1.Research progress on the effects of different myopia prevention and control methods on choroid
Shangzhu ZHANG ; Jiawei WANG ; Ruijie XI ; Song CHAI
International Eye Science 2025;25(1):70-75
In recent years, there has been a significant surge in the prevalence of myopia at younger ages in China. Numerous studies have investigated methods for preventing and controlling myopia, including orthokeratology, low-concentration atropine eye drops, light therapy, posterior scleral reinforcement, and traditional Chinese medicine. These approaches can modulate choroidal thickness, blood flow, and target various molecular mechanisms. Orthokeratology and low-concentration atropine demonstrate a thickening effect on the choroid and regulate choroidal blood flow; the use of multi-point defocus control lenses also shows promise in thickening the choroid; the influence of light and light feeding therapy on myopia prevention and control is also reflected in the choroidal thickness and blood flow; and the traditional Chinese medicine has shown good prospect in influencing the microstructure of the choroid for myopia prevention and control. However, the long-term effects of various prevention and control measures on the choroid still need to be explored with a large sample size. This article provides an overview of various methods used to regulate the choroid and prevent myopia. The mechanisms by which these interventions act on the choroid are described to provide new insights and identity novel clinical strategies for myopia management.
2.Effect of Rhei Radix et Rhizoma Before and After Steaming with Wine on Intestinal Flora and Immune Environment in Constipation Model Mice
Yaya BAI ; Rui TIAN ; Yajun SHI ; Chongbo ZHAO ; Jing SUN ; Li ZHANG ; Yonggang YAN ; Yuping TANG ; Qiao ZHANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(2):192-199
ObjectiveTo study on the different therapeutic effects and potential mechanisms of Rhei Radix et Rhizoma(RH) before and after steaming with wine on constipation model mice. MethodsFifty-four male ICR mice were randomly divided into control group, model group, lactulose group(1.5 mg·kg-1), high, medium and low dose groups of RH and RH steaming with wine(PRH)(8, 4, 1 g·kg-1). Except for the control group, the constipation model was replicated by gavage of loperamide hydrochloride(6 mg·kg-1) in the other groups. After 2 weeks of modeling, each administration group was gavaged with the corresponding dose of drug solution, and the control and model groups were given an equal volume of normal saline, 1 time/d for 2 consecutive weeks. After administration, the feces were collected for 16S rRNA sequencing, the levels of gastrin(GAS), motilin(MTL), interleukin-6(IL-6), γ-interferon(IFN-γ) in the colonic tissue were detected by enzyme-linked immunosorbent assay(ELISA), the histopathological changes of colon were observed by hematoxylin-eosin(HE) staining, flow cytometry was used to detect the proportion changes of CD4+, CD8+ and regulatory T cell(Treg) in peripheral blood. ResultsCompared with the control group, the model group showed significantly decrease in fecal number in 24 h, fecal quality and fecal water rate(P<0.01), the colon was seen to have necrotic shedding of mucosal epithelium, localized intestinal glands in the lamina propria were degenerated, necrotic and atrophied, a few lymphocytes were seen to infiltrate in the necrotic area in a scattered manner, the contents of GAS and MTL, the proportions of CD4+, CD8+ and Treg were significantly reduced(P<0.01), the contents of IL-6 and IFN-γ were significantly elevated(P<0.05, P<0.01). Compared with the model group, the fecal number in 24 h, fecal quality and fecal water rate of high-dose groups of RH and PRH were significantly increased(P<0.05, P<0.01), the pathological damage of the colon was alleviated to varying degrees, the contents of GAS, MTL, IL-6 and IFN-γ were significantly regressed(P<0.05, P<0.01), and the proportions of CD4+ and CD8+ were significantly increased(P<0.01), although the proportion of Treg showed an upward trend, there was no significant difference. In addition, the results of intestinal flora showed that the number of amplicon sequence variant(ASV) and Alpha diversity were decreased in the model group compared with the control group, and there was a significant difference in Beta diversity, with a decrease in the relative abundance of Lactobacillus and an increase in the relative abundances of Bacillus and Helicobacter. Compared with the model group, the ASV number and Alpha diversity were increased in the high-dose groups of RH and PRH, and there was a trend of regression of Beta diversity to the control group, the relative abundance of Lactobacillus increased, and the relative abundances of Bacillus and Helicobacter decreased. ConclusionRH and PRH can improve dysbacteriosis, promote immune system activation, inhibit the release of inflammatory factors for enhancing the gastrointestinal function, which may be one of the potential mechanisms of their therapeutic effect on constipation.
3.Severity Assessment Parameters and Diagnostic Technologies of Obstructive Sleep Apnea
Zhuo-Zhi FU ; Ya-Cen WU ; Mei-Xi LI ; Ping-Ping YIN ; Hai-Jun LIN ; Fu ZHANG ; Yu-Xiang YANG
Progress in Biochemistry and Biophysics 2025;52(1):147-161
Obstructive sleep apnea (OSA) is an increasingly widespread sleep-breathing disordered disease, and is an independent risk factor for many high-risk chronic diseases such as hypertension, coronary heart disease, stroke, arrhythmias and diabetes, which is potentially fatal. The key to the prevention and treatment of OSA is early diagnosis and treatment, so the assessment and diagnostic technologies of OSA have become a research hotspot. This paper reviews the research progresses of severity assessment parameters and diagnostic technologies of OSA, and discusses their future development trends. In terms of severity assessment parameters of OSA, apnea hypopnea index (AHI), as the gold standard, together with the percentage of duration of apnea hypopnea (AH%), lowest oxygen saturation (LSpO2), heart rate variability (HRV), oxygen desaturation index (ODI) and the emerging biomarkers, constitute a multi-dimensional evaluation system. Specifically, the AHI, which measures the frequency of sleep respiratory events per hour, does not fully reflect the patients’ overall sleep quality or the extent of their daytime functional impairments. To address this limitation, the AH%, which measures the proportion of the entire sleep cycle affected by apneas and hypopneas, deepens our understanding of the impact on sleep quality. The LSpO2 plays a critical role in highlighting the potential severe hypoxic episodes during sleep, while the HRV offers a different perspective by analyzing the fluctuations in heart rate thereby revealing the activity of the autonomic nervous system. The ODI provides a direct and objective measure of patients’ nocturnal oxygenation stability by calculating the number of desaturation events per hour, and the biomarkers offers novel insights into the diagnosis and management of OSA, and fosters the development of more precise and tailored OSA therapeutic strategies. In terms of diagnostic techniques of OSA, the standardized questionnaire and Epworth sleepiness scale (ESS) is a simple and effective method for preliminary screening of OSA, and the polysomnography (PSG) which is based on recording multiple physiological signals stands for gold standard, but it has limitations of complex operations, high costs and inconvenience. As a convenient alternative, the home sleep apnea testing (HSAT) allows patients to monitor their sleep with simplified equipment in the comfort of their own homes, and the cardiopulmonary coupling (CPC) offers a minimal version that simply analyzes the electrocardiogram (ECG) signals. As an emerging diagnostic technology of OSA, machine learning (ML) and artificial intelligence (AI) adeptly pinpoint respiratory incidents and expose delicate physiological changes, thus casting new light on the diagnostic approach to OSA. In addition, imaging examination utilizes detailed visual representations of the airway’s structure and assists in recognizing structural abnormalities that may result in obstructed airways, while sound monitoring technology records and analyzes snoring and breathing sounds to detect the condition subtly, and thus further expands our medical diagnostic toolkit. As for the future development directions, it can be predicted that interdisciplinary integrated researches, the construction of personalized diagnosis and treatment models, and the popularization of high-tech in clinical applications will become the development trends in the field of OSA evaluation and diagnosis.
4.Yishen Tongluo Prescription Ameliorates Oxidative Stress Injury in Mouse Model of Diabetic Kidney Disease via Nrf2/HO-1/NQO1 Signaling Pathway
Yifei ZHANG ; Xuehui BAI ; Zijing CAO ; Zeyu ZHANG ; Jingyi TANG ; Junyu XI ; Shujiao ZHANG ; Shuaixing ZHANG ; Yiran XIE ; Yuqi WU ; Zhongjie LIU ; Weijing LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(5):41-51
ObjectiveTo investigate the effect and mechanism of Yishen Tongluo prescription in protecting mice from oxidative stress injury in diabetic kidney disease (DKD) via the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1)/NAD(P)H quinone oxidoreductase 1 (NQO1) signaling pathway. MethodsSpecific pathogen-free (SPF) male C57BL/6 mice were assigned into a control group (n=10) and a modeling group (n=50). The DKD model was established by intraperitoneal injection of streptozotocin. The mice in the modeling group were randomized into a model group, a semaglutide (40 μg·kg-1) group, and high-, medium-, and low-dose (18.2, 9.1, 4.55 g·kg-1, respectively) Yishen Tongluo prescription groups, with 10 mice in each group. The treatment lasted for 12 weeks. Blood glucose and 24-h urine protein levels were measured, and the kidney index (KI) was calculated. Serum levels of creatinine (SCr), blood urea nitrogen (BUN), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were assessed. The pathological changes in the renal tissue were evaluated by hematoxylin-eosin, periodic acid-Schiff, periodic acid-silver methenamine, and Masson’s trichrome staining. Enzyme-linked immunosorbent assay kits were used to measure the levels of β2-microglobulin (β2-MG), neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), liver fatty acid-binding protein (L-FABP), nitric oxide synthase (NOS), glutathione (GSH), total antioxidant capacity (T-AOC), and 8-hydroxy-2'-deoxyguanosine (8-OHdG). Immunohistochemical staining was performed to examine the expression of Kelch-like ECH-associated protein 1 (Keap1) and malondialdehyde (MDA). Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) and Western blot were employed to determine the mRNA and protein levels, respectively, of factors in the Nrf2/HO-1/NQO1 signaling pathway. ResultsCompared with the control group, the DKD model group showed rises in blood glucose, 24-h urine protein, KI, SCr, BUN, and ALT levels, along with glomerular hypertrophy, renal tubular dilation, thickened basement membrane, mesangial expansion, and collagen deposition. Additionally, the model group showed elevated levels of β2-MG, NGAL, KIM-1, L-FABP, NOS, and 8-OHdG, lowered levels of GSH and T-AOC, up-regulated expression of MDA and Keap1, and down-regulated expression of Nrf2, HO-1, NQO1, and glutamate-cysteine ligase catalytic subunit (GCLC) (P<0.05). Compared with the model group, the semaglutide group and the medium- and high-dose Yishen Tongluo prescription groups showed reductions in blood glucose, 24-h urine protein, KI, SCr, BUN, and ALT levels, along with alleviated pathological injuries in the renal tissue. In addition, the three groups showed lowered levels of β2-MG, NGAL, KIM-1, L-FABP, NOS, and 8-OHdG, elevated levels of GSH and T-AOC, down-regulated expression of MDA and Keap1, and up-regulated expression of Nrf2, HO-1, NQO1, and GCLC (P<0.05). ConclusionYishen Tongluo prescription exerts renoprotective effects in the mouse model of DKD by modulating the Nrf2/HO-1/NQO1 signaling pathway, mitigating oxidative stress, and reducing renal tubular injuries.
5.Effect of Huangling Jidu Xizhuo Granules on NLRP3, Intestinal Flora and Short-term Prognosis in Patients with Gout
Dandan TIAN ; Shanping WANG ; Li YANG ; Tingting ZHANG ; Xi CHEN ; Chuanbing HUANG
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(5):150-156
ObjectiveTo investigate the effects of retention enema with Huangling Jiedu Xiezhuo granules(HJXG) on Nod-like receptor protein 3(NLRP3), intestinal flora, and short-term prognosis in patients with gout. MethodsA total of 60 patients with gout admitted to the hospital from January 2021 to December 2023 were selected and divided into a control group and an observation group according to the random number table method, with 30 cases in each group. The control group was treated with febuxostat, and the observation group was treated with retention enema with HJXG on the basis of the control group. After 14 days of continuous treatment, the clinical efficacy, traditional Chinese medicine (TCM) syndrome score, and visual analogue scale (VAS) pain index of the two groups were compared, and serum creatinine(SCr), blood urea nitrogen(BUN), uric acid(UA), cystatin C(CysC), β2- microglobulin(β2-MG), glomerular filtration rate test(GFR), creatinine clearance rate (Ccr), erythrocyte sedimentation rate(ESR), hypersensitive C-reactive protein,(hs-CRP), interleukin 6(IL-6), interleukin-1β(IL-1β), interleukin-18 (IL-18), NLRP3 inflammasome levels, and the number of intestinal flora were detected in the two groups. The prognosis of patients was followed up within 12 weeks. COX regression analysis was used to analyze the effect of short-term prognosis. ResultsAfter treatment, TCM syndrome scores and VAS pain index in both groups were reduced (P<0.05), and TCM syndrome scores in the observation group were significantly lower than those in the control group. After treatment, ESR, hs-CRP, IL-6, NLRP3, IL-18, and IL-1β were significantly decreased in both groups (P<0.01), and the levels of IL-6, ESR, NLRP3, and IL-18 were significantly improved in the observation group compared with the control group (P<0.05). BUN, SCr, UA, β2-MG, GFR indexes in both groups were significantly lower after treatment, Ccr indexes in both groups were significantly higher after treatment, and the levels of SCr, UA, CysC, and Ccr in the observation group were significantly better than those in the control group (P<0.05). After treatment, the intestinal flora in both groups was improved, and the observation group was significantly improved compared with the control group in terms of Lactobacillus, Proteus, Bacteroides, and Escherichia coli (P<0.05). COX regression analysis showed that retention enema with HJXG could reduce the risk of poor short-term prognosis in patients with gout compared with Western medicine alone. ConclusionThe retention enema with HJXG can improve the curative effect of patients with gout, improve the TCM syndromes, reduce inflammation, and enhance renal function, intestinal flora, and short-term prognosis.
6.Optimization of drug management model for investigator-initiated trial with benchmarking analysis
Yufei XI ; Tianxiao WANG ; Xue ZHANG ; Yingzhuo DING ; Li YAN ; Feng JIANG ; Xiangui HE ; Jiannan HUANG ; Qin LI
China Pharmacy 2025;36(3):280-284
OBJECTIVE To optimize the management model of drugs used in investigator-initiated trial (IIT). METHODS With benchmarking analysis, based on the practical work experience of a tertiary specialized hospital in the field of IIT drug management in Shanghai, a thorough review was conducted, involving relevant laws, regulations, and academic literature to establish benchmark criteria and the evaluation standards. Starting from the initiation of IIT projects, a detailed comparative analysis of key processes was carried out, such as the receipt, storage, distribution, use and recycling of drugs for trial. The deficiencies in the current management of IIT drugs were reviewed in detail and a series of optimization suggestions were put forward. RESULTS It was found that the authorized records of drug management were missing, the training before project implementation was insufficient, and the records of receipt and acceptance of IIT drugs were incomplete. In light of these existing problems, improvement measures were put forward, including strengthening the training of drug administrators and stipulating that only drug administrators with pharmacist qualifications be eligible to inspect and accept drugs, etc. The related systems were improved, and 17 key points of quality control for the management of IIT drugs were developed. CONCLUSIONS A preliminary IIT drug management system for medical institutions has been established, which helps to improve the institutional X2023076) framework of medical institutions in this field.
7.Principles, technical specifications, and clinical application of lung watershed topography map 2.0: A thoracic surgery expert consensus (2024 version)
Wenzhao ZHONG ; Fan YANG ; Jian HU ; Fengwei TAN ; Xuening YANG ; Qiang PU ; Wei JIANG ; Deping ZHAO ; Hecheng LI ; Xiaolong YAN ; Lijie TAN ; Junqiang FAN ; Guibin QIAO ; Qiang NIE ; Mingqiang KANG ; Weibing WU ; Hao ZHANG ; Zhigang LI ; Zihao CHEN ; Shugeng GAO ; Yilong WU
Chinese Journal of Clinical Thoracic and Cardiovascular Surgery 2025;32(02):141-152
With the widespread adoption of low-dose CT screening and the extensive application of high-resolution CT, the detection rate of sub-centimeter lung nodules has significantly increased. How to scientifically manage these nodules while avoiding overtreatment and diagnostic delays has become an important clinical issue. Among them, lung nodules with a consolidation tumor ratio less than 0.25, dominated by ground-glass shadows, are particularly worthy of attention. The therapeutic challenge for this group is how to achieve precise and complete resection of nodules during surgery while maximizing the preservation of the patient's lung function. The "watershed topography map" is a new technology based on big data and artificial intelligence algorithms. This method uses Dicom data from conventional dose CT scans, combined with microscopic (22-24 levels) capillary network anatomical watershed features, to generate high-precision simulated natural segmentation planes of lung sub-segments through specific textures and forms. This technology forms fluorescent watershed boundaries on the lung surface, which highly fit the actual lung anatomical structure. By analyzing the adjacent relationship between the nodule and the watershed boundary, real-time, visually accurate positioning of the nodule can be achieved. This innovative technology provides a new solution for the intraoperative positioning and resection of lung nodules. This consensus was led by four major domestic societies, jointly with expert teams in related fields, oriented to clinical practical needs, referring to domestic and foreign guidelines and consensus, and finally formed after multiple rounds of consultation, discussion, and voting. The main content covers the theoretical basis of the "watershed topography map" technology, indications, operation procedures, surgical planning details, and postoperative evaluation standards, aiming to provide scientific guidance and exploration directions for clinical peers who are currently or plan to carry out lung nodule resection using the fluorescent microscope watershed analysis method.
8.Mechanism of Yishen Tongluo Formula regulating the TLR4/MyD88/NF-κB signaling pathway to ameliorate pyroptosis in diabetic nephropathy mice
Yifei ZHANG ; Zijing CAO ; Zeyu ZHANG ; Xuehui BAI ; Jingyi TANG ; Junyu XI ; Jiayi WANG ; Yiran XIE ; Yuqi WU ; Xi GUO ; Zhongjie LIU ; Weijing LIU
Journal of Beijing University of Traditional Chinese Medicine 2025;48(1):21-33
Objective:
To investigate the mechanism of Yishen Tongluo Formula in ameliorating renal pyroptosis in diabetic nephropathy mice by regulating the toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)/nuclear factor-κB (NF-κB) signaling pathway.
Methods:
Sixty C57BL/6 male mice were randomly divided into control (10 mice) and intervention groups (50 mice) using random number table method. The diabetes nephropathy model was established by intraperitoneally injecting streptozotocin(50 mg/kg). After modeling, the intervention group was further divided into model, semaglutide (40 μg/kg), and high-, medium-, and low-dose Yishen Tongluo Formula groups (15.6, 7.8, and 3.9 g/kg, respectively) using random number table method. The high-, medium-, and low-dose Yishen Tongluo Formula groups were administered corresponding doses of medication by gavage, the semaglutide group received a subcutaneous injection of semaglutide injection, and the control group and model groups were administered distilled water by gavage for 12 consecutive weeks. Random blood glucose levels of mice in each group were monitored, and the 24-h urinary protein content was measured using biochemical method every 4 weeks; after treatment, the serum creatinine and urea nitrogen levels were measured using biochemical method. The weight of the kidneys was measured, and the renal index was calculated. Hematoxylin and eosin, periodic acid-Schiff, periodic Schiff-methenamine, and Masson staining were used to observe the pathological changes in renal tissue. An enzyme-linked immunosorbent assay was used to detect urinary β2-microglobulin (β2-MG), neutrophil gelatinase-associated lipocalin (NGAL), and kidney injury molecule-1 (KIM-1) levels. Western blotting and real-time fluorescence PCR were used to detect the relative protein and mRNA expression levels of nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3 (NLRP3), Caspase-1, gasdermin D (GSDMD), interleukin-1β (IL-1β), and interleukin-18 (IL-18) in renal tissue. Immunohistochemistry was used to detect the proportion of protein staining area of the TLR4, MyD88, and NF-κB in renal tissue.
Results:
Compared with the control group, the random blood glucose, 24-h urinary protein, serum creatinine, urea nitrogen, and renal index of the model group increased, and the urine β2-MG, NGAL, and KIM-1 levels increased. The relative protein and mRNA expression levels of NLRP3, Caspase-1, GSDMD, IL-1β, and IL-18 in renal tissue increased, and the proportion of TLR4, MyD88, and NF-κB protein positive staining areas increased (P<0.05). Pathological changes such as glomerular hypertrophy were observed in the renal tissue of the model group. Compared with the model group, the Yishen Tongluo Formula high-dose group showed a decrease in random blood glucose after 12 weeks of treatment (P<0.05). The Yishen Tongluo Formula high- and medium-dose groups showed a decrease in 24-h urinary protein, creatinine, urea nitrogen, and renal index, as well as decreased β2-MG, NGAL, and KIM-1 levels. NLRP3, Caspase-1, GSDMD, IL-1 β, and IL-18 relative protein and mRNA expression levels were also reduced, and the proportion of TLR4, MyD88, and NF-κB protein positive staining areas was reduced (P<0.05). Pathological damage to renal tissue was ameliorated.
Conclusion
Yishen Tongluo Formula may exert protective renal effects by inhibiting renal pyroptosis and alleviating tubular interstitial injury in diabetic nephropathy mice by regulating the TLR4/MyD88/NF-κB signaling pathway.
9.Mechanism of circRNA_0076631 mediated diabetic retinopathy by regulating pyroptosis
Yanyan ZHANG ; Yanyan WANG ; Xueli SHAO ; Quanyong YI ; Yahui XI
International Eye Science 2025;25(3):351-358
AIM: To investigate the role of pyroptosis in the development of diabetic retinopathy(DR)and to explore the regulatory mechanism by which circular RNA(circRNA)and its targeted microRNA(miRNA)mediate pyroptosis in DR, providing new therapeutic targets and strategies for the prevention and treatment of DR.METHODS: A streptozotocin(STZ)-induced model of type 1 diabetes in SD rats was established. The expression of circRNA_0076631, miR-214, and pyroptosis-related factors were measured in retinal tissues. CCK-8 and tube formation assays were used to detect the effect of different concentration of glucose on cell proliferation and angiogenic abilities of human retinal microvascular endothelial cells(HRMECs). The expression levels of circRNA_0076631, miR-214, and pyroptosis-related markers were evaluated through qRT-PCR and Western blot analysis, with additional experiments conducted following circRNA_0076631 knockdown to assess its effect on pyroptosis markers. Previous bioinformatics analysis and luciferase reporter assays identified a shared binding site among circRNA_0076631, miR-214, and caspase-1. To clarify the interaction between these molecules, co-transfection experiments using circRNA_0076631 inhibitors(ASO-circRNA_0076631), miR-214 overexpression transfection reagent, and miR-214 inhibitors(AMO-miR-214)were conducted to elucidate the regulatory pathway involved in DR.RESULTS: Both the diabetic rat model and D-glucose-treated HRMECs showed significantly elevated expression of circRNA_0076631 and pyroptosis-related factors(NLRP3, caspase-1, and IL-1β), while miR-214 expression was reduced(all P<0.05). The mRNA expression of pyroptosis-related factors caspase-1 was reduced after the overexpression of miR-214, and it was upregulated after the inhibition of miR-214(all P<0.05). Knockdown of circRNA_0076631 reduced the mRNA expression of pyroptosis markers caspase-1(P<0.05). Co-transfection experiments revealed that the inhibition circRNA_0076631 suppressed pyroptosis(all P<0.05), but this suppression was reversed upon co-transfection with miR-214 inhibitors, leading to increased mRNA expression of the pyroptosis marker caspase-1(all P<0.05).CONCLUSION: The circRNA_0076631 and pyroptosis play critical roles in the pathogenesis of DR, and circRNA_0076631 may regulate pyroptosis by modulating miR-214, which in turn influences the expression of caspase-1 in the pyroptosis signaling pathway, thereby contributing to DR progression. The circRNA_0076631 may serve as a novel therapeutic target, providing new insights for the prevention and treatment of DR.
10.Mechanism of circRNA_0076631 mediated diabetic retinopathy by regulating pyroptosis
Yanyan ZHANG ; Yanyan WANG ; Xueli SHAO ; Quanyong YI ; Yahui XI
International Eye Science 2025;25(3):351-358
AIM: To investigate the role of pyroptosis in the development of diabetic retinopathy(DR)and to explore the regulatory mechanism by which circular RNA(circRNA)and its targeted microRNA(miRNA)mediate pyroptosis in DR, providing new therapeutic targets and strategies for the prevention and treatment of DR.METHODS: A streptozotocin(STZ)-induced model of type 1 diabetes in SD rats was established. The expression of circRNA_0076631, miR-214, and pyroptosis-related factors were measured in retinal tissues. CCK-8 and tube formation assays were used to detect the effect of different concentration of glucose on cell proliferation and angiogenic abilities of human retinal microvascular endothelial cells(HRMECs). The expression levels of circRNA_0076631, miR-214, and pyroptosis-related markers were evaluated through qRT-PCR and Western blot analysis, with additional experiments conducted following circRNA_0076631 knockdown to assess its effect on pyroptosis markers. Previous bioinformatics analysis and luciferase reporter assays identified a shared binding site among circRNA_0076631, miR-214, and caspase-1. To clarify the interaction between these molecules, co-transfection experiments using circRNA_0076631 inhibitors(ASO-circRNA_0076631), miR-214 overexpression transfection reagent, and miR-214 inhibitors(AMO-miR-214)were conducted to elucidate the regulatory pathway involved in DR.RESULTS: Both the diabetic rat model and D-glucose-treated HRMECs showed significantly elevated expression of circRNA_0076631 and pyroptosis-related factors(NLRP3, caspase-1, and IL-1β), while miR-214 expression was reduced(all P<0.05). The mRNA expression of pyroptosis-related factors caspase-1 was reduced after the overexpression of miR-214, and it was upregulated after the inhibition of miR-214(all P<0.05). Knockdown of circRNA_0076631 reduced the mRNA expression of pyroptosis markers caspase-1(P<0.05). Co-transfection experiments revealed that the inhibition circRNA_0076631 suppressed pyroptosis(all P<0.05), but this suppression was reversed upon co-transfection with miR-214 inhibitors, leading to increased mRNA expression of the pyroptosis marker caspase-1(all P<0.05).CONCLUSION: The circRNA_0076631 and pyroptosis play critical roles in the pathogenesis of DR, and circRNA_0076631 may regulate pyroptosis by modulating miR-214, which in turn influences the expression of caspase-1 in the pyroptosis signaling pathway, thereby contributing to DR progression. The circRNA_0076631 may serve as a novel therapeutic target, providing new insights for the prevention and treatment of DR.


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