BackgroundLymph node involvement and tumor-induced lymphangiogenesis appear as the earliest features of esophageal squamous cell carcinoma (ESCC), although the molecular regulatory mechanisms involved have remained unclear. Our aim was to investigate the contribution of NF-κB and Notch1 signaling to lymph node involvement and tumor-induced lymphangiogenesis in ESCC.Material and methodsNF-κB and Notch1 expression in 60 tissue samples of ESCC were assessed by immunohistochemical staining. The correlations of NF-κB and Notch1 with lymph node involvement, lymphatic vessel density (LVD), podoplanin, and vascular endothelial growth factor-C (VEGF-C) were further evaluated to determine the association of NF-κB and Notch1 expression with tumor-induced lymphangiogenesis.ResultsChi-square tests revealed that NF-κB and Notch1 expression in ESCC tissues were significant associated with lymph node metastasis, LVD, podoplanin, and VEGF-C expression. Strong expression of NF-κB, but weak expression of Notch1, was observed in tumor tissues with lymph nodes involvement (P < 0.05 for both). The mean histoscores of LVD, podoplanin, and VEGF-C staining were higher in high-NF-κB-expressing tissue than in low-expressing tissue (P < 0.05 for each). In contrast, the mean histoscores of LVD and VEGF-C staining were lower in high-Notch1-expressing tissue than in low-expressing tissue (P < 0.05 for both). A multiple factors analysis of LVD and VEGF-C further demonstrated that LVD and VEGF-C status were significantly correlated with NF-κB and Notch1 expression in tumors. NF-κB and Notch1 expression were also significantly inversely correlated (P < 0.05).ConclusionThese results suggest that different patterns of NF-κB and Notch1 signaling contribute to lymph nodes metastasis and tumor-induced lymphangiogenesis of ESCC, and reveal that up-regulation of NF-κB is associated with down-regulation of Notch1 in tumor tissue.

BackgroundTo investigate the role of microglia polarization in the pathogenesis of diabetic retinopathy, and study the mechanism of ALKBH5-mediated m6A modification of A20 of retinal microglia polarization.MethodsDiabetics rats were constructed and the M1/M2 polarization of retinal microglia was determined using immunofluorescence, flow cytometry, and quantitative real-time PCR (qRT-PCR). Glucose at different concentrations was added to treat the microglia, and the polarization rate was detected. RNA sequencing was performed to identify the differentially expressed gene in glucose treated microglia, and A20 expression was confirmed by qRT-PCR and western blotting. Lentiviruses encoding shRNA for A20 or overexpressing A20 were constructed to clarify the role of A20 in microglia polarization in vitro and vivo. N6-methyladenosine (m6A) modification level and degradation rate of A20 were determined and m6A related proteins were detected.ResultsDiabetics rats showed a higher M1 polarization rate but lower M2 polarization rate of retinal microglia. With the increase of glucose concentration, microglia tend to polarize into M1 inflammatory type rather than M2 anti-inflammatory type. Shown by RNA sequencing, glucose treated microglia showed a differentially expressed gene profile, which was enriched in kinds of inflammatory categories and pathways. A20 expression was lower in microglia with glucose treatment, which was demonstrated to negatively regulate the M1 polarization. Moreover, intraocular injection of A20-overexpression lentiviruses (OE-A20) rectified the enhanced M1 retinal microglia polarization of diabetes rats. The higher m6A modification level and faster degradation rate of A20 was observed in glucose treated microglia, which was mediated by m6A demethylase ALKBH5.ConclusionLower expression A20 resulted in the enhanced M1 polarization of retinal microglia in diabetic retinopathy, which was caused by ALKBH5 mediated m6A modification. This study may provide new perspectives on not only the pathogenesis but also the diagnosis and treatment for diabetic retinopathy.

Background: The purpose of this study was to analyze the ocular biometric parameters of primary angle-closure disease (PACD) in younger patients and compare them with those of elderly patients.Methods: This clinic-based, cross-sectional study included 154 eyes of 154 patients with PACD, consisting of 77 eyes of patients aged 40 years or younger and 77 eyes of patients older than 40. The PACD case definition was compatible with the ISGEO definition. Anterior segment parameters were measured by ultrasound biomicroscopy, axial length (AL) and lens thickness (LT) were measured by A-scan ultrasonography measurements, and the thickness of the retina and choroid were measured by optical coherence tomography. The differences in ocular biometric parameters between different age groups were compared by independent sample t-tests or Mann-Whitney U tests, and the correlation between the parameters and age was analyzed.Results: Compared to older PACD patients, the lens vault(LV),LV/LT and subfoveal choroidal thickness (SFCT) of younger patients were larger, while the peripheral and mean iris thickness (IT), trabecular-ciliary angle (TCA), ciliary body thickness (CBT), AL and LT were smaller (all P &lt; 0.01). There was no significant difference in anterior chamber depth, anterior chamber width, pupil diameter, angle opening distance at 500 μm from the scleral spur, anterior chamber angle and iris convexity between the two groups (all P &gt; 0.05). AL, LT, IT, TCA and CBT were positively associated with age (all P &lt; 0.001), while LV and SFCT were negatively associated with age (P = 0.027 and P &lt; 0.001, respectively).Conclusions: Compared with elderly patients, younger PACD patients had more anteriorly positioned lenses, thinner and more anteriorly rotated ciliary bodies, thicker choroids, and shorter axial length. These characteristics might be important anatomical bases for the earlier onset of PACD and the higher risk of malignant glaucoma after filtering surgery.

Purpose: The purpose of this study was to describe and summarize the clinical features of congenital fibrovascular pupillary membrane-induced secondary glaucoma (CFPMSG).Design: Cross-sectional case series.Methods: Eyes of 32 patients with CFPMSG were enrolled. Demographic data, including gender, laterality, age at presentation, and age at onset of glaucoma were collected. Patients underwent comprehensive ophthalmic examinations and ultrasound biomicroscopy (UBM). CFPMSG eyes were classified into three groups based on UBM findings and intergroup analysis was performed using ANOVA.Results: The average age at presentation was 2.4 ± 4.6 months (mean ± SD) and at glaucoma onset was 3.8 ± 4.5 months. Compared to normal fellow eyes, all affected eyes had increased intraocular pressure (IOP), axial length, corneal diameter, and central corneal thickness, and decreased anterior chamber depth (ACD) (all P ≤ 0.001). Twenty-two affected eyes (68.8%) had evidence of glaucomatous optic neuropathy. Based on iris configuration on UBM, eyes were classified as 53% type I (“U” shape), 34% type II (“Y” shape), and 13% type III (no anterior chamber). IOP in types II (33.8 ± 5.9 mmHg) and III (35.2 ± 5.9 mmHg) was significantly higher than in type I eyes (26.5 ± 5.1 mmHg). The ACD was shallower in type II compared to type I (P = 0.045).Conclusion: Congenital fibrovascular pupillary membrane-induced secondary glaucoma is characterized by ocular hypertension, corneal enlargement and edema, axial length elongation, and glaucomatous optic neuropathy. Glaucoma in this condition is secondary to pupillary block and angle-closure. UBM provides important information for the diagnosis and classification of CFPMSG. This novel classification system demonstrated varying levels of severity and may guide on management of this disease.

Introduction: To investigate the long-term visual outcomes and factors associated with vision loss in Chinese patients with primary congenital glaucoma (PCG) after successful intraocular pressure (IOP) control (IOP ≤ 21 mmHg). Methods: PCG patients with IOP control who were examined in the glaucoma clinic at Zhongshan Ophthalmic Center from 2019 to 2020 were enrolled. The final visual outcome was evaluated by the best-corrected visual acuity. Univariate and multivariate analyses were used to investigate the associations of visual impairment with potential risk factors. The causes for decreased visual acuity (VA, < 20/50) were also analyzed. Results: Fifty-nine patients (95 eyes) were included in the cohort, with a mean age of 8.7 years. The mean logMAR VA was 0.62 ±0.64. The VAs of eyes treated for PCG were good (≥20/50) in 56%, fair (20/60 to 20/200) in 30%, and poor (< 20/200) in 14%. The most common cause of decreased VA was amblyopia (64.3%). Multivariate logistic regression analysis showed that undergoing multiple surgeries (OR: 4.86, 95% CI: 1.11-21.16, P=0.035) was significantly associated with visual impairment. Conclusion: The results showed that good VA was attainable in approximately half of PCG eyes under IOP control. Prompt and effective treatment of PCG, management of amblyopia and ocular comorbidities may be potential steps toward achieving good visual outcomes in PCG patients.