Effectiveness of electrical stimulation for treating male urinary incontinence after prostatectomy: a meta-analysis and systematic review

Abstract

Background:

Prostatectomy frequently leads to postoperative urinary incontinence (UI), significantly impairing patients’ quality of life. While pelvic floor muscle exercises (PFMEs) are commonly employed, the efficacy of electrical stimulation (ES) as a non-invasive adjunct remains debated. This systematic review and meta-analysis evaluated the effectiveness of ES combined with PFME versus PFME alone for post-radical prostatectomy UI.

Method:

A comprehensive search across PubMed, MEDLINE, EMBASE, Cochrane Library, and ResearchGate identified 10 randomized controlled trials meeting inclusion criteria. Outcomes included 24-hour pad test, International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF), quality of life (QOL), and incontinence control rate. Data were analyzed using Review Manager 5.4.1, employing fixed- and random-effects models.

Results:

Short-term ES (≤3 months) significantly improved ICIQ-SF scores (mean difference [MD] = −3.50; 95% confidence interval: −5.11 to −1.89, P <0.0001) and doubled incontinence control rates (risk ratio = 2.01; P = 0.01), though no improvement was observed in 24-hour pad test (MD = −50.07; P = 0.30) or QOL. Conversely, long-term ES (≥6 months) demonstrated marked reductions in urinary leakage via the 24-hour pad test (MD = −21.64; P = 0.02), but no significant differences in ICIQ-SF scores or control rates compared to PFME alone.

Conclusion:

Electrical stimulation therapy can be an effective treatment option for patients with post-RP UI. It can significantly improve UI symptoms in the short term and has a positive impact on reducing urinary leakage in the long term.

Introduction

Prostate cancer (PC) is one of the malignancies with a high incidence among men globally. Radical prostatectomy (RP) is a commonly used method for treating localized PC and is regarded as the “gold standard” for its treatment. However, postoperative urinary incontinence (UI) following RP is one of the major complications faced by patients, with incidence rates varying due to differences in definitions and assessment methods, generally ranging from 5% to over 40%^[1-3]. UI after RP primarily manifests as an early side effect, often commencing when the catheter is removed and being more severe within the first 6 months, significantly impacting patients’ health-related quality of life^[4]. The most common causes of UI after RP are urethral sphincter deficiency and bladder dysfunction. In clinical practice, non-invasive and non-surgical approaches are typically attempted first for the treatment of UI following RP.

HIGHLIGHTS

• Short-term ES + PFME doubles UI control, accelerating early recovery.

• Long-term ES reduces leakage, aids neuromuscular adaptation.

• ES bridges early PFME deficits through passive muscle activation.

• Non-invasive ES safely combines short-term relief and long-term functional recovery.

Pelvic floor muscle exercise (PFME) is a commonly employed method that improves urethral stability by strengthening the pelvic floor muscles, thereby alleviating UI symptoms^[5]. PFME can be self-managed or conducted under the guidance of a physical therapist; although it cannot cure UI, it can accelerate the recovery of continence. To assist patients in correctly contracting their pelvic floor muscles, specific biofeedback (BF) guidance programs can be used, providing visual, tactile, or auditory stimuli to guide the patients^[6]. Electrical stimulation (ES) therapy is another non-invasive treatment method that has garnered increasing attention in recent years. Functional pelvic floor electrical stimulation (PFES) artificially stimulates the pudendal nerve and its branches, eliciting direct and reflex responses in the urethral and periurethral striated muscles^[7]. PFES can be delivered through various methods and can be combined with other conservative therapies such as PFME and BF to enhance treatment efficacy. Studies have shown that PFES can significantly improve patients’ urinary control ability and reduce the occurrence of UI. Furthermore, ES therapy can be adapted to meet the needs of different patients through various stimulation modes, such as transcutaneous electrical nerve stimulation, percutaneous electrical nerve stimulation, anal electrical stimulation, and electromagnetic therapy, among others.

The effectiveness of PFME in treating female UI has been amply demonstrated in the literature. However, due to insufficient and low-quality evidence, the efficacy of conservative treatments, including PFME, BFB, and ES, for male UI following prostatectomy remains inconclusive^[8]. Several randomized clinical trials have evaluated the role of these non-invasive methods in the management of post-RP UI. Nevertheless, as stated in the Cochrane reviews and EAU guidelines, the data remain controversial, and the level of evidence is still uncertain^[3,9,10]. Therefore, we conducted a systematic review and meta-analysis specifically focusing on the role of non-invasive ES therapy in patients with post-RP UI.

Materials and methods

The meta-analysis was registered with PROSPERO and follows the guidelines outlined by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and assessing the methodological quality of systematic reviews (AMSTAR)^[11,12].

Search strategy

The three authors independently employed the PICOS strategy (population, intervention, comparison, outcome, and study design) to identify randomized controlled trials (RCTs) associated with non-invasive ES therapy for post-RP UI. The search was conducted in PubMed, MEDLINE, EMBASE, ResearchGate, and Cochrane Library databases. Figure 1 succinctly summarizes the search strategy. The search terms used were as follows: “After radical prostatectomy,” “Urinary incontinence,” “Electrical stimulation,” and “Randomized controlled trials.” Additionally, the authors meticulously reviewed the references of the retrieved articles to identify other relevant literature. It is important to note that the search was not limited by language or region, and duplicate studies were excluded.

Figure 1.

Flowchart of the study selection process.

Inclusion criteria

For consideration of inclusion in our study, RCTs must meet the following stringent criteria: (1) UI following RP, (2) patients in the experimental group received non-invasive ES therapy with or without PEMEs, while patients in the control group received only PEMEs, (3) comprehensive and accurate data must be provided, including participant sample size and results of each measurement, (4) the duration of treatment should be ≥2 months. It should be noted that compared with prospective and retrospective trials, RCTs have more rigorous requirements in terms of inclusion and exclusion.

Quality assessment

The Jadad scale and the Cochrane Risk of Bias assessment tool were employed to evaluate the quality of the selected RCTs^[13]. Our team devised a meticulous grading system to assess the excellence of each study based on the following criteria: (1) studies that fully met all quality standards and had the minimal risk of bias; (2) studies that met the majority of quality standards, albeit with a moderate level of bias; (3) studies that only partially met a few quality standards and were thus highly susceptible to bias. The entire author group reached a high degree of consensus on the adoption of this classification system.

Data extraction

Data extraction was conducted independently by each author, with disagreements resolved through consensus. Informed by relevant guidelines and literature, as well as the natural history of UI recovery following prostatectomy and the mechanisms of ES therapy, we stratified postoperative treatment into two phases: short term (≤3 months) and long term (≥6 months)^[14,15]. From each RCT, a variety of valuable information was extracted, including (1) the name of the first author; (2) the type of study; (3) the sample size of each group; (4) the mode of treatment; (5) the duration of treatment; (6) the study outcomes, encompassing the 24-hour Pad Test and International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF) for both short-term (≤3 months) and long-term (≥6 months) assessments, as well as quality of life and the incontinence control rate.

Statistical and meta-analysis

Statistical analyses were performed using Review Manager software (RevMan, version 5.4.1, Cochrane Collaboration). The efficacy of ES therapy for post-RP UI was evaluated based on the 24-hour pad test, ICIQ-SF, QOL, and incontinence control rate. We found varying ES patterns across studies. Subgroup analyses were done to compare the effects of percutaneous/perineal and transanal ES on urinary control rates and ICIQ-SF. Fixed and random-effects models were employed to assess these outcomes, with continuous data analyzed and interpreted using mean differences (MDs). For dichotomous outcomes, risk ratios (RRs) and 95% confidence intervals (CIs) were reported^[16]. Homogeneity was assumed when P >0.05. The fixed-effects model was used to investigate homogeneity, whereas the random-effects model was applied to examine heterogeneity. Additionally, the I² statistic was utilized to assess inconsistency, with a threshold of I² > 50% indicating the adoption of the random-effects model. Statistical significance was defined as P < 0.05.

Results

Characteristics of eligible studies

After applying the inclusion and exclusion criteria, a total of 438 academic publications were retrieved from the databases. Initially, we meticulously reviewed the titles and abstracts, resulting in the fair exclusion of 332 publications. Subsequently, 92 articles were discarded from the remaining pool due to lack of relevance. Finally, to ensure the integrity of the dataset, four inadvertently duplicated papers were removed. Ultimately, our study included 10 high-quality RCTs^[17–26]. The selection process is intuitively depicted in Figure 1, while Table 1 summarizes the study and patient characteristics.

Table 1.

Details of the Included studies

Study	Country	Design	Therapy in experimental group	Therapy in control group	Simple size		Follow-up (month)	ES scheme
					Trial	Control
Zhu et al. (2023)	China	RCT	Electrical stimulation	Anus lifting training therapy	27	28	3	position: transcutaneous; instrument: Foshan Shanshan Medical Technology Co., Ltd. BioStim Ble; frequency: 40 Hz; voltage: 10-15 V, treatment time: 30 min
Laurienzo et al. (2018)	Brazil	RCT	Electrical stimulation	Home exercise	42	41	6	position: transanal; instrument: Dualpex Uro 961, Quark® (Reg istration at Anvisa number 80079190018); frequency: 35 Hz; pulse width: 1 ms; rise time: 2 s; stimulus duration: 6 s; fall time: 2 s; standing time: 12 s
Yang et al. (2010)	China	RCT	Electrical stimulation + pelvic floor muscle therapy	Pelvic floor muscle therapy	40	69	6	position: transcutaneous; instrument: Shanghai Huayi Medical Instrument Co., Ltd. G6805; frequency: 2.5 Hz; voltage: 10 V; treatment time: 60 min
Yıldız et al. (2022)	Turkey	RCT	Electrical stimulation	Sham electrical stimulation	29	29	2	position: perineal; instrument: Enraf Nonius Myomed 632; frequency: 50 Hz; pulse width: 300 µs; maximum output: 100 mA; standing time: 10 s
Yamanishi et al. (2007)	Japan	RCT	Electrical stimulation	Sham electrical stimulation	26	30	12	position: transanal; instrument: unknown; frequency: 50 Hz; pulse width: 300 µs; maximum output: 70 mA; standing time: 5 s
Yokoyama et al. (2004)	Japan	RCT	Electrical stimulation	Pelvic floor muscle exercise	12	12	6	position: transanal; instrument: unknown; frequency: 20 Hz; pulse width: 300 µs; maximum output: 24 mA; treatment time: 30 min
Wille et al. (2003)	Germany	RCT	Electrical stimulation + pelvic muscle exercise	Pelvic muscle exercise	46	47	12	position: transanal; instrument: Haynl Elektronik, Schonebeck, Germany; frequency: 27 Hz; burst: 1 s; pulse train: 2 s; pulse width: 5 s; maximum output: 24 mA; treatment time: 15 min
Mariotti et al. (2009)	Italy	RCT	Electrical stimulation + biofeedback	Pelvic floor muscle exercise	30	30	6	position: transanal; instrument: InCare™; frequency: 30-50 Hz; pulse width: 300 µs; maximum output: 24 mA; treatment time: 20 min
Tang et al. (2024)	China	RCT	Electrical stimulation	Pelvic floor muscle training	40	40	2	position: transcutaneous; instrument: unknown; frequency: 20 Hz; maximum output: 5 mA; treatment time: 20 min
Moore et al. (1999)	Canada	RCT	Electrical stimulation + pelvic muscle exercise	Pelvic muscle exercise	19	18	6	position: transanal; instrument: InCare™; frequency: 50 Hz; burst: 1 s; pulse train: 1 s; pulse width: 1 s; treatment time: 30 min

The quality of eligible studies

All studies included in the analysis were RCTs, among which two were high-quality, randomized, double-blind controlled trials (Grade A). Eight RCTs were rated as Grade B. Two studies failed to complete the entire follow-up period, with a total of 10 patients lost to follow-up. Bias was observed in these articles, primarily attributable to the differences in the methods of ES employed and the varying durations of follow-up. The quality assessment of all studies is presented in Table 2. Funnel plot analysis to evaluate the publication bias of articles on the short-term efficacy (Fig. 2A) and long-term efficacy (Fig. 2B) of ES in the treatment of UI after RP.

Table 2.

Quality assessment of individual study

Study	Allocation sequence generation	Allocation concealment	Blinding	Loss to follow-up	Calculation of sample size	Statistical analysis	Level of quality
Zhu et al. (2023)	A	A	B	0	Yes	ANCOVA	B
Laurienzo et al. (2018)	A	A	A	0	Yes	ANCOVA	A
Yang et al. (2010)	A	A	B	0	Yes	ANCOVA	B
Yıldız et al. (2022)	A	A	B	1	Yes	ANCOVA	B
Yamanishi et al. (2007)	A	A	A	9	Yes	ANCOVA	A
Yokoyama et al. (2004)	A	A	B	0	Yes	ANCOVA	B
Wille et al. (2003)	A	A	B	0	Yes	ANCOVA	B
Mariotti et al. (2009)	A	A	B	0	Yes	ANCOVA	B
Tang et al. (2024)	A	A	B	0	Yes	ANCOVA	B
Moore et al. (1999)	A	A	B	0	Yes	ANCOVA	B

A, all quality criteria met (adequate): low risk of bias; B, most quality criteria met (adequate): moderate risk of bias; ANCOVA, analysis of covariance.

Figure 2.

Funnel plot analysis showed publication bias of the articles.

Efficacy

24-hour pad test

We analyzed 234 patients from five RCTs and reported the efficacy of short-term ES therapy for post-RP UI using a random-effects model (Fig. 3A). In the assessment of the 24-hour pad test, no significant differences in therapeutic effects were observed between the two groups (MD = −50.07; 95% CI: −145.46 to 45.33, P = 0.30). Subsequently, we further analyzed the therapeutic responses of 177 patients from four RCTs after long-term ES therapy (Fig. 4A). Using a fixed-effects model, a significant improvement in the 24-hour pad test was observed following long-term ES (MD = −21.64; 95% CI: −40.03 to −3.25, P = 0.02). This finding confirms that long-term ES therapy may contribute to reducing urinary leakage in patients. It is evident that ES holds certain advantages in the long-term management of post-RP UI.

Figure 3.

Forest plot comparison of changes in (A) 24-hour pad test, (B) ICIQ-SF, (C) QOL, and (D) incontinence control rate between the control group and the electrical stimulation group after short-term treatment.

Figure 4.

Forest plot comparison of changes in (A) 24-hour pad test, (B) ICIQ-SF, and (C) incontinence control rate between the control group and the electrical stimulation group after long-term treatment.

International consultation on incontinence questionnaire-short form

Five RCTs reported changes in ICIQ-SF scores among 383 patients following short-term ES therapy (Fig. 3B). Analysis using a random-effects model revealed a significant difference in ICIQ-SF scores between the ES group and the control group (MD = −3.50; 95% CI: −5.11 to −1.89, P <0.0001), with patients receiving ES therapy demonstrating marked improvement in ICIQ-SF scores compared to those in the control group. In the long-term analysis involving 248 patients from three RCTs (Fig. 4B), no significant difference in ICIQ-SF scores was observed between the groups (MD = −0.74; 95% CI: −2.81 to 1.34, P = 0.49). The analysis of ICIQ-SF scores suggests that ES therapy may accelerate the recovery of post-RP UI. However, as demonstrated in Figure 5A, no statistically significant differences were observed between stimulation sites (percutaneous/perineal vs. transanal) in terms of urinary control rates and ICIQ-SF impact (test for subgroup differences, P = 0.66).

Figure 5.

Forest plots comparing subgroups with different stimulation modes (percutaneous/perineal and transanal) after short-term treatment for (A) ICIQ-SF and (B) urinary incontinence control rate.

Incontinence control rate

We analyzed 320 patients from four RCTs to assess the effectiveness of short-term ES therapy on the control rate of UI. Given that P<0.05, we adopted a random-effects model (RR 2.01; 95% CI, 1.17-3.44; P = 0.01, I² = 81%). The results indicated that short-term application of ES significantly controlled UI (Fig. 3D). Meanwhile, an evaluation of the efficacy of long-term ES therapy in 262 patients from three RCTs showed no statistically significant difference in the control rate between the two treatment cohorts (Fig. 4C) (RR 1.15; 95% CI, 0.79–1.68; P = 0.47, I² = 94%). Electrical stimulation therapy may be beneficial for accelerating the recovery of incontinence control. Moreover, as shown in Fig 5B, our results suggest that the recovery of postoperative short-term UI may be associated with the ES modality (test for subgroup differences, P = 0.009).

Short-term treatment quality of life survey

Three RCTs reported the quality of life assessments for 136 patients after short-term ES therapy (Fig. 3C). Analysis using a random-effects model showed no significant difference in QOL scores between the ES group and the control group (SMD = 0.28; 95% CI: −0.57 to 1.14, P = 0.52).

Discussion

ES therapy for post-RP UI has garnered considerable attention in recent years and is widely applied clinically, boasting an exceptionally high safety profile. The EAU guidelines suggest that ES may lead to an increase in incontinence improvement in the short term, yet there exists contradictory evidence^[3]. In our meta-analysis, we analyzed studies that exclusively included ES protocols for the treatment of post-RP UI, aiming to determine whether the use of ES could enhance the outcomes achieved by the control group or PFME alone in both short-term and long-term treatment.

The mechanisms underlying ES therapy for post-RP UI may involve multi-pathway regulation. ES can activate the pudendal nerve and pelvic floor motor neurons, promoting neural reinnervation of the damaged sphincter and improving muscle contractility^[5]. Additionally, ES can inhibit detrusor overactivity, enhance bladder capacity perception, and alleviate urgency UI^[27]. ES can also increase blood flow perfusion in the pelvic floor region, reduce postoperative inflammatory edema, and accelerate tissue repair^[28]. Moreover, ES therapy has significant advantages. First, it has a high safety profile, with no severe adverse reactions reported in the included studies, and good patient tolerability, especially suitable for elderly patients or those with multiple comorbidities. Second, the therapeutic efficacy is remarkable, especially in the early intervention group, where the complete resolution rate of UI at 3 months post-surgery is significantly higher than that of the control group. Furthermore, ES has the potential for combined treatment, as ES combined with PFME, behavioral therapy, or medications (such as anticholinergic drugs) can have a synergistic effect^[29,30].

Our analysis revealed a striking divergence between short-term (≤3 months) and long-term (≥6 months) outcomes. In the 24-hour pad test, short-term ES failed to demonstrate significant reductions in urinary leakage (MD = −50.07; P = 0.30), whereas long-term ES yielded statistically and clinically meaningful improvements (MD = −21.64; P = 0.02). This temporal pattern aligns with the neurophysiological principles underlying ES^[19]. Electrical stimulation enhances urethral sphincter function by activating pudendal nerve pathways, a process requiring sustained neuromuscular adaptation^[7,10]. The delayed efficacy suggests that ES acts not merely as a compensatory intervention but as a modulator of long-term neural plasticity. Clinically, this underscores the necessity of advocating for extended ES regimens (≥6 months) to maximize therapeutic benefits.

Conversely, short-term ES exhibited robust effects on subjective outcomes. The ICIQ-SF scores improved significantly within 3 months (MD = −3.50; P < 0.0001), paralleled by a doubling of incontinence control rates (RR = 2.01; P = 0.01). These results imply that ES may accelerate early-phase recovery by enhancing patients’ perception of control and reducing psychosocial distress, even before objective measures (e.g., pad weight) normalize^[5,31]. This dichotomy between subjective and objective outcomes highlights the multidimensional nature of UI recovery, where psychological and functional improvements may progress asynchronously. Early intervention with ES initiated within 7–14 days post-catheter removal may accelerate short-term urinary continence recovery by leveraging neuromuscular plasticity during the critical postoperative healing phase, promoting sphincter reinnervation and reducing inflammatory edema^[32,33]. Notably, studies indicate that when ES combined with BF is promptly administered after catheter removal, it results in significantly improved urinary continence rates at 4 weeks (63.3% vs. 30.0%) and 6 months (96.7% vs. 66.7%) postoperatively^[22].

The included RCTs compared ES combined with PFME against PFME alone. Our pooled data indicate that ES confers additive benefits, particularly in accelerating short-term continence recovery. Mechanistically, PFME relies on voluntary muscle contraction, which may be suboptimal in patients with postoperative neuromuscular dysfunction^[34]. ES complements PFME by providing passive muscle activation, thereby “bridging” the gap until voluntary control is restored^[34,35]. This synergy is evident in the short-term incontinence control rates, where ES + PFME outperformed PFME monotherapy. However, the lack of long-term differences in ICIQ-SF scores (P = 0.49) and incontinence control rates (P = 0.47) suggests that PFME alone may suffice for sustained recovery once neuromuscular pathways are re-established. These findings resonate with the EAU guidelines, which advocate PFME as first-line therapy while reserving ES for patients with delayed or incomplete recovery^[3].

Despite improvements in objective and subjective UI metrics, short-term ES did not enhance QOL scores (SMD = 0.28; P = 0.52). This paradox may stem from methodological and contextual factors. First, QOL instruments such as the ICIQ-LUTSqol often emphasize physical symptoms over psychosocial domains, potentially underestimating the impact of ES on emotional well-being^[36,37]. Second, the transient nature of early UI improvements may be insufficient to override broader postoperative stressors (e.g., sexual dysfunction and fatigue)^[38]. Future trials should incorporate multidimensional QOL assessments, including patient-specific goal attainment scales, to better capture the holistic benefits of ES.

The therapeutic efficacy of ES in managing post-RP UI appears to be mediated through dual mechanisms involving both peripheral neuromuscular activation and central nervous system adaptation. First, ES delivers rhythmic electrical impulses to the pudendal nerve network, eliciting synchronized contractions of the external urethral sphincter and pelvic floor musculature that compensate for postoperative sphincteric deficiency by augmenting urethral closure pressure^[39]. Concurrently, preclinical evidence reveals that repetitive ES induces neuroplastic reorganization within the central nervous system, characterized by increased cortical representation of pelvic floor structures in sensorimotor networks^[40,41]. This Hebbian plasticity-driven cortical remodeling may facilitate the restoration of voluntary urinary control, potentially explaining the sustained clinical improvements observed during long-term follow-up despite the transient nature of direct electrical activation^[42,43].

Electrical stimulation therapy may exert potential effects on erectile dysfunction (ED) and other complications following RP. Electrical stimulation, by enhancing pelvic floor muscle strength, improving local blood circulation, and modulating neural feedback, is theoretically capable of indirectly supporting the recovery of erectile function. Pelvic floor muscle training (combined with ES) has been deemed effective in improving ED in some studies, yet it should be integrated with nerve-sparing surgery and postoperative rehabilitation programs^[44]. If the parameters of ES (such as intensity and frequency) are improperly set, muscle fatigue or temporary neural inhibition may occur, although there is no evidence to suggest that it would directly exacerbate ED. Moreover, postoperative penile shortening may be associated with scar contracture or changes in the structure of the corpora cavernosa. Electrical stimulation, by promoting tissue blood flow and reducing scar adhesion, may help maintain penile length, but this hypothesis lacks clinical data support.

Notably, the heterogeneity in ES modalities across studies complicates mechanistic interpretations. For instance, anal electrode-based ES targets the pudendal nerve more directly than transcutaneous approaches, potentially yielding stronger effects^[10,45]. In our research, ES parameters like frequency and pulse width were analyzed for their effects, which turned out to be insignificant. Most parameters were similar across trials, with 10–50 Hz commonly used in RCTs to balance efficacy and patient tolerance. However, subgroup analyses were precluded by insufficient data, urging future trials to standardize stimulation parameters (frequency, intensity, electrode placement) for cross-study comparability. Asymmetry of the funnel plot suggests the presence of small-study effects. However, sensitivity analyses confirmed the stability of the conclusions. Future research should prioritize the development of standardized protocols and rigorous reporting to minimize the risk of bias. While this meta-analysis adheres to rigorous methodology, several limitations merit discussion: The exclusion of grey literature may introduce selection bias to the published results. Variability in stimulation parameters and delivery methods introduced substantial heterogeneity. This precludes definitive conclusions about optimal ES regimens. Furthermore, only two RCTs provided data beyond the 12-month follow-up period, constraining the evaluation of the long-term durability of ES effects. Additionally, despite a comprehensive literature search, the exclusion of conference abstracts may have introduced a potential bias toward positive outcomes in the synthesized evidence base. While ES demonstrates clinically meaningful benefits, practitioners should tailor parameters to individual patient characteristics and recovery trajectories, given the heterogeneity in optimal stimulation protocols identified across studies.

Conclusion

In conclusion, this systematic review and meta-analysis provides evidence that non-invasive ES therapy can be an effective treatment option for patients with post-RP UI. It can significantly improve UI symptoms in the short term and has a positive impact on reducing urinary leakage in the long term.

Ethical approval

Not applicable.

Consent

Not applicable.

Funding

This work was supported by grants from the National Natural Science Foundation of China (No. 81972376), Natural Science Foundation of Shandong Province (No. ZR2024MH001) and the Taishan Scholars Program of Shandong Province (No. tsqn202211379).

Author contributions

G.T., X.C., and M.L.: designing the study; analyzing the extracted data; writing the first manuscript draft. G.T., C.L., and J.Z.: performing the investigation and analyzing data. H.Z.: analyzing the data; reviewing the manuscript; providing critical scientific input. All authors approved the final version of this manuscript.

Conflicts of interest disclosure

The authors declare that they have no conflict of interest.

Guarantor

Gonglin Tang, Xin Chen, and Hongwei Zhao.

Research registration unique identifying number (UIN)

PROSPERO (CRD420251013790).

Provenance and peer-review

Not commissioned, externally peer-reviewed.

Data availability statement

Supplementary digital content, available at: http://links.lww.com/JS9/E538.