Knowledge, attitude, and practices of community pharmacy staff toward antimicrobial stewardship programs: a cross-sectional study from Northeastern China

ABSTRACT

Background

Antimicrobial resistance is one of the most significant challenges of the twenty-first century, and the illegal sale of antimicrobial drugs at community pharmacies is a driver of antimicrobial resistance. This study explores the knowledge, attitudes, and practices (KAP) of pharmacy staff toward antimicrobial stewardship programs (ASPs).

Methods

We conducted a descriptive cross-sectional study among community pharmacy staff in Northeastern China, from April 1 to 31 May 2019, using a self-administered KAP questionnaire comprising 20 items. The data analysis was carried out by employing Mann-Whitney and Kruskal-Wallis tests.

Results

A response rate of 98.5% (394/400) was obtained. The majority of participants (94.9%) demonstrated a good understanding of antimicrobial use, but they lacked an adequate understanding of ASPs. Nearly half of the participants (40.6%) reported that they sold antimicrobials to patients without a prescription. Education level, age, occupation, and experience were all significantly associated (P < 0.05) with participants’ median ASPs scores. Besides, the presence of a licensed pharmacist (OR 46.327, 95% CI 2.443–878.451, P = 0.011) was the main factor associated with the pharmacy staff’s understanding of antimicrobial use policies.

Conclusions

The participants’ knowledge of antimicrobials was good, and their attitudes regarding ASPs were positive, but their practices regarding ASPs were poor.

KEYWORDS:

• Community pharmacies
• antimicrobial stewardship program
• ASP
• KAP
• China

1. Introduction

Antimicrobials are used to prevent and treat a variety of infections [1]. Since their discovery, antimicrobials have served as the cornerstone of modern medicine [2]. However, the persistent misuse of antimicrobials in human and animal health has encouraged the emergence and spread of antimicrobial resistance (AMR) [3,4]. AMR is rising to dangerously high levels in all parts of the world, as reported by numerous studies [5–8]. AMR threatens our ability to combat common infectious diseases and support modern medical procedures. According to some predictions, the deaths associated with AMR could exceed 10 million per year by 2050 [9,10].

The inappropriate use of antibiotics is common in both community and hospital settings; however, its intensity is higher in community settings, as highlighted by the World Health Organization [11]. In China, the problem of AMR is particularly challenging. China is ranked second globally in overall antibiotic consumption in the human and animal sector. Various factors trigger the abuse of antimicrobials [12]; of these factors, the knowledge, attitude, and practices (KAP) of service providers such as community pharmacists may play a leading role [13].

China has nearly 500,000 community pharmacies [14], which are the primary means by which antimicrobials are distributed [15]. However, the government has not issued mandatory stewardship programs to community pharmacies. Only some regulations have been approved, such as one passed in 2004 requiring that antibiotics be dispensed only with a valid prescription [16]. Still, the irrational sale of antibiotics by community pharmacy staff is widespread in China [17]. A recent study undertaken in three provinces of China showed that more than half of the community pharmacies dispensed antibiotics to the patients without inquiring about a valid prescription [18]. Additionally, this regulation has negatively affected the sales profits of pharmacies, leading to noncompliance by some pharmacies.

Furthermore, regulations have mandated the dispensing of antibiotics only under the guidance of a licensed pharmacist at community pharmacies [19,20]. However, according to recent statistics [14], the number of community pharmacies dramatically exceeds the total number of licensed pharmacists (419,500). This means that some patients do not receive proper medication counseling, and this lack of guidance can lead to the abuse of antimicrobials.

Antimicrobial stewardship in China is an issue with serious public health implications. A recent study found that the attitude of pharmacists regarding antimicrobial stewardship programs (ASPs) was positive. However, certain gaps in knowledge about some aspects of antimicrobials and participation in ASPs were highlighted coupled with a poor quality of pharmacy services [17,21,22]. No study has been undertaken to investigate the view of pharmacy staff toward ASPs. Therefore, this exploratory study was designed to investigate the knowledge, attitudes, and practices (KAP) of pharmacy staff toward antimicrobials and ASPs in community pharmacies in Shenyang, China.

2. Materials and methods

2.1. Study design and setting

A descriptive cross-sectional survey was carried out from April 1 to 31 May 2019, in the community pharmacies of Shenyang. Shenyang, the capital city of Liaoning Province, is a megacity located in the northeastern part of China with a population of 8.3 million and is a distinct city in terms of socio-economic status and health development, including 13 administrative divisions, including 5 districts in central urban areas, 4 districts in the suburbs, and 4 counties [23,24].

2.2. Survey design and scoring system

We reviewed the literature thoroughly before developing the questionnaire [21,25–28]. The final version of the questionnaire was checked for validation by two professors with a background in pharmacy. After a preliminary survey, we modified the initial questionnaire to clarify some questions to improve participants’ understanding.

The final approved questionnaire had 20 items with four sections. The first section comprised seven questions on the demographic history of the participants, such as age, gender, occupation, experience, type of pharmacy, and the presence of a licensed pharmacist. The second section had six questions on the knowledge of participants about antimicrobials and ASPs. A 5-point Likert scale was utilized to record participants’ responses. In this scale, scoring was 1 for ‘strongly don’t understand,’ 2 for ‘don’t understand,’ 3 for ‘neutral,’ 4 for ‘understand,’ and 5 for ‘strongly understand.’ The third section had three questions designed to give us a clear assessment of participants’ attitudes regarding ASPs. Again, we employed a 5-point Likert scale to record the responses, using 1 for ‘strongly disagree,’ 2 for ‘disagree,’ 3 for ‘neutral,’ 4 for ‘agree,’ and 5 for ‘strongly agree.’ The fourth section had four questions on participants’ practices regarding the selling of antimicrobials and was rated with a semantic differential scale, with responses recorded as ‘always,’ ‘occasionally,’ and ‘never.’

After a pilot study, the value of Cronbach’s alpha was also measured, which was 0.725, depicting good internal consistency.

2.3. Sampling

The focus of this survey was community pharmacies; there were no specific statistics as to their location. We found by reviewing the literature that the distribution of community pharmacies is correlated with a population [21], so we sampled in proportion to the population in each division, which yielded a sample size of 384.

We made the following assumptions in determining sample size:

(1) The e (margin of error) is 5%.

(2) The CI is 95%, obeying the normal distribution Z = 1.96.

(3) p is population proportion (if unknown, we used p = 0.5)

We used the following equation to calculate the sample size:

n = (z)² p (1 – p)/d²

or if p = 1/2 (0.5)

n = (z)²/4d²

We approached 400 participants to compensate for nonresponse. The specific sampling is shown in a supplementary file (Table A1). The sample area was divided into 13 administrative divisions, following Shenyang city’s regional divisions [23]. We selected the sampled sub-district using a random numbers generator.

2.4. Data collection

Data collection training sessions were planned to familiarize the data collectors about the key elements of the survey and to help them understand their roles and responsibilities. The training was given to all the members of the survey team prior to the commencement of the survey. Trained investigators administered the questionnaire to pharmacy staff in Shenyang, including managers, licensed pharmacists, and general staff.

Observational data for each pharmacy visit were recorded in form shortly after the visit. To ensure the quality and integrity of the data, the team leader visited data collection sites randomly after the questionnaire had been administered in order to verify the responses. Each questionnaire was double-checked to confirm that all of the survey items had been answered.

2.5. Data analysis

Descriptive statistical analysis was carried out to represent data as frequencies and percentages by SPSS version 16.0. We performed Kolmogorov-Smirnov and Shapiro-Wilks tests to test the normality of the data. Given the non-normal distribution of the data, we used inference statistics (Mann-Whitney and Kruskal-Wallis tests) to determine the difference in median scores. We used logistic regression to analyze the factors underlying the extent of respondents’ understanding of antimicrobial stewardship policy. A P value of less than 0.05 was considered statistically significant.

2.6. Ethics approval

Before this research was conducted, an informed consent form and other research-related documents were reviewed and approved by the Biomedical Ethics Committee for Medical Research of Xi’an Jiaotong University (2019–0153). The purpose and protocol of the study were thoroughly explained to participants, and written consent was obtained before the commencement of the study.

3. Results

3.1. Demographics and other characteristics of the study population

A total of 400 questionnaires were distributed in 226 community pharmacies. Six of the returned questionnaires were incomplete and therefore removed from the final analysis. Most community pharmacies are chained (n = 196, 86.7%). Out of 394 survey participants, most were male (n = 378, 95.9%), aged 30–39 years (n = 138, 35.0%), general staff (n = 310, 78.7%) and had a college-level education (126, 32.0%). More than half of the participants (n = 218, 55.4%) had less than five years of experience (Table 1). The distribution of the actual sampling numbers is provided in a supplementary file (Table A2).

Table 1. Characteristics of participants

Variable	Frequency	Percentage (%)
Gender
Male	16	4.1
Female	378	95.9
Ages(years)
20–29	110	27.9
30–39	138	35.1
40–49	106	26.9
≥50	40	10.1
Level of education
High school and below	106	26.9
Technical secondary school	121	30.7
College	126	32.0
Undergraduate	40	10.1
Graduate and above	1	0.3
Occupation
Manager	56	14.2
Licensed pharmacist	26	6.6
General staff	310	78.7
Other(volunteer)	2	0.5
Experience(years)
<5	218	55.4
5–10	111	28.2
11–15	38	9.6
>15	27	6.8
Type of pharmacy
Independent pharmacy	30	13.3
Chained pharmacy	196	86.7
Had a licensed pharmacist on duty
Yes	79	35.3
No	147	64.7

The pharmacies surveyed (n = 199, 88.0%) classified the antimicrobials as antibacterial, anti-inflammatory, or antibiotic. Some well-known chain pharmacies (n = 130, 57.5%) had antibacterial and anti-inflammatory counters, and some pharmacies had designated antimicrobial counters. All pharmacies had prescription drug labels to use when dispensing drugs.

3.2. Participants’ knowledge regarding antimicrobials

The survey participants had good antimicrobial-related knowledge. A majority of participants (99.5%) knew that antimicrobials are used to treat bacterial infection. A large number of respondents (91.9%) knew that the common cold and influenza are caused by viruses, and 93.4% knew that antimicrobials could not cure all disease.

To understand participants’ perception and judgment of the risk of antimicrobials, we sorted the results according to the following categories: increasing treatment costs (3.90) > causing damage to body organs (2.68) > bacterial resistance (1.73) > causing an allergic reaction (1.69).

The participants’ sources of knowledge about antimicrobials were ‘pharmacy training’ (78.7%), followed by ‘professional newspapers and books’ (72.3%), ‘representatives of pharmaceutical manufacturers’ (46.9%), ‘various promotional materials’ (27.7%), ‘television broadcast’ (9.4%), and ‘Internet’ (8.4%). The average value of the participants’ understanding of antimicrobial stewardship policies is 2.32 + 0.891.

3.3. Participants’ attitudes toward ASPs

All participants responded to three questions assessing their attitude toward ASPs. Most participants (n = 291, 73.9%; median = 5, IQR = 1) thought that ‘ASPs should be incorporated at the community pharmacy and ASPs reduce the problem of antimicrobial resistance.’ Less than half of participants (n = 160, 40.6%; median = 4, IQR = 1) strongly agreed with the statement that ‘adequate training should be provided to community pharmacists on antimicrobial use’ (Table 2).

Table 2. Participants’ attitude toward antimicrobial stewardship programs

Variable	SD	DA	N	A	SA	Median (IQR)
ASPs should be incorporated at the community-pharmacy level	0 (0.0%)	1 (0.2%)	4 (1.0%)	98 (24.9%)	291 (73.9%)	5.00 (1)
ASPs reduce the problem of antimicrobial resistance	0 (0.0%)	1 (0.2%)	4 (1.0%)	98 (24.9%)	291 (73.9%)	5.00 (1)
Adequate training should be provided to community pharmacists on antimicrobial use	0 (0.0%)	16 (4.0%)	81 (20.6%)	137 (34.8%)	160 (40.6%)	4.00 (1)

strongly disagree (SD), disagree (DA), neutral (N), agree (A), and strongly agree (SA).

3.4. Participants’ antimicrobial practices

The practices of the participants regarding ASPs were poor. Only 15.7% (n = 62, median = 2, IQR = 0) of participants reported often providing medication consultations to patients who bought antimicrobials. Close to half of participants (n = 160, 40.6%; median = 3, IQR = 1) reported having sold antimicrobials to patients without a prescription in the past week. More than half of the participants (n = 223, 56.6%; median = 2, IQR = 1) reported occasionally having received patients who took a hospital prescription to buy antimicrobial drugs. 69.5% of participants (n = 274, median = 1, IQR = 1) said they often told patients about the adverse effects of using antimicrobials (Table 3).

Table 3. Participants’ practices toward antimicrobials

Variable	Often N (%)	Occasionally N (%)	Never N (%)	Median (IQR)
In the past week, have you told patients about the adverse effects of using antimicrobials?	274 (69.5)	114 (28.9)	6 (1.6)	1.00 (1)
In the past week, have you given medication consultations to patients who bought antimicrobials at the pharmacy?	62 (15.7)	265 (67.3)	67 (17)	2.00 (0)
In the past week, have you sold antimicrobials to patients without a prescription?	2 (0.5)	160 (40.6)	232 (58.9)	3.00 (1)
In the past week, have you received patients who took a hospital prescription to buy antimicrobial drugs?	21 (5.3)	223 (56.6)	150 (38.1)	2.00 (1)

3.5. Differences in community pharmacists’ knowledge, attitude, and practices of ASPs

We checked differences in median KAP of ASPs scores across demographic groups. Neither knowledge nor attitude was shown to be significantly affected by demographics. Participants’ age, level of education, occupation, and experience showed a statistically significant difference with the median score of practices toward ASPs (P < 0.05). Gender, type of pharmacy, and whether a pharmacy had a licensed pharmacist on duty or not did not have a statistically significant difference (Table 4).

Table 4. Median scores of participants about their knowledge, attitude, and practices regarding ASPs

Variable	Category	Median Knowledge score (IQR)	P-value	Median attitude score (IQR)	P-value	Median practice score (IQR)	P-value
Gender*	Male	1(1)	0.716	5(1)	0.843	2(1)	0.291
	Female	1(1)		5(1)		2(1)
Ages (years) **	20–29	1(1)	0.769	5(1)	0.719	2(1)	<0.001
	30–39	1(1)		5(1)		2(1)
	40–49	1(1)		5(1)		2(1)
	≥50	1(1)		5(1)		2(1)
Level of education**	High school and below	1(1)	0.846	5(1)	0.246	2(1)	0.041
	Technical secondary school	1(1)		5(1)		2(1)
	College	1(1)		5(1)		2(1)
	Undergraduate	1(1)		5(1)		2(1)
	Graduate and above	1(-)		-		-
Occupation**	Manager	1(1)	0.636	5(1)	0.323	2(1)	<0.001
	Licensed pharmacist	1(1)		5(1)		2(1)
	General staff	1(1)		5(1)		2(1)
	Other	1(0)		5(1)		2(1)
Experience (years) **	<5	1(1)		5(1)	0.284	2(1)	<0.001
	5–10	1(1)	0.595	5(1)		2(1)
	11–15	1(1)		5(1)		2(1)
	>15	1(1)		5(1)		2(0)
Type of pharmacy**	Independent pharmacy	1(1)	0.917	5(1)	0.703	2(1)	0.273
	Chained pharmacy	1(1)		5(1)		2(1)
Had a licensed pharmacist on duty*	Yes	1(1)	0.958	5(1)	0.978	2(1)	0.102
	No	1(1)		5(1)		2(1)

Note: *Independent-sample Mann–Whitney U test; **independent-sample Kruskal–Wallis test.

Logistic regression analysis revealed that having a manager (OR 22.568, 95% CI 1.281–397.537, P = 0.033) and a licensed pharmacist on duty (OR 46.327, 95% CI 2.443–878.451, P = 0.011) were the factors significantly associated with participants’ understanding of antimicrobial policy (Table 5). Moreover, a pharmacy of independent type (OR 0.016, 95% CI 0.007–0.037, P < 0.001) was the factor associated with high levels of antimicrobial knowledge among staff because of pharmacy-sponsored training programs (supplementary file, Table A3).

Table 5. Logistic regression analysis of factors associated with the extent of understanding of antimicrobial stewardship policy

Variable	Category	Extent					OR	95% CI	P-value
		SDU	DU	N	U	SU
Gender	Male	3	5	6	0	2	1.153	0.430–3.093	0.777
	Female	52	197	99	19	11	1	-	-
Ages(years)	20–29	15	52	41	0	2	0.706	0.232–2.152	0.540
	30–39	22	77	29	7	3	0.629	0.233–1.697	0.360
	40–49	16	51	26	7	6	0.807	0.344–1.894	0.622
	>50	2	22	9	5	2	1	0-	-
Level of education	High school and below	19	49	24	10	4	4.259E-11	0-	0.999
	Technical secondary school	15	72	28	3	3	4.565E-11	0-	0.999
	College	18	69	36	3	0	5.231E-11	0-	0.999
	Undergraduate	3	12	17	3	5	1.552E-10	0-	0.999
	Graduate and above	0	0	0	0	1	1	-	-
Occupation	Manager	9	22	13	6	6	22.568	1.281–397.537	0.033
	Licensed pharmacist	1	7	10	5	3	46.327	2.443–878.451	0.011
	General staff	44	172	82	8	4	11.356	0.680–189.597	0.091
	Other	1	1	0	0	0	1	-	-
Experience (years)	<5	30	114	67	4	3	1.213	0.385–3.821	0.741
	5–10	19	57	24	6	5	0.958	0.340–2.700	0.935
	11–15	3	16	11	4	4	1.856	0.659–5.232	0.242
	>15	3	15	3	5	1	1	-	-
Type of pharmacy	Independent pharmacy	15	24	15	2	4	0.746	0.433–1.287	0.293
	Chained pharmacy	39	178	90	17	9	1	-	-
Had a licensed pharmacist on duty	Yes	18	57	39	13	12	1.398	0.898–2.175	0.138
	No	37	145	66	6	1	1	-	-

Abbreviation: OR, odds ratio. SDU, strongly don’t understand. DU, don’t understand. N, neutral. U, understand. SD, strongly understand.

4. Discussion

This study shows that community pharmacy staff had a good understanding of the use of antimicrobials. Most of the survey participants agreed that antimicrobials might cause AMR and allergic reactions, but they ignored the risk of increasing treatment costs. A large number of studies have already shown that the community pharmacy staff’s knowledge of antimicrobials is good, but the perception of the cost of antimicrobials and practices toward ASP was poor [21,29–32].

We found that the participants’ most common source of knowledge about antimicrobials was pharmacy training, which indicates that pharmacy training systems in China have improved in recent years. There have also been reports that pharmacy training has reduced sales of antimicrobials [21,33,34]. Our findings show clearly that the government should direct more resources toward expanding and supporting the pharmacy training system.

Most participants (73.9%) think that ‘ASPs should be incorporated at the community pharmacy and ASPs reduce the problem of antimicrobial resistance.’ Similarly, many participants (40.6%) strongly believed that ‘adequate training should be provided to community pharmacists on antimicrobial use,’ which shows a positive perception of participants regarding ASPs. Many studies have already demonstrated that ASPs are vital for reducing antimicrobial substitution [35–38]. It is, therefore, critical for the government to accelerate the implementation of ASPs in community settings.

The importance of communication with patients is well established [39,40], and a large number of participants in our study have indicated that they also (69.5%) communicate with patients about the antimicrobial adverse effects and occasionally (67.3%) had given medication consultations to patients in the past week. With the government’s emphasis on supporting pharmacies, the standard of pharmacy services in China has improved significantly [41–43].

In our study, nearly half of the participants (41.1%) said they sell antimicrobials without a prescription to patients occasionally. In comparison, 56.6% of participants occasionally received patients in hospital pharmacies who bought prescription antimicrobials in the past week. This phenomenon is common in various countries, including China [44,45], whereby pharmacists have a positive attitude toward antimicrobials, but their practices regarding ASPs are inadequate [46–48]. Some studies have shown that sometimes the general public compels the community pharmacy staff to sell antibiotics without a prescription, possibly due to their limited knowledge and awareness about antibiotics and antibiotic resistance [49].

The government needs to formulate and improve stringent policies and measures, including education of the general public, sales management of community pharmacies, and the guidance of pharmacy practices, to further prevent the inappropriate use of antimicrobials.

Education level, experience level, and the presence of a licensed pharmacist are all significantly associated with practices toward ASPs (P < 0.05). Logistic regression analysis revealed that managers and licensed pharmacists have a better understanding of antimicrobial policies (OR 22.568, 95% CI 1.281–397.537, P = 0.033; OR 46.327, 95% CI 2.443–878.451, P = 0.011) and independent pharmacy (OR 0.016, 95% CI 0.007–0.037, P < 0.001) mainly acquire antimicrobial-related knowledge through pharmacy training. Previous studies have shown that pharmacist-driven antimicrobial stewardship in an intensive care unit could decrease patient mortality and the emergence of multidrug resistance and optimize antimicrobial usage [50–52]. Hence, pharmacies should pay attention to prospective employees’ education levels, and they should have licensed pharmacists on duty according to government requirements, which will help with the implementation of ASPs.

The presence of a licensed pharmacist is one of the main factors positively affecting the stewardship of community pharmacies, as also outlined in various studies [40,51,53,54]. The American Society of Health-System Pharmacists (ASHP) has confirmed the integral role of pharmacists in ASPs [55]. Community-based ASPs have not yet been formally implemented in China. However, Chinese community pharmacists are familiar with their potential role in the ASPs team. Their positive perceptions of stewardship programs will help to tailor ASPs to comply with the requirements of the community settings [21].

5. Limitations

Several limitations should be considered before interpreting the results of our study for policy-making on community-based ASPs. First, the current study was conducted in Shenyang, which is the capital city of Liaoning Province of China. Therefore, the results cannot be generalized to all community pharmacy staff in China. Second, data were collected via a self-administered questionnaire. The major disadvantage of self-administered questionnaires is bias due to differences in respondents’ accuracy or completeness of recollection and to under- or over-reporting of knowledge, attitude, and practices. Despite these limitations, this study provides up-to-date insight into community pharmacy staff’s KAP toward community-based ASPs. The views shared in this study will help with the future development and tailoring of ASPs in community pharmacy settings in China.

6. Conclusion

This study concludes that knowledge of community pharmacy staff toward antimicrobials is good in some aspects, and their attitude regarding ASPs is positive. Unfortunately, practices regarding ASPs were found to be poor. ASPs should be widely adopted in community settings. Pharmacists should be trained in the judicial use of antimicrobials, and they should participate in antimicrobial awareness initiatives. Future studies covering different regions of China are warranted to validate the findings of this study. Additional studies to determine the impact of regulation on the sale of antimicrobials without prescription are also recommended. Finally, this study demands interventions for the betterment of practices of community pharmacists regarding ASPs.

Article highlights

• This study highlighted the views of community pharmacy staff about community-based antimicrobial stewardship programs (ASPs) in Northeast China.

• The community pharmacy staff had good knowledge about antimicrobials, and more than 90% of the community pharmacy staff were of the view that adequate training should be provided to community pharmacy staff on antimicrobial use, and ASPs should be incorporated at the community pharmacy level.

• The majority of the community pharmacy staff (84.3%) have occasionally/never given medication consultations to patients who bought antimicrobials at the pharmacy, which means there are deficiencies in pharmaceutical care services in Chinese community pharmacies.

• Development of community-based ASP guidelines with the training of community pharmacy staff, high level of pharmaceutical services, and availability of sufficient licensed community pharmacists are of urgent need.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contributions

ZF and KH made substantial contributions to the study design, data analysis, interpretation of results, and the drafting of the paper. Y.F. P.L., L.S., Z.H., C.X., Y.G., and Z.F. organized the project and were responsible for data collection. K.H., J.C., M.J., C.Y., M.Z., W.J. and Y.F. critically revised the manuscript for important intellectual content. Y.F. and J.C. obtained funding and supervised the whole study. All authors have read and approved the final version of the manuscript.

Acknowledgments

We want to express wholehearted thankfulness to participants of the study. We thank Lucy McClellan, MIA, from Liwen Bianji, Edanz Editing China (www.liwenbianji.cn/ac), for editing the English text of a draft of this manuscript.

Data availability

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Supplementary material

Supplemental data for this article can be accessed here.

Additional information

Funding

This work was funded by the National Natural Science Fund (71974156), the ‘Young Talent Support Plan,’ ‘High Achiever Plan’ of Health Science Center, Xi’an Jiaotong University, and the Central University Basic Research Fund (2015qngz05).