Study Protocol: Protocol of Intensive Care Unit Graded Mobilization (PG‐Motion) Study: A Randomized Clinical Trial

ABSTRACT

Background and Aims

Intensive care unit‐acquired weakness (ICU‐AW) is a frequent complication among critically ill patients. Although early mobilization (EM) has been shown to improve clinical outcomes, its implementation remains limited in many settings due to staffing shortages, safety concerns, and the absence of standardized protocols. In China, the uptake of EM is particularly low, partly due to the lack of dedicated rehabilitation staff in intensive care units (ICUs) and the absence of protocols suited to local staffing structures. This multicentre randomized controlled trial (PG‐Motion Study) aims to develop and evaluate a nurse‐led EM protocol tailored to the Chinese ICU context, with a focus on assessing its clinical effectiveness.

Methods

We adopted a parallel‐group randomized controlled design across 18 Grade III hospitals (China's highest‐tier medical institutions) in Beijing. Eligible patients will be individually randomized (1:1) to receive either the PG‐Motion‐guided EM protocol or routine standard care. The primary effectiveness outcomes included the incidence of ICU‐AW, defined by a Medical Research Council (MRC) sum score < 48, duration of mechanical ventilation, and ICU length of stay. Implementation fidelity will be assessed via protocol adherence. Safety monitoring will include adverse events such as falls, hemodynamic instability, and unplanned extubation. This study has been registered with the China Clinical Trial Registry (ChiCTR2000039425).

Results

Implementation of the PG‐Motion protocol is expected to establish an evidence‐based graded mobilization framework tailored to the ICU staffing conditions in China. The findings may contribute to national expert consensus and promote standardized EM practices for ICU‐AW prevention.

Conclusion

The PG‐Motion study will generate clinical and operational evidence to support a scalable nurse‐led EM protocol, potentially enhancing early rehabilitation practices in resource‐constrained ICU settings.

Trial Registration: China Clinical Trial Registry (ChiCTR2000039425).

Abbreviations

DBP

diastolic blood pressure

EM

early mobilization

HR

heart rate

ICU

intensive care unit

IMS

ICU Mobility Scale

MAP

mean arterial pressure

MRC

Medical Research Council

MV

mechanical ventilation

PG‐Motion

Protocol of ICU Graded Mobilization

PI

principal investigator

PT

physiotherapists

RR

respiratory rate

SBP

systolic blood pressure

1. Introduction

Intensive care unit‐acquired weakness (ICU‐AW) is a syndrome characterized by generalized limb and respiratory muscle weakness that develops during critical illness in the intensive care unit (ICU). It is unrelated to pre‐existing neuromuscular disorders and constitutes a common complication among critically ill patients, significantly influencing clinical outcomes.

Early Mobilization (EM) refers to a structured, multidisciplinary intervention initiated within the first 24–72 h of critical illness or ICU admission. Its aim is to reduce complications through progressive physical activities [1, 2]. Previous studies have confirmed that early physical exercises can shorten the duration of mechanical ventilation (MV) and improve functional outcomes at discharge [3, 4, 5, 6, 7, 8, 9]. However, the implementation of EM in clinical practice remains challenging due to numerous obstacles [10, 11].

Surveys conducted in various countries have indicated that the uptake of EM remains relatively low in many countries [12, 13]. For instance, a prevalence study in Switzerland found that only 33% of mechanically ventilated ICU patients received active mobilization [14], which is consistent with other studies [11, 15, 16, 17, 18]. Similarly, a national survey in China revealed that only 19% of ICUs had comprehensively or fully implemented EM protocols. Barriers to implementation included sedative use, the presence of therapeutic devices, hemodynamic or respiratory instability, limited resources, and concerns regarding clinician safety [19, 20]. Furthermore, the lack of standardized implementation guidelines significantly hampers the routine integration of EM into clinical care. Critical elements such as the mode of delivery, intervention types, frequency, duration, and intensity require further investigation [21, 22].

In an effort to facilitate EM implementation, researchers have proposed decision‐support tools [23] and a traffic light system [24]. Additionally, the development of standardized protocols has been advocated [3, 25, 26], some of which incorporate frameworks like the ICU Mobility Scale (IMS) [27, 28] and PROtocol‐based MObilizaTION [29]. However, variations in healthcare infrastructure and national conditions have limited the dissemination and adoption of these protocols. Recent surveys report that only 20%–30% of ICUs in countries, such as France, Germany, and the United Kingdom, have implemented formal EM protocols [25], while in Asian countries like Japan and China, the proportion is even lower just 16%–20% [13, 30]. This lack of standardized is a key factor contributing to the low clinical uptake of EM and is associated with an increased risk of adverse events [31].

To ensure safety during EM, a team‐based approach involving physicians, physical therapists, respiratory therapists, nurses, and nutritionists is generally recommended [12, 32]. However, the allocation of healthcare professional in Chinese ICUs differs markedly from that of high‐income countries, with many units lacking dedicated rehabilitation and respiratory therapists. This presents a major obstacle to designing and executing individualized EM programs for all ICU patients. Consequently, there is an urgent need for a simple, feasible EM protocol that can be initiated by clinical nurses and physician under the guidance of rehabilitation specialists.

In clinical practice, we have observed that in addition to basic postural adjustments, commonly used rehabilitation interventions—such as diaphragm training, limb exercises, and out‐of‐bed activities—can be complementary and broadly applicable across different stages of ICU patient rehabilitation. To enhance both the feasibility and efficacy of EM, we selected low‐risk, easily implementable interventions from these methods to develop a structured EM protocol named PG‐Motion. This protocol is a clinical protocol primarily led by ICU nurses and supported by guidance from ICU physicians and physical therapists. This model may be particularly suited to resource‐limited setting, where access to specialized physical therapy is constrained.

To evaluate the effectiveness and feasibility of PG‐Motion, we will conduct a parallel, multicentre randomized controlled trial (RCT) across 18 tertiary hospitals in Beijing, China. This will be the first large‐Scale, RCT of its kind focusing on EM in ICU patients within China. We anticipate that this study will strengthen the role of ICU nurses in rehabilitation efforts and offer valuable insights into enhancing EM implementation in settings with limited resources.

The specific aims of this study are:

• 1.To develop a comprehensive EM protocol for ICU Graded Mobilization (PG‐Motion), led by ICU nurses.
• 2.To evaluate the clinical effectiveness and feasibility of the PG‐Motion protocol.

2. Methods

2.1. Compilation and Revising PG‐Motion

We have developed the PG‐Motion protocol through a multiphase process that integrates evidence synthesis and expert consultation [33]. The initial framework was constructed based on our research team's systematic analysis of implementation barriers (e.g., staffing constraints, patient acuity), facilitating factors (e.g., multidisciplinary collaboration), and existing EM practices. The protocol incorporates graded exercise recommendations stratified according to patients' functional capacity levels, and has been contextually adapted to address institution‐specific limitation within Grade III hospitals in China (i.e., tertiary referral centers with resource profiles comparable to those of academic medical centers in the United States). Particular consideration has been given to critical care staffing models and the prevalent characteristics of ICU patients in these settings.

To ensure both clinical validity and practicality, we employed a modified Delphi method involving 28 senior intensive care specialists—including physicians, nurses, and rehabilitation therapists—all holding positions at or above the level of associate professor‐level positions. The consensus‐building process comprised two rounds of structured panel discussions, followed by iterative consultations via email, with protocol revisions informed by quantitative analysis of panel feedback (response rate: 93%). The coefficients of variation for both importance and feasibility of all items were < 0.25.

The finalized PG‐Motion protocol consists of three core components: (1) Initiation criteria and discontinuation thresholds for EM [34] (Table 1); (2) A graded EM level framework (Table 2), which employs standardized functional assessment tools (e.g., muscle strength grading, cognitive status evaluation) to categorize patients into five distinct mobility‐readiness tiers; and (3) Recommended activity protocols stratified by EM levels (Figure 1), detailing evidence‐based therapeutic exercises tailored to each patient's assessed functional tiers.

Table 1.

Initiation criteria and discontinuation thresholds for EM.

Assessment item	Indications for initiation	Indications for suspension
Cardiovascular system	HR 40~120 bpm, with no significant fluctuations SBP 90~180 mmHg, or DBP ≤ 110 mmHg, or MAP 65~110 mmHg BP variability < 20% No increase in the dosage of drugs within 2 h Dopamine ≤ 10 μg/kg/min Norepinephrine/adrenaline < 0.1 μg/kg/min No hemodynamically disruptive arrhythmias No evidence of new or untreated myocardial ischemia	HR < 40 or > 130 bpm HR > 70% of age‐predicted maximum or > 20% decrease from baseline resting HR New‐onset arrhythmias SBP > 180 mmHg or < 90 mmHg BP change > 30% from baseline MAP > 100 mmHg or < 60 mmHg New initiation or dose escalation of vasoactive drugs New‐onset signs of active bleeding
Respiratory system	RR 10~25 breaths/min SpO2 ≥ 90% For patients on Mechanical ventilation: FiO2 ≤ 60%; PEEP ≤ 10 cmH2O	RR < 5 or > 35 breaths/min SpO2 < 88% FiO2 ≥ 60% PEEP ≥ 10 cmH2O Dyspnea Persistent patient‐ventilator asynchrony despite parameter adjustments
Body temperature	Temperature ≤ 38°C No ongoing therapeutic hypothermia
Neurological system	No significant agitation or emotional instability or RASS score ≤ 1 No delirium symptoms	RASS score ≥ 2 or significant agitation New‐onset delirium Decreased level of consciousness (e.g., drop in GCS score)
Subjective symptoms	VAS pain score ≤ 3 No extreme weakness	Intolerable pain or signs of distress Severe weakness
Others	Nonterminal status with overall clinical stability Absence of any new or uncontrolled contraindications (e.g., suspected or confirmed deep vein thrombosis, active bleeding, acute coronary syndrome, acute myocarditis or pericarditis, acute heart failure, unstable arrhythmias, pseudoaneurysm or aortic dissection, unstable fractures or spinal injuries, acute cerebrovascular events, neurological deterioration, raised intracranial pressure [≥ 20 cmH2O or requiring dynamic monitoring/ventricular drainage], seizures activity, etc.)	Pallor/cyanosis Subjective complaints of discomfort of dizziness Refusal to continue mobilization Any adverse events (e.g., falls, accidental removal of tubes, lines, or catheters) Any situation deemed unsafe by clinical team

Abbreviations: BP, blood pressure; DBP, diastolic blood pressure; HR, heart rate; MAP, mean arterial pressure; RASS, Richmond Agitation Sedation Scale; RRl, respiratory rate; SBP, systolic blood pressure; VAS, Visual Analog Scale.

Table 2.

Choose the appropriate comprehensive EM level.

EM level	Consciousness GCS/RASS/S5Q	MRC Muscle Scale
EM level Ⅰ	GCS < 9 or −5 < RASS < −1 or S5Q < 3	—
	9 ≤ GCS ≤ 15 or −1 ≤ RASS ≤ 1 or S5Q ≥ 3	Grade 0~1
EM level Ⅱ	9 ≤ GCS ≤ 15 or −1 ≤ RASS ≤ 1 or S5Q ≥ 3	Grade 2
EM level Ⅲ	9 ≤ GCS ≤ 15 or −1 ≤ RASS ≤ 1 or S5Q ≥ 3	Grade 3
EM level Ⅳ	9 ≤ GCS ≤ 14 or RASS = −1 or 3 ≤ S5Q ≤ 4	≥ Grade 4
EM level Ⅴ	GCS = 15 or 0 ≤ RASS ≤ 1 or S5Q = 5	≥ Grade 4

Note: According to the consciousness and MRC Muscle scale of patients, choose the EM level. For patients who do not use sedatives, their ability to cooperate is judged by Glasgow Coma Scale (GCS) or Standardized Five Questions (S5Q) evaluating the consciousness of patients; for patients who use sedatives, the patient's ability to cooperate is evaluated through the Richmond Agitation Sedation Scale (RASS).Colors in the table indicate different training levels, consistent with the training level colors in Figure 1.

Figure 1.

Exercise items of EM in different levels (each item will be performed one or twice a day).

2.2. Feasibility Verification

Prior to initiating the multicenter RCT, a pilot study was conducted at a single center. This preliminary study enrolled 50 eligible patients who met the inclusion criteria for PG‐Motion. In accordance with the PG‐Motion protocol, these patients underwent a stepwise implementation of EM. The results showed that a compliance rate of 75% for EM among patients, with no mobilization‐related adverse events reported [33].

2.3. Study Design and Ethics

PG‐Motion is a parallel‐group, block RCT conducted across multiple centers. Participants will be followed from the day of ICU admission until the day prior to ICU discharge or 30 days after ICU admission or the day of death—whichever occurs first. The study has been registered in the China Clinical Trial Registry (ChiCTR2000039425) and approved by the Ethics Committee of General People's Liberation Army Hospital (S2021–643‐02). This protocol is reported in accordance with the SPIRIT Statement (www.spirit-statement.org) [35].

2.4. Setting and Recruitment

Participating clusters were recruited ICUs via formal letter inquiries. Following a call for participation, comprehensive ICUs from 18 Grade III hospitals in Beijing, China, were included. The inclusion criteria were as follows: (a) adult patients, and (b) the absence of an existing comprehensive protocol for EM.

2.4.1. Randomization and Masking

To address potential baseline bias arising from variations in patient characteristics across ICUs, a block randomization approach was implemented. Eligible patients in each participating ICU were randomly allocated to either the control or intervention groups in a 1:1 ratio, based on anticipated enrollment capacity derived from historical ICU admission data.

A dedicated research coordinator will generate a computer‐based randomization sequence for each ICU using http://www.randomizer.org, thereby ensuring allocation concealment. The randomization list will be sealed in opaque envelopes and securely stored by ICU head nurses. Patients will be enrolled consecutively and assigned to either group according to the pre‐generated sequence.

2.4.2. Intervention and Blinding

Patients in the controlled group will receive routine care in accordance with existing ICU treatment and nursing protocols. In addition to standard care, patients in intervention group will receive EM based on the PG‐Motion protocol. Due to the nature of the intervention, blinding of ICU clinicians is not feasible; thus, physicians and nurses will be aware of the patient's group allocation. However, patients will not be informed of their group assignment. Outcome assessors will be blinded to group allocation, with primary outcomes evaluated by trained study staff who remain unaware of the patient's group. The PG‐Motion protocol will be introduced to physicians, rehabilitation therapist, and nurses. And implement procedures will be delivered through on‐site training by the principal investigator (PI). All personnel involved in delivering the intervention must pass an assessment prior to patient enrollment.

2.5. Participants

2.5.1. Sample Size

The study will include a total of 1140 patients who are admitted to the ICU and meet the inclusion criteria. Based on previous research [36, 37], the expected incidence of ICU‐AW ranges from 25% to 75%. Taking the median value, we assume an incidence of 40% in the control group. A 10% absolute reduction in incidence is expected with implementation of the PG‐Motion protocol.

With a significance level of α = 0.05 and a power of 1 − β = 0.90, a sample size of 472 patients per group is required. Allowing for an estimated 20% loss to follow‐up, we plan to enroll 570 participants in each group, resulting in a total target sample size of 1140 patients.

2.5.2. Inclusion/Exclusion Criteria

All ICU patients present during the screening day will be assessed for eligibility.

The inclusion criteria are as follows: (a) age between 18 and 85 years inclusive; (b) an expected ICU stay of at least 48 h; (c) admission to the ICU Within the past 24 h and an APACH Ⅱ score ≥ 17.

Patients will be excluded if they: (a) have a pre‐existing central nervous system disorder or neuromuscular disease; (b) are functionally dependent at baseline, defined as a Barthel Index Score < 45 1 week prior to ICU admission, based on patient or proxy‐reported responses [38, 39].

2.5.3. Informed Consent

Eligible patients and/or their legal proxies will be fully informed about the study objective, procedures, and associated risks. Written informed consent will be obtained from patients or their proxies within 24 h of ICU admission.

2.6. Procedures and Measures

Within 24 h of ICU admission, eligible patients will be entered into our screening log. Following the provision of informed consent, relevant medical information and outcome indicators will be recorded in a Case Report Form (CRF) until the day prior to ICU discharge. For patients who prolonged ICU stay, data collection will be terminated on Day 30 of ICU admission (Figure 2). If a patient remains in the ICU for < 48 h, no identifiable information will be retained.

Figure 2.

Time schedule of enrollment, interventions, and outcome measures based on SPIRIT 2013 reporting guidelines. *The indicators of implementation need to be recorded every day.

All participating units will implement the standard ICU management protocols of Beijing, which include: daily neurological assessments, screening for delirium and pain intensity, and evaluation for early enteral feeding. For patients receiving mechanical ventilation, standard care also includes goal‐directed sedation with daily awakening trials and spontaneous breathing trials. Decisions regarding weaning from mechanical ventilation and extubation will be made by the treating physician, in accordance with the Beijing institutional protocols.

ICU medical directors will assess daily which patients are eligible for discharge, based on the following criteria: stable vital signs; no requirement for vasoactive drug; stable gas exchange (i.e., oxygen therapy delivered via nasal cannula only); and adequate pain control [40]. The intervention group will receive the same standards of care as the control group—defined by Beijing institutional protocols—with the exception of the PG‐Motion intervention.

All data from participating centers will be coded and stored in a centralized data management system developed by the Clinical Research Institute of Beijing University. A Data Safety Monitoring Board has been convened at the Clinical Research Institute of Beijing University to review adverse events and oversee trial safety monitoring.

2.6.1. Primary Outcome Measures

To assess the effect of PG‐Motion on ICU‐AW incidence, trained study personnel will use the Medical Research Council (MRC) sum score [41] to evaluate global muscle strength. Assessments will be conducted every day and the day prior to ICU discharge. An MRC sum score of < 48 will be used to define ICU‐AW. The final analysis will report the incidence of ICU‐AW in both the intervention and control groups.

2.6.2. Secondary Outcome Measures

Clinical and demographic data will be collected from the medical and nursing records, including: sex, age, diagnosis, weight, body mass index, comorbidity, APACHE II score, duration of mechanical ventilation, ICU length of stay, treatment outcome, and daily mobility types and durations.

Trained study personnel will also assess limb muscle circumference, range of motion of joints, and IMS. Diaphragm thickness and excursion will be measured using ultrasound.

To evaluate the safety of PG‐Motion, ICU nurses will document adverse events in the DRF, including falls, cardiac arrest, arrhythmia, oxygen saturation < 80% for more than 3 min, unplanned extubation, and other relevant events.

To evaluate the feasibility of PG‐Motion, ICU nurses will record the daily implementation rate of each patient's EM plan in the DRF.

2.6.3. Quality Control

Prior to patient recruitment, ICU nurses from all 18 participating hospitals will undergo training on the standardized completion of DRFs. Each ICU will be staffed with full‐time research personnel to ensure consistent data collection procedures and adherence to uniform research protocols across all sites.

In addition to the general protocol training, research staff will also receive specific instruction on the measurement of the MRC sum score, IMS, limb muscle circumference, and diaphragm thickness and excursion.

An electronic data management system has been developed by the Clinical Research Institute of Beijing University to facilitate data collection and management. This system is designed to enhance data accuracy and consistency. During the data collection period, only designated project managers will have access to the system. The project management team will conduct regular meetings and audit of the study database to monitor data integrity and protocol compliance.

2.7. Data Analysis

All statistical analyses will be conducted using SAS software version 9.4. Continuous data will be summarized by reporting the number of non‐missing values, mean, standard deviation, minimum, median, and maximum. For normally distributed continuous variables, intergroup comparisons will be performed using the independent samples t‐test. For non‐normally distributed data, the Wilcoxon rank‐sum test will be employed. Categorical data will be summarized using frequencies and percentages, based on the number of non‐missing observations. Between‐group comparisons will be conducted using the χ ² test or Fisher's exact test, as appropriate. Kaplan–Meier survival analysis will be used to plot KM curves for the incidence of ICU‐AW. The Log‐rank test will be applied to assess overall differences between groups. All statistical tests will be two‐sided, with a significance level set at p < 0.05.

3. Results

3.1. PG‐Motion Draft

The PG‐Motion draft sets out clear operational standards for initiation, temporary suspension, grading, and dynamic adjustment of EM levels for critically ill patients. The grade EM activities primarily include diaphragm training, limb mobilization, and in‐bed or out‐of‐bed activity.

From 24 h after ICU admission, patients who meet the physiological criteria outlined in the Indications for initiation (Table 1) will be considered eligible to initiate EM. During EM, any conditions listed under the Indications for suspension (Table 1) will require the immediate suspension of activity. Nurses will record the reason and timing of each EM suspension in the CRF.

Prior to EM initiating, physicians, physiotherapists (PTs), and nurses will jointly assess the patient's evaluating vital signs, level of consciousness, spontaneous breathing ability, limb strength, and other relevant indicators—to determine the appropriate EM grade. Under continuous monitoring, nurses will assist patients to complete EM once or twice per day.

3.2. Preliminary Determination of Suitable Activity Levels

Patients who are unconscious or unable to cooperate will undergo passive diaphragm training and limb exercise as the primary form of mobilization. Conscious patients will begin with Level 2 activities, which include active diaphragmatic and limb exercises initiated on the first day of mobilization. During EM, nurses will closely monitor the patient's vital signs. If the patient remains stable and reports no discomfort, the EM level may be increased by one level per day. When a patient's limbs strength exceeds Grade 3 on the MRC scale, they will progress stepwise to active out‐of‐bed activities, such as dangling at the bedside, sitting unsupported at the bed's edge, and eventually walking within the wards. If a patient becomes unable to complete an activity independently, or shows significant fluctuations in vital signs, and meets any suspension criteria, the EM level will be downgraded. For patients receiving sedatives, daily assessments of consciousness and muscle strength will be conducted following dose reduction or cessation, and activities will be adjusted accordingly [22].

3.3. Data Collection

Due to China's COVID‐19 management policies, multicentre site visits could not be conducted, resulting in a temporary suspension of the clinical research phase. However, with the full relaxation of epidemic control measures, clinical interventions and observation can now proceed as planned. Following consultation with all 18 participating hospitals, patient recruitment is scheduled to commence in January 2025 and will continue in May 2025. Study procedures are expected to be completed by mid‐2025.

4. Discussions

In recent years, the Chinese government has emphasized the importance of early rehabilitation of critically ill patients in National Health Development Plan [42]. The issue of insufficient healthcare staffing has been repeatedly highlighted in government work reports [43]. However, meaningful improvements in staffing levels may require a long timeframe to achieve.

At present, ICU human resource allocation in China continues to follow the standards outlined in the Guidelines for the Construction and Management of Critical Care Medicine, issued by the Ministry of Health in 2009 [44]. Dedicated rehabilitation therapists and nursing assistants are not consistently available in ICU settings. This situation is also common in many developing countries. The shortage of human resource in ICUs may lead to gaps in care delivery, posing a potential clinical risk [45, 46]. Therefore, optimizing protocol represents a more rapid and practical strategy to enhance the implementation of treatment and care interventions under current constraints. In response to this challenge, the Chinese government has introduced policies aimed at promoting the development of scientific and structured ICU rehabilitation programs.

This study is the first to develop a comprehensive graded EM protocol for the ICU‐AW prevention based on the staffing structure commonly found in Chinese intensive care settings. As a multicentre RCT, the study will provide feasibility data and evaluate the effectiveness of the protocol in improving EM implementation rates among ICU patients.

In addition, due to the current lack of unified standards, EM of ICU patients in China is often regarded as a voluntary nursing initiative rather than a formal therapeutic intervention, and therefore cannot be reimbursed under the national health insurance system. This situation partially undermines institutional motivation to oversee the routine implementation of EM. The PG‐Motion protocol aims to promote the development of expert consensus on EM and may provide a foundation for the future inclusion of ICU EM in national reimbursement policies.

5. Limitations

Due to the influence of the intervention content, we were unable to blind the nurses who provided the intervention measures, which may lead to partial bias in the implementation of the measures and the collection of results. We will reduce the risk of bias by using objective results, standardized protocols, and blinded evaluators. Future studies may consider selecting ICUs with little difference in patient admission and grouping randomization by unit to further reduce contamination.

Author Contributions

Bing Li: writing – review and editing, writing – original draft, methodology, formal analysis, conceptualization. Sheng Tang: writing – review and editing, methodology, investigation, formal analysis. Qinghua Zhao: writing – review and editing, methodology, investigation, formal analysis. Ping Luo: writing – review and editing, methodology, investigation, formal analysis. Lingyu Shen: writing – review and editing, writing – original draft, data curation. Mengjie Bi: writing – review and editing, writing – original draft, data curation. Yan Liu: writing – review and editing, writing – original draft, data curation. Yunjing Hou: investigation. Yanlan Ma: writing – review and editing, writing – original draft, formal analysis. All authors have read and approved the final version of the manuscript. Dr. Yanlan Ma had full access to all data in the study and assumes full responsibility for the integrity of the data and the accuracy of the data analysis.

Disclosure

The lead author Yanlan Ma affirms that this manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned (and, if relevant, registered) have been explained.

Ethics Statement

This study was approved from the Ethics Committee of General People's Liberation Army Hospital (S2021–643‐02).

Consent

Written informed consent will be obtained from each of the participants.

Conflicts of Interest

The authors declare no conflicts of interest.

Data Availability Statement

The data sets used or analyzed during the current study can be available from the corresponding author on reasonable request.