Abstract
Objective:
Vestibular migraine (VM) and Meniere's disease (MD) are episodic vertigo disorders with overlapping symptoms, often leading to misdiagnosis. This study aimed to identify a cost-effective diagnostic method to distinguish VM and MD.
Methods:
In this retrospective study, 108 VM patients and 65 MD patients were enrolled. Clinical symptoms, interictal videonystagmography (VNG) findings, and caloric test results were analyzed and compared between the two groups.
Results:
The VM group had a significantly higher proportion of females (p < 0.001). No significant differences were observed in any features of interictal nystagmus, including spontaneous or positional nystagmus (all p > 0.05). However, the caloric test revealed a significantly higher proportion of canal paresis (CP) in MD patients compared to VM patients (p < 0.001).
Conclusion:
While clinical symptom profiles effectively distinguish VM from MD, interictal nystagmus analysis has limited diagnostic value. The caloric test is a reliable and practical tool, as the presence of significant canal paresis strongly indicates MD over VM. Combining symptom evaluation with caloric testing offers a cost-effective strategy for the differential diagnosis of these common vestibular disorders.
1 Introduction
Vestibular migraine (VM) and Meniere's disease (MD) are common episodic vertigo disorders. They share similar symptoms, including nausea, vomiting, photophobia, phonophobia, tinnitus, and subjective hearing loss (Villar-Martinez and Goadsby, 2024; Hoskin, 2022). These similar symptoms often lead to misdiagnosis, especially when some VM patients do not experience headache or when some MD patients are accompanied by headache (Chen et al., 2023). The treatment approaches for VM and MD differ greatly (Smyth et al., 2022; Basura et al., 2020). Therefore, it is essential to distinguish between the two conditions using cost-effective and straightforward methods.
Clinical studies aim to distinguish VM from MD, mainly through Gadolinium-contrasted magnetic resonance imaging (Gd-MRI) and vestibular testing (Chen et al., 2023). Current theories suggest that the pathogenesis of VM involves the activation and sensitization of the trigeminal vascular system, abnormal brain ion channels, and cortical spreading depression (Espinosa-Sanchez and Lopez-Escamez, 2015). Meanwhile, MD is primarily considered a peripheral vestibular disorder caused by endolymphatic hydrops (EH; Sajjadi and Paparella, 2008). Gd-MRI can visualize endolymphatic and peri-lymphatic structures in participants (Nakashima et al., 2007). In the Gd-MRI research, Nakada et al. (2014) identified that the key distinction between VM and MD is the presence of EH: 100% in MD patients vs. only 21% in VM patients. Other researchers found similar results; Wu et al. (2016) reported that EH was present in all definite MD patients. Gürkov et al. (2014) demonstrated that a few VM patients (21%) with auditory symptoms presented EH. Furthermore, Sun et al. (2017) indicated that the location of EH was different between VM and MD patients; MD patients exhibited cochlear and vestibular EH in 100% of cases, while VM patients showed suspected cochlear EH in 10% of cases, with no vestibular EH.
However, MRI scans are relatively expensive, whereas vestibular testing is more economical and straightforward. The videonystagmography (VNG) is a diagnostic tool that records involuntary eye movements using video-oculography to objectively assess the function of the vestibular and oculomotor systems by analyzing provoked, spontaneous, and positional nystagmus (Velenovsky, 2015). Young et al. (2019) reported that ictal spontaneous vertical nystagmus was highly specific for VM (93.0%), whereas horizontal nystagmus was specific for MD (82.1). Young et al. (2022) reported that all severe MD patients with spontaneous vertigo demonstrated ictal spontaneous nystagmus. But most studies have focused on the analysis of nystagmus during the ictal VM and MD. In our clinical practice, we observe that nystagmus also occurs in interictal periods. Furthermore, patients with VM and MD during the ictal period often experience intolerance to vestibular examinations. Therefore, it is essential to identify differences between VM and MD by examining nystagmus characteristics during interictal periods. The caloric test assesses unilateral vestibular hypofunction by irrigating the external auditory canal with warm and cold water or air to induce nystagmus, and the slow-phase velocity is used to determine canal paresis (CP; Perez and Rama-Lopez, 2003). The findings of caloric tests in VM and MD remain controversial. Most studies report a higher proportion of CP in MD patients than in VM patients (Sharon and Hullar, 2014; Taylor et al., 2012; Neff et al., 2012). In comparison, Martin-Sanz et al. (2014) did not observe any significant differences (P > 0.05) in the proportion of caloric test between the VM and MD population.
In our study, we explore potential differences between VM and MD by comparing their clinical features, interictal nystagmus, and caloric testing, thereby offering a foundation for clinical differential diagnosis.
2 Materials and methods
In this retrospective study, we screened inpatient patients with VM, MD, and potential VM and MD from the hospital information systems (HIS) between January 2021 and September 2025. Diagnoses were clinically confirmed according to the VM diagnostic criteria of the International Classification of Headache Disorders, 3rd edition (ICHD-3; Arnold, 2018) and the MD diagnostic criteria of the Barany Society (Lopez-Escamez et al., 2015), based on medical records and clinical examinations (Figure 1). Patients with intracranial lesions confirmed by the magnetic resonance imaging (MRI) examination are excluded. The Ethics Committee of Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, approved this study. All patients have written informed consent.
Figure 1
Flowchart of patients included. HIS, hospital information systems; VM, vestibular migraine; MD, Meniere's disease; VNG, videonystagmography.
2.1 VNG examination procedures
The nystagmus was recorded with the VNG system, VertiGoggles (ZT-VNG-II, Shanghai ZEHNIT Medical Technology Co., Ltd., Shanghai, China). The patient lies supine with the head tilted 30 ° for a minimum recording period of 60 s for spontaneous nystagmus. In the supine roll test (SRT), the patient first lies on the exam table with the head tilted forward at 30 °. The head is then turned 90 ° to one side and maintained in this position for at least 60 s, even if no nystagmus is elicited. The patient then returns to the supine position. After a 60-s interval to avoid carry-over effects, the same procedure is repeated on the opposite side. In the Dix-Hallpike test (D-HT), the patient sits on the exam table with the head turned 45 ° to one side and eyes open, then leans back with the head hanging slightly (20–30 °) over the edge of the table. Nystagmus is recorded for at least 60 s in this position and maintained in this position for at least 60 s, even if no nystagmus is elicited. Following this, the patient returns to the sitting position. After a 60-s interval, the same procedure is performed on the other side. In the deep-head hanging test, patients lie back into a supine position with their head hanging at least 30 degrees below the horizontal plane and with a minimum recording period of 60 s (Bhattacharyya et al., 2017). While Benign Paroxysmal Positional Vertigo (BPPV) was not the focus of this study, performing the D-HT and SRT was for two reasons: first, to systematically exclude the presence of concurrent typical BPPV as part of a comprehensive vestibular assessment; and second, to characterize any provoked positional nystagmus, as a potential interictal finding in VM and MD patients. In addition to nystagmus direction, slow-phase velocity and the presence of torsional components were extracted from available VNG recordings for further interictal nystagmus characterization.
2.2 Caloric test procedures
The caloric test is performed with the patient in a supine position, head tilted forward (30 °) during bithermal water irrigations. First, cold water is used to irrigate the right and left ears. Then, warm water is used for the right and left ears. A 5-min interval is maintained between irrigations to prevent residual effects. Each irrigation lasts 30 s and uses 250 mL of water. The CP value is determined using the Jongkees formula (Jongkees et al., 1962), and a CP value of ≥25% is considered abnormal.
2.3 Statistical analysis
All statistical analyses are performed using SPSS (version 31.0, Chicago, IL, USA). Qualitative data are presented as numbers and percentages, and comparisons were made using the chi-square test or Fisher's exact test for 2 × 2 contingency tables. The normality of the quantitative data is assessed with the Shapiro-Wilk test. Data following a normal distribution are expressed as mean (standard deviation, SD), and differences are analyzed using the independent-samples t-test. For significant findings, effect sizes are reported as odds ratios (OR) with 95% confidence intervals (CI) for categorical variables and mean differences with 95% CI for continuous variables to indicate the magnitude of observed differences. Participants with missing data for a specific vestibular test were excluded only from the analyses pertaining to that test; no imputation methods were used. Two-tailed tests are used, and p < 0.05 is considered statistically significant.
3 Results
Finally, we include 108 patients with VM and 65 patients with MD. The proportion of female patients is higher in VM patients (85.2%) than in MD patients (46.2%; p < 0.001), with an odds ratio of 0.149 (95% CI: 0.072 to 0.307). There is no significant difference in age between the two groups (p = 0.153).
In the characteristics of dizziness, VM patients experience more vertigo and light-headed than MD patients (p = 0.045, with an odds ratio of 0.278 [95% CI: 0.078 to 0.995] and p = 0.019, with an odds ratio of 2.637 [95% CI: 1.203 to 5.782], respectively); there is no significant difference in rocking between the two groups (p = 0.103; Table 1).
Table 1
| Variable | VM (n = 108) | MD (n = 65) | p-value |
|---|---|---|---|
| Gender, male, n (%) | 16 (14.8) | 35 (53.8) | < 0.001*** 0.149 (0.072, 0.307) |
| Age, mean (SD), years | 63.4 (12.7) | 60.6 (12.9) | 0.153 |
| History of headache, n (%) | 56 (51.9) | 5 (7.7) | < 0.001*** 12.923 (4.815, 34.686) |
| Characteristics of dizziness | |||
| Vertigo, n (%) | 92 (85.2) | 62 (95.4) | 0.045* 0.278 (0.078, 0.995) |
| Rocking, n (%) | 34 (31.5) | 29 (44.6) | 0.103 |
| Light-headed, n (%) | 35 (32.4) | 10 (15.4) | 0.019* 2.637 (1.203, 5.782) |
Demographic information and clinical characteristics for patients with VM and MD.
Comparisons were made using Fisher's exact test for binary variables or the chi-square test as appropriate. For significant comparisons (p < 0.05), the odds ratio (95% confidence interval) is provided in parentheses.
* p < 0.05; ***p < 0.001.
VM, vestibular migraine; MD, Meniere's disease; SD, standard deviation; n, number.
We find no significant difference in nystagmus characteristics, including spontaneous nystagmus, positional nystagmus (Roll-test, Dix-Hallpike test, and deep head-hanging test), and the proportion of nystagmus direction change or nil nystagmus (all p > 0.05). Fifteen VM patients and eight MD patients lacked VNG examination data are excluded (Table 2 and Figure 2). In addition to nystagmus direction, quantitative and qualitative parameters of interictal nystagmus were further analyzed, including slow-phase velocity (SPV) and the presence of torsional components. No significant differences were observed between the VM and MD groups in SPV values for spontaneous or positional nystagmus (all p > 0.05; Table 3). Torsional components were infrequently observed and, when present, occurred with similar frequency in both groups (all p > 0.05; Table 3).
Table 2
| Nystagmus characteristic | VM (n = 93)# | MD (n = 57)# | p-value |
|---|---|---|---|
| Spontaneous nystagmus, n (%) | 17 (18.3) | 15 (26.3) | 0.244 |
| Horizontal, n (%) | 16 (17.2) | 15 (26.3) | 0.181 |
| Vertical, n (%) | 3 (3.2) | 0 (0) | 0.171 |
| Up beating nystagmus, n (%) | 0 (0) | 0 (0) | NA |
| Down beating nystagmus, n (%) | 3 (3.2) | 0 (0) | 0.171 |
| Positional nystagmus (Supine Roll-test), n (%) | 16 (17.2) | 15 (26.3) | 0.181 |
| Horizontal, n (%) | 15 (16.1) | 14 (24.6) | 0.204 |
| Vertical, n (%) | 4 (4.3) | 2 (3.5) | 0.810 |
| Up beating nystagmus, n (%) | 0 (0) | 0 (0) | NA |
| Down beating nystagmus, n (%) | 4 (4.3) | 2 (3.5) | 0.810 |
| Positional nystagmus (Dix-Hallpike test), n (%) | 22 (23.7) | 10 (17.5) | 0.375 |
| Horizontal, n (%) | 13 (14.0) | 7 (12.3) | 0.767 |
| Vertical, n (%) | 11 (11.8) | 4 (7.0) | 0.340 |
| Up beating nystagmus, n (%) | 8 (8.6) | 1 (1.8) | 0.087 |
| Down beating nystagmus, n (%) | 9 (9.7) | 3 (5.3) | 0.333 |
| Positional nystagmus (Deep head-hanging test), n (%) | 12 (12.9) | 3 (5.3) | 0.130 |
| Horizontal, n (%) | 9 (9.7) | 1 (1.8) | 0.059 |
| Vertical, n (%) | 5 (5.4) | 3 (5.3) | 0.976 |
| Up beating nystagmus, n (%) | 1 (1.1) | 1 (1.8) | 0.725 |
| Down beating nystagmus, n (%) | 4 (4.3) | 2 (3.5) | 0.810 |
| Nystagmus direction change, n (%) | 11 (11.8) | 4 (7.0) | 0.340 |
| Nil nystagmus, n (%) | 59 (63.4) | 30 (52.6) | 0.191 |
Nystagmus characteristics of patients with VM and MD.
#Fifteen VM patients and eight MD patients lacked electronystagmography examination data.
VM, vestibular migraine; MD, Meniere's disease; n, number; NA, not applicable.
Figure 2
Comparison of spontaneous nystagmus, nystagmus of Roll-test, Dix-Hallpike test, and deep head-hanging test, and nil nystagmus in VM and MD patients. VM, vestibular migraine; MD, Meniere's disease; H, horizontal; V, vertical.
Table 3
| Test condition | Parameter | VM (n = 108) | MD (n = 65) | p-value |
|---|---|---|---|---|
| Spontaneous nystagmus | SPV (°/s)# | 3.1 (2.4) | 3.0 (2.0, 4.0) | 0.303 |
| Torsional component, n (%) | 0 (0) | 0 (0) | NA | |
| SRT nystagmus | SPV (°/s) | 4.0 (2.4) | 4.9 (3.6) | 0.436 |
| Torsional component, n (%) | 1 (0.9) | 1 (1.5) | 0.715 | |
| D-HT nystagmus | SPV (°/s) | 5.0 (3.0, 11.3) | 3.0 (2.0, 4.0) | 0.053 |
| Torsional component, n (%) | 11 (10.2) | 3 (4.6) | 0.193 | |
| Deep head-hanging test nystagmus | SPV (°/s) | 2.0 (2.0, 9.8) | 2.0 (2.0, 2.0) | 0.328 |
| Torsional component, n (%) | 3 (2.8) | 2 (3.1) | 0.909 |
Nystagmus characteristics in VM and MD patients: slow-phase velocity and torsional components.※
※In a positional test where multiple nystagmus occurrences are observed, we take the average to calculate the SPV for that positional test.
#Normally distributed data are expressed as mean (SD), and comparisons between two groups are performed using independent samples t-tests; non-normally distributed data are expressed as median (Q1, Q3), and comparisons between two groups are performed using non-parametric tests.
VM, vestibular migraine; MD, Meniere's disease; SRT, Supine Roll-test; D-HT, Dix-Hallpike test; SPV, slow-phase velocity; NA, not applicable; n, number; SD, standard deviation; Q1, First quartile; Q3, Third Quartile.
In the caloric test, the proportion of CP is higher in MD patients than in VM patients (p < 0.001). Fourteen VM patients were excluded: they lacked caloric test data; 21 patients refused the examination due to intolerance to the caloric stimulation (primarily due to provocation of severe vertigo or nausea); and six patients did not undergo the test due to cerumen impaction or tympanic membrane perforation. Nine MD patients lacked caloric test data, and two patients did not undergo the test due to cerumen impaction or tympanic membrane perforation are excluded (Table 4 and Figure 3).
Table 4
| Caloric test | VM (n = 67) | MD (n = 54) | p-value |
|---|---|---|---|
| CP, n (%) | 17 (25.4) | 32 (59.3) | < 0.001*** |
Caloric test of patients with VM and MD.
※Among the 108 patients with vestibular migraine, 67 patients underwent the caloric test, 14 patients lacked caloric test data, 21 patients refused the examination due to intolerance to the caloric stimulation (primarily due to provocation of severe vertigo or nausea), and 6 patients did not undergo the test due to cerumen impaction or tympanic membrane perforation. Separately, among 65 patients with Meniere's Disease, 54 patients underwent the caloric test, 9 patients lacked caloric test data, and 2 patients did not undergo the test due to cerumen impaction or tympanic membrane perforation. ***p < 0.001. VM, vestibular migraine; MD, Meniere's disease; CP, canal paresis; n, number.
Figure 3
Comparison of canal paresis in VM and MD patients. VM, vestibular migraine; MD, Meniere's disease. ***p < 0.001.
4 Discussions
This study compared the clinical features, interictal VNG findings, and caloric testing results between patients with VM and MD. Our findings revealed that VM was more common in females. Although no significant differences in interictal nystagmus characteristics were observed between the two groups, the proportion of CP in the caloric test was significantly higher in MD than in VM. These results suggest that caloric testing may be a reliable and cost-effective method for distinguishing MD from VM in clinical practice.
Our findings both support and challenge existing research on VM and MD differentiation. The demographic and symptomatic profiles we identified closely align with previous studies. The female predominance in VM (Beh, 2022).
Our study found no significant differences in interictal nystagmus between VM and MD. Notably, a subset of patients showed transient or direction-changing positional nystagmus during tests such as the Roll test, Dix–Hallpike maneuver, or deep head-hanging test, with no apparent diagnostic specificity. The presence of such variable nystagmus patterns further supports the idea that both disorders may involve central adaptive mechanisms. In VM, transient dysfunction within vestibular nuclei and cerebellar pathways may cause mixed-pattern eye movements, as previously reported in studies of vestibulo-cerebellar modulation (Noseda, 2022; Harno et al., 2003; Zhai et al., 2025). In MD, fluctuating endolymphatic hydrops could lead to intermittent changes in labyrinthine input, resulting in dynamic central reweighting of vestibular signals (Bance et al., 1991; Nakashima et al., 2016). These overlapping pathophysiological processes could explain the nonspecific interictal nystagmus patterns seen in our study, aligning with emerging evidence that both peripheral and central mechanisms influence nystagmus phenotypes in these disorders (Pokhrel et al., 2025; Li et al., 2022; Bednarczuk et al., 2019; Lee et al., 2022, 2023).
By incorporating SPV and torsional components into the analysis of interictal nystagmus, our study provides a more comprehensive assessment of eye movement characteristics in VM and MD. Despite this expanded evaluation, no diagnostically meaningful differences were identified between the two conditions. This suggests that interictal nystagmus in both VM and MD likely reflects transient or compensated vestibular dysfunction rather than fixed peripheral or central lesions. In VM, fluctuating central vestibular network excitability may result in low-amplitude, variable nystagmus patterns, while in MD, intermittent alterations in labyrinthine input caused by endolymphatic hydrops may be partially compensated during interictal phases.
The caloric test results further support the existence of distinct vestibular mechanisms underlying VM and MD. MD is widely recognized as a peripheral disorder characterized by endolymphatic hydrops, which disrupts labyrinthine mechanics and causes asymmetric canal function (Mohseni-Dargah et al., 2023; Park et al., 2021). In contrast, VM is believed to result from temporary dysfunction within central vestibular networks, potentially mediated by trigeminovascular activation, cortical spreading depression, and abnormal ion channel activity (Smyth et al., 2022). These mechanisms of VM can produce vestibular symptoms without causing structural damage to the peripheral system, which explains why caloric asymmetry is rarely observed in VM.
From a clinical standpoint, these findings underscore the importance of integrating symptom profiles with caloric testing to improve diagnostic accuracy. A CP of ≥25% highly suggests MD, while normal caloric responses, especially in patients exhibiting migraine symptoms such as photophobia or phonophobia, more strongly suggest VM. However, it is important to note that a normal caloric test result does not rule out MD, as unilateral vestibular hypofunction may not be detectable, particularly in the early stages of the disease. Given the high cost and limited availability of gadolinium-enhanced MRI for visualizing endolymphatic hydrops, caloric testing remains a practical and valuable tool for differential diagnosis. Incorporating these insights into clinical evaluation can support more targeted treatment approaches.
4.1 Study limitations
Several limitations should be acknowledged. First, the retrospective design and single-center setting of the study may introduce selection bias. Second, the unavailability of video head impulse test (v-HIT) data represents a notable constraint, as the combination of caloric testing (assessing low-frequency function) and v-HIT (assessing high-frequency function) may offer greater diagnostic specificity, as suggested by recent literature (Chen et al., 2023; Mavrodiev et al., 2024). Third, as noted in the results, a higher proportion (38%) of VM patients were excluded from the final caloric test analysis compared to MD patients (17%). A post-hoc comparison revealed that excluded VM patients were older, and excluded MD patients more frequently reported a history of headache (Supplementary Table 1). However, the key differentiating clinical features, such as tinnitus and hearing loss in MD, and photophobia/phonophobia in VM, did not differ significantly between the included and excluded subgroups within each diagnosis. Nevertheless, this differential attrition represents a potential source of selection bias. The primary reason for exclusion in the VM group was intolerance to the caloric test, which may reflect the heightened vestibular sensitivity characteristic of the disorder. Finally, Fixation suppression testing was performed only in a subset of patients and was therefore not included in the comparative analysis, which may have limited the ability to further distinguish central from peripheral nystagmus patterns. Future prospective studies incorporating multimodal vestibular assessments are necessary to reinforce these findings.
5 Conclusions
In conclusion, characteristics of interictal nystagmus have limited diagnostic value, but caloric asymmetry is a strong indicator for differentiating the two conditions. Cost-effective vestibular function tests combined with symptom profiling may improve the diagnosis and management of VM and MD.
Statements
Data availability statement
The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.
Ethics statement
The studies involving humans were approved by the Ethics Committee of Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science. The studies were conducted in accordance with the local legislation and institutional requirements. Written informed consent for participation was not required from the participants or the participants' legal guardians/next of kin in accordance with the national legislation and institutional requirements.
Author contributions
XZ: Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Software, Supervision, Validation, Visualization, Writing – original draft, Writing – review & editing. QW: Data curation, Investigation, Supervision, Validation, Visualization, Writing – review & editing. JiaX: Data curation, Writing – review & editing. TZ: Data curation, Writing – review & editing. JinX: Data curation, Writing – review & editing. ZL: Data curation, Writing – review & editing. XY: Investigation, Writing – review & editing. HC: Funding acquisition, Investigation, Writing – review & editing. WL: Writing – review & editing. MH: Conceptualization, Data curation, Funding acquisition, Investigation, Project administration, Resources, Writing – review & editing. LC: Conceptualization, Data curation, Funding acquisition, Investigation, Supervision, Writing – review & editing.
Funding
The author(s) declared that financial support was received for this work and/or its publication. The study was supported by the 2022 Science and Technology Project of Xiangyang Science and Technology Bureau (No. 2022YL16A), the 2022 Science and Technology Project of Xiangyang Central Hospital (No. 2022YB16), the 2024 Science and Technology Project of Xiangyang Central Hospital (No. 2024YJ19B), the 2025 Science and Technology Project of Xiangyang Central Hospital (No. 2025YJ08B), and the Zhejiang Provincial Natural Science Foundation (No. LY22H090017).
Acknowledgments
We appreciate the continuous support of the physicians from the Department of Neurology, Xiangyang Central Hospital.
Conflict of interest
The author(s) declared that this work 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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Supplementary material
The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fnins.2025.1745820/full#supplementary-material
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Summary
Keywords
caloric test, differential diagnosis, Meniere's disease, nystagmus, vestibular migraine
Citation
Zhang X, Wang Q, Xu J, Zhou T, Xu J, Liu Z, Yang X, Cai H, Luo W, Hu M and Chang L (2026) Differentiating vestibular migraine from Meniere's disease: an analysis of clinical features, videonystagmography, and caloric testing. Front. Neurosci. 19:1745820. doi: 10.3389/fnins.2025.1745820
Received
13 November 2025
Revised
13 December 2025
Accepted
22 December 2025
Published
13 January 2026
Volume
19 - 2025
Edited by
Wei Shan, Capital Medical University, China
Reviewed by
Vergil Mavrodiev, University Hospital Zürich, Switzerland
Jing Wang, Fudan University, China
Updates
Copyright
© 2026 Zhang, Wang, Xu, Zhou, Xu, Liu, Yang, Cai, Luo, Hu and Chang.
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: Mei Hu, humeiyaotianhang@126.com; Liying Chang, liying_changxf@163.com
†These authors have contributed equally to this work
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