Chidamide improves gefitinib treatment outcomes in NSCLC by attenuating recruitment and immunosuppressive function of myeloid-derived suppressor cells.

Clinical resistance to EGFR tyrosine kinase inhibitors in non-small-cell lung cancer (NSCLC) remains a significant challenge. Recent studies have indicated that the number of myeloid-derived suppressor cells (MDSCs) increases following gefitinib treatment, correlating with a poor patient response in NSCLC. Our study revealed that gefitinib treatment stimulates the production of CCL2, which subsequently enhances monocyte (M)-MDSC migration to tumor sites. Chidamide, a selective inhibitor of the histone deacetylase subtype, counteracted the gefitinib-induced increase in CCL2 levels in tumor cells. Additionally, chidamide down-regulated the expression of CCR2 in M-MDSCs, inhibiting their migration. Furthermore, chidamide attenuated the immunosuppressive function of M-MDSCs both alone and in combination with gefitinib. Chidamide also alleviated tumor immunosuppression by reducing the number of M-MDSCs in LLC-bearing mice, thereby enhancing the antitumor efficacy of gefitinib. In conclusion, our findings suggest that chidamide can improve gefitinib treatment outcomes, indicating that MDSCs are promising targets in NSCLC.

miR-656-3p inhibits melanomas in vitro and in vivo by inducing senescence via inhibiting LMNB2.

BACKGROUND: Ultra-Violet Radiation (UVR) is the most significant exogenous contributor to skin aging. UVB causes the senescence of melanocytes, which results in a permanent arrest in the proliferative process. Senescence is also regarded as a physiological tumor-suppressing mechanism of normal cells. However, the mechanism of the relationship between melanocyte senescence and melanoma was not sufficiently clarified. METHODS: Melanocytes and melanoma cells were irradiated with UVB for the indicated time. The miRNA expression profile of melanocytes were obtained by miRNA sequencing and confirmed by real-time PCR. Cell count kit-8 assays, cell cycle assays were also employed to explore the effect of miR-656-3p and LMNB2 on senescence. Dual-luciferase reporter assays were applied to determine the miRNA targets. Finally, a xenograft model and a photoaging model of mice were conducted to verified the function of miR-656-3p in vivo. RESULTS: Melanoma cells did not alter into a senescence stage and the expressions of miR-656-3p had no significant changes under the same intensity of UVB radiation. miR-656-3p appeared to be upregulated in melanocytes rather than melanoma cells after UVB radiation. miR-656-3p could promote the photoaging of human primary melanocytes by targeting LMNB2. Finally, overexpression of miR-656-3p significantly induced senescence and inhibited the growth of melanomas in vitro and in vivo. CONCLUSION: Our work not only demonstrated the mechanism by which miR-656-3p induced the senescence of melanocytes but also proposed a treatment strategy for melanomas by using miR-656-3p to induce senescence.

Exosomes released by melanocytes modulate fibroblasts to promote keloid formation: a pilot study.

Keloids are a common type of pathological scar as a result of skin healing, which are extremely difficult to prevent and treat without recurrence. The pathological mechanism of keloids is the excessive proliferation of fibroblasts, which synthesize more extracellular matrices (ECMs), including type I/III collagen (COL-1/3), mucopolysaccharides, connective tissue growth factor (CTGF, also known as cellular communication network factor 2 (CCN2)), and fibronectin (FN) in scar tissue, mostly through the abnormal activation of transforming growth factor-|ß (TGF-|ß)/Smads pathway (Finnson et al., 2013; Song et al., 2018). Genetic factors, including race and skin tone, are considered to contribute to keloid formation. The reported incidence of keloids in black people is as high as 16%, whereas white people are less affected. The prevalence ratio of colored people to white people is 5:1||-||15:1 (Rockwell et al., 1989; LaRanger et al., 2019). In addition, keloids have not been reported in albinism patients of any race, and those with darker skin in the same race are more likely to develop this disease (LaRanger et al., 2019). Skin melanocyte activity is significantly different among people with different skin tones. The more active the melanocyte function, the more melanin is produced and the darker the skin. Similarly, in the same individual, the incidence of keloids increases during periods when melanocytes are active, such as adolescence and pregnancy. Keloids rarely appear in areas where melanocytes synthesize less melanin, such as in the palms and soles. Thus, the formation of keloids seems to be closely related to melanocyte activity.

Oncological safety and complication risks of mastectomy with or without breast reconstruction: A Bayesian analysis.

BACKGROUND: Currently, breast cancer patients undergoing mastectomy (MA) have three surgical options: MA only and reconstruction at the time of MA ("immediate," IBR) or at a later time ("delayed," DBR). To assess the oncological safety and complication risks associated with different surgical choices, a systematic review with Bayesian network analysis was conducted. METHODS: Cochrane library, PubMed/MEDLINE, EMBASE, and the China National Knowledge Infrastructure were systematically searched in November 2019. The odds ratios [OR] were estimated for oncological safety (including disease-free survival, overall survival, local recurrence, and distant metastases) and complication risks (including overall complications, surgical site infection, and lymphedema) among MA, IBR, and DBR groups. RESULTS: In the included 51 studies (265,522 patients), reconstruction after MA for IBR or DBR was associated with increased overall survival compared to simple MA (DBR vs. MA: OR 4.12, 95% credible interval [CrI] 1.80-10.01; IBR vs. MA: OR 1.75, 95% CrI 1.32-2.32). Additionally, IBR was associated with a decreased distant metastasis rate compared to MA (IBR vs. MA: OR 0.67, 95% CrI 0.51-0.90). However, the risk of overall complications and surgical site infection was higher in the IBR group than in the other two groups (complications, IBR vs. DBR: OR 1.40, 95% CrI 1.01-1.93; surgical site infection, IBR vs. MA: OR 1.77, 95% CrI 1.03-3.13). CONCLUSIONS: Evidence suggested that breast reconstruction, whether IBR or DBR, does not adversely affect oncological safety in the setting of breast cancer. IBR is associated with an increased risk of overall complications and surgical site infection, but technical advances in this surgical procedure have cumulated over time.

Ultraviolet B irradiation enhances the secretion of exosomes by human primary melanocytes and changes their exosomal miRNA profile.

OBJECTIVE: Melanocytes play a central role in skin homeostasis. In this study, we focus on the function of melanocyte releasing exosomes as well as exosomal microRNAs (miRNAs) and investigate whether ultraviolet B (UVB) irradiation exerts an impact on it. MATERIALS AND METHODS: Exosomes derived from human primary melanocytes were isolated through differential centrifugation and were identified in three ways, including transmission electron microscopy observation, nanoparticle tracking analysis, and Western blot analysis. Melanocytes were irradiated with UVB for the indicated time, and then melanin production and exosome secretion were measured. The exosomal miRNA expression profile of melanocytes were obtained by miRNA sequencing and confirmed by real-time PCR. RESULTS: Exosomes derived from human primary melanocytes were verified. UVB irradiation induced melanin production and increased the exosome release by the melanocytes. In total, 15 miRNAs showed higher levels in UVB-irradiated melanocyte-derived exosomes compared with non-irradiated ones, and the top three upregulated exosomal miRNAs were miR-4488, miR-320d, and miR-7704 (fold change > 4.0). CONCLUSION: It is verified for the first time that UVB irradiation enhanced the secretion of exosomes by melanocytes and changed their exosomal miRNA profile. This findings open a new direction for investigating the communication between melanocytes and other skin cells, and the connection between UVB and skin malignant initiation.

Sumoylation enhances the activity of the TGF-ß/SMAD and HIF-1 signaling pathways in keloids.

Excessive fibrosis and extracellular matrix deposition resulting from upregulation of target genes expression mediated by transforming growth factor-beta (TGF-ß)/SMAD and hypoxia inducible factor-1 (HIF-1) signaling pathways are the main mechanisms that drive keloid formation. Sumoylation is a protein posttranslational modification that regulates the function of proteins in many biological processes. In the present study, we aimed to investigate the mechanism underlying the effects of sumoylation on the TGF-ß/SMAD and HIF-1 signaling pathways in keloids. We used 2-D08 to block sumoylation and silenced the expression of sentrin sumo-specific protease 1 (SENP1) to enhance sumoylation in human foreskin fibroblasts (HFFs) and human keloid fibroblasts (HKFs). We also reduced and increased intracellular SUMO1 levels by silencing SUMO1 and transfecting cells with a SUMO1 overexpression lentivirus, respectively. Sumoylation has the ability to amplify TGF-ß/SMAD and HIF-1 signals in keloids, while SUMO1, especially the SUMO1-RanGAP1 complex, is the key molecule affecting the TGF-ß/SMAD and HIF-1 signaling pathways. In addition, we also found that hypoxia promotes sumoylation in keloids and that HIF-1α is covalently modified by SUMO1 at Lys 391 and Lys 477 in HKFs. In summary, we elucidated the role and molecular mechanism of sumoylation in the formation of keloids, providing a new perspective for a potential therapeutic target of keloids.

Comparison of meatal-based flap (Mathieu) and tubularized incised-plate (TIP) urethroplasties for primary distal hypospadias: A systematic review and meta-analysis.

PURPOSE: We conducted this meta-analysis to compare postoperative outcomes between meatal-based flap (Mathieu) and tubularized incised plate (TIP) techniques for distal hypospadias. METHODS: A comprehensive literature search of PUBMED, Web of Science, EMBASE, and Cochrane Library was conducted. Outcomes evaluated in this review were fistula, meatal stenosis, wound dehiscence and flap necrosis. We calculated odds ratio (OR) with 95% confidential interval (CI) to compare postoperative outcomes between Mathieu and TIP after data extraction and literature identification. All data were analyzed using Review Manager 5.2. In order to find potential affective factors, meta-regression and subgroup analyses were applied. RESULTS: 16 studies, 1386 patients, including 762 patients receiving Mathieu and 624 individuals subjected to TIP met the inclusion criteria. The synthetic data suggested that Mathieu and TIP were comparable in terms of fistula (OR = 0.93; 95% CI: 0.65 to 1.33; P = 0.70, I2 = 14%), wound dehiscence (OR = 0.89; 95% CI: 0.33 to 2.39; P = 0.81, I2 = 11%), and flap necrosis (OR = 1.9; 95% CI: 0.51 to 7.09; P = 0.20, I2 = 38%) without significant heterogeneity for each comparison group. Pooled estimates showed a significantly lower rate of meatal stenosis with Mathieu than with TIP (OR = 0.41; 95% CI: 0.24 to 0.73; P = 0.002, I2 = 4%). Subgroup analyses showed that the difference between Mathieu and TIP was more obvious in the studies published before 2013 in meatal stenosis. The modified Mathieu technique and a running suture for urethroplasty might be relevant to a lower rate of meatal stenosis in the data, although no statistical significance in the present effects model overall was found. One-way sensitivity analysis showed that the results were stable. There was no publication bias detected using both funnel plot and Egger's test. CONCLUSION: This meta-analysis suggested that Mathieu and TIP technique were equivalent for primary distal hypospadias in terms of fistula, wound dehiscence, and flap necrosis. Pooled estimates indicated that there was a lower rate of meatal stenosis with Mathieu rather than with TIP significantly. The modified Mathieu technique and a running suture for urethroplasty might be relevant to a lower rate of meatal stenosis. TYPE OF STUDY: Meta-analysis. LEVEL OF EVIDENCE: IV.

Auxiliary usage of botulinum toxin A in plastic surgery in China.

BACKGROUND: Currently, botulinum toxin A (BTA) is mainly used in the treatment of muscle spasms and in cosmetic procedures, and its cosmetic indications are expanding rapidly. There have been sporadic reports focused on the preoperative usage of BTA complementing plastic surgery. We briefly summarize the current experience of BTA complementing plastic surgery in China based on clinical experience. METHODS: We reported a brief review of the preoperative use of BTA as an accessory to plastic surgery (blepharoplasty, chin augmentation, mandibular angle ostectomy, rhinoplasty, hyaluronic acid fillers injection for wrinkle reduction) based on previous studies and our experience. RESULTS: Preoperative treatment with BTA in plastic surgery helps surgeons operate and results in better cosmetic results. CONCLUSIONS: Preoperative BTA treatment can reduce the occurrence of surgical complications as well as improve the surgical results in some plastic surgeries. The procedure is suitable for clinical application and worth promoting.

Comparison of Perioperative Parameters in Femtosecond Laser-Assisted Cataract Surgery Using 3 Nuclear Fragmentation Patterns.

PURPOSE: The purpose of this study was to compare the perioperative parameters of quadrant, sextant, and grid lens fragmentation patterns in femtosecond laser-assisted cataract surgery (FLACS). DESIGN: Prospective randomized clinical trial. METHODS: Setting: Eye Center of the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China. STUDY POPULATION: A total of 894 eyes in 661 patients with cataracts were enrolled. Intervention or observation procedures: the nuclear density was graded according to the Emery-Little classification. Patients received lens fragmentation using a quadrant, sextant, or grid pattern after random allocation. Evaluations included intraoperative parameters, complications, and postoperative outcomes. MAIN OUTCOME MEASUREMENTS: effective phacoemulsification time (EPT), intraoperative complications, visual acuity and intraocular pressure at one day postoperatively, as well as endothelial cell density, endothelial cell loss, and central corneal thickness at 1 week postoperatively. RESULTS: In grade 1 nuclei, the mean EPT in the grid group was the shortest compared to those in the quadrant (P = 0.011) and sextant (P = 0.001) groups. In grade 2 nuclei, all 3 patterns showed no significant differences in the mean EPT (P > 0.05). In grade 3 nuclei, the sextant group revealed shorter mean EPT than the grid (P = 0.017) and quadrant (P > 0.05) groups. In grades 4 and 5 nuclei, the quadrant pattern had the shortest mean EPT among all 3 patterns (P < 0.05). The grid pattern is associated with higher intraocular pressure in hard nuclei (grades 4 and 5) than the other 2 patterns (P < 0.05). CONCLUSIONS: The grid and quadrant patterns allow for shorter EPT in soft (grade 1) and hard (grades 4 and 5) nuclei, respectively. All 3 patterns can be selected for treating grade 2 nuclei. The sextant pattern may be the best option when treating grade 3 nuclei. The grid pattern should be avoided in hard nuclei combined with glaucoma or glaucoma suspect.

A comparative assessment of three planes of implant placement in breast augmentation: A Bayesian analysis.

BACKGROUND: Techniques based on three planes of implant placement, including the subglandular (SG), subpectoral (SP), and subfascial (SF) planes are used for breast augmentation. The placement that offers the greatest balance of risks and benefits is unclear. This study presents a systematic review with a Bayesian network meta-analysis to compare different implant placement techniques for augmentation mammaplasty. METHODS: A systematic literature search was performed. We estimated the odds ratios (ORs) for capsular contractures, hematomas, seromas, infections, reoperation rates, rippling, nipple numbness, malplacements, ruptures, and asymmetry among the different interventions. Muscle movement events and satisfaction rates were also evaluated. RESULTS: A total of 19 studies (25,744 cases) were included. SG placement significantly increased the incidence of capsular contractures (SP vs. SG: OR 0.42; 95% credible interval [CrI] 0.28-0.63; SF vs. SG: OR 0.41; 95% CrI 0.17-0.97), hematomas (SF vs. SG: OR 0.22; 95% CrI 0.06-0.63), and seromas (SF vs. SG: OR 0.04; 95% CrI 0.00-0.81) compared to other placement techniques. Muscle movement only occurred in the SP group, but it did not increase the risk of subsequent malplacements, asymmetries, or ruptures. Most patients were highly satisfied with their surgical results. Comparisons did not show significant differences in the remaining results. CONCLUSIONS: Our evidence suggests that SG placement increases the risk of capsular contractures, hematomas, and seromas. The SP and SF planes were safe and effective for controlling total complication rates and achieving high satisfaction rates; however, the long-term benefits of the SF technique require further research.

Comparative transcriptomic analysis reveals adriamycin-induced apoptosis via p53 signaling pathway in retinal pigment epithelial cells.

OBJECTIVE: This paper applied a transcriptomic approach to investigate the mechanisms of adriamycin (ADR) in treating proliferative vitreoretinopathy (PVR) using ARPE-19 cells. METHODS: The growth inhibitory effects of ADR on ARPE-19 cells were assessed by sulforhodamine B (SRB) assay and propidium iodide (PI) staining using flow cytometry. The differentially expressed genes between ADR-treated ARPE-19 cells and normal ARPE-19 cells and the signaling pathways involved were investigated by microarray analysis. Mitochondrial function was detected by JC-1 staining using flow cytometry and the Bcl-2/Bax protein family. The phosphorylated histone H2AX (γ-H2AX), phosphorylated checkpoint kinase 1 (p-CHK1), and phosphorylated checkpoint kinase 2 (p-CHK2) were assessed to detect DNA damage and repair. RESULTS: ADR could significantly inhibit ARPE-19 cell proliferation and induce caspase-dependent apoptosis in vitro. In total, 4479 differentially expressed genes were found, and gene ontology items and the p53 signaling pathway were enriched. A protein-protein interaction analysis indicated that the TP53 protein molecules regulated by ADR were related to DNA damage and oxidative stress. ADR reduced mitochondrial membrane potential and the Bcl-2/Bax ratio. p53-knockdown restored the activation of c-caspase-3 activity induced by ADR by regulating Bax expression, and it inhibited ADR-induced ARPE-19 cell apoptosis. Finally, the levels of the γ-H2AX, p-CHK1, and p-CHK2 proteins were up-regulated after ADR exposure. CONCLUSIONS: The mechanism of ARPE-19 cell death induced by ADR may be caspase-dependent apoptosis, and it may be regulated by the p53-dependent mitochondrial dysfunction, activating the p53 signaling pathway through DNA damage.

Systematic review with network meta-analysis: dual therapy for high-risk bleeding peptic ulcers.

BACKGROUND: Adding a second endoscopic therapy to epinephrine injection might improve hemostatic efficacy in patients with high-risk bleeding ulcers but the optimum modality remains unknown. We aimed to estimate the comparative efficacy of different dual endoscopic therapies for the management of bleeding peptic ulcers through random-effects Bayesian network meta-analysis. METHODS: Different databases were searched for controlled trials comparing dual therapy versus epinephrine monotherapy or epinephrine combined with another second modality until September, 30 2016. We estimated the ORs for rebleeding, surgery and mortality among different treatments. Adverse events were also evaluated. RESULTS: Seventeen eligible articles were included in the network meta-analysis. The addition of mechanical therapy (OR 0.19, 95% CrI 0.07-0.52 and OR 0.10, 95% CrI 0.01-0.50, respectively) after epinephrine injection significantly reduced the probability of rebleeding and surgery. Similarly, patients who received epinephrine plus thermal therapy showed a significantly decreased rebleeding rate (OR 0.30, 95% CrI 0.10-0.91), as well as a non-significant reduction in surgery (OR 0.47, 95% CrI 0.16-1.20). Although differing, epinephrine plus mechanical therapy did not provide a significant reduction in rebleeding (OR 0.62, 95% CrI 0.19-2.22) and surgery (OR 0.21, 95% CrI 0.03-1.73) compared to epinephrine plus thermal therapy. Sclerosant failed to confer further benefits and was ranked highest among the 5 treatments in relation to adverse events. CONCLUSIONS: Mechanical therapy was the most appropriate modality to add to epinephrine injection. Epinephrine plus thermal coagulation was effective for controlling high risk bleeding ulcers. There was no further benefit with sclerosants with regard to rebleeding or surgery, and sclerosants were also associated with more adverse events than any other modality.

Clinical comparison of patient outcomes following implantation of trifocal or bifocal intraocular lenses: a systematic review and meta-analysis.

To assess the visual effects of trifocal intraocular lenses (IOLs) compared to bifocal IOLs in cataract surgery, a meta-analysis of prospective comparative clinical trials (including 4 randomized controlled trials and 4 cohorts) was conducted. The defocus curves showed a better distance-corrected intermediate visual acuity (VA) for the trifocal group (MD -0.07; 95% CI, -0.10 to -0.05; p < 0.00001), while the VA outcomes showed no significant difference in distance VA (MD -0.03; 95% CI, -0.06 to 0.01; p = 0.13 for uncorrected distance VA and MD -0.00; 95% CI, -0.01 to 0.01; p = 0.78 for distance-corrected distance VA), near VA (MD -0.01; 95% CI, -0.07 to 0.04; p = 0.68 for uncorrected near VA and MD -0.01; 95% CI, -0.06 to 0.04; p = 0.66 for distance-corrected near VA) or refraction between the two groups. Contrast sensitivity and subjective visual quality yielded less conclusive results. Overall, a patient may achieve better intermediate VA with a trifocal IOL than with a bifocal IOL without any adverse effect on distance or near VA. The findings on contrast sensitivity and subjective visual quality were heterogeneous, with no clear results favoring either option.

Dry Eye after Small Incision Lenticule Extraction (SMILE) versus Femtosecond Laser-Assisted in Situ Keratomileusis (FS-LASIK) for Myopia: A Meta-Analysis.

PURPOSE: To compare dry eye after small incision lenticule extraction (SMILE) and femtosecond laser-assisted LASIK (FS-LASIK) for correcting myopia. METHODS: CENTRAL, Embase and PubMed were searched in November 2016. All randomized controlled trials (RCTs) and prospective cohorts that compared dry eye after SMILE with FS-LASIK were selected. RESULTS: Five cohorts and one RCT were identified for comparing dry eye after SMILE (291 eyes) and FS-LASIK (277 eyes). The pooled results revealed that the SMILE and FS-LASIK groups did not differ significantly in terms of Schirmer's I test (SIT) and tear film osmolarity (TFO) at any postoperative visits. By contrast, tear break up time (TBUT; p = 0.04 for one month, p < 0.001 for three months, and p = 0.02 for six months) and ocular surface disease index (OSDI; p < 0.001 for one month and three months, and p = 0.006 for six months) were significantly worse in the FS-LASIK group than in the SMILE group at follow-up. At six months postoperatively, TBUT and TFO values in both the SMILE and FS-LASIK groups and OSDI scores in the SMILE group returned to preoperative levels, but SIT values in both groups (p = 0.02 for the SMILE group and p < 0.001 for the FS-LASIK group) and OSDI in the FS-LASIK group (p < 0.001) were still statistically impaired. CONCLUSION: Dry eye after both SMILE and FS-LASIK usually occurs transiently. SMILE does not show obvious superiority over FS-LASIK by exhibiting similar and acceptable objective parameters, and SMILE may have milder subjective symptoms.

Small Incision Lenticule Extraction (SMILE) versus Femtosecond Laser-Assisted In Situ Keratomileusis (FS-LASIK) for Myopia: A Systematic Review and Meta-Analysis.

PURPOSE: The goal of this study was to compare small incision lenticule extraction (SMILE) with femtosecond laser-assisted in situ keratomileusis (FS-LASIK) for treating myopia. METHODS: The CENTRAL, EMBASE, PubMed databases and a Chinese database (SinoMed) were searched in May of 2016. Twelve studies with 1,076 eyes, which included three randomized controlled trials (RCTs) and nine cohorts, met our inclusion criteria. The overall quality of evidence was evaluated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) working group framework. Data were extracted and analysed at three to six months postoperatively. Primary outcome measures included a loss of one or more lines of best spectacle corrected visual acuity (BSCVA), uncorrected visual acuity (UCVA) of 20/20 or better, mean logMAR UCVA, postoperative mean spherical equivalent (SE) and postoperative refraction within ±1.0 D of the target refraction. Secondary outcome measures included ocular surface disease index (OSDI), tear breakup time (TBUT) and Schirmer's 1 test (S1T) as dry eye parameters, along with corneal sensitivity. RESULTS: The overall quality of evidence was considered to be low to very low. Pooled results revealed no significant differences between the two groups with regard to a loss of one or more lines in the BSCVA (OR 1.71; 95% CI: 0.81, 3.63; P = 0.16), UCVA of 20/20 or better (OR 0.71; 95% CI: 0.44, 1.15; P = 0.16), logMAR UCVA (MD 0.00; 95% CI: -0.03, 0.04; P = 0.87), postoperative refractive SE (MD -0.00; 95% CI: -0.05, 0.05; P = 0.97) or postoperative refraction within ±1.0 D of the target refraction (OR 0.78; 95% CI: 0.22, 2.77; P = 0.70) within six months postoperatively. The pooled analysis also indicated that the FS-LASIK group suffered more severely from dry eye symptoms (OSDI; MD -6.68; 95% CI: -11.76, -2.00; P = 0.006) and lower corneal sensitivity (MD 12.40; 95% CI: 10.23, 14.56; P < 0.00001) at six months postoperatively. CONCLUSIONS: In conclusion, both FS-LASIK and SMILE are safe, effective and predictable surgical options for treating myopia. However, dry eye symptoms and loss of corneal sensitivity may occur less frequently after SMILE than after FS-LASIK.

Diosmetin protects against retinal injury via reduction of DNA damage and oxidative stress.

Visual impairment is a global public health problem that needs new candidate drugs. Chrysanthemum is a traditional Chinese drug, famous for its eye-protective function, with an unclear mechanism of action. To determine how chrysanthemum contributes to vision, we identified, for the first time, the component of chrysanthemum, diosmetin (DIO), which acts in protecting the injured retina in an adriamycin (ADR) improving model. We observed that DIO could attenuate the apoptosis of retinal cells in Sprague-Dawley rats and verified this effect in cultured human retinal pigment epithelium (RPE) cells, ARPE-19. Our further study on the mechanism revealed the counteractive effect of DIO on the attenuation of DNA damage and oxidative stress, which occurs in a wide range of retinal disorders. These results collectively promise the potential value of DIO as a retinal-protective agent for disorders that lead to blindness. In addition, we identified, for the first time, the component of chrysanthemum, DIO, which acts in protecting the injured retina.