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Background: To 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. Methods: Diabetics 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. Results: Diabetics 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. Conclusion: Lower 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. [ABSTRACT FROM AUTHOR]

Abstract Background Post-thymectomy pain in myasthenia gravis (MG) patients can inhibit breathing and coughing. Inappropriate usage of analgesics may exacerbate respiratory inhibition and even cause myasthenic crisis. Flurbiprofen is a non-steroidal anti-inflammatory drug (NSAID) that is commonly used to control moderate postoperative pain and is not associated with respiratory inhibition. We hypothesized that flurbiprofen may provide post-thymectomy pain relief without increasing the risk of complications in MG patients. Methods Two hundred MG patients underwent extended thymectomy from March 2006 to December 2010 and were randomly allocated to a flurbiprofen group (110 patients, 50 mg intravenous flurbiprofen axetil) or a control group (90 patients, 100 mg intramuscular tramadol) as postoperative analgesia. Visual analog scale (VAS) pain score, heart rate, blood pressure, respiratory rate, pulse oximetry (SpO2), and adverse effects were recorded before and up to 24 h after drug administration. Results There were no significant differences in the preoperative clinical characteristics of the flurbiprofen and control (tramadol) groups. Both flurbiprofen and tramadol significantly alleviated post-thymectomy pain (p p 2 in either group at all time points. Conclusions Post-thymectomy intravenous administration of flurbiprofen axetil provides safe and effective analgesia for MG patients.

Abstract Background Lymph 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 methods NF-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. Results Chi-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). Conclusion These 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.

Objective: To investigate the change in choroidal components of patients with Graves' ophthalmopathy (GO) with different degrees of disease activity and severity by using the image binarisation method of optical coherence tomography (OCT)., Methods: This cross-sectional study included 151 eyes of 90 patients with GO. Patients were grouped according to the clinical activity score (CAS) and disease severity. Total choroidal area (TCA), luminal area, stromal area (SA) and choroidal vascularity index (CVI) were acquired by image binarisation of the OCT. Ocular parameters between groups were compared using generalised estimating equations, accounting for intereye correlation and adjusting for relevant factors., Results: As for the included eyes, 104 eyes were inactive GO and 47 eyes were active GO. Local choroidal thicknesses were thicker in active GO than in inactive GO. TCA and SA were significantly larger in active GO than in inactive GO group (3.44±0.91 mm 2 vs 3.14±0.88 mm 2 , p=0.046; 1.16 (1.03-1.50) mm 2 vs 1.10 (0.96-1.27) mm 2 , p=0.002, respectively). CAS was positively correlated with TCA (r=0.171, p=0.036) and SA (r=0.172, p=0.035), and negatively associated with CVI (r=-0.174, p=0.032). In multiple regression models, age, diopter and intraocular pressure (IOP) exhibited significant correlations with the SA (β=-0.006, p=0.010; β=0.076, p<0.001; β=0.015, p=0.010, respectively)., Conclusions: Thickened choroid was observed in active GO compared with inactive GO. The proportional increase of SA was augmented as the disease activity progressed. Age, diopter and IOP were independent factors that affected choroidal area and components in patients with GO. Multicentre prospective cohort studies with a large sample size are still needed., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background/aims: To distinguish the clinical feature of nanophthalmos (NNO) caused by mutations in protease serine 56 ( PRSS56 ), membrane-type frizzled-related protein ( MFRP ), myelin regulatory factor ( MYRF ) and transmembrane protein 98 ( TMEM98 ) and to evaluate the association between angle-closure glaucoma (ACG) and NNO., Methods: Variants in those four genes were identified through exome sequencing/whole genome sequencing data, and bioinformatic analysis was conducted to identify pathogenic/likely pathogenic (P/LP) variants. This observational study comprehensively summarised ophthalmological data of 67 patients with NNO from 63 families. Ocular parameters from 68 eyes without surgical treatment were subjected to further analysis., Results: Totally, 67 patients from 63 families harboured 57 P/LP variants in the four genes, including 30 in PRSS56 (47.6%), 23 in MFRP (36.5%), 5 in TMEM98 (7.9%) and 5 in MYRF (7.9%). ACG was present in 79.1% of patients. An analysis of ocular parameters from 68 eyes revealed that shorter axial length (AL), lower vitreous-to-AL ratios and severe foveal hypoplasia were associated with variants in PRSS56 and MFRP . Uveal effusion was more common in patients with PRSS56 variants, while retinitis pigmentosa was frequently observed in patients with MFRP variants. Patients with MYRF variants exhibited the thinnest retinal nerve fibre layer thickness. Patients with TMEM98 variants had an earlier average onset age of glaucoma., Conclusion: Variants in PRSS56 and MFRP are the most common genetic cause of NNO. ACG is a severe complication frequently observed in these patients. Earlier onset of ACG is observed in patients with dominant NNO, while foveal hypoplasia is more common in patients with recessive disease. Recognising these features is helpful in clinical care and genetic counselling., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: To investigate the role of microglia polarization in the pathogenesis of diabetic retinopathy, and study the mechanism of ALKBH5-mediated m 6 A modification of A20 of retinal microglia polarization., Methods: Diabetics 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. N 6 -methyladenosine (m 6 A) modification level and degradation rate of A20 were determined and m 6 A related proteins were detected., Results: Diabetics 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 m 6 A modification level and faster degradation rate of A20 was observed in glucose treated microglia, which was mediated by m 6 A demethylase ALKBH5., Conclusion: Lower expression A20 resulted in the enhanced M1 polarization of retinal microglia in diabetic retinopathy, which was caused by ALKBH5 mediated m 6 A modification. This study may provide new perspectives on not only the pathogenesis but also the diagnosis and treatment for diabetic retinopathy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer WS declared a shared affiliation with the authors to the handling editor at the time of review., (Copyright © 2022 Chen, Zhu, Wang, Dong, Yu, Su, Huang, Huo and Wan.)

Objective: To conduct signature analysis for splenic trauma in canines during hemorrhagic shock and resuscitation by contrast enhanced ultrasonography (CEUS)., Methods: Forty grade III-IV traumatic splenic lesions were established in 15 mongrel dogs. Hemorrhagic shock was induced in these animals by using the modified Wiggers's method. Animals in shock were then resuscitated with 6% hydroxyethyl starch. The features of splenic trauma during hemorrhagic shock or resuscitation were assessed by CEUS, which were compared with the data collected by contrast-enhanced computed tomography (CECT). Acoustic quantification of CEUS was performed to assess splenic blood perfusion in different stages., Results: There was no significant difference in detection rate between CEUS and CECT during hemorrhagic shock and resuscitation. Before hemorrhagic shock, there were 40 traumatic bleeding lesions and 85% of them were revealed by CEUS (34/40). With the progress in shock, CEUS revealed that the numbers of tiny branches of splenic arteries were decreased, which became thinner with no active bleeding. After fluid resuscitation, rebleeding was occurred in 30 traumatic lesions, and 28 (93.3%) of them were captured by CEUS. CEUS could also visualize the changes in splenic perfusion in different stages. During the shock, the arrival time (AT), time to peak intensity (TTP), peak intensity (PI) were significantly lower and the washout time (WT) were significantly higher than those at other stages (P<0.01)., Conclusion: CEUS not only can dynamically monitor the changes in spleen traumatic hemorrhage and recurrent hemorrhage, but also can quantitatively study the changes in spleen blood perfusion in different stages.

Purpose: To report the treatment of late-onset lens particle glaucoma associated with posterior capsule rupture during pars plana vitrectomy., Methods: Case report., Results: A 33-year-old man had severe pain and impaired vision in the left eye after vitrectomy, associated with white fleck-like particles circulating in the anterior chamber. The intraocular pressure (IOP) was 38 mmHg. The anterior lens capsule was intact, however, lens particle glaucoma was diagnosed by the slit-lamp examination, B-mode ultrasonography and ultrasound biomicroscopy (UBM). The lens material was removed by irrigation-aspiration after the patient remained face down for two hours to facilitate precipitation of the lens material from the vitreous into the anterior chamber. IOP after the procedure was 21 mmHg., Conclusion: Posterior lens capsule may be disrupted during vitrectomy. Although the anterior lens capsule is intact, lens particle glaucoma should be considered when IOP increases with particulate matter circulating in the anterior chamber. Surgical removal of this material may be sufficient to control IOP without the need for additional glaucoma surgery.