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Abstract 


The study was conducted to assess medical staffs' fear of receiving the fourth dose of the Coronavirus disease 2019 (COVID-19) vaccine. From December 17, 2022, to January 31, 2023, an online survey was conducted to assess the fear among medical staffs regarding the administration of the fourth dose of the COVID-19 vaccine. The participants were exclusively drawn from a tertiary grade hospital in Taizhou. Out of the 1, 832 medical staffs invited to participate in the questionnaire, a total of 613 (33.5%) provided valid responses for subsequent analysis. Among them, 81 (13.8%) expressed fear of receiving the fourth dose of COVID-19. The fear was significantly influenced by these factors: the presence of serious food/drug allergic reactions (OR = 3.84, 95% CI: 1.40-10.52), received booster COVID-19 vaccine (OR = 0.20, 95% CI: 0.11-0.35), opinion on vaccination requirement (OR = 0.20, 95% CI: 0.11-0.35), viewpoint (OR = 0.23, 95% CI: 0.12-0.44) with scores ≥10, and positive attitude toward vaccination (OR = 0.21, 95% CI: 0.13-0.35). Our study revealed that a subset of medical staffs still harbor apprehension toward receiving the fourth dose of the new COVID-19 vaccine. Factors influencing this fear encompass allergic reactions, booster COVID-19 vaccine, as well as opinion, viewpoint, and attitude toward vaccination. Educating medical staffs on these factors may help mitigate their fear.

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Hum Vaccin Immunother. 2023; 19(2): 2261201.
PMCID: PMC10627059
PMID: 37920885

Understanding factors affecting Chinese medical staff’s fear of receiving the fourth dose of COVID-19 vaccine: A cross-sectional study in Taizhou

Associated Data

Data Availability Statement

ABSTRACT

The study was conducted to assess medical staffs’ fear of receiving the fourth dose of the Coronavirus disease 2019 (COVID-19) vaccine. From December 17, 2022, to January 31, 2023, an online survey was conducted to assess the fear among medical staffs regarding the administration of the fourth dose of the COVID-19 vaccine. The participants were exclusively drawn from a tertiary grade hospital in Taizhou. Out of the 1, 832 medical staffs invited to participate in the questionnaire, a total of 613 (33.5%) provided valid responses for subsequent analysis. Among them, 81 (13.8%) expressed fear of receiving the fourth dose of COVID-19. The fear was significantly influenced by these factors: the presence of serious food/drug allergic reactions (OR = 3.84, 95% CI: 1.40–10.52), received booster COVID-19 vaccine (OR = 0.20, 95% CI: 0.11–0.35), opinion on vaccination requirement (OR = 0.20, 95% CI: 0.11–0.35), viewpoint (OR = 0.23, 95% CI: 0.12–0.44) with scores ≥10, and positive attitude toward vaccination (OR = 0.21, 95% CI: 0.13–0.35). Our study revealed that a subset of medical staffs still harbor apprehension toward receiving the fourth dose of the new COVID-19 vaccine. Factors influencing this fear encompass allergic reactions, booster COVID-19 vaccine, as well as opinion, viewpoint, and attitude toward vaccination. Educating medical staffs on these factors may help mitigate their fear.

KEYWORDS: Medical staffs, COVID-19, the fourth dose vaccine, fear

Introduction

The global COVID-19 pandemic caused severe illness and even death in its rapid outbreak in millions of people worldwide.1 On December 7, 2022, a formidable wave of COVID-19 infections surfaced in China, swiftly escalating into a nationwide pandemic within a brief timeframe. This outbreak resulted in a significant number of infections and exerted immense pressure on healthcare resources.2 The establishment of a robust immune barrier is therefore crucial to effectively halting the COVID-19 outbreak. The most effective and economical way to curtail disease propagation is to enhance vaccination efforts and implement herd immunity strategies.3 Studies have shown that more than 90% of severe illness and mortality associated with COVID-19 can be prevented through COVID-19 vaccine.4 A third dose (booster vaccine) significantly reduced mortality during sudden infections and severe diseases as well as Omicron variant waves.5 Despite the success and safety of the third dose in preventing infections and serious diseases, the emergence of the highly contagious Omicron variant has led to a significant number of breakthrough infections even in populations that have received three doses of the vaccine. In addition to breakthrough infections, the decline in vaccine efficacy has emerged as a critical issue in the COVID-19 pandemic.6

According to previous studies, medical staffs are at high risk of exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).7 A study involved 38 medical staffs who volunteered to receive a homologous booster dose 6 months after their third dose, and the results showed a protective immune response to the vaccine.8 The study findings indicate the initial presence of fear regarding the administration of the COVID-19 vaccine for the first three doses, albeit with variations observed among individuals.9 The most widely used vaccines in China for COVID-19 are domestic inactivated vaccines, such as “CoronaVac” produced by Sinovac and the inactivated COVID-19 vaccine produced by the Beijing Institute of Biological Products (BBIBP-CorV).10 As of February 23, 2023, approximately 850 million Chinese have completed booster immunization, including approximately 48,000 doses of inhaled adenovirus vector vaccine.11

Although the fourth dose of vaccine has not been widely administered globally, Several countries, concerned about the evident waning immunity, have already begun offering a fourth dose of COVID-19 vaccine. The fourth dose of COVID-19 vaccine has been approved in Israel.12 In May 2022, the Japanese government was contemplating the implementation of fourth dose utilizing vaccines. This measure was intended for individuals aged 60 years or older, as well as those with preexisting health conditions who received their third dose more than five months ago.13 China is considering increasing vaccination coverage for the third dose, initiating a fourth vaccination in due course to curb the COVID-19 pandemic.14 Common adverse reactions to COVID-19 vaccine include injection site pain or swelling, physical discomfort like weakness or headache, low-grade fever, and gastrointestinal reactions like nausea, vomiting, or diarrhea.15 Perceived adverse reactions, safety concerns, fear of COVID-19 contraction, genetic effects, and vaccination skepticism are potential factors contributing to vaccine-related fear.10 Fear of COVID-19 vaccine-related side effects and adverse events may impede vaccine uptake.16 Vaccination fear has been reported as an acute stress condition that may lead to severe atrial arrhythmias.17 Therefore, investigating medical staffs’ fear and the factors that influence their fear toward receiving the fourth dose of the COVID-19 vaccine is of substantial importance. And facilitate the successful implementation and advancement of the fourth-dose vaccination strategy.

Methods

Population and data collection

We conducted a population-based, cross-sectional online survey encompassing all medical staffs at a tertiary-grade hospital in Taizhou, China. In our study, data collection was performed using the Wen-Juan Xing platform, developed by Changsha Ranxing Information Technology Co., Ltd. in Hunan, China. This platform, known for its prominence as the leading online survey platform in mainland China, seamlessly integrates with WeChat. Based on the list of medical staffs of the hospital, the survey was sent to all (n = 1832) of them in December 2022. Collection period was from December 17, 2022 to January 31, 2023. A total of 613 medical staffs accepted the survey via WeChat. All procedures will follow guidelines established by investigator’s institutional Ethics Committee and in accordance with the Helsinki Declaration.

Structured questionnaires and assessment of fear

We developed a self-administered questionnaire base on previous research findings and the survey framework used to assess relevant factors.10,18,19 The questionnaire encompassed the following aspects: (1) basic demographic information, including sex, age, residence, education, occupation, cohabitation with parents, and parental status. (2) participants’ background information that encompassed chronic diseases (such as hypertension and diabetes), food/drug allergies, frequency of colds in the past year, and prior receipt of booster COVID-19 vaccine. (3) participants’ opinion, viewpoint and attitude on the fourth dose COVID-19 vaccine.

To assess the fear of receiving the fourth dose of the vaccine, they were asked: “Are you afraid of receiving your fourth dose of the vaccine?” Four response options were provided: “strongly fear,” “fear,” “unfear,” or “strongly unfear.” Responsed of “strongly fear” and “fear” were categorized as “fear” while responsed of “unfear” or “strongly unfear” were categorized as “unfear”. The medical staffs’ opinion on the necessity of the fourth dose of the COVID-19 vaccine was assessed through the question: “Do you believe you require the fourth dose against COVID-19?” Three response options were provided: “yes,” “no,” and “don’t know.” A response of “yes” indicated requirement, while the other two responses indicated no requirement. Regarding the medical staffs’ viewpoint on the effectiveness of the fourth dose of the COVID-19 vaccine, participants were asked: “What are your thoughts on the effectiveness of the fourth dose of the COVID-19 vaccine for you?” The questionnaire comprised three items that evaluated participants’ viewpoint on the fourth dose. These items assessed: (1) the personal health significance of receiving the fourth dose, (2) the perceived effectiveness of the fourth dose in preventing new cases of COVID-19, and (3) the perceived protective effects against infection provided by the fourth dose. Participants responded to these items using a 5-point Likert scale ranging from 1 (strongly disagree) to 5 (strongly agree). The lowest possible score was 3 points, the highest was 15 points, and the median score was 10 points. Scores ≥10 were considered high, while scores <10 were considered low. The attitude toward the fourth dose of the COVID-19 vaccine was measured using the question: “What is your attitude toward receiving the fourth dose of the vaccine?” Response options included: “get vaccinated as soon as possible,” “elective vaccination,” “cannot vaccinate,” “resolutely do not vaccinate,” and “discuss it later.” The first two options were considered positive, while the last three options were deemed negative. All the questions were closed-ended, and participants provided their answers by selecting checkboxes.

Quality control

To enhance the precision, coherence, and readability of the questionnaire, several measures were implemented. Firstly, all items in the questionnaire were designated as mandatory to ensure complete responses. Secondly, before conducting data analysis, logical checks were performed to identify and remove outliers. Participants who were below the age of 18 or above the age of 70, as well as those who completed the questionnaire in less than 120 seconds, were excluded from the study. Thirdly, the questionnaire underwent testing and subsequent revisions based on feedback from a test population. Which aimed to ensure the comprehensiveness, scientific validity, and clarity of the questionnaire. Furthermore, input from multiple hospital experts and consultation with domestic epidemiologists were incorporated to guarantee quality control.

Statistical analysis

Participants’ characteristics were reported as means (±SD) for continuous variables and percentage frequencies (n, %) for categorical variables. T tests were used to compare continuous data, while the χ2 test was used for categorical data comparison. Since our questionnaire required mandatory responses, there were no missing values in the dataset.

Logistic regression models were utilized to calculate odds ratios (ORs) and 95% confidence intervals (CIs) to evaluate the association between these factors and fear of the fourth dose vaccine. Only variables that demonstrated statistical significance at the P < 0.05 level in Table 1 were selected for inclusion in the multi-logistic regression analysis. A two-sided P value below 0.05 was considered statistically significant. The statistical analyses were performed using R version 4.0.5 (http://www.R-project.org, The R Foundation) and Free Statistics software version 1.7.1 (http://www.freestatistics.org).

Table 1.

Baseline characteristics of medical staffs (n = 613).

VariablesCategoriesTotal (n = 613)Unfear (n = 532)Fear (n = 81)p
Sex, n (%)    .955
 Male180 (29.4)156 (29.3)24 (29.6) 
 Female433 (70.6)376 (70.7)57 (70.4) 
Age, Mean ± SD 35.2 ± 15.035.2 ± 15.835.8 ± 7.7.737
Residence, n (%)    .604
 Urban416 (67.9)359 (67.5)57 (70.4) 
 Town/Rural197 (32.1)173 (32.5)24 (29.6) 
Education, n (%)    .662
 College and below109 (17.8)96 (18)13 (16) 
 Undergraduate and above504 (82.2)436 (82)68 (84) 
Occupation, n (%)    .382
 Nurse289 (47.1)248 (46.6)41 (50.6) 
 Doctor207 (33.8)185 (34.8)22 (27.2) 
 Others117 (19.1)99 (18.6)18 (22.2) 
Parental status, n (%)    .851
 No210 (34.3)183 (34.4)27 (33.3) 
 Yes403 (65.7)349 (65.6)54 (66.7) 
Cohabitation with parents    .204
 No248 (40.5)210 (39.5)38 (46.9) 
 Yes365 (59.5)322 (60.5)43 (53.1) 
Chronic disease    .977
 No553 (90.2)480 (90.2)73 (90.1) 
 Yes60 (9.8)52 (9.8)8 (9.9) 
Food/drug allergic reaction, n (%)  .024
 No500 (81.6)438 (82.3)62 (76.5) 
 Slight93 (15.2)81 (15.2)12 (14.8) 
 Serious20 (3.3)13 (2.4)7 (8.6) 
Frequency of colds  .280
 0–1287 (46.8)255 (47.9)32 (39.5) 
 2~3256 (41.8)220 (41.4)36 (44.4) 
 4~543 (7.0)36 (6.8)7 (8.6) 
 ≥527 (4.4)21 (3.9)6 (7.4) 
Booster COVID-19 vaccine, n (%)  < .001
 No66 (10.8)48 (9)18 (22.2) 
 Yes547 (89.2)484 (91)63 (77.8) 
Opinion on the fourth dose COVID-19 vaccine  < .001
 No requirement290 (47.3)227 (42.7)63 (77.8) 
 Requirement323 (52.7)305 (57.3)18 (22.2) 
Viewpoint of the effectiveness on the fourth dose COVID-19 vaccine, n (%) < .001
 <10379 (61.8)310 (58.3)69 (85.2) 
 ≥10234 (38.2)222 (41.7)12 (14.8) 
Attitude on the fourth dose COVID-19 vaccine, n (%) < .001
 Negative226 (36.9)171 (32.1)55 (67.9) 
 Positive387 (63.1)361 (67.9)26 (32.1) 

P value below 0.05 was considered statistically significant

Results

Baseline characteristics of the medical staffs

Out of the 1, 832 medical staffs invited to participate in the questionnaire, a total of 613 (33.5%) provided valid responses for subsequent analysis. Among them, 81 (13.8%) expressed fear of receiving the fourth dose of COVID-19. The median age of the participants was 35.2 (±15.0) years, and 433 (70.6%) were female. No statistically significant differences were observed in terms of sex, age, residence, education, occupation, and the frequency of experiencing colds per year (p > .05). However, significant differences were found in food/drug allergic reactions (p = .024) and the administration of the booster COVID-19 vaccine (p < .001). Moreover, opinion regarding the fourth COVID-19 dose vaccine (p < .001), viewpoint of its effectiveness (p < .001), and attitude toward its administration (p < .001) displayed significant associations with receiving the fourth dose vaccine (Table 1).

The distribution of fear among medical staffs

Figure 1 indicating the distribution of fear toward receiving the fourth dose of COVID-19 among medical staffs. In the subgroup reporting allergic reactions to food/drugs, no allergic reactions (62, 12.40%), slight allergic reactions (12, 12.90%), and severe allergic reactions (7, 35.00%) expressed fear of the fourth vaccine. In the subgroup of booster vaccine, those who received booster (63, 11.52%), and unbooster (18, 27.27%) expressed fear of the fourth vaccine. In the subgroup of opinion, those who opinion requirement (18, 5.57%), and those who opinion no requirement (63, 21.72%) expressed fear of the fourth vaccine. In the subgroup of viewpoint, scores ≥10 (12, 5.13%), while scores <10 (69, 18.21%) expressed fear about the fourth vaccination. In attitude subgroup, positive attitude (26, 6.72%), and negative attitude (55, 24.34%) expressed fear of the fourth vaccine. Notably, there were statistically significant association between food/drug allergic reaction (p = .014), opinion on vaccination requirement (p < .001), viewpoint (p < .001) with scores ≥10, positive attitude toward vaccination (p < .001) and fear of the fourth vaccination.

The distribution of fear towards receiving the fourth dose of COVID-19 among medical staffs.

Multiple logistic regression of factors associated with medical staffs’ fear of vaccinating the fourth dose of COVID-19

This study aimed to investigate the relationship between vaccine fear among medical staffs and potential influencing factors through multiple logistic regression analysis. Adjusting for demographic and health-related variables, a higher likelihood of vaccine fear was observed among medical staffs with history of food/drug allergies (slight vs. No: OR = 1.06, 95% CI: 0.54–2.08; serious vs. No: OR = 3.84, 95% CI: 1.4–10.52). Medical staffs who received the booster COVID-19 vaccine (yes vs. no: OR = 0.2, 95% CI: 0.12–0.35) exhibited a higher likelihood of fear. Conversely, medical staffs who required vaccination, score of viewpoint ≥10 for a fourth vaccination and held a positive attitude toward receiving it exhibited a lower likelihood of fear (OR = 0.20, 95% CI: 0.11–0.35; OR = 0.23, 95% CI: 0.12–0.44; OR = 0.21, 95% CI: 0.13–0.35) (Table 2). These findings contributed to a better understanding of the factors influencing vaccine fear among medical staffs.

Table 2.

Multiple logistic regression of factors associated with medical staffs’ fear of vaccinating the fourth dose of COVID-19 (n = 613).

VariableCategoriesUnadjusted OR (95% CI)p valueAdjusted OR (95% CI)adj. p value
Food/Drug allergic reaction     
 Slight vs. No1.05 (0.54~2.03).8931.06 (0.54~2.08).856
 Serious vs. No3.8 (1.46~9.9).0063.84 (1.4~10.52).009
Booster COVID-19 vaccine     
 Yes vs. No0.21 (0.12~0.37)< .0010.2 (0.11~0.35)< .001
Opinion on the fourth dose COVID-19 vaccine    
 Requirement vs. No requirement0.21 (0.12~0.37)< .0010.20 (0.11~0.35)< .001
Viewpoint on the effectiveness of the fourth dose COVID-19 vaccine    
 ≥10 scores vs. <10 scores0.24 (0.13~0.46)< .0010.23 (0.12~0.44)< .001
Attitude on the fourth dose COVID-19 vaccine    
 Positive vs. Negative0.22 (0.14~0.37)< .0010.21 (0.13~0.35)< .001

In multiple logistic regression, we adjusted for sex, age, residence, education, occupation, parental status, cohabitation with parents, chronic disease, frequency of colds.

Discussion

This study highlights a concerning prevalence of vaccination fear among medical staffs, with 13.2% expressing fear on the fourth dose of the COVID-19 vaccine. The investigation further revealed factors to this fear. Significant associations were observed between fear of the fourth COVID-19 dose vaccine and factors such as severe food/drug allergies, COVID-19 vaccine boosters, opinion, viewpoint, and attitude. By comprehending medical staffs’ fear on the administration of the fourth vaccine dose, we may enhance overall vaccination rates and effectively implement outbreak prevention and control measures in society.

In this study, 33.5% of respondents provided effective responses, suggesting the possibility of non-response bias. Individuals with negative views on the fourth dose may displayed a higher tendency to refrain from participating in the survey. So, we conducted an non-response bias analysis by comparing the characteristics of respondents and non-respondents. Our findings indicated no statistically significant (p > .05) in baseline data between the 613 respondents and 1219 non-respondents. Therefore, our sample distribution was representative, and there was no significant evidence of non-response bias (Appendix 1).

Vaccination fear is a concept that describes the apprehension or resistance some people display toward the administering of vaccines.20 The concept of vaccination fear is not only restricted to one particular region, it is a global phenomenon with varying degrees of severity.21 Previous studies have shown that vaccine phobia is largely focused on concerns about vaccine safety and efficacy,20,22 and distrust of the state and traditional healthcare systems as sources of health information.22,23 Some researchers have noted that health services often provide information lacking in rigor and reliable empirical data. Additionally, the absence of effective strategies to address vaccine-related concerns, coupled with biased, erroneous, or misleading information prevalent in the media and social networks, further contributes to increased fear toward vaccines.24

This study was conducted during the initial implementation of the Chinese government’s revised policies on COVID-19 prevention and control. At that time, the distribution of the second booster dose within the country was still limited, despite widespread transmission of the virus nationwide. Research specifically focused on the fear surrounding the fourth vaccine dose remains scarce. However, in light of the surge in the Omicron variant, an Israeli study demonstrated a 13% decrease in breakthrough infections among hospital staff when administering the fourth dose of the BNT162b2 vaccine, compared to the third dose.25 Consequently, the administration of a fourth vaccine dose should be considered as a measure to mitigate the risk of infection among medical staff.

During the survey period of this study, which coincided with a severe outbreak, it is noteworthy that 86.8% of respondents reported unfear on the fourth dose of COVID-19 vaccination. This aligned with the 81.1% acceptance rate observed prior to the outbreak,18 indicating that medical staffs’ fear of vaccine does not exhibit a specific temporal pattern. However, it is important to recognize that the reluctance of medical staffs to undergo vaccination can have wide-ranging societal implications, influencing behavioral patterns within the larger community.26

When evaluating the importance of booster doses, it is crucial to consider both the efficacy and safety of COVID-19 vaccines. Extensive academic researches have consistently demonstrated that a two-dose regimen provides effective protection against COVID-19 in individuals under the age of 16.27 Furthermore, safety records spanning a median duration of two months have shown no notable deviations from other viral vaccines.28

We observed a significant impact of severe food/drug allergic reactions on medical staff’s apprehension toward receiving the fourth dose. Conversely, minor allergic reactions did not significantly influence their perceptions of the vaccine. This finding held implications for our understanding and promotion of a scientific attitude. It calls for heightened vigilance regarding potential allergic reactions, particularly among individuals with a history of severe reactions.29 Prioritizing such measures in the long run contributes to safeguarding public health and individual well-being. However, it is essential to avoid making blanket statements about vaccine safety based solely on past experiences and to consider real-world data.30 Furthermore, our study revealed an association between medical staffs’ fear of receiving the fourth COVID-19 vaccine dose and their decision to receive the third dose. This aligned with findings from previous studies investigating concerns surrounding prior third doses of COVID-19 vaccine.31

The findings from Table 2 indicated a correlation between medical staffs’ acceptance of the fourth dose and their opinion, viewpoint, and attitude. To address any concerns or reservations regarding the additional COVID-19 vaccine, we propose several interventions. Firstly, it is crucial to disseminate reliable and evidence-based information to enhance understanding of the safety and efficacy of the fourth dose. Secondly, encouraging medical leaders, particularly, to publicly receive the fourth dose and endorse its safety can be impactful. Lastly, providing education and training programs aimed at fostering a positive attitude and awareness about the fourth dose among medical staff. By implementing these strategies, we anticipate an increase in acceptance of the fourth dose, thereby promoting the protection of both medical staff and the wider community.

Limitation

However, it is important to acknowledge the limitations associated with this study. Firstly, participants might have been subject to social desirability bias, meaning they may have provided responses that they deemed socially acceptable. Secondly, data was collected on a voluntary questionnaire-based survey, which introduced inherent limitations in terms of response rate. Thirdly, the study sample consisted solely of medical staff from a single tertiary-grade hospital in Taizhou, China. Therefore, the generalizability of the findings to a broader population may be limited. Lastly, as a cross-sectional survey, this study had constraints in terms of follow-up and the ability to assess changes in fear over time.

Conclusion

In conclusion, this study revealed that 13.2% of participants harbored fear regarding the administration of the fourth dose of the COVID-19 vaccine. Notably, this fear was influenced by factors such as previous experiences of severe allergic reactions, prior receipt of booster shots, and individuals’ opinion, viewpoint, and attitude toward vaccination. Interventions aimed at addressing these factors have the potential to alleviate vaccination fear among medical staffs and improve the acceptance of the fourth dose vaccination.

Acknowledgments

The authors gratefully acknowledge the supervisors and all employees who participated in this study for their assistance as well as all the experts and members of our group for their help and advice

Appendix 1. Socio-demographic characteristics of the non-respondents and respondents

VariablesTotal
(n = 1832)
Non-respondents
(n = 1219)
Respondents
(n = 613)
p
Sex, n (%)   .101
 Male494 (27.0)314 (25.8)180 (29.4) 
 Female1338 (73.0)905 (74.2)433 (7.6) 
Age, Mean ± SD36.0 ± 10.636.4 ± 7.535.2 ± 15.0.029
Education, n (%)   .127
 College and below292 (15.9)183 (15)109 (17.8) 
 Undergraduate and above1540 (84.1)1036 (85)504 (82.2) 
Type of jobs, n (%)   .693
 Nurse853 (46.6)564 (46.3)289 (47.1) 
 Doctor642 (35.0)435 (35.7)207 (33.8) 
 Others337 (18.4)220 (18)117 (19.1) 
Residence, n (%)   .666
 Urban601 (32.8)404 (33.1)197 (32.1) 
 Town/Rural1231 (67.2)815 (66.9)416 (67.9) 

Authors’ contributions

L. Huang and Y. Jiang participated in study conception and design.

W. Hong and We. Hu performed acquisition of data.

L. Huang and X. Guan performed analysis and interpretation of data.

L. Huang and W. Hong participated in drafting the article.

Y. Jiang responsible for the writing and critical reading of the manuscript.

All of the authors read and approved the final manuscript.

Disclosure statement

No potential conflict of interest was reported by the authors.

Data availability statement

The data that support the findings of this study are available on reasonable request from the corresponding author

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