-type="bibr" rid="B15">15</xref>).</p></sec>
<sec>
<title>Acupuncture vs. Conventional Medication</title>
<p>Nine studies (<xref ref-type="bibr" rid="B11">11</xref>&#x02013;<xref ref-type="bibr" rid="B14">14</xref>, <xref ref-type="bibr" rid="B16">16</xref>&#x02013;<xref ref-type="bibr" rid="B20">20</xref>) compared the effects of acupuncture with CM. Symptom score was reported in six studies (<xref ref-type="bibr" rid="B11">11</xref>&#x02013;<xref ref-type="bibr" rid="B14">14</xref>, <xref ref-type="bibr" rid="B16">16</xref>, <xref ref-type="bibr" rid="B19">19</xref>), and the results of four studies (<xref ref-type="bibr" rid="B11">11</xref>, <xref ref-type="bibr" rid="B13">13</xref>, <xref ref-type="bibr" rid="B16">16</xref>, <xref ref-type="bibr" rid="B19">19</xref>) revealed that acupuncture was superior to CM, while others (<xref ref-type="bibr" rid="B12">12</xref>, <xref ref-type="bibr" rid="B14">14</xref>) showed that acupuncture was equivalent to CM. An effective rate was reported in eight studies (<xref ref-type="bibr" rid="B11">11</xref>&#x02013;<xref ref-type="bibr" rid="B13">13</xref>, <xref ref-type="bibr" rid="B16">16</xref>&#x02013;<xref ref-type="bibr" rid="B20">20</xref>), and the results of five studies (<xref ref-type="bibr" rid="B13">13</xref>, <xref ref-type="bibr" rid="B16">16</xref>, <xref ref-type="bibr" rid="B18">18</xref>&#x02013;<xref ref-type="bibr" rid="B20">20</xref>) revealed that acupuncture was superior to CM, while others (<xref ref-type="bibr" rid="B11">11</xref>, <xref ref-type="bibr" rid="B12">12</xref>, <xref ref-type="bibr" rid="B17">17</xref>) showed that acupuncture was equivalent to CM. The MF-EGG was reported in one study (<xref ref-type="bibr" rid="B11">11</xref>), and the pooled results showed that acupuncture was equivalent to CM. PML was reported in four studies (<xref ref-type="bibr" rid="B11">11</xref>&#x02013;<xref ref-type="bibr" rid="B14">14</xref>), and the results of one study (<xref ref-type="bibr" rid="B13">13</xref>) revealed that acupuncture was superior to CM, while others (<xref ref-type="bibr" rid="B11">11</xref>, <xref ref-type="bibr" rid="B12">12</xref>, <xref ref-type="bibr" rid="B14">14</xref>) showed that acupuncture was equivalent to CM. Two studies reported the GHET (<xref ref-type="bibr" rid="B11">11</xref>, <xref ref-type="bibr" rid="B12">12</xref>), and the results showed that the therapeutic effect of acupuncture group was comparable to that of CM. In addition, it was reported that acupuncture treatment was superior to CM in NDI (<xref ref-type="bibr" rid="B19">19</xref>).</p></sec></sec></sec>
<sec sec-type="discussion" id="s4">
<title>Discussion</title>
<p>Systematic reviews/meta-analyses, as the highest level of evidence source in evidence-based medicine, have become an important basis for evidence-based decision-making (<xref ref-type="bibr" rid="B21">21</xref>). However, SRs/MAs with low quality might affect the applicability of evidence. In this study, we performed an umbrella review to collate, evaluate, and synthesize the current evidence on acupuncture for FD.</p>
<sec>
<title>Main Results</title>
<p>First, 10 SRs/MAs published between 2014 and 2021 were included, nine of which were published over the past 5 years, indicating an increasing interest in acupuncture for FD. Second, based on the AMSTAR-2 tool, the PRISMA statement, and the GRADE system, the methodological quality, reporting quality, and evidence quality, respectively, of the included studies did not meet the requirements of the Cochrane Handbook, which means that the conclusions of the included studies may be different from the real situation and cannot provide reliable evidence for the investigators. Third, there is considerable room for improving the methodological quality and reporting the quality of SRs/MAs. This study highlights common areas for improvement such as protocols designed and registered in advance, comprehensive literature search strategies, providing a transparent list of excluded trials, and declaring funding and conflicts of interest. Fourth, there is considerable room for improving the methodological quality of RCTs. This study highlights the common areas for improvement in RCTs, such as a strict implementation of randomization and allocation concealment and adequate reporting of blinding methods. In addition, while almost all outcome measures lead to positive conclusions, it is worth noting that most authors were reluctant to draw definitive conclusions on the effects of acupuncture for FD due to the small size or low quality of the RCTs.</p></sec>
<sec>
<title>Impact on Further Research</title>
<p>This study highlights several challenges for producers of SRs/MAs that should be addressed. First, by using the AMSTAR-2 tool and the PRISMA statement, it was observed that the registration of protocols was far from being appreciated by authors of SRs/MAs. Only one Cochrane SR/MA provided a protocol registration, whereas none of the other studies provided that. It is well-known that a preregistration protocol helps to improve transparency, minimize the potential risk of bias arising from the research process, reduce duplicate work between different researchers, and keep the study up-to-date (<xref ref-type="bibr" rid="B22">22</xref>). Authors are advocated to register protocols in a freely open database (PROSPERO, <ext-link ext-link-type="uri" xlink:href="http://www.crd.york.ac.uk/prospero">http://www.crd.york.ac.uk/prospero</ext-link>) to avoid study bias. Secondly, the risk of bias in identification and literature selection was far from being paid attention to by authors of SRs/MAs. That is, authors of SRs/MAs should provide a comprehensive search strategy and be aware that an appropriate range of databases or electronic sources of published literature should be included. In addition to the database search, other methods were considered for identifying relevant literature, such as meeting reports and trial registration platforms. Furthermore, a list of excluded trials and account for exclusion help to guarantee transparency; it can be presented by direct reference or as a supplementary file. Finally, funding sources should be fully reported as results from commercially funded research might be biased toward funders (<xref ref-type="bibr" rid="B23">23</xref>).</p>
<p>Based on the GRADE system, the risk of bias of the enrolled RCTs was the most common downgrading factor, indicating that the root cause of the reduced quality of evidence lies in the quality of the original RCTs. Only well-designed and rigorously conducted RCTs may reduce or avoid bias (<xref ref-type="bibr" rid="B24">24</xref>). Specific methods of randomization should be clearly described to reflect whether randomization has been successfully achieved. In addition, the information on allocation concealment and blind method should be fully reported. Due to the peculiarity of acupuncture, although blinding physicians is challenging, attempts should be made to blind patients, other caregivers, and outcome assessors to minimize the risk of bias. With the development of evidence-based acupuncture, it is hoped that researchers will continue to promote standardization and precision in the future by improving the technical operating procedures of acupuncture. Moreover, it should be realized that a large sample size and high-quality RCTs should be fundamental to high-quality evidence sources.</p></sec>
<sec>
<title>Limitations</title>
<p>This study highlights areas of improvement in the SR/MA process that may help guide future high-quality research. However, the widely used AMSTAR-2 tool, PRISMA statement, and GRADE system are all subjective evaluation tools, and the accuracy of assessor&#x00027;s assessments cannot be guaranteed.</p></sec></sec>
<sec sec-type="conclusions" id="s5">
<title>Conclusion</title>
<p>Acupuncture seems to have a promising efficacy in the treatment of FD. Although the quality of the included SRs/MAs was generally low and defects were frequent, our study highlights areas where methodologies need to be improved.</p></sec>
<sec sec-type="data-availability" id="s6">
<title>Data Availability Statement</title>
<p>The original contributions presented in the study are included in the article, further inquiries can be directed to the corresponding authors.</p></sec>
<sec id="s7">
<title>Author Contributions</title>
<p>JH and JL initiated the study design and drafted the manuscript. ML, JingM, ZL, and JinxM helped with the implementation of this work. FW and XT contributed to methodology, review, and editing. All authors read and approved the final manuscript.</p></sec>
<sec sec-type="funding-information" id="s8">
<title>Funding</title>
<p>This study was supported by the National Natural Science Foundation of China [Nos. 81873297 and 81804078], the State Administration of Traditional Chinese Medicine Digestive Refractory Disease Inheritance and Innovation Team Project [No. ZYYCXTD-C-202010], and the Excellent Young Scientist Fund of China Academy of Chinese Medical Sciences [No. ZZ13-YQ-006].</p></sec>
<sec sec-type="COI-statement" id="conf1">
<title>Conflict of Interest</title>
<p>The authors declare that the research 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="disclaimer" id="s9">
<title>Publisher&#x00027;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> </body>
<back>
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