Transcriptomic analysis reveals the critical role of Chemokine signaling in the anti-atherosclerosis effect of Xuefu Zhuyu Decoction.

ETHNOPHARMACOLOGICAL RELEVANCE: The process of atherosclerosis (AS) is complicated. Transcriptomics technology can assist in discovering the underlying mechanisms and exploring the key targets of Traditional Chinese Medicine (TCM) against atherosclerosis. AIM: This study aimed to investigate targets and signaling pathways significantly related to AS and the potential intervention targets of Xuefu Zhuyu decoction by transcriptomics. MATERIALS AND METHODS: AS models were established by subjecting ApoE-/- mice to an 8-week high-fat diet. Structural changes and plaque formation in the aortic root were observed using hematoxylin-eosin staining (HE staining), while Oil Red O staining was employed to visualize lipid deposition within the aortic root plaque. Movat staining and immunohistochemical staining were conducted to examine the components present in the aortic root plaque. Macrophage content within the plaques was observed through immunofluorescence. Additionally, mRNA sequencing was performed on aortic tissues to identify differentially expressed genes. Enrichment analysis was performed using GO and KEGG analysis. Visualization of the protein-protein interaction (PPI) network was achieved using Cytoscape 3.7.1 and STRING. Western blotting (WB) was employed to assess the protein expression of major differentially expressed genes in the aortic tissue. The drug freeze-dried powder of Xuefu Zhuyu decoction was prepared and the RAW264.7 cells were induced by lipopolysaccharide (LPS) to build an in vitro model. Real-time quantitative PCR was employed to measure the mRNA expression of major differential genes. RESULTS: After ApoE-/- mice were fed with an 8-week high-fat diet, observable changes included the thinning of the aortic root wall, the accumulation of foam cells within the plaque, and the formation of cholesterol crystals in the model group. Treatment with Xuefu Zhuyu (XFZY) decoction for 12 weeks significantly reduced the lipid deposition and the number of macrophages within the plaque (P < 0.05) and significantly increased the collagen content within the plaque (P < 0.01). Enrichment analysis revealed a high enrichment of the cytokine-cytokine receptor interaction pathway and chemokine signaling pathway. Noteworthy genes involved in this response included Ccl12, Ccl22, Cx3cr1, Ccr7, Ccr2, Tnfrsf25, and Gdf5. Xuefu Zhuyu decoction significantly downregulated the expression of CX3CL1 and CX3CR1 (P < 0.05) and upregulated the expression of GDF5 (P < 0.01). Compared with control group, the mRNA expressions of Ccl12, Ccl22, and Ccr2 were significantly upregulated in LPS-stimulated RAW264.7 cells (P < 0.05 or P < 0.01). Xuefu Zhuyu decoction significantly downregulated the expression of Ccl12, Ccl22, Cx3cr1, Ccr7 and Ccr2 (P < 0.05 or P < 0.01). CONCLUSION: Xuefu Zhuyu decoction demonstrates effective regulation of plaque components, retarding plaque progression and preserving plaque stability by modulating lipid metabolism and inflammatory responses. Subsequent transcriptome analysis identified the cytokine-cytokine receptor interaction and chemokine signaling pathway as potential key pathways for the therapeutic effects of Xuefu Zhuyu decoction. This insight not only provides crucial avenues for further exploration into the mechanisms underlying Xuefu Zhuyu decoction but also offers valuable perspectives and hypotheses for enhancing disease prevention and treatment strategies.

Mechanism of Qili Qiangxin Capsule for Heart Failure Based on miR133a-Endoplasmic Reticulum Stress.

OBJECTIVE: To investigate the pharmacological mechanism of Qili Qiangxin Capsule (QLQX) improvement of heart failure (HF) based on miR133a-endoplasmic reticulum stress (ERS) pathway. METHODS: A left coronary artery ligation-induced HF after myocardial infarction model was used in this study. Rats were randomly assigned to the sham group, the model group, the QLQX group [0.32 g/(kg·d)], and the captopril group [2.25 mg/(kg·d)], 15 rats per group, followed by 4 weeks of medication. Cardiac function such as left ventricular ejection fraction (EF), fractional shortening (FS), left ventricular systolic pressure (LVSP), left ventricular end diastolic pressure (LVEDP), the maximal rate of increase of left ventricular pressure (+dp/dt max), and the maximal rate of decrease of left ventricular pressure (-dp/dt max) were monitored by echocardiography and hemodynamics. Hematoxylin and eosin (HE) and Masson stainings were used to visualize pathological changes in myocardial tissue. The mRNA expression of miR133a, glucose-regulated protein78 (GRP78), inositol-requiring enzyme 1 (IRE1), activating transcription factor 6 (ATF6), X-box binding protein1 (XBP1), C/EBP homologous protein (CHOP) and Caspase 12 were detected by RT-PCR. The protein expression of GRP78, p-IRE1/IRE1 ratio, cleaved-ATF6, XBP1-s (the spliced form of XBP1), CHOP and Caspase 12 were detected by Western blot. TdT-mediated dUTP nick-end labeling (TUNEL) staining was used to detect the rate of apoptosis. RESULTS: QLQX significantly improved cardiac function as evidenced by increased EF, FS, LVSP, +dp/dt max, -dp/dt max, and decreased LVEDP (P<0.05, P<0.01). HE staining showed that QLQX ameliorated cardiac pathologic damage to some extent. Masson staining indicated that QLQX significantly reduced collagen volume fraction in myocardial tissue (P<0.01). Results from RT-PCR and Western blot showed that QLQX significantly increased the expression of miR133a and inhibited the mRNA expressions of GRP78, IRE1, ATF6 and XBP1, as well as decreased the protein expressions of GRP78, cleaved-ATF6 and XBP1-s and decreased p-IRE1/IRE1 ratio (P<0.05, P<0.01). Further studies showed that QLQX significantly reduced the expression of CHOP and Caspase12, resulting in a significant reduction in apoptosis rate (P<0.05, P<0.01). CONCLUSION: The pharmacological mechanism of QLQX in improving HF is partly attributed to its regulatory effect on the miR133a-IRE1/XBP1 pathway.

Application of artificial intelligence in oculoplastics.

Oculoplastics is a subspecialty of ophthalmology/dermatology concerned with eyelid, orbital, and lacrimal diseases. Artificial intelligence (AI), with its powerful ability to analyze large data sets, has dramatically benefited oculoplastics. The cutting-edge AI technology is widely applied to extract ocular parameters and to use these results for further assessment, such as screening and diagnosis of blepharoptosis and predicting the progression of thyroid eye disease. AI also assists in treatment procedures, such as surgical strategy planning in blepharoptosis. High efficiency and high reliability are the most apparent advantages of AI, with promising prospects. The possibilities of AI in oculoplastics may lie in three-dimensional modeling technology and image generation. We retrospectively summarize AI applications involving eyelid, orbital, and lacrimal diseases in oculoplastics, and we also examine the strengths and weaknesses of AI technology in oculoplastics.

Gender Disparities in the Global Burden of Refractive Disorders in Children: An Analysis From the Global Burden of Disease Study 2019.

PURPOSE: To investigate gender disparities in the global burden of refractive disorders in children younger than 15 years by year, age, and national developmental status using disability-adjusted life years (DALYs). METHODS: Global, regional, and national gender-specific DALY numbers and rates of refractive disorders in children were obtained by year (from 1990 to 2019) and age group (0 to 4, 5 to 9, and 10 to 14 years) from the Global Burden of Disease Study 2019. Data from the Inequality-adjusted Human Development Index in 2019 as an indicator of national developmental status were extracted from the Human Development Report. Pearson correlation and linear regression analyses were performed to explore the association between female-to-male DALY rate ratios and national developmental status. RESULTS: Gender disparities in DALY numbers and rates of refractive disorders in children have persisted and shown little improvement from 1990 to 2019. Girls had a higher burden than boys of the same age, and gender disparities increased with age (1.120 in preschool children aged 0 to 4 years, 1.124 in younger school-aged children aged 5 to 9 years, and 1.135 in older school-aged children aged 10 to 14 years). Female-to-male DALY rate ratios were negatively related to Inequality-adjusted Human Development Index values (standardized b = -0.189, P < .05). CONCLUSIONS: Gender disparities in the global burden of refractive disorders in children have persisted for decades, with girls who are older and from lower-income countries having a higher burden than boys. Gender-specific health policies should be made to manage refractive disorders in children. [J Pediatr Ophthalmol Strabismus. 2024;61(1):51-58.].

Sex difference in incidence of major depressive disorder: an analysis from the Global Burden of Disease Study 2019.

BACKGROUND: Major depressive disorder (MDD) is a leading mental disorder causing severe impairment. This study was aimed to evaluate sex difference in global MDD incidence by year, age, and socioeconomic status, according to the Global Burden of Disease Study 2019 (GBD 2019). METHODS: Global and national sex-specific incidence estimates of MDD, from 1990 to 2019, in different age groups, were extracted from the GBD 2019. Socioeconomic development index (SDI) as an indicator of national socioeconomic development was used. Absolute (female minus male) and relative (female to male ratio) sex difference in age-standardized incidence rates (ASRs), as well as risk ratios (RR and 95% confidence interval), were computed by year and age. Linear regression analyses were conducted to investigate socioeconomic-associated sex difference in incidence. RESULTS: Absolute and relative sex difference in ASRs showed a slight declining trend during 1990 and 2019, with absolute difference decreasing from 1818.23 to 1602.58, and relative difference decreasing from 1.71 to 1.61. Worldwide, females had a higher risk of MDD than males in 1990 (RR: 1.706 (1.705-1.706)) and 2019 (RR: 1.602 (1.619-1.620)). The highest RRs were observed in the Region of the Americas. Sex difference in incidence rates increased rapidly with age for those under 20 years old. The highest RR (1.913 (1.910-1.915)) was observed in the age group of 10-14. Relative sex difference had a significant positive relationship with SDI (standardized ß = 0.267, P < 0.001). CONCLUSIONS: Despite that slight improvement in sex difference in global MDD incidence has been achieved, sex difference still persists in the past decades, with females always having a higher incidence than males. Greater sex difference was found at younger ages and in more developed countries. The findings highlight the importance of making sex-specific health policy to reduce sex difference in MDD incidence.

Retinogenesis in a Dish: Bibliometric Analysis and Visualization of Retinal Organoids From 2011 to 2022.

Retinal organoid (RO) is the three-dimensional (3D) retinal culture derived from pluripotent or embryonic stem cells which recapitulates organ functions, which was a revolutionary milestone in stem cell technology. The purpose of this study is to explore the hotspots and future directions on ROs, as well as to better understand the fields of greatest research opportunities. Eligible publications related to RO from 2011 to 2022 were acquired from the Web of Science (WoS) Core Collection database. Bibliometric analysis was performed by using software including VOSviewer, CiteSpace, and ArcGIS. A total of 520 articles were included, and the number of annual publications showed a rapid increase with an average rate of 40.86%. The United States published the most articles (241/520, 46.35%) with highest total citation frequencies (5,344). University College London (UK) contributed the largest publication output (40/520, 7.69%) and received highest total citation frequencies. Investigative Ophthalmology & Visual Science was the most productive journal with 129 articles. Majlinda Lako contributed the most research with 32 articles, while Olivier Goureau has the strongest collaboration work. Research could be subdivided into four keyword clusters: "culture and differentiation," "morphogenesis and modeling," "gene therapy," and "transplantation and visual restoration," and evolution of keywords was identified. Last decade has witnessed the huge progress in the field of RO, which is a young and promising research area with extensive and in-depth studies. More attention should be paid to RO-related models and therapies based on specific retinal diseases, especially inherited retinopathies.

Expression of the CIC-DUX4 fusion oncoprotein mimics human CIC-rearranged sarcoma in genetically engineered mouse models.

CIC-DUX4 sarcoma (CDS) is a rare but highly aggressive undifferentiated small round cell sarcoma driven by a fusion between the tumor suppressor Capicua (CIC) and DUX4. Currently, there are no effective treatments and efforts to identify and translate better therapies are limited by the scarcity of tissues and patients. To address this limitation, we generated three genetically engineered mouse models of CDS (Ch7CDS, Ai9CDS, and TOPCDS). Remarkably, chimeric mice from all three conditional models developed spontaneous tumors and widespread metastasis in the absence of Cre-recombinase. The penetrance of spontaneous (Cre-independent) tumor formation was complete irrespective of bi-allelic CIC function and loxP site proximity. Characterization of primary and metastatic mouse tumors showed that they consistently expressed the CIC-DUX4 fusion protein as well as other downstream markers of the disease credentialing these models as CDS. In addition, tumor-derived cell lines were generated and ChIP-seq was preformed to map fusion-gene specific binding using an N-terminal HA epitope tag. These datasets, along with paired H3K27ac ChIP-seq maps, validate CIC-DUX4 as a neomorphic transcriptional activator. Moreover, they are consistent with a model where ETS family transcription factors are cooperative and redundant drivers of the core regulatory circuitry in CDS.

Global research of artificial intelligence in strabismus: a bibliometric analysis.

Purpose: To analyze the global publications on artificial intelligence (AI) in strabismus using a bibliometric approach. Methods: The Web of Science Core Collection (WoSCC) database was used to retrieve all of the publications on AI in strabismus from 2002 to 2023. We analyzed the publication and citation trend and identified highly-cited articles, prolific countries, institutions, authors and journals, relevant research domains and keywords. VOSviewer (software) and Bibliometrix (package) were used for data analysis and visualization. Results: By analyzing a total of 146 relevant publications, this study found an overall increasing trend in the number of annual publications and citations in the last decade. USA was the most productive country with the closest international cooperation. The top 3 research domains were Ophthalmology, Engineering Biomedical and Optics. Journal of AAPOS was the most productive journal in this field. The keywords analysis showed that "deep learning" and "machine learning" may be the hotspots in the future. Conclusion: In recent years, research on the application of AI in strabismus has made remarkable progress. The future trends will be toward optimized technology and algorithms. Our findings help researchers better understand the development of this field and provide valuable clues for future research directions.

Efficacy of augmented-dosed surgery versus botulinum toxin A injection for acute acquired concomitant esotropia: a 2-year follow-up.

BACKGROUND/AIMS: This study aims to evaluate the clinical efficacy of botulinum toxin type A (BTXA) injection and augmented-dosed surgery in the treatment of acute acquired concomitant esotropia (AACE), and explore potential risk factors associated with recurrence. METHODS: A total of 104 patients diagnosed with AACE between October 2020 and January 2021 were included and voluntarily chose to undergo augmented surgery or BTXA injection. The follow-up assessments ended in November 2022. Multivariable linear regression analysis was used to identify potential factors that influence the dose-response of bilateral medial rectus recession (MRrec). Kaplan-Meier survival analyses and Cox proportional hazards models were performed to evaluate rate and risk factors for AACE relapse. RESULTS: A total of 31 AACE patients chose augmented-dosed esotropia surgery, and 73 chose BTXA treatment. During the 2-year follow-up, the surgical group achieved more stable postoperative results with no recurrence of diplopia, while only 68.68% (95% CI 55.31% to 78.79%) patients achieved orthophoria in the BTXA group. For patients undergoing BTXA treatment, hours of near work per day were demonstrated to be a significant risk factor for AACE relapse (HR 1.29, 95% CI 1.00 to 1.67). The dose-response of augmented-dosed bilateral MRrec was positively correlated with preoperative deviation angle (R2=0.833; ß=0.043, 95% CI 0.031 to 0.055; p<0.001). CONCLUSION: Our findings provided quantitative evidence that augmented-dosed surgery would achieve more stable and favourable surgical outcomes for AACE patients compared with BTXA injection. However, BTXA treatment is still proposed for patients with small deviation angles due to its advantages of reduced trauma, operational simplicity, low cost and quick recovery.

Diagnosing Systemic Disorders with AI Algorithms Based on Ocular Images.

The advent of artificial intelligence (AI), especially the state-of-the-art deep learning frameworks, has begun a silent revolution in all medical subfields, including ophthalmology. Due to their specific microvascular and neural structures, the eyes are anatomically associated with the rest of the body. Hence, ocular image-based AI technology may be a useful alternative or additional screening strategy for systemic diseases, especially where resources are scarce. This review summarizes the current applications of AI related to the prediction of systemic diseases from multimodal ocular images, including cardiovascular diseases, dementia, chronic kidney diseases, and anemia. Finally, we also discuss the current predicaments and future directions of these applications.

Physical appearance perfectionism in blepharoplasty patients: A prospective observational study.

BACKGROUND: Evaluation of physical appearance perfectionism (PAP) in individuals seeking blepharoplasty would be meaningful. This study aimed to explore the relationship of demographic and psychological variables with PAP in blepharoplasty patients and further investigate the impact of blepharoplasty on PAP in these patients. METHODS: This prospective observational study included 153 patients undergoing blepharoplasty between October 2017 and June 2019. Demographic and psychological variables, and PAP, were collected preoperatively. Postoperative satisfaction with eye appearance and PAP was collected with a 6-month follow-up. RESULTS: Partial correlations analyses revealed that hope for perfection was positively associated with self-esteem (r = 0.246; P < 0.01) in 153 blepharoplasty patients. Worry about imperfection was positively related to facial appearance concern (r = 0.703; P < 0.001) and negatively related to satisfaction with eye appearance (r = -0.242; P < 0.01) and self-esteem (r = -0.533; P < 0.001). After blepharoplasty, the mean± standard deviation of satisfaction with eye appearance increased (preoperatively vs. postoperatively: 5.1 ± 2.2 vs. 7.4 ± 2.2; P < 0.001), and worry about imperfection decreased (17.0 ± 4.2 vs. 15.9 ± 4.6; P < 0.001). Whereas hope for perfection remained unchanged (23.9 ± 3.9 vs. 23.6 ± 3.9; P > 0.05). CONCLUSIONS: Appearance perfectionism was related to psychological variables rather than demographic variables in blepharoplasty patients. Preoperative evaluation of appearance perfectionism could be helpful for oculoplastic surgeons to screen for perfectionistic patients. Although some improvement in perfectionism has been observed after blepharoplasty, long-term follow-up is needed in the future.

Deep learning-based image analysis of eyelid morphology in thyroid-associated ophthalmopathy.

Background: We aimed to propose a deep learning-based approach to automatically measure eyelid morphology in patients with thyroid-associated ophthalmopathy (TAO). Methods: This prospective study consecutively included 74 eyes of patients with TAO and 74 eyes of healthy volunteers visiting the ophthalmology department in a tertiary hospital. Patients diagnosed as TAO and healthy volunteers who were age- and gender-matched met the eligibility criteria for recruitment. Facial images were taken under the same light conditions. Comprehensive eyelid morphological parameters, such as palpebral fissure (PF) length, margin reflex distance (MRD), eyelid retraction distance, eyelid length, scleral area, and mid-pupil lid distance (MPLD), were automatically calculated using our deep learning-based analysis system. MRD1 and 2 were manually measured. Bland-Altman plots and intraclass correlation coefficients (ICCs) were performed to assess the agreement between automatic and manual measurements of MRDs. The asymmetry of the eyelid contour was analyzed using the temporal: nasal ratio of the MPLD. All eyelid features were compared between TAO eyes and control eyes using the independent samples t-test. Results: A strong agreement between automatic and manual measurement was indicated. Biases of MRDs in TAO eyes and control eyes ranged from -0.01 mm [95% limits of agreement (LoA): -0.64 to 0.63 mm] to 0.09 mm (LoA: -0.46 to 0.63 mm). ICCs ranged from 0.932 to 0.980 (P<0.001). Eyelid features were significantly different in TAO eyes and control eyes, including MRD1 (4.82±1.59 vs. 2.99±0.81 mm; P<0.001), MRD2 (5.89±1.16 vs. 5.47±0.73 mm; P=0.009), upper eyelid length (UEL) (27.73±4.49 vs. 25.42±4.35 mm; P=0.002), lower eyelid length (LEL) (31.51±4.59 vs. 26.34±4.72 mm; P<0.001), and total scleral area (SATOTAL) (96.14±34.38 vs. 56.91±14.97 mm2; P<0.001). The MPLDs at all angles showed significant differences in the 2 groups of eyes (P=0.008 at temporal 180°; P<0.001 at other angles). The greatest temporal-nasal asymmetry appeared at 75° apart from the midline in TAO eyes. Conclusions: Our proposed system allowed automatic, comprehensive, and objective measurement of eyelid morphology by only using facial images, which has potential application prospects in TAO. Future work with a large sample of patients that contains different TAO subsets is warranted.

A novel standardized approach for the 3D evaluation of upper eyelid area and volume.

Background: Three-dimensional (3D) surface imaging and morphometrics are becoming the preferred craniofacial surface imaging modality. However, as a unique advantage of 3D imaging, areal and volumetric measurements have been rarely conducted and validated for evaluating soft tissue change in the periocular region, especially the upper eyelids. Therefore, based on an existing periocular landmark identification strategy, we proposed a novel modified method to define a standardized upper eyelid region for areal and volumetric measurements and validate its reliability for future clinical application. Methods: Forty-four healthy adult volunteers were enrolled in this cross-sectional study. Three-dimensional facial images were taken with a 3D imaging system. Subsequently, the upper eyelid region selection and areal and volumetric measurements were conducted using a modified landmarks localization strategy to evaluate their intrarater, interrater, and intramethod reliability. Results: Areal measurement of the upper eyelid revealed highly reliable outcomes for intraclass correlation coefficient (ICC), mean absolute difference (MAD), relative error measurement (REM), technical error of measurement (TEM), and relative technical error of measurement (%TEM) of 0.982, 0.1620 cm2, 2.9%, 0.1510 cm2, and 2.7% for intrarater reliability, respectively; 0.969, 0.2076 cm2, 3.7%, 0.1930 cm2, and 3.5% for interrater reliability, respectively; and 0.917, 0.3636 cm2, 6.5%, 0.3354 cm2, and 6.0% for intramethod reliability, respectively. Unsatisfactory results were found for the volumetric measurement of the upper eyelid: the ICC, MAD, REM, TEM, and %TEM estimates for intrarater reliability were 0.992, 0.2299 mL, 10.3%, 0.2414 mL, and 10.8%, respectively; for interrater reliability, these values were 0.985, 0.2749 mL, 12.3%, 0.3253 mL, and 14.6%, respectively; and for intramethod reliability, these values were 0.433, 1.6716 mL, 77.9%, 2.0615 mL, and 96.1%, respectively. Conclusions: This is the first study to propose a standardized upper eyelid region selection strategy and simultaneously validate its reliability for 3D areal and volumetric measurements. This study confirmed the high-level reliability of areal measurement and poor reliability of volumetric measurement based on direct measurements using a single image, which may provide better results when this method is combined with the image overlapping and registration procedure. However, this is subject to further validation. Nonetheless, this method could provide quantitative areal and volumetric data on the upper eyelids and might have widespread application potential in the future.

Bioinformatics prediction and experimental verification of a novel microRNA for myocardial fibrosis after myocardial infarction in rats.

Background: MicroRNAs (miRNAs) are endogenous noncoding single-stranded small RNAs. Numerous studies have shown that miRNAs have pivotal roles in the occurrence and development of myocardial fibrosis (MF). However, miRNA expression profile in rats with MF after myocardial infarction (MI) is not well understood. The present study aimed to find the potential miRNA for MF post MI. Methods: SPF male Sprague-Dawley (SD) rat models of acute myocardial infarction (AMI) were established by ligating the anterior descending branch of the left coronary artery, while sham-operated rats were only threaded without ligation as a control group. Hematoxylin-eosin and Masson trichrome staining were used to detect myocardial histopathological changes for model evaluation. The differentially expressed miRNAs were detected by using the Agilent Rat miRNA gene chip in the myocardial tissue of the infarct marginal zone. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed by DAVID. The expression of miR-199a-5p was verified by real-time fluorescence quantitative PCR (qRT-PCR). Transfected miR-199a-5p mimics into cardiac fibroblasts (CFs) to construct cell models of miR-199a-5p overexpression. Dual-luciferase reporter assay was employed to validate the target gene of miR-199a-5p. The protein expression of the target gene in CFs transfected with miR-199a-5p mimics were detected by Western blot. Results: Myocardial fibrosis was exacerbated in the model group compared with the control group. Thirteen differentially expressed miRNAs between the two groups were screened and their expression levels in the model group were all higher than those in the control group. The expression of miR-199a-5p was significantly increased in the model group in qRT-PCR, which was consistent with the results of the gene chip. KEGG enrichment analysis showed that the target genes of miR-199a-5p were enriched in the insulin signaling pathway. Furthermore, dual-luciferase reporter assay indicated that miR-199a-5p could negatively regulate the expression of GSK-3ß. After transfection, the expression of miR-199a-5p was increased in the miR-199a-5p mimics group. The protein expression of GSK-3ß was decreased in CFs transfected with miR-199a-5p mimics. Conclusion: Our study identified miR-199a-5p could promote the progression of myocardial fibrosis after myocardial infarction by targeting GSK-3ß, which provides novel targets for diagnosis and treatment of MF.

Automated photographic analysis of inferior oblique overaction based on deep learning.

Background: Inferior oblique overaction (IOOA) is a common ocular motility disorder. This study aimed to propose a novel deep learning-based approach to automatically evaluate the amount of IOOA. Methods: This prospective study included 106 eyes of 72 consecutive patients attending the strabismus clinic in a tertiary referral hospital. Patients were eligible for inclusion if they were diagnosed with IOOA. IOOA was clinically graded from +1 to +4. Based on photograph in the adducted position, the height difference between the inferior corneal limbus of both eyes was manually measured using ImageJ and automatically measured by our deep learning-based image analysis system with human supervision. Correlation coefficients, Bland-Altman plots and mean absolute deviation (MAD) were analyzed between two different measurements of evaluating IOOA. Results: There were significant correlations between automated photographic measurements and clinical gradings (Kendall's tau: 0.721; 95% confidence interval: 0.652 to 0.779; P<0.001), between automated and manual photographic measurements [intraclass correlation coefficients (ICCs): 0.975; 95% confidence interval: 0.963 to 0.983; P<0.001], and between two-repeated automated photographic measurements (ICCs: 0.998; 95% confidence interval: 0.997 to 0.999; P<0.001). The biases and MADs were 0.10 [95% limits of agreement (LoA): -0.45 to 0.64] mm and 0.26±0.14 mm between automated and manual photographic measurements, and 0.01 (95% LoA: -0.14 to 0.16) mm and 0.07±0.04 mm between two-repeated automated photographic measurements, respectively. Conclusions: The automated photographic measurements of IOOA using deep learning technique were in excellent agreement with manual photographic measurements and clinical gradings. This new approach allows objective, accurate and repeatable measurement of IOOA and could be easily implemented in clinical practice using only photographs.

A Fully Automatic Postoperative Appearance Prediction System for Blepharoptosis Surgery with Image-based Deep Learning.

Purpose: To automatically predict the postoperative appearance of blepharoptosis surgeries and evaluate the generated images both objectively and subjectively in a clinical setting. Design: Cross-sectional study. Participants: This study involved 970 pairs of images of 450 eyes from 362 patients undergoing blepharoptosis surgeries at our oculoplastic clinic between June 2016 and April 2021. Methods: Preoperative and postoperative facial images were used to train and test the deep learning-based postoperative appearance prediction system (POAP) consisting of 4 modules, including the data processing module (P), ocular detection module (O), analyzing module (A), and prediction module (P). Main Outcome Measures: The overall and local performance of the system were automatically quantified by the overlap ratio of eyes and by lid contour analysis using midpupil lid distances (MPLDs). Four ophthalmologists and 6 patients were invited to complete a satisfaction scale and a similarity survey with the test set of 75 pairs of images on each scale. Results: The overall performance (mean overlap ratio) was 0.858 ± 0.082. The corresponding multiple radial MPLDs showed no significant differences between the predictive results and the real samples at any angle (P > 0.05). The absolute error between the predicted marginal reflex distance-1 (MRD1) and the actual postoperative MRD1 ranged from 0.013 mm to 1.900 mm (95% within 1 mm, 80% within 0.75 mm). The participating experts and patients were "satisfied" with 268 pairs (35.7%) and "highly satisfied" with most of the outcomes (420 pairs, 56.0%). The similarity score was 9.43 ± 0.79. Conclusions: The fully automatic deep learning-based method can predict postoperative appearance for blepharoptosis surgery with high accuracy and satisfaction, thus offering the patients with blepharoptosis an opportunity to understand the expected change more clearly and to relieve anxiety. In addition, this system could be used to assist patients in selecting surgeons and the recovery phase of daily living, which may offer guidance for inexperienced surgeons as well.

Effect of WenXin KeLi on Improvement of Arrhythmia after Myocardial Infarction by Intervening PI3K-AKT-mTOR Autophagy Pathway.

Background: Myocardial infarction (MI) is an acute and serious cardiovascular disease. Arrhythmia after MI can lead to sudden cardiac death, which seriously affects the survival outcome of patients. WenXin KeLi is a Chinese patent medicine for the treatment of arrhythmia in a clinic, which can significantly improve symptoms of palpitation and play an important role in reducing the risk of arrhythmia after MI. In this study, we aimed to explore the pharmacological mechanism of WenXin KeLi in protecting the heart. Methods: The MI model was established by ligating the left coronary artery and the ventricular fibrillation threshold (VFT) was measured by electrical stimulation. The expression of connexin43 (CX43) and autophagy-related protein were measured by Western Blot, and correlation analysis was conducted to study the relationship between cardiac autophagy, CX43, and arrhythmia in rats after MI. The effects of WenXin KeLi on arrhythmia, cardiac structure, and function in MI rats were respectively observed by electrical stimulation, cardiac gross section, Masson staining, and cardiac ultrasound. The effects of WenXin KeLi on the expression of phosphoinositide 3 kinase-protein kinase B-mammalian targets of rapamycin (PI3K-AKT-mTOR) autophagy pathway and CX43 were observed by Western Blot. Results: After 4 weeks of MI, the VFT in the model group was significantly reduced, the expression levels of yeast ATG6 homolog (Beclin1), microtubule-associated protein 1A/1B-light chain 3 (LC3II/LC3I), and p-CX43 (S368) significantly increased, the expression of sequestosome-1(P62) and CX43 significantly decreased. LC3II/LC3I and Beclin1 expression were significantly negatively correlated with the VFT, and the expression of P62 and CX43 were significantly positively correlated with the VFT. LC3II/LC3I and Beclin1 expression were negatively correlated with CX43 expression, while P62 expression was positively correlated with CX43 expression. WenXin KeLi could significantly increase the VFT, reduce the deposition of collagen fibers, and increase the index levels of the left ventricular end-diastolic anterior wall (LVEDAW), interventricular septum end-diastolic (IVSED), left ventricular end-systolic anterior wall (LVESAW), interventricular septum end-systolic (IVSES), left ventricular end-diastolic posterior wall (LVEDPW), left ventricular end-systolic posterior wall (LVESPW), left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS), and reduce the index levels of the left ventricular end-diastolic dimension (LVEDD), left ventricular end-systolic dimension (LVESD), left ventricular end-diastolic volume (LVEDV) and left ventricular end-systolic volume (LVESV). WenXin KeLi could increase the expression of CX43, P62, AKT, p-PI3K, p-AKT (308), p-AKT (473), and p-mTOR and decrease the expression of LC3II/LC3I and Beclin1. Conclusion: WenXin KeLi can activate the PI3K-AKT-mTOR signaling pathway, improve cardiac autophagy and Cx43 expression in rats after MI, reduce the risk of arrhythmia after MI, and play a cardioprotective role.

A cascade eye diseases screening system with interpretability and expandability in ultra-wide field fundus images: A multicentre diagnostic accuracy study.

Background: Clinical application of artificial intelligence is limited due to the lack of interpretability and expandability in complex clinical settings. We aimed to develop an eye diseases screening system with improved interpretability and expandability based on a lesion-level dissection and tested the clinical expandability and auxiliary ability of the system. Methods: The four-hierarchical interpretable eye diseases screening system (IEDSS) based on a novel structural pattern named lesion atlas was developed to identify 30 eye diseases and conditions using a total of 32,026 ultra-wide field images collected from the Second Affiliated Hospital of Zhejiang University, School of Medicine (SAHZU), the First Affiliated Hospital of University of Science and Technology of China (FAHUSTC), and the Affiliated People's Hospital of Ningbo University (APHNU) in China between November 1, 2016 to February 28, 2022. The performance of IEDSS was compared with ophthalmologists and classic models trained with image-level labels. We further evaluated IEDSS in two external datasets, and tested it in a real-world scenario and an extended dataset with new phenotypes beyond the training categories. The accuracy (ACC), F1 score and confusion matrix were calculated to assess the performance of IEDSS. Findings: IEDSS reached average ACCs (aACC) of 0·9781 (95%CI 0·9739-0·9824), 0·9660 (95%CI 0·9591-0·9730) and 0·9709 (95%CI 0·9655-0·9763), frequency-weighted average F1 scores of 0·9042 (95%CI 0·8957-0·9127), 0·8837 (95%CI 0·8714-0·8960) and 0·8874 (95%CI 0·8772-0·8972) in datasets of SAHZU, APHNU and FAHUSTC, respectively. IEDSS reached a higher aACC (0·9781, 95%CI 0·9739-0·9824) compared with a multi-class image-level model (0·9398, 95%CI 0·9329-0·9467), a classic multi-label image-level model (0·9278, 95%CI 0·9189-0·9366), a novel multi-label image-level model (0·9241, 95%CI 0·9151-0·9331) and a lesion-level model without Adaboost (0·9381, 95%CI 0·9299-0·9463). In the real-world scenario, the aACC of IEDSS (0·9872, 95%CI 0·9828-0·9915) was higher than that of the senior ophthalmologist (SO) (0·9413, 95%CI 0·9321-0·9504, p = 0·000) and the junior ophthalmologist (JO) (0·8846, 95%CI 0·8722-0·8971, p = 0·000). IEDSS remained strong performance (ACC = 0·8560, 95%CI 0·8252-0·8868) compared with JO (ACC = 0·784, 95%CI 0·7479-0·8201, p= 0·003) and SO (ACC = 0·8500, 95%CI 0·8187-0·8813, p = 0·789) in the extended dataset. Interpretation: IEDSS showed excellent and stable performance in identifying common eye conditions and conditions beyond the training categories. The transparency and expandability of IEDSS could tremendously increase the clinical application range and the practical clinical value of it. It would enhance the efficiency and reliability of clinical practice, especially in remote areas with a lack of experienced specialists. Funding: National Natural Science Foundation Regional Innovation and Development Joint Fund (U20A20386), Key research and development program of Zhejiang Province (2019C03020), Clinical Medical Research Centre for Eye Diseases of Zhejiang Province (2021E50007).

Association of sex with the global burden of vision impairment caused by neonatal preterm birth: An analysis from the global burden of disease study 2019.

Aims: To investigate the sex-specific global burden of neonatal preterm birth (NPB) vision impairment by year, age, and socioeconomic status using years lived with disability (YLDs). Methods: The global, regional, and national sex-specific YLD numbers, crude YLD rates, and age-standardized YLD rates of NPB-related moderate and severe vision loss and blindness were obtained from the Global Burden of Disease Study 2019. The Wilcoxon test and linear regression were used to investigate the relationship between sex difference in age-standardized YLD rates and the Human Development Index (HDI). Results: Between 1990 and 2019, the gender disparity in age-standardized YLD rates for NPB-related vision impairment remained stable, increasing from 10.2 [95% uncertainty interval (UI) 6.7-14.6] to 10.4 (95% UI 6.9-15.0) for men and 10.3 (95% UI 6.8-14.7) to 10.7 (95% UI 7.2-15.1) for women, with women consistently having higher age-standardized YLD rates. Between the ages of 25 and 75, women had higher YLD rates than males, with the biggest disparity in the 60-64 age group. In 2019, sex difference in age-standardized YLD rates across 195 nations was statistically significant. Women had higher age-standardized YLD rates than men in both low (Z = -3.53, p < 0.001) and very high HDI countries (Z = -4.75, p < 0.001). Additionally, age-standardized YLD rates were found to be adversely associated with HDI (male: Standardized ß = -0.435, female: Standardized ß = -0.440; p < 0.001). Conclusion: Despite advancements in worldwide NPB health care, sexual differences in NPB-related vision impairment burden showed little change. Female had higher burden than male, particularly in low and very high socioeconomic status countries.

Automated Measurement of Ocular Movements Using Deep Learning-Based Image Analysis.

PURPOSE: Clinical assessment of ocular movements is essential for the diagnosis and management of ocular motility disorders. This study aimed to propose a deep learning-based image analysis to automatically measure ocular movements based on photographs and to investigate the relationship between ocular movements and age. METHODS: 207 healthy volunteers (414 eyes) aged 5-60 years were enrolled in this study. Photographs were taken in the cardinal gaze positions. Ocular movements were manually measured based on a modified limbus test using ImageJ and automatically measured by our deep learning-based image analysis. Correlation analyses and Bland-Altman analyses were conducted to assess the agreement between manual and automated measurements. The relationship between ocular movements and age were analyzed using generalized estimating equations. RESULTS: The intraclass correlation coefficients between manual and automated measurements of six extraocular muscles ranged from 0.802 to 0.848 (P < 0.001), and the bias ranged from -0.63 mm to 0.71 mm. The average measurements were 8.62 ± 1.07 mm for superior rectus, 7.77 ± 1.24 mm for inferior oblique, 6.99 ± 1.23 mm for lateral rectus, 6.71 ± 1.22 mm for medial rectus, 6.81 ± 1.20 mm for inferior rectus, and 6.63 ± 1.37 mm for superior oblique, respectively. Ocular movements in each cardinal gaze position were negatively related to age (P < 0.05). CONCLUSIONS: The automated measurements of ocular movements using a deep learning-based approach were in excellent agreement with the manual measurements. This new approach allows objective assessment of ocular movements and shows great potential in the diagnosis and management of ocular motility disorders.