To evaluate the long-term changes in retinochoroidal structure and perfusion status in highly myopic eyes following ICL V4c implantation, using ultra-widefield swept-source optical coherence tomography angiography (UWF-SS-OCTA) combined with a three-dimensional modelling algorithm. Prospective cohort study. Sixty-six highly myopic patients (132 eyes) underwent ICL V4c implantation surgery and completed one year of follow-up. Retinal and choroidal parameters, including retinal thickness (RT), capillary plexus density, foveal avascular zone (FAZ), retinal curvature, choroidal thickness (CT), and three-dimensional choroidal vascularity index (3D-CVI), were measured preoperatively and at multiple postoperative time points using UWF-SS-OCTA integrated with advanced 3D analytic techniques. Repeated measures mixed-effects models were applied to compare the pre- and postoperative parameters and test the correlations between parameters. The surgical outcomes are satisfactory with a stable safety profile and no major complications. RT and retinal vascular density exhibited transient changes in one month postoperatively, and gradually recovered (p < 0.05). Choroidal parameters, including CT and 3D-CVI, demonstrated a progressive and sustained postoperative increase across the 1-year follow-up, with the most pronounced changes observed in the foveal and perifoveal zones (p < 0.001). Factors of surgical duration and axial length showed significant correlation to the retinochoroidal responses (p < 0.05). Our analysis based on UWF-SS-OCTA demonstrated that ICL implantation can cause the recoverable changes of retinal structure and perfusion status, and the sustained remodeling of choroidal vascular conditions one year postoperatively in high myopia. Trial registration number : ChiCTR2500108664, registered at the Chinese Medical Research Registry. ICL implantation is an effective intraocular refractive procedure for high myopia, but its impact on retinochoroidal structure and perfusion remains incompletely understood. Conventional assessments of retinochoroidal parameters have predominantly relied on two-dimensional measurements. This study provides 3D evaluation of retinochoroidal structure and perfusion using UWF-SS-OCTA combined with AI-based reconstruction, enabling more comprehensive assessment of postoperative changes. ICL implantation induces transient retinal alterations but sustained increases in choroidal thickness and vascularity, suggesting long-term choroidal remodeling in highly myopic eyes.

AIM: To compare the accuracy of manual marking versus an image-guided system for toric implantable collamer lens (TICL) implantation and evaluate the short-term postoperative rotational stability of TICL and corneal surgically induced astigmatism vector (SIA). METHODS: Retrospective analysis was conducted on eyes with TICL alignment achieved through manual marking (n=75) or VERION image-guided system-assisted marking (n=83). Each group was further classified into horizontal and vertical subgroups based on implant orientation. Additionally, patients were categorized into superior and temporal incision subgroups according to the position of main corneal incision. The misalignment and rotational stability of TICL were analyzed using slit-lamp anterior segment photography. Surgical predictability, efficacy, safety, and corneal SIA were also evaluated. RESULTS: In general, the TICL implantation with manual and digital image-guided systems all achieved robust predictability, efficacy, and safety. The misalignment of TICL was comparable between the manual and VERION groups (0.16°±3.97° vs 0.52°±5.59°, P=0.633), while a significant difference was observed in the absolute misalignment of TICL between the two groups (3.02°±2.55° vs 4.28°±3.61°, P=0.043). There were no significant differences in the distribution of TICL misalignment between the manual and VERION groups or between horizontal and vertical implant orientation groups (P>0.05). Furthermore, different orientations of TICL placement did not show statistically significant differences in rotational stability (P=0.46). Statistically significant differences were found in anterior corneal SIA between the manual and VERION groups (0.46±0.27 vs 0.33±0.21 D, P=0.001), especially for superior incision position (0.60±0.27 vs 0.35±0.23 D, P<0.0001). The anterior SIA exhibited a significant difference between superior and temporal incisions in the manual group (0.60±0.27 vs 0.35±0.20 D, P<0.0001). CONCLUSION: Compared with the conventional manual marking method, this study indicates that the digital image-guided system with VERION is safe and effective in TICL implantation. The digital system offers the advantage of minimizing corneal SIA compared to the manual method.

The transcription factor interferon regulatory factor 3 (IRF3) initiates type I interferon transcription, which is required for host defense. Here, we identify RAD18 as a central E3 ubiquitin ligase that selectively targets phosphorylated IRF3 (p-IRF3) for autophagic degradation. RAD18 specifically promotes the dissociation of p-IRF3 from the IFNB promoter and in turn terminates its transcriptional activity. Mechanistically, RAD18 binds the p-IRF3 dimer located on the IFNB promoter and triggers K63 polyubiquitylation of p-IRF3 at Lys 193. The ubiquitylated p-IRF3 dimer consequently dissociates from the IFNB promoter, translocates out of the nucleus and undergoes OPTN-mediated autophagic degradation. Rad18fl/fl Lysm-cre mice resist lethal vesicular stomatitis virus infection in vivo due to IFNβ overproduction. In H1N1-infected human macrophages or monocytes from individuals with active systemic lupus erythematosus, RAD18 protein levels negatively correlate with p-IRF3 and IFNB1 mRNA levels. Thus, RAD18 functions as a break to terminate IRF3-driven IFNB1 transcription and may be a potential therapeutic target for RNA virus infection or autoimmune diseases. IRF3 initiates type I IFN transcription, and this is required for host defense. Here, Chen and colleagues show that RAD18 terminates the transcriptional activity of IRF3 and subsequently promotes the autophagic degradation of IRF3.

PurposeThis study aims to conduct a bibliometric analysis of global publications on the application of artificial intelligence (AI) in high myopia (HM).MethodsWe retrieved publications on AI in HM from the Web of Science Core Collection (WoSCC) database, MEDLINE and Chinese Science Citation Database (CSCD) with data up to 2024. The analysis focused on publication and citation trends, identifying key articles, influential countries, institutions, authors, and journals. Additionally, we explored research domains and emerging keywords.ResultsA total of 167 relevant publications were included. The first AI-related paper on HM was published in 2017, with a significant surge in 2021, followed by a consistent increase in publication and citation counts over the next 3 years. China emerged as the most productive country, with the most extensive international collaboration. East Asian authors dominated the top 10 most influential authors. Yang, Weihua and Investigative Ophthalmology & Visual Science (IOVS) contributed the most publications among authors and institutions, respectively. Keyword analysis revealed that retinal imaging-related terms remained a consistent research focus, while newly emerging keywords included “automated detection” and “childhood.”ConclusionRecent advancements in AI applications for HM have been significant and are expected to continue. Future research will likely focus on multimodal imaging and improving algorithm accessibility. Our findings offered the first comprehensive overview of global research on AI in HM, thus providing valuable insights for researchers to understand the current status and future trends in this field.

Objectives: To report the global burden of age-related macular degeneration (AMD) and associated risk factors between 1990 and 2021 by age, sex, and sociodemographic index (SDI) and to investigate the influence of the COVID-19 pandemic on AMD burden. Methods: Data on disability-adjusted life years (DALYs) of AMD were obtained from the Global Burden of Disease Study 2021. Joinpoint regression determined annual percentage change (APC) and average annual percentage change (AAPC). ARIMA model projected AMD burden trends, with additional analyses for frontier, decomposition, and health inequality. Results: Globally, AMD accounted for 578.02 (95% UI: 401.24-797.57) thousand DALYs in 2021, driven by population growth and aging. Age-standardized DALY rates (ASDRs) fell from 1990 to 2021 (AAPC: -0.69, 95%CI: -0.77 to -0.6), but increased in high-middle and middle SDI regions during the initial two years of the pandemic. ARIMA model forecasts a worldwide decline in ASDRs over the next 29 years. Sex disparities were significant, with women having continuously higher ASDRs, especially from 2019 to 2021. Despite some reduction in health inequality, an inverse SDI-ASDR relationship indicated ongoing socioeconomic disparities. Frontier analysis showed improvement potential across growth stages. Smoking-related AMD burden decreased globally, with a correlation between national ASDRs and PM2.5 levels. Conclusions: ASDRs due to AMD have decreased over the past 32 years, while DALYs have substantially increased. The burden is more heavily tilted toward women, the elderly, and less-developed countries, with COVID-19 further intensifying the situation. Addressing the burden requires focusing on smoking cessation and air quality improvements.

PURPOSE:To investigate the effects of 0.05% Cyclosporine A (CsA) eye drops on visual quality including corneal higher-order aberrations (HOAs) in post-refractive surgery dry eye syndrome (DES) patients. METHODS:This prospective, randomized study involves 52 patients diagnosed with post-refractive surgery DES. The control group (22 eyes) received conventional dry eye therapy (20% deproteinized calf serum, 3% diquafosol tetrasodium eye drops), and the treatment group (30 eyes) received an additional 0.05% CsA. Corneal HOAs, corneal fluorescein staining (CFS), tear break-up time (TBUT), tear meniscus height (TMH), redness index, meibography, Ocular Surface Disease Index (OSDI), and subjective visual quality scores were assessed before and after three months. RESULTS:Both groups showed significant improvements (with no significant differences between groups) in TBUT, redness index, and ODSI. Compared with the control group, corneal HOAs, visual quality subjective scores, and CFS scores improved significantly in the treatment group. For the treatment group, Z(3, 1) and Z(4, -2) over 3 mm zone as well as Z(3, 1), Z(4, -2) and Z(4, -4) term over 5 mm zone showed significant changes after three months of treatment. CONCLUSION:The administration of 0.05% CsA significantly improved tear film stability and reduced corneal HOAs, enhancing visual quality in post-refractive surgery DES patients. KEY MESSAGES:What is known Post-refractive surgery dry eye syndrome (DES) can degrade visual quality due to increased higher-order aberrations (HOAs) and tear film instability. Cyclosporine A (CsA) 0.05% has recognized anti-inflammatory effects and is commonly used to manage various types of DES. What is new The addition of 0.05% CsA to conventional DES treatment significantly improves corneal HOAs and subjective visual quality in post-refractive surgery patients. This study provides quantitative evidence that CsA not only relieves post-refractive DES symptoms but also enhances visual performance through improved tear film stability and optical quality.

OBJECTIVE:To investigate the effect of Shisiwei Jianzhong decoction (, SJD) on non-severe aplastic anemia (NSAA). METHODS:Bone marrow mesenchymal stem cells (BMSCs) were isolated from bone marrow samples of 15 NSAA patients and 3 healthy controls. Cells were treated with gradient concentrations of SJD, and a portion was transfected with a vector overexpressing the nuclear factor of activated T cells, cytoplasmic 4 (NFATC4). Cell viability and apoptosis were detected by cell counting kit-8 and flow cytometry, respectively. After adipogenic differentiation induction, lipid droplet formation in BMSCs was examined by Oil Red O staining. The expression of NFATC4, peroxisome proliferator-activated receptor gamma (PPARG), fatty acid-binding protein 4 (FABP4), peroxisome proliferator-activated receptor-gamma coactivator (PGC-1α), and acetylated PGC-1α was measured by quantitative real-time polymerase chain reaction or Western blot. RESULTS:SJD significantly increased the viability and decreased the apoptosis of NSAA-derived BMSCs. It also dose-dependently inhibited lipid droplet formation and decreased the expression of PPARG and FABP4 in NSAA-derived BMSCs. NFATC4 expression was higher in patients with NSAA than in healthy controls, and SJD downregulated its expression. NFATC4 overexpression reversed the inhibitory effect of SJD on adipogenic differentiation. Additionally, SJD promoted the deacetylation of PGC-1α in NSAA-derived BMSCs, which was also partially eliminated by NFATC4 overexpression. CONCLUSIONS:SJD inhibits adipogenic differentiation of BMSCs through downregulating NFATC4, thereby contributing to the remission of NSAA.

AIM: To investigate the morphological characteristics of retinal vessels in patients with different severity of diabetic retinopathy (DR) and in patients with or without diabetic macular edema (DME). METHODS: The 239 eyes of DR patients and 100 eyes of healthy individuals were recruited for the study. The severity of DR patients was graded as mild, moderate and severe non-proliferative diabetic retinopathy (NPDR) according to the international clinical diabetic retinopathy (ICDR) disease severity scale classification, and retinal vascular morphology was quantitatively analyzed in ultra-wide field images using RU-net and transfer learning methods. The presence of DME was determined by optical coherence tomography (OCT), and differences in vascular morphological characteristics were compared between patients with and without DME. RESULTS: Retinal vessel segmentation using RU-net and transfer learning system had an accuracy of 99% and a Dice metric of 0.76. Compared with the healthy group, the DR group had smaller vessel angles (33.68±3.01 vs 37.78±1.60), smaller fractal dimension (Df) values (1.33±0.05 vs 1.41±0.03), less vessel density (1.12±0.44 vs 2.09±0.36) and fewer vascular branches (206.1±88.8 vs 396.5±91.3), all P<0.001. As the severity of DR increased, Df values decreased, P=0.031. No significant difference between the DME and non-DME groups were observed in vascular morphological characteristics. CONCLUSION: In this study, an artificial intelligence retinal vessel segmentation system is used with 99% accuracy, thus providing with relatively satisfactory performance in the evaluation of quantitative vascular morphology. DR patients have a tendency of vascular occlusion and dropout. The presence of DME does not compromise the integral retinal vascular pattern.

Purpose To evaluate the effects of clear corneal incision (CCI) location and morphology on corneal surgically induced astigmatism (SIA) and higher-order aberrations (HOAs) in patients receiving implantable collamer lens (ICL V4c) implantation.Methods This retrospective study classified right eyes that underwent ICL implantation into two groups based on temporal or superior CCI. The Pentacam HR analyzer was used to measure the corneal astigmatism and HOAs. Analysis of the clear corneal incision (CCI) morphology, including incision width (Angle-W), incision length (IL), incision angles (Angle-En/Ex), and distance from the incision to corneal apex (Dis-En/Ex), was conducted using anterior segment optical coherence tomography (AS-OCT).Results There were 75 eyes in the temporal CCI group and 47 eyes in the superior CCI group. Both groups showed satisfactory safety and efficacy postoperatively. In the temporal CCI group, Dis-En and Dis-Ex were considerably longer, whereas the superior CCI group displayed a significantly wider Angle-W. The anterior and posterior corneal SIA were comparable in both groups. Anterior corneal SIA was significantly correlated to Dis-En and Dis-Ex in the superior CCI group. Superior CCI caused a notable rise in corneal Z (3, 3), while temporal CCI led to increased Z (3, 1). CCI morphology was correlated to corneal Z (4, -4) and Z (4, 4) in the superior CCI group.Conclusion CCI locations caused slight variations in postoperative corneal SIA and HOAs following ICL implantation. Optimal postoperative visual outcomes may be better achieved with a CCI design featuring an increased distance from the corneal centroid and a decreased Angle-W.

Endoscopy is the primary modality for detecting asymptomatic esophageal squamous cell carcinoma (ESCC) and precancerous lesions. Improving detection rate remains challenging. We developed a system based on deep convolutional neural networks (CNNs) for detecting esophageal cancer and precancerous lesions [high-risk esophageal lesions (HrELs)] and validated its efficacy in improving HrEL detection rate in clinical practice (trial registration ChiCTR2100044126 at www.chictr.org.cn ). Between April 2021 and March 2022, 3117 patients ≥50 years old were consecutively recruited from Taizhou Hospital, Zhejiang Province, and randomly assigned 1:1 to an experimental group (CNN-assisted endoscopy) or a control group (unassisted endoscopy) based on block randomization. The primary endpoint was the HrEL detection rate. In the intention-to-treat population, the HrEL detection rate [28 of 1556 (1.8%)] was significantly higher in the experimental group than in the control group [14 of 1561 (0.9%), P = 0.029], and the experimental group detection rate was twice that of the control group. Similar findings were observed between the experimental and control groups [28 of 1524 (1.9%) versus 13 of 1534 (0.9%), respectively; P = 0.021]. The system’s sensitivity, specificity, and accuracy for detecting HrELs were 89.7, 98.5, and 98.2%, respectively. No adverse events occurred. The proposed system thus improved HrEL detection rate during endoscopy and was safe. Deep learning assistance may enhance early diagnosis and treatment of esophageal cancer and may become a useful tool for esophageal cancer screening.

PURPOSE:To investigate different modes of foveal regeneration after the closure of idiopathic macular hole (IMH) or highly myopic macular hole (HMMH) by vitrectomy with internal limiting membranes peeling or flap techniques. METHODS:This retrospective observational study followed 47 IMH and 50 HMMH eyes for at least 6 months. Twenty four IMH and 25 HMMH eyes underwent internal limiting membrane peeling, whereas 23 IMH and 25 HMMH eyes received inverted internal limiting membrane flap technique. Spectral domain optical coherence tomography was used to analyze macular hole closure, foveal microstructures, and excessive gliosis as a foveal "peak-like" protuberance. RESULTS:A single procedure closed all IMH (n = 47). For HMMH, the inverted group (n = 25, 100%) closed more macular hole than the peeling group (n = 14, 56.00%) (P < 0.001). Excessive gliosis only occurred in the inverted group, and there was a significant difference (P = 0.005) in incidence between IMH (three in 23 eyes, 13.04%) and HMMH (13 in 25 eyes, 52.00%). The axial length more than 29.985 mm enhanced the risk of excessive gliosis. CONCLUSION:The inverted internal limiting membrane flap efficiently treated refractory MHs but was prone to cause excessive gliosis in highly myopic eyes. Excessive elongation of the globe (axial length > 29.985 mm) was linked to excessive gliosis growth.

Supplemental Digital Content is Available in the Text. Our study indicated that while the inverted internal limiting membrane flap surgery was beneficial in treating refractory macular holes, it was associated with excessive gliosis in highly myopic eyes. The extremely elongated globe (axial length ≥ 29.985 mm) was identified as a critical factor in the formation of the excessive gliosis. Purpose: To investigate different modes of foveal regeneration after the closure of idiopathic macular hole (IMH) or highly myopic macular hole (HMMH) by vitrectomy with internal limiting membranes peeling or flap techniques. Methods: This retrospective observational study followed 47 IMH and 50 HMMH eyes for at least 6 months. Twenty four IMH and 25 HMMH eyes underwent internal limiting membrane peeling, whereas 23 IMH and 25 HMMH eyes received inverted internal limiting membrane flap technique. Spectral domain optical coherence tomography was used to analyze macular hole closure, foveal microstructures, and excessive gliosis as a foveal “peak-like” protuberance. Results: A single procedure closed all IMH (n = 47). For HMMH, the inverted group (n = 25, 100%) closed more macular hole than the peeling group (n = 14, 56.00%) (P < 0.001). Excessive gliosis only occurred in the inverted group, and there was a significant difference (P = 0.005) in incidence between IMH (three in 23 eyes, 13.04%) and HMMH (13 in 25 eyes, 52.00%). The axial length more than 29.985 mm enhanced the risk of excessive gliosis. Conclusion: The inverted internal limiting membrane flap efficiently treated refractory MHs but was prone to cause excessive gliosis in highly myopic eyes. Excessive elongation of the globe (axial length > 29.985 mm) was linked to excessive gliosis growth.

Background and AimThe relationship between Helicobacter pylori (H. pylori) and fast plasma glucose (FPG) on nondiabetes populations is still inconclusive. Nowadays, not only the high infection rate of H. pylori but also the high FPG level is threatening the Chinese people. MethodsA retrospective cohort study has been established to analyze the relationship between H. pylori infection and FPG level, 18 164 individuals performed healthy examination in Taizhou Hospital Health Examination Center from 2017 to 2022 were included, and hematological indicators, body parameters, and H. pylori detection by C-13-urea breath test were collected from patients. The follow-up intervals were greater than 12 months. ResultsH. pylori infection was regarded as an independent risk factor for elevated FPG after multivariate logistic regression. Additionally, the average interval time were 33.6 & PLUSMN; 13.3 months. Mean changed FPG values in the persistent infection group were higher than in the subgroup of persistent negative (P = 0.029) as well as eradication infection (P = 0.007). The aforementioned changes began to appear after 2 years of follow-up. Similarly, when compared with the subgroup of persistent infection, mean changed triglyceride/high density lipoprotein (TG/HDL) values were much lower in the subgroup of persistent negative (P = 0.008) and eradication infection (P = 0.018), but the differences appeared after 3 years of follow-up. ConclusionsH. pylori infection is an independent risk factor for elevated FPG in non-diabetes mellitus (DM) individuals. Persistent H. pylori infection causes an increase in FPG level and TG/HDL, which may be a risk factor for diabetes mellitus.

Background Apical periodontitis directly affects the stress state of the affected tooth owing to the destruction of the periapical bone. Understanding the mechanical of periapical bone defects/tooth is clinically meaningful. In this study, we evaluate the effect of periapical bone defects on the stress distribution in teeth with periapical periodontitis using finite element analysis. Methods Finite element models of normal mandibular second premolars and those with periapical bone defects (spherical defects with diameters of 5, 10, 15, and 20 mm) were created using a digital model design software. The edges of the mandible were fixed and the masticatory cycle was simplified as oblique loading (a 400 N force loaded obliquely at 45° to the long axis of the tooth body) to simulate the tooth stress state in occlusion and analyze the von Mises stress distribution and tooth displacement distribution in each model. Results Overall analysis of the models : Compared to that in the normal model, the maximum von Mises stresses in all the different periapical bone defect size models were slightly lower. In contrast, the maximum tooth displacement in the periapical bone defect model increased as the size of the periapical bone defect increased (2.11–120.1% of increase). Internal analysis of tooth : As the size of the periapical bone defect increased, the maximum von Mises stress in the coronal cervix of the tooth gradually increased (2.23–37.22% of increase). while the von Mises stress in the root apical region of the tooth showed a decreasing trend (41.48–99.70% of decrease). The maximum tooth displacement in all parts of the tooth showed an increasing trend as the size of the periapical bone defect increased. Conclusions The presence of periapical bone defects was found to significantly affect the biomechanical response of the tooth, the effects of which became more pronounced as the size of the bone defect increased.

BACKGROUND Myopic traction maculopathy (MTM) are retinal disorder caused by traction force on the macula, which can lead to varying degrees of vision loss in eyes with high myopia. Optical coherence tomography (OCT) is an effective imaging technique for diagnosing, detecting and classifying retinopathy. MTM has been classified into different patterns by OCT, corresponding to different clinical strategies. PURPOSE We aimed to engineer a deep learning model that can automatically identify MTM in highly myopic (HM) eyes using OCT images. METHODS A five-class classification model was developed using 2837 OCT images from 958 HM patients. We adopted a ResNet-34 architecture to train the model to identify MTM: no MTM (class 0), extra-foveal maculoschisis (class 1), inner lamellar macular hole (class 2), outer foveoschisis (class 3), and discontinuity or detachment of foveal outer hyperreflective layers (class 4). An independent test set of 604 images from 173 HM patients was used to evaluate the model's performance. Classification performance was assessed according to the area under the curve (AUC), accuracy, sensitivity, specificity. RESULTS Our model exhibited a high training performance for classification (F1-score of 0.953; AUCs of 0.961 to 0.998). In test set, it achieved sensitivities (91.67%-97.78 %) and specificities (98.33%-99.17%) as good as, or better than, those of experienced clinicians. Heatmaps were generated to provide visual explanations. CONCLUSIONS We established a deep learning model for MTM classification using OCT images. This model performed equally well or better than retinal specialists and is suitable for large-scale screening and identifying MTM in HM eyes.

Purpose: To determine whether internal limiting membrane peeling damages retinal function in patients with an idiopathic macular hole. Methods: Retrospective case series. Forty-five eyes of 45 idiopathic macular hole patients who underwent vitrectomy with internal limiting membrane peeling with a minimum follow-up of 6 months. Each patient received a complete ophthalmological examination. The eyes were examined by microperimetry MP-3 in the central 20° visual field and optical coherence tomography angiography in the central 6 × 6 mm area. Results: Six months after the surgery, macular hole closed in each patient. Retinal sensitivity decreased significantly in the perifoveal temporal ETDRS sector (from 24.97 ± 2.67–19.98 ± 5.68 dB, P = 0.001) but not in the other sectors. Six patients (13%) developed 24 scotomas, 62.5% presented in the perifoveal temporal sector. Anatomically, bumps in the outer nuclear layer were discovered concurrent with inner retinal dimples on B-scan images, predominantly (76.8%) in the perifoveal temporal sector, which have not been previously reported. The incidence of outer nuclear layer bumps was significantly higher in patients with scotomas than in those without (83% vs. 18%, P = 0.014). Conclusion: Internal limiting membrane peeling induced functional changes specifically in the perifoveal temporal macula. Distortion in the retinal layers is proposed to underly scotomas pathogenesis.

Background: Angiotensin II (Ang II)-induced cardiac inflammation contribute to pathological cardiac remodeling and hypertensive heart failure (HF). Tabersonine (Tab) is an indole alkaloid mainly isolated from Catharanthus roseus and exhibits anti-inflammatory activity in various systems. However, the role of Tab in hypertensive HF and its molecular targets remains unknown. Hypothesis/purpose: We aimed to investigate potential cardioprotective effects and mechanism of Tab against Ang II-induced cardiac injuries.Methods: C57BL/6 mice were administered Ang II (at 1000 ng/kg/min) by micro-osmotic pump infusion for 30 days to develop hypertensive HF. Tab at 20 and 40 mg/kg/day was administered during the last 2 weeks to elucidate the cardioprotective properties. Cultured cardiomyocyte-like H9c2 cells and rat primary cardiomyocytes were used for mechanistic studies of Tab.Results: We demonstrate for the first time that Tab provides protection against Ang II-induced cardiac dysfunction in mice, associated with reduced cardiac inflammation and fibrosis. Mechanistically, we show that Tab may interacts with TAK1 to inhibit Ang II-induced TAK1 ubiquitination and phosphorylation. Disruption of TAK1 activation by Tab blocked downstream NF-Kappa B and JNK/P38 MAPK signaling activation and decreased cardiac inflammation and fibrosis both in vitro and in vivo. TAK1 knockdown also blocked Ang II-induced cardiomyocytes injuries and prevented the innately pharmacological effects of Tab.Conclusion: Our results indicate that Tab protects hearts against Ang II-mediated injuries through targeting TAK1 and inhibiting TAK1-mediated inflammatory cascade and response. Thus, Tab may be a potential therapeutic candidate for hypertensive HF.

Purpose To apply deep learning (DL) techniques to develop an automatic intelligent classification system identifying the specific types of myopic maculopathy (MM) based on macular optical coherence tomography (OCT) images using transfer learning (TL). Method In this retrospective study, a total of 3,945 macular OCT images from 2,866 myopic patients were recruited from the ophthalmic outpatients of three hospitals. After culling out 545 images with poor quality, a dataset containing 3,400 macular OCT images was manually classified according to the ATN system, containing four types of MM with high OCT diagnostic values. Two DL classification algorithms were trained to identify the targeted lesion categories: Algorithm A was trained from scratch, and algorithm B using the TL approach initiated from the classification algorithm developed in our previous study. After comparing the training process, the algorithm with better performance was tested and validated. The performance of the classification algorithm in the test and validation sets was evaluated using metrics including sensitivity, specificity, accuracy, quadratic-weighted kappa score, and the area under the receiver operating characteristic curve (AUC). Moreover, the human-machine comparison was conducted. To better evaluate the algorithm and clarify the optimization direction, the dimensionality reduction analysis and heat map analysis were also used to visually analyze the algorithm. Results Algorithm B showed better performance in the training process. In the test set, the algorithm B achieved relatively robust performance with macro AUC, accuracy, and quadratic-weighted kappa of 0.986, 96.04% (95% CI: 0.951, 0.969), and 0.940 (95% CI: 0.909–0.971), respectively. In the external validation set, the performance of algorithm B was slightly inferior to that in the test set. In human-machine comparison test, the algorithm indicators were inferior to the retinal specialists but were the same as the ordinary ophthalmologists. In addition, dimensionality reduction visualization and heatmap visualization analysis showed excellent performance of the algorithm. Conclusion Our macular OCT image classification algorithm developed using the TL approach exhibited excellent performance. The automatic diagnosis system for macular OCT images of MM based on DL showed potential application prospects.