Burden of Parkinson Disease in China, 1990–2019: Findings from the 2019 Global Burden of Disease Study

Abstract

Introduction

China has the most people with Parkinson disease (PD) in the world and is estimated to have over half of the worldwide PD population. The objective of this study was to analyze the corresponding burden of PD in China for the past decades.

Method

Data on disease burden related to PD in China were retrieved from the Global Burden of Disease (GBD) 2019 study. The estimated annual percentage changes (EAPCs) were calculated to assess temporal trends, and the ratio of years lived with disability (YLDs) to disability-adjusted life years (DALYs) was used as an index to evaluate the healthcare system.

Result

Nationally, the burden of PD increased from 1990 to 2019. Although the age-standardized incidence rate (ASIR) increased, the age-standardized death rate (ASDR) and age-standardized DALY rate both decreased. Age-standardized rates of PD in males remained higher than those in females, but trends in ASDR and the age-standardized DALY rate for females showed a pronounced decrease. The most remarkable increase in the ASIR was in individuals aged 45–49 years, with an EAPC of 1.74 (95% confidence interval, 1.26–2.21). The YLDs:DALYs ratio continuously increased compared with global figures and even with countries with high sociodemographic index (SDI).

Conclusion

Although ASDR and age-standardized DALY rates for PD have been declining, the burden of PD still needs attention as the total numbers have increased over the period. Generally, the greater burden of PD was in males. A sound health system with services tailored to PD continues to be required in the future.

Introduction

Parkinson disease (PD) is a chronic, progressive neurological disorder that was first described by James Parkinson and has become the second most common neurodegenerative disease worldwide [1]. With the progression of the disease, many patients suffer from motor complications such as dyskinesia, which may substantially increase both the financial and psychological burden of the disease, not only for the patients and their families but also on the whole of society.

In recent years, PD has been one of the fastest growing neurological disorders worldwide, and the corresponding global burden has more than doubled over the past generation [2, 3, 4, 5, 6, 7]. It is estimated that by 2030, the number of PD patients in China will increase to form over half of the world's PD patients [5]. This hypothesis is not groundless. As many previous studies have indicated [8, 9], the incidence of PD increases rapidly once the age of 50 is reached and peaks at around 80 years old. It is estimated that the proportion of people in China over 65 years of age will reach 23.9–26.9% in 2050 [10]. According to the Global Burden of Disease (GBD) 2016 findings, China had the largest increase in age-adjusted prevalence rates for PD between 1990 and 2016 (115.7%, 95% uncertainty interval [UI], 99.5%–131.0) [3]. However, recent epidemiological studies on the burden of PD, specifically in China, are scarce. In addition, the GBD 2016 findings on PD focused only on total changes from 1990 to 2016 worldwide. It is therefore important to understand the epidemic trends in order to better direct prevention and control strategies for PD. In our study, we introduce the estimated annual percentage change (EAPC) into our analysis of the burden. EAPC represents the annual change in temporal trends, which can provide more accurate information than the total percentage change.

The GBD Study 2019 contains comprehensive epidemiologic information for 369 diseases and injuries involving 204 countries and territories [11]. We aimed to use the latest data from the GBD 2019 dataset to investigate and compare temporal trends in numbers and rates of incidence and death and disability-adjusted life years (DALYs) for PD in China from 1990 to 2019. Also, we compared the years lived with disability (YLDs):DALYs ratio in terms of the sociodemographic index (SDI).

Materials and Methods

We extracted data on incidence, death, YLDs, and DALYs for PD from the website of the GBD 2019 Study, which is publicly available from the Institute for Health Metrics and Evaluation (IHME) (http://ghdx.healthdata.org/gbd- results-tool). PD incidence was estimated by random-effects meta-analysis methods, using DisMod-MR with the pooled epidemiology database. The Cause of Death Ensemble model was used to estimate the death rate. DALYs represent the number of years lost due to ill-health, disability, or early death as a measure of overall disease burden. In the GBD Study, DALYs were computed as the sum of years of life lost and YLDs for each country, age, sex, and year with 95% UIs based on the 25th and 975th values of the ordered 1,000 draws [12]. The SDI is defined as a composite indicator of income per capita, years of schooling, and fertility rate in females younger than 25 years. More details of the GBD Study 2019 methodology have been described previously [11, 13, 14, 15]. Here, we selected “China,” “global,” “low SDI,” “low-middle SDI,” “middle SDI,” “high-middle SDI,” and “high SDI” as the location; “PD” as the cause; and “incidence,” “deaths,” “YLDs,” and “DALYs (disability-adjusted life years)” for measures. The age groups were divided into 5-year age bands. The EAPCs were calculated based on a regression model: Y = α + β * X + ε (Y equals ln [age-standardized rate], X is the calendar year, and ε refers to the error term). When the natural logarithm of a rate is assumed to be linear over years, the EAPC = 100 × (exp[β]-1) and the 95% confidence interval (CI) can be obtained from the model [16]. When the range of 95% CI contained 0, whatever the EAPC was, we defined the changing trend as steady. Furthermore, we calculated the YLDs:DALYs ratio of PD from 1990 to 2019 across different SDIs.

Statistical Analysis

Descriptive analyses were conducted on PD incidence, death, and DALY data by gender and age for China from 1990 to 2019. Spearman correlation analysis was used to clarify the relationship between age-standardized rates and detailed SDIs of years for China. All calculations were performed using R software (version 4.1.2).

Results

Change in PD Incidence in China

In 1990, there were 99,235 incident cases (95% UI, 82,520 to 116,980) of PD in China. The number of incident cases increased by 2.04 (95% UI, 1.95–2.14) times, reaching 301,527 incident cases (95% UI, 250,665 to 352,351) in 2019 (Table 1). PD was only found in people aged over 20 years. Among the age groups, age 20–24 years was found to have a decreasing trend in incident cases from 1990 (187, 95% UI, 63–388) to 2019 (119, 95% UI, 37–254), whereas all other age bands showed an increasing trend in incident cases. In 1990, age 70–74 years had the highest number of incident cases at 18,107 (95% UI, 13,155 to 23,745), whereas the lowest number was in age 20–24 years (187, 95% UI, 63–388). In 2019, the incident number reached its peak at a younger age in the 65–69 years age group (51,644, 95% UI, 31,775 to 76,737), whereas the age group with the lowest incident cases remained in line with 1990 (119, 95% UI, 37–254). Regarding the rate of increase in incident numbers, the age group over 95 years saw the highest rate of increase, reaching 5.08 (95% UI, 4.49–5.88) times higher than in 1990 (Fig. 1a and online suppl. Table S1; for all online suppl. material, see www.karger.com/doi/10.1159/000527372). When analyzed by gender, in 1990, incident cases in males (54,671, 95% UI, 45,242–64,405) were higher than those in females (44,564, 95% UI, 37,226–52,577). This discrepancy still existed in 2019, when the numbers of male and female incident cases were 177,523 (95% UI, 147,310–207,731) and 124,004 (95% UI, 103,907–145,070), respectively (Table 1). Detailed analysis showed that in 1990, number of male incident cases was higher than females for people younger than 84 years of age. This gap narrowed with increasing age, with incident cases of females surpassing males from 85 years of age, when the relative ratio of males to females declined to below 1. The ratio of the sexes in 2019 was similar to that in 1990, although the proportion of males aged over 85 years slightly increased (Fig. 2).

Table 1.

Numbers and percentage changes of incidence, deaths, and DALYs for PD in China

	Counts (95% UI) in 1990	Counts (95% UI) in 2019	Percentage change in numbers between 1990 and 2019
Incidence
Total	99,235 (82,520, 116,980)	301,527 (250,665, 352,351)	2.04 (1.95, 2.14)
Male	54,671 (45,242, 64,405)	177,523 (147,310, 207,731)	2.25 (2.13, 2.37)
Female	44,564 (37,226, 52,577)	124,004 (103,907, 145,070)	1.78 (1.69, 1.88)
Deaths
Total	31,920 (28501, 35,897)	76,990 (65,124, 87,843)	1.41 (1.01, 1.88)
Male	17,025 (14,225, 19,737)	46,645 (37,826, 55,743)	1.74 (1.13, 2.52)
Female	14,896 (12,805, 17,403)	30,345 (24,484, 36,448)	1.04 (0.61, 1.57)
DALYs
Total	665,528 (590,472, 747,736)	1,554,451 (1,333,742, 1,794,868)	1.34 (1, 1.73)
Male	363,464.23 (304,829.67, 421,786.2)	942,406.22 (778,265.01, 1,117,686.52)	1.59 (1.10, 2.22)
Female	302,063.42 (258,240.2, 348,517.13)	612,044.85 (508,950.12, 715,630.3)	1.03 (0.67, 1.45)

Fig. 1.

Number of incident cases (a), deaths (b), and disability-adjusted life years (DALYs) (c) across age groups and years.

Fig. 2.

Number of incident cases and ratios of male to female incident cases based on age groups in 1990 (a) and 2019 (b).

The age-standardized incidence rate (ASIR) for PD in China increased from 13.24 per 100,000 population (95% UI, 11.16–15.46) in 1990 to 15.27 per 100,000 population (95% UI, 12.82–17.78) in 2019, with a corresponding increase in the EAPC of 0.46 (95% CI, 0.29–0.63) (Table 2). Incidence rates increased as age increased, ranging from 0.15 per 100,000 populations (95% UI, 0.04–0.31) for age 20–24 years to 214.2 per 100,000 populations (95% UI, 108.75–342.03) for age over 95 years in 2019. A trend of increasing incidence rates was seen in most age groups, and the largest one occurred in the 45–49 age group, with an EAPC of 1.74 (95% CI, 1.26–2.21). Steady incidence rate trends were seen in ages 80–84 years and 90–94 years, with respective EAPCs of 0.07 (95% CI, −0.01 to −0.15) and −0.06 (95% CI, −0.14 to 0.02). The incidence rate of PD for age group 85–89 years and over 95 years showed decreasing trends from 1990 to 2019, with EAPCs of −0.07 (−0.10 to −0.03) and −0.29 (−0.39 to −0.19), respectively (Fig. 5a, online suppl. Table S2). The ASIR and incidence rate for males of any age group were always markedly higher than those of females (Table 2, online suppl. Table S2, Fig. 5b, c). A positive association was found between ASIR and SDI from 1990 to 2019 (ρ = 0.451, p < 0.05; Fig. 6a).

Table 2.

Age-standardized rates and the corresponding EAPCs of incidence, deaths, and DALYs for PD in China

	Age-standardized rate (95% UI) in 1990	Age-standardized rate (95% UI) in 2019	EAPC in age-standardized rates between 1990 and 2019
Incidence
Total	13.24 (11.16, 15.46)	15.27 (12.82, 17.78)	0.46 (0.29, 0.63)
Male	15.99 (13.45, 18.62)	19.97 (16.86, 23.11)	0.75 (0.57, 0.93)
Female	11.24 (9.49, 13.12)	11.95 (10.04, 13.93)	0.15 (0.01, 0.28)
Death
Total	5.63 (5.04, 6.26)	4.64 (3.94, 5.27)	–0.62 (–0.73, –0.52)
Male	7.68 (6.54, 8.8)	6.99 (5.76, 8.2)	–0.08 (–0.19, 0.03)
Female	4.53 (3.9, 5.25)	3.21 (2.58, 3.84)	–1.31 (–1.45, –1.18)
DALYs
Total	96.53 (85.95, 107.69)	83.66 (72.18, 95.97)	–0.42 (–0.55, –0.28)
Male	122.84 (104.22, 140.64)	115.23 (95.98, 135.82)	–0.01 (–0.14, 0.13)
Female	79.66 (68.07, 91.63)	60.75 (50.49, 70.92)	–1.02 (–1.16, –0.88)

Fig. 5.

Estimated annual percentage change (EAPC) of incidence rate, death rate, and disability-adjusted life years (DALYs) rate by age groups and sexes (a: both; b: male; c: female).

Fig. 6.

Association between age-standardized rate and sociodemographic index (SDI) from 1990 to 2019 (a: incidence; b: death; c: disability-adjusted life years [DALYs]).

Change in Deaths from PD in China

As presented in Table 1, the total national deaths caused by PD in 1990 were 31,920 (95% UI, 28,501 to 35,897); this increased by 1.41 (95% UI, 1.01–1.88) times to 76,990 (95% UI, 65,124 to 87,843) over a 30-year period. When divided into age groups, the largest number of deaths was 7,802 (95% UI, 6,924 to 8,790; male: 4,228, 95% UI, 3,498 to 4,923; female: 3,573, 95% UI, 3,027 to 4,251) in the 75–79 years age group in 1990, whereas in 2019, the largest number of deaths, at 20,250 (95% UI, 17,133–23,110; male: 12,640, 95% UI, 10,176–14,935; female: 7,609, 95% UI, 6,093–9,198) occurred at an older age between 80 and 84 years. In addition, deaths decreased in males and females aged 20–44 years. However, from 45 years old, the total number of deaths owing to PD in China increased from 1990 to 2019, most especially in those aged over 95 years, in whom the number of deaths soared from 99 (95% UI, 80–112) in 1990 to 670 (95% UI, 512–803) in 2019 (Fig. 1b, online suppl. Table S3). In males, the most significant increase in deaths occurred in the 85–89 years age group from 1,682 (95% UI, 1,473–1,913) in 1990 to 8,908 (95% UI, 7,473–10,127) in 2019. The number of deaths in females aged over 95 increased markedly from 79 (95% UI, 62–92) in 1990 to 580 (95% UI, 434–706) in 2019 (online suppl. Table S3). Generally, death from PD in China occurred mostly in males, whether in 1990 or 2019, particularly for males aged 20–24, with males accounting for 100% of the deaths in that age group in 2019. Only at ages over 85 and over 90 in 1990 and 2019, respectively, did the ratio decline below 1 (Fig. 3).

Fig. 3.

Number of deaths and ratios of male to female deaths based on age groups in 1990 (a) and 2019 (b).

The overall age-standardized death rate (ASDR) due to PD in China was 5.63 per 100,000 population (95% UI, 5.04–6.26) in 1990 but decreased to 4.64 per 100,000 population (95% UI, 3.95–5.27) in 2019, with an EAPC of −0.62 (95% CI, −0.73 to −0.52). The decreasing trend for ASDR in females was more evident, for whom the EAPC was −1.31 (95% CI, −1.45 to −1.18). Conversely, the overall change of ASDR in males from 1990 (7.68 per 100,000 population, 95% UI, 6.54–8.8) to 2019 (6.99 per 100,000 population, 95% UI, 5.76–8.2) was steady, with an EAPC of −0.08 (95% CI, −0.19 to 0.03) (Table 2). When analyzed across different age groups, however, steady trends in death rate were only seen in those aged over 95 years (EAPC: −0.07, 95% CI, −0.29 to 0.15), with most other age groups, except 85–94 years (EAPC 85–89 years: 0.52, 95% CI, 0.36–0.68; 90–94 years: 0.54, 95% CI, 0.28–0.80), showing a decreasing trend (online suppl. Table S4). Interestingly, the declining trends for females were always more obvious than those for males in any age group (Fig. 5, online suppl. Table S4). The negative correlation between SDI and ASDR for PD in China was obvious (ρ = −0.8753, p < 0.0001; Fig. 6b).

Change in DALYs from PD in China

At the national level, DALYs due to PD in China were 655,528 (95% UI, 590,472–747,736) in 1990, of which 363,464 (95% UI, 304,830–421,786) were in males and 302,063 (95% UI, 258,240–348,517) were in females. The number increased 1.34 (95% UI, 1.00–1.73) times to 1,554,451 (95% UI, 1,333,742–1,794,868) in 2019, with this total comprising 942,406 (95% UI, 778,265–1,117,687) DALYs in males and 612,045 (95% UI, 508,950–715,630) in females (Table 1). However, this increasing trend was not seen in all age groups. In the age groups under 30 years, a downward trend was seen from 1990 (20–24 years: 455, 95% UI, 339–562; 25–29 years: 660, 95% UI, 436–1,026) to 2019 (20–24 years: 181, 95% UI, 138–238; 25–29 years: 509, 95% UI, 268–878), both in males (20–24 years: 367, 95% UI, 253–457 in 1990; 151, 95% UI, 115–197 in 2019; 25–29 years: 405, 95% UI, 261–640 in 1990; 332, 95% UI, 188–555 in 2019) and females (20–24 years: 88, 95% UI, 64–120 in 1990; 30, 95% UI, 19–47 in 2019; 25–29 years: 255, 95% UI, 156–408 in 1990; 177, 95% UI, 85–343 in 2019). Additionally, the total number of DALYs of the age group 35–39 years decreased from 2,790 (95% UI, 1,957–3,942) in 1990 to 2,780 (95% UI, 1,718–4,250) in 2019, although the change in males (1,682, 95% UI, 1,184–2,401 in 1990, 1,731, 95% UI, 1,082–2,615 in 2019) showed an opposite trend to females (1,107, 95% UI, 754 to 1,590 in 1990; 1,049, 95% UI, 623 to 1,691 in 2019) (Fig. 1c; 4, online suppl. Table S5).

Fig. 4.

Number of disability-adjusted life years (DALYs) and ratios of male to female DALYs based on age groups in 1990 (a) and 2019 (b).

Although the total number of DALYs owing to PD in China showed an increasing trend, the age-standardized DALY rate for PD decreased from 1990 (96.53 per 100,000 population, 95% UI, 85.95–107.69) to 2019 (83.66 per 100,000 population, 95% UI, 72.18–95.97), with a corresponding EAPC of −0.42 (95%CI, −0.55 to −0.28) (Table 2). Except for the steady trend for age between 85 and 89 years (EAPC: −0.09, 95% CI, −0.30 to 0.02), trends in all age groups showed a consistent decrease according to the EAPC results and their 95% CIs. Similarly, this decreasing trend was shown in females from 79.66 per 100,000 population (95% UI, 68.07–91.63) in 1990 to 60.75 per 100,000 population (95% UI, 50.49–70.92) in 2019, with a corresponding EAPC of −1.02 (95% CI, −1.16 to −0.88). This trend was seen for all age groups in females. However, a decreasing DALY rate in males was only seen in age group 80–84 years, with an EAPC of −0.28 (95% CI, −0.38 to −0.18). Increasing trends for age-standardized DALYs in males were seen in most age groups, although the overall trend was steady from 1990 (122.84 per 100,000 population, 95% UI, 104.22–140.66) to 2019 (115.23 per 100,000 population, 95% UI, 95.98–135.82), with EAPC of −0.01 (95% CI, −0.14 to 0.13) (Fig. 5, Table S6). The age-standardized rates of DALYs were also negatively associated with SDI in China over the period (ρ = −0.7148, p < 0.0001; Fig. 6c).

YLDs:DALYs Ratio for PD from 1990 to 2019

In general, whether globally or according to SDI, age-standardized YLDs:DALYs ratios for PD showed increasing trends from 1990 to 2019. The ratio for low SDI was steady and lowest at 0.11 before 2015, thereafter increasing to 0.12 in 2016. The increase in ratio for low-middle SDI occurred earlier in 2013, from 0.12 to 0.13. After that point, the ratio fluctuated between 0.13 and 0.14. The changing trends in ratio for middle SDI were similar to those worldwide, particularly after 1998. The YLDs:DALYs ratio for high-middle SDI increased from 0.18 to 0.22 over the 30 years from 1990 to 2019. It surpassed the ratio for high SDI, which changed less dramatically. However, China, as a middle SDI country, experienced a dramatic increase in YLDs:DALYs ratio for PD from 0.16 in 1990 to 0.25 in 2019, which is significantly larger than the maximum ratio presenting for high-middle SDI (Fig. 7).

Fig. 7.

Ratio of years lived with disability (YLDs) to disability-adjusted life years (DALYs) in China, globally, and by SDI, from 1990 to 2019.

Discussion

To our knowledge, this is the first study to provide a detailed analysis of the disease burden of PD in China for the years 1990–2019, using the latest data extracted from GBD 2019. Our findings show that China has made substantial achievements in managing the burden of PD, although the burden continues to grow.

Given China's aging population and rapid growth, it is not surprising to find an accordant increase in absolute numbers of both incidence of and deaths from PD in China from 1990 to 2019. A trend toward younger age of patients with PD is apparent. This phenomenon can be attributed to improvements in diagnosis, such as through door-to-door surveys [17], people's improved awareness of their health [18], and the increasing experience of clinicians in diagnosing and managing PD. However, the majority of patients are still diagnosed above the age of 50, emphasizing that PD remains primarily a disease of the elderly.

Referring to sex-specific differences, men are shown to have a higher predominance of PD, whether in incidence or mortality, in most age groups, and ASDRs, age-standardized DALY rates, and their corresponding trends declined more markedly in females. Discrepancies in rates for PD by gender have been found in previous studies [1, 19, 20]. De Miranda and colleagues [21] observed that female rats were less susceptible to rotenone-induced neurodegeneration than male rats, possibly resulting from the preserved autograph of α-synuclein. In addition, a meta-analysis by Patrie [20] indicated that estrogen in females may have a neuroprotective function. Women also present greater levodopa bioavailability and corresponding lower levodopa clearance levels [22, 23]. The longer life expectancy of females may explain the higher proportion of elderly women over 85 years with PD. Although women have a lower risk of PD than men, they may get less medical support and have a higher risk of developing complications [24, 25, 26]. We did not have enough data to establish the detailed reasons for this discrepancy, but this could be the focus of future studies.

The YLDs:DALYs ratio has been used in many previous studies as an indicator of the efficiency of the healthcare system [27, 28, 29, 30]. In fact, both DALYs and YLDs were conceptualized by the GBD study as tools to improve the capacity of professionals to assess population health and establish evidence-based decision-making in public health [31, 32]. The higher proportion of YLDs to DALYs reflects less premature death from disease and its complications, expressed as years of life lost. Unparalleled to the global trend, China has had the largest YLDs:DALYs ratio for PD, compared with different SDI countries, since 2000. We explain this by a number of factors. First, PD is being detected earlier than ever before. With more and more studies being published on the disease, clinical doctors are able to diagnose patients as soon as motor features such as static tremor and rigidity, or even non-motor features such as hyposmia and rapid eye movement sleep behavior disorder, appear. In addition, in high and middle SDI countries, people are more aware of their own health and may seek medical help earlier than people in low SDI countries. Second, treatment of PD has improved. Since the Chinese PD and Movement Disorders Society (CMDS) published its first guideline for PD treatment in 2006 [33], it has been corrected several times and the latest update was released in 2020 [34]. Instead of solo drug therapy, a comprehensive therapy system is highly recommended, including the departments of neurosurgery, neuropsychology, and neurorehabilitation. The treatment is more personalized according to the age, cognitive condition, type of onset, and so on. Apart from the motor symptoms, the non-motor symptoms of PD are also highly concerned. The more detailed and feasible treatment of non-motor symptoms, such as rapid eye movement sleep behavior disorder [35] and Parkinson disease dementia [36], has also been brought forward. Besides, a more rounded rehabilitation system has been established and implemented in many cities. The effects of physical exercise, especially the traditional activities like Tai Chi and Baduanjin, have been proven to be underestimated [37, 38]. Third, the health system in China is sound in terms of managing PD. Considerable priority has been given to PD in China with the development of the national economy. For instance, the number of publications related to PD in China has ranked second only to the USA [39]. The economic burden of the disease on families has been significantly relieved with the inclusion of PD into major disease insurance in the Chinese government insurance system since 2007 [40]. Finally, increasing life expectancy, differing quality of data collection, and other factors may have also contributed to the result.

The strengths of our study lie in our systematic use of data (from the GBD 2019 study) and the methods used to estimate the burden of PD in China from 1990 to 2019. The GBD 2019 study is an unparalleled source of up-to-date data that provides access to its data sources, research methods, and results. Moreover, its original estimates of disease burden are revised based on new data and improved methods to afford current estimates of disease burdens [11].

There were several limitations in this study. First, the quality and quantity of data determined the accuracy and robustness of GBD estimates, which was probably impacted by the potential bias derived from the miscoding and misclassification of disease. PD is accompanied by clinical challenges, including difficulties in diagnosis, misdiagnosis, and interference in diagnosis. Second, the diagnosis and definition of PD have been refined in countries over time, and this was the main source of potential bias. Third, further investigations should focus on a more detailed burden of PD in different provinces in China.

In conclusion, despite the national incidence, number of deaths, and DALYs for PD increasing from 1990 to 2019, the ASDR and age-standardized DALYs declined, especially in females. More early-onset PD was diagnosed. Past and current treatment and related policies have been effective in China, but the burden of PD still needs full attention and sound guidelines.

Statement of Ethics

This study protocol was reviewed and approved by the Medical Ethics Committee of the Fourth Affiliated Hospital Zhejiang University School of Medicine, approval number K2020058. Informed consent was waived because no identifiable information was included in the analyses.

Conflict of Interest Statement

The authors have no conflicts of interest to declare.

Funding Sources

This work was supported by the Major Health Science and Technology Program of Zhejiang Province (No. WKJ-ZJ-2208 to G.Z.).

Author Contributions

Author contributions were made as follows: Zhilin Zheng: acquisition of data for the work, statistical analysis of data for the work, and original draft preparation; Zeyu Zhu and Chen Zhou: statistical analysis and interpretation of data for the work; Lanxiao Cao: revision of the manuscript for content; Guohua Zhao: design of the work and revision of the manuscript for content.

Data Availability Statement

The datasets supporting the conclusions of this article are included within the article and its additional files.

Supplementary Material

Supplementary data

Funding Statement

This work was supported by the Major Health Science and Technology Program of Zhejiang Province (No. WKJ-ZJ-2208 to G.Z.).