As a new approach for percutaneous coronary intervention, distal transradial approach (dTRA) is increasingly applied in clinical practice. Thus dTRA is superior to transradial artery approach in improving patient and surgeon comfort, reducing the incidence of complications and forearm arterial injuries, while it also has many limitations, such as lower success rate, longer learning cycle, higher level of puncture site pain, and relatively higher incidence of radial artery spasm. And dTRA has also been used as an approach for acute coronary syndrome and complex percutaneous coronary intervention. But it still needs further verification whether dTRA is suitable for mass promotion and application. This paper reviews and analyzes the strengths, weaknesses, opportunities and challenges of dTRA, in order to provide a theoretical basis for scientific and rational application of dTRA in percutaneous coronary intervention.
Percutaneous coronary diagnosis and intervention via distal transradial artery approach has become one of the hot research topics in the field of coronary angiography and intervention. Compared with transradial approach, the distal transradial artery approach has the advantages of higher patient comfort and fewer related complications; however, due to the tortuosity of radial artery and relatively small size of distal radial artery, there is a significant learning curve for distal transradial artery approach puncture. This paper analyzes and summarizes the common causes (mainly including patient factors and operational factors) and treatment strategies of distal transradial artery approach puncture failure based on the experience of more than 2 000 cases, in order to provide a reference for improving the success rate of puncture and promoting the application of distal transradial artery approach.
Percutaneous coronary intervention (PCI) via distal transradial artery approach (dTRA) is effective in reducing the incidence of radial artery occlusion, however, there are no reports on the feasibility, safety and timing of secondary PCI via dTRA domestically.
To explore the feasibility, safety and timing of secondary PCI via dTRA.
A total of 70 patients who were to undergo secondary PCI via dTRA in Fuwai Hospital, CAMS&PUMC from July 2021 to July 2022 were consecutively included and divided into ≤30 d group (n=33) and >30 d group (n=37) according to the time interval since the last PCI via dTRA. The general clinical data, operation-related indicators, coronary artery lesions and radial artery inner diameters at 5, 10 and 15 cm proximal to the radial styloid process before and 24 h after PCI were compared between the two groups.
The dTRA puncture and catheterization were successfully conducted in 69 of 70 patients, with a success rate of 98.6% (69/70) . Second PCI via dTRA was successfully completed in 66 of 67 patients assessed for secondary PCI, with a success rate of 98.5% (66/67) . There were significantly difference in age, platelet count, incidence of diabetes, number of lesioned vessels and ACC/AHA coronary artery lesions typing (P<0.05) . The compression bandage was released 3 hafter surgery, and the radial artery pulsation on the puncture side was palpable immediately and 24 h after surgery, and none of the patients occurred radial artery occlusion, with the radial artery patency rate of 100.0% (69/69) . The radial artery inner diameters at 5, 10 and 15 cm proximal to the radial styloid process in ≤30 d group were significantly greater than that in >30 d group before and 24 h after PCI when comparing between the two groups, respectively (P<0.05) . Radial artery inner diameter at 15 cm proximal to the radial styloid process 24 h after PCI was smaller than that before surgery in ≤30 d group, radial artery inner diameter at 5 cm proximal to the radial styloid process 24 h after PCI was smaller than that before surgery in >30 d group (P<0.05) .
Secondary PCI via dTRA is safe and feasible independent of first dTRA PCI time (≤30 days or >30 days from the first dTRA PCI) , and the timing of secondary PCI via dTRA should be determined according to the patient's condition and puncture site.
The incidence of radial artery occlusion (RAO) after coronary intervention via transradial artery approach (TRA) is high. But there is a lack of long-term follow-up studies with a large sample size on retrograde recanalization of occluded radial artery via distal transradial artery approach (dTRA) .
To assess the feasibility of dTRA for retrograde recanalization of occluded radial artery.
Forty-four patients undergoing retrograde recanalization via dTRA for treating RAO after coronary intervention via TRA were consecutively recruited from Shenzhen People's Hospital from June 2019 to December 2021. The primary observation index was postprocedural radial artery patency. And secondary observation index included possible predictors of failed retrograde recanalization, incidence of adverse events during hospitalization, and patency rates of radial artery at 3, 6 and 12 months after procedure.
The success rate of postprocedural radial artery patency was 88.6% (39/44) , and divided into groups of successful (n=39) and failed (n=5) according to the result of the procedure. Compared with the successful group, the failed group had higher percentages of diabetics, current smokers and chronic total occlusion of the coronary artery, as well as a significantly lower prevalence of undergoing balloon angioplasty (P<0.05) . There was significant intergroup difference in the times of coronary interventions (P<0.05) ; there was no significant intergroup difference in the incidence of bleeding or hematoma at the access site during hospitalization (P>0.05) . The patency rates of radial artery in successful group were 48.7% (19/39) , 43.6% (17/39) , and 35.9% (14/39) at 3, 6, and 12 months after procedure, respectively.
The dTRA may be feasible for retrograde recanalization of occluded radial artery, which showed a high procedural success rate up to 88.6%, but the long-term patency rate was less than 50.0%. Diabetes, smoking, times of coronary interventions, chronic total occlusion of coronary artery, and receiving no balloon angioplasty may be influencing factors of failed retrograde recanalization of occluded radial artery via dTRA. And dTRA for retrograde recanalization of occluded radial artery is recommended for patients with RAO who also require elective coronary intervention.
Cerebral angiography is an important means for the assessment of cerebrovascular diseases. In recent years, distal transradial artery approach (dTRA) has gradually been used in cerebral angiography, but there are few reports on its effectiveness and safety.
To compare the effectiveness, patient safety and satisfaction between transradial artery approach (TRA) and dTRA in cerebral angiography.
Totally 135 patients who were hospitalized in Department of Neurosurgery, Wujin Hospital Affiliated to Jiangsu University from January 2020 to June 2022 for cerebral angiography were selected. They were divided into TRA group (n=72) and dTRA group (n=63) by the approach used in cerebral angiography, and the puncture time, duration of cerebral angiography, puncture success rate, X-ray exposure time, incidence of puncture site complications and serious cardiovascular and cerebrovascular events within three days after cerebral angiography, and levels of pain and satisfaction within 24 hours after cerebral angiography were compared between the groups.
The mean puncture time in dTRA group was much longer than that of TRA group (P<0.05) . The mean duration of cerebral angiography was also significantly longer in dTRA group (P<0.05) . The puncture success rate in dTRA group was much lower (P<0.05) . There was no statistically significant difference between the groups in terms of average X-ray exposure time or the incidence of puncture site complications within three days after cerebral angiography (P>0.05) . No serious cardiovascular and cerebrovascular events occurred in both groups within three days after cerebral angiography. dTRA group had much lighter pain level and significantly higher satisfaction within 24 hours after cerebral angiography than TRA group (P<0.05) .
Compared with TRA, dTRA is also safe and effective for cerebral angiography, and helps to reduce patients' pain level and improve their satisfaction, so dTRA can be used as one alternative approach for cerebral angiography, but it requires higher level of puncture skills and takes a longer time, so operators need to spend a certain amount of time on relevant learning and training.
Prevalence and Associated Factors of Depression among Middle-aged and Elderly Women YE Haichun1, YAN Yajie2,3, WANG Quan2, 3* 1.School of Nursing, Shandong Xiehe University, Jinan 250109, China 2.School of Health Sciences, Wuhan University, Wuhan 430071, China 3.Global Health Institute, Wuhan University, Wuhan 430072, China *Corresponding author: WANG Quan, Associate professor, Master supervisor. E-mail: wangquan73@whu.edu.cn 【Abstract】Background Depression is a common mental illness threatening physical and psychological health of middle-aged and elderly people. However, there are few large-scale studies focusing on depression and its influencing factors in middle-aged and elderly Chinese women. Objective To investigate the depression prevalence and associated factors in middle-agedand elderly Chinese women, providing evidence for exploring mental health and effective interventions in this population.Methods This study was conducted from January to March 2021. Data were obtained from the China Health and RetirementLongitudinal Study (CHARLS), involving 7963 women at age 45 or over, including demographic characteristics, physicalhealth status, socio-economic features, life satisfaction, regional distribution(eastern, central or western China), and depressive prevalence assessed by the 10-item Centre for Epidemiologic Studies Depression Scale (CES-D-10). The score of CES-D-10 ≥ 10 was considered as depressive symptoms. Robust OLS regression, robust Tobit regression and robust Logit regression were used to identify associated factors of depressive symptoms. Results The median CES-D-10 score of the participants was 8(4, 14)points. Except for 4490 cases(56.39%), the remaining 3473 cases (43.61%) were found with depressive symptoms, including1715(41.52%) aged 45-59 years, and 1758(45.88%) aged 60 or over. Analyses using three regression models indicated that age and age squared(OR=1.099, 0.999), education level (OR=0.897), living in rural or urban areas (OR=0.731), self-rated health (OR=1.245), physical disability (OR=1.332), chronic disease (OR=1.172), troubled with body pains(OR=1.579), BADL (activities of daily living) disability(OR=1.734), IADL(instrumental activities of daily living) disability(OR=1.967), living with spouse(partner)or not(OR=0.763), number of children(OR=1.074), using the internet or not(OR=0.773), having care support or not when needed (OR=1.509), having debt(OR=1.017), life satisfaction (OR=2.150), and regional distribution (OR=1.275) were associated with depression(P<0.05). Conclusion According to the data analysis of this study, the prevalence of depressive symptoms among middle-aged and elderly Chinese women was high, accounting for more than 40%. To control and prevent depressive symptoms to improve mental health status in this population, it is suggested to improve their education level, physical health status, family relations and life satisfaction, reduce their debt-financed consumption, and to offer them more ways to access information, and more social support, as well as to promote urbanization. 【Key words】 Depression; Middle aged; Aged; Femininity; China Health and Retirement Longitudinal Survey; Root cause analysis Studies have shown that depression, as a common psychological disorder among middle-aged and elderly people, can contribute to a high risk of self-harm and suicide [1-2], as well as the risk of cognitive dysfunction and senile dementia [3], which not only reduces the quality of life of middle-aged and elderly people, but a big contributor to the family economic burden and national medical and health resources burden [4]. A great deal of research indicating that there is a gender gap in depression, which is more common in middle-aged and elderly women [5-7].The transition of family identity of middle-aged womenis highly consistent with the China's reform and opening up, the transition period of family and social ethics, and they are more adversely affected in life and psychology.Therefore, it is of great practical importance to understand the mental health status of middle-aged and elderly women in China, especially to explore as many influencing factors as possible.Given this, the study used the 2018 survey data of the China Health and Retirement Longitudinal Survey (CHARLS) to analyze prevalence and associated factors of depression in middle-aged and elderly Chinese women, providing evidence for exploring mental health and effective interventions in this population. 1.Objectivesand Methods 1.1. Objectives This study was conducted from January to March 2021. Data were obtained from the fourth wave survey data of the China Health and Retirement Longitudinal Study (CHARLS, wave 4), which was released in September 2020 and involved 19816 respondents from 150 counties/districts and 450 villages/communities, with good sample representation [8]. Inclusion criteria :(1) age ≥ 45 years; (2) female; (3) respondents who clearly responded to the 10-item version of the Centre for Epidemiological Studies Depression Scale. Exclusion criteria: inability to complete the survey or refusal to participate in the survey. After removing samples with missing selected variables, a total of 7963 middle-aged and elderly women were included in the study. The CHARLS was approved by the Ethical Review Committee of Peking University. (IRB00001052-11015) andthe informed consent was signedat the time of participation with all participants. 1.2. Methods 1.2.1.The investigation content of CHARLS related to the study The contents included demographic characteristics (age, education levels, residency), physical health status (self-reported health, physical disability, chronic disease, troubled with body pains,BADL disability, IADL disability), sociological characteristics (living with spouse/partner or not, number of family members, number of children, number of children who visit their parents at least once a month, caring for grandchildren, number of still alive parents, social activities, using the internet or not, and having care support or not when needed), economic characteristics (having jobs other than self-employed agricultural, individual income, having debt, retirement), life satisfaction, and regional distribution.For BADL, respondents were asked to answer whether they had difficulty in six activities of daily living included dressing, bathing/showering, feeding oneself, getting in or out of bed, using the toilet, and controlling urination and defecation, while theIADL contained doing household chores, cooking, shopping, managing finances, taking medications, and using telephone calls. For both BADL and IADL, answers were categorized as: “do not have any difficulty”, “have difficulties but still can do it”, “have difficulties and help is needed”, “cannot complete it”. Those respondents who reported any difficulty in any item of BADL/IADL were defined as having BADL disability or IADL disability [9]. 1.2.2.Measures of depression The 10-item version of the Centre for Epidemiological Studies Depression Scale (CES-D-10)was used to assess depression in middle-aged and elderly women.The CES-D-10 was revised by ANDRESEN et al. [10] based on the results of item analysis to overcome the problems of long answer time, sensitive item content and high rejection rate in the original CES-D-20.The CES-D-10 scale included the following: (1) I was bothered by things that do not usually bother me. (2) I had trouble keeping my mind on what I was doing. (3) I felt depressed. (4) I felt that everything I did was an effort. (5) I felt hopeful about the future. (6) I felt fearful. (7) My sleep was restless. (8) I was happy. (9) I felt lonely. (10) I could not get “going”.By asked respondents “How often this past week did you ...” answered the above ten items, each item was scored from 0 to 3:“rarely or none of the time (less than 1 day) was scored as 0,” “some or a little of the time(1–2 days) was scored as 1,”, “occasionally or a moderate amount of the time(3–4 days) was scored as 2,” “most or all of the time (5–7 days) was scored as 3.”The responses the two positive feelings of the item 5 and the item 8 were scored as 3, 2, 1 and 0. The total CES-D 10 score ranged from 0 to 30, respondents were classified as scores 10-30 being having depression symptoms and those with scores 0-9 as being without depression symptoms. With a higher score indicating a greater severity of depressive symptoms [10]. The Cronbach’s alpha of CES-D-10 was 0.788[11]. 1.3. Statistical analysis Statistical analyses were performed using Stata version 14.1 software. The measurement data that did not conform to normal distribution were described by M (P25, P75), and counting data were described in relative numbers. Robust OLS regression, Tobit regression and Logit regression were used to analyze the influencing factors of depression in middle-aged and elderly women. Two sided P<0.05 was considered as statistically significant. 2. Results 2.1. The characteristics of the sample Among 7963 middle-aged and elderly women, 4131 (51.88%) were aged from 45 to 59, and 3832 (48.12%) were aged 60 and above. Other demographic characteristics, physical health status, sociological characteristics, economic characteristics, life satisfaction and regional distribution are shown in Table 1. Table 1. Characteristics of 7963 middle-aged and elderly women.
Note: BADL, basic activities of daily living; IADL, instrumental activities of daily living; The number of family members, number of children, number of children who visit their parents at least once a month, the number of still alive parents (including foster parents, father, mother, father-in-law, mother-in-law), individual income, and having debt were recorded as continuous variables and not listed in the table 1. 2.2. Prevalence of depression in middle-aged and elderly women Among 7963 middle-aged and elderly women, the median CES-D-10 score of the participants was 8(4, 14)points. Except for 4490 cases (56.39%), the remaining 3473 cases (43.61%) were found with depressive symptoms, including 1715(41.52%) aged 45-59 years, and 1758(45.88%) aged 60 or over. 2.3. Regression analysis of the influencing factors of depression in middle-aged and elderly women Based on the analysis of relevant literature[12-13], we selected demographic characteristics, physical health status, sociological and economic characteristics, life satisfaction and regional distribution of middle-aged and elderly women as independent variables. For age, the quadratic term of age was introduced in regression according to existing literature[14]. The CES-D-10 scoreof middle-aged and elderly women wasseen as dependent variables, and the above independent variables were included for OLS regression analysis (the assignments of variables used in the study are all shown in Table 2).The multi-collinearity test was performed first, and it was found that the maximum VIF of each variable except age and its quadratic term was 1.88, indicating that there was no multi-collinearity problem.Then,heteroscedasticity test was carried out and it was found that there was heteroscedasticity, so robust OLS regression was used. The result of the robust OLS regression analysis showed that age and age squared, education level, residency, self-reported health, physical disability, chronic disease, troubled with body pains, BADL disability, IADL disability, living with spouse (partner) or not, number of family members, number of children, using the internet or not, having care support or not when needed, having jobs other than self-employed agricultural or not, individual income, having debt, life satisfaction, and regional distribution were correlated with depression in middle-aged and elderly women (P<0.05). Table 2. Assignment of variables possibly associated with depression among middle-aged and elderly women. Note: CES-D, Center for Epidemiologic Studies Depression Scale; BADL, basic activities of daily living; IADL, instrumental activities of daily living. The total CES-D-10 score of 10 items ranged from 0 to 30, and does not conform to normal distribution, OLS regression may produce estimation errors, so the dependent variables and independent variables are included for further analysis in robust Tobit regression, and the results show that age and age squared, education level, residency, self-reported health, physical disability, chronic disease, troubled with body pains, BADL disability, IADL disability, living with spouse (partner) or not, number of family members, number of children, using the internet or not, having care support or not when needed, having jobs other than self-employed agricultural or not, having debt, life satisfaction, and regional distribution were associated with depression in middle-aged and elderly women (P<0.05). With or without depressive symptoms as dependent variables, the above independent variables were included for robust Logit regression. The results indicated that age and age squared, education level, residency, self-reported health, physical disability, chronic disease, troubled with body pains, BADL disability, IADL disability, living with spouse (partner) or not, number of children, using the internet or not, having care support or not when needed, having debt, life satisfaction, and regional distribution have significant impact on depression in middle-aged and elderly women (P<0.05) (Table 3). The results of the three regression models showed that age and age squared, education level, living in rural or urban areas, self-rated health, physical disability, chronic disease, troubled with body pains, BADL disability, IADL disability, living with spouse (partner) or not, number of children, using the internet or not, having care support or not when needed, having debt, life satisfaction, and regional distribution were associated with depression. Table 3. Robust OLS regression, robust Tobit regression and robust Logit regression analyses of influencing factors possibly associated with depression among middle-aged and elderly women. Note: BADL, basic activities of daily living; IADL, instrumental activities of daily living; a, Chi-square statistic. 3. Discussion Previous studies have found that the rate ofdepression for women was higher than that for men,and the prevalence of depressive symptoms in middle-aged and elderly women in China was 43.2% [15].The results of this study showed that middle-aged and elderly women with depressive symptoms accounted for 43.61% (3473/7963), which was close to the above results.Demographic variables, including age, education levels and residency, can affect the depressive symptoms of middle-aged and elderly women. Among them, the influence of age on depressive symptoms was relatively complex, asthe coefficient of age’s level valuewas significantly positive and coefficient of age squaredwas significantly negative, which was in the shape of inverted U-shaped parabola, and the peak age of onset was 52 years old.This was similar to the results of relevant domestic studies, depression symptoms firstworsened and then alleviated with age, and the peak age of onset was between 50 and 60 years old[14].One study reported that higher education level reduced the correlation between social isolation and depressive symptoms in men, but not in women [16]. However, the results of this study showed that the higher level of education, the lower the risk of depression symptoms in middle-aged and elderly women, which was consistent with the results of Li J S et al. [14].The results of our study showed that compared with living in rural areas, middle-aged and elderly women living in urban areas had a lower risk of developing depressive symptoms, which was similar to the results of HE et al. [17],Kong XK et al. [18]. The improvement of the level of urbanization significantly reduced the rate of depression. Results indicated that physical health status was related to depressive symptoms in middle-aged and elderly women, including poor self-rated health, physical disability, chronic disease,troubled with body pains, BADL disability, IADL disability, which werethe influencing factorsfor depression symptoms in those population, supported by relevant research findings [19-21].The results suggestedthat medical workers should attach great importance to the physical health of those population and minimize the negative impact of physical illness on mental health. The results of the study showed that the number of children was associated withdepressive symptoms in middle-aged and elderly women, similar to previous literature [22]. The more the number of children, the higher the risk of depression symptoms they were.Thereasons why middle-aged and elderly females were more affected by depression symptomscould be attributed to two aspects: on the one hand, the large number of childrenincreases the cost of living, education and healthcare for middle-aged and elderly women, leading to a heavier economic burden.On the other hand, employment, marriage and other problems of multiple children may also increase the psychological burden of middle-aged and elderly women, and then lead to developing depression.In contrast, if living togetherwith a spouse or a partner, the symptoms of depression can be reduced. A spouse or a partner can take careeach other andsolve some tough problems together,especially when it comes to the children.Our study found that surfing the internet or not was also associated with depressive symptoms in middle-aged and elderly women, and the reason was that surfing the internet increased access to information and interpersonal communication. Our results also indicated thathaving care support or not when needed was related to depressive symptoms in middle-aged and older women. When they without care support from family members, relatives and friendswhen needed, depressive symptoms were evident, which may be related to the lack of relevant social support.This result pushed urgent requirements for us to concern overthe mental health status of the special groups and the government to improve the elder social security system. The results of this study also showed that having debt was associated withdepressive symptoms in middle-aged and elderly women.Over-consumption and debt management have gradually become a common economic phenomenon, but the modern financial consciousness has not followed up, resulting in middle-aged and elderly women have more psychological pressure for debt. Life satisfaction was correlated with depression symptoms in middle-aged and elderly women, which was confirmed in previous studies[23], indicating thatpeople who were less satisfied with their lives had more negative psychological feelings and were more prone to be depressed. Moreover,as confirmedin several studies [24-25],there was an imbalance in the regional distribution of depression symptoms in China, which may be closely related to the level of economic development among regions. Much can be doneby relevant institutions and departments to narrow the regional differences between middle-aged and elderly women, improve the level of social equity, and promote the healthy development of mental healthof this populationin different regions. To sum up, according to the data analysis of this study, the prevalence of depressive symptoms among middle-aged and elderly Chinese women was high, accounting for more than 40%. To control and prevent depressive symptoms to improve mental health status in this population, it is suggested to improve their education level, physical health status, family relations and life satisfaction, reduce their debt-financed consumption, and to offer them more ways to access information, and more social support, as well as to promote urbanization. Acknowledgments The authors would like to thank the Institute of Social Science Survey of Peking University for their organizing of CHARLS, and all the participants, investigators and assistants of CHARLS. Author Contributions All authors have approved the final manuscript. Declaration of Competing Interest None. References [1] Yi S W. Depressive symptoms on the geriatric depression scale and suicide deaths in older middle-aged men: a prospective cohort study[J]. J Prev Med Public Health, 2016,49(3):176-82. DOI:10.3961/jpmph.16.012. [2] FERRARI A J, SOMERVILLE A J, BAXTER A J, et al. Global variation in the prevalence and incidence of major depressive disorder: a systematic review of the epidemiological literature[J]. Psychol Med, 2013,43(3):471-81. DOI: 10.1017/S0033291712001511. [3] HESER K, TEBARTH F, WIESE B, et al. Age of major depression onset, depressive symptoms, and risk for subsequent dementia: results of the German study on Ageing, Cognition, and Dementia in Primary Care Patients (AgeCoDe)[J]. Psychol Med, 2013,43(8):1597-610. DOI: 10.1017/S0033291712002449. [4] LI Z, ZHEN W, MAO Z F. Depression and its influencing factors of the elderly in a community, Wuhan[J]. Modern Preventive Medicine, 2018,45(1):102-105. [5] ZHANG W J, WEI M. The evaluation of the mortality and life expectancy of Chinese population[J]. Population Journal, 2016,38(3):18-28. DOI: 10.16405/j.cnki.1004-129X.2016.03.002. [6] ZHOU Z, PAN L L,FANG Y. Associationbetween psychosocial factors and risk of depressive symptoms in the elderly [J]. Chinese Journal of Gerontology, 2019,39(16):4092-4094. DOI: 10.3969/j.issn.1005-9202.2019.16.071. [7] WU S, ZHANG F Y, ZANG Z Y, et al. Analysis on depression and life satisfaction of the elderly in China and influencing factors[J]. J Zhengzhou Univ: MedSci, 2019,54(1):88-92. DOI: 10.13705/j.issn.1671-6825.2018.06.157. [8] LIU S Y, QIAO Y N, WU Y, et al. The longitudinal relation between depressive symptoms and change in self-rated health: a nationwide cohort study[J]. J Psychiatr Res, 2021,136:217-223. DOI:10.1016/j.jpsychires. 2021.02.039. [9] LI M M, FU Y N, WU M C, et al. Correlation between activities of daily living and depression in the elderly[J]. Modern Preventive Medicine, 2017,44(21): 3957-3961. [10] ANDRESEN E M, MALMGREN J A, CARTER W B, et al. Screening for depression in well older adults: evaluation of a short form of the CES-D[J]. Am J Prev Med, 1994,10(2):77-84. DOI: 10.1016/S0749-3797(18)30622-6. [11] CHEN J F, FANG M W,XIAO C H, et al. Activities of daily living and depressive symptoms in the Chinese elderly[J]. Chinese General Practice, 2020,23(22):2852-2855. DOI: 10.12114/j.issn.1007-9572. 2019.00.693. [12] LI L, MA M Y,PENG H Y, et al. Prevalence and associated factors of depressive symptoms in China's rural elderly[J]. Chinese General Practice, 2021,24(27):3432-3438. DOI: 10.12114/j.issn.1007-9572.2021.00.577. [13] LIU H, FAN X, LUO H, et al. Comparison of depressive symptoms and its influencing factors among the elderly in urban and rural areas: evidence from the China Health and Retirement Longitudinal Study (CHARLS)[J]. Int J Environ Res Public Health, 2021,18(8):3886. DOI: 10.3390/ijerph18083886. [14] LI J S, MA W J. Prevalence and influencing factors of depression symptom among middle-aged and elderly people in China[J]. Chin J Public Heal, 2017,33(2):177-181. DOI: 10.11847/zgggws2017-33-02-02. [15] LI Y, HE Y, ZHAO L, et al. Sociodemographic disparity of the depression prevalence in China: findings from the China Health and Retirement Longitudinal study[J].Int J Gerontol, 2019,13(1):33-37. DOI: 10.6890/IJGE.201903_13(1).0007. [16] LUO F, GUO L, THAPA A, et al. Social isolation and depression onset among middle-aged and older adults in China: Moderating effects of education and gender differences[J]. J Affect Disord, 2021,283:71-76. DOI: 10.1016/j.jad.2021.01.022. [17] HE S, SONG D, JIAN W Y. The association between urbanization and depression among the middle-aged and elderly: a longitudinal study in China[J].Inquiry, 2020,57:1-9. DOI: 10.1177/0046958020965470. [18] KONG X K, XIAO Q L, LI J. Urban-rural comparison on the risk factors of geriatric depressive symptoms[J]. Chin Ment Health J, 2018,32(8):648-655. DOI: 10.3969/j.issn.1000-6729.2018.08.005. [19] JIANG C H, ZHU F, QIN T T. Relationships between chronic diseases and depression among middle-aged and elderly people in China: a prospective study from CHARLS[J]. Curr Med Sci, 2020,40(5):858-870. DOI:10.1007/s11596-020-2270-5. [20] WANG X H, ZHAO S X, CAO J, et al. Correlation between depression and low back pain of elderly women in rural areas of China[J].Chinese Journal of Disease Control & Prevention, 2020,24(10):1215-1218. DOI:10.16462/j.cnki.zhjbkz.2020.10.020. [21] HE M, MA J, REN Z, et al. Association between activities of daily living disability and depression symptoms of middle-aged and older Chinese adults and their spouses:a community based study[J]. J Affect Disord, 2019,242:135-142. DOI:10.1016/j.jad.2018.08.060. [22] HU Z, WU Y Y, YANG H L, et al.Effects of fertility behaviors on depression among the elderly: empirical evidence from China[J]. Front Public Health, 2021,8:570832. DOI:10.3389/fpubh.2020.570832. [23] LEE S W, CHOI J S, LEE M. Life satisfaction and depression in the oldest old: a longitudinal study[J]. Int J Aging Hum Dev, 2020,91(1): 37-59. DOI:10.1177/0091415019843448. [24] TAO H W, ZHANG X, WANG Z. The eastern-middle-western depression and the determinants among Chinese rural elderly[J]. Chinese Journal of Disease Control & Prevention, 2018,22(7):696-699. DOI: 10.16462/j.cnki.zhjbkz.2018.07.010. [25] WANG L, ZHANG X. The sexual disparity and determinants of depressive symptoms among the rural elderly in China[J]. Chinese Journal of Disease Control & Prevention, 2018,22(11):1148-1151. DOI: 10.16462/j.cnki.zhjbkz.2018.11.013. (Received: 6 June 2021; Revised: 27 August 2021)
【Abstract】Background Frailty-related issue is increasingly prominent with the acceleration of aging in China.However, domestic research on frailty is still in its infancy characterized by non-objective diagnosis basis, unclear pathogenesis and imperfect interventions.Objective To investigate the correlation of 25-hydroxyvitamin D and interleukin-6 with frailty in elderly patients with chronic disease in the stable phase，so asto explore objective diagnostic basis and new interventions for frailty. Methods A total of 152 inpatients （≥ 60 years old） with chronic disease in the stable phase were recruited from Department of Geriatrics，the First People's Hospital of Yunnan Province（hereinafter referred to as “the department of the hospital”） from November 2020 to April 2021. Clinic and laboratory data were collected. Comprehensive geriatric assessment was conducted via an internet-based platform of the Comprehensive Geriatric Assessment（inpatient version） developed by the department of the hospital，among which frailty was assessed by the Chinese version of Fried Frailty Phenotype，a component of the assessment scale. Results Among the 152 patients，47（30.9%） had no frailty，51（33.6%） had pre-frailty and 54（35.6%） had frailty. According to the binary Logistic regression analysis，disability〔OR=6.162，95%CI（1.091，34.789），P=0.039〕， 25-hydroxyvitamin D〔OR=0.901，95%CI（0.825，0.985），P=0.022〕 and interleukin-6〔OR=1.103，95%CI（1.012，1.201），P=0.025〕 were influencing factors for frailty in elderly patients with chronic disease in the stable phase. Conclusion Sufficient 25-hydroxyvitamin D may be associated with decreased risk of frailty and elevated interleukin-6 may be associated with increased risk of frailty in elderly patients with chronic disease in the stable phase. So these two indicators may be potential targets for predicting and treating frailty.
【Key words】 Frailty；Aged；Chronic disease；25-hydroxy-vitamin D；Vitamin D；Interleukin-6
【Chinese Library Classification Number】R 151.1 【Document Identification Code】A
1.Introduction
Frailty is a special state in which the physical functions of the elderly gradually decline. It is characterized by weakened muscle strength and endurance, decreased physiological functions, increased vulnerability, decreased anti-stress ability with subsequent adverse consequences such as falls, disability, cognitive impairment, mental abnormalities, and even death[1][2]. To identify high-risk older adults, Fried et al.[3]roposed the use of a clinical phenotype to characterize frailty, which consisted of five body components, including decreased muscle strength, reduced walking speed, fatigue, reduced physical activity and unconscious weight loss. These criteria are now widely used in clinical research for the diagnosis of frailty.
With the aging of the Chinese population, the problem of frailty in old age is increasingly serious. However, frailty specific diagnosis is not objective, the pathogenesis is not clear, and the intervention is not sound, indicating that the current research on this matter is yet in its infancy. Although there are previous studies that have explored the possibility of symptoms related to the geriatric syndrome, such as cognitive function, daily activity ability, anxiety and depression and others, to diagnose frailty more confidently and precisely, data on the correlation between 25- hydroxyvitamin D (25(OH)D), interleukin (IL)-6 and frailty in elderly are still missing. Therefore, we aim to explore the correlation between senile frailty and 25(OH)D and IL-6, so asto lay a foundation for the objective diagnosis and intervention of senile frailty in the future.
2 Objects and Methods
2.1 Research objects
152 patients at the age of 60 years and above, diagnosed with a chronic disease in the stable phase were recruited at the Department of Geriatrics, the First People's Hospital of Yunnan Province, China. The inclusion criteria were as follows: 1) previously hospitalized patients with no new disease, aged ≥ 60 years without new disease, 2) patients with no communication barriers and able to cooperate in the comprehensive geriatric assessment (CGA), and 3) patients who were voluntarily participating in the study and have signed the informed consent. The applied exclusion criteria were: 1) elderly people who have been supplemented with Vitamin D and anti-inflammatory drugs in the past one month, 2) patients, who were diagnosed with acute infectious diseases recently, 3) patients with serious physical and/or mental diseases with communication barriers, who were unable to complete the Fried scale assessment, 4) patients who were bedridden or unstable for a long time and 5) patientswho had insufficient information on the evaluation scale or laboratory data.
This study was implemented after approval of the Medical Ethics Committee of the First People's Hospital of Yunnan Province (No. KHLL2021-KY034).
2.2 Data Collection
2.2.1 General information
Patients’ general information, including age, gender, height, body mass, body mass index (BMI), educational level, allergyhistory, vision or hearing loss, presence or absence of dentures, marital status, eating habits, sleep time, sleep aids supplementation, current smoking (referring to smoking in the last 30 days before the survey), current drinking (referring to the alcohol consumption in the last 30 days before the survey) were collected.
2.2.2 Comprehensive Geriatric Assessment (CGA)
The internet-based platform of the Comprehensive Geriatric Assessment (inpatient version) is a software independently developed by the Department of Geriatrics, First People's Hospital of Yunnan Province, China and was applied in the current study. It consists of several national general assessment scales and has certain intelligence. The calculated scores and evaluation results were given automatically according to each assessment option following the criteria and reference scope formulated by various general scales. The researchers collected patients’ data through a WeChat mini-program or computer, and Excel forms were automatically generated for data summary later. The assessors were geriatricians who have received the "Comprehensive Geriatric Assessment System" software training. The assessment included mainly nutritional status assessment and the Micronutrient Assessment Scale (MNA-SF) was used. Values ≥ 24 were considered as indicators of good nutrition, betwen17 and 24 were designated as potential malnutrition, while between 0 and 17 were classified as malnutrition. The cognitive function assessment was according to the Simple Mental State Examination Scale (MMSE), where values between 0 and 9 were classified as a severe impairment, between 10 and 20 - as moderate impairment, between 21 and 26 were classified as mild impairment, while scores between 27 and 30 were designated as cognitive normal functions. Evaluation of anxiety and depression followed the Geriatric Depression Scale (GDS-15), where scores ≥ 6 indicated anxiety and depression. Evaluation of depression following the Self-rating Depression Scale (SDS) was used and the T scores <50 indicated no presence of depression, whereas T ≥ 50 was classified as a depressive mental state. The evaluation of anxiety was according to the Self-rating Anxiety Scale (SAS), where scores <50 indicated lack of anxiety, while equal and above 50 was categorized as anxiety. Daily living ability assessment was according to the basic Living activity ability (BADL) scale, where scores between 91 and 100 were indicators of good daily living function, between 61 and 90 were regarded as mild functional impairment, between 41 and 60 was labeled as moderate functional impairment, between 21 and 40 were considered as severe functional impairment, whereas patients with scores between 0 and 20 were grouped as completely disabled. Instrumental living ability assessment was according to the Instrumental Ability of Daily Living (IADL) scale was used to assess whether patients were able to go shopping, go out for activities, cook food, maintain household chores and wash clothes. Those who need assistance in 3 or more of these criteria were considered disabled. The sleep status assessment was done according to the Assens Insomnia Scale (AIS), where scores between 0 and 3 indicated good sleep, between 4 and 6 spoke for potential insomnia, whereas between 7 and 24 indicated insomnia. Fall risk assessment was according to the Morse Fall Risk Assessment Scale, where scores between 0 and 24 classified the patients at low risk of fall, between 25 and 44 categorized the patients at moderate risk, whereas scores equal and above ≥ 45 categorized the elderly people at severe risk. The balance function evaluation was agreeing with the Tinetti balance and gait scale, where scores less than 15 indicated the risk of falling, between 15 and 24 designated balance dysfunction, whereas scores ≥ 24 indicated good physical function. The visual simulation method was used for pain evaluation. Scores equal to 0 indicated lack of pain, between 1 and 3 designated mild pain, between 4 and 6 showed the presence of moderate pain, whereas between 7 and 10 indicated presence of severe pain. The evaluation of urinary incontinence was in harmony with the Incontinence Questionnaire Simple Form (ICI-Q-SF), where scores equal to 0 classified the patients into the group of asymptomaticurinary incontinence, between 1 and 7 determined the elderly people with mildurinary incontinence, between 8 and 14 indicated moderateurinary incontinence, whereas the scores between 15 and 21 indicated that the patients had severe urinary incontinence. Constipation was assessed using the Roma = 3 \* ROMAN III Scale (≥2). Other parameters that were taken into account included falls (within the last 1 year), the number of chronic diseases, the coexistence of multiple diseases (≥ 2 diseases), multiple medications (≥ 5 oral medications), the number of medications and others. All these allowed to assess and diagnose frailty and evaluating scores are presented in Table 1.
Table 1 Contents of the Chinese version of Fried method for evaluation and classification of frailty among elderly people
variable
Overall
(n=288)
Non-Frailty(n=87)
Pre-Frailty(n=93)
Frailty(n=108)
χ2(F) value
P value
age a(years)
67.501
<0.001**
<75 years old
111(38.5)
50(67.8)
37(39.8)
15(13.9)
≥75,<85 years old
92(31.9)
24(27.6)
35(37.6)
33(30.6)
≥85 years old
82(29.5)
4(4.6)
21(22.6)
60(55.6)
gender b
1.527
0.466
male
173(60.1)
48(55.2)
56(60.2)
69(63.9)
Female
115(39.9)
39(44.8)
39(36.1)
BMI a,mean ± SD
23.28±4.14
23.63±3.41
23.42±5.54
22.87±3.15
0.897
0.409
Education level b
7.599
0.269
illiteracy
12(4.2)
1(1.1)
6(6.5)
5(4.6)
primary school
155(53.8)
51(58.6)
44(47.3)
Middle school
66(29.9)
15(17.2)
26(28.0)
25(23.1)
College degree and above
55(19.1)
20(23.0)
17(18.3)
18(16.7)
Vision condition b
9.617
0.008*
normal
87(30.2)
39(41.9)
24(22.2)
decline
201(69.8)
63(72.4)
54(58.1)
84(77.8)
Hearing condition b
20.417
41(44.1)
26(24.1)
52(55.9)
82(75.9)
marital status b
4.667
0.097
Married
222(77.1)
72(82.8)
74(79.6)
76(70.4)
Divorced/Widowed
66(22.9)
19(20.4)
32(29.6)
Eating habits b
2.114
0.347
Light diet mainly
248(86.1)
71(81.6)
82(88.2)
95(88.0)
Mainly salty and greasy diet
40(13.9)
16(18.4)
11(11.8)
13(12.0)
sleeping time(h) a ,mean ± SD
6.74±1.69
7.08±1.78
7.19±2.09
1.459
0.234
Smoking status b
1.363
0.506
Not currently smoking
224(77.8)
65(74.7)
76(81.7)
83(76.9)
Current smoking
64(22.2)
22(25.3)
Drinking situation b
3.529
0.171
Not currently drinking
242(84.0)
68(78.2)
92(85.2)
Current drinking
46(16.0)
19(21.8)
16(14.8)
Number of chronic diseases (species) a,mean ± SD
7.72±3.39
6.70±3.59
7.46±3.45
8.75±4.23
7.297
0.001*
Polypharmacy(kind) b
14.734
No Polypharmacy
103(35.8)
44(50.6)
33(35.5)
There are Polypharmacy (≥5 species)
185(64.2)
43(49.4)
60(64.5)
Note: The lack of compliance with any of the items listed in Table 1 indicated a lack of frailty. The compliance with 1 and/or 2 items indicated a pre-frailty condition, while the compliance with 3 items was firmly diagnosed as frailty; IPAQ = International Physical Activity Scale
2.2.3 Laboratory examination
30 ml of fasting venous blood was collected from the hospitalized elderly patients from 6:00 to 8:00 am and sent to the clinical laboratory of our hospital for testing. The automatic analyzer Xiang Instrument L1550 was used for blood samples analyse. The blood was centrifuged at 3 500 r/min for 5 min. The detected parameters included the white blood cells (WBC) and red blood cells count (RBC), haemoglobin (Hb), platelets (PLT) and neutrophils count (NEUT), as well as the C-reactive protein (CRP). The aspartate (AST) and alanine aminotransferase (ALT) were detected by the rate method. Triacylglycerols (TG) were detected by the deionization glycerol method, the total protein (TP) was detected by the biuret method, albumin (ALB) was detected by the bromocresol green method, while the total cholesterol (TC) was detected by the cholesterol oxidase method. High density (HDL) and low-density lipoproteins (LDL) were detected by the elimination method. Blood sodium (Na+), blood potassium (K+) and blood chlorine (Cl-) were detected by the ion-selective electrode method. Creatinine (Cr) and glycosylated haemoglobin (HbA1c) were assayed by enzyme reactions. Urea nitrogen (BUN) was assayed by the urease UV rate method. Uric acid (UA) was assayed by enzyme calorimetry. Blood calcium (Ca2+) was assessed by the arsenazo ⅲ method. The Hexokinase method was used for assessing the amount of fasting blood glucose. Fructosamine was detected by the tetrazolium blue method. Thyroid-stimulating hormone (TSH), triiodothyronine (T3), thyroid hormone (T4), free triiodothyronine (FT3), free thyroid hormone (FT4), ferritin, vitamin B12, folic acid, 25(OH)D, estradiol, testosterone, homocysteine (Hcy), fasting insulin (FINS) were detected by electrochemiluminescence. Activated partial thrombin time (APTT), prothrombin time (PT), thrombin time (TT) and D-dimer (DD2) were detected by the magnetic bead method or by immunoturbidimetry. Tumour necrosis factor (TNF), IL-10, IL-6, IL-12P70, IL-1 and IL-8 were detected by chemiluminescence.
2.2.4 Data quality control
To assure the gathered data quality all assessment physicians passed the training programme for assessment of the Comprehensive Geriatric Assessment System Software Platform (Inpatient version). All incomplete or inconsistent data were regarded as invalid data and thus excluded from the study.
2.3 Statistical Methods
SPSS 23.0 software was used for statistical analysis. The measurement data (
3 Results
152 elderly patients were included in the study, among them, 47 (30.9%) had no frailty, 51 (33.6%) had early frailty and 54 (35.6%) had frailty.
3.1 Comparison of general data and geriatric syndrome of patients with different degrees of frailty
There were no significant differences in gender, height, body mass, BMI, education level, food or drug allergy, denture, marital status, eating habits, sleep time, use of sleeping supplementation, current smoking and alcohol consumption, present anxiety, fall, pain, urinary incontinence, constipation and multiple diseases among patients with different degrees of frailty (P > 0.05). There were statistically significant differences in age, visual impairment, hearing impairment, nutritional status, cognitive function, presence of anxiety and depression, presence of anxiety, daily living ability, disability, sleep status, fall risk, balance function, number of chronic diseases, multiple medications, number of medications（P <0.05). These data are shown in Table 2.
Table 2 Comparison of clinical data and geriatric syndromes in participants by level of frailty
frailty degree
no frailty (n=47)
pre-frailty（n=51）
frailty (n=54)
Age (±s, years)
74.45±8.035
80.29±8.81
85.17±7.06
22.678a
<0.001
Gender〔n(%)〕
1.263
0.532
25（53.2）
32（62.7）
34（63.0）
female
22（46.8）
19（37.3）
20（37.0）
height(±s,m)
1.60±0.88
1.61±0.06
1.62±0.08
0.815a
0.444
Body mass(±s,kg)
59.57±11.15
58.52±10.63
60.60±10.30
0.494
0.611
BMI（ ±s，kg/m2）
24.47±2.69
24.17±1.90
23.84±2.21
0.959a
0.385
Education level〔n(%)〕
13.692
0.090
0（0.0）
2（3.9）
4（7.4）
17（36.2）
13（25.5）
18（33.3）
junior high school
20（42.6）
13（24.1）
high school
5（10.6）
15（29.4）
9（16.7）
8（15.7）
10（18.5）
Food or medicineHistory of allergies〔N(%)〕
11（23.4）
0.776
0.678
Vision loss〔N(%)〕
30（63.8）
31（60.8）
44（81.5）
6.138
0.046
Hearing loss〔N(%)〕
9.790
0.007
Have false teeth〔n（%）〕
25（49.0）
33（61.1）
1.602
0.449
8（17.0）
16（29.6）
2.224
0.329
Eating habits〔n(%)〕
0.035
0.983
Light diet
40（85.1）
44（86.3）
46（85.2）
Greasy diet
7（14.9）
7（13.7）
8（14.8）
sleeping time(±s,h/d)
6.55±1.84
7.18±2.17
7.22±1.81
1.794a
0.170
TakeSleeping aids〔N(%)〕
9（17.6）
11（20.4）
0.218
Current smoking〔N(%)〕
13（27.7）
12（23.5）
17（31.5）
0.829
0.661
Current drinking〔 N (%)
9（19.1）
10（19.6）
0.024
0.988
Nutritional status〔n(%)〕
30.644
Good nutrition
29（61.7）
23（45.1）
Potential malnutrition
16（34.0）
26（51.0）
23（42.6）
Severe malnutrition
2（4.3）
Cognitive function〔n(%)〕
51.111
Good cognitive function
33（70.2）
21（41.2）
13（8.6）
Mild cognitive impairment
24（47.1）
Moderate cognitive impairment
1（2.1）
6（11.8）
Severe cognitive impairment
0.（0.0）
Anxiety and depression
〔N(%)〕
19（40.4）
35（68.6）
43（79.6）
17.495
Existence suppression
Depression〔N(%)〕
18（38.3）
36（70.6）
42（77.8）
18.654
ExistenceWorry state〔N(%)〕
3（5.9）
5（9.3）
1.084
0.581
Ability of daily living [n (%)]
87.800
Good daily function
3（5.5）
Mild dysfunction
22（43.1）
19（35.2）
Moderate dysfunction
7（13.0）
Severe dysfunction
25（46.3）
Disability〔N(%)〕
48（90.6）
51.821
Sleep condition〔n(%)〕
12.017
0.017
Sleep well
18（35.3）
Potential insomnia
11（21.6）
14（25.9）
Insomnia
24（44.4）
Nearly 1 yearFall〔n（%）〕
1.616
0.446
Risk of falling [n(%)]
9.603
0.048
Low risk
39（83.0）
37（72.5）
31（57.4）
Moderate risk
6（12.8）
Severe risk
12（22.2）
Balance function〔n(%)〕
16.314
0.003
Function well
28（59.6）
15（27.8）
Balance disorder
Risk of falling
21（38.9）
Have pain〔N(%)〕
26（56.5）
29（56.9）
32（59.3）
0.094
0.954
Urinary incontinence〔N(%)〕
3（6.4）
3.614
0.164
constipate〔N(%)〕
14（27.5）
0.503
0.778
Number of chronic diseases
(±s, kind)
4.87±2.29
5.86±2.12
6.39±2.80
4.985a
0.008
Multiple diseases coexist
45（95.7）
51（100.0）
52（96.3）
2.104
0.349
Multi-drug〔N(%)〕
24（51.1）
38（74.5）
36（66.7）
6.046
0.049
Number of medications(±s, kind)
5.15±2.53
6.22±2.82
6.81±3.35
3.987
0.021
Note: Pain = mild pain + moderate pain + severe pain; urinary incontinence = mild urinary incontinence + moderate urinary incontinence + severe urinary incontinence; a represents F value; BMI = body mass index
3.2 Comparison of the laboratory examination indexes of the elderly patients with different degrees of frailty
There were no significant differences in the WBC, RBC, PLT, NEUT, CRP, AST, TG, TP, TC, HDL, LDL, K+, Cr, HbA1c, BUN, UA, Ca2+, fasting blood glucose, glucosamine, TSH, T3, T4, FT3, FT4, ferritin, vitamin B12, folic acid, testosterone, FINS, TT, TNF, IL-10, IL-12P70, IL-1 among the studied patients with different degrees of frailty (P>0.05). Statistically significant differences were found in the Hb, ALT, ALB, Na+, Cl-, (25(OH)D, estradiol, Hcy,, APTT, PT, DD2, IL-6 and IL-8 (P<0.05). These parameters and interactions are shown in Table 3.
Table 3 Comparison of the laboratory indicators in the elderly participants by the level of frailty
Z( F ) value
WBC 〔M（P25，P75），
×109 /L〕
6.82（5.26，7.76）
6.16（4.89，7.22）
5.93（5.07，7.26）
1.520
0.285
RBC〔M（P25，P75），
×1012/L〕
4.34（3.99，4.64）
4.39（4.07，4.71）
4.10（3.44，4.59）
8.158
0.077
Hb（g/L）
132.43±24.84
137.43±17.65
121.44±27.33
6.276
0.002
PLT〔M（P25，P75），
210.00（168.00，248.00）
194.00（151.00，235.00）
180.50（137.00，224.25）
4.028
NEUT〔M（P25，P75），
4.54（2.74，5.35）
3.81（2.95，4.71）
4.09（2.95，4.96）
1.487
0.084
CRP〔M（P25，P75）， mg/L〕
2.35（0.50，20.75）
3.04（1.31，11.42）
11.17（2.67，28.05）
8.650
0.056
AST〔M（P25，P75）， U/L〕
20.00（15.00，27.00）
19.00（15.00，24.00）
18.50（15.00，26.00）
0.419
0.770
ALT 〔M（P25，P75）,U/L〕
14.00（10.00，25.00）
16.00（10.00，20.00）
12.00（8.00，19.00）
4.242
0.030
TG 〔M（P25，P75）,mmol/L〕
1.18（0.85，1.84）
1.25（0.85，1.96）
1.10（0.74，1.61）
2.263
0.439
TP（g/L）
64.28±7.07
63.48±6.60
63.72±9.38
0.133
0.875
ALB（g/L）
37.20±4.96
36.50±4.14
34.18±3.52
7.250
0.001
TC（mmol/L）
4.16±1.25
4.11±1.00
3.87±1.05
1.040
0.356
HDL（mmol/L）
1.08±0.37
1.05±0.28
1.00±0.28
0.803
0.450
LDL（mmol/L）
2.51±1.00
2.43±0.79
2.28±0.87
0.936
0.395
Na+（mmol/L）
139.34±2.96
139.51±2.87
137.33±4.02
6.844
K+（mmol/L）
3.96±0.47
4.00±0.45
3.97±0.49
0.034
0.966
Cl-〔M（P25，P75），
mmol/L〕
108.00（106.00，110.00）
107.00（105.00，110.00）
106.00（102.75，108.00）
9.637
Cr〔M（P25，P75）,μmol/L〕
72.00（60.00，90.00）
77.00（63.00，95.00）
83.00（67.50，114.00）
5.176
0.147
HbA1c〔M（P25，P75），%〕
6.25（5.82，7.75）
6.31（5.81，7.74）
6.02（5.57，6.82）
4.246
0.160
BUN〔M（P25，P75），μmol/L〕
6.40（4.90，8.70）
6.80（4.90，8.90）
7.85（5.68，10.10）
3.946
0.225
UA〔M（P25，P75）μmol/L〕
362.00（285.00，425.00）
396.00（339.00，457.00）
346.00（261.25，504.75）
4.083
0.069
Ca2+〔M（P25，P75），mmol/L〕
2.19（2.09，2.28）
2.19（2.10，2.26）
2.18（2.10，2.24）
0.486
Fasting blood glucose〔M（P25，P75）, mmol/L]
5.40（4.60，6.80）
4.90（4.40，6.60）
4.85（4.20，6.00）
3.010
0.140
Fructosamin〔M（P25，P75）,μmol/L]
1.60（1.46，1.76）
1.55（1.44，1.66）
1.54（1.37，1.70）
1.231
0.786
TSH〔M（P25，P75），mU/L〕
2.83（1.49，4.38）
2.73（1.50，4.51）
2.28（1.30，4.51）
0.231
0.544
T3〔M（P25，P75），nmol/L〕
1.04（0.81，1.30）
0.95（0.80，1.28）
0.96（0.72，1.16）
2.450
0.277
T4〔M（P25，P75）nmol/L〕
76.33（66.67，80.07）
76.33（65.58，90.15）
72.55（64.11，83.71）
0.809
0.781
FT3〔M（P25，P75），pmol/L〕
4.37（3.92，4.97）
4.29（3.41，4.77）
4.17（3.16，4.70）
3.854
FT4〔M（P25，P75），pmol/L〕
12.41（10.88，14.53）
12.25（9.92，14.72）
13.23（11.67，15.14）
2.435
0.238
APTT（s）
36.01±4.19
37.51±4.44
39.29±5.53
5.943
PT〔M（P25，P75），s〕
12.80（12.20，13.40）
12.90（12.40，13.50）
13.30（12.78，14.18）
12.309
0.010
TT〔M（P25，P75），s〕
18.10（17.20，18.80）
18.30（17.60，19.20）
18.00（17.18，18.70）
2.184
0.668
DD2(ug/ml)
1.18（0.90，2.11）
1.33（1.00，2.06）
2.00（1.29，4.39）
16.137
0.009
Ferritin〔M（P25，P75）, ng/ml〕
237.07（181.59，418.50）
225.96（95.43，378，26）
224.03（106.48，480.20）
1.025
0.676
Vitamin B12〔M（P25，P75）, pmol/L〕
297.00（225.00，498.77）
344.00（224.00，462.00）
394.50（260.25，924.50）
5.727
0.654
Folic acid 〔M（P25，P75）,nmol/L〕
15.50（9.80，22.80）
15.50（9.60，24.80）
12.70（7.68，28.25）
0.733
0.325
25（OH）D（μg/L）
22.72±9.69
19.60±9.42
17.14±6.59
5.282
0.006
Estradiol (Pmol/L)
111.61±53.60
125.17±62.47
149.60±52.97
5.919
Testosterone (nmol/L)
1.86（0.51，13.24）
2.84（0.54，15.20）
4.77（0.57，13.51）
0.162
Hcy〔M（P25，P75），μmol/L〕
14.40（11.90，17.95）
16.80（14.20，19.10）
17.95（15.00，23.63）
7.705
0.015
FINS〔M（P25， P75），U/L〕
6.92（4.94，11.52）
6.06（3.90，9.04）
6.77（4.16，8.62）
2.150
0.600
TNF〔M（P25，P75），ng/L〕
5.98（4.18，12.87）
6.32（4.18，13.20）
6.15（5.20，10.39）
0.597
0.832
IL-10〔M（P25，P75），ng/L〕
4.33（3.48，5.38）
4.75（3.70，6.30）
4.92（3.68，6.46）
3.196
IL-6〔M（P25，P75）,ng/L〕
12.61（5.95，18.37）
20.88（7.82，34.01）
25.29（17.21，46.79）
31.520
IL-12P70〔M（P25， P75），ng/L〕
5.22（3.57，5.92）
4.99（2.04，5.80）
5.56（4.64，6.32）
4.078
0.165
IL-1ß〔M（P25，P75），ng/L〕
4.65（3.64，7.59）
4.93（3.45，8.02）
4.65（3.91，7.22）
0.408
0.873
IL-8〔M（P25，P75），ng/L〕
19.46（12.77，38.93）
41.67（18.53，90.28）
25.65（14.64，60.40）
8.685
Note: WBC=white blood cell count, RBC=red blood cell count, Hb=hemoglobin, PLT=platelet count, NEUT=neutrophil fraction, CRP=C reactive protein, AST=aspartate aminotransferase, ALT=alanine aminotransferase, TG=triacylglycerol, TP=total protein, ALB=albumin, TC=total cholesterol, HDL=high-density lipoprotein, LDL=low-density lipoprotein, Na+=serum sodium, K+=serum potassium, Cl-= blood chlorine, Cr= creatinine, HbA1c= glycosylated hemoglobin, BUN= urea nitrogen, UA= uric acid, Ca2+=blood calcium, TSH= thyroid stimulating hormone, T3= triiodothyronine, T4= thyroid hormone, FT3= Free triiodothyronine, FT4 = free thyroid hormone, 25 (OH) D = 25 hydroxyvitamin D, Hcy = homocysteine, FINS = fasting insulin, APTT = activated partial thromboplastin time, PT = coagulation proenzyme time, TT = thrombin time, DD2 = D-dimer, TNF = tumor necrosis factor, IL = interleukin; a represents F value
3.3 Binary Logistic regression analysis
Taking frailty of elderly patients with stable chronic diseases as a dependent variable, where 1 indicated lack of frailty and 2 designated pre-frailty and frailty, all variables with statistically significant differences (P<0.05) demonstrated in Tables 1 and 2 were taken as independent variables. These included the age (assigned: measured value), vision (where 0 was normal and 1 was decreased), hearing (where 0 was normal and 1 was accepted as decreased), nutritional status (where 0 indicated good nutrition, 1 - potential malnutrition and 2 - malnutrition), cognitive function (where 0 was normal cognition and 1 was cognitive impairment), anxiety and depression states (where 0 was accepted as no anxiety and depression state, whereas 1 was classified with anxiety and depression state, depression state (where 0 indicated no depression state, whereas 1 indicated presence of such), daily living ability (where 0 was indicative of good daily life function, while 1signified dysfunction of daily life), disability (where 0 indicated not disabled and 1 - complete disability), sleep status (with 0 equal to good sleep, 1equal to potential insomnia, whereas 2 represented insomnia), risk of fall (where 0 indicated low risk, 1- moderate risk, while 2 indicated severe risk), balance function (where 0 stood for good physical function, 1 for balance dysfunction, whereas 2 indicated risk of fall), number of chronic diseases (measured value), multiple medications (where 0 indicated none and 1 indicated presence), number of medications (measured value), Hb (measured value), ALT (measured value), ALB (measured value), Na+ (measured value), Cl- (measured value), 25- (OH) D (measured value), estradiol (measured value), Hcy (measured value), APTT (measured value), PT (measured value), DD2 (measured value), IL-6 (measured value), IL-8 (measured value). Binary Logistic regression analysis showed that the disability, 25-(OH)D and IL-6 were the independent influencing factors in elderly patients with stable chronic diseases (P<0.05), as shown in Table 4.
Table 4 Binary logistic regression analysis of frailty in elderly patients with chronic disease
β
SE
Wald x2 value
OR（95%CI）
Disability
1.818
0.883
4.240
0.039
6.162（1.091，34.789）
25-（OH）D
-0.104
0.045
5.238
0.022
0.901（0.825，0.985）
IL-6
0.098
0.044
5.008
0.025
1.103(1.012,1.201)
4 Discussion
4.1 Occurrence of senile frailty and independent related factors
Our results showed that the overall incidence of frailty in the studied hospitalized elderly patients was 35.6% (54/152), which was similar to the results of Lai Xiaoxing et al.[4], Wei Yin et al.[5]and others[6], where the estimated incidence rate was 31.3%, 34.4% and 35.4%, respectively, which was higher than that estimated one by Wang Wanwan et al.[7], whose calculations showed an incidence of the frailty of 25.1%. Interestingly, these estimations were lower than that by Jin Qiulu et al.[8], who found that the frailty rate of elderly patients (≥ 80 years old) was 41.6%. These differences in the prevalence and incidence rate of frailty among elderly people may be due to different assessment tools, age, and study subjects.However,overall, the prevalence of frailty in China is not optimistic.Considering that is often followed by a variety of adverse consequences[1-2], early screening, prevention and intervention can greatly reduce the prevalence and hospitalization rate of elderly people with frailty.
Other authors’ studies in the United States, Mexico, Australia and other countries have shown that Vitamin D (25(OH)D) is an independent factor affecting frailty[9][11]. In addition, another analysis involving that 20 355 subjects from 13 studies demonstrated a significant inverse relationship between the 25(OH)D levels in patients’ blood results and increased frailty severity (following Fried's phenotypic definition) in both the original analysis and sensitivity analysis[12]. The results of our study are consistent with those of the above. However, according to a cross-sectional study of community women aged ≥ 75 years in Belgium, there no relationship between low vitamin D levels and lower limb muscle strength and grip strength was estimated[13]. The reason for this variance may be that the study from Belgium only targeted community women ≥ 75 years. Moreover, the levels of 25(OH)D in the blood are influenced by multiple factors, such as gender, age, geography and others, therefore these results may be somewhat limited.
According to multiple other meta-analyses, frailty and early frailty were associated with higher levels of CRP and IL-6[14][15]. This was confirmed by a recent meta-analysis of 23 910 older adults, where the authors proved that frailty and pre-frailty were associated with higher levels of inflammatory factors, especially CRP and IL-6[16]. Our research results were similar to the above studies. Although CRP was not an independent risk factor for frailty in our study, the single factor comparison was still statistically significant (P<0.05). The reason for this difference may be that the sample size of this study, which we understand that is relatively small. Second, the subjects were elderly patients with stable chronic diseases, and CRP was an acute phase reactant[17], therefore it was possible to rise under a variety of pathophysiological conditions. Therefore, this non-specific inflammatory marker was not considered as necessarily related to frailty[18].
4.2 25(OH)D, IL-6 and senile frailty are interrelated in elderly patients
25(OH)D is the major circulating metabolite of Vitamin D which is a globally recognized marker reflecting the Vitamin D status. Vitamin D deficiency is often associated with muscle weakness[19]. Vitamin D receptors (VDRs) are distributed in multiple target organs such as skin and muscles[20].VDRs act as nuclear receptor-mediated gene effects. VDRs bind to (1,25-(OH)2D) to induce the proliferation and differentiation of muscle fiber, and also affect the synthesis of related proteins. On the other hand, VDRs can also activate signal transduction pathways that can induce MAP kinase and phospholipase C through non-nuclear receptor-mediated non-genetic effects, so that a large number of calcium ions can rapidly flow into cells and affect muscle contraction[21][22]. Therefore, the possible mechanisms of 25(OH)D deficiency leading to frailty are due to affected muscle strength, resulting in decreased grip strength [23][24] and because of reduced development of muscle cells, ultimately leading to unconscious weight loss[25]. In addition, Vitamin D deficiency can also cause osteolysis secondary to hyperparathyroidism, leading to osteoporosis and even fracture, which can aggravate the progression of frailty and osteoporosis, leading to disability and other adverse events.
IL-6 levels increase with age[14], and high IL-6 can be used as a predictor of both the occurrence of sarcopenia and the adverse outcomes of frailty and sarcopenia, such as disability, functional decline and even death[26]. IL-6 can inhibit TNF-α and IL-1β and induce the production of CRP, fibrinogen and other acute-phase reactants[14], it can also indirectly reduce growth hormone (GH) and insulin-like growth factor 1 (IGF-1) levels, reduce protein synthesis and lead to sarcopenia. In addition, increased serum IL-6 and CRP levels were also associated with decreased grip strength[27]. The study of Maet al.[28]included 130 elderly patients and showed that IL-6 was negatively correlated with the strength and gait speed of the frailty elderly. IL-6 levels were also inversely associated with exercise tolerance in older adults after adjustment for age and gender. Therefore, we suggested that IL-6 could be applied as a biomarker for functional decline and frailty.
All the above studies suggest that high IL-6 levels are associated with senile frailty, and Vitamin D deficiency may be involved in inflammation and immune system activation[29]. Moreover, data are suggesting that Vitamin D supplementation reduced the levels of IL-6 in peripheral blood, inhibiting the production of IL-6 by peripheral blood monocytes, macrophages and T cells[30][31], and thus upregulating the expression of anti-inflammatory factors (such as IL-10) and inflammatory suppressor molecules[32].
4.3 Vitamin D supplementation as an intervention for reducing senile frailty
Some relevant epidemiological studies suggested that Vitamin D had a potential role in maintaining and improving muscle strength, function and physical performance, thus maintaining the independence of elderly people[33]. Other authors’ results demonstrated that the combined supplementation of elderly people with calcium and Vitamin D reduced the incidence of fractures and the risk of falls among them[34][36]. In addition, a randomized controlled trial of 5,615 participants showed only a slight improvement in the overall muscle strength after baseline Vitamin D supplementation[37]. Some data show that Vitamin D supplementation in elderly people may take longer or larger doses are needed before its beneficial effect on the muscles is present[38], to slow the progression of frailty[39]. Nonetheless, Cummingset al.[40]confirmed that the high-dose Vitamin D supplementation increased the risk of falls. Therefore, the ideal supplementation threshold for Vitamin D is a major question that needs special attention. According to the American Institute of Medicine, concentrations of 25(OH)D above 50 nmol/L are fully sufficient for human needs [41], while the American Endocrine Society sets the sufficient threshold above 72.5 nmol/L, the insufficiency threshold between 52.5 and 72.5 nmol/L, while the deficiency threshold is set at daily uptake concentrations less than 50 nmol/L[42]. Thus it can be seen that the dose critical value of vitamin D supplementation in the intervention of senile frailty needs further investigation.
5 Conclusion
The detected prevalence of senile frailty in hospitalized patients is not optimistic at all and is a burden to the medical and social systems in China. Therefore, the early screening, diagnosis and intervention of frailty are particularly essential. In this study, 25(OH)D and IL-6 were found to be independently correlated with frailty in elderly patients with stable chronic diseases. This indicates that 25(OH)D played as a protective factor of frailty in elderly patients with stable chronic diseases, while IL-6 was a risk factor. Therefore, 25(OH)D and IL-6 are expected to be predictors or objective biological indicators for the diagnosis of frailty in elderly patients with stable chronic diseases. In addition, Vitamin D supplementation may help prevent or delay senile frailty, though its dosage needs to be further discussed.
The innovativeness of this study can be summarized as follows:
1. The mobile software platform was successfully used to replace the traditional paper version for the evaluation of the senile frailty and related symptoms, which greatly reduced data collection time and statistical errors, thus increasing the reliability of the data.
2. The study of the senile frailty from the direction of the objective biomarkers in haematology and the mechanism of their action was described, which covered the lack of domestic research in this area.
3. This study proposed that 25-hydroxyvitamin D and interleukin-6 may be predictive or diagnostic factors of frailty in elderly patients with stable chronic diseases. Moreover, the hypothesis that Vitamin D supplementation of elderly patients may be a potential target for interventions is raised.
Like any other study, ours has some limitations too. The study was cross-sectional with a small sample size, which could not directly explore the causal relationship between the 25-hydroxyvitamin D, interleukin-6 and frailty. Second. it was a single-centre study with certain regional limitations. Finally, the subjects of this study were hospitalized elderly patients with stable chronic diseases, which could not represent the whole elderly population.
Author contribution: Dai Jingrong was responsible for the conception and design of the paper, the analysis and interpretation of the results, as well as the writing of the paper; Li Yan carried out the implementation and feasibility analysis of the research and was responsible for the quality control and review of the paper. Data collection was done by Li Jie, He Xu and Li Yang; He Xu and Li Yang, whosorted out and input data; Li Jie conducted the statistical processing and revised the paper; Dai Jingrong and Li Yan were responsible for the supervision and management of the article.
No conflict of interest is declared.
References
[1] APÓSTOLO J，COOKE R，BOBROWICZ-CAMPOS E，et al. Effectiveness of interventions to prevent pre-frailty and frailty progression in older adults：a systematic review［J］. JBI Database System Rev Implement Rep，2018，16（1）：140-232. DOI：10.11124/JBISRIR-2017-003382.
[2] HOOGENDIJK E O，AFILALO J，ENSRUD K E，et al. Frailty：implications for clinical practice and public health［J］.Lancet，2019，394（10206）：1365-1375. DOI：10.1016/S0140-6736（19）31786-6.
[3] FRIED L P，TANGEN C M，WALSTON J，et al. Frailty in older adults：evidence for a phenotype［J］. J Gerontol A Biol Sci Med Sci，2001，56（3）：M146-156. DOI：10.1093/gerona/56.3.m146.
[4] LAI X X，BO L，ZHU H W，et al. Relationship between sleep disorders and frailty in elderly inpatients［J］. Pract Geriatr， 2021，35（1）：24-27.
[5] WEI Y，CAO Y P，YANG X L，et al. Frailty syndrome in hospitalized geriatric patients and its risk factors［J］. Fudan Univ J Med Sci，2018，45（4）：496-502.
[6] VU H T T，NGUYEN T X，NGUYEN T N，et al. Prevalence of frailty and its associated factors in older hospitalised patients in Vietnam［J］. BMC Geriatr，2017，17（1）：216. DOI： 10.1186/s12877-017-0609-y.
[7] WANG W W，LI Y Y，SHI X T，et al. Frailty-related factors and degree of association of frailty with malnutrition in elderly inpatients［J］. Chinese General Practice，2021，24（6）：678- 684. DOI：10.12114/j.issn.1007-9572.2020.00.594
[8] JIN Q L，HU S，CHEN R，et al. Comprehensive geriatric assessment for screening risk factors and frailty in elderly inpatients［J］. Chinese General Practice，2018，21（27）： 3296-3301. DOI：10.12114/j.issn.1007-9572.2018.00.150.
[9] KOJIMA G，TANABE M.Frailty is highly prevalent and associated with vitamin D deficiency in male nursing home residents［J］. J Am Geriatr Soc，2016，64（9）：e33-35. DOI：10.1111/jgs.14268.
[10] WONG Y Y，MCCAUL K A，YEAP B B，et al. Low vitamin D status is an independent predictor of increased frailty and allcause mortality in older men：the Health in Men Study［J］. J Clin Endocrinol Metab，2013，98（9）：3821-3828. DOI：10.1210/ jc.2013-1702.
[11] GUTIÉRREZ-ROBLEDO L M，ÁVILA-FUNES J A，AMIEVA H，et al. Association of low serum 25-hydroxyvitamin D levels with the frailty syndrome in Mexican community-dwelling elderly［J］. Aging Male，2016，19（1）：58-63. DOI： 10.3109/13685538.2015.1105796.
[12] SMIT E，CRESPO C J，MICHAEL Y，et al. The effect of vitamin D and frailty on mortality among non-institutionalized US older adults［J］. Eur J Clin Nutr，2012，66（9）：1024-1028. DOI：10.1038/ejcn.2012.67.
[13] MATHEÏ C，VAN POTTELBERGH G，VAES B，et al. No relation between vitamin D status and physical performance in the oldest old：results from the Belfrail study［J］. Age Ageing， 2013，42（2）：186-190. DOI：10.1093/ageing/afs186.
[14] SOYSAL P，STUBBS B，LUCATO P，et al. Inflammation and frailty in the elderly：a systematic review and metaanalysis［J］. Ageing Res Rev，2016，31：1-8. DOI：10.1016/j. arr.2016.08.006.
[15] MARCOS-PÉREZ D，SÁNCHEZ-FLORES M，PROIETTI S，et al. Association of inflammatory mediators with frailty status in older adults：results from a systematic review and meta-analysis［J］. Geroscience，2020，42（6）：1451-1473. DOI：10.1007/ s11357-020-00247-4.
[16] SOYSAL P，ARIK F，SMITH L，et al. Inflammation，frailty and cardiovascular disease［J］. Adv Exp Med Biol，2020，1216： 55-64. DOI：10.1007/978-3-030-33330-0_7.
[17] KANE A E，SINCLAIR D A.Frailty biomarkers in humans and rodents：Current approaches and future advances［J］.Mech Ageing Dev，2019，180：117-128. DOI：10.1016/j. mad.2019.03.007.
[18] BAYLIS D，BARTLETT D B，SYDDALL H E，et al. Immuneendocrine biomarkers as predictors of frailty and mortality：a 10- year longitudinal study in community-dwelling older people［J］. Age （Dordr），2013，35（3）：963-971. DOI：10.1007/ s11357-012-9396-8.
[19] WIMALAWANSA S J，RAZZAQUE M S，AL-DAGHRI N M.Calcium and vitamin D in human health：hype or real?［J］. J Steroid Biochem Mol Biol，2018，180：4-14. DOI：10.1016/j. jsbmb.2017.12.009.
[20] ABRAMS G D，FELDMAN D，SAFRAN M R.Effects of vitamin D on skeletal muscle and athletic performance［J］. J Am Acad Orthop Surg，2018，26（8）：278-285. DOI： 10.5435/JAAOS-D-16-00464.
[21] CEGLIA L，HARRIS S S.Vitamin D and its role in skeletal muscle［J］. Calcif Tissue Int，2013，92（2）：151-162. DOI： 10.1007/s00223-012-9645-y.
[22] HAMILTON B.Vitamin D and human skeletal muscle［J］. Scand J Med Sci Sports，2010，20（2）：182-190. DOI：10.1111/ j.1600-0838.2009.01016.x.
[23] VITALE C，JANKOWSKA E，HILL L，et al. Heart Failure Association/European Society of Cardiology position paper on frailty in patients with heart failure［J］. Eur J Heart Fail，2019，21（11）： 1299-1305. DOI：10.1002/ejhf.1611.
[24] K I T S U T ， K A B A S A W A K ， I T O Y ， e t a l . L o w s e r u m 25-hydroxyvitamin D is associated with low grip strength in an older Japanese population［J］. J Bone Miner Metab，2020，38（2）： 198-204. DOI：10.1007/s00774-019-01040-w.
[25] CEGLIA L，HARRIS S S.Vitamin D and its role in skeletal muscle［J］. Calcif Tissue Int，2013，92（2）：151-162. DOI： 10.1007/s00223-012-9645-y.
[26] CESARI M，KRITCHEVSKY S B，NICKLAS B，et al. Oxidative damage，platelet activation，and inflammation to predict mobility disability and mortality in older persons：results from the health aging and body composition study［J］. J Gerontol A Biol Sci Med Sci，2012，67（6）：671-676. DOI：10.1093/gerona/glr246.
[27] TIAINEN K，HURME M，HERVONEN A，et al. Inflammatory markers and physical performance among nonagenarians［J］. J Gerontol A Biol Sci Med Sci，2010，65（6）：658-663. DOI： 10.1093/gerona/glq056.
[28] MA L N，SHA G M，ZHANG Y X，et al. Elevated serum IL-6 and adiponectin levels are associated with frailty and physical function in Chinese older adults［J］. Clin Interv Aging，2018，13：2013- 2020. DOI：10.2147/CIA.S180934.
[29] BRUYÈRE O，CAVALIER E，BUCKINX F，et al. Relevance of vitamin D in the pathogenesis and therapy of frailty［J］. Curr Opin Clin Nutr Metab Care，2017，20（1）：26-29. DOI： 10.1097/MCO.0000000000000334.
[30] PARTAN R U，HIDAYAT R，SAPUTRA N，et al. Seluang fish （Rasbora spp.） oil decreases inflammatory cytokines via increasing vitamin D level in systemic lupus erythematosus［J］.Open Access Maced J Med Sci，2019，7（9）：1418-1421. DOI：10.3889/oamjms.2019.308.
[31] MOTAMED S，NIKOOYEH B，KASHANIAN M，et al. Efficacy of two different doses of oral vitamin D supplementation on inflammatory biomarkers and maternal and neonatal outcomes［J］. Matern Child Nutr，2019，15（4）：e12867. DOI：10.1111/mcn.12867.
[32] VANHERWEGEN A S，GYSEMANS C，MATHIEU C.Vitamin D endocrinology on the cross-road between immunity and metabolism［J］. Mol Cell Endocrinol，2017，453：52-67. DOI：10.1016/j.mce.2017.04.018.
[33] POJEDNIC R M，CEGLIA L.The emerging biomolecular role of vitamin D in skeletal muscle［J］. Exerc Sport Sci Rev，2014，42 （2）：76-81. DOI：10.1249/JES.0000000000000013.
[34] BISCHOFF-FERRARI H A，ORAV E J，ABDERHALDEN L， et al. Vitamin D supplementation and musculoskeletal health［J］. Lancet Diabetes Endocrinol，2019，7（2）：85. DOI：10.1016/ s2213-8587（18）30347-4.
[35] WEAVER C M，ALEXANDER D D，BOUSHEY C J，et al. Calcium plus vitamin D supplementation and risk of fractures： an updated meta-analysis from the National Osteoporosis Foundation［J］. Osteoporos Int，2016，27（1）：367-376. DOI：10.1007/s00198-015-3386-5.
[36] MURAD M H，ELAMIN K B，ABU ELNOUR N O，et al. Clinical review：the effect of vitamin D on Falls：a systematic review and meta-analysis［J］. J Clin Endocrinol Metab，2011，96（10）： 2997-3006. DOI：10.1210/jc.2011-1193.
[37] BEAUDART C，BUCKINX F，RABENDA V，et al. The effects of vitamin D on skeletal muscle strength，muscle mass，and muscle power：a systematic review and meta-analysis of randomized controlled trials［J］. J Clin Endocrinol Metab，2014，99（11）： 4336-4345. DOI：10.1210/jc.2014-1742.
[38] REMELLI F，VITALI A，ZURLO A，et al. Vitamin D deficiency and sarcopenia in older persons［J］. Nutrients，2019，11（12）： E2861. DOI：10.3390/nu11122861.
[39] SELDEEN K L，BERMAN R N，PANG M H，et al. Vitamin D insufficiency reduces grip strength，grip endurance and increases frailty in aged C57Bl/6J mice［J］. Nutrients，2020，12（10）： E3005. DOI：10.3390/nu12103005.
[40] CUMMINGS S R，KIEL D P，BLACK D M.Vitamin D supplementation and increased risk of falling：a cautionary tale of vitamin supplements retold［J］. JAMA Intern Med，2016，176（2）： 171-172. DOI：10.1001/jamainternmed.2015.7568.
[41] Dietary reference intakes for calcium and vitamin D［M］. Washington，D.C.：National Academies Press，2011.
[42] HOLICK M F，BINKLEY N C，BISCHOFF-FERRARI H A，et al. Evaluation，treatment，and prevention of vitamin D deficiency：an Endocrine Society clinical practice guideline［J］. J Clin Endocrinol Metab，2011，96（7）：1911-1930. DOI：10.1210/jc.2011- 0385.
Table 1 Comparison of general characteristics of PD patients by sex
Note: arepresents Z value, brepresents χ 2 value, and the residual test statistic value represents t value. MOF= Major osteoporotic fractures, HF= Hip fractures, UPDRS III= Parkinson's Disease Unified Assessment Scale Part III Exercise, MNA= Simplified Nutrition Assessment Scale, BFR= Body Fat percentage, BMI= body Index, AC= Upper arm Circumference, WHR= Waist-to-hip fat ratio, BBS=Berg Balance Scale, ABC= Activity balance confidence Scale.
Table 2 Correlation analysis of fracture risk and T-score of femoral neck bone mineral density with other indicators in PD patients by sex
