To identify the differentially expressed genes in the orbital tissues of patients with thyroid eye disease (TED). The microarray datasets on the orbital tissues of TED patients were collected from the Gene Expression Omnibus DataSets. Upon filtering, the differentially expressed genes (DEGs) of the selected dataset were determined and evaluated by gene ontology analysis. The expressions of genes related to the TED pathophysiological changes were validated by SYBR Green polymerase chain reaction (PCR) and immunofluorescence analyses on separate TED and control orbital tissue specimens. Analysis on the orbital tissue samples of TED patients in the GSE58331 dataset identified 74 DEGs. Gene ontology analysis revealed that the DEGs are involved in the endocytosis, innate immunity, and extracellular matrix. Out of the 10 selected genes, only S100A9 showed significant upregulation in the orbital tissues of TED patients as compared to that of the control subjects (P = 0.006) in the SYBR Green PCR validation experiment. Immunofluorescence analysis confirmed significantly elevated expression of S100A9 in the orbital tissues of TED patients (P = 0.008). The receiver-operating characteristic curve (ROC) analysis demonstrated that the area under the ROC curve of S100A9 was 0.79 for the discrimination of the TED patients from the control subjects. This study revealed the upregulation of S100A9 in the orbital tissues of TED patients, suggesting that it could be involved in the development of TED.
Purpose: Keloid (KD) and hypertrophic scars are prevalent and result from excessive growth of dermal tissue after skin damage. This review focused on the clinical application of the ultra-pulsed CO(2 )fractional laser combined with recombinant human epidermal growth factor (rHEGF) gel in patients with eyelid KD. Methods: Patients (N = 98) with KD who underwent surgery were randomly divided into a study group (ultra-pulsed CO2 fractional laser combined with rHEGF gel therapy, N = 49) and a control group (ultra-pulsed CO2 fractional laser therapy, N = 49). Besides, 5 cases dropped out of the study, including 2 cases in the study group and 3 cases in the control group. Finally, 47 cases of the study group and 46 cases of the study group were included in the analysis. The clinical baseline data such as sex, age, body mass index, scar area, etiology, Vancouver Scar Scale score, Patient and Observer Scar Assessment Scale score, four-item itch questionnaire score, serum interleukin-6 (IL-6), IL-10, and tumor necrosis factor-alpha level expression were recorded in the study group (N = 47) and the control group (N = 46). Results: There was no significant difference in gender, age, body mass index, scar area, etiology, Vancouver Scar Scale score, Patient and Observer Scar Assessment Scale score, 4-item itch questionnaire score, IL-6, IL-10, and tumor necrosis factor-alpha levels between the patients treated with ultra-pulse CO2 fractional laser + rHEGF gel and those only treated with ultra-pulse CO2 fractional laser (p > 0.05). Vancouver Scar Scale scores, Patient and Observer Scar Assessment Scale scores, and four-item itch questionnaire scores of patients with eyelid KD decreased to a greater extent than those treated with ultra-pulsed CO(2 )fractional laser combined with rHEGF gel (p <0.01). Compared with ultra-pulsed CO2 fractional laser treatment, ultra-pulsed CO2 fractional laser combined with rHEGF gel was more efficacious in treating patients with eyelid KD, with a lower incidence of adverse effects and a 1-year recurrence rate. Conclusions: Ultra-pulsed CO2 fractional laser combined with rHEGF gel can significantly improve the scar status and scar itching in patients with eyelid KD, with an obvious therapeutic effect, a low incidence of adverse effects, a 1-year recurrence rate, and high safety, which is worthy of popularization and application.
Aims: To analyse the characteristics and trends of non-tumour-related eye removal in southern China from 2009 to 2018. Methods: This retrospective observational study reviewed inpatient data from the Zhongshan Ophthalmic Center between 2009 and 2018 to identify the characteristics and trends of nontumour enucleation/evisceration. The chi-square test was used to assess differences in age, sex, and aetiology, whereas linear regression was used to analyse the significance of trends from 2009 to 2018 across subgroups. The nonquadratic Mann-Kendall test was used to evaluate trends in the aetiology and types of ocular injuries. Results: A total of 1824 patients (mean age: 28 years, standard deviation: 19.2) underwent nontumour-related eye removal during the study period. The major causes were trauma (72.6 %) and perforation (7.7 %). Work-related injuries constituted 30.5 % of ocular trauma cases, representing a moderate increase over the past decade. Nevertheless, no statistically significant trends were identified in the aetiology or specific causes of ocular trauma. Conclusions: From 2009 to 2018, the rate of nontumorous eye removal remained stable, with ocular trauma being the leading cause in southern China. Translational relevance: The findings highlight the need for preventive measures against workrelated injuries leading to enucleation and the importance of rigorous childcare to mitigate the risk of eye removal due to trauma.
Purpose To assess microvascular damage in exfoliation syndrome (XFS) patients with spectral-domain optical coherence tomography (OCT) and the correlations between OCT angiography (OCTA) parameters and systemic blood parameters in XFS. Methods Twenty-one XFS eyes and 23 healthy eyes were included in this cross-sectional study. The foveal avascular zone (FAZ) area, vessel density (VD), thickness of the layers of the ganglion cell complex (GCC), homocysteine (Hcy) level, neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) were compared between the two groups. The correlations between OCTA parameters and systemic blood parameters were analyzed. Receiver operating characteristic curve analysis was performed to evaluate the ability of the OCTA parameters to predict XFS. Results Compared with healthy controls, XFS patients had an enlarged FAZ area and a lower VD in the superficial vascular complex (SVC). The GCL thickness map and VD map of the SVC and deep vascular complex (DVC) revealed the presence of pathological damage at the outer superior (OS) and outer inferior (OI) sectors in XFS patients. In XFS patient, the FAZ area and OS VD of the SVC were strongly correlated with the Hcy levels, and the OS VD of the SVC was significantly negatively correlated with the NLR and PLR. The areas under the receiver operating characteristic curve for the SVC FAZ area and OS VD in predicting XFS were both >0.67. Conclusions The pixel-level FAZ algorithm and VD map derived from OCTA can reflect microvascular damage in XFS. The fundus lesions observed in XFS are accompanied by systemic circulatory changes.
Autoimmune uveitis (AU), a sight-threatening inflammatory eye disease, is a leading cause of irreversible vision loss. Current treatments are limited by suboptimal efficacy and significant complications, highlighting the need for new therapeutic strategies. Exendin-4 (Ex-4), a glucagon-like peptide-1 receptor agonist primarily used for glycemic control and weight management, has recently shown potential anti-inflammatory effects. However, its role in AU remains unexplored. Here, we demonstrated that Ex-4 treatment effectively alleviated EAU symptoms. Our analysis revealed that Ex-4 partially reversed both the proportional changes and transcriptional alterations in immune cell populations during EAU. Bioinformatic analysis showed that Ex-4 suppressed the EAU-induced upregulation of Pim1 expression. Subsequent experiments revealed that Ex-4 restored the effector T (Teff) /regulatory T (Treg) cell balance via the suppression of the PIM1-protein kinase B (AKT)-Forkhead box O1 (FOXO1) pathway.These effects were further observed in patients with Vogt-Koyanagi-Harada disease (VKH), a human uveitis. Our study provides valuable insights into Ex-4- mediated immune modulation and highlights potential therapeutic targets for autoimmune uveitis.
The mechanisms regulating organ size remain poorly understood. Here, we show that FREM2 is a critical modulator of lung size. Frem2 mutant mice exhibit defects in the formation of elastic fibers around mesothelial cells, which compromises phosphorylated myosin light chain (pMLC) signaling and mesothelial cell polarization, leading to lung growth inhibition. These processes are regulated in part through inhibition of p38-mediated upregulation of matrix metalloproteinase-2, as pharmacological decrease of p38 phosphorylation or MMP activity partially attenuates the Frem2 mutant lung phenotypes. Disruption of ROCK function also leads to defects in elastic fiber organization and mesothelial cell polarity, while inhibition of Vangl2-regulated mesothelial cell polarity causes defects in pMLC abundance and elastic fiber structure. Collectively, these processes constitute a positive feedback loop to regulate lung size. Notably, Frem2 mutant mice also display defects in the formation of the mesothelium and reduced growth of other internal organs. Importantly, patients with FREM2 mutations exhibit smaller lungs. These results reveal a shared role and mechanism for the mesothelium in organ size control.
AIM: To evaluate refraction and ocular biological characteristics in children with unilateral congenital ptosis. METHODS: In this cross-sectional study, 200 Chinese children (3-15y) with unilateral congenital ptosis were evaluated. Cycloplegic refraction and ocular biological measurements were taken from Oct. 2020 to Aug. 2022. RESULTS: In patients with congenital ptosis, the prevalence of with-the-rule astigmatism and oblique astigmatism was significantly high. The cornea was flatter in ptotic eyes [K1 (42.37±1.62 vs 42.78±1.51 D), K2 (43.8±1.86 vs 44.2±1.64 D), corneal power (Km; 43.09±1.68 vs 43.49±1.53 D), all P<0.001]. Axial length (AL) was longer in ptotic eyes (22.55 vs 22.51 mm, P=0.012). The white-to-white (WTW) was significantly smaller in ptotic eyes (11.49 vs 11.65 mm, P<0.001). The central corneal thickness (CCT) was greater in ptotic eyes (553.50 vs 545.00 µm, P<0.001). No significant differences were found in anterior chamber depth (AD), lens thickness (LT) and vitreous thickness (VT) between ptotic and fellow eyes (P>0.05). In addition, the incidence of amblyopia in ptosis eyes was 32.0%, which was significantly higher than that in the normal population. CONCLUSION: Ptotic eyes have longer AL, flatter, thicker and smaller corneas than fellow eyes. The congenital ptosis increases the risk of amblyopia. The results suggest that regular examinations of refractive status and ocular biological parameters such as AL, are essential for children with unilateral congenital ptosis.
Background Acute lymphoblastic leukemia (ALL) is one of the most common pediatric cancers, characterized by the malignant proliferation of leukemic cells. Despite advancements in treatment, the prognosis for refractory and relapsed ALL remains poor, underscoring the need for novel therapeutic targets and approaches. Methods To investigate the anti-leukemic properties of MG132, MTS assays were employed to assess cell viability, and flow cytometry was used to evaluate apoptosis. Mechanistic studies, including qRT-PCR, Western blotting, and lentivirus-mediated FOXO3a knockdown, were conducted to explore MG132’s effects on the Akt/FOXO3a/Bim signaling pathway. A xenograft mouse model was utilized to validate the in vivo efficacy of MG132 in suppressing tumor growth. Results MG132 inhibited cell proliferation and induced apoptosis in both ALL cell lines and primary cells in a concentration-dependent manner. Mechanistic studies revealed that MG132 promoted FOXO3a nuclear localization by suppressing Akt phosphorylation and preventing FOXO3a degradation, leading to increased Bim expression. Furthermore, FOXO3a knockdown significantly reduced MG132’s anti-proliferative effects. In vivo, MG132 markedly inhibited tumor growth in the xenograft model. Conclusion These findings suggest that MG132 exerts potent anti-leukemic effects through modulation of the Akt/FOXO3a/Bim axis, offering a promising therapeutic avenue for treating ALL.
Abstract Background The treatment of all-trans retinoic acid (ATRA) and arsenical agent has revolutionarily improved the prognosis of acute promyelocytic leukemia (APL) both in adults and children. Nevertheless, coagulation disorder and differentiation syndrome (DS) are the main causes of early death in APL patients. Early chemotherapy to reduce leukocytes during induction is an important measure to reduce complications and mortality. However, the incidence of hyperleukocytosis (WBC > 10 × 109/L) was significantly higher in pediatric patients without chemotherapy than in adults. Although ATRA plus arsenic is the standard therapy for non-high-risk adult patients, it remains controversial whether chemotherapy is necessary for induction therapy in pediatric APL. Methods This study was designed as a multicenter randomized controlled trial. Children with APL were randomly assigned into experimental group (ATRA-RIF plus chemotherapy) and control group (ATRA-RIF). The experimental group was treated with ATRA-RIF plus chemotherapy for induction, while the control group was treated with ATRA-RIF alone. In addition, both groups received the same regimen of ATRA-RIF plus chemotherapy for consolidation and maintenance. Discussion This trial aims to compare the efficacy of ATRA-RIF plus chemotherapy versus ATRA-RIF in pediatric non-high-risk patients with APL to demonstrate that chemotherapy during induction therapy can reduce the incidence of complications such as hyperleukocytosis and DS, thereby reducing mortality. Trial registration Chinese Clinical Trials Registry, ID: ChiCTR2000038877. Registered on October 8, 2020, https://www.chictr.org.cn/showproj.html?proj=60733. V1.0 date 08/01/2020.
Purpose: To evaluate the expression of sry-box transcription factor 9 (SOX9) in orbital fibroblasts (OFs) of thyroid eye disease (TED) and to find its potential role and underlying mechanism in orbital fibrosis. Methods: OFs were cultured from orbital connective tissues obtained from patients with TED (n = 10) and healthy controls (n = 6). SOX9 was depleted by small interfering RNA or overexpressed through lentivirus transduction in OFs. Fibroblast contractile activity was measured by collagen gel contraction assay and proliferation was examined by EdU assay. Transcriptomic changes were assessed by RNA sequencing. Results: The mRNA and protein levels of SOX9 were significantly higher in OFs cultured from patients with TED than those from healthy controls. Extracellular matrix-related genes were down-regulated by SOX9 knockdown and up-regulated by SOX9 overexpression in TED-OFs. SOX9 knockdown significantly decrease the contraction and the antiapoptotic ability of OFs, whereas the overexpression of SOX9 increased the ability of transformation, migration, and proliferation of OFs. SOX9 knockdown suppressed the expression of phosphorylated ERK1/2, whereas its overexpression showed the opposite effect. Epidermal growth factor receptor (EGFR) is one of the notably down-regulated genes screened out by RNA sequencing. Chromatin immunoprecipitation-qPCR demonstrated SOX9 binding to the EGFR promoter. Conclusions: A high expression of SOX9 was found in TED-OFs. SOX9 can activate OFs via MAPK/ERK1/2 signaling pathway, which in turn promotes proliferation and differentiation of OFs. EGFR was a downstream target gene of SOX9. SOX9/EGFR can be considered as therapeutic targets for the treatment of orbital fibrosis in TED.
PurposeTo evaluate the clinical usefulness of digital radiography dacryocystography in patients with primary acquired nasolacrimal duct obstruction prior to endoscopic dacryocystorhinostomy.MethodsAll dacryocystography images from 129 patients with primary acquired nasolacrimal duct obstruction were analyzed. Each group was assessed for postoperative epiphora severity using Munk's score via telephone follow-up three years post-surgery. Receiver operating characteristic (ROC) curve was plotted to obtain a suitable cutoff value of the transverse diameter of the lacrimal sac (LS), used to categorize LS size into small (≤4.350mm) and large (>4.350mm).ResultsAnalysis of the transverse diameter of the LS among 129 patients showed a negative correlation between it and Munk’s score (r =-0.282, p =0.001). There was a statistical difference between the surgical outcomes and the sizes of the LS (p =0.041). The ROC curve analysis showed that the transverse diameter of the LS at 4.350mm was the ideal cutoff value for the outcome of endoscopic dacryocystorhinostomy, with a sensitivity of 42.2%, and specificity of 92.3%. After adjusting for the age and sex, the small LS was associated with an increased risk of postoperative failed outcome (adjusted odds ratio [95% CI]: 8.628 [1.074, 69.335]).ConclusionThe small LS was independently associated with the failed surgical outcome. Furthermore, the preoperative measurement of the LS transverse diameter serves as one of the reliable predictors for postoperative epiphora severity.
PURPOSE:The aim of this study was to analyze the characteristics of CT-measured intersection angle (FB-BNLD) between the frontal bone and bony nasolacrimal duct and to provide suggestions for treating primary acquired nasolacrimal duct obstruction (PANDO) patients in West China. METHODS:Three hundred and nine participants' CT were, respectively, evaluated with RadiAnt DICOM Viewer. We defined the FB-BNLD angle >0° as the anterior type and the FB-BNLD angle ≤0° as the posterior type. RESULTS:The mean FB-BNLD was -2.52° (95% CI, -3.16° to -1.88°) across all participants, of whom 37.2% were of the anterior type and 62.8% of the posterior type. Approximately 65.0% of the female patients had a posterior FB-BNLD type, and 54.2% of the male patients had an anterior FB-BNLD type (p = .002). Posterior FB-BNLD was the dominant type in the PANDO and control groups (p = .011), and the angle of FB-BNLD was statistically different in both groups (PANDO group, -2.54° to -0.71°; control group, -4.42° to -2.67°; p < .001). Among the male participants, the type of FB-BNLD differed between the two groups (p = .036), with differences in the angle of FB-BNLD (PANDO group, 0.59° to 5.13°; control group, -4.08° to 1.89°; p = .034). There was no difference in the type of FB-BNLD in female participants between the two groups (p = .051). CONCLUSION:The present study revealed individual differences in the type of FB-BNLD, with anterior-type majority in males and posterior-type dominance in females. Evaluating the FB-BNLD type on CT can provide a fast method for knowing the nasolacrimal duct condition during planning for lacrimal manipulation.
Background: Realgar-Indigo naturalis formula (RIF) containing A S as a major ingredient is an oral arsenic available in China. The efficacy of RIF on pediatric acute promyelocytic leukemia (APL) is comparable to arsenic trioxide (ATO). However, it remains to be explored that the effects of these two arsenicals on differentiation syndrome (DS) and coagulation disorder which are the two main life-threatening events in children with APL. Procedure: We analyzed 68 consecutive children with newly diagnosed APL involved in SCCLG-APL study (NCT02200978). Patients received all-trans retinoic acid (ATRA) on day 1 of induction therapy. ATO (0.16 mg/kg·d) or RIF (135 mg/kg·d) was administrated on day 5 after mitoxantrone on day 3 (non-high-risk group, NHR) or day 2-4 (high-risk group, HR). Results: The incidences of DS were 3.0% and 5.7% in ATO (n = 33) and RIF (n = 35) groups ( p = 0.590), and 10.3% and 0% in patients with and without differentiation-related hyperleukocytosis, respectively ( p = 0.04). The dynamic changes of WBC between the ATO and RIF groups were not statistically different. However, patients with high WBC counts or percentage of promyelocytes in peripheral blood tended to develop differentiation-related hyperleukocytosis. The improvement of coagulation indexes in the ATO and RIF groups had no statistical difference. Fibrinogen and prothrombin time had the quickest recovery rate. Conclusions: This study provides evidences that the incidence of DS and recovery of coagulopathy are similar whenever treating with RIF or ATO in children with APL.
BackgroundThe aim was to clarify the distributions of bacteria in the conjunctival sac and lacrimal sac in patients with chronic dacryocystitis.MethodsIn total, 297 (322 eyes) chronic dacryocystitis patients who underwent nasal endoscopic dacryocystorhinostomy (EN-DCR) were included. Conjunctival sac secretions from the affected eye were collected preoperatively, and lacrimal sac retention fluid from the affected side in the same patient was collected intraoperatively. Bacterial culture and drug sensitivity testing were performed to determine bacterial distributions.ResultsIn total, 127 bacterial isolates (49 species) were detected in 123 eyes in the conjunctival group, with a positivity rate of 38.2% (123/322); 85 bacterial isolates (30 species) were detected in 85 eyes in the lacrimal sac group, with a positivity rate of 26.4% (85/322). The positivity rates were significantly different (P = 0.001) between two groups. The gram-negative bacilli proportion in the lacrimal sac group (36/85, 42.4%) was significantly higher than that in the conjunctival sac group (37/127, 29.2%) ( P = 0.047). Positive conjunctival sac secretion culture (123/322) was significantly associated with increased ocular secretion (281/322, 87.3%) (P = 0.002). Among the culture-positive bacteria in the conjunctival sac group and the lacrimal sac group, 30/127, 23.6% and 43/127, 26.7% and 21/85, 24.7% and 20/85, 23.5% were resistant to levofloxacin and tobramycin, respectively.ConclusionsThis study illustrated differences in bacterial distributions between conjunctival sac secretions and retained lacrimal sac fluid in chronic dacryocystitis patients, with a higher proportion of gram-negative bacilli in lacrimal sac secretions. The ocular surface flora in chronic dacryocystitis patients is partially resistant to levofloxacin and tobramycin, which need to be considered by ophthalmologists.
Ptosis is a common ophthalmologic condition, and the diagnosis is primarily based on ocular appearance. The diagnosis of such conditions can be improved using emerging technology such as artificial intelligence-based methods. However, unified data collection and labeling standards have not yet been established. This directly impacts the accuracy of ptosis diagnosis based on appearance alone. Therefore, in the present study, we aimed to establish a procedure to obtain and label images to devise a recommendation system for optimal recognition of ptosis based on ocular appearances. This would help to standardize and facilitate data sharing and serve as a guideline for the development and improvisation of algorithms in artificial intelligence for ptosis.
Early detection of visual impairment is crucial but is frequently missed in young children, who are capable of only limited cooperation with standard vision tests. Although certain features of visually impaired children, such as facial appearance and ocular movements, can assist ophthalmic practice, applying these features to real-world screening remains challenging. Here, we present a mobile health (mHealth) system, the smartphone-based Apollo Infant Sight (AIS), which identifies visually impaired children with any of 16 ophthalmic disorders by recording and analyzing their gazing behaviors and facial features under visual stimuli. Videos from 3,652 children (≤48 months in age; 54.5% boys) were prospectively collected to develop and validate this system. For detecting visual impairment, AIS achieved an area under the receiver operating curve (AUC) of 0.940 in an internal validation set and an AUC of 0.843 in an external validation set collected in multiple ophthalmology clinics across China. In a further test of AIS for at-home implementation by untrained parents or caregivers using their smartphones, the system was able to adapt to different testing conditions and achieved an AUC of 0.859. This mHealth system has the potential to be used by healthcare professionals, parents and caregivers for identifying young children with visual impairment across a wide range of ophthalmic disorders.
Lutein (LU) is a carotenoid that has recently been implicated in multiple roles in fibrosis, inflammation, and oxidative stress. Thyroid-associated ophthalmopathy (TAO) is particularly relevant to these pathological changes. We thus aim to probe the potential therapeutic effects of TAO in an in vitro model. We used LU pre-treating OFs derived from patients with TAO or not, then treated with TGF-β1(or IL-1β)to induce fibrosis (or inflammation). We analyzed the different expressions of related genes and proteins, and the molecular mechanism pathway on TAO OFs was screened by RNA sequencing, which is identified in vitro. We found that LU attenuates fibrotic and inflammatory effects in TAO. LU inhibited ACTA2, COL1A1, FN1, and CTGF mRNA expression and suppressed α-SMA, and FN1 protein expression induced by TGF-β1. Besides, LU suppressed OFs migration. Besides, it is shown that LU suppressed inflammation-related genes, such as IL-6, IL-8, CXCL1, and MCP-1. Moreover, LU inhibited oxidative stress induced by IL-1β, which is analyzed by DHE fluorescent probe staining. RNA sequencing suggested ERK/AP-1 pathway may be the molecular mechanism of LU protective effect on TAO, which is identified by RT-qPCR and western-blot. In summary, this study provides the first evidence that LU significantly attenuates the pathogenic manifestations of TAO by inhibiting the expression of fibrotic and inflammation-related genes and ROS produced by OFs. These data suggested that LU may be a potential medicine for TAO.
Background and objectives: Previous studies on ptosis recurrence after correction surgery have tended to focus on postoperative complications, surgical methods and suspension materials, few have mentioned refractive error. This research is to investigate the potential relation between refractive error and recurrence after correction surgery in pediatric patients with simple congenital ptosis. Materials and Methods: We conducted a retrospective analysis of data from patients with simple congenital ptosis who were treated at Zhongshan Ophthalmic Center (ZOC) between 2017 and 2020. In total, 111 eyelids of 85 patients without surgery-related complications who underwent frontalis muscle flap suspension (FMFS) for simple congenital ptosis were included. Postoperative changes in eyelid height were assessed. Cycloplegic refraction was assessed before surgery and during the follow-up period (every 3 months after surgery). Recurrence in the postoperative period was defined as a marginal reflex distance 1 (MRD1) of <1 mm. Results: There were 16 recurrence and 69 non-recurrence cases, with no statistically significant differences, in terms of patient age at the time of surgery, patient sex, or preoperative MRD1, between the recurrence and non-recurrence groups. The postoperative cylindrical diopter (adjusted odds ratio [OR] = 0.432, p = 0.005), laterality (adjusted OR = 0.202, p = 0.006), and preoperative MRD1 (adjusted OR = 0.617, p = 0.019) were associated with ptosis recurrence after surgery. Differences between the recurrence and non-recurrence groups in spherical diopter and spherical equivalent (SE) before and after surgery were not statistically significant. In addition, preoperative refractive error and postoperative spherical diopter were not significantly associated with ptosis recurrence after correction surgery. Conclusions: Ptosis recurrence after FMFS in pediatric cases of congenital ptosis is associated with refractive error. Timely refractive correction and amblyopia treatment may help to reduce ptosis recurrence.
Retinal ischemia-reperfusion (RIR) injury caused by high intraocular pressure (IOP) is an important risk factor contributing to retinal ganglion cell (RGC) death, eventually causing blindness. A key progressive pathological process in the development of RIR is the death of RGCs. However, the detailed mechanisms underlying RGC death caused by RIR have not yet been clearly elucidated, and effective treatments are lacking. Ferroptosis is a recently defined form of programmed cell death that is closely related to organ injury. Melatonin (MT) is a promising neuroprotective agent, but its effects on RIR injury remain unclear. In this study, murine models of acute ocular hypertension and oxygen and glucose deprivation/reoxygenation (OGD/R) model were adopted to simulate retinal ischemia. MT alleviated retinal damage and RGC death in RIR mice, significantly attenuating RIR-induced ferroptosis. Furthermore, MT reduced the expression of p53, a master regulator of ferroptosis pathways, and the upregulation of p53 promoted ferroptosis and largely abolished the neuroprotective effects of MT. Mechanistically, the overexpression (OE) of p53 suppressed the expression of the solute carrier family 7 member 11 (Slc7a11), which was accompanied by increased 12-lipoxygenase (Alox12) expression, triggering retinal ferroptosis. Moreover, MT-ameliorated apoptosis, neuroinflammation and microglial activation were observed. In summary, MT conferred neuroprotection against RIR injury by inhibiting p53-mediated ferroptosis. These findings indicate that MT is a retina-specific ferroptosis inhibitor and a promising therapeutic agent for retinal neuroprotection.
Realgar-Indigo naturalis formula (RIF), an oral traditional Chinese medicine mainly containing Realgar (As4S4), is highly effective in treating adult acute promyelocytic leukemia (APL). However, the treatment efficacy and safety of RIF have not been verified in pediatric patients. SCCLG-APL group conducted a multicenter randomized non-inferiority trial to determine whether intravenous arsenic trioxide (ATO) can be substituted by oral RIF in treating pediatric APL. Of 176 eligible patients enrolled, 91 and 85 were randomized to ATO and RIF groups, respectively. Patients were treated with the risk-adapted protocol. Induction, consolidation, and 96-week maintenance treatment contained all-trans-retinoic acid and low-intensity chemotherapy, and either ATO or RIF. The primary endpoint was 5-year event-free survival (EFS). The secondary endpoints were adverse events and hospital days. After a median 6-year follow-up, the 5-year EFS was 97.6% in both groups. However, the RIF group had significantly shorter hospital stays and lower incidence of infection and tended to have less cardiac toxicity. All 4 relapses occurred within 1.5 years after completion of maintenance therapy. No long-term arsenic retentions were observed in either group. Substituting oral RIF for ATO maintains treatment efficacy while reducing hospitalization and adverse events in treating pediatric APL patients, which may be a future treatment strategy for APL.