Comprehensive Assessment of Posterior Corneal Asphericity Change Calculated by Tangential Radius of Curvature After FS-LASIK and SMILE.

PURPOSE: To evaluate changes in posterior corneal asphericity (ΔQ) using the tangential radius of curvature after femtosecond laser-assisted in situ keratomileusis (FS-LASIK) and small incision lenticule extraction (SMILE) procedures. METHODS: One hundred twenty right eyes of myopic patients who underwent either FS-LASIK or SMILE procedures were analyzed using Sirius 3D corneal topography for assessment. The tangential radius was employed to calculate both preoperative and postoperative posterior corneal Q-values across each semimeridian. After both surgical interventions, the ΔQ value variations across the 360° semimeridional regions of the posterior corneal surface were compared. RESULTS: A marked postoperative increase in the posterior corneal Q-value was documented. No significant differences were noted between the postoperative Q-values or ΔQ-values of the two surgical approaches. Among patients with moderate myopia, postoperative Q-value exhibited considerably lower increases and ΔQ-value significantly smaller than their counterparts with high myopia. Moreover, the fluctuation in ΔQ across semimeridional regions was less evident in patients with moderate myopia than in those with high myopia. Notably, the degree of ΔQ fluctuation across semimeridional regions was similar between both surgical categories. These data offer insights into variations in the posterior corneal surface after refractive surgeries depending on the degree of myopia, illuminating their clinical relevance. CONCLUSIONS: Both FS-LASIK and SMILE introduce notable changes to posterior corneal asphericity among patients with different myopia intensities. Furthermore, the influence on the asphericity across the entire posterior surface is similarly distributed between FS-LASIK and SMILE techniques. [J Refract Surg. 2024;40(3):e133-e141.].

SADSNet: A robust 3D synchronous segmentation network for liver and liver tumors based on spatial attention mechanism and deep supervision.

Highlights: • Introduce a data augmentation strategy to expand the required different morphological data during the training and learning phase, and improve the algorithm's feature learning ability for complex and diverse tumor morphology CT images.• Design attention mechanisms for encoding and decoding paths to extract fine pixel level features, improve feature extraction capabilities, and achieve efficient spatial channel feature fusion.• The deep supervision layer is used to correct and decode the final image data to provide high accuracy of results.• The effectiveness of this method has been affirmed through validation on the LITS, 3DIRCADb, and SLIVER datasets. BACKGROUND: Accurately extracting liver and liver tumors from medical images is an important step in lesion localization and diagnosis, surgical planning, and postoperative monitoring. However, the limited number of radiation therapists and a great number of images make this work time-consuming. OBJECTIVE: This study designs a spatial attention deep supervised network (SADSNet) for simultaneous automatic segmentation of liver and tumors. METHOD: Firstly, self-designed spatial attention modules are introduced at each layer of the encoder and decoder to extract image features at different scales and resolutions, helping the model better capture liver tumors and fine structures. The designed spatial attention module is implemented through two gate signals related to liver and tumors, as well as changing the size of convolutional kernels; Secondly, deep supervision is added behind the three layers of the decoder to assist the backbone network in feature learning and improve gradient propagation, enhancing robustness. RESULTS: The method was testing on LITS, 3DIRCADb, and SLIVER datasets. For the liver, it obtained dice similarity coefficients of 97.03%, 96.11%, and 97.40%, surface dice of 81.98%, 82.53%, and 86.29%, 95% hausdorff distances of 8.96 mm, 8.26 mm, and 3.79 mm, and average surface distances of 1.54 mm, 1.19 mm, and 0.81 mm. Additionally, it also achieved precise tumor segmentation, which with dice scores of 87.81% and 87.50%, surface dice of 89.63% and 84.26%, 95% hausdorff distance of 12.96 mm and 16.55 mm, and average surface distances of 1.11 mm and 3.04 mm on LITS and 3DIRCADb, respectively. CONCLUSION: The experimental results show that the proposed method is effective and superior to some other methods. Therefore, this method can provide technical support for liver and liver tumor segmentation in clinical practice.

MTAN: A semi-supervised learning model for kidney tumor segmentation.

BACKGROUND: Medical image segmentation is crucial in disease diagnosis and treatment planning. Deep learning (DL) techniques have shown promise. However, optimizing DL models requires setting numerous parameters, and demands substantial labeled datasets, which are labor-intensive to create. OBJECTIVE: This study proposes a semi-supervised model that can utilize labeled and unlabeled data to accurately segment kidneys, tumors, and cysts on CT images, even with limited labeled samples. METHODS: An end-to-end semi-supervised learning model named MTAN (Mean Teacher Attention N-Net) is designed to segment kidneys, tumors, and cysts on CT images. The MTAN model is built on the foundation of the AN-Net architecture, functioning dually as teachers and students. In its student role, AN-Net learns conventionally. In its teacher role, it generates objects and instructs the student model on their utilization to enhance learning quality. The semi-supervised nature of MTAN allows it to effectively utilize unlabeled data for training, thus improving performance and reducing overfitting. RESULTS: We evaluate the proposed model using two CT image datasets (KiTS19 and KiTS21). In the KiTS19 dataset, MTAN achieved segmentation results with an average Dice score of 0.975 for kidneys and 0.869 for tumors, respectively. Moreover, on the KiTS21 dataset, MTAN demonstrates its robustness, yielding average Dice scores of 0.977 for kidneys, 0.886 for masses, 0.861 for tumors, and 0.759 for cysts, respectively. CONCLUSION: The proposed MTAN model presents a compelling solution for accurate medical image segmentation, particularly in scenarios where the labeled data is scarce. By effectively utilizing the unlabeled data through a semi-supervised learning approach, MTAN mitigates overfitting concerns and achieves high-quality segmentation results. The consistent performance across two distinct datasets, KiTS19 and KiTS21, underscores model's reliability and potential for clinical reference.

Mesenchymal stem cells transplantation combined with IronQ attenuates ICH-induced inflammation response via Mincle/syk signaling pathway.

BACKGROUND: Intracerebral hemorrhage (ICH) is a severe brain-injured disease accompanied by cerebral edema, inflammation, and subsequent neurological deficits. Mesenchymal stem cells (MSCs) transplantation has been used as a neuroprotective therapy in nervous system diseases because of its anti-inflammatory effect. Nevertheless, the biological characteristics of transplanted MSCs, including the survival rate, viability, and effectiveness, are restricted because of the severe inflammatory response after ICH. Therefore, improving the survival and viability of MSCs will provide a hopeful therapeutic efficacy for ICH. Notably, the biomedical applications of coordination chemistry-mediated metal-quercetin complex have been verified positively and studied extensively, including growth-promoting and imaging probes. Previous studies have shown that the iron-quercetin complex (IronQ) possesses extraordinary dual capabilities with a stimulating agent for cell growth and an imaging probe by magnetic resonance imaging (MRI). Therefore, we hypothesized that IronQ could improve the survival and viability of MSCs, displaying the anti-inflammation function in the treatment of ICH while also labeling MSCs for their tracking by MRI. This study aimed to explore the effects of MSCs with IronQ in regulating inflammation and further clarify their potential mechanisms. METHODS: C57BL/6 male mice were utilized in this research. A collagenase I-induced ICH mice model was established and randomly separated into the model group (Model), quercetin gavage group (Quercetin), MSCs transplantation group (MSCs), and MSCs transplantation combined with IronQ group (MSCs + IronQ) after 24 h. Then, the neurological deficits score, brain water content (BWC), and protein expression, such as TNF-α, IL-6, NeuN, MBP, as well as GFAP, were investigated. We further measured the protein expression of Mincle and its downstream targets. Furthermore, the lipopolysaccharide (LPS)-induced BV2 cells were utilized to investigate the neuroprotection of conditioned medium of MSCs co-cultured with IronQ in vitro. RESULTS: We found that the combined treatment of MSCs with IronQ improved the inflammation-induced neurological deficits and BWC in vivo by inhibiting the Mincle/syk signaling pathway. Conditioned medium derived from MSCs co-cultured with IronQ decreased inflammation, Mincle, and its downstream targets in the LPS-induced BV2 cell line. CONCLUSIONS: These data suggested that the combined treatment exerts a collaborative effect in alleviating ICH-induced inflammatory response through the downregulation of the Mincle/syk signaling pathway following ICH, further improving the neurologic deficits and brain edema.

Carbon Nanotube Polymer Scaffolds as a Conductive Alternative for the Construction of Retinal Sheet Tissue.

With the great success of graphene in the biomedical field, carbon nanotubes have attracted increasing attention for different applications in ophthalmology. Here, we report a novel retinal sheet composed of carbon nanotubes (CNTs) and poly(lactic-co-glycolic acid) (PLGA) that can enhance retinal cell therapy. By tuning our CNTs to regulate the mechanical characteristics of retina sheets, we were able to improve the in vitro viability of retinal ganglion cells derived from human-induced pluripotent stem cells incorporated into CNTs. Engrafted retinal ganglion cells displayed signs of regenerating processes along the optic nerve. Compared with PLGA scaffolds, CNT-PLGA retinal sheet tissue has excellent electrical conductivity, biocompatibility, and biodegradation. This new biomaterial offers new insight into retinal injury, repair, and regeneration.

Biodegradable scaffolds facilitate epiretinal transplantation of hiPSC-Derived retinal neurons in nonhuman primates.

Transplantation of stem cell-derived retinal neurons is a promising regenerative therapy for optic neuropathy. However, significant anatomic differences compromise its efficacy in large animal models. The present study describes the procedure and outcomes of human-induced pluripotent stem cell (hiPSC)-derived retinal sheet transplantation in primate models using biodegradable materials. Stem cell-derived retinal organoids were seeded on polylactic-coglycolic acid (PLGA) scaffolds and directed toward a retinal ganglion cell (RGC) fate. The seeded tissues showed active proliferation, typical neuronal morphology, and electrical excitability. The cellular scaffolds were then epiretinally transplanted onto the inner surface of rhesus monkey retinas. With sufficient graft-host contact provided by the scaffold, the transplanted tissues survived for up to 1 year without tumorigenesis. Histological examinations indicated survival, further maturation, and migration. Moreover, green fluorescent protein-labeled axonal projections toward the host optic nerve were observed. Cryopreserved organoids were also able to survive and migrate after transplantation. Our results suggest the potential efficacy of RGC replacement therapy in the repair of optic neuropathy for the restoration of visual function. STATEMENT OF SIGNIFICANCE: In the present study, we generated a human retinal sheet by seeding hiPSC-retinal organoid-derived RGCs on a biodegradable PLGA scaffold. We transplanted this retinal sheet onto the inner surface of the rhesus monkey retina. With scaffold support, donor cells survive, migrate and project their axons into the host optic nerve. Furthermore, an effective cryopreservation strategy for retinal organoids was developed, and the thawed organoids were also observed to survive and show cell migration after transplantation.

Islet1 and Brn3 Expression Pattern Study in Human Retina and hiPSC-Derived Retinal Organoid.

This study was conducted to determine the dynamic Islet1 and Brn3 (POU4F) expression pattern in the human fetal retina and human-induced pluripotent stem cell- (hiPSC-) derived retinal organoid. Human fetal eyes from 8 to 27 fetal weeks (Fwks), human adult retina, hiPSC-derived retinal organoid from 7 to 31 differentiation weeks (Dwks), and rhesus adult retina were collected for cyrosectioning. Immunofluorescence analysis showed that Islet1 was expressed in retinal ganglion cells in the fetal retina, human adult retina, and retinal organoids. Unexpectedly, after Fwk 20, Brn3 expression gradually decreased in the fetal retina. In the midstage of development, Islet1 was detected in bipolar and developing horizontal cells. As the photoreceptor developed, the Islet1-positive cone precursors gradually became Islet1-negative/S-opsin-positive cones. This study highlights the distinguishing characteristics of Islet1 dynamic expression in human fetal retina development and proposes more concerns which should be taken regarding Brn3 as a cell-identifying marker in mature primate retina.

Establishing a Surgical Procedure for Rhesus Epiretinal Scaffold Implantation with HiPSC-Derived Retinal Progenitors.

BACKGROUND: To develop an effective surgical procedure for cellular scaffold epiretinal implantation in rhesus, facilitating subsequent epiretinal stem cell transplantation. METHODS: Retinal progenitors were seeded onto a poly(lactic-co-glycolic) acid (PLGA) scaffold. First, the cellular scaffolds were delivered by 18G catheter or retinal forceps into rabbit epiretinal space (n = 50). Then, the cell survival rate was evaluated by Cell Counting Kit-8 (CCK-8). Second, three methods of scaffold fixation, including adhesion after gas-liquid exchange (n = 1), tamponade by hydrogel (n = 1), and fixation by retinal tacks (n = 4), were performed in rhesus monkeys. After one month, fundus photography and SD-OCT were performed to assess the outcomes, and histological examination was performed to evaluate proliferation. RESULTS: The cell survival rate was significantly higher in the catheter group. Follow-up examination showed that retinal tack fixation was the only method to maintain the scaffolds attached to host retina for at least 3 weeks, which is the minimal time required for cell integration. Histological staining demonstrated slight glial fibrillary acidic protein (GFAP) accumulation in the retinal tack insertion area. CONCLUSIONS: The established surgical procedure offers a new insight into research of epiretinal cell replacement therapy in rhesus eyes. The successful delivery and long-term fixation provide a prerequisite for cell migration and integration.

Alpha 1-antitrypsin inhibits microglia activation and facilitates the survival of iPSC grafts in hypertension mouse model.

This study was conducted to investigate the use of Alpha 1-antitrypsin (AAT) to inhibit microglia activation in chronic hypertension model and provide a permissive environment for stem cell transplantation. Chronic ocular hypertension of C57BL/6 mice using magnetic microbead injection was induced 3 weeks prior to iPSCs transplantation. The ocular hypertension model was assessed histologically and intraocular pressure was measured. Survival of grafted cells and microglia activation were examined by flow cytometry and immunofluorescence in AAT and PBS treated hosts. Retinal cytokines expression was also detected by real-time PCR. Chronic ocular hypertension resulted in persistent microglia activation and stem cell grafts loss. AAT treatment significantly inhibited microglia activation and facilitated the survival of transplant iPSCs 4w post transplantation compared to PBS treatment. AAT holds tremendous potential for the clinical application to control neuroinflammation factor in glaucoma and improve the stem cell replacement therapy of retinal neurodegenerative disease.

HiPSC-derived retinal ganglion cells grow dendritic arbors and functional axons on a tissue-engineered scaffold.

Numerous therapeutic procedures in modern medical research rely on the use of tissue engineering for the treatment of retinal diseases. However, the cell source and the transplantation method are still a limitation. Previously, it was reported that a self-organizing three-dimensional neural retina can be induced from human-induced pluripotent stem cells (hiPSCs). In this study, we disclose the generation of retinal ganglion cells (RGCs) from the neural retina and their seeding on a biodegradable poly (lactic-co-glycolic acid) (PLGA) scaffold to create an engineered RGC-scaffold biomaterial. Moreover, we explored the dendritic arbor, branching point, functional axon and action potential of the biomaterial. Finally, the cell-scaffold was transplanted into the intraocular environment of rabbits and rhesus monkeys. STATEMENT OF SIGNIFICANCE: As a part of the mammalian central nervous system (CNS), the retinal ganglion cell (RGC) shows little regenerative capacity. With the use of medical biomaterial for cells seeding and deliver, a new domain is now emerging that uses tissue engineering therapy for retinal disease. However, previous studies utilized RGCs from rodent model, which has limitations for human disease treatment. In the present study, we generated RGCs from hiPSCs-3D neural retina and then seeded these RGCs on PLGA scaffold to create an engineered RGC-scaffold biomaterial. Moreover, we assessed the transplantation method for biomaterial in vivo. Our study provides a technique to produce the engineered human RGC-scaffold biomaterial.

[Prevalence of peripheral arterial disease and its correlative risk factors in Xinjiang Uygur and Kazak adult populations].

OBJECTIVE: To investigate the prevalence of peripheral arterial disease (PAD) and its correlative risk factors in Xinjiang Uygur and Kazak adult populations. METHODS: The subjects over the age of 35 years old in Urumqi, Karamay City, Fukang City, Turpan Region, Hotan Prefecture and Yili Kazak Autonomous Prefecture were selected by the four-stage random sampling method. The investigators collected the data of PAD prevalence in different nationalities, different age groups and different gender groups and analyzed its risk factors. RESULTS: The prevalence of PAD in Uygur and Kazak adults was 6.46% (n = 542). The standardized prevalence was 6.51%. The prevalence of PAD was 7.05% (n = 315) in Uygur adults and 5.79% (n = 227) in Kazak adults. The standardized prevalence in the Uygur and Kazak adults was 7.08% and 5.83% respectively. The prevalence of PAD of different nationalities was different (χ(2) = 5.55, P < 0.05). And its prevalence was 4.49% (n = 170) in males and 8.08% (n = 372) in females. The standardized prevalence was 4.30% in males and 7.90% in females. The prevalence of PAD in males and females was significantly different (χ(2) = 44.26, P < 0.01). The multivariate logistic regression analysis was performed. Age (OR = 1.01, 95%CI 1.00 - 1.02), females (OR = 1.75, 95%CI 1.45 - 2.14), overweight or obesity (OR = 1.04, 95%CI 1.01 - 1.06), diabetes (OR = 1.59, 95%CI 1.01 - 2.36), elevated systolic blood pressure (OR = 1.02, 95%CI 1.01 - 1.03), elevated diastolic blood pressure (OR = 1.08, 95%CI 1.01 - 1.11) and history of coronary heart disease (OR = 1.69, 95%CI 1.14 - 2.50) were associated with an elevated prevalence of PAD. CONCLUSION: The prevalence of PAD is lower in Xinjiang Uygur and Kazak adult populations. Females, age, overweight or obesity, diabetes, elevated systolic blood pressure and a history of coronary heart disease are risk factors of PAD.