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<front>
<journal-meta>
<journal-id journal-id-type="publisher-id">Front. Cardiovasc. Med.</journal-id>
<journal-title>Frontiers in Cardiovascular Medicine</journal-title>
<abbrev-journal-title abbrev-type="pubmed">Front. Cardiovasc. Med.</abbrev-journal-title>
<issn pub-type="epub">2297-055X</issn>
<publisher>
<publisher-name>Frontiers Media S.A.</publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="doi">10.3389/fcvm.2023.1113509</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Cardiovascular Medicine</subject>
<subj-group>
<subject>Systematic Review</subject>
</subj-group>
</subj-group>
</article-categories>
<title-group>
<article-title>Effects of inspiratory muscle training in patients with hypertension: a meta-analysis</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author" equal-contrib="yes"><name><surname>Zheng</surname><given-names>ShuQi</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="author-notes" rid="an1"><sup>&#x2020;</sup></xref><uri xlink:href="https://loop.frontiersin.org/people/2120350/overview"/></contrib>
<contrib contrib-type="author" equal-contrib="yes"><name><surname>Zhang</surname><given-names>Qi</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="author-notes" rid="an1"><sup>&#x2020;</sup></xref><uri xlink:href="https://loop.frontiersin.org/people/2060179/overview" /></contrib>
<contrib contrib-type="author" equal-contrib="yes"><name><surname>Li</surname><given-names>ShuiYan</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="author-notes" rid="an1"><sup>&#x2020;</sup></xref><uri xlink:href="https://loop.frontiersin.org/people/1786649/overview" /></contrib>
<contrib contrib-type="author"><name><surname>Li</surname><given-names>Shilin</given-names></name>
<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
<xref ref-type="aff" rid="aff2"><sup>2</sup></xref><uri xlink:href="https://loop.frontiersin.org/people/1821877/overview" /></contrib>
<contrib contrib-type="author"><name><surname>Yao</surname><given-names>Qiuru</given-names></name>
<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
<xref ref-type="aff" rid="aff3"><sup>3</sup></xref></contrib>
<contrib contrib-type="author"><name><surname>Zheng</surname><given-names>Xiaoyan</given-names></name>
<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
</contrib>
<contrib contrib-type="author"><name><surname>Li</surname><given-names>Gege</given-names></name>
<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
<xref ref-type="aff" rid="aff2"><sup>2</sup></xref><uri xlink:href="https://loop.frontiersin.org/people/2059699/overview" /></contrib>
<contrib contrib-type="author"><name><surname>Zeng</surname><given-names>Yuting</given-names></name>
<xref ref-type="aff" rid="aff2"><sup>2</sup></xref><uri xlink:href="https://loop.frontiersin.org/people/2120487/overview" /></contrib>
<contrib contrib-type="author"><name><surname>Chen</surname><given-names>Ling</given-names></name>
<xref ref-type="aff" rid="aff2"><sup>2</sup></xref><uri xlink:href="https://loop.frontiersin.org/people/2177097/overview" /></contrib>
<contrib contrib-type="author"><name><surname>Chen</surname><given-names>Shuping</given-names></name>
<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
<xref ref-type="aff" rid="aff2"><sup>2</sup></xref><uri xlink:href="https://loop.frontiersin.org/people/905060/overview" /></contrib>
<contrib contrib-type="author" corresp="yes"><name><surname>He</surname><given-names>Longlong</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="corresp" rid="cor1">&#x002A;</xref></contrib>
<contrib contrib-type="author" corresp="yes"><name><surname>Zou</surname><given-names>Jihua</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="aff4"><sup>4</sup></xref>
<xref ref-type="corresp" rid="cor1">&#x002A;</xref><uri xlink:href="https://loop.frontiersin.org/people/903834/overview" /></contrib>
<contrib contrib-type="author" corresp="yes"><name><surname>Zeng</surname><given-names>Qing</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="corresp" rid="cor1">&#x002A;</xref><uri xlink:href="https://loop.frontiersin.org/people/1789059/overview" /></contrib>
</contrib-group>
<aff id="aff1"><label><sup>1</sup></label><institution>School of Rehabilitation Sciences, Southern Medical University</institution>, <addr-line>Guangzhou</addr-line>, <country>China</country></aff>
<aff id="aff2"><label><sup>2</sup></label><institution>Department of Rehabilitation Medicine, Zhujiang Hospital, Southern Medical University</institution>, <addr-line>Guangzhou</addr-line>, <country>China</country></aff>
<aff id="aff3"><label><sup>3</sup></label><institution>School of Nursing, Southern Medical University</institution>, <addr-line>Guangzhou</addr-line>, <country>China</country></aff>
<aff id="aff4"><label><sup>4</sup></label><institution>Faculty of Health and Social Sciences, The Hong Kong Polytechnic University</institution>, <addr-line>Hong Kong</addr-line>, <country>China</country></aff>
<author-notes>
<fn fn-type="edited-by"><p><bold>Edited by:</bold> Guido Iaccarino, University of Naples Federico II, Italy</p></fn>
<fn fn-type="edited-by"><p><bold>Reviewed by:</bold> Daniel Langer, KU Leuven, Belgium Alexandre Prado, Federal University of Mato Grosso, Brazil Erik Hulzebos, University Medical Center Utrecht, Netherlands</p></fn>
<corresp id="cor1"><label>&#x002A;</label><bold>Correspondence:</bold> Qing Zeng <email>zengqingyang203@126.com</email> Jihua Zou <email>zoujihua@i.smu.edu.cn</email> Longlong He <email>957995818@qq.com</email></corresp>
<fn fn-type="equal" id="an1"><label><sup>&#x2020;</sup></label><p>These authors have contributed equally to this work</p></fn>
</author-notes>
<pub-date pub-type="epub"><day>23</day><month>05</month><year>2023</year></pub-date>
<pub-date pub-type="collection"><year>2023</year></pub-date>
<volume>10</volume><elocation-id>1113509</elocation-id>
<history>
<date date-type="received"><day>01</day><month>12</month><year>2022</year></date>
<date date-type="accepted"><day>28</day><month>04</month><year>2023</year></date>
</history>
<permissions>
<copyright-statement>&#x00A9; 2023 Zheng, Zhang, Li, Li, Yao, Zheng, Li, Zeng, Chen, Chen, He, Zou and Zeng.</copyright-statement>
<copyright-year>2023</copyright-year><copyright-holder>Zheng, Zhang, Li, Li, Yao, Zheng, Li, Zeng, Chen, Chen, He, Zou and Zeng</copyright-holder><license license-type="open-access" xlink:href="http://creativecommons.org/licenses/by/4.0/">
<p>This is an open-access article distributed under the terms of the <ext-link ext-link-type="uri" xlink:href="http://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.</p></license>
</permissions>
<abstract><sec><title>Objective</title>
<p>To explore the effects of inspiratory muscle training (IMT) on hypertension and provide guidance for its clinical application as an auxiliary approach.</p>
</sec><sec><title>Methods</title>
<p>Articles published prior to July 2022 were searched in Cochrane Library, Web of Science, PubMed, Embase, CNKI, and Wanfang databases. Included were randomized controlled studies that used IMT to treat individuals with hypertension. The mean difference (MD) was computed using the Revman 5.4 software. In individuals with hypertension, the effects of IMT on systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), and pulse pressure (PP) were compared and studied.</p>
</sec><sec><title>Results</title>
<p>There were found to be eight randomized controlled trials totaling 215 patients. According to a meta-analysis, the IMT reduced the SBP (MD: &#x2212;12.55&#x2005;mmHg, 95&#x0025; CI: &#x2212;15.78, &#x2212;9.33), DBP (MD: &#x2212;4.77&#x2005;mmHg, 95&#x0025; CI: &#x2212;6.00, &#x2212;3.54), HR (MD: &#x2212;5.92&#x2005;bpm, 95&#x0025; CI: &#x2212;8.72, &#x2212;3.12), and PP (MD: &#x2212;8.92 mmHg, 95&#x0025; CI: &#x2212;12.08, &#x2212;5.76) in patients with hypertension. In subgroup analyses, low-intensity IMT showed a better reduction in SBP (MD: &#x2212;14.47&#x2005;mmHg, 95&#x0025; CI: &#x2212;17.60, &#x2212;11.34), DBP (MD: &#x2212;7.70&#x2005;mmHg, 95&#x0025; CI: &#x2212;10.21, &#x2212;5.18).</p>
</sec><sec><title>Conclusion</title>
<p>IMT may become an auxiliary means to improve the four hemodynamic indexes (SBP, DBP, HR and PP) in patients with hypertension. In subgroup analyses, low-intensity IMT was more effective in regulating blood pressure than medium-high-intensity IMT.</p>
</sec><sec><title>Systematic Review Registration</title>
<p><ext-link ext-link-type="uri" xlink:href="https://www.crd.york.ac.uk/prospero/">https://www.crd.york.ac.uk/prospero/</ext-link>, identifier: CRD42022300908.</p>
</sec>
</abstract>
<kwd-group>
<kwd>hypertension</kwd>
<kwd>blood pressure</kwd>
<kwd>inspiratory muscle training</kwd>
<kwd>IMT</kwd>
<kwd>meta&#x2014;analysis</kwd>
</kwd-group><contract-num rid="cn001">82002380, 82205245</contract-num><contract-num rid="cn002">X202012121325S, X202112121184</contract-num><contract-num rid="cn003">B521ZJ0102</contract-num><contract-num rid="cn004">202206252011533513</contract-num><contract-sponsor id="cn001">National Nature Science Foundation of China (NSFC)</contract-sponsor><contract-sponsor id="cn002">College Student&#x0027;s Innovative Entrepreneurial Training Plan Program for Southern Medical University</contract-sponsor><contract-sponsor id="cn003">Southern Medical University Scientific Research Enlightenment Project</contract-sponsor><contract-sponsor id="cn004">Guangdong Province Health Appropriate Technology Promotion Project</contract-sponsor><counts>
<fig-count count="8"/>
<table-count count="4"/><equation-count count="0"/><ref-count count="51"/><page-count count="0"/><word-count count="0"/></counts><custom-meta-wrap><custom-meta><meta-name>section-at-acceptance</meta-name><meta-value>Hypertension</meta-value></custom-meta></custom-meta-wrap>
</article-meta>
</front>
<body><sec id="s1" sec-type="intro"><label>1.</label><title>Introduction</title>
<p>In the world, hypertension affects 31.1&#x0025; of adults, making it one of the most prevalent chronic illnesses (<xref ref-type="bibr" rid="B1">1</xref>). Type 2 diabetes, heart failure, and stroke could be secondary to hypertension (<xref ref-type="bibr" rid="B2">2</xref>&#x2013;<xref ref-type="bibr" rid="B5">5</xref>), resulting in the death of patients with heart diseases and stroke, which are seriously endangering human health (<xref ref-type="bibr" rid="B6">6</xref>). Therefore, a novel treatment is urgently needed to control the further deterioration of hypertension. According to a meta-analysis, physical exercise helps people with hypertension lower their blood pressure (BP) (<xref ref-type="bibr" rid="B7">7</xref>). IMT has been shown to be a crucial component in the rehabilitation of hypertension as an innovative physical activity strategy (<xref ref-type="bibr" rid="B8">8</xref>).</p>
<p>Inspiratory muscle training (IMT) is performed using a small and special breathing device that can provide resistance for inhalation [such as PowerBreath&#x00AE; (<xref ref-type="bibr" rid="B9">9</xref>)], which, with better tolerance and efficiency, can be used as an important adjunct therapy for patients with hypertension (<xref ref-type="bibr" rid="B10">10</xref>). The underlying mechanism for the ability of IMT to lower BP may be the central respiratory network, and its interaction with the sympathetic nerve drive and vagus nerve activity may be affected by an increase in inspiratory muscle strength, which also promotes cardiopulmonary coupling (<xref ref-type="bibr" rid="B11">11</xref>). Recent research suggests (<xref ref-type="bibr" rid="B12">12</xref>) that IMT with a 30&#x0025; MIP may be able to lower BP in people with essential hypertension, as well as isolated systolic hypertension patients whose resting BP is elevated (<xref ref-type="bibr" rid="B13">13</xref>). However, the impact of IMT on hypertension is still debatable. Beltrami (<xref ref-type="bibr" rid="B14">14</xref>) has regarded the effects of IMT on hypertension as exaggerated. It (<xref ref-type="bibr" rid="B15">15</xref>) shows that IMT has no obvious effects on the BP of patients with hypertension, and slow breathing is more effective than IMT in lowering BP (<xref ref-type="bibr" rid="B16">16</xref>). Da Silva (<xref ref-type="bibr" rid="B17">17</xref>) has shown that loaded respiratory training can reduce BP in hypertension, however, only two RCTs were analyzed in this literature resulting in low confidence in the results. To sum up, the effects of IMT on hypertension should be further explored.</p>
<p>Furthermore, studies (<xref ref-type="bibr" rid="B18">18</xref>) have also demonstrated that patients with hypertension can have their BP under control by monitoring hemodynamic indicators, like systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), and pulse pressure (PP). The goal of this study was to conduct a meta-analysis evaluating the benefits of IMT for individuals with hypertension in order to determine how IMT affects people with hemodynamic indices of hypertension and to provide guidance and evidence for the clinical application of IMT.</p>
</sec>
<sec id="s2" sec-type="methods"><label>2.</label><title>Methods</title>
<p>The Cochrane Cooperation Organization&#x0027;s (<xref ref-type="bibr" rid="B19">19</xref>) and PRISMA guidelines for systematic evaluation and meta-analysis (<xref ref-type="bibr" rid="B20">20</xref>) were followed in conducting this meta-analysis. The protocol has a PROSPERO registration (registration code CRD42022300908). This study was based on the existing published literature, therefore, ethical approval is not required.</p>
<sec id="s2a"><label>2.1.</label><title>Eligibility criteria</title>
<p>Using PICOS elements as a basis, the eligibility criteria were defined (<xref ref-type="bibr" rid="B21">21</xref>): (1) population: patients enrolled in clinical trials who have SBP greater than 130&#x2005;mmHg and/or DBP greater than 80&#x2005;mmHg (<xref ref-type="bibr" rid="B22">22</xref>); (2) intervention: IMT was utilized in the intervention group; (3) comparison: in the control group, a blank control, sham IMT therapy, or traditional training, were implemented; (4) outcome: mean BP or PP in mmHg, HR in bpm, and standard deviation or standard error; (5) study type: randomized controlled trials. Additionally, we excluded trials according to the exclusion criteria: (1) study types were conference abstracts, non-randomized controlled trials, retrospective studies, animal experiments, case reports, etc.; (2) participants in clinical trials who had other cardiovascular and cerebrovascular diseases or metabolic diseases; (3) inability to obtain the full text and complete data.</p>
</sec>
<sec id="s2b"><label>2.2.</label><title>Search strategy</title>
<p>To locate any pertinent randomized controlled trials (RCTs), the following databases were thoroughly searched: Web of Science, the Cochrane Library, PubMed, Embase, CNKI, and Wanfang databases. The literature search was carried out without language restrictions or a beginning date until July 2022 using the following terms: &#x201C;high blood pressure&#x201D;, &#x201C;hypertension&#x201D;, &#x201C;blood pressure&#x201D;, &#x201C;diastolic blood pressure&#x201D;, &#x201C;systolic blood pressure&#x201D;, &#x201C;systolic blood pressure&#x201D;, &#x201C;pulse pressure&#x201D;, &#x201C;heart rate&#x201D;, &#x201C;breathing exercise&#x201D;, &#x201C;inspiratory muscle training&#x201D;, &#x201C;inspiratory loaded breathing training&#x201D;, &#x201C;high-resistance inspiratory muscle strength training&#x201D;, &#x201C;slow load breathing training&#x201D;, and &#x201C;IMT.&#x201D; We contacted the authors via email for additional information in cases of insufficient data, and the available data were used to run analyses if they failed to respond within 14 days.</p>
</sec>
<sec id="s2c"><label>2.3.</label><title>Study selection</title>
<p>Relevant literature was searched using the following process: The first step was a preliminary screening using the title and abstract, which was then loaded into Endnote X9 software, where duplicate literature was then removed. The remaining full text of literature was carefully examined in light of the established inclusion and exclusion criteria, and any content that did not meet the standards was eliminated. The whole screening process was independently performed by two reviewers (GL and LC). The third reviewer (YZ) was ready for consultation if there were any discrepancies between the two independent reviewers.</p>
</sec>
<sec id="s2d"><label>2.4.</label><title>Data extraction</title>
<p>Two researchers (SZ and SYL) independently retrieved the following information: the first author, publication year, sample size, average age, type of hypertension, gender, medication, load intensity, intervention time, training time, training frequency, respiratory rate, training equipment, data (SBP, DBP, HR, and PP) of the intervention group and control group data, time of measurement, equipment of measurement, and position of measurement. When there was insufficient data, we emailed the authors for additional information, and if they didn&#x0027;t reply within a week, we ran analyses using the data that were available instead.</p>
</sec>
<sec id="s2e"><label>2.5.</label><title>Quality assessment</title>
<p>The quality of each study was assessed by two researchers (QZh and SZ) using a modified Jadad quality scale (<xref ref-type="bibr" rid="B23">23</xref>) that included four questions related to scientific rigor, such as the generation of a random sequence, randomization concealment, blind method, withdrawal number, and reasons. The highest score on the modified Jadad quality scale is 7, with 1, 2, and 3 denoting low quality and 4, 5, 6, and 7 denoting high quality (<xref ref-type="bibr" rid="B24">24</xref>).</p>
</sec>
<sec id="s2f"><label>2.6.</label><title>Data analysis</title>
<p>The Cochrane Handbook for Systematic Reviews of Interventions was used to analyze the data. For continuous variables, the mean difference (MD) and 95&#x0025; confidence interval (CI) were used to compare net changes (i.e., IMT vs. control group). For each study group and important outcome, mean and standard deviations (SD) were gathered in order to calculate the effect size. A negative effect size indicated that IMT effectively reduced SBP, DBP, HR, and PP. Using the heterogeneity chi-square test and <italic>I</italic><sup>2</sup> statistics, this study quantitatively discussed the heterogeneity of various studies. These relevant data results were analyzed using the Revman5.4 software. The pooled MD and the 95&#x0025; CI were represented graphically using a forest plot. According to its weight in the meta-analysis, each study was represented in the plot by a square. The threshold for statistical significance was a two-sided <italic>P</italic> value of 0.05. As the number of included researches was lower than ten pieces of research, we did not use statistical or graphical methods to evaluate publication bias.</p>
</sec>
</sec>
<sec id="s3" sec-type="results"><label>3.</label><title>Results</title>
<sec id="s3a"><label>3.1.</label><title>Selection</title>
<p>The initial search identified 5,754 pieces of literature, 5,141 of which were left after eliminating duplicate literature using the EndNote x9 software. Only 104 publications, chosen based on titles and abstracts, were used for the rest of the analysis. Eight RCTs (<xref ref-type="bibr" rid="B12">12</xref>, <xref ref-type="bibr" rid="B13">13</xref>, <xref ref-type="bibr" rid="B15">15</xref>, <xref ref-type="bibr" rid="B25">25</xref>&#x2013;<xref ref-type="bibr" rid="B29">29</xref>), seven in English and one in Chinese, were eventually included in this study after carefully reading the whole text (<xref ref-type="fig" rid="F1">Figure&#x00A0;1</xref>). Following a full-text analysis, the main reasons for exclusion were: full text not being accessible; duplicate data; non-RCTs; other interventions; and other connected disorders.</p>
<fig id="F1" position="float"><label>Figure 1</label>
<caption><p>Flow chart of search retrieval and screening.</p></caption>
<graphic xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="fcvm-10-1113509-g001.tif"/>
</fig>
</sec>
<sec id="s3b"><label>3.2.</label><title>Participant characteristics</title>
<p>Eight studies with a total sample size of 215 patients aged between 50 and 70 years were finally analyzed: seven clinical trials were designed as parallel trials (<xref ref-type="bibr" rid="B12">12</xref>, <xref ref-type="bibr" rid="B13">13</xref>, <xref ref-type="bibr" rid="B15">15</xref>, <xref ref-type="bibr" rid="B25">25</xref>&#x2013;<xref ref-type="bibr" rid="B29">29</xref>) and only one study (<xref ref-type="bibr" rid="B28">28</xref>) was a cross-over trial. Based on the type of hypertension, three studies (<xref ref-type="bibr" rid="B12">12</xref>, <xref ref-type="bibr" rid="B15">15</xref>, <xref ref-type="bibr" rid="B25">25</xref>) essential hypertension, three (<xref ref-type="bibr" rid="B13">13</xref>, <xref ref-type="bibr" rid="B26">26</xref>, <xref ref-type="bibr" rid="B27">27</xref>) isolated systolic hypertension, and two (<xref ref-type="bibr" rid="B28">28</xref>, <xref ref-type="bibr" rid="B29">29</xref>) only described as hypertension. One study (<xref ref-type="bibr" rid="B28">28</xref>) did not record the drug information of patients, while the other seven studies (<xref ref-type="bibr" rid="B12">12</xref>, <xref ref-type="bibr" rid="B13">13</xref>, <xref ref-type="bibr" rid="B15">15</xref>, <xref ref-type="bibr" rid="B25">25</xref>&#x2013;<xref ref-type="bibr" rid="B27">27</xref>, <xref ref-type="bibr" rid="B29">29</xref>) had records of drug information, mainly including angiotensin-converting enzyme inhibitors, calcium blockers, angiotensin II receptor blockers, and beta-blockers. Characteristics of the participants was shown in <xref ref-type="table" rid="T1">Table&#x00A0;1</xref>.</p>
<table-wrap id="T1" position="float"><label>Table 1</label>
<caption><p>Characteristics of participants.</p></caption>
<table frame="hsides" rules="groups">
<colgroup>
<col align="left"/>
<col align="center"/>
<col align="center"/>
<col align="center"/>
<col align="left"/>
<col align="left"/>
<col align="left"/>
</colgroup>
<thead>
<tr>
<th valign="top" align="left">Study</th>
<th valign="top" align="center">Design of trials</th>
<th valign="top" align="center">Sample size</th>
<th valign="top" align="center">Age (years)</th>
<th valign="top" align="center">Stage of hypertension</th>
<th valign="top" align="center">Gender</th>
<th valign="top" align="center">Medication</th>
</tr>
</thead>
<tbody>
<tr>
<td valign="top">Craighead DH 2021 (<xref ref-type="bibr" rid="B29">29</xref>)</td>
<td valign="top">Parallel</td>
<td valign="top">IMST: 18<break/>C: 18</td>
<td valign="top">IMST: 67&#x2009;&#x00B1;&#x2009;2<break/>C: 67&#x2009;&#x00B1;&#x2009;2</td>
<td valign="top">Hypertension</td>
<td valign="top">IMST:<break/>F:9, M:9<break/>C: F:8, M:10</td>
<td valign="top">Antihypertensive or other prescription medications (eg, statins)</td>
</tr>
<tr>
<td valign="top">Ferreira JB 2013 (<xref ref-type="bibr" rid="B12">12</xref>)</td>
<td valign="top">Parallel</td>
<td valign="top">IMT: 6<break/>P-IMT: 7</td>
<td valign="top">IMT: 61.8&#x2009;&#x00B1;&#x2009;11.1<break/>P-IMT: 52.1&#x2009;&#x00B1;&#x2009;8.8</td>
<td valign="top">Essential hypertension</td>
<td valign="top">IMT:<break/>F:3, M:3<break/>P-IMT: <break/>F:5, M:2</td>
<td valign="top">Diuretics<break/>&#x03B2;-receptor blocker<break/>Calcium channel blocker<break/>ACE-l</td>
</tr>
<tr>
<td valign="top">Jones CU 2010 (<xref ref-type="bibr" rid="B25">25</xref>)</td>
<td valign="top">Parallel</td>
<td valign="top">LB: 10<break/>C: 10</td>
<td valign="top">LB: 50&#x2009;&#x00B1;&#x2009;5<break/>C: 51&#x2009;&#x00B1;&#x2009;5</td>
<td valign="top">Essential hypertension Stage I/II</td>
<td valign="top">LB:<break/>F:7, M:3<break/>C: F:5, M:5</td>
<td valign="top">Enalapril<break/>atenolol<break/>hydrochorothiazide</td>
</tr>
<tr>
<td valign="top">Ublosakka-Jones C 2017 (<xref ref-type="bibr" rid="B26">26</xref>)</td>
<td valign="top">Parallel</td>
<td valign="top">LB: 10<break/>C: 9</td>
<td valign="top">LB: 65<break/>C: 65</td>
<td valign="top">Isolated systolic hypertension</td>
<td valign="top">LB:<break/>F:6, M:4<break/>C: F;6, M:3</td>
<td valign="top">Diuretic<break/>Ang ll receptor blockers<break/>Calcium channel blockers<break/>&#x03B2;-receptor blocker<break/>Metformin</td>
</tr>
<tr>
<td valign="top">Ublosakka-Jones C 2018 (<xref ref-type="bibr" rid="B27">27</xref>)</td>
<td valign="top">Parallel</td>
<td valign="top">LB: 16<break/>C: 16</td>
<td valign="top">LB: 66.4&#x2009;&#x00B1;&#x2009;4.2<break/>C: 68.2&#x2009;&#x00B1;&#x2009;4.8</td>
<td valign="top">Isolated systolic hypertension</td>
<td valign="top">LB:<break/>F:8, M:8<break/>C: F:8, M:8</td>
<td valign="top">Diuretics<break/>Ang Il receptors blocker<break/>Calcium channel blocker</td>
</tr>
<tr>
<td valign="top">Ublosakka-Jones C 2019 (<xref ref-type="bibr" rid="B13">13</xref>)</td>
<td valign="top">Parallel</td>
<td valign="top">LB: 10<break/>C: 10</td>
<td valign="top">LB: 67&#x2009;&#x00B1;&#x2009;6<break/>C: 69&#x2009;&#x00B1;&#x2009;3</td>
<td valign="top">Isolated systolic hypertension</td>
<td valign="top">LB:<break/>F:5, M:5<break/>C: F:6, M:4</td>
<td valign="top">ACE-l<break/>Calcium channel blocker<break/>Alpha-blocker</td>
</tr>
<tr>
<td valign="top">Yuenyongchaiwat K 2019 (<xref ref-type="bibr" rid="B28">28</xref>)</td>
<td valign="top">Crossover</td>
<td valign="top">20</td>
<td valign="top">58.25&#x2009;&#x00B1;&#x2009;13.78</td>
<td valign="top">Hypertension</td>
<td valign="top">M:50<break/>F:50</td>
<td valign="top">&#x2014;</td>
</tr>
<tr>
<td valign="top">Zhu K 2021 (<xref ref-type="bibr" rid="B15">15</xref>)</td>
<td valign="top">Parallel</td>
<td valign="top">LB: 26<break/>C: 28</td>
<td valign="top">LB: 56.2&#x2009;&#x00B1;&#x2009;8.1<break/>C: 53.1&#x2009;&#x00B1;&#x2009;7.9</td>
<td valign="top">Essential hypertension</td>
<td valign="top">LB:<break/>F:18, M:10<break/>C: F:15, M: 11</td>
<td valign="top">Diuretic<break/>Calcium channel blocker<break/>&#x03B2;-receptor blocker<break/>ACE-l<break/>Ang ll receptor blockers<break/>&#x03B1;-receptor blocker</td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<fn id="table-fn1"><p>BMI, body mass index; LB, loaded breathing; ULB, unloaded breathing; Con, control groups; IMT, inspiratory muscle training; P-IMT, placebo-inspiratory muscle training; IMST, inspiratory muscle strength training; M, man; F, female; ACE-l, angiotensin-converting enzyme inhibitory.</p></fn>
</table-wrap-foot>
</table-wrap>
</sec>
<sec id="s3c"><label>3.3.</label><title>Measurements on hemodynamic parameters</title>
<p>Ambulatory BP and PP were measured in two studies (<xref ref-type="bibr" rid="B12">12</xref>, <xref ref-type="bibr" rid="B29">29</xref>) and resting BP and PP were measured before and 10&#x2005;min after intervention in the other two studies (<xref ref-type="bibr" rid="B15">15</xref>, <xref ref-type="bibr" rid="B28">28</xref>). BP and PP were measured every morning in three studies (<xref ref-type="bibr" rid="B13">13</xref>, <xref ref-type="bibr" rid="B25">25</xref>, <xref ref-type="bibr" rid="B27">27</xref>). Resting BP and PP were measured before and 8 weeks after training (<xref ref-type="bibr" rid="B26">26</xref>). The position of BP measurements was simply described in the patient&#x0027;s non-dominant arm in five articles (<xref ref-type="bibr" rid="B12">12</xref>, <xref ref-type="bibr" rid="B13">13</xref>, <xref ref-type="bibr" rid="B24">24</xref>, <xref ref-type="bibr" rid="B26">26</xref>, <xref ref-type="bibr" rid="B28">28</xref>). In one study, the position was depicted on the left semi-flexed arm at the heart-level height (<xref ref-type="bibr" rid="B28">28</xref>), but another article said the position was the patient&#x0027;s right upper brachial artery pressure (<xref ref-type="bibr" rid="B15">15</xref>). The remaining RCT indicated that this position was on each subject&#x0027;s arm 1 inch above the elbow over the brachial artery (<xref ref-type="bibr" rid="B26">26</xref>). As for measuring equipment, these studies used Oscar 2 (SunTech Medical) (<xref ref-type="bibr" rid="B29">29</xref>), DynaMAPA&#x00AE; monitor (Cardios, S&#x00E3;o Paulo, Brazil) (<xref ref-type="bibr" rid="B12">12</xref>), Ri-champion (Rudolf Riester GMBH Co, Germany) (<xref ref-type="bibr" rid="B13">13</xref>, <xref ref-type="bibr" rid="B25">25</xref>, <xref ref-type="bibr" rid="B27">27</xref>), BSM-6701 bedside monitor (Nihon Kohden, Tokyo, Japan) (<xref ref-type="bibr" rid="B26">26</xref>), Philips Intellivue MP20 bedside monitor (Nihon Kohden, Tokyo, Japan) (<xref ref-type="bibr" rid="B28">28</xref>), and Yuwell desktop sphygmomanometer (<xref ref-type="bibr" rid="B15">15</xref>) respectively. The measurement time, position, and equipment of PP and HR in 8 RCTS were also shown in <xref ref-type="table" rid="T2">Table&#x00A0;2</xref>.</p>
<table-wrap id="T2" position="float"><label>Table 2</label>
<caption><p>Hemodynamic parameters of participants.</p></caption>
<table frame="hsides" rules="groups">
<colgroup>
<col align="left"/>
<col align="left"/>
<col align="left"/>
<col align="left"/>
<col align="left"/>
<col align="left"/>
<col align="left"/>
<col align="left"/>
</colgroup>
<thead>
<tr>
<th valign="top" align="left" rowspan="2">Study</th>
<th valign="top" align="center" rowspan="2">SBP (mmHg)</th>
<th valign="top" align="center" rowspan="2">DBP (mmHg)</th>
<th valign="top" align="center" rowspan="2">HR (bpm)</th>
<th valign="top" align="center" rowspan="2">PP (mmHg)</th>
<th valign="top" align="center" colspan="3">Measurements</th>
</tr>
<tr>
<th valign="top" align="center">Time</th>
<th valign="top" align="center">Position</th>
<th valign="top" align="center">Equipment</th>
</tr>
</thead>
<tbody>
<tr>
<td valign="top" align="left">Craighead DH 2021 (<xref ref-type="bibr" rid="B29">29</xref>)</td>
<td valign="top" align="left">IMST:131&#x2009;&#x00B1;&#x2009;3<break/>C:135&#x2009;&#x00B1;&#x2009;3</td>
<td valign="top" align="left">IMST:75&#x2009;&#x00B1;&#x2009;2<break/>C:74&#x2009;&#x00B1;&#x2009;2</td>
<td valign="top" align="left">&#x2014;</td>
<td valign="top" align="left">&#x2014;</td>
<td valign="top" align="left">ABPM was measured at baseline and after 6 weeks of IMST or sham training.</td>
<td valign="top" align="left">BP:<break/>the subject&#x0027;s non-dominant arm</td>
<td valign="top" align="left">BP:<break/>Oscar 2; (SunTech Medical)</td>
</tr>
<tr>
<td valign="top" align="left">Ferreira JB 2013 (<xref ref-type="bibr" rid="B12">12</xref>)</td>
<td valign="top" align="left">IMT: 133.1&#x2009;&#x00B1;&#x2009;9.8<break/>IMT: 130&#x2009;&#x00B1;&#x2009;6.4</td>
<td valign="top" align="left">IMT: 80.6&#x2009;&#x00B1;&#x2009;12.3<break/>P-IMT: 86.4&#x2009;&#x00B1;&#x2009;9.3</td>
<td valign="top" align="left">IMT:61.3&#x2009;&#x00B1;&#x2009;12.7<break/>P-IMT:71.0&#x2009;&#x00B1;&#x2009;14.7</td>
<td valign="top" align="left">&#x2014;</td>
<td valign="top" align="left">ABPM was measured before and after the interventions.<break/>HR was acquired immediately before and after the interventions.</td>
<td valign="top" align="left">BP:<break/>the subject&#x0027;s non-dominant arm<break/>HR:<break/>ECG electrodes</td>
<td valign="top" align="left">BP:<break/>DynaMAPA&#x00AE; monitor (Cardios, S&#x00E3;o Paulo, Brazil)<break/>HR:<break/>Biopac MP150 system(Biopac, California, USA)</td>
</tr>
<tr>
<td valign="top" align="left">Jones CU 2010 (<xref ref-type="bibr" rid="B25">25</xref>)</td>
<td valign="top" align="left">LB: 142&#x2009;&#x00B1;&#x2009;8.9<break/>ULB: 141&#x2009;&#x00B1;&#x2009;5.9<break/>C: 142&#x2009;&#x00B1;&#x2009;9.6</td>
<td valign="top" align="left">LB:87&#x2009;&#x00B1;&#x2009;5.2<break/>ULB: 85&#x2009;&#x00B1;&#x2009;4.4<break/>C: 87&#x2009;&#x00B1;&#x2009;5.3</td>
<td valign="top" align="left">LB: 75&#x2009;&#x00B1;&#x2009;5.8<break/>ULB:74&#x2009;&#x00B1;&#x2009;5.6<break/>C:73&#x2009;&#x00B1;&#x2009;7.3</td>
<td valign="top" align="left">LB: 55&#x2009;&#x00B1;&#x2009;9.4<break/>ULB:57&#x2009;&#x00B1;&#x2009;4.9<break/>C:56&#x2009;&#x00B1;&#x2009;9.8</td>
<td valign="top" align="left">HR, BP and PP were made in every morning between 7.00 and 9.00 am before the patients began training and in the week following the last training session.</td>
<td valign="top" align="left">BP/PP/HR:<break/>the subject&#x0027;s non-dominant arm</td>
<td valign="top" align="left">BP/PP/HR:<break/>Ri-champion(Rudolf Riester GMBH Co, Germany)</td>
</tr>
<tr>
<td valign="top" align="left">Ublosakka-Jones C 2017 (<xref ref-type="bibr" rid="B26">26</xref>)</td>
<td valign="top" align="left">LB: 139&#x2009;&#x00B1;&#x2009;10<break/>C: 139&#x2009;&#x00B1;&#x2009;10</td>
<td valign="top" align="left">LB: 73&#x2009;&#x00B1;&#x2009;13<break/>C: 76&#x2009;&#x00B1;&#x2009;9</td>
<td valign="top" align="left">LB: 68&#x2009;&#x00B1;&#x2009;8<break/>C: 68&#x2009;&#x00B1;&#x2009;11</td>
<td valign="top" align="left">LB: 67&#x2009;&#x00B1;&#x2009;7<break/>C: 63&#x2009;&#x00B1;&#x2009;8</td>
<td valign="top" align="left">Resting BP and HR were reported for assessment before and immediately after the 8-week training period.</td>
<td valign="top" align="left">BP/PP:<break/>each subject&#x0027;s arm 1 inch above<break/>the elbow over the brachial artery<break/>HR:<break/>ECG electrodes</td>
<td valign="top" align="left">BP/PP:<break/>BSM-6701 bedside monitor (Nihon Kohden, Tokyo, Japan)<break/>HR:<break/>BiopacTM SS11LA (BIOPAC System)</td>
</tr>
<tr>
<td valign="top" align="left">Ublosakka-Jones C 2018 (<xref ref-type="bibr" rid="B27">27</xref>)</td>
<td valign="top" align="left">LB: 141.5&#x2009;&#x00B1;&#x2009;6.5<break/>C: 141.4&#x2009;&#x00B1;&#x2009;4.8</td>
<td valign="top" align="left">LB: 70.4&#x2009;&#x00B1;&#x2009;3.2<break/>C: 73.0&#x2009;&#x00B1;&#x2009;7.5</td>
<td valign="top" align="left">LB: 71.2&#x2009;&#x00B1;&#x2009;6.9<break/>C: 72.5&#x2009;&#x00B1;&#x2009;11.6</td>
<td valign="top" align="left">LB: 71.1&#x2009;&#x00B1;&#x2009;6.6<break/>C: 63.7&#x2009;&#x00B1;&#x2009;9.7</td>
<td valign="top" align="left">HR, BP and PP were carried out, every morning before 9:00 am during the 2 week run-in and the following 8 week training period.</td>
<td valign="top" align="left">BP/PP/HR:<break/>the subject&#x0027;s non-dominant arm</td>
<td valign="top" align="left">BP/PP/HR:<break/>ri-championN (Jungingen, Germany)</td>
</tr>
<tr>
<td valign="top" align="left">Ublosakka-Jones C 2019 (<xref ref-type="bibr" rid="B13">13</xref>)</td>
<td valign="top" align="left">LB: 143&#x2009;&#x00B1;&#x2009;9<break/>C: 137&#x2009;&#x00B1;&#x2009;7</td>
<td valign="top" align="left">LB:80&#x2009;&#x00B1;&#x2009;8<break/>C:76&#x2009;&#x00B1;&#x2009;12</td>
<td valign="top" align="left">LB: 72&#x2009;&#x00B1;&#x2009;13.4<break/>C: 71&#x2009;&#x00B1;&#x2009;13.8</td>
<td valign="top" align="left">LB: 63&#x2009;&#x00B1;&#x2009;5.7<break/>C: 76&#x2009;&#x00B1;&#x2009;7.3</td>
<td valign="top" align="left">HR, BP and PP data were noted every day before 9:00 am,together with a record of their training, during the 2-week run-in,the following 8-week training period.</td>
<td valign="top" align="left">BP/PP/HR:<break/>the subject&#x0027;s non-dominant arm</td>
<td valign="top" align="left">BP/PP/HR:<break/>ri-championN (Jungingen, Germany)</td>
</tr>
<tr>
<td valign="top" align="left">Yuenyongchaiwat K 2019 (<xref ref-type="bibr" rid="B28">28</xref>)</td>
<td valign="top" align="left">LB: 139.15&#x2009;&#x00B1;&#x2009;15.82<break/>C: 138.65&#x2009;&#x00B1;&#x2009;14.21</td>
<td valign="top" align="left">LB: 82.95&#x2009;&#x00B1;&#x2009;10.48<break/>C: 83.60&#x2009;&#x00B1;&#x2009;9.21</td>
<td valign="top" align="left">LB: 80.50&#x2009;&#x00B1;&#x2009;15.59<break/>C: 78.35&#x2009;&#x00B1;&#x2009;15.60</td>
<td valign="top" align="left">&#x2014;</td>
<td valign="top" align="left">HR, BP and PP were performed prior to and after intervention with the 10-min resting.</td>
<td valign="top" align="left">BP/PP/HR:<break/>on the left semi- flexed arm at the heart-level height</td>
<td valign="top" align="left">BP/PP/HR:<break/>Philips Intellivue MP20 bedside monitor (Nihon Kohden, Tokyo, Japan)</td>
</tr>
<tr>
<td valign="top" align="left">Zhu K 2021 (<xref ref-type="bibr" rid="B15">15</xref>)</td>
<td valign="top" align="left">LB: 137&#x2009;&#x00B1;&#x2009;19<break/>C:134&#x2009;&#x00B1;&#x2009;21</td>
<td valign="top" align="left">LB: 89&#x2009;&#x00B1;&#x2009;13<break/>C: 87&#x2009;&#x00B1;&#x2009;11</td>
<td valign="top" align="left">LB: 77&#x2009;&#x00B1;&#x2009;5<break/>C: 74&#x2009;&#x00B1;&#x2009;6</td>
<td valign="top" align="left">&#x2014;</td>
<td valign="top" align="left">HR, BP and PP were performed prior to and after intervention with the 10-min resting.</td>
<td valign="top" align="left">BP:<break/>Patient&#x0027;s right upper brachial artery pressure<break/>HR:<break/>The pulse of the wrist</td>
<td valign="top" align="left">BP:<break/>Yuwell desktop sphygmomanometer<break/>HR:<break/>&#x2014;</td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<fn id="table-fn2"><p>LB, loaded breathing; ULB, unloaded breathing; Con, control groups; IMT, inspiratory muscle training; P-IMT, placebo-inspiratory muscle training; IMST, inspiratory muscle strength training; SBP, systolic blood pressure; DBP, diastolic blood pressure; BP, blood pressure; HR, heart rate; ABPM, ambulatory blood pressure monitoring.</p></fn>
</table-wrap-foot>
</table-wrap>
</sec>
<sec id="s3d"><label>3.4.</label><title>Intervention characteristics</title>
<p>Five (<xref ref-type="bibr" rid="B12">12</xref>, <xref ref-type="bibr" rid="B13">13</xref>, <xref ref-type="bibr" rid="B25">25</xref>&#x2013;<xref ref-type="bibr" rid="B27">27</xref>) intervention groups were low-intensity IMT; two (<xref ref-type="bibr" rid="B15">15</xref>, <xref ref-type="bibr" rid="B28">28</xref>) were medium-intensity IMT; and one study (<xref ref-type="bibr" rid="B29">29</xref>) was high-intensity IMT. Six studies (<xref ref-type="bibr" rid="B13">13</xref>, <xref ref-type="bibr" rid="B15">15</xref>, <xref ref-type="bibr" rid="B26">26</xref>&#x2013;<xref ref-type="bibr" rid="B29">29</xref>) showed no intervention in the control group; one study (<xref ref-type="bibr" rid="B12">12</xref>) showed placebo-IMT; and another study (<xref ref-type="bibr" rid="B27">27</xref>) included both the control group without intervention measures and placebo-IMT. Two studies (<xref ref-type="bibr" rid="B13">13</xref>, <xref ref-type="bibr" rid="B27">27</xref>) used the BreatheMAX device; two studies (<xref ref-type="bibr" rid="B15">15</xref>, <xref ref-type="bibr" rid="B29">29</xref>) used the POWERbreathe device; two studies (<xref ref-type="bibr" rid="B25">25</xref>, <xref ref-type="bibr" rid="B26">26</xref>) used a water pressure threshold bottle; one study (<xref ref-type="bibr" rid="B12">12</xref>) used the Threshold Inspiratory Muscle Trainer (HealthScan Products Inc., Cedgrove, New Jersey), and one study (<xref ref-type="bibr" rid="B28">28</xref>) used the TU-Breath Training device. The intervention duration of one (<xref ref-type="bibr" rid="B29">29</xref>) study was 6 weeks&#x0027; one study (<xref ref-type="bibr" rid="B28">28</xref>) was 1 week, and the remaining six studies (<xref ref-type="bibr" rid="B12">12</xref>, <xref ref-type="bibr" rid="B13">13</xref>, <xref ref-type="bibr" rid="B15">15</xref>, <xref ref-type="bibr" rid="B25">25</xref>&#x2013;<xref ref-type="bibr" rid="B27">27</xref>) were 8 weeks. Characteristics of the intervention was described in <xref ref-type="table" rid="T3">Table&#x00A0;3</xref>.</p>
<table-wrap id="T3" position="float"><label>Table 3</label>
<caption><p>Characteristics of the intervention.</p></caption>
<table frame="hsides" rules="groups">
<colgroup>
<col align="left"/>
<col align="left"/>
<col align="center"/>
<col align="left"/>
<col align="left"/>
<col align="left"/>
<col align="left"/>
</colgroup>
<thead>
<tr>
<th valign="top" align="left">Study</th>
<th valign="top" align="center">Intensity</th>
<th valign="top" align="center">Duration of intervention</th>
<th valign="top" align="center">Training session (min)</th>
<th valign="top" align="center">Weekly frequency</th>
<th valign="top" align="center">Respiratory rate</th>
<th valign="top" align="center">Device</th>
</tr>
</thead>
<tbody>
<tr>
<td valign="top">Craighead DH 2021 (<xref ref-type="bibr" rid="B29">29</xref>)</td>
<td valign="top">Week 1: 55&#x0025; MIP<break/>week 2: 65&#x0025; MIP<break/>week 3&#x2013;6: 75&#x0025; MIP</td>
<td valign="top">6 weeks</td>
<td valign="top">30 inspiratory maneuvers per day</td>
<td valign="top">6 days per week</td>
<td valign="top">30 inspiratory maneuvers (5 sets of 6, 1-min rest between sets)</td>
<td valign="top">POWERbreathe K3</td>
</tr>
<tr>
<td valign="top">Ferreira JB 2013 (<xref ref-type="bibr" rid="B12">12</xref>)</td>
<td valign="top">30&#x0025; MIP</td>
<td valign="top">8 weeks</td>
<td valign="top">30&#x2005;min</td>
<td valign="top">7 days per week</td>
<td valign="top">15 to 20 breaths/min</td>
<td valign="top">Threshold Inspiratory Muscle<break/>Training device</td>
</tr>
<tr>
<td valign="top">Jones CU 2010 (<xref ref-type="bibr" rid="B25">25</xref>)</td>
<td valign="top">20&#x2005;cm H<sub>2</sub>0</td>
<td valign="top">8 weeks</td>
<td valign="top">30&#x2005;min</td>
<td valign="top">Twice a day, 7 days a week</td>
<td valign="top">5&#x2005;s rest after every 6 deep breaths</td>
<td valign="top">Water Pressure Threshold Bottle</td>
</tr>
<tr>
<td valign="top">Ublosakka-Jones C 2017 (<xref ref-type="bibr" rid="B26">26</xref>)</td>
<td valign="top">20&#x2005;cm H<sub>2</sub>0</td>
<td valign="top">8 weeks</td>
<td valign="top">30&#x2005;min</td>
<td valign="top">Twice a day, 7 days a week</td>
<td valign="top">5&#x2005;s rest after every 6 deep breaths</td>
<td valign="top">Water Pressure Threshold Bottle</td>
</tr>
<tr>
<td valign="top">Ublosakka-Jones C 2018 (<xref ref-type="bibr" rid="B27">27</xref>)</td>
<td valign="top">25&#x0025; MIP</td>
<td valign="top">8 weeks</td>
<td valign="top">60 breaths a day</td>
<td valign="top">7 days per week</td>
<td valign="top">6 breaths per minute with an inspiratory time of 4&#x2005;s and expiratory time of 6&#x2005;s</td>
<td valign="top">BreatheMAX</td>
</tr>
<tr>
<td valign="top">Ublosakka-Jones C 2019 (<xref ref-type="bibr" rid="B13">13</xref>)</td>
<td valign="top">25&#x0025; MIP</td>
<td valign="top">8 weeks</td>
<td valign="top">60 breaths a<break/>day</td>
<td valign="top">7 days per week</td>
<td valign="top">6 breaths per minute with an inspiratory time of 4s and expiratory time of 6s</td>
<td valign="top">BreatheMAX</td>
</tr>
<tr>
<td valign="top">Yuenyongchaiwat K 2019 (<xref ref-type="bibr" rid="B28">28</xref>)</td>
<td valign="top">40&#x0025; MIP</td>
<td valign="top">1 weeks</td>
<td valign="top">10&#x2005;min</td>
<td valign="top">7 days per week</td>
<td valign="top">Three sets of 10 breathing exercises</td>
<td valign="top">TU-Breath<break/>Training</td>
</tr>
<tr>
<td valign="top">Zhu K 2021 (<xref ref-type="bibr" rid="B15">15</xref>)</td>
<td valign="top">40&#x0025; MIP</td>
<td valign="top">8 weeks</td>
<td valign="top">Continuous training for 30 times was 1 group, 2 groups per day</td>
<td valign="top">4 days per week</td>
<td valign="top">&#x2013;</td>
<td valign="top">POWERbreathe</td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<fn id="table-fn3"><p>MIP, maximal inspiratory pressure.</p></fn>
</table-wrap-foot>
</table-wrap>
</sec>
<sec id="s3e"><label>3.5.</label><title>Quality assessment results including research</title>
<p>According to the improved Jadad scale, low quality was defined as 1&#x2013;3 points and high quality as 4&#x2013;7 points. Seven studies (<xref ref-type="bibr" rid="B12">12</xref>, <xref ref-type="bibr" rid="B13">13</xref>, <xref ref-type="bibr" rid="B15">15</xref>, <xref ref-type="bibr" rid="B26">26</xref>&#x2013;<xref ref-type="bibr" rid="B29">29</xref>) scored &#x003E;3 points and were classified as high-quality literature, while one study (<xref ref-type="bibr" rid="B25">25</xref>) received 3 points and was labeled as low-quality literature. The quality of the included RCT studies was shown in <xref ref-type="table" rid="T4">Table&#x00A0;4</xref>.</p>
<table-wrap id="T4" position="float"><label>Table 4</label>
<caption><p>The modified jadad scores of the included studies.</p></caption>
<table frame="hsides" rules="groups">
<colgroup>
<col align="left"/>
<col align="center"/>
<col align="center"/>
<col align="center"/>
<col align="center"/>
<col align="center"/>
</colgroup>
<thead>
<tr>
<th valign="top" align="left">First author (Year)</th>
<th valign="top" align="center">Randomization</th>
<th valign="top" align="center">Allocation concealment</th>
<th valign="top" align="center">Blinding</th>
<th valign="top" align="center">Withdrawals and dropouts</th>
<th valign="top" align="center">Total</th>
</tr>
</thead>
<tbody>
<tr>
<td valign="top" align="left">Craighead DH 2021 (<xref ref-type="bibr" rid="B29">29</xref>)</td>
<td valign="top" align="center">2</td>
<td valign="top" align="center">2</td>
<td valign="top" align="center">2</td>
<td valign="top" align="center">1</td>
<td valign="top" align="center">7</td>
</tr>
<tr>
<td valign="top" align="left">Ferreira JB 2013 (<xref ref-type="bibr" rid="B12">12</xref>)</td>
<td valign="top" align="center">2</td>
<td valign="top" align="center">1</td>
<td valign="top" align="center">2</td>
<td valign="top" align="center">1</td>
<td valign="top" align="center">6</td>
</tr>
<tr>
<td valign="top" align="left">Jones CU 2010 (<xref ref-type="bibr" rid="B25">25</xref>)</td>
<td valign="top" align="center">1</td>
<td valign="top" align="center">1</td>
<td valign="top" align="center">0</td>
<td valign="top" align="center">1</td>
<td valign="top" align="center">3</td>
</tr>
<tr>
<td valign="top" align="left">Ublosakka-Jones C 2017 (<xref ref-type="bibr" rid="B26">26</xref>)</td>
<td valign="top" align="center">1</td>
<td valign="top" align="center">2</td>
<td valign="top" align="center">1</td>
<td valign="top" align="center">1</td>
<td valign="top" align="center">5</td>
</tr>
<tr>
<td valign="top" align="left">Ublosakka-Jones C 2018 (<xref ref-type="bibr" rid="B27">27</xref>)</td>
<td valign="top" align="center">1</td>
<td valign="top" align="center">2</td>
<td valign="top" align="center">0</td>
<td valign="top" align="center">1</td>
<td valign="top" align="center">4</td>
</tr>
<tr>
<td valign="top" align="left">Ublosakka-Jones C 2019 (<xref ref-type="bibr" rid="B13">13</xref>)</td>
<td valign="top" align="center">1</td>
<td valign="top" align="center">1</td>
<td valign="top" align="center">1</td>
<td valign="top" align="center">1</td>
<td valign="top" align="center">4</td>
</tr>
<tr>
<td valign="top" align="left">Yuenyongchaiwat K 2019 (<xref ref-type="bibr" rid="B28">28</xref>)</td>
<td valign="top" align="center">1</td>
<td valign="top" align="center">1</td>
<td valign="top" align="center">1</td>
<td valign="top" align="center">1</td>
<td valign="top" align="center">4</td>
</tr>
<tr>
<td valign="top" align="left">Zhu K 2021 (<xref ref-type="bibr" rid="B15">15</xref>)</td>
<td valign="top" align="center">2</td>
<td valign="top" align="center">1</td>
<td valign="top" align="center">1</td>
<td valign="top" align="center">1</td>
<td valign="top" align="center">5</td>
</tr>
</tbody>
</table>
</table-wrap>
</sec>
<sec id="s3f"><label>3.6.</label><title>Main results</title>
<sec id="s3f1"><label>3.6.1.</label><title>Effects of IMT on systolic blood pressure</title>
<p>SBP after treatment was compared between the intervention group using IMT and the control group. The results demonstrated that IMT might lower the SBP of patients with hypertension; According to data analysis from seven trials using a random effect model, IMT could improve the SBP of patients with hypertension. [<italic>n</italic>&#x2009;&#x003D;&#x2009;228, MD&#x2009;&#x003D;&#x2009;&#x2212;12.55&#x2005;mmHg, 95&#x0025;CI (&#x2212;15.78, &#x2212;9.33), <italic>P&#x2009;</italic>&#x003C;&#x2009;0.01] (<xref ref-type="fig" rid="F2">Figure&#x00A0;2</xref>).</p>
<fig id="F2" position="float"><label>Figure 2</label>
<caption><p>Meta-analysis forest of diagram of systolic blood pressure.</p></caption>
<graphic xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="fcvm-10-1113509-g002.tif"/>
</fig>
</sec>
<sec id="s3f2"><label>3.6.2.</label><title>Effects of IMT on diastolic blood pressure</title>
<p>After analyzing the DBP data in the IMT and control groups, high heterogeneity was found (<italic>I<sup>2</sup></italic>&#x2009;&#x003D;&#x2009;45&#x0025;). Therefore, for the meta-analysis, we used a fixed effects model. The results demonstrated that IMT training was more successful than a control group in decreasing DBP in patients with hypertension [<italic>n</italic>&#x2009;&#x003D;&#x2009;228, MD&#x2009;&#x003D;&#x2009;&#x2212;4.77&#x2005;mmHg, 95&#x0025; CI (&#x2212;6.00, &#x2212;3.54), <italic>P&#x2009;</italic>&#x003C;&#x2009;0.01] (<xref ref-type="fig" rid="F3">Figure&#x00A0;3</xref>).</p>
<fig id="F3" position="float"><label>Figure 3</label>
<caption><p>Meta-analysis forest diagram of diastolic blood pressure.</p></caption>
<graphic xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="fcvm-10-1113509-g003.tif"/>
</fig>
</sec>
</sec>
<sec id="s3g"><label>3.7.</label><title>Secondary results</title>
<sec id="s3g1"><label>3.7.1.</label><title>Effects of IMT on heart rate</title>
<p>Because Daniel H 2021 (<xref ref-type="bibr" rid="B29">29</xref>) study could not obtain relevant data, we analyzed the data from two groups of patients post-treatment in the other seven trials. According to the results of the fixed effect model, IMT had a stronger impact on lowering the HR of patients with hypertension than the control group [<italic>n</italic>&#x2009;&#x003D;&#x2009;199, MD&#x2009;&#x003D;&#x2009;&#x2212;5.92&#x2005;bpm, 95&#x0025; CI (&#x2212;8.72, &#x2212;3.12), <italic>P&#x2009;</italic>&#x003C;&#x2009;0.01] (<xref ref-type="fig" rid="F4">Figure&#x00A0;4</xref>).</p>
<fig id="F4" position="float"><label>Figure 4</label>
<caption><p>Meta-analysis forest diagram of heart rate.</p></caption>
<graphic xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="fcvm-10-1113509-g004.tif"/>
</fig>
</sec>
<sec id="s3g2"><label>3.7.2.</label><title>Effects of IMT on pulse pressure</title>
<p>Four studies provided results for PP with a total of 92 patients. The heterogeneity (<italic>I<sup>2</sup></italic>&#x2009;&#x003D;&#x2009;17&#x0025;) was small; thus, it was decided to use the fixed effect model, and the analysis&#x0027;s findings revealed that IMT could reduce the PP of patients with hypertension [<italic>n</italic>&#x2009;&#x003D;&#x2009;92, MD&#x2009;&#x003D;&#x2009;&#x2212;8.92&#x2005;mmHg, 95&#x0025; CI (&#x2212;12.08, &#x2212;5.76), <italic>P&#x2009;</italic>&#x003C;&#x2009;0.01] (<xref ref-type="fig" rid="F5">Figure&#x00A0;5</xref>). As interventions in these four studies were all low-intensity IMT, the subgroup analysis was not performed.</p>
<fig id="F5" position="float"><label>Figure 5</label>
<caption><p>Meta-analysis forest diagram of pulse pressure.</p></caption>
<graphic xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="fcvm-10-1113509-g005.tif"/>
</fig>
</sec>
</sec>
<sec id="s3h"><label>3.8.</label><title>Subgroup analysis</title>
<sec id="s3h1"><label>3.8.1.</label><title>Effects of IMT on systolic blood pressure</title>
<p>About 30&#x0025; of MIP is considered low-intensity IMT (<xref ref-type="bibr" rid="B30">30</xref>), whereas &#x003E;30&#x0025; MIP is medium-high-intensity IMT. Eight studies were divided into two groups: low-intensity IMT and medium-high-intensity IMT, and two subgroup analyses were conducted. Subgroup analyses showed that low-intensity IMT was effective in decreasing SBP of patients with hypertension [<italic>n</italic>&#x2009;&#x003D;&#x2009;105, MD&#x2009;&#x003D;&#x2009;&#x2212;14.47&#x2005;mmHg, 95&#x0025; CI (&#x2212;17.60, &#x2212;11.34), <italic>P&#x2009;</italic>&#x003C;&#x2009;0.01] (<xref ref-type="fig" rid="F6">Figure&#x00A0;6</xref>); however, medium-high-intensity IMT had no positive effects on reducing SBP of patients with hypertension [<italic>n</italic>&#x2009;&#x003D;&#x2009;123, MD&#x2009;&#x003D;&#x2009;&#x2212;5.95&#x2005;mmHg, 95&#x0025; CI (&#x2212;17.43, 5.53), <italic>P</italic>&#x2009;&#x003D;&#x2009;0.31] (<xref ref-type="fig" rid="F6">Figure&#x00A0;6</xref>).</p>
<fig id="F6" position="float"><label>Figure 6</label>
<caption><p>Meta-analysis forest diagram of subgroup analysis of systolic blood pressure.</p></caption>
<graphic xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="fcvm-10-1113509-g006.tif"/>
</fig>
</sec>
<sec id="s3h2"><label>3.8.2.</label><title>Effects of IMT on diastolic blood pressure</title>
<p>Similarly, a subgroup analysis was carried out on the DBP data from eight trials, which were separated into two groups: low-intensity IMT and medium-high-intensity IMT. Sub-group analysis showed that low-intensity IMT could improve the DBP of patients with hypertension [<italic>n</italic>&#x2009;&#x003D;&#x2009;106, MD&#x2009;&#x003D;&#x2009;&#x2212;7.70&#x2005;mmHg, 95&#x0025; CI (&#x2212;10.21, &#x2212;5.18), <italic>P</italic>&#x2009;&#x003C;&#x2009;0.01] (<xref ref-type="fig" rid="F7">Figure&#x00A0;7</xref>); however, medium-high-intensity IMT did not help reduce the DBP of patients with hypertension [<italic>n</italic>&#x2009;&#x003D;&#x2009;123, MD&#x2009;&#x003D;&#x2009;&#x2212;3.85&#x2005;mmHg, 95&#x0025; CI (&#x2212;5.26, &#x2212;2.44), <italic>P</italic>&#x2009;&#x003D;&#x2009;0.01] (<xref ref-type="fig" rid="F7">Figure&#x00A0;7</xref>).</p>
<fig id="F7" position="float"><label>Figure 7</label>
<caption><p>Meta-analysis forest diagram of subgroup analysis of diastolic blood pressure.</p></caption>
<graphic xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="fcvm-10-1113509-g007.tif"/>
</fig>
</sec>
<sec id="s3h3"><label>3.8.3.</label><title>Effects of IMT on heart rate</title>
<p>Since the relevant data could not be obtained in Daniel H 2021 (<xref ref-type="bibr" rid="B29">29</xref>), a subgroup analysis was carried out on the remaining seven studies. According to the results of the subgroup analysis, low-intensity IMT [<italic>n</italic>&#x2009;&#x003D;&#x2009;199, MD&#x2009;&#x003D;&#x2009;&#x2212;7.05&#x2005;bpm, 95&#x0025; CI (&#x2212;10.53, &#x2212;3.56), <italic>P</italic>&#x2009;&#x003C;&#x2009;0.01] (<xref ref-type="fig" rid="F8">Figure&#x00A0;8</xref>) and medium-high-intensity IMT [<italic>n</italic>&#x2009;&#x003D;&#x2009;74, MD&#x2009;&#x003D;&#x2009;&#x2212;6.34&#x2005;bpm, 95&#x0025; CI (&#x2212;10.70, &#x2212;1.99), <italic>P</italic>&#x2009;&#x003D;&#x2009;0.004] (<xref ref-type="fig" rid="F8">Figure&#x00A0;8</xref>) could effectively slow down the HR of patients with hypertension.</p>
<fig id="F8" position="float"><label>Figure 8</label>
<caption><p>Meta-analysis forest diagram of subgroup analysis of heart rate.</p></caption>
<graphic xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="fcvm-10-1113509-g008.tif"/>
</fig>
</sec>
</sec>
</sec>
<sec id="s4" sec-type="discussion"><label>4.</label><title>Discussion</title>
<p>This meta-analysis set out to assess the impact of IMT hemodynamic indexes on hypertension. Through analysis of eight RCT items (<xref ref-type="bibr" rid="B12">12</xref>, <xref ref-type="bibr" rid="B13">13</xref>, <xref ref-type="bibr" rid="B15">15</xref>, <xref ref-type="bibr" rid="B25">25</xref>&#x2013;<xref ref-type="bibr" rid="B29">29</xref>), IMT was proven to improve the hemodynamic indexes (SBP, DBP, HR, and PP) of patients with hypertension. However, low-intensity IMT was superior to medium-high-intensity IMT in regulating BP.</p>
<p>Having a high prevalence and incidence of hypertension is a significant public health concern because deaths and diseases of hypertension and cardiovascular systems are closely linked (<xref ref-type="bibr" rid="B31">31</xref>). Physical activity is one of the treatments for patients with hypertension (<xref ref-type="bibr" rid="B7">7</xref>). In these meta-analyses, it could be concluded that aerobic exercise (<xref ref-type="bibr" rid="B32">32</xref>), isometric exercise (<xref ref-type="bibr" rid="B32">32</xref>), breathing-control (<xref ref-type="bibr" rid="B33">33</xref>), and unload respiratory muscle training (<xref ref-type="bibr" rid="B17">17</xref>) had the effect in reducing BP in patients with hypertension. Our meta-analysis showed that IMT, an innovative physical activity, also had an active reduction in BP which was consistent with the conclusion of the analysis showing that the antihypertensive drug was effective in SBP and DBP within 6 months (&#x2212;4.2/&#x2212;2.0&#x2005;mmHg) (<xref ref-type="bibr" rid="B34">34</xref>). Among the RCTs included in this literature, seven studies (<xref ref-type="bibr" rid="B12">12</xref>, <xref ref-type="bibr" rid="B13">13</xref>, <xref ref-type="bibr" rid="B15">15</xref>, <xref ref-type="bibr" rid="B25">25</xref>&#x2013;<xref ref-type="bibr" rid="B27">27</xref>, <xref ref-type="bibr" rid="B29">29</xref>) clearly indicated that patients were still receiving medication and one study (<xref ref-type="bibr" rid="B28">28</xref>) did not clearly indicate whether patients were receiving medication or not. Combined with the effect size of the antihypertensive drug, we speculated that IMT may further reduce BP in hypertensive patients on the basis of medication. The reason for the inconsistency between these two studies may be that fewer articles have been published on hypertension in the latter study and the heterogeneity among RCTs is high. Lowering BP is quite important in the clinic. Studies suggested that every reduction of 5&#x2005;mmHg BP can significantly reduce the risk of type 2 diabetes (<xref ref-type="bibr" rid="B5">5</xref>), heart failure (<xref ref-type="bibr" rid="B35">35</xref>), and stroke (<xref ref-type="bibr" rid="B36">36</xref>), thus it is possible that lowering BP is a means of preventing type 2 diabetes, heart failure, and stroke. And the safety of IMT in these diseases has been established (<xref ref-type="bibr" rid="B37">37</xref>&#x2013;<xref ref-type="bibr" rid="B39">39</xref>). Therefore, IMT can be used as adjunct training for hypertension to lower BP and minimize the chance of developing secondary conditions in clinic.</p>
<p>It is possible that IMT lowers BP through a variety of mechanisms. IMT may have decreased BP based on changes in breathing patterns and reflex mechanisms (<xref ref-type="bibr" rid="B25">25</xref>). For example, the respiratory muscle metaboreflex activation in patients with hypertension will be activated in advance during exercise, whereas increasing the inspiratory muscle strength of patients with hypertension through IMT can slow down the early appearance of this reflex, thus reducing the hyperactivity of peripheral sympathetic nerves, which could control the rise in BP (<xref ref-type="bibr" rid="B40">40</xref>). In addition, arterial stiffness is one of the important inducements to develop and maintain hypertension (<xref ref-type="bibr" rid="B41">41</xref>). IMT could reduce SBP in patients with hypertension, which may be related to IMT altering endothelial and smooth muscle function, thereby affecting aortic stiffness (<xref ref-type="bibr" rid="B16">16</xref>). Regarding DBP, respiratory resistance can raise intrathoracic pressure, lower cardiac output, and decrease systemic venous return due to pulmonary artery compression (<xref ref-type="bibr" rid="B42">42</xref>). As a result of the significant decrease in cardiac output, which also causes a reduction in ventricular filling, the result is a reduction in DBP. Low-intensity IMT reduced BP more than high-intensity IMT; this may be related to the greater contraction intensity of respiratory muscles in medium-high-intensity IMT, which more likely stimulates mechanoreceptors in the muscles, and muscle contraction leads to increased vasculature pressure, which results in increased BP (<xref ref-type="bibr" rid="B43">43</xref>).</p>
<p>The role of HR in hypertension has been established. Patients with hypertension frequently have an increase in HR, which has been linked to an independent predictor of poor cardiovascular and death outcomes (<xref ref-type="bibr" rid="B44">44</xref>). Therefore, there is a need to evaluate how IMT affects HR in individuals with hypertension. Our meta-analysis showed a result that IMT was linked to an effect size of &#x2212;5.29&#x2005;bpm on the HR, which was similar to the results of pursed-lip breathing (&#x2212;3.85&#x2005;bpm) (<xref ref-type="bibr" rid="B45">45</xref>) and high-intensity interval training (&#x2212;2.17&#x2005;bpm) (<xref ref-type="bibr" rid="B46">46</xref>) decreasing in HR. This reduction in HR has important clinical implications for patients with hypertension. A 10&#x2005;bpm rise in HR resulted in an 8&#x0025; increase in the incidence of hypertension (<xref ref-type="bibr" rid="B47">47</xref>), while a drop in HR was associated with a reduced cardiovascular death rate in the long-term follow-up procedure (<xref ref-type="bibr" rid="B48">48</xref>). IMT can regulate HR probably because it can decrease cardiac sympathetic nerve activity and increase the expression of parasympathetic nerves at rest (<xref ref-type="bibr" rid="B49">49</xref>). In the included studies, only four RCTs evaluated PP in hypertension before and after IMT. PP is another predictor of hypertension events that, in some cases, has a superior predictive capability to SBP or DBP alone (<xref ref-type="bibr" rid="B50">50</xref>, <xref ref-type="bibr" rid="B51">51</xref>). Our meta-analysis discovered an improvement in PP in patients with hypertension, which is associated with the outcome of the present study that SBP decreases more obviously than DBP. Therefore, IMT may reduce HR and PP while dropping BP, minimizing the risk of unfavorable cardiovascular and fatal consequences.</p>
<p>It is the first meta-analysis to focus on the impact of IMT on the four hemodynamic indexes of patients with hypertension, and our analysis provides evidence for IMT as a clinical auxiliary means for improving hemodynamic indexes and decreasing the risk of some secondary disorders in individuals with hypertension. However, future research will be required to establish the most appropriate type, timing, number of sessions each week, and sessions per breath for optimal treatment outcomes. Moreover, in order to better understand the circadian behavior of BP and HR, it would also be interesting to evaluate 24-hour ambulatory BP and HR measurements.</p>
<p>The study limitations are mainly manifested in the following aspects: (1) a small number of RCTs were included in this investigation, and the bulk of them had modest sample sizes; therefore, the total sample size was small; (2) some heterogeneity problems encountered in this study may be due to different equipment, training frequency, training duration, intervention time, and intervention intensity; (3) since the respective number of different types of hypertension was very small in the included studies, this study did not do a subgroup analysis of distinct kinds of hypertension.</p>
</sec>
<sec id="s5" sec-type="conclusions"><label>5.</label><title>Conclusion</title>
<p>IMT may become an auxiliary means to improve the four hemodynamic indexes (SBP, DBP, HR and PP) in patients with hypertension. Furthermore, low-intensity IMT was preferred over medium-high-intensity IMT in subgroup analyses for regulating SBP and DBP. Both low and medium-high-intensity IMT could reduce the HR of patients with hypertension. However, the training time, respiratory rate, and training frequency of IMT, as well as the therapeutic effects on different types of hypertension, should be further explored.</p>
</sec>
</body>
<back>
<sec id="s6" sec-type="data-availability"><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 author/s.</p>
</sec>
<sec id="s7" sec-type="author-contributions"><title>Author contributions</title>
<p>QZe, JZ and LH: conceptualization and design, article typographic logic; GL, LC and YZ: Study selection and data extraction; QZh, SZ and SYL: data analysis and interpretation, article editing; SLL, QY, XZ and SC: study supervision and article revising. The article&#x0027;s submission was reviewed and approved by all authors.</p>
</sec>
<sec id="s8" sec-type="funding-information"><title>Funding</title>
<p>The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by the National Nature Science Foundation of China (NSFC) (Project No. 82002380 and No. 82205245), College Student&#x0027;s Innovative Entrepreneurial Training Plan Program for Southern Medical University (Project No. X202012121325S and No. X202112121184), and Southern Medical University Scientific Research Enlightenment Project (Project No. B521ZJ0102), Guangdong Province Health Appropriate Technology Promotion Project (Project No. 202206252011533513).</p>
</sec>
<ack><title>Acknowledgment</title>
<p>The author group would like to thank the English Language Institute (<ext-link ext-link-type="uri" xlink:href="https://www.enago.cn">www.enago.cn</ext-link>) for providing the English touch-ups.</p>
</ack>
<sec id="s9" sec-type="COI-statement"><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 id="s11" sec-type="disclaimer"><title>Publisher&#x0027;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>
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