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Objective: Xueshuantong (lyophilized) for injection (XST) is an effective botanical drug for treating unstable angina pectoris (UAP). However, a meta-analysis of XST combined with conventional treatment (CT) against UAP has not been conducted. Therefore, this study aimed to investigate the effectiveness and safety of XST combined with CT for UAP patients compared to CT alone.Methods: Randomized controlled trials (RCT) of XST in UAP patients were retrieved from the Cochrane Library, PubMed, Web of Science, EMBASE, CNKI, VIP, Wanfang, and Chinese Biological Medicine Database databases. A meta-analysis was performed using Revman 5.4 and Stata 16.0, and the quality of the included literature was evaluated based on the Cochrane risk-of-bias 2.0 (RoB2.0) tool. The aggregate 95% confidence intervals (CIs), mean difference (MD), and relative risk (RR) estimates were calculated. A GRADE assessment was performed using GRADEprofiler 3.6, and trial sequent analysis was performed using TSA 0.9.Results: Thirty-four studies involving 3,518 patients were included in the analysis. The combination of CT with XST improved the comprehensive clinical efficacy (RR = 1.22, 95% CI: 1.18–1.26, p < 0.00001) and ECG improvement (RR = 1.24, 95% CI: 1.18–1.31, p < 0.00001). The frequency of angina attacks was lower (MD = −0.73, 95% CI: −0.92 to −0.55, p < 0.00001), and the duration was shorter (MD = −1.08, 95% CI: −1.44 to −0.72, p < 0.00001) in the group that received CT combined with XST compared to the one without XST. Total cholesterol levels (MD = −1.30, 95% CI: −1.83 to −0.78, p < 0.00001) and triglyceride levels (MD = −0.76, 95% CI: −0.93 to −0.59, p < 0.00001) were lower in patients who received CT in combination with XST than those who received CT alone. CT combined with XST reduced whole blood viscosity (MD = −0.72, 95% CI = −0.99 to −0.44, p < 0.00001) and plasma viscosity (MD = −0.24, 95% CI: −0.46 to −0.03, p = 0.03). There was no statistically significant difference in the incidence of cardiovascular events or adverse events among patients treated with the combination of XST and CT compared to CT alone. The GRADE assessment indicated that the composite quality of the evidence was low. The trial sequent analysis showed an adequate sample size and stable findings for the clinical efficacy of CT combined with XST for unstable angina.Conclusion: The present systematic review and meta-analysis conditionally indicate that XST combined with CT improved the clinical outcomes of patients with unstable angina more than CT alone with a better safety profile. However, the results need further validation due to limitations in the quality of the included studies.Systematic Review Registration:https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022357395.

Thyroid associated ophthalmopathy (TAO) is an orbital autoimmune inflammatory disease that is commonly associated with thyroid dysfunction. Although the etiology of TAO is unclear, ROS accumulation and oxidative stress have been closely linked to the pathogenesis of TAO. Ferroptosis is an iron-dependent programmed cell death characterized by intracellular labile iron levels, excessive accumulation of reactive oxygen species (ROS) and lipid peroxidation. Currently, there are few reports regarding the role of ferroptosis in TAO. This article aimed to identify ferroptosis-related genes (FRGs) with diagnostic and therapeutic potential in TAO and explore their relationship with immune cells and lncRNAs. GSE58331 was downloaded from Gene Expression Omnibus (GEO) database. A total of 162 DEGs were identified between 27 TAO samples and 22 health samples from GSE58331, among which six FRGs (CYBB, CTSB, SLC38A1, TLR4, PEX3, and ABCC1) were obtained. The AUC of SLC38A1, TLR4, PEX3 in lacrimal gland tissues was greater than 80 which suggested high diagnostic value in TAO. The result of immune cell infiltrate analysis indicated increased infiltration of monocytes (p < 0.001), macrophages M0(p = 0.039), mast cells activated (p = 0.008), and neutrophils (p = 0.045) in orbital tissues from TAO patients. Meanwhile, mast cells resting (p = 0.043) and macrophages M2 (p = 0.02) showed reduced infiltration in TAO samples. There were no gender differences in immune cell infiltration in the TAO patients. Two differentially expressed lncRNAs, LINC01140 and ZFHX4-AS1, in TAO groups were identified as ferroptosis-related lncRNAs. CYBB-LINC01140-TLR4, CYBB- LINC01140- SLC38A1, TLR4- LINC01140- SLC38A1, and CTSB- ZFHX4-AS1- CYBB may be potential RNA regulatory pathways in TAO. Targeted drugs and transcription factors for differential expressed FRGs were also screened out in our study. In vitro, experiments revealed that CTSB, PEX3, ABCC1 and ZFHX4-AS1(lncRNA) were differentially expressed in orbital fibroblasts (OFs) between TAO groups and healthy controls at the transcriptional level.

Thyroid-associated ophthalmopathy (TAO) is a complicated orbitopathy related to dysthyroid, which severely destroys the facial appearance and life quality without medical interference. The diagnosis and management of thyroid-associated ophthalmopathy are extremely intricate, as the number of professional ophthalmologists is limited and inadequate compared with the number of patients. Nowadays, medical applications based on artificial intelligence (AI) algorithms have been developed, which have proved effective in screening many chronic eye diseases. The advanced characteristics of automated artificial intelligence devices, such as rapidity, portability, and multi-platform compatibility, have led to significant progress in the early diagnosis and elaborate evaluation of these diseases in clinic. This study aimed to provide an overview of recent artificial intelligence applications in clinical diagnosis, activity and severity grading, and prediction of therapeutic outcomes in thyroid-associated ophthalmopathy. It also discussed the current challenges and future prospects of the development of artificial intelligence applications in treating thyroid-associated ophthalmopathy.

PurposeA six-category model of common retinal diseases is proposed to help primary medical institutions in the preliminary screening of the five common retinal diseases.MethodsA total of 2,400 fundus images of normal and five common retinal diseases were provided by a cooperative hospital. Two six-category deep learning models of common retinal diseases based on the EfficientNet-B4 and ResNet50 models were trained. The results from the six-category models in this study and the results from a five-category model in our previous study based on ResNet50 were compared. A total of 1,315 fundus images were used to test the models, the clinical diagnosis results and the diagnosis results of the two six-category models were compared. The main evaluation indicators were sensitivity, specificity, F1-score, area under the curve (AUC), 95% confidence interval, kappa and accuracy, and the receiver operator characteristic curves of the two six-category models were compared in the study.ResultsThe diagnostic accuracy rate of EfficientNet-B4 model was 95.59%, the kappa value was 94.61%, and there was high diagnostic consistency. The AUC of the normal diagnosis and the five retinal diseases were all above 0.95. The sensitivity, specificity, and F1-score for the diagnosis of normal fundus images were 100, 99.9, and 99.83%, respectively. The specificity and F1-score for RVO diagnosis were 95.68, 98.61, and 93.09%, respectively. The sensitivity, specificity, and F1-score for high myopia diagnosis were 96.1, 99.6, and 97.37%, respectively. The sensitivity, specificity, and F1-score for glaucoma diagnosis were 97.62, 99.07, and 94.62%, respectively. The sensitivity, specificity, and F1-score for DR diagnosis were 90.76, 99.16, and 93.3%, respectively. The sensitivity, specificity, and F1-score for MD diagnosis were 92.27, 98.5, and 91.51%, respectively.ConclusionThe EfficientNet-B4 model was used to design a six-category model of common retinal diseases. It can be used to diagnose the normal fundus and five common retinal diseases based on fundus images. It can help primary doctors in the screening for common retinal diseases, and give suitable suggestions and recommendations. Timely referral can improve the efficiency of diagnosis of eye diseases in rural areas and avoid delaying treatment.

Background: Growing evidence has recently revealed the characteristics of long noncoding (lncRNA)/circular RNA (circRNA)-microRNA (miRNA)-mRNA networks in numerous human diseases. However, a scientific lncRNA/circRNA-miRNA-mRNA network related to Graves’ ophthalmopathy (GO) remains lacking.Materials and methods: The expression levels of RNAs in GO patients were measured through high-throughput sequencing technology, and the results were proven by quantitative real-time PCR (qPCR). We constructed a protein-protein interaction (PPI) network using the Search Tool for the Retrieval of Interacting Genes (STRING) database and identified hub genes by the Cytoscape plug-in CytoHubba. Then, the miRNAs related to differentially expressed lncRNAs/circRNAs and mRNAs were predicted through seed sequence matching analysis. Correlation coefficient analysis was performed on the interesting RNAs to construct a novel competing endogenous RNA (ceRNA) network.Results: In total, 361 mRNAs, 355 circRNAs, and 242 lncRNAs were differentially expressed in GO patients compared with control patients, 166 pairs were identified, and ceRNA networks were constructed. The qPCR results showed that 4 mRNAs (THBS2, CHRM3, CXCL1, FPR2) and 2 lncRNAs (LINC01820:13, ENST00000499452) were differentially expressed between the GO patients and control patients.Conclusion: An innovative lncRNA/circRNA-miRNA-mRNA ceRNA network between GO patients and control patients was constructed, and two important ceRNA pathways were identified, the LINC01820:13-hsa-miR-27b-3p-FPR2 ceRNA pathway and the ENST00000499452-hsa-miR-27a-3p-CXCL1 pathway, which probably affect the autoimmune response and inflammation in GO patients.

Purpose: We examined the macular microvascular changes of the macula in neuromyelitis optica spectrum disorder (NMOSD) patients and its association with their disability and other clinical variables.Methods: Thirty-four NMOSD (13 patients without optic neuritis, NMOSD-NON, and 21 patients with a history of optic neuritis, NMOSD-ON) and 44 healthy controls (HCs) were included in the study. Optical coherence tomographic angiography (OCTA) was used to image the superficial (SCP), deep (DCP), and whole capillary plexus (WCP) in a 2.5-mm-diameter concentric circle [excluding the foveal avascular zone (FAZ)]. An algorithm (Dbox) was used to quantify the complexity of the three capillary layers by fractal analysis. We also evaluated the expanded disability scale status (EDSS).Results: Dbox values were significantly reduced in SCP (p < 0.001), DCP (p < 0.001), and WCP (p = 0.003) of NMOSD when compared with HCs. Dbox values were significantly reduced in NMOSD eyes with optic neuritis when compared with healthy controls (p < 0.001) and eyes without optic neuritis (p = 0.004) in the SCP. In the DCP, eyes with optic neuritis showed significantly reduced Dbox values when compared with eyes without optic neuritis (p = 0.016) and healthy controls (p < 0.001); eyes without optic neuritis showed significantly reduced Dbox values (p = 0.007) in the DCP when compared with healthy controls. A significant negative correlation (Rho = −0.475, p = 0.005) was shown between the superficial macula Dbox values and the EDSS in NMOSD patients. Additionally, a negative correlation (Rho = −0.715, p = 0.006) was seen in the superficial Dbox values in [e]eyes without optic neuritis and EDSS.Conclusions: Macular microvascular damage in the superficial plexus is associated with disability in NMOSD. Macular microvascular alterations arise independently of the occurrence of ON in NMOSD.

Background: Determining the early changes of brain structure that occur from vegetative state/unresponsive wakefulness syndrome (VS/UWS) to a minimally conscious state (MCS) is important for developing our understanding of the processes underlying disorders of consciousness (DOC), particularly during spontaneous recovery from severe brain damage. Objective: This study used a multi-modal neuroimaging approach to investigate early structural changes during spontaneous recovery from VS/UWS to MCS. Methods: The Coma Recovery Scale-Revised (CRS-R) score, 24-h electroencephalography (EEG), and ultra-high field 7 Tesla Magnetic Resonance Imaging were used to investigate a male patient with severe brain injury when he was in VS/UWS compared to MCS. Using white matter connectometry analysis, fibers in MCS were compared with the same fibers in VS/UWS. Whole brain analysis was used to compare all fibers showing a 10% increase in density with each other as a population. Results: Based on connectometry analysis, the number of fibers with increased density, and the magnitude of increase in MCS compared to VS/UWS, were greatest in the area of the temporoparietal junction (TPJ), and were mostly located in the right hemisphere. These results are in accordance with the active areas observed on 24-h EEG recordings. Moreover, analysis of different fibers across the brain, showing at least a 10% increase in density, revealed that altered white matter connections with higher discriminative weights were located within or across visual-related areas, including the cuneus_R, calcarine_R, occipital_sup_R, and occipital_mid_R. Furthermore, the temporal_mid_R, which is related to the auditory cortex, showed the highest increase in connectivity to other areas. This was consistent with improvements in the visual and auditory components of the CRS-R, which were greater than other improvements. Conclusion: These results provide evidence to support the important roles for the TPJ and the visual and auditory sensory systems in the early recovery of a patient with severe brain injury. Our findings may facilitate a much deeper understanding of the mechanisms underlying conscious-related processes and enlighten treatment strategies for patients with DOC.