1.Mechanism of Xiezhuo Jiedu Prescription in Treatment of Ulcerative Colitis by Inhibiting Ferroptosis and Alleviating Intestinal Mucosal Injury Based on Nrf2/SLC7A11/GPX4 Signaling Pathway
Qiang CHUAI ; Wenjing ZHAI ; Sujie JIA ; Xiaomeng LANG ; Jie REN ; Xin KANG ; Shijie REN ; Xingchi LIU ; Xin LIU ; Xiaohong JIANG ; Jianping LIU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(1):160-169
ObjectiveTo investigate the mechanism of Xiezhuo Jiedu prescription in the treatment of ulcerative colitis (UC) by inhibiting ferroptosis and alleviating intestinal mucosal injury based on the nuclear factor E2 related factor 2/solute carrier family 7 member/glutathione peroxidase 4 (Nrf2/SLC7A11/GPX4) signaling pathway. MethodsA total of 60 male SD rats were divided into a normal group, a model group, high- and low-dose Xiezhuo Jiedu prescription groups (26.64 and 13.32 g·kg-1, respectively), a ferroptosis inhibitor group (Ferrostatin-1, 0.005 g·kg-1), and a mesalazine group (0.27 g·kg-1), with 10 rats in each group. A UC rat model was established by intrarectal administration of trinitrobenzene sulfonic acid (TNBS)-ethanol. The normal group and the model group were intragastrically administered normal saline. The other groups were given intragastric administration according to the corresponding dosage for 7 d. The general condition, disease activity index (DAI) score, colon length, and mucosal injury index (CDMI) score were observed in each group. The pathological changes of colon tissue in each group were observed by hematoxylin-eosin (HE) staining. The intestinal mucosa and mitochondrial morphology in each group were observed by transmission electron microscopy. The expression levels of Occludin, Claudin-1, mucin 2 (MUC2), and E-cadherin in intestinal tissue were detected by immunofluorescence (IF). Enzyme-linked immunosorbent assay (ELISA) was used to detect the expression levels of serum tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-10 (IL-10) in each group, and a lactic acid assay kit or ELISA was employed to detect the expression levels of reactive oxygen species (ROS), ferrous ions (Fe2+), glutathione (GSH), malondialdehyde (MDA), 4-hydroxynonenal (4-HNE), diamine oxidase (DAO), and D-lactate (D-LA). Real-time quantitative polymerase chain reaction (Real-time PCR) was applied to detect the mRNA expression levels of Nrf2, SLC7A11, GPX4, Occludin, Claudin-1, MUC2, and E-cadherin in each group, and Western blot was adopted to detect the protein expression levels of Nrf2, p-Nrf2, SLC7A11, and GPX4 in each group. ResultsCompared with the normal group, rats in the model group exhibited listlessness, sluggish response, and mucopurulent and bloody stools. The model group also showed significantly increased DAI score, colon length, CDMI score, and expression levels of TNF-α, IL-6, ROS, Fe2+, MDA, 4-HNE, DAO, and D-LA (P<0.01). In addition, it presented significantly decreased IF values of Occludin, Claudin-1, MUC2, and E-cadherin and mRNA and protein expression levels of IL-10, GSH, Nrf2, p-Nrf2, SLC7A11, and GPX4 (P<0.01). There were different degrees of improvement in each administration group after treatment, and the improvement was the most significant in the high-dose Xiezhuo Jiedu prescription group (P<0.01). ConclusionXiezhuo Jiedu prescription may alleviate intestinal mucosal injury by inhibiting ferroptosis of intestinal epithelial cells via regulating the Nrf2/SLC7A11/GPX4 signaling pathway, thereby exhibiting efficacy in the treatment of UC.
2.Effect and mechanism of Buyang Huanwu Decoction in improving neurological function in ischemic stroke rats based on IRE1α/ASK1/JNK pathway.
Xin-Rong ZHANG ; Tian-Lang WANG ; Jia-Hao ZHANG ; Lu JIN ; Jian-Bo WANG ; Ya-Nan XUE ; Yi QU
China Journal of Chinese Materia Medica 2025;50(14):3857-3867
This study aimed to investigate the effect and mechanism of Buyang Huanwu Decoction in regulating endoplasmic reticulum stress via the inositol-requiring enzyme 1α(IRE1α)/apoptosis signal-regulating kinase 1(ASK1)/c-Jun N-terminal kinase(JNK) pathway to improve neurological function in rats with cerebral ischemia/reperfusion injury(CIRI). SPF-grade male sprague-dawley(SD) rats were randomly divided into Sham group, model group, Buyang Huanwu Decoction group, and edaravone group. Except for the Sham group, the other groups were subjected to the modified suture method to establish a middle cerebral artery occlusion/reperfusion(MCAO/R) model. After treatment, neurological function was assessed using the Zea Longa scoring system. Gait analysis was used to detect the motor function. Detection of relative infarct area in brain tissue using 2,3,5-triphenyltetrazolium chloride(TTC) staining. Nissl staining was used to observe the structure of neuronal cells. Western blot and real-time fluorescence quantitative PCR(RT-qPCR) were used to detect IRE1α, ASK1, JNK, B cell lymphoma-2(Bcl-2), Bcl-2 related X protein(Bax), and Caspase-3 in the brain tissue. Immunohistochemistry was used to detect the positive expression of IRE1α, ASK1, and JNK. Immunofluorescence was used to detect the fluorescence expression levels of Bax, Bcl-2, and Caspase-3. The results showed that compared with the Sham group, the model group exhibited increased neurological scores(P<0.01), increased ratio of ground contact area and strength in both forelimbs(P<0.01), enlarged relative infarct area of brain tissue(P<0.05), and a reduced number of Nissl staining-positive cells(P<0.01). The protein and mRNA expression levels of IRE1α, ASK1, JNK, Bax, and Caspase-3 in brain tissue were significantly elevated, while those of Bcl-2 were decreased(P<0.05). Compared with the model group, both the Buyang Huanwu Decoction group and edaravone group showed reduced neurological scores(P<0.05), decreased ratio of ground contact area and strength in both forelimbs(P<0.05), smaller relative infarct area(P<0.05), alleviated neuronal damage, and increased number of Nissl staining-positive cells(P<0.05). The expression levels of IRE1α, ASK1, JNK, Bax, and Caspase-3 protein and mRNA in brain tissue were significantly reduced, while those of Bcl-2 were significantly increased(P<0.05). The results indicated that Buyang Huanwu Decoction can effectively improve brain injury in CIRI rats, and its mechanism of action may be related to regulating the endoplasmic reticulum stress IRE1α/ASK1/JNK signaling pathway.
Animals
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Male
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Rats, Sprague-Dawley
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Protein Serine-Threonine Kinases/genetics*
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Drugs, Chinese Herbal/administration & dosage*
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Rats
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MAP Kinase Kinase Kinase 5/genetics*
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Ischemic Stroke/physiopathology*
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Humans
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MAP Kinase Signaling System/drug effects*
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Apoptosis/drug effects*
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Endoribonucleases/genetics*
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JNK Mitogen-Activated Protein Kinases/genetics*
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Endoplasmic Reticulum Stress/drug effects*
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Multienzyme Complexes
3.Hypoxia inhibits chondrocyte pyroptosis via HIF1α/NIX-mediated mitochondrial autophagy
Shiqi LUO ; Xia WEI ; Lang JIA
Academic Journal of Naval Medical University 2025;46(5):594-601
Objective To observe the effect of hypoxia(HX)on autophagy and pyroptosis-related protein expression of interleukin(IL)-1β-induced chondrocytes,and explore its mechanism of cartilage protection.Methods The expression of Bcl2/adenovirus E1B interacting protein 3-like(BNIP3L/NIX)in normal and osteoarthritis chondrocytes was analyzed by bioinformatics method.The primary chondrocytes from the knee joints of C57BL/6J neonatal mice were extracted and assigned to control group,IL-1β group,HX group,or IL-1β+HX group.The cells were treated with 10 ng/mL IL-1β for 24 h to simulate osteoarthritis-like chondrocyte injury,and HX treatment was by incubation with 1%O2 for 24 h.The expression levels of collagen typeⅡ α1(COL2α1),matrix metalloproteinase 13(MMP13),a disintegrin and metalloproteinase with thrombospondin 5(ADAMTS5),nucleotide-binding oligomerization domain-like receptor 3(NLRP3),gasdermin D N-terminal domain(GSDMD-N),apoptosis-associated speck-like protein containing a CARD(ASC),IL-18,hypoxia induced factor 1α(HIF1α),NIX,Beclin1,microtubule-associated protein-light chain 3(LC3),and p62 proteins were detected by Western blotting in each group.Results Bioinformatics analysis showed that the expression of NIX was lower in osteoarthritis chondrocytes than in normal chondrocytes.Western blotting showed that compared to the control group,the IL-1β group showed significant decreases in COL2α1 and NIX protein expression(both P<0.05)and significant increases in MMP13,ADAMTS5,NLRP3,GSDMD-N,ASC,IL-18 and HIF1α protein expression(all P<0.01).Compared to the IL-1β group,the IL-1β+HX group showed significant increases in COL2α1,HIF1α,NIX,Beclin1,and LC3 Ⅱ/LC3Ⅰ(all P<0.01)and significant decreases in MMP13,ADAMTS5,NLRP3,GSDMD-N,ASC,IL-18 and p62(all P<0.01).Compared to the control group,the HX group exhibited significant increases in HIF1α,NIX,Beclin1,and LC3Ⅱ/LC3Ⅰ(all P<0.01)and decreases in p62,NLRP3,GSDMD-N and IL-18(all P<0.05).Conclusion Hypoxia may eliminate NLRP3 inflammasome and inhibit chondrocyte pyroptosis through HIF1α/NIX-mediated mitochondrial autophagy,thereby reducing IL-1β-induced chondrocyte injury.
4.Exploration of Decision-Making Methods Based on Syndrome Differentiation by “Data-Knowledge” Dual-Driven Models: A Case Study of Gastric Precancerous State
Weichao XU ; Yanru DU ; Xiaomeng LANG ; Yingying LOU ; Wenwen JIA ; Xin KANG ; Shuo GUO ; Kun ZHANG ; Chunzhi SU ; Junbiao TIAN ; Xiaona WEI ; Qian YANG
Journal of Traditional Chinese Medicine 2024;65(2):154-158
Data analysis models may assist the transmission of traditional Chinese medicine (TCM) experience and clinical diagnosis and treatment, and the possibility of constructing a “data-knowledge” dual-drive model was explored by taking gastric precancerous state as an example. Data-driven is to make clinical decisions around data analysis, and its syndrome-differentiation decision-making research relies on hidden structural models and partially observable Markov decision-making processes to identify the etiology of diseases, syndrome elements, evolution of pathogenesis, and syndrome differentiation protocols; knowledge-driven is to make use of data and information to promote decision-making and action processes, and its syndrome-differentiation decision-making research relies on convolutional neural networks to improve the accuracy of local disease identification and syndrome differentiation. The “data-knowledge” dual-driven model can make up for the shortcomings of single-drive numerical simulation accuracy, and achieve a balance between local disease identification and macroscopic syndrome differentiation. On the basis of previous research, we explored the construction method of diagnostic assisted decision-making platform for gastric precancerous state, and believed that the diagnostic and decision-making ability of doctors can be extended through the assistance of machines and algorithms. Meanwhile, the related research methods were integrated and the core features of gastric precancerous state based on TCM syndrome differentiation and endoscopic pathology diagnosis and prediction were obtained, and the elements of endoscopic pathology recognition based on TCM syndrome differentiation were explored, so as to provide ideas for the in-depth research and innovative application of cutting-edge data analysis technology in the field of intelligent TCM syndrome differentiation.
5.Minimally invasive aortic valve replacement with Perceval sutureless aortic bioprosthesis through upper ministernotomy or right anterior thoracotomy
Peng YANG ; Yi XIE ; Chenhao WANG ; Yu LIU ; Qianlei LANG ; Wenfan LI ; Jia HU
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2024;31(03):439-445
Objective To evaluate the clinical effect of minimally invasive aortic valve replacement with Perceval sutureless aortic bioprosthesis in upper ministernotomy or right anterior thoracotomy. Methods From March to November 2022, the patients with simple aortic valve disease were enrolled in the Department of Cardiovascular Surgery of West China Hospital, Sichuan University. After preoperative evaluation, Perceval sutureless bioprosthesis was successfully used to perform aortic valve replacement through the upper ministernotomy or right anterior thoracotomy. The perioperative clinical data and ultrasonic measurement data of all patients were recorded. Results A total of 5 patients with simple aortic valve disease were included, including 3 females and 2 males, with a mean age of 71.2 years. Perceval sutureless bioprosthesis was successfully implanted in 5 patients, with a success rate of 100%. There were 3 patients receiving upper ministernotomy and 2 patients receiving right anterior thoracotomy. Two patients underwent ascending aortic plasty at the same time. The mean cardiopulmonary bypass time was 61.0 min, and aortic cross-clamping time was 32.2 min. All patients were discharged successfully without perivalvular leakage, atrioventricular block or stroke. Conclusion The implantation method of Perceval sutureless bioprosthesis is simple, which can effectively reduce the perioperative risk by shortening the overall operation time, cardiopulmonary bypass time and aortic cross-clamping time. At the same time, its clinical application has promoted the development and popularization of minimally invasive aortic valve replacement, which together with Perceval sutureless bioprosthesis effectively combinates surgical effect and minimally invasive treatment, and has a good clinical application prospect because of its reliable safety and effectiveness.
6.Two-stage retrograde hybrid repair in the surgical treatment of acute aortic dissection complicated with distal malperfusion syndrome
Peng YANG ; Yi XIE ; Yu LIU ; Yu ZHANG ; Qianlei LANG ; Wenfan LI ; Chenhao WANG ; Zhenghua XIAO ; Jia HU
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2024;31(04):585-593
Objective To evaluate the clinical efficacy of two-stage retrograde hybrid repair for acute aortic dissection involving the aortic arch complicated with distal malperfusion syndrome. Methods From May 2019 to December 2022, the patients presented with acute aortic dissection involving the aortic arch complicated with distal malperfusion syndrome treated in the Department of Cardiovascular Surgery of West China Hospital, Sichuan University were enrolled. After preoperative evaluation, all patients underwent priority emergency interventional surgery to improve distal malperfusion, and then underwent two-stage hybrid surgery to repair proximal aortic lesions. The perioperative clinical and imaging data were retrospectively analyzed. Results Five patients were collected, including 4 males and 1 female, with a median age of 58 years. The main manifestations were lower limb ischemia and renal insufficiency in 3 patients, and poor intestinal perfusion in 2 patients. All patients were given priority to interventional surgery to implant graft stents or bare stents and necessary branch artery intervention, and then successfully performed two-stage hybrid surgery, including type Ⅰhybrid surgery for 2 patients, type Ⅱ hybrid surgery for 1 patient and type Ⅲ hybrid surgery for the other 2 patients, with a success rate of 100.0%. All patients were discharged successfully, and the function of the organs with poor perfusion returned to normal. Only 1 patient recovered to grade 4 muscle strength of the diseased lower limbs upon discharge. No adverse events such as amputation, exploratory laparotomy and intestinal resection or long-term hemodialysis occurred. Conclusion The application of two-stage retrograde hybrid repair in the surgical treatment of acute aortic dissection involving the aortic arch complicated with distal malperfusion syndrome is safe and effective, and is helpful to improve the perioperative survival rate, and clinical outcomes of such patients.
7.Advances of Near-Infrared Spectroscopy in Cancer Diagnosis
Wei-Wei LANG ; Jia-Chen LI ; Lin-Yi DONG ; Li HAN
Chinese Journal of Analytical Chemistry 2024;52(9):1225-1233
Near-infrared(NIR)spectroscopy reflects the vibrational information of hydrogen-containing groups,allowing the detection of changes in components such as proteins and lipids in biological samples caused by diseases.Due to the advantages such as rapidity,non-destructiveness and non-invasiveness,NIR spectroscopy has been widely used in disease diagnosis.Malignant tumor cells exhibit significant differences in structure and composition compared to normal cells,and abnormal metabolic functions cause changes in the composition of biological tissues and fluids,leading to the variation in spectra.This makes NIR spectroscopy a promising tool for detecting cancer.However,severe overlapping of spectral peaks in the spectra requires the help of chemometrics methods to analyze the spectra and extract diagnostic information.This review summarizes the recent advances in NIR spectroscopy technology in cancer detection,including the methods of spectral preprocessing,diagnosis modeling and the development in NIR hyperspectral imaging combined with deep learning methods.The quantitative information and structural changes of molecules in biological systems can be extracted.Furthermore,the sensitivity of NIR spectra to water is utilized to analyze the content and structural changes of water induced by cancer and its role in cancer detection.
8.Scoping review of fatigue status and its influencing factors in patients receiving maintenance hemodialysis
Meili JIA ; Yiting NAN ; Shu WU ; Zhiyuan LIU ; Siyu LI ; Xiulan WANG ; Yanmei LANG
Chinese Journal of Modern Nursing 2024;30(24):3221-3231
Objective:To summarize the current research status, assessment tools, and influencing factors of fatigue in patients receiving maintenance hemodialysis (MHD) and provide a reference for the management of fatigue in this patient population.Methods:A literature search was conducted in databases including PubMed, Web of Science, ProQuest, Cochrane Library, Science Direct, Embase, CINAHL, China National Knowledge Infrastructure, WanFang Data, VIP, and China Biology Medicine disc for studies related to fatigue in patients receiving MHD. The search timeframe was from establishing the databases to January 23, 2024.Results:A total of 46 studies were included. Various assessment tools for fatigue in patients receiving MHD were identified, though specific tools were limited. The Short Form 36 Vitality Subscale (SF-36 VS) was the most commonly used assessment tool. The main factors influencing fatigue in these patients included sociodemographic, dialysis-related, disease-related, physical, nutritional, and psychological factors.Conclusions:Fatigue is a significant symptom in patients receiving MHD. Healthcare professionals must develop specific tools for accurately assessing fatigue in this population and explore standardized management plans.
9.Mechanism of Modified Guizhi Fulingwan in Regulating Mitochondrial Apoptosis Pathway Through PTEN/PI3K/Akt Pathway to Prevent Colorectal Adenoma in Mice
Sujie JIA ; Longhui LIU ; Yifan ZHANG ; Xiaomeng LANG ; Jianping LIU ; Xin KANG ; Chaodi SUN ; Jingyuan LIU
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(19):10-20
ObjectiveTo investigate the effect and mechanism of modified Guizhi Fulingwan in preventing colorectal adenoma (CRA) in mice by regulating mitochondrial apoptosis pathway through the regulation of the phosphatase and tensin homolog (PTEN)/phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) pathway. MethodSixty SPF-grade male C57BL/6 mice were randomly divided into six groups: Normal group, model group, low, medium, and high dose groups of modified Guizhi Fulingwan (13, 26, 52 g·kg-1·d-1), and positive control aspirin group (0.015 g·kg-1·d-1). A mouse model of CRA was chemically induced using azoxymethane (AOM) and dextran sulfate sodium (DSS). During the modeling process, mice received modified Guizhi Fulingwan or aspirin. Body weight of mice was measured weekly during the treatment. After 9 weeks, the number of adenomas formed was observed. Serum levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) were determined by enzyme-linked immunosorbent assay (ELISA). Hematoxylin-eosin (HE) staining was used to observe the histopathologic changes in adenoma tissues. The expression of Cyclin D1 and proliferative nuclear antigen (Ki67) was detected by immunohistochemistry (IHC). Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) was used to assess the apoptosis in adenoma tissues. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) and Western blot were used to observe the mRNA and protein expression levels of PTEN, PI3K, Akt, phosphorylated PI3K (p-PI3K), phosphorylated Akt (p-Akt), B-cell lymphoma-2 (Bcl-2), Bcl-2 associated X protein (Bax), cytochrome C (Cyt C), Caspase-9, and caspase-3. ResultCompared with the normal group, the model group showed no significant change in body weight from week 1 to week 2, but a significant decrease from week 3 to week 9 (P<0.05,P<0.01). The colorectal length was significantly shortened, and the colorectal weight increased with visible varying sized tumor-like protrusions on the mucosal surface (P<0.01). Serum levels of TNF-α, IL-6, and IL-1β were elevated (P<0.01). Histopathology showed disordered epithelial gland structure, elongated nuclei with pathological mitosis, and numerous lymphocytic infiltrations in the lamina propria. The positive expression rates of Cyclin D1 and Ki67 were significantly increased (P<0.01), while the apoptosis rate of adenoma cells was significantly decreased (P<0.01). Expression levels of PI3K, Akt, Bcl-2 mRNA and proteins, as well as p-PI3K and p-Akt proteins, were significantly increased (P<0.01), whereas PTEN, Bax, Cyt C, Caspase-9, and Caspase-3 mRNA and protein levels were significantly decreased (P<0.05, P<0.01). Compared with the model group, all drug treatment groups showed an increase in body weight (P<0.01), decreased intestinal weight, increased colorectal length, reduced number of adenomas significantly (P<0.05, P<0.01), and significantly lowered serum levels of TNF-α, IL-6, and IL-1β (P<0.01). Histopathology indicated improved glandular structure and reduced neutrophil infiltration in the mucosal lamina propria. The positive expression rates of Cyclin D1 and Ki67 significantly decreased (P<0.01), while the apoptosis rate of adenoma cells significantly increased (P<0.05, P<0.01). Expression levels of PI3K, Akt, Bcl-2 mRNA and proteins, and p-PI3K and p-Akt proteins were significantly reduced (P<0.05, P<0.01), while PTEN, Bax, Cyt C, Caspase-9, and Caspase-3 mRNA and protein levels significantly increased (P<0.05, P<0.01). The high-dose modified Guizhi Fulingwan group exhibited the most significant intervention effects. ConclusionModified Guizhi Fulingwan may prevent CRA in mice by regulating the PTEN/PI3K/Akt signaling pathway and inducing the mitochondrial apoptosis pathway.
10.Effect of peripheral defocus spectacle lenses and orthokeratology lenses on myopia progression control and vision-related quality of life in children
Haitao ZHOU ; Minglong ZUO ; Jia LANG ; Ting SHEN ; Xiaoyan LYU ; Junhui ZHANG ; Yuanyuan WANG
International Eye Science 2024;24(10):1629-1633
AIM:To explore the effect of the peripheral defocus spectacle lenses and orthokeratology(OK)on the control of myopia progression and the impact on vision related quality of life in children and adolescents.METHODS:Prospective study. A total of 237 children initially diagnosed with myopia in the ophthalmology department of Huzhou Central Hospital from January 2021 to January 2022 were selected and divided into two groups according to different correction methods: peripheral defocus spectacle lenses group(105 cases, 105 eyes)and OK lens group(132 cases, 132 eyes). The Vision Related Quality of Life Questionnaire for Primary and Secondary School Students was used to follow up the both groups of myopic children, and the best corrected visual acuity(BCVA), spherical equivalent(SE), and axial length(AL)were recorded at the first visit and 1 a of follow-up.RESULTS:After wearing lenses for 1 a, both the peripheral defocus spectacle lenses group and OK lens group showed an increase in SE and AL, but there was no statistical difference between two groups(P>0.05). The changes in SE and AL in the peripheral defocus spectacle lenses group were greater than those in the OK lens group(all P=0.001). After 1 a of follow-up, in the emotional dimension scores, the peripheral defocus spectacle lenses group of children's vision-related quality of life scales scored higher than in the OK lens group(P<0.05). Compared with the baseline value, the change in the emotional dimension scores of the OK lens group was greater than that in the peripheral defocus spectacle lens group(P<0.05).CONCLUSION:OK lenses are superior to peripheral defocus spectacle lenses in controlling the progression of myopia in children and adolescents. Both correction methods can significantly improve myopic children's vision-related quality of life, with OK lenses being better at improving the emotional dimension of vision-related quality of life.

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