1.Clinical observation of Zhengxintai granules in the treatment of microvascular angina for acute ST-segment elevation myocardial infarction patients with qi deficiency and blood stasis syndrome after PCI
Wenhui MA ; Ying ZHANG ; Lei LIU ; Xiuyan YU ; Yali CHEN ; Liming CHEN
China Pharmacy 2026;37(15):2023-2029
OBJECTIVE To investigate the clinical efficacy and safety of Zhengxintai granules as in the treatment of microvascular angina (MVA) following percutaneous coronary intervention (PCI) in patients with acute ST-segment elevation myocardial infarction (STEMI) and qi deficiency and blood stasis syndrome. METHODS Patients with STEMI and qi deficiency and blood stasis syndrome who underwent PCI and developed MVA and were admitted to the Jinan Fourth People’s Hospital (Jinan Cardiovascular Hospital) from March 2022 to March 2025 were selected, they were randomly divided into the control group and the observation group according to a random number table, with 76 cases in each group. Patients in the control group received conventional Western medicine treatment combined with a placebo, while patients in the observation group received Zhengxintai granules (5 mg per dose, three times daily, for 8 weeks) in addition to conventional Western medicine treatment. The clinical efficacy [including the total effective rate of traditional Chinese medicine (TCM) syndrome improvement and the total effective rates of Western clinical efficacy] was compared between the two groups. The following indicators were detected before and after treatment: TCM syndrome scores, angina pectoris episodes [daily attack frequency, duration per attack, Visual Analogue Scale (VAS) score], cardiac function indicators [lactate dehydrogenase (LDH), N-terminal pro-B-type natriuretic peptide (NT-proBNP), left ventricular end-diastolic dimension (LVEDD), left ventricular end-systolic dimension (LVESD), left ventricular ejection fraction (LVEF), cardiac output (CO), fractional shortening (FS)], coagulation function indicators [thrombin time (TT), prothrombin time (PT), fibrinogen (FIB)], fibrinolytic marker (D-dimer), vascular endothelial function indicators [vascular endothelial growth factor (VEGF), nitric oxide (NO), endothelin-1 (ET-1)] and myocardial microcirculation hemodynamic indicators [end-diastolic velocity (EDV), peak systolic velocity (PSV), resistance index (RI), pulsatility index (PI)]. The quality of life [Seattle Angina Questionnaire (SAQ) score] and the incidence of adverse reactions were also compared between the two groups. RESULTS There was no patient dropout during the entire course of the study. The total effective rates of improvement in TCM syndromes and the total effective rates of Western clinical efficacy in the observation group were significantly higher than those in the control group (93.42% vs. 82.89%, 94.74% vs. 84.21%, P<0.05). Before the treatment, the comparison of each examination indicator between the two groups showed no statistically significant differences (P>0.05). Compared with before treatment, the TCM syndrome scores, the number of daily angina pectoris attacks and the duration of each attack, the VAS scores, LDH, NT-proBNP, FIB, D-dimer, ET-1 levels, LVEDD, LVESD, RI and PI after treatment in both groups were significantly reduced, shortened or decreased (P<0.05); VEGF and NO levels, LVEF, CO, FS, TT, PT, EDV, PSV, and the standard scores of five dimensions including angina pectoris stability, as well as the total scores of SAQ, all significantly increased or prolonged (P<0.05). Furthermore, the improvements in the aforementioned indicators (except for LVEF) in the observation group were significantly greater than those in the control group (P<0.05). There was no statistically significant difference in the total incidence of adverse reactions between the two groups (P>0.05). CONCLUSIONS Zhengxintai granules, when used as an adjunct to conventional Western medicine, can significantly alleviate the related symptoms of MVA in STEMI patients with qi deficiency and blood stasis syndrome after PCI, repair damaged cardiac function, restore the balance of the coagulation-fibrinolysis system, improve vascular endothelial function and myocardial microcirculation perfusion, and significantly enhance the quality of life of patients
2.Space radiation safety issues and protective measures for astronauts
Yali ZHAO ; Pengbo LOU ; Wei LU ; Hua ZHANG ; Pengfei ZOU ; Dawei WU
Chinese Journal of Radiological Medicine and Protection 2025;45(2):155-162
Space radiation is the most important environmental harmful factor in long-term manned spaceflight and deep space exploration, and it may produce deterministic and stochastic effects on tissues and organs. In-depth research into the biological effects, mechanisms, and protective measures of space radiation is essential and serves as an important foundation for exploring radiation biology and promoting major manned space projects. Firstly, this review introduces the spatiotemporal distribution characteristics of space radiation during low-earth orbit flights, manned lunar landings, and deep space exploration missions, as well as the health risks and challenges it posed to astronauts. Then, it discusses medical requirements and exposure limits, risk assessment, and protection technologies included in the space radiation protection system established internationally and over 30 years of Chinese manned spaceflight departments. Finally, it outlines the subsequent work and prospects for further research.
3.Application of noninvasive ultrasonic hemodynamic monitoring in critically ill neonates in plateau area
Zhen'e XU ; Weili ZHANG ; Yali YANG ; Chenxia XU ; Baquxi XIANG
Chongqing Medicine 2025;54(10):2326-2330
Objective To evaluate the clinical value of non-invasive ultrasound hemodynamic monito-ring in critically ill neonates in plateau area(altitude>2 500 m).Methods A total of 205 critically ill neo-nates admitted to the NICU of Qamdo People's Hospital from September 2023 to December 2024 were ran-domly divided into the control group(n=105)and the observation group(n=100)using a random number table.There was no statistically significant difference in the baseline data between the two groups(P>0.05).The observation group underwent noninvasive ultrasonic hemodynamic monitoring within 12 hours of admis-sion,measuring corrected flow time(FTC),stroke volume(SV),cardiac index,systemic vascular resistance index(SVRI),and myocardial contractility index(SMII).The control group received conventional monito-ring.The treatment was adjusted based on the results.The above parameters were remeasured 4-8 hours af-ter treatment adjustment.Hospital stay and 28 d survival rate were compared between the two groups.Multi-ple linear regression and binary logistic regression were used to analyze the factors influencing hospital stay and 28 d survival rate,respectively.Results Compared to pre-treatment levels,the observation group showed significant post-treatment decreases in FTC[(364.03±47.70)ms vs.(414.09±52.20)ms]and SVRI[(1 521.00±186.93)dyn·s·(cm5)-1·(m2)-1 vs.(1 720.00±347.31)dyn·s·(cm5)-1·(m2)-1].Con-versely,significant increases were observed in SV[(5.23±0.66)mL vs.(5.09±0.88)mL],cardiac index[(3.35±1.17)L·min-1·(m2)-1 vs.(3.19±0.99)L·min-1·(m2)-1],and SMII[(0.56±0.10)W/m2 vs.(0.51±0.14)W/m2](P<0.05).The observation group had a significantly shorter hospital stay than the control group[(11.53±3.61)d vs.(13.83±2.56)d,P<0.05].The 28 d survival rate was higher in the ob-servation group(100.0%vs.98.1%),although the difference was not statistically significant(P>0.05).Multiple linear regression analysis revealed that both gestational age and cardiac index were negatively correla-ted with the duration of hospital stay.Binary logistic regression analysis indicated that birth weight was a sig-nificant factor influencing the 28 d survival rate(OR=4.600,95%CI:2.465-10.654,P=0.001).Conclusion Non-invasive ultrasonic hemodynamic monitoring can facilitate early identification of hemodynamic alterations in critically ill neonates in platean area,which could guide treatment and potentially reducing hospital stay.
4.Mechanism of Action of Kaixinsan in Ameliorating Alzheimer's Disease
Xiaoming HE ; Xiaotong WANG ; Dongyu MIN ; Xinxin WANG ; Meijia CHENG ; Yongming LIU ; Yetao JU ; Yali YANG ; Changbin YUAN ; Changyang YU ; Li ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(1):20-29
ObjectiveTo investigate the mechanism of action of Kaixinsan in the treatment of Alzheimer's disease (AD) based on network pharmacology, molecular docking, and animal experimental validation. MethodsThe Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) and the Encyclopedia of Traditional Chinese Medicine(ETCM) databases were used to obtain the active ingredients and targets of Kaixinsan. GeneCards, Online Mendelian Inheritance in Man(OMIM), TTD, PharmGKB, and DrugBank databases were used to obtain the relevant targets of AD. The intersection (common targets) of the active ingredient targets of Kaixinsan and the relevant targets of AD was taken, and the network interaction analysis of the common targets was carried out in the STRING database to construct a protein-protein interaction(PPI) network. The CytoNCA plugin within Cytoscape was used to screen out the core targets, and the Metascape platform was used to perform gene ontology(GO) functional enrichment analysis and Kyoto encyclopedia of genes and genomes(KEGG) pathway enrichment analysis. The “drug-active ingredient-target” interaction network was constructed with the help of Cytoscape 3.8.2, and AutoDock Vina was used for molecular docking. Scopolamine (SCOP) was utilized for modeling and injected intraperitoneally once daily. Thirty-two male C57/BL6 mice were randomly divided into blank control (CON) group (0.9% NaCl, n=8), model (SCOP) group (3 mg·kg-1·d-1, n=8), positive control group (3 mg·kg-1·d-1 of SCOP+3 mg·kg-1·d-1 of Donepezil, n=8), and Kaixinsan group (3 mg·kg-1·d-1 of SCOP+6.5 g·kg-1·d-1 of Kaixinsan, n=8). Mice in each group were administered with 0.9% NaCl, Kaixinsan, or Donepezil by gavage twice a day for 14 days. Morris water maze experiment was used to observe the learning memory ability of mice. Hematoxylin-eosin (HE) staining method was used to observe the pathological changes in the CA1 area of the mouse hippocampus. Enzyme linked immunosorbent assay(ELISA) was used to determine the serum acetylcholine (ACh) and acetylcholinesterase (AChE) contents of mice. Western blot method was used to detect the protein expression levels of signal transducer and activator of transcription 3(STAT3) and nuclear transcription factor(NF)-κB p65 in the hippocampus of mice. ResultsA total of 73 active ingredients of Kaixinsan were obtained, and 578 potential targets (common targets) of Kaixinsan for the treatment of AD were screened out. Key active ingredients included kaempferol, gijugliflozin, etc.. Potential core targets were STAT3, NF-κB p65, et al. GO functional enrichment analysis obtained 3 124 biological functions, 254 cellular building blocks, and 461 molecular functions. KEGG pathway enrichment obtained 248 pathways, mainly involving cancer-related pathways, TRP pathway, cyclic adenosine monophosphate(cAMP) pathway, and NF-κB pathway. Molecular docking showed that the binding of the key active ingredients to the target targets was more stable. Morris water maze experiment indicated that Kaixinsan could improve the learning memory ability of SCOP-induced mice. HE staining and ELISA results showed that Kaixinsan had an ameliorating effect on central nerve injury in mice. Western blot test indicated that Kaixinsan had a down-regulating effect on the levels of NF-κB p65 phosphorylation and STAT3 phosphorylation in the hippocampal tissue of mice in the SCOP model. ConclusionKaixinsan can improve the cognitive impairment function in SCOP model mice and may reduce hippocampal neuronal damage and thus play a therapeutic role in the treatment of AD by regulating NF-κB p65, STAT3, and other targets involved in the NF-κB signaling pathway.
5.Meta Analysis of the Diagnostic Value of Serum Mycoplasma Pneumoniae Specific Antibody Detection for Mycoplasma Pneumoniae Pneumonia in Children
Xueling ZHANG ; Qingqin YIN ; Xirong WU ; Xiaohui LIU ; Meiru YAN ; Yali LIU ; Baoping XU
Journal of Modern Laboratory Medicine 2025;40(4):188-193
Objective To evaluate the diagnostic value of positive serum specific antibodies to Mycoplasma pneumoniae(MP)in children with Mycoplasma pneumoniae pneumonia(MPP).Methods PubMed,Cochrane Library,Embase,Sinomed,CNKI,Wanfang and VIP databases were searched for studies on the detection of MPP based on antibodies from the establishment of the database to March 31,2023.After literature screening and data extraction,STATA 16.0 software was used for Meta-analysis.Results A total of 9 literatures and 2 148 clinical samples were included.The combined sensitivities[M(95%CI)]of particle agglutination assay(PA)and enzyme-linked immunosorbent assay(ELISA)were 50%(31~69)and 88%(85~90),and the combined specificities[M(95%CI)]were 88%(76~95)and 88%(62~97).The combined diagnostic odds ratio(DOR)[M(95%CI)]were 5.61(3.30~9.53)and 43.82(12.78~150.19),and the summary receiver operating characteristic curve(SROC)area under the curve(AUC)were 0.80 and 0.88,respectively.Conclusion Serum MP specific antibody detection can be used for diagnosis and screening of children MPP,but needs to be combined with clinical symptoms improve the accuracy of the diagnosis.
6.Effects of Kanxin Powder on Neuroinflammation in APP/PS1 Mice Based on WDFY1/TLR4/NF-κB Signaling Pathway
Yali YANG ; Dongyu MIN ; Yongming LIU ; Changbin YUAN ; Yetao JU ; Yuanyu LIANG ; Meijia CHENG ; Xiaoming HE ; Changyang YU ; Li ZHANG
Chinese Journal of Information on Traditional Chinese Medicine 2025;32(5):90-97
Objective To observe the effect of Kaixin Powder on neuroinflammation in APP/PS1 mice by regulating WDFY1/TLR4/NF-κB signaling pathway;To explore its mechanism of intervening in Alzheimer disease(AD).Methods APP/PS1 transgenic mice were randomly divided into model group,donepezil hydrochloride group(0.66 mg/kg),and Kaixin Powder low-,medium-and high-dosage groups(1.625,3.25,6.5 g/kg),C57BL/6J mice were set as blank control group,with 8 mice in each group,and corresponding drug intervention was given to medicaction group for 24 weeks.Morris water maze,Y maze and novel object recognition experiments were conducted to assess the cognitive function and learning and memory abilities of mice,immunohistochemical staining was used to detect the deposition of β-amyloid protein(Aβ)in hippocampus,the morphology and Nissl bodies of hippocampal CA1 neurons were observed using HE staining and Nissl staining,ELISA was used to detect the serum contents of interleukin(IL)-6,IL-17,IL-1β and tumor necrosis factor-α(TNF-α),Western blot was used to detect the protein expression of calcium-binding adapter molecule 1(Iba1),glial fibrillary acidic protein(GFAP),WDFY1,Toll like receptor 4(TLR4),Toll like receptor associated molecule(TRAM),TIR domain adapter protein(TRIF),NF-κB p65 and p-NF-κB p65 in hippocampal tissue,RT-qPCR was used to detect the mRNA expression of WDFY1,TLR4,TRAM,TRIF and NF-κB p65 in hippocampal tissue.Results Compared with the blank control group,the model group had significantly prolonged escape latency,reduced platform crossings,decreased autonomous reaction alternation rate and relative recognition index(P<0.05,P<0.01),with increased deposition of Aβ in hippocampal tissue(P<0.01),damaged morphological structure of neurons,reduced number of neurons and Nissl bodies,the serum contents of IL-6,IL-17,IL-1β and TNF-α significantly increased,the expression of Iba1,GFAP,WDFY1,TLR4,TRAM,TRIF,p-NF-κB p65 protein and WDFY1,TLR4,TRAM,TRIF mRNA in hippocampal tissue significantly increased(P<0.01).Compared with the model group,Kaixin Powder groups and donepezil hydrochloride group had significantly shortened escape latency and increased platform crossings,autonomous reaction alternation rate and relative recognition index(P<0.05,P<0.01),hippocampal Aβ deposition reduced in Kaixin Powder medium-,high-dosage groups and donepezil hydrochloride group,the morphological structure of neurons recovered,the number of neurons and Nissl bodies increased,the serum contents of IL-6,IL-17,IL-1β and TNF-α significantly decreased(P<0.05,P<0.01),and the protein expression of Iba1,GFAP,WDFY1,TLR4,TRAM,TRIF,p-NF-κB p65 and the mRNA expressions of WDFY1,TLR4,TRAM and TRIF in hippocampal tissue significantly decreased(P<0.05,P<0.01).Conclusion Kaixin Powder can improve cognitive function and learning and memory abilities in AD model mice,alleviate hippocampal neuron damage and Aβ deposition,inhibit the activation of microglia and astrocytes,and thereby reduce serum inflammatory cytokine release.Its mechanism may be related to regulating the WDFY1/TLR4/NF-κB signaling pathway to inhibit neuroinflammation.
7.Overview of the scope of research on maternal-fetal attachment in assisted reproductive technology for pregnant women
Xuzhen CHENG ; Yali CHANG ; Yan LYU ; Fang ZHANG ; Xinfen XU
Chinese Journal of Practical Nursing 2025;41(1):69-77
Objective:To conduct a scoping review of the related research on the maternal-fetal attachment in pregnant women after assisted reproductive technology (ART), summarize the research status of maternal-fetal attachment, and provide reference for future research prospects.Methods:A search was conducted for studies published in PubMed, Embase, EBSCO, Web of Science, Scopus, Cochrane Library, China National Knowledge Infrastructure, Wanfang, and Chinese Medical Journal Full-text Database, from the date of database construction to January 24, 2024. The results of the literature were screened, extracted, and summarized.Results:A total of 15 studies were included. Among them, 14 observational studies reported that the overall status of maternal-fetal attachment of ART pregnant women was in good condition, but the data sources of domestic research were insufficient. Three evaluation tools were used in 15 articles. The related factors were summarized as demographic factors (age and personality traits), pregnancy-related factors (such as conception method, gestational age, history of infertility, history of miscarriage, etc), and psychosocial factors (such as anxiety, depression, conflicts, attitudes towards childbirth, acceptance of pregnancy, social support, marital satisfaction, etc). Four studies put forward suggestions or conducted intervention studies on improving maternal-fetal attachment of ART pregnant women.Conclusions:There is a lack of attention to the maternal-fetal attachment of ART pregnant women in China. Due to the complexity and diversity of its influencing factors, we should deeply explore the characteristics of maternal-fetal attachment development of ART pregnant women at all stages of pregnancy, and carry out more high-quality research. At the same time, we should pay attention to and carry out early screening of maternal-fetal attachment disorders, formulate targeted interventions, so as to promote the establishment of high-quality maternal-fetal attachment, and lay a solid foundation for future maternal-infant relationships.
8.Summary of the best evidence for nursing management of patent foramen ovale for cTEE detection
Yali MA ; Yan XU ; Bei ZHAO ; Yuqing GUO ; Guanghui ZHANG
Chinese Journal of Practical Nursing 2025;41(28):2169-2177
Objective:To retrieve, screen, evaluate and integrate the relevant evidence of nursing management for patent foramen ovale detected by contrast transesophageal echocardiography (cTEE) to provide a basis for clinical practice.Methods:A systematic search was conducted in relevant Chinese and English databases, guideline websites, and professional association websites such as China National Knowledge Infrastructure, Wanfang database, PubMed, and MedLink, etc. Relevant literatures on the detection of patent foramen ovale by cTEE were included, including guidelines, expert conconsensus, clinical decisions, evidence summaries, and systematic reviews. The search period was from the establishment of the database to July 31, 2024. Two evidence-based nursing researchers evaluated the quality of the literature and extracted relevant evidence in combination with clinical situations.Results:A total of 15 literatures were included. Among them, there were 3 guidelines, 6 expert consensuses, 3 clinical decisions, 2 quasi-experiments, and 1 systematic review. Thirty pieces of evidence were summarized from five aspects: assessment, education and publicity, preparation before examination, detection during examination, care after examination.Conclusions:The best evidence for the nursing management of patent foramen ovale detected by cTEE is of high quality and strong authority, which can provide evidence-based basis for standardizing clinical practice and accurately and efficiently detecting patent foramen ovale.
9.The TSLP gene polymorphisms in asthmatic children and their association with serum TSLP level and gene-environment interactions analysis
Zhumei LI ; Yali ZHANG ; Guihong WU ; Wenjuan MENG ; Xiaoping ZHU
Immunological Journal 2025;41(4):243-250
Objective To explore the association of the TSLP gene polymorphisms at rs3806932,rs11466741 and rs2289278 loci with childhood asthma and serum TSLP levels,and to analyze the effects of gene-environment interactions on asthma risk in children.Methods A total of 145 children with asthma and 108 healthy controls were included.Genotyping was performed using KASP and MassARRAY SNP technologies,and serum TSLP levels were measured by ELISA.Differences in allele and genotype frequencies between the two groups were analyzed,along with the impact of genetic models on asthma risk.Differences in serum TSLP levels across groups were compared.Linkage disequilibrium and haplotype analysis were performed using Haploview 4.2,and GMDR 0.9 software was used to assess gene-environment interactions.Results No significant differences were found in the allele and genotype frequencies of the three TSLP gene loci between the two groups(P>0.05).Under the co-dominant model,children with the AG genotype at the rs3806932 locus had 1.750 times the risk of developing asthma compared to those with the AA genotype(95%CI:1.018-3.010,P=0.043).Under co-dominant and overdominant models,children with the CT genotype at the rs11466741 locus had 1.705 times the asthma risk compared to those with the CC genotype(95%CI:1.006-2.891,P=0.048),and 1.698 times the risk compared to those with the CC-TT genotype(95%CI:1.019-2.827,P=0.041).Serum TSLP levels were significantly higher in asthma patients with the CT genotype than those with the CC genotype at the rs11466741 locus(P=0.032).Serum TSLP levels were higher in the asthma group with allergic rhinitis(AR)compared to the group without AR(P<0.01).No significant differences were observed in the distribution of haplotypes frequencies(AC,GT,GC)between the two groups(P>0.05).GMDR analysis showed that the highest asthma risk was observed in children with heterozygous genotypes(CT,AG)at both rs11466741 and rs2289278,or those with the CT genotype at rs11466741,a history of passive smoking,and a cesarean section delivery(P<0.05).Conclusion Polymorphisms in the TSLP gene at rs3806932 and rs11466741 are associated with an increased risk of childhood asthma.Variants at the rs11466741 locus affect serum TSLP levels in children with asthma.Asthma combined with AR leads to elevation of serum TSLP levels.The interaction between rs11466741 and rs2289278,along with environmental factors(passive smoking and cesarean section),contributes to the increase of asthma risk in children.
10.Interactions among risk factors of diabetic retinopathy
Xiaojia SUN ; Guoheng ZHANG ; Ziyi ZHOU ; Yali NIU ; Hua FENG ; Ling WANG ; Guorui DOU
Chinese Journal of Experimental Ophthalmology 2025;43(1):38-46
Objective:To investigate the interaction of risk factors for diabetic retinopathy (DR) occurrence.Methods:A cross-sectional study was performed.A total of 6 783 diabetic patients with complete survey data from 2005 to 2018 in the National Health and Nutrition Survey database were enrolled, among which 4 426 patients were included according to inclusion criteria and were divided into non-DR diabetes group of 3 491 cases and DR group of 935 cases.The related risk factors were collected, including age, gender, race, residential status, education, annual household income, body mass index (BMI), fasting glucose, glycosylated hemoglobin, duration of diabetes, family history of diabetes, comorbidities, smoke, alcohol use, sleep, physical activity.Patient Health Questionnaire (PHQ-9) was used to assess the psychological status.After the categorization of all variables, risk factors of DR were analyzed by logistic regression, and the interaction between factors was further analyzed.Results:Multivariate analysis showed that female[odds ratio ( OR)=1.33, 95% confidence interval ( CI): 1.02-1.72], duration of diabetes ≥10 years ( OR=1.03, 95% CI: 1.02-1.04), insulin therapy ( OR=2.38, 95% CI: 1.87-3.05), urinary albumin creatinine ratio (UACR) ≥30 mg/g ( OR=1.55, 95% CI: 1.22-1.96) and depression ( OR=1.44, 95% CI: 1.13-1.83) were risk factors for DR, and BMI≤28 kg/m 2 ( OR=0.70, 95% CI: 0.55-0.89) was a protective factor for DR.Furthermore, interaction analysis revealed additive interaction between UACR ≥30 mg/g and insulin therapy [relative excess risk due to interaction ( RERI)=2.46, 95% CI: 0.84-4.09, attributable proportion due to interaction ( AP)=0.44, 95% CI: 0.26-0.63, synergy index ( S)=2.16, 95% CI: 1.37-3.41).The UACR ≥30 mg/g and longer diabetic duration ≥10 years had both multiplicative ( OR=1.67, 95% CI: 1.00-2.76) and additive interactions ( RERI=2.02, 95% CI: 0.79-3.25, AP=0.47, 95% CI: 0.27-0.66, S=2.53, 95% CI: 1.37-4.68). Conclusions:Patients with diabetes treated with insulin, with a duration of diabetes ≥10 years and accompanied by UACR ≥30 mg/g are at higher risk of developing DR than those with a single risk factor.

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