1.Establishment and Evaluation of an Oxidative Stress Model of Atopic Dermatitis Induced by 2,4-dinitrofluorobenzene
Chang LIU ; Xuesong XIANG ; Huihuang HE ; Xiaoqing CHEN ; Wenhong QIU
Laboratory Animal and Comparative Medicine 2026;46(1):46-54
Objective To establish an oxidative stress mouse model of atopic dermatitis (AD) by applying 2,4-dinitrofluorobenzene (DNFB) to the back and post-auricular skin of KM mice, and to evaluate the regulatory role of the RAGE-NLRP3 axis (receptor for advanced glycation end products-NOD-like receptor family, pyrin domain containing 3 axis) in AD-related oxidative stress, thereby providing a potential therapeutic target for AD treatment. Methods Twenty SPF-grade female KM mice were randomly divided into a control group (Control group) and an experimental group (DNFB group), with 10 mice in each group. Mice in the Control group were treated with an acetone-olive oil vehicle (acetone: olive oil = 3:1) on their back and post-auricular skin. Mice in the DNFB group were treated with 0.5% DNFB (prepared by adding 0.5 g DNFB per 100 mL of acetone-olive oil vehicle) on the same areas, once daily for 14 consecutive days. The severity of skin lesions was scored on days 2, 4, 6, 9, 12, and 14 of treatment. On day 14, scratching behavior and ear thickness were evaluated. Ear swelling was evaluated on the final day by measuring bilateral ear thickness three times with a vernier caliper; the three measurements were averaged. HE staining was used to observe morphological and structural changes of cells in the back skin tissues. The mRNA and protein expression levels of RAGE (receptor for advanced glycation end products) in skin tissues were detected by quantitative real-time PCR, Western blot, and immunohistochemical staining. The mRNA expression levels of oxidative stress-related molecules, including NLRP3 (NOD-like receptor family, pyrin domain containing 3), caspase-1 (cysteine-dependent aspartate-specific protease 1), and IL-1β (Interleukin-1β), were detected by quantitative real-time PCR. Results On day 14, the back skin lesion scores of the Control group and DNFB group were (0.20±0.42) and (9.93±1.30) (P<0.000 1), respectively. Scratching behavior scores were (5.00±2.05) and (49.26±8.49) episodes, respectively (P<0.000 1), and ear thicknesses were (213.00±11.87) μm and (765.93±140.47) μm (P<0.000 1), respectively. The DNFB group exhibited marked skin dryness, desquamation, and thickening. HE staining results showed that skin inflammation was obvious in the DNFB group, consistent with the pathological features of AD. Quantitative real-time PCR and Western blot results showed that compared with the Control group, the mRNA expression level of RAGE in skin tissues of the DNFB group was significantly increased (P<0.05), and the protein expression level of RAGE was also significantly increased (P<0.01). Immunohistochemical staining results showed that compared with the Control group, skin tissue sections of the DNFB group exhibited thickened stratum corneum and fibrotic proliferation of fibroblasts in the interstitium under microscopic observation, with a significant increase in RAGE protein expression in the skin tissues (P<0.01). Quantitative real-time PCR results showed that the mRNA expression levels of NLRP3, caspase-1, and IL-1β in skin tissues of the DNFB group were all significantly increased (P<0.01). Conclusion The AD mouse oxidative stress model has been successfully established by topical DNFB application. RAGE may promote the development of AD by regulating the NLRP3 inflammasome and IL-1β release, forming an oxidative-inflammatory cascade, suggesting that it could be a potential therapeutic target for AD.
2.Optimization of Quality Standards for Polygalae Radix Based on Characteristic Chromatograms and QAMS for Xanthones
Humin XIE ; Xiaoqing CUI ; Weihong FENG ; Yu LU ; Xiaoqian LIU ; Xiaoli SUN ; Yanrong LI ; Zhimin WANG ; Chun LI
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(9):196-204
ObjectiveTo address the limitations of the current quality standard for Polygalae Radix(PR), which relies on a single component for quality assessment and struggles to holistically control its intrinsic quality, by constructing a comprehensive quality evaluation system integrating "macro-characterization of chemical profile, synchronous quantification of multiple index components, and quantitative analysis of multi-components by single marker(QAMS) for key component groups". This study aims to facilitate the scientific revision of the quality standard for PR. MethodsHigh performance liquid chromatography(HPLC) characteristic chromatograms were established for 11 batches of PR medicinal materials(YZ), 10 batches of PR decoction pieces(YP), and 10 batches of licorice-processed PR decoction pieces(ZYZ), followed by similarity evaluation and identification of common peaks. HPLC-QAMS was developed for xanthones(sibiricaxanthone B, polygalaxanthone Ⅺ, polygalaxanthone Ⅲ) in the characteristic chromatograms. Simultaneously, the external standard method(ESM) was used to determine the contents of the corresponding xanthones and 3,6'-disinapoyl sucrose in YZ, YP, and ZYZ, followed by multivariate statistical analysis and Spearman correlation analysis. ResultsThe similarity between the characteristic chromatograms of 31 batches of PR samples and the reference chromatogram was>0.9. A total of 13 common peaks were identified, and 10 of these peaks were characterized through reference standard comparison. The successfully constructed QAMS method showed that the relative correction factors(RCFs) of sibiricaxanthone B and polygalaxanthone Ⅺ to polygalaxanthone Ⅲ were 0.76 and 0.88, and their relative retention times(RRTs) were 0.85 and 0.97, respectively. The results calculated by the QAMS method showed no significant difference from those obtained by the ESM. According to the limit standard for polygalaxanthone Ⅲ in the 2020 edition of the Pharmacopoeia of the People's Republic of China(hereinafter referred to as the Chinese Pharmacopoeia), the pass rate of 31 batches of samples was only 19.35%. Multivariate statistical analysis indicated certain compositional differences between different batches of YZ and YP, as well as between YP and ZYZ, with 3,6'-disinapoyl sucrose identified as the main differentiating component. Furthermore, correlation analysis revealed that the content of polygalaxanthone Ⅲ was positively correlated with the contents of sibiricaxanthone B and polygalaxanthone Ⅺ, but showed no association with the content of 3,6'-disinapoyl sucrose. ConclusionIt is recommended that the content limit for polygalaxanthone Ⅲ in YZ,YP and ZYZ be revised to not less than 0.07%, or the total content of polygalaxanthone Ⅲ, sibiricaxanthone B and polygalaxanthone Ⅺ be not less than 0.18%. The newly established triple quality control model of "holistic control via characteristic chromatograms, precise quantification of oligosaccharide esters, and efficient detection of xanthones by QAMS" provides a systematic and precise solution for quality evaluation of PR and similar Chinese herbal medicines.
3.Arginine Metabolic Disorder in Heart Failure Rats: Analysis Based on Targeted Metabolomics and Bioinformatics
Zeyu LI ; Xiaoqing WANG ; Zhengyu FANG ; Yurou ZHAO ; He XIAO ; Penghaobang LIU ; Haiming ZHANG ; Chunyan LIU ; Yanhong HU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(10):229-237
ObjectiveThis study systematically analyzed the arginine metabolic dysregulation in the rat model of heart failure (HF), providing a modern scientific basis for elucidating the pathogenesis of HF and offering new insights for the prevention and treatment of HF with traditional Chinese medicine (TCM). MethodsA thoracotomy was performed to ligate the left anterior descending coronary artery of rats, which induced acute myocardial ischemia and thus led to the development of post-myocardial infarction heart failure. The rats were divided into a sham surgery group and a model group, with eight rats in each group. Serum targeted metabolomics analysis was performed using ultra-performance liquid chromatography-triple quadrupole mass spectrometry (UPLC-TQ-S), and the spatial distribution of metabolites in cardiac tissue was observed using airflow-assisted desorption electrospray ionizationmass spectrometry imaging (AFADESI-MSI). Targets associated with HF and arginine metabolism were screened from databases including GeneCards and the Gene Expression Omnibus (GEO), a protein-protein interaction (PPI) network was constructed, and enrichment analysis of the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) was performed. Finally, molecular docking was conducted to verify the binding between core metabolic components and key targets, and potential TCMs were predicted based on the core pathways and targets. ResultsCompared with the sham surgery group, the levels of arginine and citrulline in the serum of model rats were significantly decreased (P<0.01), while those of proline, ornithine, creatine, creatinine and glutamate were significantly increased (P<0.05, P<0.01). Cardiac mass spectrometry imaging showed a decreased abundance of arginine in the local myocardial tissue. Bioinformatics analysis identified 24 core functional targets, such as the angiotensin-converting enzyme (ACE), neuronal nitric oxide synthase (NOS1), 5-hydroxytryptamine receptor 2A (HTR2A), and epidermal growth factor receptor (EGFR), and enrichment analysis indicated that these targets were significantly involved in the calcium signaling pathway, neuroactive ligand-receptor interactions, and phosphatidylinositol signaling pathway. Molecular docking confirmed strong binding activities between arginine, citrulline and HTR2A, as well as between creatine, creatinine and EGFR. Based on pathway-target prediction, potential TCM interventions, such as ginseng and magnolia, were identified. ConclusionThis study revealed characteristic arginine metabolic disorder in HF, and the core targets of HF were closely associated with the phosphatidylinositol signaling pathway. It provides a modern biological interpretation of the pathogenesis of HF in TCM from the perspectives of metabolites and signaling pathways, and offers valuable insights for targeted therapy of HF and the development of TCM.
4.Arginine Metabolic Disorder in Heart Failure Rats: Analysis Based on Targeted Metabolomics and Bioinformatics
Zeyu LI ; Xiaoqing WANG ; Zhengyu FANG ; Yurou ZHAO ; He XIAO ; Penghaobang LIU ; Haiming ZHANG ; Chunyan LIU ; Yanhong HU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(10):229-237
ObjectiveThis study systematically analyzed the arginine metabolic dysregulation in the rat model of heart failure (HF), providing a modern scientific basis for elucidating the pathogenesis of HF and offering new insights for the prevention and treatment of HF with traditional Chinese medicine (TCM). MethodsA thoracotomy was performed to ligate the left anterior descending coronary artery of rats, which induced acute myocardial ischemia and thus led to the development of post-myocardial infarction heart failure. The rats were divided into a sham surgery group and a model group, with eight rats in each group. Serum targeted metabolomics analysis was performed using ultra-performance liquid chromatography-triple quadrupole mass spectrometry (UPLC-TQ-S), and the spatial distribution of metabolites in cardiac tissue was observed using airflow-assisted desorption electrospray ionizationmass spectrometry imaging (AFADESI-MSI). Targets associated with HF and arginine metabolism were screened from databases including GeneCards and the Gene Expression Omnibus (GEO), a protein-protein interaction (PPI) network was constructed, and enrichment analysis of the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) was performed. Finally, molecular docking was conducted to verify the binding between core metabolic components and key targets, and potential TCMs were predicted based on the core pathways and targets. ResultsCompared with the sham surgery group, the levels of arginine and citrulline in the serum of model rats were significantly decreased (P<0.01), while those of proline, ornithine, creatine, creatinine and glutamate were significantly increased (P<0.05, P<0.01). Cardiac mass spectrometry imaging showed a decreased abundance of arginine in the local myocardial tissue. Bioinformatics analysis identified 24 core functional targets, such as the angiotensin-converting enzyme (ACE), neuronal nitric oxide synthase (NOS1), 5-hydroxytryptamine receptor 2A (HTR2A), and epidermal growth factor receptor (EGFR), and enrichment analysis indicated that these targets were significantly involved in the calcium signaling pathway, neuroactive ligand-receptor interactions, and phosphatidylinositol signaling pathway. Molecular docking confirmed strong binding activities between arginine, citrulline and HTR2A, as well as between creatine, creatinine and EGFR. Based on pathway-target prediction, potential TCM interventions, such as ginseng and magnolia, were identified. ConclusionThis study revealed characteristic arginine metabolic disorder in HF, and the core targets of HF were closely associated with the phosphatidylinositol signaling pathway. It provides a modern biological interpretation of the pathogenesis of HF in TCM from the perspectives of metabolites and signaling pathways, and offers valuable insights for targeted therapy of HF and the development of TCM.
5.Influence of Gene Mutation on the Effectiveness of Arsenic-Containing Herbal Compound Formula in Treatment of Myelodysplastic Syndromes of Different TCM Patterns
Zichun WANG ; Zhuo CHEN ; Dexiu WANG ; Haiyan XIAO ; Weiyi LIU ; Ruibai LI ; Chi LIU ; Fengmei WANG ; Shanshan ZHANG ; Mingjing WANG ; Liu LI ; Xiaoqing GUO ; Hongzhi WANG ; Xudong TANG
Journal of Traditional Chinese Medicine 2025;66(14):1463-1472
ObjectiveTo observe the effect of gene mutation on the effectiveness of arsenic-containing Chinese herbal compound formulas in the treatment of myelodysplastic syndromes (MDS) of different traditional Chinese medicine (TCM) patterns, so as to provide the basis for the clinical application. MethodsClinical data of 442 MDS patients who were treated with arsenic-containing herbal compound formulas were retrospectively collected, including the baseline demographic and clinical characteristics of the patients. Based on the TCM four examinations, the patients were divided into the spleen-kidney deficiency group as well as the qi-yin deficiency group, and according to the results of the next-generation sequencing (NGS) test, they were divided into the group with and without gene mutation respectively. The influence of gene mutation on the clinical effectiveness of patients with different TCM patterns was analyzed, the baseline demographic and clinical characteristics of the patients with different outcomes of the two TCM patterns were compared, and multivariate Logistic regression analysis was conducted on the influencing factors of the effective rate of MDS patients with gene mutation. ResultsA total of 190 cases were included in the spleen-kidney deficiency group (119 cases with gene mutation) and 43 cases in the qi-yin deficiency group (23 cases with gene mutation). No statistically significant differences were noted in effectiveness assessment, total effective rate, and total response rate between the spleen-kidney deficiency group and the qi-yin deficiency group (P>0.05). In the spleen-kidney deficiency group, the total effective rate of MDS with gene mutation was 65.55% (78/119), which was lower than 80.28% (57/71) of MDS without gene mutation, with statistical significance (P = 0.033), while no statistical differences in effectiveness assessment and total response rate were noted (P>0.05). In the qi-yin deficiency group, no statistical differences were observed in effectiveness assessment, total effective rate, and total response rate of the patients in with or without gene mutation (P>0.05). In the spleen-kidney deficiency group with gene mutation, the rate of complex karyotype (P = 0.031) and the mutation rate of CBL gene (P = 0.032) in the ineffective population were higher than those in the effective population, while the mutation rate of DDX41 gene in the effective population was higher than that in the ineffective population (P = 0.033). No statistically significant differences were found in other gene mutations, age, gender distribution, number of gene mutations, bone marrow hyperplasia degree, blast cell range, reticular fiber tissue proliferation or not, and prognosis of chromosomal abnormalities between the effective and ineffective populations (P>0.05). In the qi-yin deficiency group with gene mutation, no statistically significant differences were found in various items between populations with different outcomes (P>0.05). Multivariate Logistic regression analysis showed that complex karyotype, CBL mutation, and DDX41 mutation were independently associated with the effective rate of MDS with spleen-kidney deficiency and gene mutation (P<0.05). DDX41 mutation was an independent protective factor in the spleen-kidney deficiency group (OR>1), while complex karyotype and CBL mutation were independent risk factors (OR<1). ConclusionThe arsenic-containing TCM compound formulas exhibited better effectiveness in MDS with spleen-kidney deficiency pattern without mutation; and in MDS with spleen-kidney deficiency pattern without complex karyotypes, CBL mutation, and with DDX41 mutations. Furthermore, DDX41 mutation was an independent protective factor in the spleen-kidney deficiency group, while complex karyotype and CBL mutation were independent risk factors. In MDS with qi-yin deficiency pattern, gene mutation-related factors showed no significant impact on the effectiveness of arsenic-containing TCM compound formulas.
6.Network meta-analysis of first-line treatment of metastatic colorectal cancer with different chemotherapy combination regimens
Xiaoqing ZHANG ; Shuai LIU ; Kai ZHANG ; Beibei JI ; Wei LUAN
China Pharmacy 2025;36(17):2197-2204
OBJECTIVE To systematically evaluate the efficacy and safety of different chemotherapy combination regimens for first-line treatment of metastatic colorectal cancer (mCRC). METHODS PubMed, Cochrane Library, Embase and Web of Science were electronically searched to collect randomized controlled clinical trial (RCT) on first-line treatment for mCRC from January 1, 2000 to February 16, 2025. Two reviewers independently screened literature, extracted data and assessed the risk of bias of the included studies. Network meta-analysis was performed by using R4.4.3 and Stata 17.0 software. RESULTS A total of 28 RCTs, involving 16 intervention measures, were included. In terms of prolonging progression-free survival (PFS) and overall survival (OS), FOLFOX (5-fluorouracil+oxaliplatin+calcium folinate regimen)+cetuximab had the highest probability of ranking first. In terms of improving objective response rate (ORR), FOLFOXIRI (5-fluorouracil+oxaliplatin+irinotecan+calcium folinate regimen)+ bevacizumab and FOLFOX+bevacizumab+nivolumab had the highest probability of ranking first; in terms of the incidence of grade 3 or higher adverse reactions, FOLFOXIRI+panitumumab had the highest probability of ranking first; in subgroup analysis of KRAS wild-type patients, FOLFIRI (5-fluorouracil+irinotecan+calcium folinate regimen)+panitumumab and FOLFIRI+bevacizumab had the highest probability of ranking first in terms of prolonging PFS and OS, respectively; in terms of ORR, FOLFOXIRI+ cetuximab had the highest probability of ranking first. CONCLUSIONS In first-line treatment for mCRC, FOLFOX combined with targeted therapy has advantages in terms of efficacy and safety. However, individualized treatment strategies should be formulated based on the KRAS gene status and tumor location of patients.
7.TCM Treatment of Lung Cancer Based on AMPK Signaling Pathway: A Review
Chengzhi WANG ; Yifan LIU ; Zhenyao YANG ; Wenjun LI ; Xiaoqing ZHANG ; Dongdong LI ; Peimin LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(21):291-298
As a common malignant tumor of the respiratory system, the incidence and mortality of lung cancer are still rising year by year. Its pathogenesis is complex, the prognosis is poor, and it seriously affects human physical and mental health. Although existing Western medical treatments can inhibit tumor growth to a certain extent and relieve patients' painful symptoms, problems such as postoperative recurrence and metastasis, numerous adverse reactions, and the tendency to develop drug resistance make the overall therapeutic effect unsatisfactory. Therefore, it is urgent to seek more efficient and safer treatments. Adenosine monophosphate-activated protein kinase (AMPK) signaling pathway can regulate the growth, differentiation, apoptosis, and autophagy of lung cancer cells, and is extensively involved in the occurrence and development of lung cancer, thus being regarded as an important target for anti-lung cancer therapy. Traditional Chinese medicine (TCM) exerts anti-lung cancer effects through multiple pathways, mechanisms, and targets, with advantages such as preventing postoperative recurrence and metastasis, alleviating the adverse reactions of radiotherapy and chemotherapy, and improving quality of life. TCM has therefore become a key approach in current anti-lung cancer treatment. Studies have found that active components of Chinese medicine, including flavonoids, saponins, polyphenols, and terpenes, as well as Chinese medicine compound prescriptions such as Guiqi Yiyuan extract, Qingzao Jiufei decoction, and Yiqi Fuzheng formula, have significant regulatory effects on AMPK and its interacting signaling pathways. These effects include inducing autophagy and apoptosis of lung cancer cells, modulating macrophage polarization, inhibiting epithelial-mesenchymal transition, reversing drug resistance, and blocking the cell cycle, thereby exerting anti-lung cancer activity. This article reviews and summarizes recent studies on the anti-lung cancer effects of TCM, and discusses the mechanisms by which TCM regulates the AMPK signaling pathway in the treatment of lung cancer, with the aim of providing ideas and references for the development of new clinical anti-lung cancer drugs.
8.TCM Treatment of Lung Cancer Based on AMPK Signaling Pathway: A Review
Chengzhi WANG ; Yifan LIU ; Zhenyao YANG ; Wenjun LI ; Xiaoqing ZHANG ; Dongdong LI ; Peimin LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(21):291-298
As a common malignant tumor of the respiratory system, the incidence and mortality of lung cancer are still rising year by year. Its pathogenesis is complex, the prognosis is poor, and it seriously affects human physical and mental health. Although existing Western medical treatments can inhibit tumor growth to a certain extent and relieve patients' painful symptoms, problems such as postoperative recurrence and metastasis, numerous adverse reactions, and the tendency to develop drug resistance make the overall therapeutic effect unsatisfactory. Therefore, it is urgent to seek more efficient and safer treatments. Adenosine monophosphate-activated protein kinase (AMPK) signaling pathway can regulate the growth, differentiation, apoptosis, and autophagy of lung cancer cells, and is extensively involved in the occurrence and development of lung cancer, thus being regarded as an important target for anti-lung cancer therapy. Traditional Chinese medicine (TCM) exerts anti-lung cancer effects through multiple pathways, mechanisms, and targets, with advantages such as preventing postoperative recurrence and metastasis, alleviating the adverse reactions of radiotherapy and chemotherapy, and improving quality of life. TCM has therefore become a key approach in current anti-lung cancer treatment. Studies have found that active components of Chinese medicine, including flavonoids, saponins, polyphenols, and terpenes, as well as Chinese medicine compound prescriptions such as Guiqi Yiyuan extract, Qingzao Jiufei decoction, and Yiqi Fuzheng formula, have significant regulatory effects on AMPK and its interacting signaling pathways. These effects include inducing autophagy and apoptosis of lung cancer cells, modulating macrophage polarization, inhibiting epithelial-mesenchymal transition, reversing drug resistance, and blocking the cell cycle, thereby exerting anti-lung cancer activity. This article reviews and summarizes recent studies on the anti-lung cancer effects of TCM, and discusses the mechanisms by which TCM regulates the AMPK signaling pathway in the treatment of lung cancer, with the aim of providing ideas and references for the development of new clinical anti-lung cancer drugs.
9.Enhancing Disciplinary Development Through Journal Columns: Taking the "Clinical Practice Guidelines"Column in Medical Journal of Peking Union Medical College Hospital as an Example
Meihua WU ; Hui LIU ; Qi ZHOU ; Qianling SHI ; Na LI ; Yule LI ; Xiaoqing LIU ; Kehu YANG ; Jinhui TIAN ; Long GE ; Bin MA ; Xiuxia LI ; Xuping SONG ; Xiaohui WANG ; Yaolong CHEN
Medical Journal of Peking Union Medical College Hospital 2025;16(5):1315-1324
To explore the role of the "Clinical Practice Guidelines" column and others in the We collected papers published by the Lanzhou University Evidence-Based Medicine Center team in the "Clinical Practice Guidelines" column and others from 2018 to 2025. These publications were analyzed across multiple dimensions, including authorship and institutional affiliations, citation metrics, and research themes and content. A total of 59 papers were included in the analysis, with authors representing 70 domestie and international research institutions. The cumulative citation count was 639, with the highest single-paper citation frequency reaching 101. The average citation per paper was 10.8, and total downloads exceeded 30 000. The content focused on key themes such as guideline terminology, development methodology, guideline evaluation, and dissemination and implementation. The evolution of research topics progressed from critiques of common misconceptions and hot topies in the field to multidimensional evaluations of thecurrent state of Chinese guidelines, culminating in the fommulation of industry standards for guidelines. These contributions have provided critical references for translating guideline theory into practice in China and have garnered widespread attention and discussion among scholars in the field. The "Clinical Practice Guidelines" column and others in the
10.Research progress on peripheral defocus-based optical interventions combined with other therapies for myopia control
Xiaoqing LIU ; Jinhai ZHONG ; Quan LIN
International Eye Science 2025;25(11):1814-1819
The global myopia epidemic presents a significant public health challenge, necessitating diverse intervention strategies. The primary objective of myopia management is to achieve a dual therapeutic effect: providing children with clear, comfortable, and sustained vision, while also curbing rapid myopic progression to prevent high myopia. Optical interventions based on the theory of peripheral retinal defocus have become first-line treatments owing to their dual capacity for vision correction and axial elongation control. For children with myopia who show suboptimal response to defocus-based optical interventions, combination therapy has gradually emerged as a new clinical trend. Current combination strategies primarily include defocus-based optical interventions combined with low-concentration atropine, red-light therapy, and vision training, among others. This review summarizes available evidence on these three combination strategies, focusing on clinical efficacy, safety, and underlying mechanisms, with the aim of supporting evidence-based and personalized myopia management plans for clinicians.

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