- 1. School of Medicine, Shihezi University, Shihezi 832003, China;
- 2. Department of Ophthalmology, General Hospital of Xinjiang Military Region, Urumqi 834000, China;
Tian Yanming,
Email: tianyanming@163.com
Diabetic retinopathy (DR) is a serious complication of diabetes mellitus that not only impairs vision and quality of life but has also emerged as a leading cause of blindness in working-age individuals. Long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (LncMALAT1) is a non-coding RNA molecule that regulates gene expression and has been implicated in the pathogenesis and progression of DR. It exerts its effects through the modulation of various pathological processes, including inflammation, oxidative stress, angiogenesis, and apoptosis. Notably, alterations in the expression levels of LncMALAT1 may serve as potential biomarkers for the early diagnosis of DR. Furthermore, interventions targeting LncMALAT1, employing antioxidants, anti-angiogenic agents, traditional Chinese medicine, and gene therapy, present promising avenues for its potential development as an effective therapeutic target for DR.
| 1. | GBD 2021 Diabetes Collaborators. Global, regional, and national burden of diabetes from 1990 to 2021, with projections of prevalence to 2050: a systematic analysis for the Global Burden of Disease Study 2021[J]. Lancet, 2023, 402(10397): 203-234. DOI: 10.1016/S0140-6736(23)01301-6. |
| 2. | Teo Z L, Tham YC, Yu M, et al. Global prevalence of diabetic retinopathy and projection of burden through 2045: systematic review and meta-analysis[J]. Ophthalmology, 2021, 128(11): 1580-1591. DOI: 10.1016/j.ophtha.2021.04.027. |
| 3. | Sun H, Saeedi P, Karuranga S, et al. IDF diabetes atlas: global, regional and country-level diabetes prevalence estimates for 2021 and projections for 2045[J/OL]. Diabetes Res Clin Pract, 2022, 183: 109119[2021-12-06]. https://pubmed.ncbi.nlm.nih.gov/34879977/. DOI: 10.1016/j.diabres.2023.110945. |
| 4. | 中华医学会眼科学分会眼底病学组, 中国医师协会眼科医师分会眼底病学组. 我国糖尿病视网膜病变临床诊疗指南(2022年)-基于循证医学修订[J]. 中华眼底病杂志, 2023, 39(2): 99-124. DOI: 10.3760/cma.j.cn511434-20230110-00018.Fundus Disease Group of Ophthalmological Society of Chinese Medical Association, Fundus Disease Group of Ophthalmologist Branch of Chinese Medical Doctor Association. Evidence-based guidelines for diagnosis and treatment of diabetic retinopathy in China (2022)-revised based on evidence-based medicine[J]. Chin J Ocul Fundus Dis, 2023, 39(2): 99-124. DOI: 10.3760/cma.j.cn511434-20230110-00018. |
| 5. | Statello L, Guo CJ, Chen LL, et al. Gene regulation by long non-coding RNAs and its biological functions[J]. Nat Rev Mol Cell Biol, 2021, 22(2): 96-118. DOI: 10.1038/s41580-020-00315-9. |
| 6. | Geng M, Liu W, Li J, et al. LncRNA as a regulator in the development of diabetic complications[J/OL]. Front Endocrinol (Lausanne), 2024, 15: 1324393[2024-02-08]. https://pubmed.ncbi.nlm.nih.gov/38390204/. DOI: 10.3389/fendo.2024.1324393. |
| 7. | Antonetti DA, Silva PS, Stitt AW. Current understanding of the molecular and cellular pathology of diabetic retinopathy[J]. Nat Rev Endocrinol, 2021, 17(4): 195-206. DOI: 10.1038/s41574-020-00451-4. |
| 8. | Schmidt LH, Spieker T, Koschmieder S, et al. The long noncoding MALAT-1 RNA indicates a poor prognosis in non-small cell lung cancer and induces migration and tumor growth[J]. J Thorac Oncol, 2011, 6(12): 1984-1992. DOI: 10.1097/JTO.0b013e3182307eac. |
| 9. | Su Y, Wu H, Pavlosky A, et al. Regulatory non-coding RNA: new instruments in the orchestration of cell death[J/OL]. Cell Death Dis, 2016, 7(8): e2333[2016-08-11]. https://pubmed.ncbi.nlm.nih.gov/27512954/. DOI: 10.1038/cddis.2016.210. |
| 10. | Yan B, Tao ZF, Li XM, et al. Aberrant expression of long noncoding RNAs in early diabetic retinopathy[J]. Invest Ophthalmol Vis Sci, 2014, 55(2): 941-951. DOI: 10.1167/iovs.13-13221. |
| 11. | Biswas S, Thomas AA, Chen S, et al. MALAT1: An epigenetic regulator of Inflammation in diabetic retinopathy[J/OL]. Sci Rep, 2018, 8(1): 6526[2018-04-25]. https://pubmed.ncbi.nlm.nih.gov/29695738/. DOI: 10.1038/s41598-018-24907-w. |
| 12. | Liu JY, Yao J, Li XM, et al. Pathogenic role of lncRNA-MALAT1 in endothelial cell dysfunction in diabetes mellitus[J/OL]. Cell Death Dis, 2014, 5(10): e1506[2014-10-30]. https://pubmed.ncbi.nlm.nih.gov/25356875/. DOI: 10.1038/cddis.2014.466. |
| 13. | Zhang YL, Hu HY, You ZP, et al. Targeting long non-coding RNA MALAT1 alleviates retinal neurodegeneration in diabetic mice[J]. Int J Ophthalmol, 2020, 13(2): 213-219. DOI: 10.18240/ijo.2020.02.03. |
| 14. | Kovoor E, Chauhan S K, Hajrasouliha A. Role of inflammatory cells in pathophysiology and management of diabetic retinopathy[J]. Surv Ophthalmol, 2022, 67(6): 1563-1573. DOI: 10.1016/j.survophthal.2022.07.008. |
| 15. | Haydinger CD, Oliver GF, Ashander LM, et al. Oxidative stress and its regulation in diabetic retinopathy[J/OL]. Antioxidants (Basel), 2023, 12(8): 1649[2023-08-21]. https://pubmed.ncbi.nlm.nih.gov/37627644/. DOI: 10.3390/antiox12081649. |
| 16. | Kang Q, Yang C. Oxidative stress and diabetic retinopathy: Molecular mechanisms, pathogenetic role and therapeutic implications[J/OL]. Redox Biol, 2020, 37: 101799[2020-11-13]. https://pubmed.ncbi.nlm.nih.gov/33248932/. DOI: 10.1016/j.redox.2020.101799. |
| 17. | Tian Y, Cheng W, Wang H, et al. Ascorbic acid protects retinal pigment epithelial cells from high glucose by inhibiting the NF-κB signal pathway through MALAT1/IGF2BP3 axis[J/OL]. Diabet Med, 2023, 40(5): e15050[2023-01-20]. https://pubmed.ncbi.nlm.nih.gov/36661363/. DOI: 10.1111/dme.15050. |
| 18. | Jiang X, Liu Y, Wang Y, et al. Long non-coding RNA MALAT1 is involved in retinal pigment epithelial cell damage caused by high glucose treatment[J]. Mol Med Rep, 2022, 25(5): 177. DOI: 10.3892/mmr.2022.12693. |
| 19. | Wang Y, Wang L, Guo H, et al. Knockdown of MALAT1 attenuates high-glucose-induced angiogenesis and inflammation via endoplasmic reticulum stress in human retinal vascular endothelial cells[J/OL]. Biomed Pharmacother, 2020, 124: 109699[2020-01-25]. https://pubmed.ncbi.nlm.nih.gov/31986419/. DOI: 10.1016/j.biopha.2019.109699. |
| 20. | Radhakrishnan R, Kowluru RA. Long noncoding RNA MALAT1 and regulation of the antioxidant defense system in diabetic retinopathy[J]. Diabetes, 2021, 70(1): 227-239. DOI: 10.2337/db20-0375. |
| 21. | Ling S, Birnbaum Y, Nanhwan MK, et al. MicroRNA-dependent cross-talk between VEGF and HIF1α in the diabetic retina[J]. Cell Signal, 2013, 25(12): 2840-2847. DOI: 10.1016/j.cellsig.2013.08.039. |
| 22. | Zhao R, Qian L, Jiang L. miRNA-dependent cross-talk between VEGF and Ang-2 in hypoxia-induced microvascular dysfunction[J]. Biochem Biophys Res Commun, 2014, 452(3): 428-435. DOI: 10.1016/j.bbrc.2014.08.096. |
| 23. | Moore JB 4th, Uchida S. Functional characterization of long noncoding RNAs[J]. Curr Opin Cardiol, 2020, 35(3): 199-206. DOI: 10.1097/HCO.0000000000000725. |
| 24. | Zhao W, Liu Y, Li C, et al. Mechanisms of MALAT1 regulating proliferative diabetic retinopathy via targeting miR-126-5p[J]. Am J Transl Res, 2023, 15(5): 3279-3289. |
| 25. | Chen Z, Yang J, Gao Y, et al. LncRNA MALAT1 aggravates the retinal angiogenesis via miR-320a/HIF-1α axis in diabetic retinopathy[J/OL]. Exp Eye Res, 2022, 218: 108984[2022-02-21]. https://pubmed.ncbi.nlm.nih.gov/35202706/. DOI: 10.1016/j.exer.2022.108984. |
| 26. | Li X. lncRNA MALAT1 promotes diabetic retinopathy by upregulating PDE6G via miR-378a-3p[J]. Arch Physiol Biochem, 2024, 130(2): 119-127. DOI: 10.1080/13813455.2021.1985144. |
| 27. | Tan A, Li T, Ruan L, et al. Knockdown of malat1 alleviates high-glucose-induced angiogenesis through regulating miR-205-5p/VEGF-A axis[J/OL]. Exp Eye Res, 2021, 207: 1085859[2021-04-20]. https://pubmed.ncbi.nlm.nih.gov/33887222/. DOI: 10.1016/j.exer.2021.108585. |
| 28. | Han N, Tian W, Yu N, et al. YAP1 is required for the angiogenesis in retinal microvascular endothelial cells via the inhibition of MALAT1-mediated miR-200b-3p in high glucose-induced diabetic retinopathy[J]. J Cell Physiol, 2020, 235(2): 1309-1320. DOI: 10.1002/jcp.29047. |
| 29. | Liu P, Jia SB, Shi JM, et al. LncRNA-MALAT1 promotes neovascularization in diabetic retinopathy through regulating miR-125b/VE-cadherin axis[J/OL]. Biosci Rep, 2019, 39(5): BSR20181469[2019-05-15]. https://pubmed.ncbi.nlm.nih.gov/30988072/. DOI: 10.1042/BSR20181469. |
| 30. | Arun G, Aggarwal D, Spector DL. MALAT1 long non-coding RNA: functional implications[J]. Noncoding RNA, 2020, 6(2): 22. DOI: 10.3390/ncrna6020022. |
| 31. | 杨大伟, 黄庆, 周连吉, 等. LncRNA MALAT1在2型糖尿病患者中的表达及临床意义[J]. 中国老年学杂志, 2022, 42(1): 15-18. DOI: 10.3969/j.issn.1005-9202.2022.01.004.Yang DW, Huang Q, Zhou LJ, et al. Expression and clinical significance of LncRNA MALAT1 in patients with type 2 diabetes[J]. Chinese Journal of Gerontology, 2022, 42(1): 15-18. DOI: 10.3969/j.issn.1005-9202.2022.01.004. |
| 32. | Li J, Wang C, Shao C, et al. Expression and diagnostic value of lncRNA MALAT1 and NLRP3 in lower limb atherosclerosis in diabetes[J]. BMC Endocr Disord, 2024, 24(1): 28. DOI: 10.1186/s12902-024-01557-w. |
| 33. | Rajabinejad M, Asadi G, Ranjbar S, et al. The MALAT1-H19/miR-19b-3p axis can be a fingerprint for diabetic neuropathy[J]. Immunol Lett, 2022, 245: 69-78. DOI: 10.1016/j.imlet.2022.03.004. |
| 34. | Zhou LJ, Yang DW, Ou LN, et al. Circulating expression level of lncRNA Malat1 in diabetic kidney disease patients and its clinical significance[J/OL]. J Diabetes Res, 2020, 2020: 4729019[2020-08-01]. https://pubmed.ncbi.nlm.nih.gov/32832561/. DOI: 10.1155/2020/4729019. |
| 35. | Su X, Huang H, Lai J, et al. Long noncoding RNAs as potential diagnostic biomarkers for diabetes mellitus and complications: a systematic review and meta-analysis[J/OL]. J Diabetes, 2023, 16(2): e13510[2023-12-23]. https://pubmed.ncbi.nlm.nih.gov/38140829/. DOI: 10.1111/1753-0407.13510. |
| 36. | Shaker OG, Abdelaleem OO, Mahmoud RH, et al. Diagnostic and prognostic role of serum miR-20b, miR-17-3p, HOTAIR, and MALAT1 in diabetic retinopathy[J]. IUBMB life, 2019, 71(3): 310-320. DOI: 10.1002/iub.1970. |
| 37. | 邱煜焱, 杨旭, 苟文军, 等. 2型糖尿病患者血清lncRNA MALAT1表达水平与视网膜病变的关系[J]. 眼科新进展, 2022, 42(12): 971-974. DOI: 10.13389/j.cnki.rao.2022.0199.Qiu YY, Yang X, Gou WJ, et al. Relationship between the expression level of long non-coding ribonucleic acid metastasis associated lung adenocarcinoma transcript 1 in serum and retinopathy in patients with type 2 diabetes mellitus[J]. Rec Adv Ophthalmol, 2022, 42(12): 971-974. DOI: 10.13389/j.cnki.rao.2022.0199. |
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- 1. GBD 2021 Diabetes Collaborators. Global, regional, and national burden of diabetes from 1990 to 2021, with projections of prevalence to 2050: a systematic analysis for the Global Burden of Disease Study 2021[J]. Lancet, 2023, 402(10397): 203-234. DOI: 10.1016/S0140-6736(23)01301-6.
- 2. Teo Z L, Tham YC, Yu M, et al. Global prevalence of diabetic retinopathy and projection of burden through 2045: systematic review and meta-analysis[J]. Ophthalmology, 2021, 128(11): 1580-1591. DOI: 10.1016/j.ophtha.2021.04.027.
- 3. Sun H, Saeedi P, Karuranga S, et al. IDF diabetes atlas: global, regional and country-level diabetes prevalence estimates for 2021 and projections for 2045[J/OL]. Diabetes Res Clin Pract, 2022, 183: 109119[2021-12-06]. https://pubmed.ncbi.nlm.nih.gov/34879977/. DOI: 10.1016/j.diabres.2023.110945.
- 4. 中华医学会眼科学分会眼底病学组, 中国医师协会眼科医师分会眼底病学组. 我国糖尿病视网膜病变临床诊疗指南(2022年)-基于循证医学修订[J]. 中华眼底病杂志, 2023, 39(2): 99-124. DOI: 10.3760/cma.j.cn511434-20230110-00018.Fundus Disease Group of Ophthalmological Society of Chinese Medical Association, Fundus Disease Group of Ophthalmologist Branch of Chinese Medical Doctor Association. Evidence-based guidelines for diagnosis and treatment of diabetic retinopathy in China (2022)-revised based on evidence-based medicine[J]. Chin J Ocul Fundus Dis, 2023, 39(2): 99-124. DOI: 10.3760/cma.j.cn511434-20230110-00018.
- 5. Statello L, Guo CJ, Chen LL, et al. Gene regulation by long non-coding RNAs and its biological functions[J]. Nat Rev Mol Cell Biol, 2021, 22(2): 96-118. DOI: 10.1038/s41580-020-00315-9.
- 6. Geng M, Liu W, Li J, et al. LncRNA as a regulator in the development of diabetic complications[J/OL]. Front Endocrinol (Lausanne), 2024, 15: 1324393[2024-02-08]. https://pubmed.ncbi.nlm.nih.gov/38390204/. DOI: 10.3389/fendo.2024.1324393.
- 7. Antonetti DA, Silva PS, Stitt AW. Current understanding of the molecular and cellular pathology of diabetic retinopathy[J]. Nat Rev Endocrinol, 2021, 17(4): 195-206. DOI: 10.1038/s41574-020-00451-4.
- 8. Schmidt LH, Spieker T, Koschmieder S, et al. The long noncoding MALAT-1 RNA indicates a poor prognosis in non-small cell lung cancer and induces migration and tumor growth[J]. J Thorac Oncol, 2011, 6(12): 1984-1992. DOI: 10.1097/JTO.0b013e3182307eac.
- 9. Su Y, Wu H, Pavlosky A, et al. Regulatory non-coding RNA: new instruments in the orchestration of cell death[J/OL]. Cell Death Dis, 2016, 7(8): e2333[2016-08-11]. https://pubmed.ncbi.nlm.nih.gov/27512954/. DOI: 10.1038/cddis.2016.210.
- 10. Yan B, Tao ZF, Li XM, et al. Aberrant expression of long noncoding RNAs in early diabetic retinopathy[J]. Invest Ophthalmol Vis Sci, 2014, 55(2): 941-951. DOI: 10.1167/iovs.13-13221.
- 11. Biswas S, Thomas AA, Chen S, et al. MALAT1: An epigenetic regulator of Inflammation in diabetic retinopathy[J/OL]. Sci Rep, 2018, 8(1): 6526[2018-04-25]. https://pubmed.ncbi.nlm.nih.gov/29695738/. DOI: 10.1038/s41598-018-24907-w.
- 12. Liu JY, Yao J, Li XM, et al. Pathogenic role of lncRNA-MALAT1 in endothelial cell dysfunction in diabetes mellitus[J/OL]. Cell Death Dis, 2014, 5(10): e1506[2014-10-30]. https://pubmed.ncbi.nlm.nih.gov/25356875/. DOI: 10.1038/cddis.2014.466.
- 13. Zhang YL, Hu HY, You ZP, et al. Targeting long non-coding RNA MALAT1 alleviates retinal neurodegeneration in diabetic mice[J]. Int J Ophthalmol, 2020, 13(2): 213-219. DOI: 10.18240/ijo.2020.02.03.
- 14. Kovoor E, Chauhan S K, Hajrasouliha A. Role of inflammatory cells in pathophysiology and management of diabetic retinopathy[J]. Surv Ophthalmol, 2022, 67(6): 1563-1573. DOI: 10.1016/j.survophthal.2022.07.008.
- 15. Haydinger CD, Oliver GF, Ashander LM, et al. Oxidative stress and its regulation in diabetic retinopathy[J/OL]. Antioxidants (Basel), 2023, 12(8): 1649[2023-08-21]. https://pubmed.ncbi.nlm.nih.gov/37627644/. DOI: 10.3390/antiox12081649.
- 16. Kang Q, Yang C. Oxidative stress and diabetic retinopathy: Molecular mechanisms, pathogenetic role and therapeutic implications[J/OL]. Redox Biol, 2020, 37: 101799[2020-11-13]. https://pubmed.ncbi.nlm.nih.gov/33248932/. DOI: 10.1016/j.redox.2020.101799.
- 17. Tian Y, Cheng W, Wang H, et al. Ascorbic acid protects retinal pigment epithelial cells from high glucose by inhibiting the NF-κB signal pathway through MALAT1/IGF2BP3 axis[J/OL]. Diabet Med, 2023, 40(5): e15050[2023-01-20]. https://pubmed.ncbi.nlm.nih.gov/36661363/. DOI: 10.1111/dme.15050.
- 18. Jiang X, Liu Y, Wang Y, et al. Long non-coding RNA MALAT1 is involved in retinal pigment epithelial cell damage caused by high glucose treatment[J]. Mol Med Rep, 2022, 25(5): 177. DOI: 10.3892/mmr.2022.12693.
- 19. Wang Y, Wang L, Guo H, et al. Knockdown of MALAT1 attenuates high-glucose-induced angiogenesis and inflammation via endoplasmic reticulum stress in human retinal vascular endothelial cells[J/OL]. Biomed Pharmacother, 2020, 124: 109699[2020-01-25]. https://pubmed.ncbi.nlm.nih.gov/31986419/. DOI: 10.1016/j.biopha.2019.109699.
- 20. Radhakrishnan R, Kowluru RA. Long noncoding RNA MALAT1 and regulation of the antioxidant defense system in diabetic retinopathy[J]. Diabetes, 2021, 70(1): 227-239. DOI: 10.2337/db20-0375.
- 21. Ling S, Birnbaum Y, Nanhwan MK, et al. MicroRNA-dependent cross-talk between VEGF and HIF1α in the diabetic retina[J]. Cell Signal, 2013, 25(12): 2840-2847. DOI: 10.1016/j.cellsig.2013.08.039.
- 22. Zhao R, Qian L, Jiang L. miRNA-dependent cross-talk between VEGF and Ang-2 in hypoxia-induced microvascular dysfunction[J]. Biochem Biophys Res Commun, 2014, 452(3): 428-435. DOI: 10.1016/j.bbrc.2014.08.096.
- 23. Moore JB 4th, Uchida S. Functional characterization of long noncoding RNAs[J]. Curr Opin Cardiol, 2020, 35(3): 199-206. DOI: 10.1097/HCO.0000000000000725.
- 24. Zhao W, Liu Y, Li C, et al. Mechanisms of MALAT1 regulating proliferative diabetic retinopathy via targeting miR-126-5p[J]. Am J Transl Res, 2023, 15(5): 3279-3289.
- 25. Chen Z, Yang J, Gao Y, et al. LncRNA MALAT1 aggravates the retinal angiogenesis via miR-320a/HIF-1α axis in diabetic retinopathy[J/OL]. Exp Eye Res, 2022, 218: 108984[2022-02-21]. https://pubmed.ncbi.nlm.nih.gov/35202706/. DOI: 10.1016/j.exer.2022.108984.
- 26. Li X. lncRNA MALAT1 promotes diabetic retinopathy by upregulating PDE6G via miR-378a-3p[J]. Arch Physiol Biochem, 2024, 130(2): 119-127. DOI: 10.1080/13813455.2021.1985144.
- 27. Tan A, Li T, Ruan L, et al. Knockdown of malat1 alleviates high-glucose-induced angiogenesis through regulating miR-205-5p/VEGF-A axis[J/OL]. Exp Eye Res, 2021, 207: 1085859[2021-04-20]. https://pubmed.ncbi.nlm.nih.gov/33887222/. DOI: 10.1016/j.exer.2021.108585.
- 28. Han N, Tian W, Yu N, et al. YAP1 is required for the angiogenesis in retinal microvascular endothelial cells via the inhibition of MALAT1-mediated miR-200b-3p in high glucose-induced diabetic retinopathy[J]. J Cell Physiol, 2020, 235(2): 1309-1320. DOI: 10.1002/jcp.29047.
- 29. Liu P, Jia SB, Shi JM, et al. LncRNA-MALAT1 promotes neovascularization in diabetic retinopathy through regulating miR-125b/VE-cadherin axis[J/OL]. Biosci Rep, 2019, 39(5): BSR20181469[2019-05-15]. https://pubmed.ncbi.nlm.nih.gov/30988072/. DOI: 10.1042/BSR20181469.
- 30. Arun G, Aggarwal D, Spector DL. MALAT1 long non-coding RNA: functional implications[J]. Noncoding RNA, 2020, 6(2): 22. DOI: 10.3390/ncrna6020022.
- 31. 杨大伟, 黄庆, 周连吉, 等. LncRNA MALAT1在2型糖尿病患者中的表达及临床意义[J]. 中国老年学杂志, 2022, 42(1): 15-18. DOI: 10.3969/j.issn.1005-9202.2022.01.004.Yang DW, Huang Q, Zhou LJ, et al. Expression and clinical significance of LncRNA MALAT1 in patients with type 2 diabetes[J]. Chinese Journal of Gerontology, 2022, 42(1): 15-18. DOI: 10.3969/j.issn.1005-9202.2022.01.004.
- 32. Li J, Wang C, Shao C, et al. Expression and diagnostic value of lncRNA MALAT1 and NLRP3 in lower limb atherosclerosis in diabetes[J]. BMC Endocr Disord, 2024, 24(1): 28. DOI: 10.1186/s12902-024-01557-w.
- 33. Rajabinejad M, Asadi G, Ranjbar S, et al. The MALAT1-H19/miR-19b-3p axis can be a fingerprint for diabetic neuropathy[J]. Immunol Lett, 2022, 245: 69-78. DOI: 10.1016/j.imlet.2022.03.004.
- 34. Zhou LJ, Yang DW, Ou LN, et al. Circulating expression level of lncRNA Malat1 in diabetic kidney disease patients and its clinical significance[J/OL]. J Diabetes Res, 2020, 2020: 4729019[2020-08-01]. https://pubmed.ncbi.nlm.nih.gov/32832561/. DOI: 10.1155/2020/4729019.
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