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SYSTEMATIC REVIEW article

Front. Public Health, 02 October 2025

Sec. Children and Health

Volume 13 - 2025 | https://doi.org/10.3389/fpubh.2025.1677592

This article is part of the Research TopicTraditional, Complementary and Integrative Medicine – Advances in Traditional Medicine and Knowledge for Sustainable Global DevelopmentView all 4 articles

The effectiveness of acupuncture in the treatment of Tourette syndrome in Chinese children: a systematic review and meta-analysis

Qian-Qian ZhouQian-Qian Zhou1Zi-Chen LiZi-Chen Li1Zhuo-Ya HuZhuo-Ya Hu1Juan TangJuan Tang1Peng TangPeng Tang1Qi-Rui WuQi-Rui Wu1Zhong-Qi DengZhong-Qi Deng1Wen-Bin MaWen-Bin Ma2Lei Lan
Lei Lan1*
  • 1Acupuncture and Tuina College, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China
  • 2School of Health and Rehabilitation, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China

Objective: As a prominent complementary and alternative therapy, acupuncture is widely used to treat Tourette syndrome in children. This review aims to evaluate its clinical efficacy and provide evidence-based support for acupuncture in pediatric Tourette syndrome.

Methods: We systematically searched six databases: China National Knowledge Infrastructure, Wanfang Database, VIP Information Chinese Journal Service Platform, PubMed, Cochrane Central Register of Controlled Trials, and Embase, from their inception to 10 April 2025. Randomized controlled trials comparing acupuncture alone versus medication, or acupuncture plus other treatments versus other treatments alone, for children tic disorder were included.

Results: Thirty-two studies were included, with 2,201 participants. Acupuncture may be more effective in improving motor tics symptoms than dopamine agonist [WMD −3.04, 95% CI (−3.77, −2.31), RD 0.38 (0.29, 0.46)], slightly improving vocal tics [WMD −2.39, 95% CI (−3.51, −1.26), RD 0.21 (0.10, 0.35)] and overall condition [WMD −5.56, 95% CI (−7.28, −3.83), RD 0.05 (0.02, 0.09)], but having little difference in functional impairment [WMD −2.27, 95% CI (−3.58, −0.96), RD 0.14 (0.09, 0.20)]. Acupuncture may be more effective than blank treatment on basis of other therapies in improving motor tics [WMD −2.51, 95% CI (−3.54, −1.49), RD 0.31 (0.19, 0.41)] and vocal tics [WMD −2.56, 95% CI (−3.66, −1.45), RD 0.28 (0.15, 0.40)], but slightly improving functional impairment [WMD −2.91, 95% CI (−4.64, −1.19), RD 0.13 (0.05, 0.23)] and overall symptom severity [WMD −5.57, 95% CI (−7.47, −3.68), RD 0.11 (0.06, 0.17)].

Conclusion: Chinese children with Tourette syndrome using acupuncture may experience more improvement in motor tics symptoms than those using dopamine agonist. Acupuncture combined with other therapies may bring Chinese children with Tourette syndrome symptom relief in motor tics and vocal tics more than those alone. All results are supported by low-quality evidence.

Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/view/CRD42023444312, identifier CRD42023444312.

1 Introduction

Tourette’s syndrome (TS) is a prevalent chronic neuropsychiatric disorder representing a distinct chronic subtype of tic disorders: onset occurs before age 18, with a duration exceeding 1 year; it involves both motor and vocal tics, which may occur asynchronously. This distinguishes it from chronic tic disorders presenting solely with one tic type and transient tic disorders lasting less than 1 year. Patients typically present with semivoluntary muscle twitching in the head, face, shoulders, neck, and limbs, alongside abnormal vocalizations. These symptoms are frequently accompanied by psychological comorbidities such as attention deficit hyperactivity disorder and obsessive-compulsive disorder (1). The causes and mechanisms of the disease remain unclear, and treatment primarily involves symptomatic drug therapy (2). Long-term medication use often leads to adverse neurological reactions, such as blurred vision, drowsiness, fatigue, nausea, and vomiting, making it difficult for children to comply with long-term medication regimens, resulting in suboptimal treatment outcomes (3). Acupuncture is a non-pharmacological therapy for neurological disorders. Research indicates that acupuncture has demonstrated substantial efficacy in treating such conditions, including central nervous system disorders such as stroke and migraine, and peripheral nervous system disorders such as Bell’s palsy and trigeminal neuralgia. With its minimal adverse reactions, acupuncture is gaining increasing acceptance among practitioners and patients alike (4, 5). This study aims to evaluate the clinical efficacy of acupuncture in treating children with TS and provide evidence-based medical for acupuncture treatment of childhood Tourette syndrome.

2 Methods

2.1 Literature search

We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines (6) to report our systematic review and registered it in PROSPERO (registration number: CRD42023444312). The search strategy is as follows: (1) Database Search: China National Knowledge Infrastructure, Wanfang Data Online Knowledge Service Platform, VIP Information Chinese Journal Service Platform, PubMed, Cochrane Central Register of Controlled Trials, and Embase Database. (2) Manual Search: (1) China Clinical Trials Registry (search terms: Tourette syndrome AND acupuncture); (2) Included literature from published systematic reviews and their reference lists. The search was conducted up to 10 April 2025, with no language restrictions. (Database search terms and search results are listed in Supplementary Table 1).

2.2 Literature screen and data extraction

After removing duplicate documents using Endnote 21 software, four researchers (QQZ, ZCL, ZYH, JT) independently read the titles, abstracts, and full texts of all documents to determine the final documents to be included. In case of disagreement, the issue was resolved through discussion or by the third party (PT, LL). Data extraction was conducted independently by four researchers (QQZ, ZCL, ZYH, JT) in a blinded fashion. The extracted data included: literature characteristics (title, authors, publication year, age, disease duration, sample size, intervention and control measures), methodological information (randomization method, allocation concealment, use of blinding, loss to follow-up), and outcome measures (tics, vocal tics, functional impairment, adverse reactions). After extraction, we applied the following inclusion and exclusion criteria.

Inclusion criteria: (1) patients diagnosed with TS according to the diagnostic criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) (7), with a disease duration of over 1 year and no tic-free periods exceeding 2 months, aged <18 years,(2) acupuncture vs. western medicine, acupuncture vs. blank control, with a follow-up ≥4 weeks, (3) randomized controlled trial (RCT), (4) primary outcomes involved tic symptoms, coprolalia symptoms, and functional impairment, and secondary outcomes were adverse reactions.

Exclusion criteria: (1) Semi-randomized controlled trials; (2) Tics attributable to other neurological disorders.

2.3 Risk of bias assessment

The risk of bias in the included RCTs was assessed independently by two reviewers (QQZ, ZCL) using the Cochrane Risk of Bias 1.0 tool (8, 9). The following domains were rated: (1) random sequence generation; (2) allocation concealment; (3) blinding of participants and personnel; (4) blinding of outcome assessment; (5) incomplete outcome data; (6) selective reporting; and (7) other sources of bias.

2.4 Data analysis

Continuous variables were analyzed using the weighted mean difference (WMD) and corresponding confidence interval (95% CI); binary variables were analyzed using the relative risk (RR) and 95% CI. All meta-analyses were performed using a random-effects model in Stata 17 software. Heterogeneity was assessed using the I2 value and Q test, with an I2 value ≥ 50% indicating high heterogeneity. Subgroup analysis was conducted to identify sources of heterogeneity. To better interpret the clinical significance of effect sizes, we defined an effect size of ≥30% reduction from baseline as the minimal clinically important difference (MCID), and calculated the risk difference (RD) between groups to quantify between-group differences.

2.5 Certainty of evidence

We used the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) method to assess the certainty of evidence for each outcome (10). Evidence from RCTs started at high quality but can be downgraded to high, moderate, low, or very low quality based on factors such as risk of bias, consistency, directness, precision, and publication bias.

3 Results

3.1 Literature screening

Database search yielded 3,391 records. Manual search yielded 54 records from 11 published systematic reviews (1121). Thirty-two studies were ultimately included (Figure 1).

Figure 1
Flowchart detailing the study selection process for a review. Left side: 3391 records identified from databases, 88 duplicates removed, 3303 records screened, 2962 excluded, 341 reports sought, 239 not retrieved, 102 assessed, 70 excluded for various reasons, resulting in 32 studies included. Right side: 54 records identified via citation searching, all 54 assessed, 54 excluded for reasons including ineligible population and intervention, resulting in 0 studies included.

Figure 1. Literature screening process and results of acupuncture for children with TS.

3.2 Characteristics of included studies

Thirty-two studies (2252) were included, involving 2,201 patients, with 28.17% being female. All included studies were conducted in China, and 10 studies (22, 25, 29, 34, 36, 4244, 48, 51) received funding support. Among the 25 studies reporting participants’ specific ages, the average age of participants was 8.84 years, with the shortest intervention duration being 28 days and the longest being 120 days. This included 15 acupuncture vs. medication control studies (2231, 3336, 52), 11 acupuncture combined with medication vs. medication alone control studies (38, 39, 41, 43, 44, 4650, 52, 53), 4 studies comparing acupuncture combined with Chinese herbal medicine vs. Chinese herbal medicine alone (32, 37, 45, 51), 1 study comparing acupuncture combined with ear acupuncture vs. ear acupuncture alone (42), and 1 study comparing acupuncture combined with cognitive behavioral therapy vs. cognitive behavioral therapy alone (40). Fourteen studies (22, 24, 2830, 3335, 43, 44, 46, 48, 49, 51) reported adverse reactions. The detailed information of the included studies can be seen in Table 1.

Table 1
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Table 1. Baseline characteristics of included studies.

3.3 Risk of bias

All of the 32 included studies showed that 26 (81%) had adequate randomization sequence generation, 3 (9%) had adequate allocation concealment (22, 35, 36), and 3 (9%) had blinding of data collectors, data processors, and data analysts (22, 35, 36). Six studies reported patient attrition (27, 32, 37, 48, 51, 53), but the attrition rates did not exceed 20% in any case (Supplementary Table 3).

3.4 Acupuncture vs. medicine

3.4.1 Motor tic symptoms

Low-quality evidence (4 studies, 288 participants) suggested that acupuncture may lessen motor tics symptoms in children with TS than DA [WMD −3.04, 95% CI (−3.77, −2.31), RD 0.38 (0.29, 0.46) (Figure 2; Table 2)] (25, 26, 30, 35).

Figure 2
A forest plot comparing acupuncture and medicine across different studies. It shows the mean differences with 95% confidence intervals visualized by squares and diamonds. Studies are divided into DA and Non-DA categories. The plot indicates heterogeneity with statistics provided for each group and overall. The overall test favors acupuncture with a mean difference of -1.74, 95% confidence interval from -3.40 to -0.08.

Figure 2. Acupuncture vs. medicine evaluation of efficacy of motor tics.

Table 2
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Table 2. GRADE evidence quality rating of the clinical efficacy of acupuncture versus medicine therapy for children with TS.

3.4.2 Vocal tic symptoms

Low-quality evidence (7 studies, 475 participants) suggested that acupuncture may slightly improve vocal tics symptoms in children with TS compared to conventional medication [WMD −2.39, 95% CI (−3.51, −1.26), RD 0.21 (0.10, 0.35) (Figure 3, Table 2)] (25, 26, 30, 31, 33, 35, 36).

Figure 3
The forest plot compares the average differences and confidence intervals of acupuncture versus pharmacotherapy in treating vocal cord spasms across seven studies. Squares represent weighted mean differences from individual studies, while diamonds indicate overall effects. Confidence intervals extending beyond the zero line suggest a mixed-effect pattern, with most studies supporting acupuncture. The overall test favors with a mean difference of -2.39, 95% confidence interval from -3.51 to -1.26.

Figure 3. Acupuncture vs. medicine evaluation of efficacy of vocal tics.

3.4.3 Functional impairment

Low-quality evidence (4 studies, 300 participants) suggested that acupuncture may has a negligible effect on functional impairment in children with TS [WMD −2.27, 95% CI (−3.58, −0.96), RD 0.05 (0.02, 0.09) (Figure 4; Table 2)] (25, 26, 30, 31).

Figure 4
The efficacy differences between acupuncture and drug therapy in TS children's functional impairment were compared by forest map in the four studies, showing mean difference and confidence interval。The overall test favors with a mean difference of -2.27, 95% confidence interval from -3.58 to -0.96.

Figure 4. Acupuncture vs. medicine evaluation of efficacy of functional improvement.

3.4.4 Overall symptom severity

Low-quality evidence (13 studies, 995 participants) suggested that acupuncture may slightly control overall symptom severity in children with TS [WMD −5.56, 95% CI (−7.28, −3.83), RD 0.14 (0.09, 0.20) (Figure 5; Table 2)] (2231, 33, 34, 52).

Figure 5
The forest plot compares the effectiveness of acupuncture versus medication in controlling overall symptom severity in children with Tourette Syndrome (TS). Each study presents average differences and 95% confidence intervals. Overall, acupuncture demonstrated greater efficacy, indicated by green diamonds labeled

Figure 5. Acupuncture vs. medicine evaluation of efficacy of overall symptom efficacy evaluation.

3.4.5 Adverse reactions

Low-quality evidence (7 studies, 476 participants) suggested that acupuncture treatment for children with TS has less adverse reactions than DA, [RR 0.34, 95%CI (0.24, 0.49) (Figure 6; Table 2)] (22, 24, 2830, 34, 35). One article (33) compared the acupuncture group with the drug group, and found no difference in the incidence of adverse reactions between the two groups.

Figure 6
The forest plot analyzed seven adverse reactions to acupuncture and medication(DA) in children with tic disorders. Each study included a relative risk ratio and its 95% confidence interval. The overall relative risk ratio(RR) was 0.34, with a 95% confidence interval of (0.24,0.49).

Figure 6. Acupuncture vs. DA group analysis of the incidence of adverse reactions.

3.5 Acupuncture vs. blank control on basis of usual care

3.5.1 Motor tic symptoms

Low-quality evidence (10 studies, 722 participants) suggested that acupuncture may lessen more motor tics symptoms in children with TS than blank treatment on basis of usual care [WMD −2.51, 95% CI (−3.54, −1.49), RD 0.31 (0.19, 0.41) (Figure 7; Table 3)] (38, 4143, 4547, 4951).

Figure 7
This forest plot compares the efficacy of acupuncture therapy with a blank control group in reducing motorized seizures (TS) symptoms in children, presenting mean differences and 95% confidence intervals. All difference values fall to the left of the zero line. The overall effect size is-2.51, with a confidence interval of [-3.54, -1.49]. The figure displays heterogeneity statistics and weight percentages, indicating statistically significant results overall. This suggests acupuncture therapy may demonstrate greater efficacy compared to no treatment.

Figure 7. Acupuncture vs. blank control on basis of usual care evaluation of efficacy of motor tics.

Table 3
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Table 3. GRADE evidence quality rating of the clinical efficacy of acupuncture versus blank therapy for children with TS.

3.5.2 Vocal tic symptoms

Low-quality evidence (10 studies, 722 participants) suggested that acupuncture may improve vocal tics symptoms in children with TS compared to blank treatment on basis of usual care [WMD −2.56, 95% CI (−3.66, −1.45), RD 0.28 (0.15, 0.40) (Figure 8; Table 3)] (38, 4143, 4547, 4951).

Figure 8
This study compared the efficacy of acupuncture versus placebo in 10 clinical trials for improving vocalized seizures (TS) symptoms in children. Each trial presented sample sizes, mean values, and standard deviations for both groups, with graphical representations of mean differences and 95% confidence intervals. The overall results indicated that acupuncture may demonstrate superior effectiveness. The overall test favors with a mean difference of -2.56, 95% confidence interval from -3.66 to -1.45.

Figure 8. Acupuncture vs. blank control on basis of usual care evaluation of efficacy of vocal tics.

3.5.3 Functional impairment

Low-quality evidence (2 studies, 100 participants) suggested that acupuncture with DA may lessen functioning impairment than DA [WMD −2.91, 95% CI (−4.64, −1.19), RD 0.13 (0.05, 0.23) (Figure 9; Table 3)] (38, 42, 45, 49, 51).

Figure 9
Forest plot comparing acupuncture and blank intervention across six studies. Each study's mean difference, confidence interval, and weight percentage are shown with squares and horizontal lines. Diamonds represent overall effects for DA and Non-DA groups, with an overall effect near zero. Heterogeneity statistics are provided for each grouping.

Figure 9. Acupuncture vs. blank control on basis of usual care evaluation of efficacy of functional improvement.

3.5.4 Overall symptom severity

Low-quality evidence (14 studies, 935 participants) suggested that acupuncture may be superior in improving overall symptoms severity in children with TS than blank treatment [WMD −5.57, 95% CI (−7.47, −3.68), RD 0.11 (0.06, 0.17) (Figure 10; Table 3)] (32, 3741, 4446, 4851, 53).

Figure 10
The forest plot presents the efficacy comparison between acupuncture and a blank control group in multiple studies for improving overall symptom severity in children with Tourette Syndrome (TS). The average difference and 95% confidence intervals of each study are presented in hatched boxes. The chart shows an overall effect size favoring the acupuncture group. The overall test favors with a mean difference of -5.57, 95% confidence interval from -7.47 to -3.68.

Figure 10. Acupuncture vs. blank control on basis of usual care evaluation of efficacy of overall symptom efficacy evaluation.

3.5.5 Adverse reactions

Low-quality evidence (6 studies, 411 participants) suggested that the incidence of adverse reactions in children with TS treated with acupuncture combined with other therapies is not significantly different from that in children treated with other therapies alone, [RR 0.56, 95%CI (0.30, 1.04), (Figure 11; Table 3)] (43, 44, 46, 48, 49, 51).

Figure 11
Forest plot illustrating six studies comparing acupuncture to a blank intervention. Each study's relative risk (RR) with a ninety-five percent confidence interval (CI) is displayed. The overall RR is 0.56, favoring acupuncture with an I-squared of thirty-one point three percent, indicating low heterogeneity. The studies vary in their weight percentages, with Kong Y 2017 contributing the most at forty-two percent. Weights are derived from a random effects analysis.

Figure 11. Acupuncture vs. blank control on basis of usual care analysis of the incidence of adverse reactions.

4 Discussion

4.1 Overall findings

Compared with pharmacotherapy, acupuncture may alleviate more motor tics symptoms with less adverse effects, but it may bring about slight improvement in vocal tics, functional impairments, and overall symptom severity in Chinese children with TS. Compared with blank treatment, acupuncture may alleviate more motor tics, vocal tics symptoms, functional impairments, and overall symptom severity in Chinese children with TS.

4.2 Relation of other studies

We identified eleven systematic reviews on acupuncture treatment for childhood tic disorders (1121). After screening their included studies, we excluded those that enrolled patients with chronic or transient tic disorders, or that used ineligible comparators or outcomes (Supplementary Table 2).

The latest systematic review (21) included 26 studies, with a search cut-off date of October 2023. The results indicated that acupuncture is more effective than most existing treatments in alleviating motor and vocal tics in children with TS, while also reducing the incidence of adverse reactions. However, some outcome measures in the included studies only reported treatment efficacy rates, failing to clearly assess improvements in tic symptom-related scores. Additionally, the study did not include outcomes related to functional impairments in children with TS, focusing solely on motor and vocal tics. Finally, the study did not assess the certainty of the evidence, lacking a certain degree of professionalism.

This study included 18 RCTs not included in the latest review and excluded 12 studies included in the review, with specific reasons as follows: (1) Six studies had questionable inclusion criteria for children with TS, including patients with chronic tic disorder and transient tic disorder (5459), (2) Two studies had acupuncture intervention durations of less than 28 days (60, 61), (3) Four studies did not report reasonable tic symptom scores (6265). Our findings lead to a more cautious conclusion than the latest review and emphasize that the role of acupuncture in the treatment of TS in children requires further clinical research to confirm. (Supplementary Table 2).

4.3 Strengths and limitations

The strengths of this study include a comprehensive search for eligible RCTs and a focus on patient-reported outcome measures, with analysis conducted across three domains: motor tics, vocal tics, and functional impairment. We used the GRADE method to assess the certainty of the evidence and referenced the latest research results from the BMJ (66) and Cochrane Collaboration (10) for methodological exploration: first, we calculated the scores where the reduction rate in each YGTSS subscale reached at least 30%, defining this as the MCID. We then calculated the probability of achieving this value in the acupuncture group and the control group, respectively, and used the RD to display the between-group differences, thereby making the findings more accessible and clinically interpretable.

This study has limitations. Only three studies (22, 35, 36) adequately described random-sequence generation, allocation concealment, participant blinding, and implementation details. Additionally, due to the special nature of acupuncture procedures, it was not possible to blind patients or operators, resulting in a high risk of bias. Our review was based on the Chinese population, which limits its generalizability. Evidence from other populations is therefore needed for further analysis.

4.4 Implications

Chinese children with TS who receive acupuncture may experience greater relief of motor tics and fewer adverse effects compared with those on pharmacotherapy. Relative to no-treatment controls, these children also demonstrate larger reductions in vocal tics, functional impairment, and overall symptom severity. Low-certainty evidence underpins these conclusions on basis of Chinese population. Future trials should adopt rigorous methodological safeguards to minimize bias, and additional well-designed RCTs are required to clarify the efficacy of acupuncture for pediatric tic disorders.

5 Conclusion

Compared to pharmacotherapy, acupuncture may relieve more motor tics symptoms with less adverse effects, but it may slightly improve vocal tics, functional impairments, and overall symptom severity in Chinese children with TS. Compared to blank treatment, acupuncture may alleviate more motor tics, vocal tics symptoms, functional impairments, and overall symptom severity in Chinese children with TS. All results are supported by low-quality evidence.

Data availability statement

The original contributions presented in the study are included in the article/Supplementary material, further inquiries can be directed to the corresponding author.

Author contributions

Q-QZ: Formal analysis, Software, Resources, Investigation, Writing – review & editing, Conceptualization, Project administration, Methodology, Funding acquisition, Data curation, Writing – original draft. Z-CL: Writing – review & editing, Writing – original draft, Conceptualization, Methodology, Project administration, Resources, Formal analysis, Software, Funding acquisition, Data curation. Z-YH: Writing – original draft, Conceptualization, Software, Investigation, Resources, Methodology, Formal analysis, Project administration, Data curation. JT: Writing – original draft, Data curation, Resources, Conceptualization, Formal analysis, Project administration, Investigation, Methodology. PT: Validation, Visualization, Project administration, Writing – original draft, Software, Investigation. Q-RW: Investigation, Software, Visualization, Writing – original draft, Project administration, Validation. Z-QD: Methodology, Writing – original draft, Formal analysis. W-BM: Methodology, Writing – original draft. LL: Methodology, Writing – review & editing, Formal analysis, Project administration, Data curation, Conceptualization, Investigation, Software, Writing – original draft, Resources, Funding acquisition.

Funding

The author(s) declare that financial support was received for the research and/or publication of this article. This study was funded by the Chengdu University of Traditional Chinese Medicine University-Institute Joint Innovation Fund (Grant No. LH202402049) and Sichuan provincial project (Grant No. 2022YFS0401).

Conflict of interest

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.

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The authors declare that no Gen AI was used in the creation of this manuscript.

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Supplementary material

The Supplementary material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fpubh.2025.1677592/full#supplementary-material

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Keywords: acupuncture, Tourette syndrome, children, systematic review, meta-analysis

Citation: Zhou Q-Q, Li Z-C, Hu Z-Y, Tang J, Tang P, Wu Q-R, Deng Z-Q, Ma W-B and Lan L (2025) The effectiveness of acupuncture in the treatment of Tourette syndrome in Chinese children: a systematic review and meta-analysis. Front. Public Health. 13:1677592. doi: 10.3389/fpubh.2025.1677592

Received: 01 August 2025; Accepted: 17 September 2025;
Published: 02 October 2025.

Edited by:

Georg Johannes Seifert, Charité Universitätsmedizin Berlin - Charité Competence Center for Traditional and Integrative Medicine (CCCTIM), Germany

Reviewed by:

Valeria Sajin, Asklepios Klinik St. Georg, Germany
Paulo Sargento, Escola Superior de Saúde Ribeiro Sanches, Portugal
Ibrahim Serag, Mansoura University, Egypt

Copyright © 2025 Zhou, Li, Hu, Tang, Tang, Wu, Deng, Ma and Lan. 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.

*Correspondence: Lei Lan, bGFubGVpQGNkdXRjbS5lZHUuY29t

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