Introduction
CVD encompassing coronary artery disease, cerebrovascular accidents, and peripheral arterial disorders1 persist as the predominant contributor to global morbidity and mortality2. In 2021, there were 612 million cases of CVD globally, accounting for 26.8% of all deaths3 highlighting the urgent need for effective preventive strategies. CVD often strikes acutely, primarily due to blood clots or blockages that restrict blood flow to the heart or brain, resulting in irreversible damage, so prevention is the most cost-effective strategy for reducing its harm.
Epidemiological evidence has established hypertension, diabetes, and obesity as modifiable risk determinants for CVD pathogenesis4. Current clinical guidelines (e.g., American Heart Association/American College of Cardiology and European Society of Cardiology) have identified dietary modification as a core strategy for primary prevention and secondary management of CVD4,5. With advancing research on obesity and hypertensive diseases, various dietary patterns have been proposed to prevent or mitigate associated metabolic abnormalities.
Recent advances have validated multiple dietary patterns for reducing the risk of CVD, although their relative effectiveness remains controversial. Although low-fat diets (LFD) have historically been the dominant recommended approach for lipid management, large randomized trials have shown that their impact on CVD outcomes is limited6. In contrast, Mediterranean diet (MED), rich in monounsaturated fats, polyphenols and omega-3 fatty acids, demonstrates pleiotropic benefits including systolic blood pressure and anti-inflammatory effects, as evidenced by the landmark PREDIMED trial7.
Similarly, high-protein diets (HPD) and ketogenic diets (KD) show promise for weight loss and insulin sensitivity enhancement8, 9–10 yet KD’s long-term cardiovascular safety remains debated due to potential lipid profile alterations11, 12, 13–14. Moreover, low-carbohydrate diet (LCD) aim to reduce body weight by limiting carbohydrate intake to less than 20%. However, such diets usually increase the intake of saturated fatty acids, which may elevate low-density lipoprotein cholesterol (LDL-C), and thus their effects on cardiovascular disease deserve further study15.
In contrast, DASH diet, recommended for individuals with hypertension, helps prevent CVD by lowering blood pressure16. Vegetarian diet, by limiting meat consumption and promoting the intake of fruits and vegetables, is effective in reducing obesity incidence17,18. And intermittent fasting (IF) achieves rapid weight loss19.
Despite accumulating evidence, critical knowledge gaps obstruct clinical translation. Existing meta-analyses rely predominantly on pairwise comparisons20 failing to provide cross-modal evaluations of heterogeneous dietary interventions. This limitation prevents personalized recommendations for distinct cardiovascular risk profiles. To address this gap, we conducted the first NMA comparing eight major dietary patterns—LFD, MED, KD, LCD, HPD, Vegetarian, IF, and DASH—against control diets (CD). By quantifying their differential effects on body composition, lipid profiles, glycemic markers, and blood pressure, this study aims to guide precision nutrition strategies for targeted CVD risk management.
Methods
This systematic review and NMA was registered on PROSPERO (CRD42024551289). The reporting of this review and NMA adheres to the PRISMA extension statement for reporting systematic reviews incorporating network meta-analyses.
Search strategy
We conducted a comprehensive literature search in PubMed, Web of Science, Embase, and The Cochrane Library, covering all articles published up to June 2024. Only studies published in English were included. The search was performed using a combination of Medical Subject Headings (MeSH), Emtree terms, and free-text terms relevant to different dietary patterns and cardiovascular risk factors. Search terms: “Cardiovascular disease” “Intermittent Fasting” “Diet, Ketogenic” “Diet, Vegetarian” “Diet, Fat-Restricted” “Diet, Carbohydrate- Restricted” “Diet, High-Protein Low-Carbohydrate” “Diet, Mediterranean” “Dietary Approaches To Stop Hypertension” “Randomized controlled trial”. The search steps in The Cochrane Library are shown in Table 1, and other databases were adapted based on The Cochrane Library’s search strategy.
Table 1. Search strategies in the Cochrane library.
Step | Search strategy |
|---|---|
#1 | Mesh descriptor: [Cardiovascular Diseases] explode all trees |
#2 | Mesh descriptor: [Intermittent Fasting] explode all trees |
#3 | Mesh descriptor: [Diet, Ketogenic] explode all trees |
#4 | Mesh descriptor: [Diet, Vegetarian] explode all trees |
#5 | Mesh descriptor: [Diet, Fat-Restricted] explode all trees |
#6 | Mesh descriptor: [Diet, Carbohydrate-Restricted] explode all trees |
#7 | Mesh descriptor: [Diet, High-Protein Low-Carbohydrate] explode all trees |
#8 | Mesh descriptor: [Diet, Mediterranean] explode all trees |
#9 | Mesh descriptor: [Dietary Approaches To Stop Hypertension] explode all trees |
#10 | #2 OR #3 OR #4 OR #5 OR #6 OR #7 OR #8 OR #9 |
#11 | #1 AND #10 |
Inclusion and exclusion criteria
RCTs involving dietary patterns (LFD, MED, KD, LCD, HPD, Vegetarian, IF, and DASH) were included. These dietary patterns were described in detail in supplementary materials Table S1. Eligible studies were those involving participants aged 18 or older, with no other non-dietary patterns. The studies had to report on at least one of the following outcome categories: anthropometric, glycemic, lipid, or blood pressure-related factors, with corresponding 95% confidence intervals (CI). Control groups were based on CD.
After a preliminary search, all the retrieved literature was imported into EndNote 20 and only one duplicate of the literature was retained. Following the established inclusion and exclusion criteria, the retrieved literature underwent initial screening, after which the remaining literature was independently reviewed and screened by two researchers (Y.S. and M.S.). Any discrepancies in the results were resolved through discussion with a third researcher (J.H.).
Primary outcomes
The primary outcomes were changes in lipid and glucose levels measured via biochemical assays such as total triglycerides (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), LDL-C, Glucose and C-reactive protein (CRP). Secondary outcomes included changes in body composition and blood pressure, which were used to assess weight loss effectiveness across dietary patterns such as weight, body mass index (BMI), waist, systolic blood pressure (SBP) and diastolic blood pressure (DBP).
Data extraction
The following data were extracted from the included studies: first author, publication year, study design, population characteristics (e.g., sample size, gender, mean age, and baseline BMI), intervention duration, and cardiovascular risk outcomes (body composition, lipid profiles, fasting glucose, insulin levels, and blood pressure). All data extraction was independently completed by two researchers (Y.S. and Y.Z.), and the differences were resolved through discussion with a third researcher (J.H.).
Risk of bias assessment
The risk of bias for the included studies was evaluated using a modified version of the Cochrane Risk of Bias Tool 2. A study was classified as high risk of bias if one of the five domains was rated as high. Two independent reviewers conducted the assessment, with disagreements resolved by consensus or, if necessary, by consulting a senior reviewer.
Statistical analysis
Mean differences (MD) were used as effect size measures for continuous outcomes. Given the expected methodological heterogeneity, a random-effects model was employed to estimate effect sizes and their 95% CIs. Missing standard deviations were imputed according to the method proposed by Furukawa et al.21. For outcomes reported as medians with interquartile ranges, means and standard deviations were estimated using the approach recommended by Hozo et al.22. Statistical analyses were performed using R version 4.4.1. Network plots were generated based on sample sizes, and heterogeneity was assessed using comparison-adjusted funnel plots with the metafor package. A Bayesian NMA model was implemented using the JAGS package with Markov Chain Monte Carlo (MCMC) sampling to compare dietary patterns pairwise. Each intervention was ranked for each outcome using the Surface Under the Cumulative Ranking curve (SUCRA), and the rankings were visualized in a heatmap (rankogram; http://rh.ktss.ca/) to identify the relatively optimal dietary patterns.
Results
Study selection
A total of 8,890 relevant studies were identified from PubMed, Web of Science, Embase, and The Cochrane Library. In addition, we conducted a search on ClinicalTrials.gov. The main reason no literature was included was that most of the literature retrieved had already been included. And the literature that was not included had interventions that were not the dietary patterns we were interested in or did not report outcome data, such as the study published in 2019 by Javad Nasrollahzadeh et al.23. After removing duplicates (n = 1,868), 7,022 articles remained. Based on the titles and abstracts, 212 articles were selected for full-text review. The detailed reasons for the inclusion exclusion of the 212 articles can be found in Table S2 of the supplementary material. Finally, 21 RCTs were included in the analysis19,22,24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41–42 (Fig. 1).
Fig. 1 [Images not available. See PDF.]
Flowchart of literature screening.
Study characteristics
The characteristics of the 21 included RCTs are summarized in Table 2. The trials examined nine different dietary patterns, with CD as the control group. Most of the studies were conducted in Europe (38.1%) and North America (33.3%). Sample sizes mostly ranged from 10 to 50 participants (47.6%), and the intervention duration was typically 1 to 12 weeks (71.4%).
Table 2. Basic characteristics of included studies and patients.
Characteristic | No. (%) of Randomized Clinical Trials (N = 21) | Characteristic | No. (%) of Randomized Clinical Trials (N = 21) |
|---|---|---|---|
Year of publication | Age, mean, y | ||
2001–2005 | 2(9.52) | 18–45 | 11(52.4) |
2006–2010 | 2(9.52) | 46–55 | 6(28.6) |
2011–2015 | 2(9.52) | 56–65 | 3(14.3) |
2016–2020 | 9(42.9) | 66–75 | 1(4.76) |
2021–2024 | 5(21.8) | > 75 | 0(0.00) |
Continent | %male | ||
Europe | 8(38.1) | 0-49.9% | 14(66.7) |
North America | 7(33.3) | 50%−100% | 7(33.3) |
Asia | 4(19.1) | Not reported | 0(0.00) |
South America | 0(0.00) | BMI | |
Africa | 0(0.00) | < 20 | 0(0.00) |
Oceania | 2(9.52) | 20-24.9 | 1(4.76) |
Sample size (no. of participants) | 25-29.9 | 9(42.9) | |
10–50 | 10(47.6) | 30-34.9 | 6(28.6) |
51–100 | 5(21.8) | 35–40 | 3(14.3) |
101–150 | 3(14.3) | > 40 | 0(0.00) |
> 150 | 3(14.3) | Not reported | 2(9.52) |
Duration of intervention | |||
1–12 weeks (3 months) | 15(71.4) | ||
13–24 weeks (6 months) | 4(19.1) | ||
24–52 weeks (12 months) | 1(4.76) | ||
52–104 weeks (24 months) | 1(4.76) | ||
> 24 months | 0(0.00) | ||
Participant characteristics
Table 2 presents the basic characteristics of the patients included in the study. Overall, the majority of participants were young or middle-aged (52.4%), with a predominance of female participants in most studies (66.7%). Additionally, most participants were either overweight (42.9%) or mildly obese (28.6%).
Consistency testing
The network evidence plots for certain outcomes are presented in Fig. 2, while additional network diagrams are available in the supplementary materials. Since no closed loops were formed in the network diagrams, there was no need for consistency testing.
Fig. 2 [Images not available. See PDF.]
Network evidence map for TG, Weight and SBP.
NMA results
Body composition
Compared to CD, the KD and LCD significantly reduced body weight and waist circumference. Other dietary patterns, although demonstrating a trend toward reducing weight, BMI, and waist circumference, did not achieve statistical significance. The two-by-two comparison table of the effects of different dietary patterns on other body components are shown in the Supplementary Material (Tables 4, 5 and 6). The NMA ranked KD and HPD as the most effective for reducing body weight and BMI, while KD and LCD were optimal for waist circumference reduction. These rankings are visualized using SUCRA scores in a heatmap (Fig. 3).
Fig. 3 [Images not available. See PDF.]
Heatmap of SUCRA scoring levels for NMA.
Blood pressure
DASH diet significantly reduced both systolic and diastolic blood pressure compared to CD (Table S7-8). IF also significantly reduced SBP. Other dietary patterns did not show statistically significant effects on blood pressure. DASH diet and IF were ranked as the most effective interventions for controlling blood pressure in the NMA (Fig. 3).
Lipid and glucose levels
Both the HPD and KD significantly reduced TG, while the LCD and LFD significantly increased HDL-C levels (Table S11-12). DASH diet and LCD were the most effective at lowering glucose levels (Table S9). Although other interventions showed trends toward reducing TC, LDL-C, and CRP (Table S10 and Table S13-14), these changes were not statistically significant compared to CD. The NMA identified KD and HPD as the most effective diets for reducing TG and TC, LCD and LFD for increasing HDL-C, and DASH diet and LCD for lowering glucose levels.
Risk of bias assessment
The risk of bias assessment indicated that 85.7% of studies were at high risk of bias due to lack of participant blinding, while 38.1% did not report allocation concealment. However, overall, the studies showed a low risk of bias, with only two demonstrating high risk in outcome measurement. Funnel plots suggested minimal publication bias, as most studies were symmetrically distributed around the top of the funnel (Figs. 4 and 5).
Fig. 4 [Images not available. See PDF.]
Risk of bias assessment table.
Fig. 5 [Images not available. See PDF.]
Correction-comparison funnel plot.
Discussion
As the first comprehensive NMA comparing eight prevalent dietary patterns against customary diets, this study provides novel insights into their differential impacts on CVD biomarkers. CVD remains a leading global cause of morbidity and mortality, characterized by acute onset and substantial disease burden. Substantial evidence identifies modifiable metabolic derangements—including obesity, dyslipidemia, and hypertension—alongside suboptimal lifestyle behaviors as pivotal CVD risk determinants43. The burgeoning popularity of IF for weight management40 has prompted scientific inquiry into whether such dietary strategies could effectively mitigate CVD risk through metabolic optimization. Our findings reveal a nuanced landscape: While no universal dietary solution emerged, customary diets demonstrated inferiority across most outcomes. Notably, KD and HPD showed superior efficacy for weight and BMI reduction, whereas KD and LCD excelled in waist circumference management. Blood pressure control was optimally achieved through DASH and IF interventions. Lipid profile improvements exhibited diet-specific patterns: KD and HPD for TG and TC reduction; LCD and LFD for HDL-C elevation; KD and LCD for LDL-C lowering. Glycemic control was most effectively attained through DASH and LCD regimens.
Obesity, a well-established modifiable risk factor for CVD, exerts its detrimental effects through pathological adipose tissue expansion. This process drives the secretion of pro-inflammatory adipokines that induce insulin resistance, accelerate atherosclerosis, and ultimately potentiate cardiovascular dysfunction. Our NMA identified KD as the optimal intervention for body composition regulation, demonstrating superior efficacy in reducing body weight (MD −10.5 kg), BMI (−3.57 kg/m²), and waist circumference (−5.13 cm) compared to CD. These findings align with recent clinical recommendations by Bellanti et al.44. who advocate very low-calorie KD protocols for obesity management. Another study on gut flora also showed that the KD reduced the abundance of the gut bacterium Lactobacillus murinus ASF361, which encodes bile salt hydrolase (BSH). The reduction of ASF361 or the inhibition of BSH activity increased circulating levels of taurodeoxycholic acid (TDCA) and taurosugar deoxycholic acid (TUDCA), which in turn reduce energy absorption by inhibiting intestinal carbonic anhydrase 1 expression, leading to weight loss45. Furthermore, the effects of HPD on weight and BMI control have also been demonstrated in several studies, where high-protein diets not only increased satiety but also facilitated the maintenance of fat-free mass, which is closely related to the body’s resting energy expenditure, and high-protein diets increased the body’s resting energy expenditure through the maintenance or increase of fat-free mass, which was effective in reducing body weight46.
Hypertension remains a pivotal modifiable risk factor in cardiovascular disease pathogenesis. The DASH diet, specifically designed to combat elevated blood pressure, demonstrates superior antihypertensive efficacy through its dual mechanisms of sodium restriction and nutrient optimization. Our NMA corroborates these established benefits while revealing an unexpected finding: IF exhibits comparable blood pressure-lowering effects (SBP reduction: −5.98 mmHg vs. control). This observation aligns with the systematic evidence synthesis by Chanthawat Patikorn et al.47whose study identified consistent blood pressure improvements across IF interventions. Mechanistically, IF enhances parasympathetic activation through brain-derived neurotrophic factor (BDNF)-mediated cholinergic neurotransmission. Elevated BDNF levels potentiate acetylcholine synthesis in vagal neurons, which subsequently binds to muscarinic receptors in the sinoatrial node to reduce heart rate47. Concurrently, acetylcholine induces nitric oxide-dependent vasodilation in peripheral vasculature, collectively contributing to blood pressure normalization48. These neurohumoral modulations position IF as a complementary non-pharmacological strategy to DASH dietary protocols, offering synergistic pathways for cardiovascular risk mitigation.
Glycemic dyslipidemia was associated with many chronic diseases and promotes the development of cardiovascular disease. Our study showed that the HPD and the KD were effective in reducing TG, which is consistent with the findings of previous studies, mainly due to restriction of dietary carbohydrate intake49. High-density lipoprotein cholesterol (HDL-C) is often considered the “good” cholesterol because of its key protective role in cardiovascular health. The primary function of HDL-C is reverse cholesterol transport, i.e., the transport of excess cholesterol from peripheral tissues such as the arterial wall back to the liver for metabolism and elimination, thereby reducing the risk of atherosclerosis. Our study showed that LCD diet and LFD diet were optimal in increasing HDL-C, which is consistent with the results of a secondary analysis of data from a randomized controlled trial of dietary patterns and risk factors for cardiovascular disease by Chio Yokose et al.50. In addition our study showed that the DASH diet and LCD diet were optimal for glycemic reduction, which is not in line with previous reports in the literature, as the meta-analysis by Abolfazl Lari et al. showed no significant effect of the DASH diet on glycemia51which may be due to the fact that only one of the studies on the DASH diet that we included reported on the effect on glycemia, which may be due to publication bias and thus a risk factor for the results. The effect of the LCD diet on glycemic control is in line with previous studies, and in a review by Richard D Feinman et al. 12 points of evidence were given to recommend a low-carbohydrate diet as the first diet for glycemic control52. For TC and LDL-C our study did not find a significant difference between these dietary patterns and the habitual diet, but both were on the trend of improvement.
Traditional nutrition RCTs often focus on single-nutrient interventions (e.g., reducing fat intake or supplementing specific vitamins)53. However, this approach has notable limitations. For instance, the early “cholesterol hypothesis” overemphasized fat restriction to reduce cardiovascular risk, yet ignored that excessive limitation could lead to deficiencies in fat-soluble vitamins (e.g., vitamins D, E, K)54 and essential fatty acids (e.g., ω−3), ultimately posing adverse health effects. In contrast, dietary pattern highlight the synergistic effects of multiple foods and nutrients. Research indicates that the collective health benefits of dietary patterns significantly exceed the sum of isolated nutrient actions55. Taking Mediterranean diet as an example: Mediterranean diet has been known for its richness in fruits, vegetables, whole grains, legumes, nuts, olive oil and fish, as well as moderate amounts of dairy and poultry, and limiting red meat and processed foods56. It reduces LDL-C and TG levels while elevating HDL-C, as well as increasing adiponectin concentration and suppresses inflammatory responses. These changes help reduce atherosclerotic plaque formation and arterial stiffness56.
Overall, different dietary patterns may lead to a reduced or increased risk of developing cardiovascular disease by influencing different cardiovascular risk factors. In our study, the KD diet demonstrated superior outcomes on a variety of measures. The KD diet was originally developed for the treatment of epilepsy and is characterized by a very low carbohydrate intake, a high fat intake, and approximately 20% protein57. Despite its effectiveness, this diet has been controversial due to the negative perception of fat and its potential risk for cardiovascular disease. Some studies have shown that the KD diet does not significantly alter lipid levels58whereas others have reported an increase in LDL cholesterol59which may increase the risk of cardiovascular disease60 However, randomized controlled trials have also demonstrated that the KD diet reduces LDL cholesterol, cholesterol levels, body weight, and blood pressure46. Furthermore, it may prevent cardiovascular disease by stabilizing the vascular endothelial system8. More research is needed to resolve the current debate surrounding the KD diet. It is critical to seek guidance from a qualified dietitian on how to appropriately implement a KD diet for CVD prevention and weight loss. Of course, in clinical practice it may be necessary to select the most appropriate intervention strategy based on the goals.
Limitations
This study has several limitations. First, the inclusion criteria did not stratify participants based on age, gender, or disease duration, which may have influenced the effects of the dietary patterns. Second, while a NMA was conducted, the relatively small sample sizes and limited number of included studies may have reduced the statistical power of the results. In addition, the mediating effect of weight change was not assessed, and different dietary patterns may work together to improve cardiovascular risk through metabolic modulation (e.g., ketone body production, fatty acid oxidation) and weight-dependent pathways, which needs to be further elucidated in longitudinal studies combined with biomarker analysis. Lastly, the search was restricted to English-language databases, which may have introduced selection bias and limited the comprehensiveness of the findings.
Conclusion
This paper summarizes and ranks the effects of commonly used dietary patterns on CVD risk factors. The results of the NMA suggest that the KD and LCD are optimal for managing body composition, while the DASH diet and IF are most effective for controlling blood pressure. For dyslipidemia and hyperglycemia, the LCD and HPD may offer better outcomes. All three diets—KD, LCD, and HPD—restrict carbohydrate intake, and this restriction appears to be beneficial in preventing CVD. These findings can guide clinicians in providing dietary recommendations for individuals at high risk of CVD.
Author contributions
Conceptualization, Y.S., J.H., and M.S.; methodology, Y.S. and J.H.; literature search, Y.S. and M.S.; data curation, Y.S. and Y.Z.; writing—original draft preparation, Y.S. and M.S.; writing—review and editing, Y.S., J.H., Y.Z. and M.S. All authors have read and agreed to the published version of the manuscript.
Funding
This work was supported by the Deep Blue Nursing Research Program of Naval Medical University (Grant No. 2022KYG21): “Construction and Application of a Home-Based Care Management Protocol for Peritoneal Dialysis Catheter and Exit-Site Based on the PRECEDE-PROCEED Model”.
Data availability
Reported data from RCT studies included in this net meta-analysis can be found in the original RCT studies cited in the References section.
Declarations
Competing interests
The authors declare no competing interests.
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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Abstract
Cardiovascular disease (CVD) is a major global health concern associated with modifiable risk factors including obesity, hypertension, dyslipidemia, and hyperglycemia. While various dietary patterns have demonstrated cardiovascular benefits, their comparative effectiveness remains unclear. This network meta-analysis (NMA) systematically evaluates the impact of eight dietary patterns on cardiovascular risk markers. We included randomized controlled trials (RCTs) assessing low-fat, Mediterranean, ketogenic, low-carbohydrate, high-protein, vegetarian, intermittent fasting, and DASH diets. A random-effects model analyzed mean differences (MD) in body composition (weight, BMI, waist circumference), lipid profiles (triglycerides, total cholesterol, HDL-C, LDL-C), glycemic markers (glucose), and blood pressure (systolic/diastolic). Dietary efficacy was ranked via Surface Under the Cumulative Ranking Curve (SUCRA) scores. Among 21 RCTs (1,663 participants), ketogenic (MD -10.5 kg, 95% CI -18.0 to -3.05; SUCRA 99) and high-protein diets (MD -4.49 kg, 95% CI -9.55 to 0.35; SUCRA 71) showed superior efficacy for weight reduction. For waist circumference, ketogenic (MD -11.0 cm, 95% CI -17.5 to -4.54; SUCRA 100) and low-carbohydrate diets (MD -5.13 cm, 95% CI -8.83 to -1.44; SUCRA 77) achieved greatest reductions. DASH diet most effectively lowered systolic blood pressure (MD -7.81 mmHg, 95% CI -14.2 to -0.46; SUCRA 89), while intermittent fasting also demonstrated significant blood pressure-lowering effects (MD -5.98 mmHg, 95% CI -10.4 to -0.35; SUCRA 76). Low-carbohydrate (MD 4.26 mg/dL, 95% CI 2.46–6.49; SUCRA 98) and low-fat diets (MD 2.35 mg/dL, 95% CI 0.21–4.40; SUCRA 78) optimally increased HDL-C. Diet-specific cardioprotective effects were observed: ketogenic and high-protein diets excel in weight management, DASH and intermittent fasting in blood pressure control, and carbohydrate-restricted diets in lipid modulation. These findings support personalized dietary strategies for targeted CVD risk factor management.
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Details
1 Nephrology, Changhai Hospital, Naval Medical University, 200433, Shanghai, China (ROR: https://ror.org/02bjs0p66) (GRID: grid.411525.6) (ISNI: 0000 0004 0369 1599)
2 Community Health Service Center, Songnan Town, Baoshan District, 200441, Shanghai, China