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.

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.

Application of optical coherence tomography angiography in the assessment of diabetic macular edema staging and laser photocoagulation efficacy.

OBJECTIVE: This study aimed to analyze the effect of optical coherence tomography angiography (OCTA) on diabetic macular edema (DME) staging and assess the efficacy of laser photocoagulation. METHODS: Eighty-six patients (141 eyes) with suspected DME who visited our hospital from August 2019 to March 2022 were selected and underwent fundus angiography and OCTA. The two examination methods were compared in terms of their efficacy in macular edema staging. Subsequently, the sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of OCTA in diagnosing DME were assessed using fundus angiography as the gold standard. In patients with clinically significant macular edema (CSME) treated with laser photocoagulation, the central concave non-perfused zone (FAZ), vascular density (VD), central macular retinal thickness (CRT), whole retinal blood flow density (FD-300), superficial capillary plexus (SCP), and deep capillary plexus (DCP) were measured using the OCTA 3 mm × 3 mm mode before treatment, at 3 months after treatment, and at 6 months after treatment. SCP, deep capillary plexus (DCP), blood flow density (VD), best corrected visual acuity (BCVA), and central retinal thickness (CRT) were recorded before treatment, 3 months after treatment, and 6 months after treatment. The correlation between BCVA and pre-treatment OCTA parameters at 6 months after treatment was analyzed using Pearson's correlation. RESULTS: Fundus angiography was performed in 86 patients (141 eyes) with suspected DME. Of the 141 eyes, 44 had no leakage, 52 had diffuse edema, 40 had focal macular edema, and 5 had eyes ischemia. A total of 97 eyes showed CSME on fundus angiography. Using fundus angiography as the gold standard, OCTA exhibited a sensitivity of 97.94 %, a specificity of 63.64 %, and an accuracy of 87.23 % in diagnosing CSME. The Kappa value between OCTA and fundus angiography was 0.674. The receiver operating characteristic curve revealed that the area under the curve (AUC) of OCTA in diagnosing CSME was 0.808 (95 % confidence interval: 0.717-0.899). The BCVA was higher, while the CRT was lower in CSME patients at 3 and 6 months after treatment (P<0.05). No significant difference was observed in the OCTA parameters in CSME patients at 3 months after treatment compared with that before treatment (P>0.05). Similarly, no significant difference was found in the FD300 of CSME patients at 6 months after treatment compared with that before treatment (P>0.05). However, the FAZ area, DCP-VD (overall, central concave, and paracentral concave), and SCP-VD (overall, central concave, and paracentral concave) were higher in CSME patients at 6 months after treatment compared with that before treatment (P<0.05). Pearson's correlation showed that BCVA was positively correlated with pre-treatment FAZ area, DCP-VD, and SCP-VD (r>0, P<0.05), and negatively associated with CRT (r<0, P<0.05). CONCLUSION: OCTA exhibited high sensitivity and specificity in diagnosis and staging DME. It adeptly captures the microvascular and visual changes in the central macular recess before and after laser photocoagulation therapy, which can quantitatively guide the follow-up treatment of DME.

Association between red blood cell distribution width/albumin ratio and all-cause mortality or cardiovascular diseases mortality in patients with diabetic retinopathy: A cohort study.

BACKGROUND: Red blood cell distribution width/albumin ratio (RAR) has been reported as an independent risk factor for diabetic retinopathy (DR), while its association and predictive value in the prognosis of DR patients has not been reported. This study aims to explore the association and predictive value of RAR in the prognosis of DR patients. METHODS: This was a retrospective cohort study based on the National Health and Nutrition Examination Survey (NHANES). The independent variable was RAR, and dependent variables were all-cause mortality and cardiovascular diseases (CVD) mortality. The association between RAR and the risk of all-cause mortality and CVD mortality was assessed using univariate and multivariate cox regression models. The results were shown as HR (hazard ratio) with 95% confidence intervals (CIs). Subgroup analysis based on age or hyperlipidemia was performed. The discrimination of the prediction model was assessed using concordance index (C-index). RESULTS: A total of 725 eligible patients were finally included in this study. The increase of RAR was associated with increased risk of all-cause mortality (HR: 1.15, 95%CI: 1.01-1.31) and CVD mortality (HR: 1.35, 95%CI: 1.12-1.63) after adjusting the covariates. We also found the significant association between higher RAR and higher risk of CVD mortality in DR patients with age < 65 years (HR: 1.35, 95%CI: 1.09-1.67) and with hyperlipidemia (HR: 1.34, 95%CI: 1.10-1.64). C-index of RAR for all-cause mortality and CVD mortality was 0.63 (95%CI: 0.59-0.67) and 0.65 (95%CI: 0.59-0.71), respectively. CONCLUSIONS: Higher RAR was associated with the higher risk of all-cause mortality and CVD mortality in DR patients, and RAR may be a useful predictor for the prognosis of DR patients.

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.

SCTV-UNet: a COVID-19 CT segmentation network based on attention mechanism.

The global outbreak of COVID-19 has become an important research topic in healthcare since 2019. RT-PCR is the main method for detecting COVID-19, but the long detection time is a problem. Therefore, the pathological study of COVID-19 with CT image is an important supplement to RT-RCT. The current TVLoss-based segmentation promotes the connectivity of diseased areas. However, normal pixels between some adjacent diseased areas are wrongly identified as diseased pixels. In addition, the proportion of diseased pixels in CT images is small, and the traditional BCE-based U-shaped network only focuses on the whole CT without diseased pixels, which leads to blurry border and low contrast in the predicted result. In this way, this paper proposes a SCTV-UNet to solve these problems. By combining spatial and channel attentions on the encoder, more visual layer information are obtained to recognize the normal pixels between adjacent diseased areas. By using the composite function DTVLoss that focuses on the pixels in the diseased area, the problem of blurry boundary and low contrast caused by the use of BCE in traditional U-shaped networks is solved. The experiment shows that the segmentation effect of the proposed SCTV-UNet has significantly improved by comparing with the SOTA COVID-19 segmentation networks, and can play an important role in the detection and research of clinical COVID-19.

Changes of Volume Parameters in the Treatment of Graves Ophthalmopathy by Endoscopic Transethmoidal Decompression of the Orbital Inner Wall Combined with Fat Decompression.

Objective: To observe the orbital volume changes and the analysis of surgical effect of Graves orbitopathy (GO) after endoscopic medial wall decompression combined with muscle cone fat. Methods: Twenty-two patients (30 eyes) with Graves orbital disease who visited the Department of Ophthalmology of Ningbo Medical Center from December 2019 to September 2021 were retrospectively collected. All patients were diagnosed as nonorganic active stage before operation, and all of them received endoscopic transethmoidal decompression of the medial orbital wall combined with intramuscular orbital fat decompression due to decreased vision, visual field defect or color vision disorder, and concomitant proptosis. Regular follow-up after operation. The curative effect is judged according to the degree of improvement of visual acuity, color vision, degree of correction of exophthalmos, diplopia, and other complications at 9 months after operation. Orbital CT combined with computer aided measurement software (Mimics 21) was used to measure the changes of orbital volume before and after exophthalmos surgery. The relationship between the value and eyeball regression is analyzed. Results: Preoperative exophthalmos ranged from 17.4 mm to 27.6 mm, with an average of (22.08 ± 2.86) mm. The postoperative exophthalmos was 14-25 mm, with an average of (19.52 ± 3.10) mm. Among them, 7 eyes (23.3%) had exophthalmos regression less than 1 mm, 6 eyes (20%) had a regression of 1-2 mm, 7 eyes (23.3%) had a regression of 2-3 mm, 5 eyes (16.7%) had a regression of 3-4 mm, and 5 eyes (16.7%) had a regression of 4-5.3 mm. The exophthalmos after operation was significantly lower than that before operation, and the difference was statistically significant (t = 9.909, P < 0.05). The preoperative orbital volume was 18.6 cm3-25.3 cm3 with an average of (22.39 ± 1.91) cm3. The postoperative orbital volume was 19.8 cm3-26.6 cm3, with an average of (23.89 ± 1.90) cm3.The orbital volume change range is 0.1 cm3-3.8 cm3, and the average orbital volume change is (1.51 ± 1.00) cm3. Compared with preoperative orbital volume, the difference was statistically significant (t = -8.074, P < 0.05). Conclusion: Endoscopic decompression of the medial orbital wall through the ethmoid approach combined with decompression of the orbital fat within the muscle cone can effectively correct the exophthalmos while decompressing the orbital apex, and it is minimally invasive and has no facial scars. It has the advantages of extremely low incidence of postoperative diplopia and eye shift. There is a significant correlation between orbital volume changes and the regression of exophthalmos, which can provide reference for clinical guidance of surgical methods and prediction of surgical results.

LncRNA AK077216 is downregulated in diabetic retinopathy and inhibited the apoptosis of retinal pigment epithelial cells by downregulating miR-383.

LncRNA AK077216 is a novel lncRNA with critical role in osteoclastogenesis and bone resorption. Our preliminary RNA-seq data suggested its downregulated expression pattern in diabetic retinopathy (DR). We therefore further investigated the function of AK077216 in DR. Plasma samples used in this study were derived from blood, which was extracted from 60 diabetic retinopathy patients. AK077216 in plasma of DR patients, diabetic patients (DB) and controls (Control) was detected by RT-qPCR. ROC curve analysis was performed to evaluate the diagnostic value of plasma AK077216 for DR. It was found that plasma AK077216 was downregulated only in DR patients but not in diabetic patients (no obvious complications) comparing to healthy controls. Downregulation of AK077216 distinguished DR patients from diabetic patients and healthy controls. High glucose treatment failed to significantly affect AK077216 expression in cells of human retinal pigment epithelial cell line ARPE-19. MiR-383 was inversely correlated with AK077216 in DR patients. AK077216 overexpression caused miR-383 downregulation, but miR-383 overexpression did not significantly alter AK077216 expression. AK077216 overexpression inhibited ARPE-19 cell apoptosis, while miR-383 overexpression played an opposite role and attenuated the effects of AK077216 overexpression. Therefore, AK077216 is downregulated in diabetic retinopathy and inhibited the apoptosis of ARPE-19 cells by downregulating miR-383.

Changes in anthocyanins and volatile components of purple sweet potato fermented alcoholic beverage during aging.

Purple sweet potato was fermented into alcoholic beverage. By using LC-MS analysis, 12 types of anthocyanins were found in the purple sweet potato alcoholic beverage (PSPFAB); these were based on cyanidin and peonidin as aglycones. The anthocyanins in young PSPFAB mainly consisted of acylates. The acylated anthocyanins, however, degraded gradually with aging. Cyanidin 3-sophoroside-5-glucoside and peonidin 3-sophoroside-5-glucoside were found to be major anthocyanins in the PSPFAB after two years of aging. Moreover, 52 kinds of volatile components were detected in PSPFAB by GC-MS analysis. Alcohol and ester substances constituted a major proportion of these volatile components of PSPFAB. After two years of aging, levels of high-alcohols such as 1-pentanol remarkably decreased to below the detection limit, while the level of total esters increased significantly. Such variation of aromas enriched and improved the flavor of PSPFAB.

Nucleosome Positioning with Set of Key Positions and Nucleosome Affinity.

The formation and precise positioning of nucleosome in chromatin occupies a very important role of study in life process. Today, many researchers discover that the positioning where the location of a DNA sequence fragment wraps around a histone in genome is not random but regular. However, the positioning is closely relevant to the concrete sequence of core DNA. So in this paper, we analyzed the relation between the affinity and sequence structure of core DNA sequence, and extracted the set of key positions. In these positions, the nucleotide sequences probably occupied mainly action in the binding. First, we simplified and formatted the experimental data by the affinity. Then, to find the key positions in the wrapping, we used neural network to analyze the positive and negative effect of nucleosome generation for every position in core DNA sequences. However, we reached a class of weights with every position to describe this effect. Finally, based on the positions with high weights, we analyzed the reason why the chosen positions are key positions, and used these positions to construct a model of nucleosome positioning predict. Experimental results show the effectiveness of our method.