Abstract Microelectromechanical systems (MEMS)‐based devices, characterized by miniaturization, high sensing performance, integration, and enhanced comfort, have been increasingly employed in diagnosis, treatment, and monitoring in ophthalmology. MEMS‐based devices have been widely used to design sensors that enable real‐time monitoring of physiological and chemical markers in vitro and tear biomarkers in vivo. MEMS‐based technology improves resolution, imaging depth, speed, and precision in optical coherence tomography and microscopy. MEMS‐based devices overcome biological barriers, enable targeted drug delivery, and allow feedback‐controlled release for high efficacy and low side effects. MEMS‐based retinal prostheses restore visual perception by electrically stimulating retinal neurons. MEMS‐based surgical tools enhance surgical precision, minimizes infection risks, and improves patient outcomes. MEMS‐based wearable products monitor blink frequency and eye tracking for improvement of the life quality. Thus, we systematically summarized advances in MEMS‐based devices for accurate diagnosis, effective treatment, and daily monitoring in ophthalmology. The challenges and potential development directions of MEMS‐based devices applied to ophthalmological diseases were discussed. This review highlights the current applications and future potential of MEMS‐based devices in revolutionizing eye health.

Background or Purpose:To explore the value of predictive models assisted diagnosis of benign and malignant lacrimal gland tumor based on dynamic contrast enhanced (DCE) combined with conventional MRI. Methods:This study retrospectively analyzed the patients with primary lacrimal gland tumors using conventional and DCE-MRI. 15 base predictive models were conducted to compare the diagnostic value. Results:A total number of 76 patients were enrolled, including 41 were malignant, 35 were benign. Compared with the benign and malignant tumors, MRI parameters including tumor diameter, tumor shape, adjacent bone damage, Ktrans, Kep, Ve and TIC were selected into predictive models. Six-performance metrics of models with DCE quantitative parameters was significantly better than the models without. According to the test results, Extra Trees Classifier (ET) showed the highest MCC and F1 score, the accuracy was 91 %, precision was 100 %, and the recall was 83 %, based on DCE quantitative parameters plus conventional MRI features. Discussion or Conclusions:Our findings indicate that the predictive models based on DCE quantitative parameters plus conventional MRI features have shown better performance than the models based on conventional MRI features alone. ET could be selected as the best model in the diagnosis of benign and malignant lacrimal tumors.

Purpose:To develop and validate a deep learning model for automated macular hole (MH) staging using optical coherence tomography (OCT) images. Methods:This retrospective study included OCT-confirmed MH images collected between July 2019 and October 2024. After quality control and redundancy screening, 6,243 representative OCT images were retained. Highly similar consecutive scans were excluded through combined manual review and program-assisted similarity assessment before model development. Models were developed using standardized preprocessing and five-fold cross-validation. ResNet-based and Swin Transformer-based architectures were constructed and compared. ResNet-18 was further optimized by integrating deformable convolution (DCNv2) and efficient channel attention (ECA). Results:Swin Transformer Tiny achieved high training accuracy but showed unstable performance on the test set. In contrast, the optimized ResNet-18 demonstrated more consistent classification results across validation folds. The optimized ResNet-18 achieved accuracy, precision, recall, F1-score, specificity, and AUC values of 98.23%, 97.17%, 96.90%, 97.00%, 99.44%, and 99.76%, respectively. External validation showed consistent classification accuracy on independent data. Conclusion:The optimized ResNet-18 achieved accurate and stable MH staging using OCT images under a standardized training framework. Compared with deeper CNN and Transformer-based architectures, the proposed model demonstrated more reliable performance under limited-data conditions. These findings support the feasibility of automated MH staging using OCT images.

There are numerous types of orbital tumors, among which orbital ameloblastoma is a rare metastatic benign tumor that often originates in the jaw and later metastasizes to the orbit. The mystery of it lies in that, although it is classified as a benign tumor, it exhibits high recurrence and malignant potential with high invasiveness, posing a serious threat to ocular health and the quality of life of patients. The prognosis of orbital ameloblastoma is relatively poor, but there is still hope. With aggressive treatment and close follow-up observation, patients may still have the possibility of achieving a longer survival period and a better quality of life. The global incidence of ameloblastoma is 0.92 cases per million people per year. According to world literature reports, there are 32 cases of maxillary bone metastasis to the orbit and 4 cases of mandibular bone metastasis to the orbit. With more and more cases and related research being reported, it is necessary to comprehensively review the etiology, clinical manifestations, diagnosis, treatment, and prognosis of orbital ameloblastoma, in order to enhance ophthalmologists' understanding and diagnostic and treatment skills of this disease, and ultimately improve patients' prognosis and quality of life.

Micromirror technology is one of the current research hotspots. In this work, what we believe to be a novel electrostatic 2-DOF micromirror structure with double-biased torsional axes is proposed. By introducing internal resonance, synchronous motions of the two axes with a locked frequency ratio under a single driving force were achieved within a wide frequency range. The mechanical structure can thus be greatly simplified, as well as the operating frequency band is broadened. Also, two driving methods were proposed to realize the density spot acquisition with a 1:2 frequency ratio. The macroscopic experiment is further carried out to verify the validity of the theoretical model, which successfully realized a 1:2 internal resonance. The structural optimization design of internal resonance micromirrors is discussed, and a band expansion of at least 135.58% can be achieved in the simulation results. Compared with the traditional resonant micromirrors, the proposed one greatly increases the operating band at a very small sacrifice of vibration amplitude, and the resonant state can be guaranteed in complex environments. This novel micromirror provides a new chip solution for portable devices in complex environments and greatly simplifies the structure of dual-axis resonant micromirrors, reduces processing costs, and improves processing reliability.

In this paper, we proposed an eye-tracking system featuring a small size and high scanning frequency, utilizing an electrostatic biaxial scanning mirror fabricated through a micro-electro-mechanical system (MEMS) process. A laser beam is directed onto the mirror, and the two axes of the mirror generate a Lissajous scanning pattern within an artificial eyeball. The scanning pattern reflected from the eyeball is detected by a linear photodiode sensor array (LPSA). The direction and rotation angle of the artificial eyeball result in varying grayscale values across a series of pixels detected by the LPSA, in which the average grayscale values change accordingly. By performing a linear fit between different rotation angles of the same eye movement direction and the corresponding grayscale values, we can determine the correlation between the direction of eye movement and the signal magnitude received by the LPSA, thereby enabling precise eye tracking. The results demonstrated that the minimum resolution was 0.6°. This preliminary result indicates that the system has good accuracy. In the future, this eye-tracking system can be integrated into various wearable glasses devices and applied in various fields, including medicine and psychology.

Background: The expression of serum progranulin (PGRN) and the related immunological mechanisms of peripheral blood mononuclear cells (PBMCs) CD4 + T cells exosomes in thyroid-associated ophthalmopathy (TAO) are currently hot topics of research. Material and Method: A total of 27 patients with active TAO and 59 healthy individuals were included in the study for comparison. PBMCs were isolated from the patients' blood, and naïve CD4+ T cells were purified using human naïve CD4 microbeads. One co-culture group was not supplemented with PGRN, serving as the PGRN-untreated group (AG), while another group was supplemented with extracted PGRN, serving as the PGRN-treated group (BG). CD4+ T cells derived from the blood of healthy individuals were used as the control group (CG). Result: The serum PGRN concentration in TAO patients was visibly higher as against the CG; The contents of interleukin (IL-10), IL-4, and IL-17 in BG were visibly lower as against AG; The protein and mRNA expression of cytokines in BG were visibly lower as against AG; The proliferation level of CD4 + T cells was visibly lower, and the apoptosis level was visibly higher in BG as against AG (P < 0.05). Conclusion: PGRN may be implicated in the pathogenesis of TAO. It could modulate the immune response by reducing cytokine release in CD4+ T cell-derived exosomes, inhibiting the proliferation of CD4+ T cells, and promoting their apoptosis.

Eye tracking technology has shown a wide range of applications, while conventional camera-based systems face an inherent trade-off between power consumption and accuracy. In this work, we proposed what we believe to be a novel eye tracking method that utilizes an 8 kHz-driven MEMS mirror to achieve one-dimensional (1D) rotational scanning. By modulating the duty cycle and phase of the drive signal, the laser beam is precisely scanned to the cornea surface of the eye. Gaze direction is then estimated by analyzing the peak time interval of the reflected signal, thereby minimizing computational load and reducing power consumption. Experimental results show that the system achieves high accuracy of less than 0.5° and remains stable during simulated saccade while ensuring low latency. This work offers a viable pathway toward highly integrated next-generation eye tracking systems.

Orbital ameloblastoma is a rare benign tumor with metastatic potential, typically exhibiting follicular or plexiform histopathological patterns. Ameloblastoma commonly occurs in the jaws and rarely metastasizes; when it does, the lungs and lymph nodes are the most frequent secondary sites. In the world's reported literature, there are 32 cases of maxillary ameloblastoma metastasizing to the orbit, with only 4 cases of mandibular ameloblastoma metastasizing to the orbit. The mystery lies in its high recurrence rate and aggressive malignant potential despite being classified as a benign tumor, posing a serious threat to the ocular health and quality of life of patients. This article reports an unusual case of a female patient who was initially diagnosed with mandibular ameloblastoma 17 years ago. Despite undergoing treatment, the tumor recurred and unusually metastasized to the orbit, resulting in a massive lesion that compressed the tissues surrounding the eyeball. She complained of gradual vision loss in her right eye, redness of the eye, and incomplete eyelid closure. Magnetic resonance imaging (MRI) scans of the orbit indicated a lesion measuring approximately 5.8 cm*5.1 cm*5.7 cm (centimeter, cm). The clinical diagnosis is recurrent ameloblastoma of the right orbital, with the histopathological subtype being the basal cell type. The patient underwent 2 successful partial excisions of the orbital tumor, effectively relieving the compression on the eyeball caused by the tumor. Currently, the 22-month follow-up after the second surgery has shown satisfactory results, with the patient's visual function being preserved. The patient exhibited significant facial disfigurement at the time of presentation to the ophthalmology department, attributable to the large size of the orbital mass. Inadequate awareness of this uncommon pathology may result in misdiagnosis as basal cell carcinoma or other malignant orbital neoplasms. Despite the preservation of visual function, limited understanding of the disease could lead to overly aggressive surgical management. Therefore, this case is reported to provide insights into the diagnosis, management, and prognosis, serving as a reference for clinicians encountering similar presentations.

Orbital bone defect repair is both challenging and crucial and requires the comprehensive consideration of anatomical complexity, functional preservation, aesthetic outcomes, postoperative risks, and long-term effects. Polyetheretherketone (PEEK) is a promising orthopedic substitute material due to its cortical bone-like elastic modulus, biocompatibility, chemical stability, and natural radiolucency. However, PEEK is bioinert and lacks interfacial bioactivity, which limits its ability to promote bone growth and osseointegration. In this study, we fabricated porous PEEK scaffolds using Fused Deposition Modeling (FDM) 3D printing technology. We employed a phase-transitioned lysozyme (PTL) nanofilm as the organic matrix template to construct a robust hydroxyapatite (HAp) coating both inside and outside the porous PEEK scaffold, generating HAp@PTL@PO-PEEK. The PTL nanofilm acted as a strong glue, enhancing the interfacial bonding strength between the HAp coating and PEEK. In vitro cell biology experiments revealed that HAp@PTL@PO-PEEK promoted the proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells. Furthermore, the modified scaffolds exhibited excellent osteoconductivity and osteoinductivity in the in vivo repair of rabbit orbital bone defects, promoting new bone formation and guiding new bone growth into the scaffold. Therefore, HAp@PTL@PO-PEEK scaffolds hold potential for clinical craniomaxillofacial bone regeneration and repair.

Objective:To investigate the effect of tumor necrosis factor-α (TNF-α) on the differentiation of orbital fibroblasts (OF) in thyroid-associated ophthalmopathy (TAO) and its regulation mechanism.Methods:Six patients (six eyes) diagnosed with TAO were collected in Tianjin Medical University Eye Hospital from December 2019 to August 2020.Adipose connective tissue was collected during the orbital decompression surgery.OF was isolated and cultured using the tissue block method and vimentin was identified by immunofluorescence.Lipogenic differentiation of OF was induced and identified by oil red O staining.Complete culture medium containing 0, 0.1, 1.0 and 10.0 μg/L TNF-α was used to induce the dedifferentiation of orbital mature adipocytes.Primary culturing cells, 14-day differentiation cells and 20-day dedifferentiation cells were collected.The relative mRNA expression levels of peroxisomal proliferation-activated receptor (PPARγ), extracellular regulatory protein kinase1 (ERK1), ERK2 and fat-coated protein1 (perilipin1) were detected by real-time fluorescent quantitative PCR.The relative protein expression levels of PPARγ, P-ERK1/2 and perilipin1 were detected by Western blot.Results:Human TAO-derived OF were successfully cultured in vitro, spindle-shaped or polygonal, tightly arranged in a vortex pattern, and immunofluorescence staining for vimentin was positive.After OF adipogenic differentiation, lipid droplet structures could be seen in the cytoplasm of some cells, and the stained lipid droplet structures in the cytoplasm could be seen by oil red O staining, which confirmed that the cells obtained after differentiation were adipocytes.Dedifferentiation of adipocytes was induced by 0.1, 1.0, and 10.0 μg/L TNF-α.With the extension of induction time, the volume of lipid droplets in the cytoplasm and the number of cells containing lipid droplets decreased.Lipid droplets disappeared in the cytoplasm on the 20th day of dedifferentiation, and the cells became long spindle-shaped and tightly arranged, dedifferentiated into fibroblast-like cells.Real-time fluorescence quantitative PCR detection results showed that the relative expression levels of PPARγ, ERK1, ERK2 and perilipin1 mRNA in 14-day differentiation group were 4.26±0.09, 2.01±0.09, 3.23±0.10 and 8.69±0.33, respectively, which were significantly higher than 1.00±0.09, 1.05±0.19, 1.00±0.10 and 1.05±0.07 in primary group, and 1.06±0.03, 1.15±0.11 and 6.27±0.09 in 20-day dedifferentiation group (all at P<0.05). Western blot analysis showed that the expression levels of PPARγ, ERK1/2 and perilipin1 proteins in 14-day differentiation group were 1.07±0.03, 1.00±0.03 and 1.13±0.02, respectively, which were significantly higher than 0.37±0.02, 0.29±0.02 and 0.00±0.00 in primary group, and 0.20±0.02, 0.38±0.06 and 0.00±0.00 in 20-day dedifferentiation group (all at P<0.001). Conclusions:TNF-α has a dedifferentiation effect on TAO orbital adipocytes.The mechanism may be related to the downregulation of ERK1/2-PPARγ-perilipin1 signaling pathway.

Objective:To investigate the effects of sclerostin (SOST) and WNT/CTNNB1 signaling pathway on the cell cycle, migration and invasion of human uveal melanoma (UM) cells and its related mechanism.Methods:UM tissues from 20 cases of epithelioid UM and 16 cases of spindle cell type UM were collected.The contents of SOST, Wnt-1 and Catenin beta-1 proteins in the collected tissues were detected by immunohistochemical staining.Three human UM tissue derived cell lines OCM-1 (primary spindle cell type), Mum-2B (metastatic epithelioid) and Mum-2C (metastatic spindle cell type) were selected and divided into three groups, blank control group not transfected, empty vector group transfected with SOST negative control vector and SOST siRNA group transfected with SOST siRNA.After 24-hour transfection, the mRNA and protein expression levels of SOST, CTNNB1, WNT protein family 1 (WNT1), CCND1, matrix metalloproteinase (MMP)2 and MMP9 were detected by real-time fluorescence quantitative PCR and Western blot, respectively.The invasion and migration ability of the transfected cells were measured by transwell method, and the cell cycle distribution was detected by flow cytometry.Another 9 female BALB/c nude mice were selected and randomized into OCM-1 group, OCM-1 empty vector group and SOST shRNA group, inoculated with OCM-1 without lentivirus infection, OCM-1 with blank lentivirus infection and OCM-1 with SOST shRNA lentivirus infection, respectively.Six weeks after inoculation, the in situ formation of tumor was observed.The interaction between SOST and low density lipoprotein receptor related protein(LRP)-5/6 in OCM-1 cells was explored by co-immunoprecipitation assay.The study protocol was approved by the Ethics Committee of Tianjin Medical University Eye Hospital (2018KY[L]-20).Results:Immunohistochemical staining results showed that the SOST expression level was higher and the expression levels of Wnt-1 and Catenin beta-1 were lower in spindle cell type UM tissues than in epithelioid UM tissues, and the differences were all statistically significant (all at P<0.01). The real-time fluorescence quantitative PCR results showed that the relative expression of SOST mRNA was significantly lower and the relative expressions of CCND1, WNT1 and MMP9 mRNA were significantly higher in SOST siRNA groups than in corresponding empty vector groups in the three cell lines (all at P<0.05). In OCM-1 and Mum-2C cell lines, the relative expressions of CTNNB1 mRNA were significantly higher in SOST siRNA groups than in empty vector groups (all at P<0.01). Western blot results showed that the relative expression of SOST protein was significantly lower and the relative expressions of Wnt-1, Catenin beta-1, cyclin-D1, MMP2 and MMP9 proteins were significantly higher in SOST siRNA groups than in empty vector groups (all at P<0.01). Transwell assay showed that the cell invasion and migration ability of SOST siRNA group was significantly higher than that of blank control group and empty vector group in the three cell lines (all at P<0.01). Flow cytometry showed that the proportion of G1-phase cells and the G1/S-phase ratio were significantly lower in SOST siRNA group than in blank control groups and empty vector groups (all at P<0.01). The eyeball volume of OCM-1 group, OCM-1 empty vector group and SOST shRNA group was (42.7±4.6), (49.0±22.9) and (135.2±32.7)mm 3, respectively, showing a significant overall difference ( F=19.963, P<0.01). The eyeball volume of SOST shRNA group was larger than that of OCM-1 group and OCM-1 empty vector group, and the differences were statistically significant (both at P<0.05). Co-immunoprecipitation results showed that SOST could interact with LRP-5 and LRP-6 by binding to them, respectively. Conclusions:Silencing SOST can promote the invasion and migration of UM cells, and increase the proportion of UM cells in the division phase.Silencing SOST can promote tumor growth in eyes of nude mice.SOST may play this function by interacting with the membrane receptor LRP-5/LRP-6 and then regulating the WNT/CTNNB1 signal pathway.

Retinoblastoma (RB) is one of the most common ophthalmic tumors, and most of the patients have been identified as advanced at the time of diagnosis, which is directly related to high mortality. Recent studies showed that long noncoding RNA (lncRNA) and miRNAs play key roles in the development、progression、or treatment of cancer, such as RB. However, the role of lncRNA -TP73-AS1 in RB remains unclear. In this study, we performed functional and mechanistic investigation of miRNA-874-3p-TP73-AS1 interaction in RB. The experiments results revealed that miRNA-874-3p had anti-oncogenic functions in RB. Moreover, the bioinformatics analysis shown that TP73-AS1 could bind to miRNA-874-3p. TP73-AS1 was inversely correlated with miRNA-874-3p expression. Furthermore, studies confirmed that TP73-AS1 negatively regulated miRNA-874-3p expression via functioning as a ceRNA. In a word, our results suggest that the TP73-AS1/ miRNA-874-3p / TFAP2B (transcription factor activating enhancer-binding protein 2B) pathway contributes to the progression of RB, which may provide novel insights into the function of lncRNA-driven retinoblastogenesis.

During Graves' disease (GD) treatment, Graves' ophthalmopathy (GO) is often ignored because only mild ocular symptoms are present in early GD. Therefore, we performed isobaric tags for relative and absolute quantification (iTRAQ) analysis and measured relevant endocrine hormones to identify predisposing factors of GO. Serum samples from 3 patients with mild GD and GO and 3 patients with GD but without GO were analyzed by iTRAQ. Based on their clinical data, 60 patients with GD were divided into the GO-free and GO groups. All patients were followed up for 7 months. Their eye conditions and changes in related biochemical indexes were recorded. The iTRAQ results showed that RhoA expression was upregulated and correlated significantly with the tight junction pathway and immunity. The changes in FT3 and RhoA from baseline to 7 months, the FT3 and RhoA baseline levels, and the TRAb titer levels in patients with GD significantly differed between the groups. ELISA and western blotting for RhoA, TRAb, and FT3 in the serum samples from GO patients showed significant upregulation, as well as elevated serum RhoA and TRAb levels in the mild stage of GO. At 7 months, the serum RhoA and FT3 levels were elevated. RhoA is a potential biomarker for mild GO. In GD patients, if an elevated serum RhoA level is accompanied by an elevated TRAb or FT3 level, GO is highly likely to occur, even when obvious ocular symptoms are absent.

Objective:Uveal melanoma (UM) is the most frequent primary eye cancer in adults with a 50% mortality rate. Characterizing the fundamental signaling pathways that drive UM is of importance for the development of targeted therapy. This study aims to probe the impact of sclerostin (SOST) on malignant progression of UM and regulation of Wnt/β-catenin signaling.Methods:Epithelial-type (n=20) and spindle-type (n=16) UM tissues were collected for immunohistochemical staining of SOST, Wnt-1, and β-catenin expressions. SOST was silenced in three UM cell lines (primary spindle-type OCM-1 cells, metastatic epithelial Mum-2B cells, and metastatic spindle-type Mum-2C cells) through transfecting specific siRNA. RT-qPCR and Western blot were presented for examining the levels of SOST, and markers in Wnt/β-catenin signaling. Flow cytometry, MTT, EdU, transwell, and tube formation assays were conducted, respectively. By implanting BALB/c nude murine models in situ, the function of SOST on tumor growth was investigated, followed by immunofluorescence double staining of SOST and LRP5/6.Results:Low SOST expression as well as high Wnt-1 and β-catenin expressions were found in epithelial-type (high malignancy) than spindle-type (low malignancy) UM tissues. Silencing SOST activated the markers in Wnt/β-catenin signaling as well as accelerated cell cycle progression, migration, invasion, angiogenesis, and reduced apoptosis in UM cells. In situ tumor formation in murine eyes showed that SOST knockdown promoted tumor growth. Moreover, SOST interacted with LRP5/LRP6.Conclusion:SOST silencing may facilitate the malignant progression of UM cells through activating Wnt/β-catenin signaling. Mechanistically, SOST may exert this function by interacting with LRP5/LRP6 membrane receptors.

Retinoblastoma (RB) is the most common intraocular malignancy in children. It has been previously reported that p38 MAPK is related to the pathogenesis of RB. Here we aim at investigating how p38 MAPK affected RB progression through mediating USP22/SIRT1/SOST axis. In this study, Thirty-two cases of RB and normal retinal tissues were collected. The expression of p38 MAPK, phosphorylation of p38 MAPK (P-p38 MAPK), USP22, SIRT1 and SOST in clinical tissues and cells was measured using RT-qPCR, IHC assay or western blot analysis. Cell proliferation was detected by CCK-8. Apoptosis rate of cells was examined by flow cytometry. Cell migration was evaluated using scratch test. Cell invasion ability was examined by Transwell assay. Co-immunoprecipitation (CO-IP) was utilized to measure the deubiquitination of USP22 on SIRT1. In vivo, mice were respectively injected with plasmids and the tumor growth as well as the tumor weight were detected. Results showed that p38 MAPK, P-p38 MAPK and SOST were poorly expressed in RB tissues and cells whereas USP22 and SIRT1 were overly expressed. P-p38 MAPK inhibited the expression of USP22, and overexpression of USP22 eliminated the inhibitory roles of P-p38 MAPK on tumor growth, as well as cell proliferation, migration and invasion. USP22 stabilized and promoted the expression of SIRT1 through its deubiquitination function. Silencing the expression of SIRT1 contributed to boosted expression of SOST, thus suppressing the growth of tumor cells. Collectively, the phosphorylation of p38 MAPK regulates the SIRT1/SOST axis to protect against RB via silencing USP22. The findings present some cues for a further approach to RB.

Purpose Uveal melanoma (UM) is the most common intraocular malignant tumor in adults. Due to the lack of effective treatments for metastatic UM, the survival of UM has not changed over the past 3 decades. Therefore, it is important to identify essential genes regulating the metastasis of UM. Methods In this study, a genome-wide CRISPR knockout screen in an orthotopic mouse model of UM was performed to identify the regulatory genes conferring the metastatic phenotype. Loss-of-function analyses were performed to explore the function of G protein pathway suppressor 2 (GPS2) in UM metastasis in vitro and in vivo. RNA sequencing was performed to investigate the molecular mechanism underlying the function of GPS2 as a tumor suppressor in UM. Results Among the highest-ranking genes, we found several validated tumor suppressors, such as SHPRH , GPS2 , PRPH2 , and hsa-mir-1229; GPS2 was chosen as the candidate gene for further studies. GPS2 was lower expressed in the tumor tissues of UM patients. Furthermore, knocking-down GPS2 promoted the proliferation and metastatic abilities of UM cells both in vivo and in vitro . Finally, analysis of the transcriptome data revealed that silencing GPS2 upregulates oncogenic signaling pathways MAPK and PI3K-Akt, and in the meantime downregulates tumor suppressor signaling pathway Slit/Robo in UM cells. Conclusion Altogether, our study proved that the GPS2 gene functions as a tumor suppressor and might be a novel potential therapeutic target for UM treatment.

Melanoma is a malignant tumor derived from melanocytes, which is the most fatal skin cancer. The present study aimed to explore and elucidate the candidate genes in melanoma and its underlying molecular mechanism. A total of 1,156 differentially expressed genes were obtained from the GSE46517 dataset of Gene Expression Omnibus database using the package "limma" in R. Based on two algorithms (LASSO and SVM-RFE), we obtained three candidate DEGs (LTBP4, CDHR1, and MARCKSL1). Among them, LTBP4 was identified as a diagnostic marker of melanoma (AUC = 0.985). Down-regulation of LTBP4 expression was identified in melanoma tissues and cells, which predicted poor prognosis of patients with melanoma. Cox analysis results discovered that LTBP4 with low expression was an independent prognostic factor for overall survival in patients with melanoma. LTBP4 inhibition reduced cell apoptosis and promoted cell proliferation and metastasis. These changes were correlated with the expression levels of caspase-3, Ki67 and E-cadherin. Further, as indicated by tumor formation study of nude mice, LTBP4 silencing improved the tumorigenic ability of melanoma cells. Knockdown of LTBP4 increased the percentage of active TGFβ1 secreted by melanoma cells. CTGF, Gyr61, and Birc5 expression levels were reduced, YAP1 phosphorylation was inhibited, and YAP1 was translocated from the cytoplasm to the nucleus in melanoma cells treated with TGF-β1. These effects were reversed by LTBP4 overexpression. As evidenced by immunofluorescent staining, Western blotting and luciferase reporter assay, LTBP4 overexpression activated the Hippo signaling pathway, which was characterized by the increased nuclear-cytoplasmic translocation of YAP1 and the enhanced phosphorylation of YAP1, MST1, and MOB1. In addition, the effects of LTBP4 overexpression on inhibiting CTGF, Cyr61 and Birc5 expression, promoting the apoptosis, and inhibiting the metastasis and proliferation of melanoma cells were reversed by the overexpression of YAP1 or MST1. In conclusion, the LTBP4-TGFβ1-Hippo-YAP1 axis is a critical pathway for the progression of skin melanoma.

目的 探讨应用鼻内镜手术治疗鼻眶沟通性黏液囊肿的效果和联合外路手术的适应证.方法 回顾性分析接受手术治疗的鼻眶沟通性黏液囊肿患者的病历资料,分析手术入路和治疗效果.结果 纳入36例患者的54个副鼻窦黏液囊肿,包括额窦29个、筛窦21个、蝶窦2个、上颌窦2个.囊肿侵犯眼眶外上/外下象限6例,内上/内下象限30例.22例(61.1％)采用鼻内镜手术,均为囊肿侵犯眼眶内上/内下象限.14例(38.9％)采用鼻内镜-外路联合手术,其中8例侵犯眼眶内上/内下象限,6例侵犯眼眶外上/外下象限.2种手术术后眼球突出等症状均明显缓解.外路手术出现脑脊液漏1例,鼻内镜手术出现中鼻甲粘连1例.随访12～61个月,手术后窦口再狭窄的发生率为8.3％(3/36),均发生在额窦手术后.鼻内镜手术未见囊肿复发,鼻内镜-外路联合手术1例复发.结论 鼻内镜手术治疗鼻眶沟通性黏液囊肿安全、可行,对于囊肿在额窦外侧远端、侵犯眼眶外上/外下象限、额筛窦囊肿伴厚壁骨性间隔者,可选择鼻内镜-外路联合手术治疗.