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<front>
<journal-meta>
<journal-id journal-id-type="publisher-id">Front. Physiol.</journal-id>
<journal-title>Frontiers in Physiology</journal-title>
<abbrev-journal-title abbrev-type="pubmed">Front. Physiol.</abbrev-journal-title>
<issn pub-type="epub">1664-042X</issn>
<publisher>
<publisher-name>Frontiers Media S.A.</publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="publisher-id">1070754</article-id>
<article-id pub-id-type="doi">10.3389/fphys.2022.1070754</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Physiology</subject>
<subj-group>
<subject>Original Research</subject>
</subj-group>
</subj-group>
</article-categories>
<title-group>
<article-title>Effects of traditional Chinese herb hot compress combined with therapeutic exercise on pain, proprioception, and functional performance among older adults with knee osteoarthritis: A randomized controlled trial</article-title>
<alt-title alt-title-type="left-running-head">Wang et al.</alt-title>
<alt-title alt-title-type="right-running-head">
<ext-link ext-link-type="uri" xlink:href="https://doi.org/10.3389/fphys.2022.1070754">10.3389/fphys.2022.1070754</ext-link>
</alt-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name>
<surname>Wang</surname>
<given-names>Jingwen</given-names>
</name>
<xref ref-type="aff" rid="aff1">
<sup>1</sup>
</xref>
<uri xlink:href="https://loop.frontiersin.org/people/2054268/overview"/>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Liu</surname>
<given-names>Wei</given-names>
</name>
<xref ref-type="aff" rid="aff2">
<sup>2</sup>
</xref>
</contrib>
<contrib contrib-type="author" corresp="yes">
<name>
<surname>Fu</surname>
<given-names>Haitao</given-names>
</name>
<xref ref-type="aff" rid="aff3">
<sup>3</sup>
</xref>
<xref ref-type="corresp" rid="c001">&#x2a;</xref>
</contrib>
</contrib-group>
<aff id="aff1">
<sup>1</sup>
<institution>College of Sports and Health</institution>, <institution>Shandong Sport University</institution>, <addr-line>Jinan</addr-line>, <country>China</country>
</aff>
<aff id="aff2">
<sup>2</sup>
<institution>Department of Rehabilitation</institution>, <institution>Neck Shoulder Back and Leg Pain Hospital</institution>, <institution>Shandong First Medical University</institution>, <addr-line>Jinan</addr-line>, <country>China</country>
</aff>
<aff id="aff3">
<sup>3</sup>
<institution>Athletic Training Division</institution>, <institution>Shandong Sport University</institution>, <addr-line>Jinan</addr-line>, <country>China</country>
</aff>
<author-notes>
<fn fn-type="edited-by">
<p>
<bold>Edited by:</bold> <ext-link ext-link-type="uri" xlink:href="https://loop.frontiersin.org/people/923238/overview">Lin Wang</ext-link>, Shanghai University of Sport, China</p>
</fn>
<fn fn-type="edited-by">
<p>
<bold>Reviewed by:</bold> <ext-link ext-link-type="uri" xlink:href="https://loop.frontiersin.org/people/2053274/overview">Qingguang Liu</ext-link>, Tongji University, China</p>
<p>
<ext-link ext-link-type="uri" xlink:href="https://loop.frontiersin.org/people/2085624/overview">Yi Jia</ext-link>, North University of China, China</p>
</fn>
<corresp id="c001">&#x2a;Correspondence: Haitao Fu, <email>fuhaitao@sdpei.edu.cn</email>
</corresp>
<fn fn-type="other">
<p>This article was submitted to Skeletal Physiology, a section of the journal Frontiers in Physiology</p>
</fn>
</author-notes>
<pub-date pub-type="epub">
<day>14</day>
<month>12</month>
<year>2022</year>
</pub-date>
<pub-date pub-type="collection">
<year>2022</year>
</pub-date>
<volume>13</volume>
<elocation-id>1070754</elocation-id>
<history>
<date date-type="received">
<day>15</day>
<month>10</month>
<year>2022</year>
</date>
<date date-type="accepted">
<day>28</day>
<month>11</month>
<year>2022</year>
</date>
</history>
<permissions>
<copyright-statement>Copyright &#xa9; 2022 Wang, Liu and Fu.</copyright-statement>
<copyright-year>2022</copyright-year>
<copyright-holder>Wang, Liu and Fu</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>
<p>
<bold>Background:</bold> Knee osteoarthritis (KOA) is one of the most common chronic progressive diseases with degenerative destruction of articular cartilage and bone, leading to knee pain, impaired proprioception, and reduced functional performance. This study was to investigate the effects of an 8-week Traditional Chinese herb hot compress (TCHHC) combined with therapeutic exercise (TE) on pain, proprioception, and functional performance among older adults with KOA.</p>
<p>
<bold>Methods:</bold> Twenty-seven older adults with KOA were recruited and randomly assigned to the TCHHC &#x2b; TE or TE groups. Thirteen participants received TCHHC &#x2b; TE, and fourteen received TE. At pre- (week 0) and post-intervention (week 9), their pain, joint proprioception, and functional performance were measured. Two-way ANOVA with repeated measures was adopted to analyze the data.</p>
<p>
<bold>Results:</bold> Compared with week 0, the pain score, proprioception thresholds of knee extension and ankle plantarflexion, and the times of TUG and 20-m walk tests decreased more significantly in the TCHHC &#x2b; TE group than in the TE group at week 9.</p>
<p>
<bold>Conclusion:</bold> Compared with TE, the 8-week TCHHC &#x2b; TE was superior in relieving pain, recovering proprioception, and improving functional performance among older adults with KOA. It is recommended that TCHHC should be adopted prior to TE to enhance the effects of KOA rehabilitation.</p>
</abstract>
<kwd-group>
<kwd>osteoarthritis</kwd>
<kwd>pain</kwd>
<kwd>proprioception</kwd>
<kwd>functional performance</kwd>
<kwd>Chinese herbs</kwd>
<kwd>therapeutic exercise</kwd>
</kwd-group>
</article-meta>
</front>
<body>
<sec id="s1">
<title>1 Introduction</title>
<p>Knee osteoarthritis (KOA) is one of the most common chronic progressive diseases, with a prevalence of 30%&#x2013;40% among older adults over 65&#xa0;years of age, posing a serious health risk (<xref ref-type="bibr" rid="B24">Helmick et al., 2008</xref>). KOA is associated with degenerative destruction of articular cartilage and bone, leading to knee pain (<xref ref-type="bibr" rid="B17">Glyn-Jones et al., 2015</xref>), impaired proprioception (<xref ref-type="bibr" rid="B42">Segal et al., 2010</xref>), and reduced functional performance (<xref ref-type="bibr" rid="B22">Hawker, 2019</xref>).</p>
<p>Pain is the predominant and most common clinical symptom of KOA, which was believed to be caused by the uneven load at the knee and the increased pressure on the tibiofemoral joint (<xref ref-type="bibr" rid="B3">Beaupr&#xe9; et al., 2000</xref>). Pain has been commonly assessed by the Western Ontario and McMasters Osteoarthritis Index (WOMAC) (<xref ref-type="bibr" rid="B47">Sisante et al., 2020</xref>). Proprioception is closely related to the developmental process of KOA (<xref ref-type="bibr" rid="B52">van der Esch et al., 2007</xref>), and the impairment of proprioception of the knee and ankle joints led to decreased lower extremity joint balance and coordination among older adults with KOA (<xref ref-type="bibr" rid="B21">Hassan et al., 2001</xref>; <xref ref-type="bibr" rid="B27">Knoop et al., 2011</xref>). Although KOA affects mostly the knee joint, ankle proprioception is closely related to balance control (<xref ref-type="bibr" rid="B20">Han et al., 2015</xref>). Compared with their healthy counterparts, older adults with KOA have worse functional performance, which affects their ability of daily activities and increases the risk of falls (<xref ref-type="bibr" rid="B2">Anderson et al., 2019</xref>). Timed up &#x26; Go (TUG) (<xref ref-type="bibr" rid="B38">Podsiadlo and Richardson, 1991</xref>; <xref ref-type="bibr" rid="B13">Dobson et al., 2012</xref>) and 20-m walk tests (<xref ref-type="bibr" rid="B34">Motyl et al., 2013</xref>) have been used effectively to quantify functional performance among older adults with KOA.</p>
<p>Older adults with KOA typically receive surgical, pharmacological, and non-pharmacological treatments (<xref ref-type="bibr" rid="B5">Brophy and Fillingham, 2022</xref>). Surgery is generally used in the late-stage and can improve symptoms of KOA (<xref ref-type="bibr" rid="B58">Xue et al., 2022</xref>), however, with a high cost (<xref ref-type="bibr" rid="B44">Serikova-Esengeldina et al., 2022</xref>); Non-steroidal antiinflammatory, opioids, or nutritional drugs are usually used in pharmacological treatments (<xref ref-type="bibr" rid="B37">Persson et al., 2018</xref>), and side effects on the liver and kidneys have been reported (<xref ref-type="bibr" rid="B64">Zhang et al., 2019b</xref>). Non-pharmacological treatments have been recommended as the primary treatments for KOA (<xref ref-type="bibr" rid="B5">Brophy and Fillingham, 2022</xref>). Among them, therapeutic exercise (TE), such as resistance training or joint mobilization, has the potential effects to relieve pain (<xref ref-type="bibr" rid="B26">Juhl et al., 2014</xref>), recover proprioception (<xref ref-type="bibr" rid="B28">Lai et al., 2018</xref>), and improve functional performance (<xref ref-type="bibr" rid="B15">Fransen et al., 2002</xref>). Resistance training improves muscle strength and functional performance (<xref ref-type="bibr" rid="B12">de Rooij et al., 2017</xref>). Joint mobilization balances the load at the knee and relieves pain (<xref ref-type="bibr" rid="B8">Chen H. et al., 2019</xref>), as well as improves proprioception by enhancing sensory input to the central nervous system about postural movements (<xref ref-type="bibr" rid="B40">Saunders et al., 2005</xref>). However, a previous meta-analysis study showed that the effect size of TE remained small to moderate (<xref ref-type="bibr" rid="B16">Fransen et al., 2015</xref>). Therefore, there is room to improve its effectiveness on KOA.</p>
<p>Traditional Chinese herb hot compress (TCHHC) has been widely used in the treatment of chronic diseases such as KOA (<xref ref-type="bibr" rid="B59">Yuan et al., 2015</xref>). It fully synergizes the warming effect, which has been shown to slightly improve pain, functional performance and quality of life in older adults with KOA (<xref ref-type="bibr" rid="B1">Aciksoz et al., 2017</xref>), and the pharmacological effect, which reduces inflammation for pain relief by promoting synovial fluid flow and reducing the release of inflammatory substances into the synovial fluid (<xref ref-type="bibr" rid="B54">Wang et al., 2010</xref>). Combined with the above-mentioned effects of resistance training and joint mobilization, TCHHC &#x2b; TE has the potential to relieve pain, improve proprioception, and functional performance.</p>
<p>To the best of our knowledge, no studies have explored the effects of TCHHC &#x2b; TE on pain relief, proprioception recovery, and functional performance improvement among older adults with KOA. It was hypothesized that compared with TE, TCHHC &#x2b; TE was superior in relieving pain, recovering proprioception, and reducing the times of TUG and 20-m walk tests.</p>
</sec>
<sec sec-type="materials|methods" id="s2">
<title>2 Material and methods</title>
<sec id="s2-1">
<title>2.1 Sample size estimates</title>
<p>The sample size was estimated by An <italic>a priori</italic> power analysis (G&#x2a;Power Version 3.1). Based on a previous report compared the pain score (interaction &#x3c;0.001, &#x3b7;2<sub>p</sub> &#x3d; 0.638) and proprioception (interaction &#x3d; 0.006, &#x3b7;2<sub>p</sub> &#x3d; 0.267) among older adults with KOA before and after a TE therapy or health lecture series (<xref ref-type="bibr" rid="B46">Shen et al., 2021</xref>). By setting the significance level to 0.05 and the statistical power to 80%, the minimum total sample size of this study should be 6 (calculated by pain score) and 26 (calculated by proprioception), respectively.</p>
</sec>
<sec id="s2-2">
<title>2.2 Participants</title>
<p>All participants were recruited and all the data were collected in the Neck, Shoulder, Back, and Leg Pain Hospital, Jinan, China, from June 2020 to November 2021. The inclusion criteria included the following: 1) 65&#xa0;years old or older; 2) at least one knee was diagnosed with KOA according to the clinical criteria of the American College of Rheumatology; 3) a radiographic grade of 2 or higher by the Kellgren/Lawrence scale (K/L). The exclusion criteria included the following: 1) had a neurodegenerative disease or neurosensory disorder affecting the knee other than the KOA; 2) had a traumatic injury of the lower extremity joint in the past 3&#xa0;months; 3) had planned for a total knee replacement in the following months; 4) had a history of allergies to Traditional Chinese herbs; 5) had received other KOA treatments, including steroids, intra-articular injection or other analgesic drugs within previous 3&#xa0;months.</p>
<p>Thirty-four participants who met the above criteria were assigned to the TCHHC &#x2b; TE or the TE groups at a ratio of 1:1 by computer-generated randomization procedure. Allocation concealment was ensured because allocation information was protected in opaque sealed envelopes and kept by investigators involved in participant recruitment. This study was single-blinded, with the investigators were blinded and participants knew the randomized assignments.</p>
<p>The participants in the TCHHC &#x2b; TE group received TCHHC &#x2b; TE, and those in the TE group received TE for 8&#xa0;weeks. The participants were excluded with below 80% attendance rate (<xref ref-type="bibr" rid="B49">Song et al., 2020</xref>). The attendance rate is calculated by dividing the number of sessions completed by each participant by the total number of sessions. In the TCHHC &#x2b; TE group, two participants were excluded due to their lower attendance rate (73% and 70%), and two were excluded due to co-intervention. In the TE group, two were excluded due to their lower attendance rate (74% and 72%), and one was excluded due to co-intervention. The reasons for failing to attend were transportation difficulties, bad weather, and family commitments. Co-intervention including steroids, intra-articular injections or other pain medications. Final analyses were conducted among thirteen participants in the TCHHC &#x2b; TE group and fourteen in the TE group (<xref ref-type="fig" rid="F1">Figure 1</xref>).</p>
<fig id="F1" position="float">
<label>FIGURE 1</label>
<caption>
<p>Chart flow.</p>
</caption>
<graphic xlink:href="fphys-13-1070754-g001.tif"/>
</fig>
<p>All participants were required to sign informed consent before participation. The project was approved by the Ethics Committee of Neck, Shoulder, Back, and Leg Pain Hospital (2021009) and conformed to the guidelines of the Declaration of Helsinki, and was registered in the Chinese Clinical Trial Registry with a registration number of ChiCTR2100052450.</p>
</sec>
<sec id="s2-3">
<title>2.3 Interventions</title>
<p>Both groups received three sessions (Tuesday, Thursday, and Saturday) of the intervention per week for 8&#xa0;weeks. Participants were tested successively on Monday of the ninth week. In each session, the participants in the TCHHC &#x2b; TE group received 30&#xa0;min of TCHHC, 30&#xa0;min of joint mobilization, and 30&#xa0;min of resistance training. The TE group received 30&#xa0;min of joint mobilization, 30&#xa0;min of resistance training, and 30&#xa0;min of health lecture series.</p>
<p>The dosage of the herbs was confirmed by the Apoplectic Joint Disease Pulse Syndrome and Treatment, Guizhi Shaoyao Zhimu Decoction, prescribed by Zhang Zhongjing, a famous Chinese medical practitioner of the Eastern Han Dynasty (from about 150 to 154 to about 215 to 219, A.D.) (<xref ref-type="bibr" rid="B11">Daily et al., 2017</xref>) and provided by the Neck, Shoulder, Back, and Leg Pain Hospital. The types and dosages of hot compress herbs are shown in <xref ref-type="table" rid="T1">Table1</xref>. The herbs were ground into 0.2&#xa0;mm power in the hospital by the Dade medicine machine (model DF-20, Wenling Linda Machinery Co., Ltd, China), and mixed in a cloth bag of about 15&#xa0;cm length&#x2a;15&#xa0;cm width after heating in a microwave oven for 40&#xa0;s to make the temperature of the medicine bag reach 40&#x2013;42&#xb0;C, measured using the Raytek MiniTemp&#x2122; non-contact infrared thermometer (Raytek, United States). After cleaning the skin with saline gauze, the bag was quickly applied to the knee joint for about 30&#xa0;min (<xref ref-type="fig" rid="F2">Figure 2A</xref>).</p>
<table-wrap id="T1" position="float">
<label>TABLE 1</label>
<caption>
<p>Components of Traditional Chinese herbs.</p>
</caption>
<table>
<thead valign="top">
<tr>
<th align="center">Components</th>
<th align="center">Amount (g)</th>
<th align="center">Components</th>
<th align="center">Amount (g)</th>
</tr>
</thead>
<tbody valign="top">
<tr>
<td align="center">Cassia twig</td>
<td align="center">30</td>
<td align="center">White mustard seed</td>
<td align="center">30</td>
</tr>
<tr>
<td align="center">Paeony root</td>
<td align="center">20</td>
<td align="center">Sichuan ox knee</td>
<td align="center">25</td>
</tr>
<tr>
<td align="center">Myrrh</td>
<td align="center">20</td>
<td align="center">Mulberry parasitic</td>
<td align="center">25</td>
</tr>
<tr>
<td align="center">Ephedra root</td>
<td align="center">20</td>
<td align="center">Parsnip</td>
<td align="center">20</td>
</tr>
<tr>
<td align="center">Atractylodes macrocephala</td>
<td align="center">20</td>
<td align="center">Hot dog ridge</td>
<td align="center">30</td>
</tr>
<tr>
<td align="center">Frankincense</td>
<td align="center">20</td>
<td align="center">Antler gum</td>
<td align="center">30</td>
</tr>
<tr>
<td align="center">Prepared aconite</td>
<td align="center">25</td>
<td align="center">Anemarrhena asphodeloides</td>
<td align="center">20</td>
</tr>
<tr>
<td align="center">Prepared Sichuan black</td>
<td align="center">25</td>
<td align="left"/>
<td align="left"/>
</tr>
</tbody>
</table>
</table-wrap>
<fig id="F2" position="float">
<label>FIGURE 2</label>
<caption>
<p>Illustrations of TCHHC <bold>(A)</bold>, resistance training <bold>(B)</bold>, and joint mobilization <bold>(C)</bold>.</p>
</caption>
<graphic xlink:href="fphys-13-1070754-g002.tif"/>
</fig>
<p>The TE intervention included two parts, namely, resistance training (static and dynamic) and joint mobilization. During static resistance training, the participants lay in a supine position, contracted their quadriceps to keep their heels slightly off the bed for 10&#xa0;s, and relaxed for 10&#xa0;s, repeating about 50 reps per session. During dynamic resistance training, the participant sat in a training chair and flexed and extended the knee at approximately 90&#xb0; to 170&#xb0; with a weight adjustable bag (between 9.8 and 15N depending on the participant&#x2019;s knee recovery) strapped to the ankle to increase knee extension resistance for about 100 reps per session (<xref ref-type="fig" rid="F2">Figure 2B</xref>). The joint mobilization was based on Maitland&#x2019;s method in Australia (<xref ref-type="bibr" rid="B10">Courtney et al., 2010</xref>). The participants lay in a supine position and received joint mobilization conducted by physical therapists about 8 times per session. The joint mobilization technique involved the following: medial and lateral sliding of the patella, and up and down, anterior and posterior sliding of the tibiofibular joint, anterior and posterior sliding of the tibiofemoral joint, and long-axis traction (<xref ref-type="fig" rid="F2">Figure 2C</xref>).</p>
<p>All participants in the TE group participated in the health lecture series for 8&#xa0;weeks, three sessions per week. One session of health lecture lasted for 30&#xa0;min, including knowledge about KOA, awareness of chronic diseases, psychological health education, nutritional meals, scientific exercise, and exchange of experience. The format of the lecture was to watch selected TV programs or read related magazines.</p>
</sec>
<sec id="s2-4">
<title>2.4 Testing protocol</title>
<sec id="s2-4-1">
<title>2.4.1 Pain</title>
<p>The pain score of the more affected lower extremity was assessed by five pain items of the WOMAC before and after the 8-week intervention, and its validity and reliability have been demonstrated (<xref ref-type="bibr" rid="B4">Bellamy et al., 1988</xref>). In each item, 0 points represented &#x201c;no pain,&#x201d; whereas 10 points represented &#x201c;the worst pain possible&#x201d;. Higher scores indicate more severe pain.</p>
</sec>
<sec id="s2-4-2">
<title>2.4.2 Proprioceptive</title>
<p>The proprioceptive thresholds of knee flexion/extension, ankle dorsi/plantarflexion, and inversion/eversion of the more affected lower extremity were measured by proprioception devices (Sunny, AP-II, China). The test showed a good two-time-point intraclass correlation coefficient ((ICC &#x3d; 0.737&#x2013;0.935) (<xref ref-type="bibr" rid="B51">Sun et al., 2015</xref>). The proprioception devices collected the minimum angular motion that the patient was able to detect during knee flexion/extension, ankle dorsi/plantarflexion, and inversion/eversion. The devices consist of a platform that can rotate within the frontal and sagittal planes. The platform is driven by 2 electric motors at an angular velocity of 0.4&#xb0;/s. An electronic goniometer in the devices recorded the angular displacement of the platform. Each participant was seated on a height-adjustable chair with their foot placed on the platform. During the ankle proprioception test, the knee and hip joints were flexed at 90&#xb0;, and the leg was perpendicular to the surface of the platform when the platform was placed in a horizontal position. During the knee proprioception test, the lateral axis of the instrumentation was parallel with the mediolateral axis of the knee joint. The hip and knee joints were each positioned at 90&#xb0;, whereas the ankle joint was at the neutral position. Approximately 50% subject&#x2019;s lower extremity weight was rested on the platform by using the thigh cuff suspension system to control unwanted sensory cues from the contact between the platform and the plantar surface of the foot. The participant sat with their eyes closed and wore headphones with music playing to eliminate potential environmental visual and auditory stimulation. The participant was instructed to concentrate on their foot and to press the hand switch to stop the movement of the platform when they could sense motion followed by identification of the rotation direction. The motor was operated to rotate with a random time interval ranging from 2&#xa0;s to 10&#xa0;s after an indication to start a trial. At least five trials were performed for each direction to reduce random measurement errors (<xref ref-type="bibr" rid="B50">Song et al., 2021</xref>).</p>
</sec>
<sec id="s2-4-3">
<title>2.4.3 TUG test</title>
<p>The TUG test showed good reliability between raters (ICC &#x3d; 0.99) and within the same raters on two consecutive tests (ICC &#x3d; 0.99) (<xref ref-type="bibr" rid="B38">Podsiadlo and Richardson, 1991</xref>). The participants were seated in a 46&#xa0;cm high seat. When the assistant gave the &#x201c;go&#x201d; command, the participants stood up and moved forward a 3-m distance as fast as possible, then turned around and sat back down. The time was taken from when they left the chair until they returned to the chair, in seconds. Shorter time represents better functional performance. Three successful trials were collected.</p>
</sec>
<sec id="s2-4-4">
<title>2.4.4 20-m walk test</title>
<p>The 20-m walk test showed good two-time-point reliability (Spearman r &#x3d; 0.94&#x2013;0.99) (<xref ref-type="bibr" rid="B34">Motyl et al., 2013</xref>). The participants walked as fast as possible within a 20-m distance. Shorter time represents better functional performance. Three successful trials were collected.</p>
</sec>
</sec>
<sec id="s2-5">
<title>2.5 Statistical analysis</title>
<p>All variables were statistically analyzed using SPSS 26.0 (IBM SPSS, Armonk, NY, United States). The normality of all outcome variables was tested using Shapiro-Wilk tests. Two-way (group by time) ANOVAs with repeated measures were used to test the differences in dependent variables before and after the intervention. If significant interactions were detected, the stratified t-tests with the Bonferroni adjustment were performed. If there is no interaction, pre-and post-tests were compared by combining the two groups. Partial eta squared (&#x3b7;2<sub>p</sub>) was used to represent the effect size of the two-way ANOVA&#x2019;s main effects and interactions. The thresholds for &#x3b7;2<sub>p</sub> were as follows: 0.01&#x2013;0.06 for small, 0.06&#x2013;0.14 for moderate, and&#x3e;0.14 for large (<xref ref-type="bibr" rid="B65">Ledolter and Kardon, 2020</xref>). Cohen&#x2019;s <italic>d</italic> was used to represent the effect size of <italic>post hoc</italic> pairwise comparisons (Cohen, 1988). The thresholds for Cohen&#x2019;s <italic>d</italic> were as follows: &#x3c;0.20 for trivial, 0.21&#x2013;0.50 for small, 0.51&#x2013;0.80 for medium, and &#x3e;0.81 for large (J, 1988). The significance level was set at 0.05 (<xref ref-type="bibr" rid="B65">Ledolter and Kardon, 2020</xref>).</p>
</sec>
</sec>
<sec sec-type="results" id="s3">
<title>3 Results</title>
<p>No side effects were observed during the intervention, e.g., pain exacerbation, allergic reaction, redness, or heat burn due to the hot compress on the superficial joints. The Shapiro-Wilk test confirmed that all dependent variables were normally distributed. Independent t-tests showed no significant differences in age (<italic>p</italic> &#x3d; 0.794), weight (<italic>p</italic> &#x3d; 0.962), height (<italic>p</italic> &#x3d; 0.467), body mass index (<italic>p</italic> &#x3d; 0.841), and leg length (<italic>p</italic> &#x3d; 0.639) between the two groups (<xref ref-type="table" rid="T2">Table 2</xref>).</p>
<table-wrap id="T2" position="float">
<label>TABLE 2</label>
<caption>
<p>Demographic characteristics of practitioners.</p>
</caption>
<table>
<thead valign="top">
<tr>
<th align="center"/>
<th align="center">TCHHC &#x2b; TE (<italic>n</italic> &#x3d; 13)</th>
<th align="center">TE (<italic>n</italic> &#x3d; 14)</th>
<th align="center">
<italic>p</italic>-value</th>
</tr>
</thead>
<tbody valign="top">
<tr>
<td align="center">More affected leg</td>
<td align="center">5R, 8L</td>
<td align="center">6R, 8L</td>
<td align="center">--</td>
</tr>
<tr>
<td align="center">K/L</td>
<td align="center">4 II, 7 III, 2 IV</td>
<td align="center">4 II, 8 III, 2 IV</td>
<td align="center">--</td>
</tr>
<tr>
<td align="center">Age (y)</td>
<td align="center">72.0 &#xb1; 5.4</td>
<td align="center">72.6 &#xb1; 5.9</td>
<td align="center">0.794</td>
</tr>
<tr>
<td align="center">Weight (kg)</td>
<td align="center">69.9 &#xb1; 5.2</td>
<td align="center">70.0 &#xb1; 7.7</td>
<td align="center">0.962</td>
</tr>
<tr>
<td align="center">Height (cm)</td>
<td align="center">162.2 &#xb1; 4.1</td>
<td align="center">163.6 &#xb1; 5.7</td>
<td align="center">0.467</td>
</tr>
<tr>
<td align="center">BMI (kg/m<sup>2</sup>)</td>
<td align="center">26.7 &#xb1; 2.2</td>
<td align="center">26.5 &#xb1; 2.5</td>
<td align="center">0.841</td>
</tr>
<tr>
<td align="center">Leg length (cm)</td>
<td align="center">82.3 &#xb1; 3.1</td>
<td align="center">81.7 &#xb1; 3.4</td>
<td align="center">0.639</td>
</tr>
</tbody>
</table>
</table-wrap>
<p>The pain score was presented in <xref ref-type="table" rid="T3">Table 3</xref>. Significant interactions were detected in 2 items (walk on the ground: <italic>p</italic> &#x3d; 0.009, &#x3b7;2<sub>p</sub> &#x3d; 0.245 and go up or down stairs: <italic>p</italic> &#x3d; 0.006, &#x3b7;2<sub>p</sub> &#x3d; 0.266) of the WOMAC scores, and the total score (<italic>p</italic> &#x3d; 0.047, &#x3b7;2<sub>p</sub> &#x3d; 0.148). At week 9, the go up or down stair (<italic>p</italic> &#x3d; 0.002, <italic>d</italic> &#x3d; 1.327) and total (<italic>p</italic> &#x3d; 0.035, <italic>d</italic> &#x3d; 0.798) scores were lower in the TCHHC &#x2b; TE group compared with those in the TE group. Compared to week 0, the sleep at night (<italic>p</italic> &#x3c; 0.001, &#x3b7;2<sub>p</sub> &#x3d; 0.395), sit or lying (<italic>p</italic> &#x3d; 0.001, &#x3b7;2<sub>p</sub> &#x3d; 0.364), and stand straight (<italic>p</italic> &#x3c; 0.001, &#x3b7;2<sub>p</sub> &#x3d; 0.424) scores were lower at week 9 in both groups.</p>
<table-wrap id="T3" position="float">
<label>TABLE 3</label>
<caption>
<p>Pain score of the more affected at weeks 0 and 9.</p>
</caption>
<table>
<thead valign="top">
<tr>
<th rowspan="2" align="left">Pain score</th>
<th rowspan="2" align="left"/>
<th rowspan="2" align="center">TCHHC &#x2b; TE (<italic>n</italic> &#x3d; 13)</th>
<th rowspan="2" align="center">TE (<italic>n</italic> &#x3d; 14)</th>
<th colspan="2" align="left">Time</th>
<th colspan="2" align="left">Group</th>
<th colspan="2" align="center">Time<xref ref-type="table-fn" rid="Tfn1">
<sup>a</sup>
</xref> group</th>
<th colspan="2" align="center">Post hoc</th>
</tr>
<tr>
<th align="left">p</th>
<th align="left">&#x3b7;<sup>2</sup>
<sub>p</sub>
</th>
<th align="left">p</th>
<th align="left">&#x3b7;<sup>2</sup>
<sub>p</sub>
</th>
<th align="left">p</th>
<th align="left">&#x3b7;<sup>2</sup>
<sub>p</sub>
</th>
<th align="left">p</th>
<th align="left">
<italic>d</italic>
</th>
</tr>
</thead>
<tbody valign="top">
<tr>
<td rowspan="2" align="left">Walk on the ground</td>
<td align="center">Week 0</td>
<td align="center">5.08 &#xb1; 2.25</td>
<td align="center">4.95 &#xb1; 1.38</td>
<td align="left">--</td>
<td align="left">--</td>
<td align="left">--</td>
<td align="left">--</td>
<td align="left">0.009</td>
<td align="left">0.245</td>
<td align="left">
<xref ref-type="table-fn" rid="Tfn1">
<sup>a</sup>
</xref>
<sup>1</sup> &#x3c; 0.001,<xref ref-type="table-fn" rid="Tfn1">
<sup>a</sup>
</xref>
<sup>2</sup> &#x3c; 0.001</td>
<td align="left">
<xref ref-type="table-fn" rid="Tfn1">
<sup>a</sup>
</xref>
<sup>1</sup> &#x3d; 1.605,<xref ref-type="table-fn" rid="Tfn1">
<sup>a</sup>
</xref>
<sup>2</sup> &#x3d; 1.874</td>
</tr>
<tr>
<td align="center">Week 9</td>
<td align="center">1.85 &#xb1; 1.63<xref ref-type="table-fn" rid="Tfn1">
<sup>a</sup>
</xref>
<sup>1</sup>
</td>
<td align="center">2.50 &#xb1; 1.22<xref ref-type="table-fn" rid="Tfn1">
<sup>a</sup>
</xref>
<sup>2</sup>
</td>
<td align="left"/>
<td align="left"/>
<td align="left"/>
<td align="left"/>
<td align="left"/>
<td align="left"/>
<td align="left">--</td>
<td align="left">--</td>
</tr>
<tr>
<td rowspan="2" align="left">Go up or down stairs</td>
<td align="center">Week 0</td>
<td align="center">6.62 &#xb1; 2.22</td>
<td align="center">6.61 &#xb1; 1.75</td>
<td align="left">--</td>
<td align="left">--</td>
<td align="left">--</td>
<td align="left">--</td>
<td align="left">0.006</td>
<td align="left">0.266</td>
<td align="left">
<xref ref-type="table-fn" rid="Tfn1">
<sup>a</sup>
</xref>
<sup>1</sup> &#x3c; 0.001,<xref ref-type="table-fn" rid="Tfn1">
<sup>a</sup>
</xref>
<sup>2</sup> &#x3c; 0.001</td>
<td align="left">
<xref ref-type="table-fn" rid="Tfn1">
<sup>a</sup>
</xref>
<sup>1</sup> &#x3d; 2.316,<xref ref-type="table-fn" rid="Tfn1">
<sup>a</sup>
</xref>
<sup>2</sup> &#x3d; 1.822</td>
</tr>
<tr>
<td align="center">Week 9</td>
<td align="center">2.15 &#xb1; 1.28<xref ref-type="table-fn" rid="Tfn1">
<sup>a</sup>
</xref>
<sup>1</sup>
<xref ref-type="table-fn" rid="Tfn2">
<sup>b</sup>
</xref>
</td>
<td align="center">3.79 &#xb1; 1.19<xref ref-type="table-fn" rid="Tfn1">
<sup>a</sup>
</xref>
<sup>2</sup>
</td>
<td align="left"/>
<td align="left"/>
<td align="left"/>
<td align="left"/>
<td align="left"/>
<td align="left"/>
<td align="left">
<xref ref-type="table-fn" rid="Tfn2">
<sup>b</sup>
</xref> &#x3d; 0.002</td>
<td align="left">
<xref ref-type="table-fn" rid="Tfn2">
<sup>b</sup>
</xref> &#x3d; 1.327</td>
</tr>
<tr>
<td rowspan="2" align="left">Sleep at night</td>
<td align="center">Week 0</td>
<td align="center">4.23 &#xb1; 2.65</td>
<td align="center">4.36 &#xb1; 2.27</td>
<td align="left">&#x3c;0.001</td>
<td align="left">0.395</td>
<td align="left">0.596</td>
<td align="left">0.011</td>
<td align="left">0.302</td>
<td align="left">0.043</td>
<td align="left">--</td>
<td align="left">--</td>
</tr>
<tr>
<td align="center">Week 9</td>
<td align="center">1.31 &#xb1; 1.25</td>
<td align="center">1.64 &#xb1; 1.40</td>
<td align="left"/>
<td align="left"/>
<td align="left"/>
<td align="left"/>
<td align="left"/>
<td align="left"/>
<td align="left">--</td>
<td align="left">--</td>
</tr>
<tr>
<td rowspan="2" align="left">Sit or lying</td>
<td align="center">Week 0</td>
<td align="center">2.85 &#xb1; 1.95</td>
<td align="center">2.64 &#xb1; 1.28</td>
<td align="left">0.001</td>
<td align="left">0.364</td>
<td align="left">0.835</td>
<td align="left">0.002</td>
<td align="left">0.745</td>
<td align="left">0.004</td>
<td align="left">--</td>
<td align="left">--</td>
</tr>
<tr>
<td align="center">Week 9</td>
<td align="center">1.23 &#xb1; 0.93</td>
<td align="center">1.29 &#xb1; 1.14</td>
<td align="left"/>
<td align="left"/>
<td align="left"/>
<td align="left"/>
<td align="left"/>
<td align="left"/>
<td align="left">--</td>
<td align="left">--</td>
</tr>
<tr>
<td rowspan="2" align="left">Stand straight</td>
<td align="center">Week 0</td>
<td align="center">2.62 &#xb1; 1.80</td>
<td align="center">2.92 &#xb1; 1.77</td>
<td align="left">&#x3c;0.001</td>
<td align="left">0.424</td>
<td align="left">0.059</td>
<td align="left">0.135</td>
<td align="left">0.257</td>
<td align="left">0.051</td>
<td align="left">--</td>
<td align="left">--</td>
</tr>
<tr>
<td align="center">Week 9</td>
<td align="center">1.38 &#xb1; 0.96</td>
<td align="center">1.79 &#xb1; 1.37</td>
<td align="left"/>
<td align="left"/>
<td align="left"/>
<td align="left"/>
<td align="left"/>
<td align="left"/>
<td align="left">--</td>
<td align="left">--</td>
</tr>
<tr>
<td rowspan="2" align="left">Total score</td>
<td align="center">Week 0</td>
<td align="center">22.38 &#xb1; 7.43</td>
<td align="center">20.35 &#xb1; 6.07</td>
<td align="left">--</td>
<td align="left">--</td>
<td align="left">--</td>
<td align="left">--</td>
<td align="left">0.047</td>
<td align="left">0.148</td>
<td align="left">
<xref ref-type="table-fn" rid="Tfn1">
<sup>a</sup>
</xref>
<sup>1</sup> &#x3c; 0.001,<xref ref-type="table-fn" rid="Tfn1">
<sup>a</sup>
</xref>
<sup>2</sup> &#x3c; 0.001</td>
<td align="left">
<xref ref-type="table-fn" rid="Tfn1">
<sup>a</sup>
</xref>
<sup>1</sup> &#x3d; 2.246,<xref ref-type="table-fn" rid="Tfn1">
<sup>a</sup>
</xref>
<sup>2</sup> &#x3d; 1.760</td>
</tr>
<tr>
<td align="center">Week 9</td>
<td align="center">7.92 &#xb1; 3.92<xref ref-type="table-fn" rid="Tfn1">
<sup>a</sup>
</xref>
<sup>1</sup>
<xref ref-type="table-fn" rid="Tfn2">
<sup>b</sup>
</xref>
</td>
<td align="center">11.00 &#xb1; 3.80<xref ref-type="table-fn" rid="Tfn1">
<sup>a</sup>
</xref>
<sup>2</sup>
</td>
<td align="left"/>
<td align="left"/>
<td align="left"/>
<td align="left"/>
<td align="left"/>
<td align="left"/>
<td align="left">
<xref ref-type="table-fn" rid="Tfn2">
<sup>b</sup>
</xref> &#x3d; 0.035</td>
<td align="left">
<xref ref-type="table-fn" rid="Tfn2">
<sup>b</sup>
</xref> &#x3d; 0.798</td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<fn id="Tfn1">
<label>
<sup>a</sup>
</label>
<p>Denotes significant different between weeks 0 and 9 in each group.</p>
</fn>
<fn id="Tfn2">
<label>
<sup>b</sup>
</label>
<p>Denotes significant difference between the two groups at week 9.</p>
</fn>
<fn>
<p>TCHHC: traditional chinese herb hot compress.</p>
</fn>
<fn>
<p>TE: therapeutic exercise.</p>
</fn>
</table-wrap-foot>
</table-wrap>
<p>The proprioceptive thresholds were presented in <xref ref-type="table" rid="T4">Table 4</xref>. Significant interactions were detected in proprioception thresholds of knee extension (<italic>p</italic> &#x3d; 0.018, &#x3b7;2<sub>p</sub> &#x3d; 0.203) and ankle plantarflexion (<italic>p</italic> &#x3d; 0.010, &#x3b7;2<sub>p</sub> &#x3d; 0.235). Post hoc comparisons showed that compared with week 0, the proprioception thresholds of the knee extension and ankle plantarflexion of both groups (TCHHC &#x2b; TE: <italic>p</italic> &#x3c; 0.001, <italic>d</italic> &#x3d; 1.870, <italic>p</italic> &#x3c; 0.001, <italic>d</italic> &#x3d; 2.434; TE: <italic>p</italic> &#x3d; 0.007, <italic>d</italic> &#x3d; 0.927; <italic>p</italic> &#x3c; 0.001, <italic>d</italic> &#x3d; 1.352) decrease at week 9. The proprioception threshold of the knee extension was lower in the TCHHC &#x2b; TE group compared with those in the TE group at week 9 (<italic>p</italic> &#x3d; 0.022, <italic>d</italic> &#x3d; 0.967). Significant time effects were detected in proprioception thresholds of knee flexion (<italic>p</italic> &#x3c; 0.001 &#x3b7;2<sub>p</sub> &#x3d; 0.540), ankle dorsiflexion (<italic>p</italic> &#x3c; 0.001 &#x3b7;2<sub>p</sub> &#x3d; 0.446), ankle inversion (<italic>p</italic> &#x3d; 0.048, &#x3b7;2<sub>p</sub> &#x3d; 0.148) and eversion (<italic>p</italic> &#x3d; 0.008, &#x3b7;2<sub>p</sub> &#x3d; 0.246).</p>
<table-wrap id="T4" position="float">
<label>TABLE 4</label>
<caption>
<p>Proprioception thresholds of the more affected knee joint, ankle sagittal plane, and ankle frontal plane at weeks 0 and 9.</p>
</caption>
<table>
<thead valign="top">
<tr>
<th rowspan="2" align="left">Proprioception threshold (&#xb0;)</th>
<th rowspan="2" align="left"/>
<th rowspan="2" align="left">TCHHC &#x2b; TE (<italic>n</italic> &#x3d; 13)</th>
<th rowspan="2" align="left">TE (<italic>n</italic> &#x3d; 14)</th>
<th colspan="2" align="left">Time</th>
<th colspan="2" align="left">Group</th>
<th colspan="2" align="center">Time<xref ref-type="table-fn" rid="Tfn3">
<sup>a</sup>
</xref> group</th>
<th colspan="2" align="center">Post hoc</th>
</tr>
<tr>
<th align="left">p</th>
<th align="left">&#x3b7;<sup>2</sup>
<sub>p</sub>
</th>
<th align="left">p</th>
<th align="left">&#x3b7;<sup>2</sup>
<sub>p</sub>
</th>
<th align="left">p</th>
<th align="left">&#x3b7;<sup>2</sup>
<sub>p</sub>
</th>
<th align="left">p</th>
<th align="left">
<italic>d</italic>
</th>
</tr>
</thead>
<tbody valign="top">
<tr>
<td rowspan="2" align="left">Knee flexion</td>
<td align="center">Week 0</td>
<td align="center">3.29 &#xb1; 1.57</td>
<td align="center">2.34 &#xb1; 1.04</td>
<td align="left">&#x3c;0.001</td>
<td align="left">0.540</td>
<td align="left">0.095</td>
<td align="left">0.108</td>
<td align="left">0.296</td>
<td align="left">0.043</td>
<td align="left">--</td>
<td align="left">--</td>
</tr>
<tr>
<td align="center">Week 9</td>
<td align="center">1.76 &#xb1; 0.51</td>
<td align="center">1.46 &#xb1; 0.69</td>
<td align="left"/>
<td align="left"/>
<td align="left"/>
<td align="left"/>
<td align="left"/>
<td align="left"/>
<td align="left">--</td>
<td align="left">--</td>
</tr>
<tr>
<td rowspan="2" align="left">Knee extension</td>
<td align="center">Week 0</td>
<td align="center">4.29 &#xb1; 1.72</td>
<td align="center">3.31 &#xb1; 1.64</td>
<td align="left">--</td>
<td align="left">--</td>
<td align="left">--</td>
<td align="left">--</td>
<td align="left">0.018</td>
<td align="left">0.203</td>
<td align="left">
<xref ref-type="table-fn" rid="Tfn3">
<sup>a</sup>
</xref>
<sup>1</sup> &#x3c; 0.001,<xref ref-type="table-fn" rid="Tfn3">
<sup>a</sup>
</xref>
<sup>2</sup> &#x3d; 0.007</td>
<td align="left">
<xref ref-type="table-fn" rid="Tfn3">
<sup>a</sup>
</xref>
<sup>1</sup> &#x3d; 1.870,<xref ref-type="table-fn" rid="Tfn3">
<sup>a</sup>
</xref>
<sup>2</sup> &#x3d; 0.927</td>
</tr>
<tr>
<td align="center">Week 9</td>
<td align="center">1.32 &#xb1; 0.31<xref ref-type="table-fn" rid="Tfn3">
<sup>a</sup>
</xref>
<sup>1</sup>
<xref ref-type="table-fn" rid="Tfn4">
<sup>b</sup>
</xref>
</td>
<td align="center">1.99 &#xb1; 0.93<xref ref-type="table-fn" rid="Tfn3">
<sup>a</sup>
</xref>
<sup>2</sup>
</td>
<td align="left"/>
<td align="left"/>
<td align="left"/>
<td align="left"/>
<td align="left"/>
<td align="left"/>
<td align="left">
<xref ref-type="table-fn" rid="Tfn4">
<sup>b</sup>
</xref> &#x3d; 0.022</td>
<td align="left">
<xref ref-type="table-fn" rid="Tfn4">
<sup>b</sup>
</xref> &#x3d; 0.967</td>
</tr>
<tr>
<td rowspan="2" align="left">Ankle plantarflexion</td>
<td align="center">Week 0</td>
<td align="center">4.40 &#xb1; 1.29</td>
<td align="center">3.53 &#xb1; 1.22</td>
<td align="left">--</td>
<td align="left">--</td>
<td align="left">--</td>
<td align="left">--</td>
<td align="left">0.010</td>
<td align="left">0.235</td>
<td align="left">
<xref ref-type="table-fn" rid="Tfn3">
<sup>a</sup>
</xref>
<sup>1</sup> &#x3c; 0.001,<xref ref-type="table-fn" rid="Tfn3">
<sup>a</sup>
</xref>
<sup>2</sup> &#x3c; 0.001</td>
<td align="left">
<xref ref-type="table-fn" rid="Tfn3">
<sup>a</sup>
</xref>
<sup>1</sup> &#x3d; 2.434,<xref ref-type="table-fn" rid="Tfn3">
<sup>a</sup>
</xref>
<sup>2</sup> &#x3d; 1.352</td>
</tr>
<tr>
<td align="center">Week 9</td>
<td align="center">1.68 &#xb1; 0.61<xref ref-type="table-fn" rid="Tfn3">
<sup>a</sup>
</xref>
<sup>1</sup>
</td>
<td align="center">2.10 &#xb1; 0.65<xref ref-type="table-fn" rid="Tfn3">
<sup>a</sup>
</xref>
<sup>2</sup>
</td>
<td align="left"/>
<td align="left"/>
<td align="left"/>
<td align="left"/>
<td align="left"/>
<td align="left"/>
<td align="left">--</td>
<td align="left">--</td>
</tr>
<tr>
<td rowspan="2" align="left">Ankle dorsiflexion</td>
<td align="center">Week 0</td>
<td align="center">3.10 &#xb1; 1.13</td>
<td align="center">3.22 &#xb1; 1.26</td>
<td align="left">&#x3c;0.001</td>
<td align="left">0.446</td>
<td align="left">0.479</td>
<td align="left">0.020</td>
<td align="left">0.674</td>
<td align="left">0.007</td>
<td align="left">--</td>
<td align="left">--</td>
</tr>
<tr>
<td align="center">Week 9</td>
<td align="center">1.95 &#xb1; 0.70</td>
<td align="center">2.27 &#xb1; 0.80</td>
<td align="left"/>
<td align="left"/>
<td align="left"/>
<td align="left"/>
<td align="left"/>
<td align="left"/>
<td align="left">--</td>
<td align="left">--</td>
</tr>
<tr>
<td rowspan="2" align="left">Ankle inversion</td>
<td align="center">Week 0</td>
<td align="center">5.72 &#xb1; 2.44</td>
<td align="center">6.04 &#xb1; 3.65</td>
<td align="left">0.048</td>
<td align="left">0.148</td>
<td align="left">0.670</td>
<td align="left">0.007</td>
<td align="left">0.921</td>
<td align="left">0.000</td>
<td align="left">--</td>
<td align="left">--</td>
</tr>
<tr>
<td align="center">Week 9</td>
<td align="center">4.54 &#xb1; 2.50</td>
<td align="center">4.97 &#xb1; 1.67</td>
<td align="left"/>
<td align="left"/>
<td align="left"/>
<td align="left"/>
<td align="left"/>
<td align="left"/>
<td align="left">--</td>
<td align="left">--</td>
</tr>
<tr>
<td rowspan="2" align="left">Ankle eversion</td>
<td align="center">Week 0</td>
<td align="center">5.51 &#xb1; 2.58</td>
<td align="center">5.71 &#xb1; 2.93</td>
<td align="left">0.008</td>
<td align="left">0.246</td>
<td align="left">0.268</td>
<td align="left">0.049</td>
<td align="left">0.198</td>
<td align="left">0.065</td>
<td align="left">--</td>
<td align="left">--</td>
</tr>
<tr>
<td align="center">Week 9</td>
<td align="center">3.51 &#xb1; 1.21</td>
<td align="center">4.98 &#xb1; 1.99</td>
<td align="left"/>
<td align="left"/>
<td align="left"/>
<td align="left"/>
<td align="left"/>
<td align="left"/>
<td align="left">--</td>
<td align="left">--</td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<fn id="Tfn3">
<label>
<sup>a</sup>
</label>
<p>Denotes significant different between weeks 0 and 9 in each group.</p>
</fn>
<fn id="Tfn4">
<label>
<sup>b</sup>
</label>
<p>Denotes significant difference between the two groups at week 9.</p>
</fn>
<fn>
<p>TCHHC: traditional chinese herb hot compress.</p>
</fn>
<fn>
<p>TE: therapeutic exercise.</p>
</fn>
</table-wrap-foot>
</table-wrap>
<p>The times of TUG and 20-m walk tests were presented in <xref ref-type="table" rid="T5">Table 5</xref>. Significant interactions were detected in the TUG (<italic>p</italic> &#x3d; 0.046, &#x3b7;2<sub>p</sub> &#x3d; 0.150) and 20-m walk (<italic>p</italic> &#x3d; 0.008, &#x3b7;2<sub>p</sub> &#x3d; 0.249) tests. Post hoc comparisons showed that compared with week 0, the times of the TUG and 20-m walk tests of both groups (TCHHC &#x2b; TE: <italic>p</italic> &#x3c; 0.001, <italic>d</italic> &#x3d; 4.420, <italic>p</italic> &#x3c; 0.001, <italic>d</italic> &#x3d; 3.400; TE: <italic>p</italic> &#x3c; 0.001, <italic>d</italic> &#x3d; 3.113; <italic>p</italic> &#x3c; 0.001, <italic>d</italic> &#x3d; 2.543) decrease at week 9. The times of the TUG and 20-m walk tests was lower in the TCHHC &#x2b; TE group compared with those in the TE group at week 9 (<italic>p</italic> &#x3d; 0.022, <italic>d</italic> &#x3d; 0.957; <italic>p</italic> &#x3d; 0.044, <italic>d</italic> &#x3d; 0.820).</p>
<table-wrap id="T5" position="float">
<label>TABLE 5</label>
<caption>
<p>The times of TUG and 20-m walk tests at weeks 0 and 9.</p>
</caption>
<table>
<thead valign="top">
<tr>
<th rowspan="2" align="left">Variables</th>
<th rowspan="2" align="left"/>
<th rowspan="2" align="left">TCHHC &#x2b; TE (<italic>n</italic> &#x3d; 13)</th>
<th rowspan="2" align="left">TE (<italic>n</italic> &#x3d; 14)</th>
<th colspan="2" align="left">Time</th>
<th colspan="2" align="left">Group</th>
<th colspan="2" align="center">Time<xref ref-type="table-fn" rid="Tfn5">
<sup>a</sup>
</xref> group</th>
<th colspan="2" align="center">Post hoc</th>
</tr>
<tr>
<th align="left">p</th>
<th align="left">&#x3b7;<sup>2</sup>
<sub>p</sub>
</th>
<th align="left">p</th>
<th align="left">&#x3b7;<sup>2</sup>
<sub>p</sub>
</th>
<th align="left">p</th>
<th align="left">&#x3b7;<sup>2</sup>
<sub>p</sub>
</th>
<th align="left">p</th>
<th align="left">
<italic>d</italic>
</th>
</tr>
</thead>
<tbody valign="top">
<tr>
<td rowspan="2" align="left">TUG (s)</td>
<td align="center">Week 0</td>
<td align="center">11.67 &#xb1; 1.07</td>
<td align="center">11.48 &#xb1; 1.14</td>
<td align="left">--</td>
<td align="left">--</td>
<td align="left">--</td>
<td align="left">--</td>
<td align="left">0.046</td>
<td align="left">0.150</td>
<td align="left">
<xref ref-type="table-fn" rid="Tfn5">
<sup>a</sup>
</xref>
<sup>1</sup> &#x3c; 0.001,<xref ref-type="table-fn" rid="Tfn5">
<sup>a</sup>
</xref>
<sup>2</sup> &#x3c; 0.001</td>
<td align="left">
<xref ref-type="table-fn" rid="Tfn5">
<sup>a</sup>
</xref>
<sup>1</sup> &#x3d; 4.420,<xref ref-type="table-fn" rid="Tfn5">
<sup>a</sup>
</xref>
<sup>2</sup> &#x3d; 3.113</td>
</tr>
<tr>
<td align="center">Week 9</td>
<td align="center">7.41 &#xb1; 0.80<xref ref-type="table-fn" rid="Tfn5">
<sup>a</sup>
</xref>
<sup>1</sup>
<xref ref-type="table-fn" rid="Tfn6">
<sup>b</sup>
</xref>
</td>
<td align="center">8.23 &#xb1; 0.91<xref ref-type="table-fn" rid="Tfn5">
<sup>a</sup>
</xref>
<sup>2</sup>
<xref ref-type="table-fn" rid="Tfn6">
<sup>b</sup>
</xref>
</td>
<td align="left"/>
<td align="left"/>
<td align="left"/>
<td align="left"/>
<td align="left"/>
<td align="left"/>
<td align="left">
<xref ref-type="table-fn" rid="Tfn6">
<sup>b</sup>
</xref> &#x3d; 0.022</td>
<td align="left">
<xref ref-type="table-fn" rid="Tfn6">
<sup>b</sup>
</xref> &#x3d; 0.957</td>
</tr>
<tr>
<td rowspan="2" align="left">20-m walk (s)</td>
<td align="center">Week 0</td>
<td align="center">16.61 &#xb1; 1.95</td>
<td align="center">15.73 &#xb1; 1.58</td>
<td align="left">--</td>
<td align="left">--</td>
<td align="left">--</td>
<td align="left">--</td>
<td align="left">0.008</td>
<td align="left">0.249</td>
<td align="left">
<xref ref-type="table-fn" rid="Tfn5">
<sup>a</sup>
</xref>
<sup>1</sup> &#x3c; 0.001,<xref ref-type="table-fn" rid="Tfn5">
<sup>a</sup>
</xref>
<sup>2</sup> &#x3c; 0.001</td>
<td align="left">
<xref ref-type="table-fn" rid="Tfn5">
<sup>a</sup>
</xref>
<sup>1</sup> &#x3d; 3.400,<xref ref-type="table-fn" rid="Tfn5">
<sup>a</sup>
</xref>
<sup>2</sup> &#x3d; 2.543</td>
</tr>
<tr>
<td align="center">Week 9</td>
<td align="center">10.83 &#xb1; 1.18<xref ref-type="table-fn" rid="Tfn5">
<sup>a</sup>
</xref>
<sup>1</sup>
<xref ref-type="table-fn" rid="Tfn6">
<sup>b</sup>
</xref>
</td>
<td align="center">11.90 &#xb1; 1.42<xref ref-type="table-fn" rid="Tfn5">
<sup>a</sup>
</xref>
<sup>2</sup>
<xref ref-type="table-fn" rid="Tfn6">
<sup>b</sup>
</xref>
</td>
<td align="left"/>
<td align="left"/>
<td align="left"/>
<td align="left"/>
<td align="left"/>
<td align="left"/>
<td align="left">
<xref ref-type="table-fn" rid="Tfn6">
<sup>b</sup>
</xref> &#x3d; 0.044</td>
<td align="left">
<xref ref-type="table-fn" rid="Tfn6">
<sup>b</sup>
</xref> &#x3d; 0.820</td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<fn id="Tfn5">
<label>
<sup>a</sup>
</label>
<p>Denotes significant different between weeks 0 and 9 in each group.</p>
</fn>
<fn id="Tfn6">
<label>
<sup>b</sup>
</label>
<p>Denotes significant difference between the two groups at week 9.</p>
</fn>
<fn>
<p>TCHHC: traditional chinese herb hot compress.</p>
</fn>
<fn>
<p>TE: therapeutic exercise.</p>
</fn>
</table-wrap-foot>
</table-wrap>
</sec>
<sec sec-type="discussion" id="s4">
<title>4 Discussion</title>
<p>This study investigated the effects of an 8-week TCHHC &#x2b; TE on pain, proprioception, and functional performance among older adults with KOA. The results supported our hypothesis. Compared with TE, TCHHC &#x2b; TE was superior in relieving pain, recovering proprioception, and improving functional performance among older adults with KOA.</p>
<p>At week 9, pain scores decreased in both groups, and the decrease was more significant in the TCHHC &#x2b; TE group than in the TE group. The effects of TE on pain relief have been well documented (<xref ref-type="bibr" rid="B26">Juhl et al., 2014</xref>; <xref ref-type="bibr" rid="B61">Zeng et al., 2021</xref>). Resistance training increases the muscle strength of the lower extremity, improved the stability of knee joints, and reduces the wear between articular cartilage to relieve pain (<xref ref-type="bibr" rid="B8">Chen H. et al., 2019</xref>). Joint mobilization reduces the excitability of nerves to relieve pain (<xref ref-type="bibr" rid="B40">Saunders et al., 2005</xref>). Our results showed that TCHHC &#x2b; TE significantly relieved pain among older adults with KOA compared to TE. Similar results were reported, supporting that the addition of TCHHC to TE enhanced the relief of knee pain (<xref ref-type="bibr" rid="B9">Chen S. et al., 2019</xref>). There are several possible mechanisms for TCHHC &#x2b; TE&#x2019;s superior effects for pain relief, as follows. 1. Cao (<xref ref-type="bibr" rid="B6">Cao et al., 2016</xref>) et al. reported that the herbs have been demonstrated to be effective at promoting absorption of inflammatory substances and eliminating swelling by increasing blood circulation in clinical observation. In this study, some of the components of the herbs are effective in relieving pain, e.g., peony root reduces the expression level of substance P, which is the most important element in pain perception (<xref ref-type="bibr" rid="B55">Wang et al., 2013</xref>). Prepared sichuan black and sichuan ox knee reduces the level of pro-inflammatory cytokines (TNF-&#x3b1;, IL-1&#x3b2;, IL-6, and IL-17A) in serum, increases the viscosity of intra-articular knee joint fluid, and eliminates swelling and promotes blood circulation (<xref ref-type="bibr" rid="B56">Weng et al., 2014</xref>; <xref ref-type="bibr" rid="B31">Li et al., 2017</xref>; <xref ref-type="bibr" rid="B63">Zhang et al., 2019a</xref>). Miyajima (<xref ref-type="bibr" rid="B33">Miyajima et al., 2013</xref>) et al. point out that hot compress increases the temperature of local tissues and reduces the excitability of afferent nerves, and helps control swelling and reduce pain. TCHHC allow herbs to penetrate the skin barrier through a warming effect, immediately reaching and acting on the affected areas. TCHHC can regulate the imbalance of the levels of anti-inflammatory factors (TGF-&#x3b2;1, IL-13), pro-inflammatory cytokines (IL-1&#x3b2;, IL-6), and pain mediators (PGE2, 5-HT), thus relieving pain (<xref ref-type="bibr" rid="B36">Orita et al., 2011</xref>). 2. TE facilitates TCHHC&#x2019;s pain-relieving effects, by enhancing TE enhances blood and lymphatic fluid circulation, as well as promoting local vasodilation (<xref ref-type="bibr" rid="B19">Guo et al., 2021</xref>); thus, it increases the absorption of herbs into the skin and promotes anti-inflammatory and pain-relieving effects.</p>
<p>At week 9, the proprioception thresholds of the knee extension and ankle plantar flexion decreased significantly in both groups, and the decrease was more significant in the TCHHC &#x2b; TE group than in the TE group. Previous studies showed that TE has a positive effect on the proprioception of knee and ankle joints (<xref ref-type="bibr" rid="B46">Shen et al., 2021</xref>), which is consistent with our study. As the most important proprioceptor within the knee joint, the muscle spindles are stimulated by muscle lengthening, speed, or acceleration (<xref ref-type="bibr" rid="B36">Orita et al., 2011</xref>).TE releases and stretches the tensed muscles around the knee joint, coordinates the contraction ability between muscles, and enhances muscle spindle sensitivity to improve proprioception among older adults with KOA (<xref ref-type="bibr" rid="B15">Fransen et al., 2002</xref>). There are several possible reasons why TCHHC &#x2b; TE had a superior effect on proprioception, as follows. 1. In this study, some of the components of the herbs have been proven to recover proprioception, such as cassia twig, mulberry parasitic, and antler gum prevent the loss of proteoglycans and accelerate the proliferation of chondrocytes to protect joint cartilage cells and improve their metabolism (<xref ref-type="bibr" rid="B57">Xu and Liu, 2004</xref>; <xref ref-type="bibr" rid="B14">Fan et al., 2012</xref>), reduce the damage to mechanoreceptors, promote neuromuscular control, and improve proprioception (<xref ref-type="bibr" rid="B7">Chen et al., 2016</xref>). Nagashima et al. (<xref ref-type="bibr" rid="B35">Nagashima et al., 2006</xref>) and Rusminingsih et al. (<xref ref-type="bibr" rid="B39">Rusminingsih et al., 2020</xref>) pointed out that hot compresses applied to the knee joint to dilate blood vessels, increases the excitability of motor neurons and recruits many motor neurons to participate in activities (<xref ref-type="bibr" rid="B29">Levine, 2007</xref>), facilitates sensory input. 2. TCHHC enhanced TE&#x2019;s effects on proprioception. By reducing the excitability of nerve endings and eliminating swelling, thereby allowing the adhesions and atrophy of the knee joint and its surrounding soft tissues to recover as much as possible (<xref ref-type="bibr" rid="B62">Zhang et al., 2015</xref>), which facilitates the sensitivity of muscle spindles (<xref ref-type="bibr" rid="B54">Wang et al., 2010</xref>; <xref ref-type="bibr" rid="B45">SH, 2012</xref>).</p>
<p>At week 9, the times of TUG and 20-m walk decreased significantly in both groups, and the decrease was more significant in the TCHHC &#x2b; TE group than in the TE group. TCHHC &#x2b; TE is more effective in improving functional performance, which is consistent with a previous study (<xref ref-type="bibr" rid="B48">Song, 2022</xref>). Another study has shown that herbs are used to enhance muscle strength and function performance (<xref ref-type="bibr" rid="B43">Sellami et al., 2018</xref>). The level of magnesium (Mg) (<xref ref-type="bibr" rid="B60">Zeng et al., 2015</xref>) and calcium (Ca<sup>&#x2b;</sup>) (<xref ref-type="bibr" rid="B30">Li et al., 2016</xref>) in the serum are significantly decreased among older adults with KOA, which reduces their functional performance, increases the risk of falls, and accelerates the deterioration of KOA (<xref ref-type="bibr" rid="B53">Veronese et al., 2017</xref>; <xref ref-type="bibr" rid="B23">Heffernan et al., 2020</xref>). Some of the Traditional Chinese Herbs, e.g., paeony root, ephedra root, atractylodes macrocephala reduce pro-inflammatory cytokines such as TNF- <italic>&#x3b1;</italic> and interleukins, inhibit the production of matrix metalloproteinases (<xref ref-type="bibr" rid="B59">Yuan et al., 2015</xref>; <xref ref-type="bibr" rid="B32">Malemud, 2017</xref>), thereby improve the level of Mg and Ca<sup>&#x2b;</sup> in serum (<xref ref-type="bibr" rid="B18">Gunn et al., 2013</xref>; <xref ref-type="bibr" rid="B63">Zhang et al., 2019a</xref>). In addition, parsnip and anemarrhena asphodeloides reduce the expression of fibroblast-like synoviocytes and receptor activator for NF-kB ligand, inhibit the activation of osteoclasts, and reduce the destruction of cartilage, bone, and tendon (<xref ref-type="bibr" rid="B59">Yuan et al., 2015</xref>). Previous studies have pointed out that hot compress promotes blood circulation, activates the motor cortex, and facilitates the recovery of adhesions and atrophy of the muscles and soft tissues around the knee joint (<xref ref-type="bibr" rid="B62">Zhang et al., 2015</xref>). Therefore, TCHHC is more effective in improving functional performance by expands capillaries, promotes blood circulation, and releases muscle tension (<xref ref-type="bibr" rid="B41">Sava&#x15f; et al., 2019</xref>). The combination of TE facilitates herb penetration in the affected area, reduces stress-related muscle tension, improves lower extremity coordination, and enhances muscle strength to improve functional performance (<xref ref-type="bibr" rid="B19">Guo et al., 2021</xref>).</p>
<p>This study has several limitations. First of all, the effects of the TCHHC are possibly attributed to Chinese herbs or hot compress, further studies are recommended to further investigate their specific effects. Second, there was no follow-up after the 8-week intervention, and it was impossible to determine how long the effects would last.</p>
</sec>
<sec sec-type="conclusion" id="s5">
<title>5 Conclusion</title>
<p>Compared with TE, the 8-week TCHHC &#x2b; TE was superior in relieving pain, recovering proprioception, and improving functional performance among older adults with KOA. It is recommended that TCHHC should be adopted prior to TE to enhance the effects of KOA rehabilitation.</p>
</sec>
</body>
<back>
<sec sec-type="data-availability" id="s6">
<title>Data availability statement</title>
<p>The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found below: DOI:10.57760/sciencedb.02151.</p>
</sec>
<sec id="s7">
<title>Ethics statement</title>
<p>The studies involving human participants were reviewed and approved by the Ethics Committee of Neck, Shoulder, Back, and Leg Pain Hospital. The patients/participants provided their written informed consent to participate in this study.</p>
</sec>
<sec id="s8">
<title>Author contributions</title>
<p>JW designed the study and drafted the manuscript. WL was responsible for recruiting patients and collecting data. HF provided efforts in data analysis and revised the manuscript. All authors have read and agreed to the published version of the manuscript.</p>
</sec>
<sec id="s9">
<title>Funding</title>
<p>This research was funded by the Shandong Province under Grant Chinese Medicine Science and Technology Project (2021M249); the Shandong Young Innovative Talent Team of China (2019-183) and the China National Natural Science Foundation (12102235).</p>
</sec>
<ack>
<p>The authors would like to thank Peixin Shen, Xinheng Che, Bo Gao, Qi Wang, Yaya Pang, Xiaoli Ma, and Xiaohui Duan, graduate students at Shandong Sport University, for participating in the experiment and data acquisition for this work.</p>
</ack>
<sec sec-type="COI-statement" id="s10">
<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="s11">
<title>Publisher&#x2019;s note</title>
<p>All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.</p>
</sec>
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