LncRNA XIST promotes neovascularization in diabetic retinopathy by regulating miR-101-3p/VEGFA.

Objective: This study sought to investigate the regulation of long noncoding RNA (lncRNA) XIST on the microRNA (miR)-101-3p/vascular endothelial growth factor A (VEGFA) axis in neovascularization in diabetic retinopathy (DR). Materials and methods: Serum of patients with DR was extracted for the analysis of XIST, miR-101-3p, and VEGFA expression levels. High glucose (HG)-insulted HRMECs and DR model rats were treated with lentiviral vectors. MTT, transwell, and tube formation assays were performed to evaluate cell viability, migration, and angiogenesis, and ELISA was conducted to detect the levels of inflammatory cytokines. Dual-luciferase reporter, RIP, and RNA pull-down experiments were used to validate the relationships among XIST, miR-101-3p, and VEGFA. Results: XIST and VEGFA were upregulated and miR-101-3p was downregulated in serum from patients with DR. XIST knockdown inhibited proliferation, migration, vessel tube formation, and inflammatory responsein HG-treated HRMECs, whereas the above effects were nullified by miR-101-3p inhibition or VEGFA overexpression. miR-101-3p could bind to XIST and VEGFA. XIST promoted DR development in rats by regulating the miR-101-3p/VEGFA axis. Conclusion: LncRNA XIST promotes VEGFA expression by downregulating miR-101-3p, thereby stimulating angiogenesis and inflammatory response in DR.

Leveraging pQTL-based Mendelian randomization to identify new treatment prospects for primary biliary cholangitis and primary sclerosing cholangitis.

Primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) are autoimmune disorders characterized by progressive and chronic damage to the bile ducts, presenting clinicians with significant challenges. The objective of this study is to identify potential druggable targets to offer new avenues for treatment. A Mendelian randomization analysis was performed to identify druggable targets for PBC and PSC. This involved obtaining Cis-protein quantitative trait loci (Cis-pQTL) data from the deCODE database to serve as exposure. Outcome data for PBC (557 cases and 281,127 controls) and PSC (1,715 cases and 330,903 controls) were obtained from the FINNGEN database. Colocalization analysis was conducted to determine whether these features share the same associated SNPs. Validation of the expression level of druggable targets was done using the GSE119600 dataset and immunohistochemistry for clinical samples. Lastly, the DRUGBANK database was used to predict potential drugs. The MR analysis identified eight druggable targets each for PBC and PSC. Subsequent summary-data-based MR and colocalization analyses showed that LEFTY2 had strong evidence as a therapeutic candidate for PBC, while HSPB1 had moderate evidence. For PSC, only FCGR3B showed strong evidence as a therapeutic candidate. Additionally, upregulated expression of these genes was validated in PBC and PSC groups by GEO dataset and clinical samples. This study identifies two novel druggable targets with strong evidence for therapeutic candidates for PBC (LEFTY2 and HSPB1) and one for PSC (FCGR3B). These targets offer new therapeutic opportunities to address the challenging nature of PBC and PSC treatment.

Novel insights into the pathogenesis of thyroid eye disease through ferroptosis-related gene signature and immune infiltration analysis.

Thyroid eye disease (TED) has brought great physical and mental trauma to patients worldwide. Although a few potential signaling pathways have been reported, knowledge of TED remains limited. Our objective is to explore the fundamental mechanism of TED and identify potential therapeutic targets using diverse approaches. To perform a range of bioinformatic analyses, such as identifying differentially expressed genes (DEGs), conducting enrichment analysis, establishing nomograms, analyzing weighted gene correlation network analysis (WGCNA), and studying immune infiltration, the datasets GSE58331, GSE105149, and GSE9340 were integrated. Further validation was conducted using qPCR, western blot, and immunohistochemistry techniques. Eleven ferroptosis-related DEGs derived from the lacrimal gland were originally screened. Their high diagnostic value was proven, and diagnostic prediction nomogram models with high accuracy and robustness were established by using machine learning. A total of 15 hub gene-related DEGs were identified by WGCNA. Through CIBERSORTx, we uncovered five immune cells highly correlated with TED and found several special associations between these immune cells and the above DEGs. Furthermore, EGR2 from the thyroid sample was revealed to be closely negatively correlated with most DEGs from the lacrimal gland. High expression of APOD, COPB2, MYH11, and MYCN, as well as CD4/CD8 T cells and B cells, was verified in the periorbital adipose tissues of TED patients. To summarize, we discovered a new gene signature associated with ferroptosis that has a critical impact on the development of TED and provides valuable insights into immune infiltration. These findings might highlight the new direction and therapeutic strategies of TED.

Impact of insomnia upon inflammatory digestive diseases and biomarkers: a two-sample mendelian randomization research on Europeans.

BACKGROUND: A number of observational studies indicate that insomnia is linked to inflammatory digestive diseases (IDDs). However, the definite relationship between insomnia and IDDs remains unclear. METHODS: We obtained the publicly available data from genome-wide association studies (GWAS) to conduct two-sample Mendelian randomization (MR) for association assessment. Five MR analysis methods were used to calculate the odds ratio (OR) and effect estimate, and the heterogeneity and pleiotropy tests were performed to evaluate the robustness of the variable instruments (IVs). RESULTS: One exposure and twenty outcome datasets based on European populations were included in this study. Using the inverse variance weighted method, we found insomnia was closely correlated with esophageal ulcer (OR = 1.011, 95%CI = 1.004-1.017, p = 0.001) and abdominal pain (effect estimate = 1.016, 95%CI = 1.005-1.026, p = 0.003). Suggestive evidence of a positively association was observed between insomnia and duodenal ulcer (OR = 1.006, 95%CI = 1.002-1.011, p = 0.009), gastric ulcer (OR = 1.008, 95%CI = 1.001-1.014, p = 0.013), rectal polyp (OR = 1.005, 95%CI = 1.000-1.010, p = 0.034), haemorrhoidal disease (OR = 1.242, 95%CI = 1.004-1.535, p = 0.045) and monocyte percentage (effect estimate = 1.151, 95%CI = 1.028-1.288, p = 0.014). No correlations were observed among other IDDs, phenotypes and biomarkers. CONCLUSIONS: Our MR study assessed the relationship between insomnia and IDDs/phenotypes/biomarkers in depth and revealed potential associations between insomnia and ulcers of the esophagus and abdominal pain.

Long Noncoding RNA MIAT Modulates Chronic Retinal Ischemia-Reperfusion Injury in Mice via the microRNA-203-3p/SNAI2 Axis.

Retinal ischemia-reperfusion injury (RIRI) is a vital pathological process of multiple ocular diseases. This study aimed at investigating the effects of the MIAT/miR-203-3p/SNAI2 axis on RIRI. RIRI was produced by inducing an exceedingly high intraocular pressure (IOP) in mice. Mouse retinal ganglion cells (RGCs) were subjected to oxygen-glucose deprivation/reoxygenation (OGD/R) to mimic in vitro models. Relevant oligonucleotides or plasmids were transfected into OGD/R-induced RGCs in vitro or injected into RIRI mice models in vivo via a vitreous cavity. The findings of our paper indicated that MIAT and SNAI2 were highly expressed and miR-203-3p was lowly expressed in mouse RIRI tissues and OGD/R-induced RGCs. Interfering MIAT promoted the viability of OGD/R-induced RGCs, decreased apoptosis, and reduced oxidative stress in vitro. Silencing MIAT increased retinal neuronal cell numbers and decreased retinal neuronal cell apoptosis in mouse RIRI tissues in vivo. MIAT sponged miR-203-3p, and miR-203-3p targeted and inhibited SNAI2 expression. SNAI2 up-regulation or miR-203-3p down-regulation reversed the protective effects of MIAT down-regulation on RIRI in mice and OGD/R-induced RGCs. MIAT sponges miR-203-3p upregulated the expression of SNAI2, thereby promoting RIRI in mice. In summary, MIAT may be a therapeutic target for the treatment of chronic RIRI.

A Modified Double-Eyelid Blepharoplasty: Tarsus Linkage Mechanism.

BACKGROUND: Double-eyelid blepharoplasty is the most popular plastic surgery in East Asia. The incisional methods are divided into two schools. The traditional method produces a stable eyelid, but will leave a postoperative scar. The other is represented by "Park," creating dynamic double-eyelid technology. Its advantage is that there is only mild scarring, but its disadvantages are asymmetry, corneal exposure, and loss of the palpebral furrow. Due to these various complications, we here propose an improved incisional blepharoplasty with the tarsus linkage mechanism. METHODS: This work covers 482 patients who underwent surgery from March 2018 to March 2022. All patients completed 6 months of postoperative follow-up. The basic procedure described here involves removing the pre-tarsal tissue without completely incising the orbicularis and suturing the orbicularis and the tarsus into a unit. This connection provides a more robust and stable eyelid adhesion. RESULTS: As reported by physicians, 412 patients (85.5%) had satisfactory results, 69 patients (14.3%) had somewhat satisfactory results, and 1 patient (0.2%) had unsatisfactory results. As reported by the patients, 424 patients (88.0%) were satisfied, 57 patients (11.8%) were somewhat satisfied, and 1 patient (0.2%) was unsatisfied. CONCLUSION: This study proposes a modified double-eyelid blepharoplasty with the tarsus linkage mechanism. It is suitable for most primary eye cases, particularly in patients with lax upper lid skin and high levels of upper orbital fat. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

The outcomes of endoscopic orbital decompression combined with fat decompression for thyroid-associated ophthalmopathy.

PURPOSE: To present the clinical features of thyroid-associated ophthalmopathy (TAO) with different CT types, and to report the outcomes of endoscopic orbital decompression combined with fat decompression (EOD-FD). PATIENTS AND METHODS: Thirty-four patients with TAO who underwent EOD-FD between December 2020 and March 2022 in the Ophthalmology Department of Li Huili Hospital Affiliated with Ningbo University, were included in this retrospective interventional case series. Patients were categorized into two groups based on the results of computerized tomography (CT) scans: muscle expansion type and fat hyperplasia type. RESULTS: Thirty-four TAO patients (55 eyes) were included in this study, and the mean age was 38.62 years (range 22-60 years). The average eye protrusion (EP) reduced from preoperative 23.20 mm to postoperative 19.66 mm (p < 0.0001). Mean intraocular pressure (IOP) decreased from 20.11 mmHg at baseline to 17.29 mmHg postoperatively (p < 0.0001), with a reduction of 2.84 mmHg (14.12%). Twenty cases of muscle expansion and fourteen cases of fat hyperplasia were definite by CT imaging. The mean IOP in the muscle expansion group was higher than that in the fat hyperplasia group (p < 0.05). Elevated intraocular pressure (IOP) occurred in 23 eyes (36.11%), and it was associated with extraocular muscle involvement, gender, and EP. In 3 cases of impaired vision, the mean best corrected visual acuity (VA) improved from 0.4 preoperatively to 0.84 postoperatively (p < 0.01). There were 8 cases with visual field (VF) damage and/or corneal epithelium damage, and all these damages were reversible. CONCLUSION: In this study, we describe the clinical features and experience of EOD-FD in patients with TAO. EOD-FD is an effective technique in reducing IOP and proptosis, with a low incidence of postoperative diplopia.

Clinical Features of Glaucoma Associated with Cytomegalovirus Corneal Endotheliitis.

Purpose: The purpose of this study was to highlight the manifestations of glaucoma associated with cytomegalovirus (CMV) corneal endotheliitis. Methods: We reviewed the 34 patients that met the diagnostic criteria for CMV endotheliitis in our hospital, with special attention to the glaucoma status, including onset of glaucoma, glaucoma in the fellow eye, visual field defects, intraocular pressure, and final outcomes. Results: Thirty-four eyes of 34 patients (mean age, 69.1 ± 13.1 years; 31 males [91.2%]) with CMV corneal endotheliitis were enrolled. Thirty-two eyes (94.1%) had a history of a glaucoma diagnosis, which had been treated for 10.0 ± 10.1 years. Glaucoma in the fellow eye was noted in 16 cases (47.1%) and a history of Posner-Schlossman syndrome was noted in 13 cases (38.2%). Visual fields measured using a Humphrey field analyzer were normal-to-early stage (MD>-6dB) in 16 eyes (47.1%) and middle-to-late stage (MD≤-6dB) in 18 eyes (52.9%). The intraocular pressure decreased from 22.4 ± 10.6 mmHg at the initial visit to 14.9 ± 7.9 mmHg after medical treatment, including 0.5% topical ganciclovir (GCV) with and without a systemic anti-CMV agent, corticosteroid eye drops, and an anti-glaucoma agent (p<0.01). During the follow-up period of 4.8 ± 3.0 years (range, 0.2-10 years), 16 eyes (47.1%) required glaucoma surgery, including filtering surgery (7 eyes) and trabeculotomy only (9 eyes). Conclusion: Our case series showed that most of the patients with CMV corneal endotheliitis had glaucoma. Although medical therapy, including 0.5% topical GCV, had efficacy in lowering the intraocular pressure, one-half of the cases required glaucoma surgery. Therefore, ophthalmologists should strive to make an earlier diagnosis of CMV corneal endotheliitis by utilizing PCR testing of aqueous humor samples to prevent sight-threatening glaucomatous damage.

Successful treatment of aortic dissection with pulmonary embolism: A case report.

BACKGROUND: Aortic dissection (AD) and pulmonary embolism (PE) are both life-threatening disorders. Because of their conflicting treatments, treatment becomes difficult when they occur together, and there is no standard treatment protocol. CASE SUMMARY: A 67-year-old man fell down the stairs due to syncope and was brought to our hospital as a confused and irritable patient who was uncooperative during the physical examination. Further examination of the head, chest and abdomen by computed tomography revealed a subdural hemorrhage, multiple rib fractures, a hemopneumothorax and a renal hematoma. He was admitted to the Emergency Intensive Care Unit and given a combination of oxygen therapy, external rib fixation, analgesia and enteral nutrition. The patient regained consciousness after 2 wk but complained of abdominal pain and dyspnea with an arterial partial pressure of oxygen of 8.66 kPa. Computed tomography angiograms confirmed that he had both AD and PE. We subsequently performed only nonsurgical treatment, including nasal high-flow oxygen therapy, nonsteroidal analgesia, amlodipine for blood pressure control, beta-blockers for heart rate control. Eight weeks after admission, the patient improved and was discharged from the hospital. CONCLUSION: Patients with AD should be alerted to the possibility of a combined PE, the development of which may be associated with aortic compression. In patients with type B AD combined with low-risk PE, a nonsurgical, nonanticoagulant treatment regimen may be feasible.

Long-term outcomes of Descemet stripping automated endothelial keratoplasty for bullous keratopathy after argon laser iridotomy.

PURPOSE: To report the long-term outcomes of Descemet stripping automated endothelial keratoplasty (DSAEK) for bullous keratopathy secondary to argon laser iridotomy (BK-ALI). STUDY DESIGN: Retrospective chart review. METHODS: Forty-five eyes from 41 consecutive patients with BK-ALI who underwent DSAEK from July 2007 to December 2013 were retrospectively analyzed. Best spectacle-corrected visual acuity (BCVA), endothelial cell density (ECD), and any complications were investigated over a 10-year postoperative period. RESULTS: The mean BCVA improved from 0.80 logMAR before DSAEK to 0.28 logMAR at 6 months after DSAEK; the mean values showed an additional slight improvement between 6 months and 10 years after the surgery (P < .01). The mean ECD decreased from 2864 cells/mm2 at baseline to 2269 cells/mm2 (20.8% loss) at 6 months post-DSAEK, and this decreasing trend continued throughout the 10 years after DSAEK (P < .01). The mean ECD was 1148 cells/mm2 (59.9% loss) after 5 years, and 568 cells/mm2 (80.2% loss) after 10 years. No graft deaths were observed throughout the 10-year period (5-year follow-up rate 60.0%, 10-year follow-up rate 20.0%). CONCLUSIONS: The 10-year outcomes of DSAEK for BK-ALI were excellent with a high graft survival rate.

Visualization of the Retina in Intact Eyes of Mice and Ferrets Using a Tissue Clearing Method.

Purpose: Visualization of specific cells and structures in intact organs would greatly facilitate our knowledge about pathological changes; therefore, a tissue clearing method applicable to the intact eye may be valuable. Here we report a novel imaging method for the retina using the hyperhydration-based tissue clearing technique CUBIC (Clear, Unobstructed Brain/Body Imaging Cocktails and Computational Analysis). Methods: Eyes of Institute of Cancer Research (ICR) mice, C57BL/6 mice, and normally pigmented sable ferrets (Mustela putorius furo) were used. Intact eyes were subjected to CUBIC, melanin bleaching with H2O2, and immunostaining. Images of the retina in intact eyes were taken using epifluorescence microscopes and confocal microscopes. Results: The combination of melanin bleaching and CUBIC efficiently made the eyes of C57BL/6 mice transparent. By combining melanin bleaching, CUBIC, and immunostaining, we succeeded in visualization of retinal structures from the outside of the intact eyes of mice. Furthermore, we found that our methods were applicable not only to mouse eyes but also to ferret eyes, which are much larger than those of mice. Conclusions: Our method was useful for visualizing specific cells and structures in the retina of intact eyes with single-cell resolution without making tissue sections. Translational Relevance: This simple and efficient method can be applicable to various rodent models, including those associated with glaucoma or myopia, and will facilitate evaluating the effects of novel therapy for relevant eye diseases by visualizing changes from the retina to the sclera at both molecular and macroscopic levels simultaneously in a whole-eye preparation.