Introduction {#sec2-0300060520920051}
============

Nasogastric tube (NGT) feeding, defined as the delivery of nutrients through the nasal route into the stomach via a feeding tube,^[@bibr1-0300060520920051]^ is a common procedure for providing nutritional support in patients who are unable to ingest food orally because of health issues^[@bibr2-0300060520920051]^ or for patients whose nutrition intake is insufficient.

Over 790,000 NGTs were delivered by the National Health Service Supply Chain in 2015,^[@bibr3-0300060520920051]^ and approximately 6.6 million patients undergo NGT intubation in China each year.^[@bibr4-0300060520920051]^ Several studies have identified a theory--practice gap among nurses with respect to their practices of NGT placement and management of complications during feeding.^[@bibr5-0300060520920051],[@bibr6-0300060520920051]^ Inappropriate practices, including the inability to confirm the tube location, may cause adverse events, even death. Therefore, it is important to investigate whether nurses have adopted safe practices.

Nasogastric feeding is one of the most common nursing procedures used in clinical settings. The standards extensively used in China in terms of nasogastric feeding are based on the Practice Guideline of Clinical Nursing^[@bibr7-0300060520920051]^ and Basic Nursing.^[@bibr8-0300060520920051]^ The former does not describe the method of NGT placement or the method of confirming the position of the NGT. The latter introduces the method of NGT placement and three traditional methods to confirm the position of the NGT (gastric juice suction, auscultation of injected air, and observation of air bubbles). NGTs are usually inserted blindly by nurses who cannot see where the tube is going as it passes out of sight through the patient's nose and throat. Thus, the placement and patency of NGTs should be checked before administration of medication or commencement of feeding.^[@bibr9-0300060520920051]^ However, methods used for feeding tube confirmation and the frequency of their usage vary widely.^[@bibr10-0300060520920051]^ Unfortunately, adverse events including pneumonia, pneumothorax, and death are positively correlated with inconsistent nursing practices in the placement of feeding tubes.^[@bibr11-0300060520920051]^ Between September 2011 and March 2016 in the United Kingdom, 95 incidents of NGT misplacement were reported.^[@bibr3-0300060520920051]^ In China, Lu et al.^[@bibr12-0300060520920051]^ studied 30 patients with nasogastric feeding in the neurosurgery department and reported the incidence of diarrhea, vomiting and aspiration, constipation, gastric retention, and gastrointestinal bleeding was 30.0%, 43.3%, 73.3%, 33.3%, and 23.3%, respectively. Liu et al.^[@bibr13-0300060520920051]^ analyzed 85 patients with severe stroke who had hyperglycemia and found that 71.76% had gastric retention. Moreover, in terms of methods for predicting the NGT insertion length, measurements from the nose to the ear lobe to the xiphoid process of the sternum (NEX) or from the forehead to the xiphoid process (FX) frequently appear in nursing textbooks and are taught in nursing schools.^[@bibr8-0300060520920051],[@bibr14-0300060520920051]^ However, Chen et al.^[@bibr15-0300060520920051]^ and Taylor et al.^[@bibr16-0300060520920051]^ have shown that the length using the NEX method was insufficient. Furthermore, it was suggested that the NEX and Hanson's method should never be used for measuring the NGT length prior to insertion in adults.^[@bibr17-0300060520920051]^ Current research regards the method that takes into account sex (gender), weight, and nose to the umbilicus with an adult's head resting flat on the bed (GWNUF) as the best available method.^[@bibr14-0300060520920051],[@bibr17-0300060520920051]^

Gastric access for feeding is less invasive than other methods of artificial feeding because the NGT is easy to insert and remove. Nasogastric feeding allows for normal absorption of nutrients, which provides greater versatility in the diet.^[@bibr18-0300060520920051]^ In addition, nasogastric feeding can stimulate the gastric phase of digestion and does not divert from potential sites for the absorption of nutrients.^[@bibr19-0300060520920051]^ Despite the advantages of NGT use, some patients have complications linked to either the enteral access itself or to enteral feeding.^[@bibr20-0300060520920051]^

Several issues related to NGT positioning and techniques (such as feeding access and gastrointestinal intolerance) often interrupt enteral nutrition (EN).^[@bibr21-0300060520920051][@bibr22-0300060520920051]--[@bibr23-0300060520920051]^ Feeding intolerance (FI) is the primary reason for discontinuing EN.^[@bibr24-0300060520920051],[@bibr25-0300060520920051]^ Gungabissoon et al.^[@bibr26-0300060520920051]^ defined FI as any of the following: large gastric residual volume (GRV), vomiting/emesis, diarrhea, abdominal distension, or subjective discomfort. The prevalence of FI was 30.5% to 38.3% and occurred after a median 3 days from commencement of EN.^[@bibr26-0300060520920051][@bibr27-0300060520920051]--[@bibr28-0300060520920051]^ GRVs are widely used to assess FI; however, the definition and management of excessive GRV remain controversial.^[@bibr27-0300060520920051],[@bibr29-0300060520920051]^

Clinical nurses are responsible for inserting the NGT, confirming its placement, administering feedings, and monitoring or handling complications. It has been shown that adherence to standardized guidelines via a nurse-led EN feeding procedure (for an early start and timely increase of EN) improves the nutritional intake of patients.^[@bibr30-0300060520920051]^ There is a paucity of studies on whether practices among Chinese nurses are consistent with the current best practices for nasogastric feeding. Hence, it is imperative to investigate whether clinical nurses' practices are in accordance with evidence-based best practice guidelines so that nursing administrators and clinical nurses can improve nasal feeding for patients. Therefore, the purpose of this study was to evaluate Chinese clinical nurses' current NGT intubation and feeding practices for adults.

Methods {#sec3-0300060520920051}
=======

Design {#sec4-0300060520920051}
------

This was a multicenter cross-sectional descriptive study.

Sampling and participants {#sec5-0300060520920051}
-------------------------

Participants were recruited using convenience sampling. A sample size of 408 was required based on the following formula^[@bibr31-0300060520920051]^: n = P(1−P)/(E^2^/Z^2^+P(1−P)/N), α = 0.05, P = 50%, Z = 1.96, E = 0.05, N≈3000, with 20% of the estimated sample added to offset attrition of the sample.

Registered nurses who met all of the following requirements were included in this study: holding a nursing practice certificate of the People's Republic of China; working in the wards (where clinical nurses are commonly in charge of enteral nutrition) of three comprehensive tertiary grade A hospitals in Xiamen (Zhongshan Hospital, affiliated to Xiamen University, which has 38 departments and 2000 beds; The First Affiliated Hospital of Xiamen University, with 52 departments and 2500 beds; and Xiamen Hospital of Traditional Chinese Medicine, which has 32 departments and 1200 beds); and willing to participate in the study. Exclusion criteria included administrative-level nurses as well as nurses working in the outpatient service, operating room, and emergency department.

Instrument {#sec6-0300060520920051}
----------

We used a self-designed Chinese version of a questionnaire, comprising 30 questions and based on clinical practice guidelines and other relevant literature involving NGT intubation and feeding procedures in adults.^[@bibr1-0300060520920051],[@bibr9-0300060520920051],[@bibr32-0300060520920051][@bibr33-0300060520920051][@bibr34-0300060520920051][@bibr35-0300060520920051]--[@bibr36-0300060520920051]^ The draft of the questionnaire was revised after review by an expert panel comprising five senior nurses with at least 10 years' clinical experience. The final version of the questionnaire contained two parts: participants' demographic characteristics (including department, age, working seniority, sex, educational level, classification, whether a clinical nurse specialist in EN, and frequency of nasogastric feeding); the other part included questions about nasogastric feeding practices, which involved placement of the NGT, EN administration, and management of FI. The expert panel used four-point Likert rating scales (1 = not relevant, 2 = somewhat relevant, 3 = quite relevant, 4 = highly relevant) to assess the relevance of each item and the research content. The questionnaire is considered reliable, with a scale-level content validity index (S-CVI) of 0.98.

Data collection procedures {#sec7-0300060520920051}
--------------------------

Data collection was conducted between February and April 2018, as follows. Researchers went to each department and explained the purpose and scope of this study to the head nurse, to obtain permission for data collection. Then, participants were given a paper-and-pencil questionnaire to complete individually. Nurses returned the completed questionnaire in a sealed envelope to the head nurse of each ward. One week later, researchers collected the questionnaires from the head nurses.

Ethical considerations {#sec8-0300060520920051}
----------------------

This study was approved by the Committee for Medical Ethics of Xiamen Zhongshan Hospital, affiliated to Xiamen University (No: xmzsyy2019033). The survey purpose, benefits, disadvantages, and notes for completing the form were explained to all participants. Participants were considered to have provided their consent by replying to the survey questions.

Data analysis {#sec9-0300060520920051}
-------------

Descriptive data were used to present the results of nurses' responses as frequency and percentage. The chi-squared test was applied to examine statistically significant differences in the sample characteristics and nurses' practices between departments. We considered *p* value \<0.05 as indicating statistical significance. All statistical analyses were performed with IBM SPSS v. 22.0 software (IBM Corp., Armonk, NY, USA).

Results {#sec10-0300060520920051}
=======

Characteristics of participants {#sec11-0300060520920051}
-------------------------------

Of the 560 questionnaires distributed to participants, 464 (82.9%) were completed and returned. The demographic characteristics of study participants are shown in [Table 1](#table1-0300060520920051){ref-type="table"}. Among participants, 168 (36.2%) were from internal medicine, and 433 (93.3%) were women. In addition, nurses with an undergraduate-level education (324/69.8%), junior nurses (276/9.5%), and nurses who performed nasal feeding every day (218/47.0%) respectively accounted for the largest proportion with respect to education, classification, and frequency of nasogastric feeding.

###### 

Characteristics of study participants (N = 464).

![](10.1177_0300060520920051-table1)

  Characteristics                    n     \%     Mean (SD)
  ---------------------------------- ----- ------ --------------
  Department                                      
   Medical unit                      168   36.2   
   Surgical unit                     137   29.5   
   Intensive care unit               159   34.3   
  Age (years)                        464          31.66 (6.33)
  Work experience (years)            464          9.46 (6.82)
  Sex                                             
   Male                              31    6.7    
   Female                            433   93.3   
  Highest educational level                       
   Technical secondary school        6     1.3    
   College diploma                   133   28.7   
   Undergraduate degree              324   69.8   
   Master's degree                   1     0.2    
  Classification                                  
   Junior                            276   59.5   
   Mid-level                         157   33.8   
   Senior                            31    6.7    
  Frequency of nasogastric feeding                
   Daily                             218   47.0   
   Few times a week                  143   30.8   
   Weekly                            11    2.4    
   Monthly                           26    5.6    
   Other                             66    14.2   

Abbreviation: SD, standard deviation.

NGT intubation and feeding practices {#sec12-0300060520920051}
------------------------------------

NGT intubation and feeding practices among participants are shown in [Table 2](#table2-0300060520920051){ref-type="table"}. A total 369 (79.5%) nurses chose the FX method to determine the NGT length before catheterization; no nurses adopted the GWNUF method. To confirm the location of the NGT, most nurses regarded traditional methods as the gold standard, namely, auscultation of injected air (233/50.2%), the bubble test (161/34.7%), or observing feeding tube aspirate (159/34.3%); only 125 (26.9%) chose radiography as the gold standard. In addition, 384 (82.8%) nurses observed feeding tube aspirate during the process of blind insertion whereas most nurses observed the external length of the tube to confirm its location when starting nasal feeding. In addition, 431 (92.9%) nurses always marked the exit site of the NGT after verifying its location. For EN management, 417 (89.9%) nurses always raised the backrest of the bed 30° to 45° before nasal feeding. However, only 84 (18.1%) nurses chose intermittent feeding, and nearly half (203/43.8%) chose bolus feeding. More than half of nurses (55.0%) used sterile normal saline as the solution for oral care, and only 36.6% used chlorhexidine. For FI monitoring, only 77 (16.6%) nurses thought that the maximum GRV threshold was 250 mL, and 207 (44.6%) thought it was 200 mL. In the case of high GRV and diarrhea, 391 (84.3%) and 209 (45%) nurses, respectively, chose to discontinue nasal feeding immediately.

###### 

Practices of NGT intubation and feeding (N = 464).

![](10.1177_0300060520920051-table2)

  Practices                                                                                           n     \%
  --------------------------------------------------------------------------------------------------- ----- ------
  *Placement of NGT*                                                                                        
  Methods used to determine internal length of the NGT                                                      
   FX                                                                                                 369   79.5
   NEX                                                                                                168   36.2
   Hanson method ((\[NEX--50 cm\]/2)+50 cm)                                                           7     1.5
   GWNUF                                                                                              0     0
  Methods considered the gold standard to confirm placement of blindly inserted NGT                         
   Auscultation of injected air                                                                       233   50.2
   Bubble test                                                                                        161   34.7
   Observing feeding tube aspirate                                                                    159   34.3
   Radiography                                                                                        125   26.9
   Observing a change in the external tube length                                                     83    17.9
   pH testing of aspirate                                                                             80    17.2
   Observing signs of respiratory distress                                                            65    14.0
   Capnography                                                                                        12    2.6
  Methods to confirm placement of blindly inserted NGT during tube insertion procedure                      
   Observing feeding tube aspirate                                                                    384   82.8
   Observing a change in the external tube length                                                     348   75.0
   Observing signs of respiratory distress                                                            326   70.3
   Auscultation of injected air                                                                       305   65.7
   Bubble test                                                                                        238   51.3
   pH testing of aspirate                                                                             33    7.1
   Radiography                                                                                        24    5.2
   Capnography                                                                                        18    3.9
  Methods to confirm placement of blindly inserted NGT after feeding is started                             
   Observing a change in the external tube length                                                     348   75.0
   Observing feeding tube aspirate                                                                    357   76.9
   Observing signs of respiratory distress                                                            304   65.5
   Auscultation of injected air                                                                       203   43.8
   Bubble test                                                                                        185   39.9
   pH testing of aspirate                                                                             28    6.0
   Radiography                                                                                        24    5.2
   Capnography                                                                                        13    2.8
  Time point NGT location is checked                                                                        
   During insertion procedure                                                                         368   79.3
   Before each bolus or intermittent feeding                                                          358   77.2
   Before medication administration                                                                   357   76.9
   During bedside handover                                                                            189   40.7
   At 4-hour intervals during continuous feeding                                                      172   37.1
  Exit site of NGT marked after location verification                                                       
   Always                                                                                             431   92.9
   Sometimes                                                                                          20    4.3
   Never                                                                                              13    2.8
  *EN administration*                                                                                       
  Time to initiate feeding adult critically ill patients with hemodynamic stability after admission         
   ≤48 hours after admission                                                                          439   94.6
   \>48 hours after admission                                                                         25    5.4
  EN formulations discarded within 24 hours of preparation if not used                                      
   Yes                                                                                                458   98.7
   No                                                                                                 6     1.3
  Longest time EN formulas are exposed to room temperature                                                  
   4 hours                                                                                            381   82.1
   6 hours                                                                                            44    9.5
   8 hours                                                                                            26    5.6
   10 hours                                                                                           13    2.8
  Patient placed (without contraindications) in backrest elevation of 30°--45° before feeding               
   Always                                                                                             417   89.9
   Sometimes                                                                                          36    7.8
   Never                                                                                              11    2.4
  Patient placed in semi-recumbent position for at least 30 to 60 minutes                                   
   Always                                                                                             397   85.6
   Sometimes                                                                                          54    11.6
   Never                                                                                              13    2.8
  Method used to administer EN                                                                              
   Bolus feeding                                                                                      203   43.8
   Continuous feeding                                                                                 166   35.8
   Intermittent feeding                                                                               84    18.1
   Feeding method selected according to physicians orders                                             11    2.3
  Volume that should not be exceeded during each bolus feeding                                              
   400 mL                                                                                             461   99.4
   500 mL                                                                                             2     0.4
   600 mL                                                                                             1     0.2
  Time points when tube is flushed                                                                          
   Before intermittent or bolus feeding                                                               417   89.9
   After intermittent or bolus feeding                                                                372   80.2
   At 4-hour intervals with continuous EN                                                             324   69.8
   After GRV measurement                                                                              270   58.2
  Solution used to flush the tube                                                                           
   Warm boiled water                                                                                  442   95.3
   Cold boiled water                                                                                  10    2.2
   Normal saline                                                                                      9     1.9
   Sterile water                                                                                      3     0.6
  Solution used for oral care in adult critically ill patients                                              
   Sterile normal saline                                                                              255   55.0
   Chlorhexidine mouth wash                                                                           170   36.6
   Warm water                                                                                         20    4.3
   Furacilin solution                                                                                 11    2.4
   Kangfuxin Ye                                                                                       8     1.7
  Monitoring and managing FI                                                                                
  Frequency of GRV monitoring                                                                               
   Every 4--8 hours                                                                                   291   62.7
   Never                                                                                              96    20.7
   Every 6 hours                                                                                      40    8.6
   Every 8 hours                                                                                      37    8.0
  Method used to measure GRV                                                                                
   Syringes                                                                                           450   97.0
   Scintigraphy                                                                                       6     1.3
   Refractometry                                                                                      6     1.3
   Breath tests                                                                                       2     0.4
  Threshold of high GRV                                                                                     
   200 mL                                                                                             207   44.6
   150 mL                                                                                             117   25.2
   250 mL                                                                                             77    16.6
   100 mL                                                                                             63    13.6
  How to deal with high GRV                                                                                 
   Stop feeding immediately                                                                           391   84.3
   Use prokinetic agents                                                                              251   54.1
   Slow infusion speed                                                                                210   45.3
   Perform abdominal massage for the patient                                                          190   40.9
   Report to the doctor for further examination                                                       9     1.9
  How to determine when FI is present                                                                       
   Observe for abdominal distention and/or discomfort                                                 442   95.3
   Observe for nausea and/or vomiting                                                                 370   79.7
   Measure GRV                                                                                        364   78.4
   Listen for bowel sounds                                                                            211   45.5
  What to do when the patient has diarrhea                                                                  
   Feeding continued while evaluating the etiology of diarrhea to determine appropriate treatment     255   55.0
   Cease EN immediately                                                                               209   45.0

Abbreviations: NGT, nasogastric tube; NEX, nose--ear--xiphoid; FX, forehead--xiphoid; GWNUF, gender, weight, and nose to umbilicus with adult's head flat on the bed; EN, enteral nutrition; GRV, gastric residual volume; FI, feeding intolerance.

Discussion {#sec13-0300060520920051}
==========

NGT placement presents an intrinsic risk to patient safety as it is carried out blindly.^[@bibr2-0300060520920051]^ Therefore, it is very important to determine the location of the NGT. Our survey showed that nurses used various methods to check the NGT position. Although several guidelines suggest that radiography is the gold standard for confirming NGT placement,^[@bibr32-0300060520920051],[@bibr36-0300060520920051][@bibr37-0300060520920051]--[@bibr38-0300060520920051]^ we found that many nurses still regarded auscultation, observation of feeding tube aspirate, or the bubble test as the gold standard. In reality, however, there are many difficulties for clinical nurses in performing radiography. For example, a doctor's order is needed to perform radiography, and access to an X-ray machine is not always available; in addition, the costs related to radiography are relatively high. Therefore, observing the external length of the tube as well as the three traditional methods above are widely used by Chinese nurses. We found that most (95%) nurses used traditional (but inaccurate) methods in clinical practice, including observing feeding tube aspirate, observing the external tube length, watching for signs of respiratory distress, auscultation, and the bubble test. These findings were consistent with those of previous reports.^[@bibr6-0300060520920051],[@bibr10-0300060520920051],[@bibr39-0300060520920051]^ Unlike in the United Kingdom where pH testing is recommended as the first-line test method,^[@bibr40-0300060520920051]^ this procedure was rarely adopted by the nurses surveyed in our study.

Nearly all (98.5%) nurses used NEX or FX measurement alone or in combination. Current literature recommends the GWNUF method as the most appropriate means of measuring the NGT length prior to insertion in adults.^[@bibr14-0300060520920051],[@bibr17-0300060520920051]^ Nevertheless, no nurses in our study used this method. Most nurses confirmed the NGT location on various occasions, such as during the insertion procedure, before intermittent feeding, and before medication administration, and they always marked the exit site of the NGT after verifying its location. These practices meet the current recommended guidelines.^[@bibr32-0300060520920051],[@bibr36-0300060520920051]^

Our study showed that most participants correctly followed the guidelines for initiation time of feeding, storage of EN formulations, body position placement, and tube flushing. These findings were in line with those of previous studies.^[@bibr6-0300060520920051],[@bibr39-0300060520920051]^ We also found that bolus feeding was the most commonly used form of administering EN. Currently, no form of EN delivery is widely accepted as the best in this field.^[@bibr33-0300060520920051],[@bibr41-0300060520920051],[@bibr42-0300060520920051]^ However, rather than using the recommended chlorhexidine mouthwash,^[@bibr34-0300060520920051],[@bibr43-0300060520920051]^ many clinical nurses used sterile normal saline when providing oral care to critically ill patients.

In the present study, we found that many nurses used syringes to measure GRV every 4 hours, and that the most frequently used GRV threshold values were 150 mL and 200 mL. These findings were partly in accordance with other surveys.^[@bibr6-0300060520920051],[@bibr29-0300060520920051]^ When dealing with high GRV, many participants stopped feeding immediately. According to the 2015 Canadian Clinical Practice Guidelines for critically ill patients with a GRV between 250 mL and 500 mL (inclusive), frequent examination of residuals every 4 or every 8 hours should be regarded as the best strategy to optimize EN.^[@bibr33-0300060520920051]^ Moreover, the Society of Critical Care Medicine (SCCM) and American Society for Parenteral and Enteral Nutrition (ASPEN) recommend that GRVs should not be included as part of regular care for patients in the intensive care unit (ICU) who are receiving EN. If GRVs are used in the ICU, discontinuing EN with GRV \<500 mL and no other signs of intolerance should be avoided.^[@bibr34-0300060520920051]^ Hence, the definition and management of excessive GRV remain controversial.

Despite appropriate monitoring and management of FI representing a main task in nursing, it is difficult to quantify the signs of intolerance.^[@bibr29-0300060520920051]^ In the present survey, we found that several participants determined this intolerance based on bowel sounds, which is not a reliable indicator of normal bowel function.^[@bibr29-0300060520920051]^ SCCM and ASPEN support the premise that evidence of bowel function and bowel sounds are not required for initiation of EN.^[@bibr34-0300060520920051]^ When patients developed diarrhea, nearly half of clinical nurses surveyed reported ceasing administration of EN immediately. However, SCCM and ASPEN recommend that EN should not be discontinued based solely on the occurrence of diarrhea; instead, EN should be continued until the etiology of diarrhea is determined and the appropriate treatment(s) administered.^[@bibr34-0300060520920051]^

Conclusions {#sec14-0300060520920051}
===========

Our study demonstrated that some aspects of nurses' practices regarding nasogastric feeding were not consistent with international guidelines, which may predispose patients to underfeeding. The practice gaps found in this survey highlight the need to realign nurses with evidence-based best practices. Our survey provides a fundamental reference for interventional and educational programs in this field.

Relevance to clinical practice {#sec15-0300060520920051}
==============================

Although this survey was conducted in China, NGT-related issues occur in other countries. Our study may serve as an impetus for nursing administrators and clinical nurses to revise their nasogastric feeding procedures to comply with evidence-based guidelines, thereby ensuring the safe and effective management of patients receiving nasogastric feeding. Our study findings indicated that some aspects of nurses' nasogastric feeding practices were inconsistent with the current guidelines, which may predispose patients to underfeeding.The theory--practice gaps identified in this study suggest a need to improve the level of nurses' practices to the required standards.Further interventional or educational programs in this field should be conducted based on the fundamental data provided in our study.

Abbreviations {#sec17-0300060520920051}
=============

NGT: nasogastric tube

EN: enteral nutrition

NEX: nose--ear--xiphoid

FX: forehead--xiphoid

GRV: gastric residual volume

GWNUF: gender, weight, and nose to umbilicus with the adult's head flat on the bed

FI: feeding intolerance

S-CVI: scale-level content validity index

SCCM: Society of Critical Care Medicine

ASPEN: American Society for Parenteral and Enteral Nutrition.

We appreciate the help provided by the clinical departments of the three comprehensive tertiary grade A hospitals in Xiamen (The First Affiliated Hospital of Xiamen University, Zhongshan Hospital affiliated to Xiamen University, and Xiamen Hospital of Traditional Chinese Medicine) during the data collection.

Author contributions {#sec20-0300060520920051}
====================

Study design: Li-chun Xu, Xiao-jin Huang, and Hai-hua Zhu; data collection: Li-chun Xu, Hai-hua Zhu, and Jun-yi Zheng; data analysis: Li-chun Xu and Jun-yi Zheng; and manuscript writing: Li-chun Xu, Bi-xia Lin, and Xiao-jin Huang. All authors reviewed the final manuscript.

Data availability {#sec16-0300060520920051}
=================

The datasets generated and analyzed in the present study are available from the corresponding author on reasonable request.

Declaration of conflicting interest {#sec19-0300060520920051}
===================================

The authors declare that there is no conflict of interest.

Funding {#sec18-0300060520920051}
=======

This study was funded by the Bureau of Science and Technology of Xiamen (Number: 3502Z20134017).

ORCID iD
========

Hai-hua Zhu <https://orcid.org/0000-0002-1574-9562>

[^1]: These authors contributed equally to this work.
