Effects of social support, hope and resilience on depressive symptoms among patients with newly diagnosed prostate cancer

DOI: https://doi.org/10.21203/rs.2.20543/v1

Abstract

Background

The prevalence of depression symptoms and related modifiable factors in prostate cancer (PCa) are not well evaluated. We aimed to assess the effects of perceived social support, hope and resilience on depressive symptoms in newly diagnosed PCa patients, and to evaluate the role of hope and resilience as mediators of that relationship.

Method

A cross-sectional study was analyzed in consecutive inpatients with PCa during the months of January 2018 and August 2019. A questionnaire was administered to 667 patients. All registered patients were all volunteers and anonymous. Depressive symptoms, perceived social support, hope and resilience were measured anonymously. Out of 667 patients, a total of 564 effective respondents became our subjects. Hierarchical linear regression was used to identify the factors associated with depressive symptoms. Asymptotic and resampling strategies were used to conduct the mediating effects of hope and resilience

Results

The prevalence of depressive symptoms was 65.9% in PCa patients . Hierarchical regression analyses indicated that perceived social support, hope, and resilience together accounted for 27.5% variance of depressive symptoms. Support from family, hope, and resilience significantly associated with depressive symptoms, respectively. Hope (a*b = -0.0783, BCa95% CI:–0.134 to–0.0319, p < 0.05), and resilience (a*b = -0.1315, BCa95% CI:–0.1894 to–0.0783, p < 0.05) significantly mediated the association between perceived social support and depressive symptoms.

Conclusions

The high prevalence of depressive symptoms among newly diagnosed PCa patients should receive more attention. Perceived social support, hope and resilience could be positive resources for combating depressive symptoms, and hope and resilience mediated the association between perceived social support and depressive symptoms. Enhancing social support, particularly the support form family, and improving patients’ outlook and resilience may be potential targets for future psychosocial interventions aimed at reducing depressive symptoms.

Introduction

Prostate cancer (PCa) is the second commonest diagnosed malignancy and the fifth leading cause of cancer mortality in men, accounting for a substantial public health burden [1]. Similar to other Asia countries where PCa incidence and mortality have been historically low, the trend of PCa incidence and mortality has experienced significant increases in China, and the average age at diagnosis declined slightly [2]. PCa incidence in 2000 (1.6 per 100,000) was four-times higher than in 2012 (5.3 per 100,000), and the mortality rate more than doubled during this period (1.0 per 100,000 in 2002 and 2.5 per 100,000 in 2012) [3]. PCa symptoms and side effects of treatment (e.g., radical prostatectomy, external beam radiotherapy) include pain, fatigue, and impairment in urinary and sexual functioning [4]. Therefore, in addition to mortality concerns, men with PCa are at risk for psychological distress, and one of our studies was to address the specific psychological concerns associated with the diagnosis and treatment of PCa.

Depression is one of the most commonly experienced psychological conditions experienced by cancer patients[5, 6] and are associated with unique psychophysiological side effects that importantly encompass poorer treatment outcomes, increased periods of hospitalization, impaired endocrine-immune function and higher mortality rates[79]. Watts et al. identified pretreatment, on-treatment and post-treatment depression rates of 17.27%, 14.70% and 18.44%, suggesting that prevalence of depression in men with PCa, across the treatment spectrum, is relatively high[5]. With the advances in treatment efficacy, there has been an increasing interest about psychological distress in PCa survivors, but not much is generally known regarding the mental health issues of newly diagnosed patients.

To our knowledge, the prevalence and associated protective factors of depression were seldomly studied in newly diagnosed PCa patients. Besides the demographic-clinical variables, more insight is needed into psychosocial factors among PCa patients against depression because they could be modified through appropriate psychosocial interventions [10, 11]. It is generally known that social support could protect cancer patients from the adverse psychological effects, and act as buffer against cancer-related stress among people suffering from cancer [1214]. However, the process through which social support influences psychological well-being has not been adequately explored. Among non-cancer populations, psychological capital and resilience significantly mediate the relations between social support and depression [15, 16]. Several studies also found the mediating roles of coping strategies and perceived stress between social support, quality of life (QoL) and emotional well-being in cancer patients [17, 18]. The above studies suggested that social support not only revealed a direct effect but also exerted an indirect effect on depression through triggering modifiable factors. Therefore, in-depth research on both direct and indirect effects of social support on depression should be conducted to develop more effective strategies for depression prevention and treatment.

Hope is identified as a positive motivational state that consists of two parts: 1) Agency thinking: Which involves perception about one’s ability to initiate and sustain motivation toward a goal 2) Pathways thinking: Which involves thinking about the methods or routs of reaching the desired goals [19]. Hope is an important and positive factor in their lives of cancer patients (e.g., help one adjust to cancer and reduce psychological distress [20]. Additionally, the comprehensive concept of resilience has been introduced in referring protective individual attributes in the adaptation to cancer [21]. Resilience has been defined as an individual’s capacity to maintain psychological and physical well-being in the face of significant life adversities or risks [22]. Hope and resilience referred to the internally positive psychological resource, and they could be recognized as a positive personality [1922]. An individual’s hope and resilience are not entirely innate and that an individual can develop these strengths under certain interventions in cancer patients [23, 24].

Hope and resilience were associated with QoL and psychological problems among different types of cancer [12, 25]. In addition, resilience mediated the association between symptom distress and quality of life in cancer patients [26]. Tae et al. also found the mediating role of self-esteem and hope between antecedent variables and depression in Korean women with breast cancer [27]. Nevertheless, the roles of social support, hope and resilience in combating depression have not been studied among PCa patients in China. Besides, whether hope and resilience mediates the association between social support and depression has not been evaluated.

In light of the above concerns, the aim of the present study was to assess the depression among PCa patients as well as to explore the protective effects of social support, hope and resilience on depression. More importantly, we aimed to confirm whether hope and resilience mediated the association between social support and depression.

Method

Study design and sample

A cross-sectional study was analyzed in consecutive inpatients with PCa during January 2018 and August 2019. The study took place at the Department of Urology in our Hospital, which is the main provider of cancer services to a geographically defined area of 8.2 million people. The eligibility criteria for patient recruitment were (1) age 18 years or older, (2) being histologically diagnosed with PCa, (3) aware of the cancer diagnosis, (4) able to understand and read Chinese well enough to answer the questionnaires. Exclusion criteria were the following: (1) patients had a history of psychiatric problems before cancer diagnose, (2) patients had intellectual and/or cognitive impairments, (3) patients had other active cancers. All registered patients were all volunteers and anonymous. The volunteer patients’ attending physicians discussed eligibility on a case-by-case basis to avoid biased judgment and selection bias. After obtaining patient written consent, clinical data was collected from the medical record and a set of self-report questionnaires were distributed to patients at the time of hospitalization. Among a total of 667 registered patients, 10 patients refused to participate, and 5 patients had other active cancers. Of 652 eligible patients for this study, 88 were excluded from analysis (> 30% missing data). Finally, we received effective responses from 564 PCa patients with effective response rate 86.5%. The Committee on Human Experimentation of our hospital reviewed this study, provided the ethics for the approval of this study, and determined that the study procedures were in accordance with the ethical standards.

Questionnaires

Beside demographic and cancer-related variables, the following questionnaires were adopted:

Depression

Depression was measured by the Center for Epidemiologic Studies Depression Scale (CES-D), which is a 20-item measure of the severity of depressive symptoms [28]. Items are ranked on a four-point frequency scale from 0 (never) to 3 (always). Higher scores reflect worse depressive symptoms, and a score ≥16 indicates probable clinical depression [28]. The CES-D was validated in cancer patients [29], and Cronbach’s alpha for CES-D was 0.794 in this study.

Perceived social support

Perceived social support was measured by the Multidimensional Scale of Perceived Social Support (MSPSS) [30], which is 12-item measure of the sources of perceived social support, rated on a seven-point scale from 1 (very strongly disagree) to 7 (very strongly agree). It provides a summary score (12 to 84), as well as three subscales for perceived support from family, friends, and significant others. The MSPSS was validated and commonly used in Chinese cancer patients [12,14]. In this study, the Cronbach’s alpha was 0.942, 0.923, 0.896, and 0.931 respectively for MSPSS, family, friends, and significant others subscales.

Hope

For hope, we correlated this with “hope” and this was measured by the Adult Hope Scale (AHS) which included eight items and four filler items rated on 4-point scales (1 = strongly disagree, 4 = strongly agree) [19]. The AHS contains four Agency and four Pathways items, and a high score denotes a higher level of pathways and agency. The hope level is the sum of the agency and pathways items. The AHS and its Chinese version have been used in cancer patients with acceptable validity and reliability [25]. The Cronbach’s alpha was 0.742, 0.772, and 0.849 respectively for the pathway, agency and AHS.

Resilience

The 14-items version of Resilience Scale (RS-14), a short version of the original RS (i.e. RS-25), was used to assess resilience [31]. RS-14 consists of 14 items rated on a 7-point scale, ranging from 1 (strongly disagree) to 7 (strongly agree). The total score ranges from 14 to 98 scores, with higher scores indicating higher resilience. The Chinese version of RS-14 had a good validity and reliability among cancer patients [32]. In this study, the Cronbach’s alpha was 0.959 for RS-14.

Statistical methods

The Statistical Package for the Social Sciences (SPSS, version 13.0) was used to perform the statistical analyses, with two-tailed probability value of < 0.05 considered to be statistically significant. The distributions of CES-D in categorical variables were calculated using independent sample t-test and one way analysis of variance (ANOVA). When one-way ANOVA was found to be significant, least-significant-difference (LSD) was done to perform multiple comparisons. Pearson’s correlation was used to examine correlations among psychosocial variables. Hierarchical regression analysis was used to explore the effects of perceived social support, hope and resilience on depression with adjustment for demographics and clinical variables related to depression in univariate analysis (p < 0.05). There were two models (Model 1 and Model 2) in Step 2. Total score of MSPSS was added in Model 1, and three subscales of MSPSS (others, friend and family) were added in Model 2. Due to the high correlations among the MSPSS subscales, these variables were adjusted in the stepwise regression in Step 2 (Model 2).We provided data including R2, adjusted R2 (Adj.R2), R2-changes, F, standardized regression coefficient (β) and p value for each step in the regression model. Asymptotic and resampling strategies were used to examine the mediating roles (a*b product) of hope and resilience on the association between perceived social support and depression [33]. In these equations, perceived social support was modeled as the independent variable, CES-D score as the dependent variable, hope and resilience as the mediators. The auxiliary routine estimate was based on 5000 bootstrap samples. Then, the bias-corrected and accelerated 95% confidence interval (BCa95% CI) for each a*b product was investigated, and a BCa95% CI not including 0 indicated a significant mediating role. All study variables were centralized before analysis to account for differences in scale scores. Moreover, tolerance (> 0.10) and variance inflation factor (< 10) were used to check for multicollinearity.

Results

In the present study, the patients (N = 564) were in the age range of 18–80 (Mean ± SD: 59.66 ± 11.21), and the number of months after diagnosis was in the range of 1-237 (Mean ± SD: 11.76 ± 22.93). Demographic and clinical factors of patients and distributions of depressive symptoms in categorical items were shown in Table 1. Patients with a higher level of education had a lower level of depressive symptoms. Results also indicated that patients whose time since diagnosis was within 3 months had a higher level of depressive symptoms as well as patients at cancer stage II had higher scores of CES-D.

Table 1
CES-D scores in demographic and clinical variables (N = 564)
 
N(%)
CES-D
t/F value
p-value
Demographic variables
       
Age
   
0.482
0.547
≤ 55
227(40.2)
22.53 ± 9.54
   
56–65
193(34.2)
23.77 ± 8.34
   
≥ 66
144(25.6)
23.32 ± 9.86
   
Marital status
   
0.574
0.532
Married/living with a partner
495(87.8)
23.07 ± 9.16
   
Single/widowed/divorced
69(12.2)
23.89 ± 9.50
   
Education
   
8.903
< 0.001
Middle school or below
265(46.9)
24.29 ± 9.12b
   
High school
144(25.5)
24.37 ± 8.16b
   
Junior college or above
156(27.6)
20.48 ± 9.32a
   
Clinical variables
       
Time since diagnosis
   
3.021
0.025
≤ 3
143(25.3)
25.09 ± 8.36a
   
4–6
139(24.6)
23.35 ± 9.02
   
7–12
194(34.4)
22.14 ± 10.09b
   
> 12
88(15.6)
22.51 ± 8.84
   
Cancer stage
   
-2.245
0.007
I
298(52.8)
22.31 ± 9.41a
   
II
266(47.2)
24.47 ± 8.82b
   
Treatment type
   
-1.207
0.214
No treatment
5(0.8)
-
   
Surgery
290(51.4)
22.97 ± 9.36
   
Combined treatment
269(47.7)
23.54 ± 8.28
   
Chemotherapy
2(0.2)
-
   
Metastasis
   
-
-
No
559(99.1)
-
   
Yes
5(0.9)
-
   
Abbreviations: CES-D = Center for Epidemiologic Studies Depression Scale.
a,bCalculated by least-significant-difference (LSD), mean scores for depression with unequal superscripts differ significantly at the p < 0.05 level.

In Table 2, Pearson’s correlation coefficients were calculated among study variables. Perceived social support, hope and resilience was negatively associated with depressive symptoms (r = ranged from − 0.337 to-0.447; p < 0.01). Additionally, the prevalence of depressive symptoms in PCa patients was 65.9% (N = 372).

Table 2
Means, standard deviation, range and zero-order correlations (Pearson’s r) among study variables
Variables
CES-D scores ≥ 16
Mean ± SD
Range
1
2
3
4
5
6
7
1. CES-D
372(65.9%)
23.72 ± 9.24
0–44
1
-0.398**
-0.364**
-0.404**
-0.337**
-0.424**
-0.447**
2. Total-MSPSS
 
58.07 ± 16.25
20–84
 
1
0.959**
0.961**
0.923**
0.467**
0.503**
3. MSPSS-others
 
19.58 ± 6.02
4–28
   
1
0.912**
0.834**
0.442**
0.484**
4. MSPSS-family
 
20.37 ± 6.62
6–28
     
1
0.834**
0.475**
0.493**
5. MSPSS-friend
 
19.05 ± 5.74
6–28
       
1
0.483**
0.465**
6. AHS
 
21.74 ± 4.21
8–32
         
1
0.546**
7.RS-14
 
65.58 ± 17.03
14–98
           
1
Abbreviations: SD = standard deviation; CES-D = Center for Epidemiologic Studies Depression Scale; MSPSS = Multidimensional Scale of Perceived Social Support; AHS = Adult Hope Scale; RS-14 = 14-items version of Resilience Scale
** Correlation is significant at the 0.01 level (two-tailed).

Hierarchical regression analysis results were presented in Table 3. Psychosocial variables together accounted for an additional 27.5% variance to the prediction of depression. In Step 2 Model 1, perceived social support was significantly and negatively associated with depressive symptoms (β = -0.377, p < 0.001). In Step 2 Model 2, perceived social support-family was significantly and negatively associated with depressive symptoms (β = -0.387, p < 0.001). Hope and resilience were significantly and negatively associated with depressive symptoms in Step 3 Model 1 and Model 2. In addition, the effect of perceived social support on depressive symptoms in Step 3 was reduced compared with that in Step 2, as indicated by smaller β coefficients. Tolerance (range: 0.573–0.986) and variance inflation (range: 1.014–1.797) did not indicate an obvious multicollinearity problem.

Table 3
Results from the hierarchical regression analyses.
Variables
Step1(β)
Step2(β)
 
Step3(β)
Model 1
Model 2
 
Model 1
Model 2
Covariates
           
Age
0.035
0.031
0.039
 
0.034
0.037
Gender
0.024
0.043
0.041
 
0.033
0.034
Education1
0.196***
0.104*
0.097*
 
0.049
0.045
Education2
0.172**
0.103*
0.107*
 
0.044
0.046
Time since diagnosis
-0.027
0.023
0.028
 
0.021
0.026
Cancer stage
0.106*
0.064
0.063
 
0.054
0.055
Social support
           
Perceived social support
 
-0.377***
   
-0.168***
 
Perceived social support-others
   
-
   
-
Perceived social support-family
   
-0.387***
   
-0.183***
Perceived social support-friend
   
-
   
-
Psychological resource
           
Hope
       
-0.176***
-0.175***
Resilience
       
-0.270***
-0.264***
F
4.247***
17.064***
17.681***
 
24.648***
25.229***
R2
0.044
0.177
0.182
 
0.286
0.291
Adj.R2
0.033
0.166
0.172
 
0.275
0.279
R2-changes
0.044
0.133
0.138
 
0.109
0.109
Abbreviations: β = standardized regression coefficient; Education1 = Middle school or below vs. Junior college or above; Education2 = High school vs. Junior college or above; Adj.R2 = adjusted R2.
There were two models (Model 1 and Model 2) in Step 2. Perceived social support (total score) was added in Model 1, and its components were added in Model 2 adjusted by the stepwise regression due to the high correlations among the MSPSS subscales
* p < 0.05, ** p < 0.01, *** p < 0.001

Path coefficients (a) (between social support and mediators) and (b) (between mediators and depressive symptoms), a*b products, and BCa 95% CI for these products are presented in Table 4. Perceived social support was significantly and positively associated with hope and resilience. Consistent with the results from hierarchical regression, hope and resilience were significantly and negatively associated with depressive symptoms after controlling for covariates. Thus, significant mediating roles of hope (a*b = -0.0783, BCa95% CI:–0.134 to–0.0319, p < 0.05) and resilience (a*b = -0.1315, BCa95% CI:–0.1894 to–0.0783, p < 0.05) on the association between perceived social support and depressive symptoms were revealed. The same conclusion also applies to perceived support from family considered as independent variable.

Table 4
Multiple mediation of the indirect effects of perceived social support on depressive symptoms through changes in hope and resilience (n = 564; 5000 bootstrap resamples)
Independent
variable X
Mediators M
Dependent variable Y
Effect of X on M(a)
Effect of M on Y(b)
Indirect effect (a*b)b
BCa95% CIa
Total indirect effect (a*b)b
BCa95% CIa
Direct effect (c’)
Total effect (c)
Low
High
Low
High
   
social support
Hope
Depression
0.4490***
-0.1764***
-0.0783
-0.1341
-0.0319
-0.2098
-0.2734
-0.1524
-0.1668***
-0.3776***
Resilience
0.4878***
-0.2698***
-0.1315
-0.1894
-0.0783
         
social support-family
Hope
Depression
0.4311***
-0.1753***
-0.0754
-0.1256
-0.0320
-0.2014
-0.2682
-0.1434
-0.1842***
-0.3857***
Resilience
0.4762***
-0.2645***
-0.1261
-0.1847
-0.0764
         
All the coefficients are standardized regression coefficients and adjusted for age, gender, education, cancer stage and time since diagnosis
***p < 0.001
a BCa = Bias corrected and accelerated bootstrapping confidence intervals that include corrections for both median bias and skew. BCa95%Confidence intervals (BCa95%CI) containing 0 is interpreted as not significant.
b Bootstrap results for indirect effects after bias corrected

Discussion

Results indicated that PCa patients in China seriously suffered from depressive symptoms, and perceived social support (especially the patient’s perception of social support from family), hope and resilience can be positive resources for reducing depressive symptoms. This is the first study to verify the mediating roles of a hope and resilience on the association between perceived social support and depressive symptoms using a relatively large sample (N > 500).

The prevalence of depressive symptoms in PCa patients was 65.9% in our study. We compared our results with other empirical studies of depression in PCa patients using the same cut-off: (1) Hoyt and Carpenter reported the prevalence of depressive symptoms (23%, N = 15) in patients who had undergone radical prostatectomy or radiation therapy for localized PCa [34]; (2) Lin et al. found that 75 Taiwan patients (56.4%) had depression scores greater than or equal to 16 on the CES-D [35]; (3) The prevalence of depressive symptoms among Kinlock’s sample of Black men was approximately 33% [36]. The prevalence of depressive symptoms in our study was very high, and there might be two reasons for this situation. First, these studies were mainly from developed countries or regions, which may have lower prevalence of mental health problems as compared to developing countries like mainland China. Second, these newly diagnosed PCa patients might face the physiological, psychological and interpersonal challenges across the first year after the cancer diagnosis. These unique characteristics, combined with the psychological issues that received little attention in Chinese cancer patients, might aggravate patients’ psychological problem.

Our results indicated that an increase in perceived social support has some correlation with depressive symptoms in these patients yet hope and resilience were negatively associated with depressive symptoms in PCa patients. It has been generally suggested that social support decreased cancer-related stress and had the potential for combating psychological problems [1214, 18], and our results were consistent with previous studies. However, only social support from family was significantly associated with depressive symptoms. To date, few studies explore which sources of social support is the main essential resource for combating depression in cancer patients. This could be attributed to the fact that family is the bedrock of Chinese society, and the care and concern of family members are of great importance for cancer patients. Psychosocial interventions involving family members have been also proven to be beneficial for depression in cancer patients [37]. On the other hand, due to the embarrassment of changed self-image/body image and altered sexual/urinary function, PCa patients might not ask for support from friends or significant others, and may distance themselves from friends and family members.

Furthermore, after controlling for social support, hope and resilience also accounted for an additional and moderate proportion of variance to depressive symptoms (10.9%). Regarded as positive psychological resources, hope and resilience have been proven to be beneficial in cancer patients. Hope might provide cancer patients positive coping strategies for depression, including sustaining the movement toward achieving a goal and providing the pathways of reaching the desired goals [20, 23]. Resilient patients might show more emotional stability when faced with adversity and obstacle caused by cancer [21, 24]. These findings prompted us to believe that both positive experiences regarding one’s own goal and route (hope) and positive adaptation in the context of traumatic events (resilience) were important to effectively ameliorate and even overcome depressive symptoms in PCa patients.

An important finding was that hope and resilience mediated the negative relationship between perceived social support and depressive symptoms using the non-parametric bootstrapping procedure. Besides the direct effect of perceived social support on depression, PCa patients who perceive more social support, especially perceived support from family, might be more likely to experience higher levels of hope and resilience, which in turn reduced their depressive symptoms. Additionally, because of the larger direct effects of resilience on depressive symptoms, the indirect effect of resilience was larger than that of hope in the multiple mediators analysis, indicating the importance of patients’ capacity to maintain and recover the psychological well-being in the face of cancer.

Implications

The prevalence of depressive symptoms among PCa patients should receive more attention in Chinese medical settings. Moreover, the present study indicated, that more effort should be devoted to improve the social support (especially family support), as well as to elevate hope and resilience in PCa patients. For example, the provision of helpful social support to husbands/partners, parents and children of PCa patients could be substantial in reducing depressive symptoms. Family members also should not give up providing reassurance and spending time with patients as a result of fear/anxiety of the cancer, and the potential loss of family members [38]. In addition, strategies for increasing hope and resilience should be applied to PCa patients. Based on Snyder’s theory of hope and the findings of previous studies, Berendes et al. developed a psychological intervention module including five important components, 1) discussing with patients understanding of cancer, 2) identifying objective and creating an ordering of important goals, 3) clarifying realistic short- and long-term goals achievable within the context of cancer, 4) recognizing the multiple pathways toward goals and selecting pathways with the highest chance of success, and 5) finding ways to increase agency and monitor their pathway to the goal [23]. In order to improve resilience, a recent review indicated that though stress management and resilience training, which is a brief, group-based cognitive behavioral therapy, patients were taught to redirect their perceptions of cancer and focus on adjustment and growth (e.g., gratitude, acceptance, purpose)[24]. Interventions (e.g., meaning-making interventions) that targeted other aspects of the cancer experience (e.g., self-esteem, optimism, and self-efficacy) might in fact indirectly enhance resilience as well [39].

Limitation

First, we used a convenient sample, which limited the generalizability of the findings to other cancer patients. Second, depression measured by the self-report of CES-D mainly referred to the depressive symptom in our study. Third, data was mainly obtained using self-administered questions, so there was a possibility of recall and reporting bias. Finally, our study was cross-sectional, and thus we are unable to assess the causal relations among study variables. Further longitudinal studies are needed to validate the current findings.

Conclusion

PCa patients in China suffer from severe depressive symptoms, perceived social support, hope and resilience had protective effects for combating depressive symptom. Additionally, hope and resilience mediated the association between perceived social support and depressive symptom. Therefore, perceived social support (especially support from family) and psychological resources (hope and resilience) investment should be contained in depression preventions and treatments targeting PCa patients.

Abbreviations

CES-D: Center for Epidemiologic Studies Depression Scale;MSPSS: Multidimensional Scale of Perceived Social Support;AHS: Adult Hope Scale

Declarations

Acknowledgements

We thank Yilong Yang from the department of Social Medicine, School of Public Health, China Medical University for statistical assistance and guidance.

Authors’ contributions

(I) Conception and design: Y Yang; (II) Administrative support: Y Yang, M Sun ; (III) Provision of study materials or patients: M Sun; (IV) Collection and assembly of data: X Zhao, M Sun ; (V) Data analysis and interpretation: X Zhao, Y Yang; (VI)

Manuscript writing: All authors; (VII) Final approval of manuscript: All authors.

Funding

Basic research projects of Liaoning higher education institutions (No. LQNK201713).

Availability of data and materials

The data were used under license for the current study, and so are not publicly available. Data are however available from the authors upon reasonable request and with the permission of the Shengjing Hospital.

Ethics approval and consent to participate

This analysis was approved by The Clinical Medical Research Ethics Committee of Shengjing Hospital of China Medical University. The privacy consent was achieved by all patients.

Competing interests

All authors declare that they have no conflict of interest.

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