A Novel Splicing Mutation Leading to Wiskott-Aldrich Syndrome from a Family.

Wiskott-Aldrich syndrome (WAS) is a rare X-linked recessive genetic disease characterized by clinical symptoms such as eczema, thrombocytopenia with small platelets, immune deficiency, prone to autoimmune diseases, and malignant tumors. This disease is caused by mutations of the WAS gene encoding WASprotein (WASP). The locus and type of mutations of the WAS gene and the expression quantity of WASP were strongly correlated with the clinical manifestations of patients. We found a novel mutation in the WAS gene (c.931 + 5G > C), which affected splicing to produce three abnormal mRNA, resulting in an abnormally truncated WASP. This mutation led to a reduction but not the elimination of the normal WASP population, resulting in causes X-linked thrombocytopenia (XLT) with mild clinical manifestations. Our findings revealed the pathogenic mechanism of this mutation.

Single-Cell Transcriptomic Sequencing Reveals Tissue Architecture and Deciphers Pathological Reprogramming During Retinal Ischemia in Macaca fascicularis.

Purpose: Acute retinal arterial ischemia diseases (ARAIDs) are ocular emergencies that require immediate intervention within a restricted therapeutic window to prevent blindness. However, the underlying molecular mechanisms contributing to the pathogenesis of ARAIDs remain enigmatic. Herein, we present the single-cell RNA sequencing (scRNA-seq) alterations during ischemia in the primate retina as a preliminary endeavor in understanding the molecular complexities of ARAIDs. Methods: An ophthalmic artery occlusion model was established through ophthalmic artery ligation in two Macaca fascicularis. scRNA-seq and bioinformatics analyses were used to detect retinal changes during ischemia, which are further validated by immunofluorescence analysis. Western blot and flow cytometry assays were performed to measure the microglia polarization status. Results: The findings of this study reveal notable changes in the retina under acute ischemic conditions. Particularly, retinal ischemia compromised mitochondrial functions of rod photoreceptors, partly leading to the rapid loss of healthy rods. Furthermore, we observed a noteworthy transcriptional alteration in the activation of microglia induced by ischemia. The targeted correction of the proinflammatory cytokine CXCL8 effectively suppresses microglia M1 polarization in retinal ischemia, ultimately reducing the proinflammatory transformation in vitro. In addition, retina ischemia induced the apoptotic inclination of endothelial cells and the heightened interaction with microglia, which signifies the influence of microglia in disrupting the retinal-blood barrier. Conclusions: Our research has successfully identified and described the pathologic alterations occurring in several cell types during a short period of ischemia. These observations provide valuable insights for ameliorating retinal damage and promoting the restoration of vision.

NSUN2-mediated m5 C RNA methylation dictates retinoblastoma progression through promoting PFAS mRNA stability and expression.

BACKGROUND: The precise temporal and spatial regulation of N5 -methylcytosine (m5 C) RNA modification plays essential roles in RNA metabolism, and is necessary for the maintenance of epigenome homeostasis. Howbeit, the mechanism underlying the m5 C modification in carcinogenesis remains to be fully addressed. METHODS: Global and mRNA m5 C levels were determined by mRNA isolation and anti-m5 C dot blot in both retinoblastoma (RB) cells and clinical samples. Orthotopic intraocular xenografts were established to examine the oncogenic behaviours of RB. Genome-wide multiomics analyses were performed to identify the functional target of NSUN2, including proteomic analysis, transcriptome screening and m5 C-methylated RNA immunoprecipitation sequencing (m5 C-meRIP-seq). Organoid-based single-cell analysis and gene-correlation analysis were performed to verify the NSUN2/ALYREF/m5 C-PFAS oncogenic cascade. RESULTS: Herein, we report that NSUN2-mediated m5 C RNA methylation fuels purine biosynthesis during the oncogenic progression of RB. First, we discovered that global and mRNA m5 C levels were significantly enriched in RBs compared to normal retinas. In addition, tumour-specific NSUN2 expression was noted in RB samples and cell lines. Therapeutically, targeted correction of NSUN2 exhibited efficient therapeutic efficacy in RB both in vitro and in vivo. Through multiomics analyses, we subsequently identified phosphoribosylformylglycinamidine synthase (PFAS), a vital enzyme in purine biosynthesis, as a downstream candidate target of NSUN2. The reintroduction of PFAS largely reversed the inhibitory phenotypes in NSUN2-deficient RB cells, indicating that PFAS was a functional downstream target of NSUN2. Mechanistically, we found that the m5 C reader protein ALYREF was responsible for the recognition of the m5 C modification of PFAS, increasing its expression by enhancing its RNA stability. CONCLUSIONS: Conclusively, we initially demonstrated that NSUN2 is necessary for oncogenic gene activation in RB, expanding the current understanding of dynamic m5 C function during tumour progression. As the NSUN2/ALYREF/m5 C-PFAS oncogenic cascade is an important RB trigger, our study suggests that a targeted m5 C reprogramming therapeutic strategy may be a novel and efficient anti-tumour therapy approach.

[Hematological Neoplasms Secondary to Malignant Solid Tumors with Radiotherapy and Chemotherapy: a Clinical and Prognostic Analysis].

OBJECTIVE: To explore the clinical characteristics, treatment and prognosis of therapy-related hematological neoplasms patients secondary to malignant solid tumors. METHODS: The clinical features, treatment and prognosis of 36 hematological neoplasms patients secondary to malignant solid tumors with radiotherapy and chemotherapy in the Second Hospital of Shanxi Medical University were retrospectively analyzed. RESULTS: The 36 patients with therapy-related hematological neoplasms had a median age of 60 (47-81) years, 14 were male and 22 were female. Among them, 22 cases were acute myeloid leukemia, 5 cases were acute lymphoblastic leukemia, 4 cases were multiple myeloma, 3 cases were myelodysplastic syndrome, and 2 cases were non-hodgkin's lymphoma. The median latency of malignant tumor to hematological neoplasm was 42.5 (12-120) months. The median survival time of therapy-related hematological neoplasms was 10.5 (1-83) months, and the 3-year overall survival (OS) rate was 24.3%. The therapy-related acute myeloid leukemia patients had a very poor prognosis, with a median survival of 7 (1-83) months and a 3-year OS rate of 21.4%. CONCLUSION: The prognosis of therapy-related hematological neoplasms secondary to malignant solid tumors with radiotherapy and chemotherapy is poor, and individualized treatment should be implemented according to the clinical situation of patients.

Molecular pathogenesis of a novel Met394Thr variant causing hemophilia B.

BACKGROUND: Hemophilia B (HB), a rare bleeding disorder, shows X-linked recessive inheritance and is caused by heterogeneous variants in the FIX gene (F9) encoding coagulation factor IX (FIX). This study aimed to investigate the molecular pathogenesis of a novel Met394Thr variant causing HB. METHODS: We used Sanger sequencing to analyze F9 sequence variants in members of a Chinese family with moderate HB. Subsequently, we performed in vitro experiments on the identified novel FIX-Met394Thr variant. In addition, we performed bioinformatics analysis of the novel variant. RESULTS: We identified a novel missense variant (c.1181T>C, p.Met394Thr) in a Chinese family with moderate HB in the proband. The proband's mother and grandmother were carriers for the variant. The identified FIX-Met394Thr variant did not affect the transcription of F9 and the synthesis and secretion of FIX protein. The variant may, therefore, affect the physiological function of FIX protein by disrupting its spatial conformation. In addition, another variant (c.88+75A>G) in intron 1 of F9 was identified in the grandmother, which may also affect FIX protein function. CONCLUSION: We identified FIX-Met394Thr as a novel causative variant of HB. Further understanding of the molecular pathogenesis underlying FIX deficiency may guide novel strategies for precision HB therapy.

DeepFundus: A flow-cytometry-like image quality classifier for boosting the whole life cycle of medical artificial intelligence.

Medical artificial intelligence (AI) has been moving from the research phase to clinical implementation. However, most AI-based models are mainly built using high-quality images preprocessed in the laboratory, which is not representative of real-world settings. This dataset bias proves a major driver of AI system dysfunction. Inspired by the design of flow cytometry, DeepFundus, a deep-learning-based fundus image classifier, is developed to provide automated and multidimensional image sorting to address this data quality gap. DeepFundus achieves areas under the receiver operating characteristic curves (AUCs) over 0.9 in image classification concerning overall quality, clinical quality factors, and structural quality analysis on both the internal test and national validation datasets. Additionally, DeepFundus can be integrated into both model development and clinical application of AI diagnostics to significantly enhance model performance for detecting multiple retinopathies. DeepFundus can be used to construct a data-driven paradigm for improving the entire life cycle of medical AI practice.

Thymidine Kinase 1 Drives Skin Cutaneous Melanoma Malignant Progression and Metabolic Reprogramming.

Background: Thymidine kinase 1 (TK1) is a cell cycle-dependent kinase that catalyzes the addition of a gamma-phosphate group to thymidine. The protumorigenic role of TK1 has been reported in various malignancies. However, the role of TK1 in skin cutaneous melanoma (SKCM) remains unclear. This study aimed to explore the molecular function of TK1 in SKCM progression. Methods: Bioinformatics data were acquired from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). Subcutaneous xenografts were established to observe the effect of TK1 knockdown on the proliferation of SKCM cells in vivo. RNA sequencing (RNA-seq; deposited in Sequence Read Archive, SRX10950283-SRX10950285 for A375 control cells and SRX10950286-SRX10950288 for TK1-silenced A375 cells) and immunoprecipitation-mass spectrometry (IP-MS) were used to analyze TK1-related genes and pathways. Seahorse XF Cell Mito tests and glycolysis stress assays were conducted for metabolic testing. Results: TK1 was upregulated in malignant SKCM compared to that in normal tissues and cell lines. Elevated expression of TK1 was associated with poor prognosis. In vitro and in vivo assays demonstrated that TK1 promoted the proliferation and migration of SKCM cells. Moreover, TK1 was strongly associated with multiple intracellular metabolic pathways, facilitating cell mitochondrial respiration and glycolysis in SKCM malignant progression. Conclusions: TK1 drives SKCM malignant progression and supports metabolic reprogramming, indicating that TK1 serves as a therapeutic target for SKCM.

One-pot synthesis of aminated cellulose nanofibers by "biological grinding" for enhanced thermal conductivity nanocomposites.

Aminated cellulose nanofibers (A-CNF) with high thermostability (>350 ℃), high crystallinity (81.25 %), and high dispersion stability were extracted from "biological grinding" biomass through one-pot microwave-hydrothermal synthesis. Worm-eaten wood powder (WWP) as the product of "biological grinding" by borers is a desirable lignocellulose for fabricating A-CNF in a green and cost-effective way since it is a well-milled fine powder with dimension of dozens of microns, which can be used directly, saving energy and labor. Generated A-CNF proved to be an excellent reinforcing and curing agent for constructing high performance epoxy nanocomposites. The nanocomposites exhibited a thermal conductivity enhancement of about 120 %, coefficient of thermal expansion reduction of 78 %, and Young's modulus increase of 108 % at a low A-CNF loading of 1 wt.%, demonstrating their remarkable reinforcing potential and effective stress transfer behavior. The process proposed herein might help to bridge a closed-loop carbon cycle in the whole production-utilization of biomass.

Novel insights on targeting ferroptosis in cancer therapy.

Ferroptosis belongs to a novel form of regulated cell death. It is characterized by iron dependence, destruction of intracellular redox balance and non-apoptosis. And cellular structure and molecules level changes also occur abnormally during ferroptosis. It has been proved that ferroptosis exist widespreadly in many diseases, such as heart disease, brain damage or alzheimer disease. At the same time, the role of ferroptosis in cancer cannot be underestimated. More and more indications have told that ferroptosis is becoming a powerful weapon against cancer. In addition, therapies rely on ferroptosis have been applied to the clinic. Therefore, it is necessary to understand this newly discovered form of cell death and its connection with cancer. This review summarizes the mechanism of ferroptosis, ferroptosis inducers based on different targets and inspection methods. At last, we analyzed the relationship between ferroptosis and malignancies, in order to provide a novel theory basis for cancer treatment.

Dinutuximab Synergistically Enhances the Cytotoxicity of Natural Killer Cells to Retinoblastoma Through the Perforin-Granzyme B Pathway.

PURPOSE: Conventional chemotherapy and enucleation usually fail to cure advanced retinoblastoma. We investigated the retinoblastoma immune microenvironment and the efficacy of the combination of dinutuximab and CD16-expressing NK-92MI (NK-92MIhCD16-GFP) cells on retinoblastoma cells in this study. PATIENTS AND METHODS: Immunohistochemistry and flow cytometry (FC) were performed to assess the expression level of GD2 in retinoblastoma tissues and cells. Gene set enrichment analysis (GSEA), immunohistochemisrztry and immunocytochemistry were conducted to assess the retinoblastoma immune microenvironment and the integrity of the blood-retinal barrier (BRB). After overexpressing CD16 in NK-92MI cells, fluorescence-activated cell sorting (FACS) was applied to select the positive subpopulation. LDH assays and FC were used to detect LDH release and apoptosis in retinoblastoma cells subjected to a combination of dinutuximab and NK-92MIhCD16-GFP cells. Finally, the release of perforin-granzyme B and the expression of CD107a in NK-92MIhCD16-GFP stimulated by retinoblastoma cells were assessed via enzyme-linked immunosorbent assays (ELISAs) and FC in the presence of dinutuximab or an isotype control. RESULTS: GD2 was heterogeneously expressed in retinoblastoma tissues and cell lines and positively correlated with proliferation and staging. GSEA revealed the immunosuppressive status of retinoblastoma microenvironment. The immune cell profile of retinoblastoma tissues and vitreous bodies suggested BRB destruction. LDH release and apoptosis in retinoblastoma cells caused by NK-92MIhCD16-GFP cells were significantly enhanced by dinutuximab. Finally, the release of perforin-granzyme B and the expression of CD107a in NK-92MIhCD16-GFP cells stimulated by retinoblastoma cells were obviously increased by dinutuximab. CONCLUSION: This study indicates that retinoblastoma impairs the integrity of the BRB and contributes to dysregulated immune cell infiltrates. GD2 is a specific target for natural killer (NK) cell-based immunotherapy and that the combination of dinutuximab and NK-92MIhCD16-GFP cells exerts potent antitumor effects through antibody-dependent cell-mediated cytotoxicity.

Immunological analyses reveal an immune subtype of uveal melanoma with a poor prognosis.

Uveal melanoma is an aggressive intraocular malignancy that often exhibits low immunogenicity. Metastatic uveal melanoma samples frequently exhibit monosomy 3 or BAP1 deficiency. In this study, we used bioinformatic methods to investigate the immune infiltration of uveal melanoma samples in public datasets. We first performed Gene Set Enrichment/Variation Analyses to detect immunological pathways that are altered in tumors with monosomy 3 or BAP1 deficiency. We then conducted an unsupervised clustering analysis to identify distinct immunologic molecular subtypes of uveal melanoma. We used CIBERSORT and ESTIMATE with RNA-seq data from The Cancer Genome Atlas and the GSE22138 microarray dataset to determine the sample-level immune subpopulations and immune scores of uveal melanoma samples. The Kaplan-Meier method and log-rank test were used to assess the prognostic value of particular immune cells and genes in uveal melanoma samples. Through these approaches, we discovered uveal melanoma-specific immunologic features, which may provide new insights into the tumor microenvironment and enhance the development of immunotherapies in the future.

Cholesterol modification of SDF-1-specific siRNA enables therapeutic targeting of angiogenesis through Akt pathway inhibition.

Neovascularization during ocular tissue repair can cause severe visual loss in the optical axis and is therefore an issue of considerable concern to ophthalmologists. Here, we introduced a cholesterol-modified siRNA delivery system targeting stromal cell-derived factor 1 (SDF-1) to treat ocular angiogenesis in vivo. SDF-1 expression was analyzed in rat endothelial progenitor cells (EPCs) and bone marrow mesenchymal stem cells (BMSCs) using quantitative PCR (qPCR). Migration ability of BMSC and HUVEC were assessed through transwell assay. The proliferation effect of chol-siSDF1 on HUVEC was measured by colony formation assay. In vivo anti-angiogenic effects of chol-siSDF1 were tested in a cornea alkali burn model and the area of cornea neovascularization was measured using computer-imaging analysis system. Then phosphorylated Akt and total Akt protein levels were measured through western blot. Results turned out that rat EPCs and BMSCs showed high SDF-1 mRNA expression, which can be down-regulated by using chol-siSDF-1. Chol-siSDF-1 could significantly inhibit migration of BMSC and HUVEC. In addition, chol-siSDF1 also could inhibit HUVEC proliferation and exert a significant anti-angiogenic effect in corneal alkali burn model. As for the mechanism, chol-siSDF1 may inhibit the neovascularization, proliferation and metastasis through inhibiting the Akt signaling pathway. Thus, cholesterol modification of siRNA targeting SDF-1 displays an effective inhibition of migration and angiogenesis, with a much longer duration of inhibition effect.

Assessment of Ocular Surface Damage during the Course of Type 2 Diabetes Mellitus.

PURPOSE: To investigate the impact of disease duration on the ocular surface during the course of type 2 diabetes mellitus compared with nondiabetic controls. METHODS: One hundred twenty diabetic patients were divided into three groups according to disease duration: less than 5 years, 5-10 years, and over 10 years. All eyes were imaged using a corneal topographer (Oculus Keratograph 5M). Tear film measurements and meibography were also recorded. Meibomian gland changes were scored from 0 to 6 (meiboscore). RESULTS: The noninvasive breakup time first (NIKBUT-1st) and noninvasive breakup time average (NIKBUT-avg) were significantly shorter in the over 10 years diabetic group compared with the control group (P=0.0056 and P=0.010, resp.). Tear meniscus height (TMH) was significantly lower in the over 10 years diabetic group compared with the control group (P=0.0016) and the 5 years group (P=0.0061). We also found that more patients in the over 10 years diabetic group showed bulbar and limbal hyperemia compared with the control group (bulbar hyperemia: P=0.049; limbal hyperemia: P=0.026). The meiboscore in the over 10 years diabetic group was significantly higher compared with the other three groups (P < 0.05). Bulbar hyperemia showed a significant negative correlation with NIKBUT-1st in the over 10 years diabetic group (r=-0.35 and P < 0.05). CONCLUSION: Ocular surface damage in long-term type 2 diabetes is more severe than that in patients with shorter disease duration.

Enhanced bioactivity and osteoinductivity of carboxymethyl chitosan/nanohydroxyapatite/graphene oxide nanocomposites.

Tissue engineering approaches combine a bioscaffold with stem cells to provide biological substitutes that can repair bone defects and eventually improve tissue functions. The prospective bioscaffold should have good osteoinductivity. Surface chemical and roughness modifications are regarded as valuable strategies for developing bioscaffolds because of their positive effects on enhancing osteogenic differentiation. However, the synergistic combination of the two strategies is currently poorly studied. In this work, a nanoengineered scaffold with surface chemistry (oxygen-containing groups) and roughness (R q = 74.1 nm) modifications was fabricated by doping nanohydroxyapatite (nHA), chemically crosslinked graphene oxide (GO) and carboxymethyl chitosan (CMC). The biocompatibility and osteoinductivity of the nanoengineered CMC/nHA/GO scaffold was evaluated in vitro and in vivo, and the osteogenic differentiation mechanism of the nanoengineered scaffold was preliminarily investigated. Our data demonstrated that the enhanced osteoinductivity of CMC/nHA/GO may profit from the surface chemistry and roughness, which benefit the ß1 integrin interactions with the extracellular matrix and activate the FAK-ERK signaling pathway to upregulate the expression of osteogenic special proteins. This study indicates that the nanocomposite scaffold with surface chemistry and roughness modifications could serve as a novel and promising bone substitute for tissue engineering.

Rabbit Model of Corneal Endothelial Injury Established Using the Nd: YAG Laser.

PURPOSE: To develop a new rabbit model of corneal endothelial injury using a neodymium-doped yttrium aluminum garnet (Nd:YAG) laser. METHODS: The corneal endothelia of 2 groups of New Zealand white rabbits were treated with an Nd:YAG laser in a uniformly scattered fashion. Rabbits in group A underwent laser burns on the whole corneal endothelium, including the limbus area, whereas rabbits in group B were subjected to laser burns in the central 9-mm diameter zone of the endothelium. Slit-lamp biomicroscopy, optical coherence tomography, applanation tonometry, confocal microscopy, scanning electron microscopy, and histological examinations were performed during 4 weeks of follow-up. RESULTS: In both groups, dotted or focal corneal endothelium defects were directly observed. The stroma was intact. Right after laser application, a series of clinical manifestations appeared, including subepithelial and stromal edema, increased central corneal thickness, and corneal opacity. Laser burn had more notable effects in group A than in group B. In both groups, we observed no damage to the intraocular structures, and intraocular pressure was normal after laser treatment. CONCLUSIONS: Nd:YAG laser treatment in a 9-mm diameter zone of the endothelium can effectively induce bullous keratopathy in a rabbit, whereas treatment for the entire corneal endothelium maintains bullous keratopathy for a longer period. The procedure is simple and reproducible, and it retains normal intraocular structures. This study provided a promising model for future research into endothelial cell damage and for the development of new therapies.

Treatment of Myopic Foveoschisis with Air Versus Perfluoropropane: A Retrospective Study.

BACKGROUND The aim of this study was to compare the efficacy of air and perfluoropropane (C3F8) combined with vitrectomy to treat myopic foveoschisis (MF). MATERIAL AND METHODS A retrospective comparison of a consecutive series of surgical patients was performed. Ninety-seven eyes of 91 patients with MF were assigned to undergo 23G vitrectomy. After internal limiting membrane (ILM) peeling, the vitreous cavity was filled with air in 48 eyes of 45 patients (Air Group). Fluid-air exchange was performed in 49 eyes of 46 patients (C3F8 Group) followed by an injection of 14% C3F8. Patients were evaluated using best-corrected visual acuity (BCVA) and optical coherence tomography. RESULTS Preoperatively, there was no significant difference in clinical features between the groups. After surgery, BCVA was markedly improved and the foveoschisis height was reduced in both groups compared with baseline (P<0.01), but the difference between the groups was not significant (P>0.05). No significant differences were noted in BCVA improvement and retinal restoration (P=0.33 and 0.39, respectively) in the mild and moderate subgroups (foveoschisis height ≤400 µm) between the tamponades. However, in the severe group (foveoschisis height >400 µm), C3F8 had a more favorable cure rate and foveoschisis height reduction improvement compared with air (P=0.04 and 0.04, respectively) at the last visit. CONCLUSIONS Vitrectomy combined with ILM peeling is effective in the treatment of myopic foveoschisis, and the choice of tamponade depends on the severity of foveoschisis. Air can be used for patients with a foveoschisis height ≤400 µm, but C3F8 is more effective for patients with a foveoschisis height >400 µm.

Poly (fumaroyl bioxirane) maleate: A potential functional scaffold for bone regeneration.

Proper scaffolds combined with mesenchymal stem cells (MSCs) represent a promising strategy for repairing bone defects. In a previous study, poly (fumaroyl bioxirane) maleate (PFM), a newly developed functional polymer with numerous functional groups, exhibited excellent biocompatibility and enhanced the alkaline phosphatase (ALP) activity of osteoblasts in vitro. Here, to provide further and comprehensive insight into the application of PFM in bone tissue engineering, we investigated the osteoinductive potential of PFM cultured with rat adipose-derived mesenchymal stem cells (rADSCs). The results showed that PFM resulted in greater proliferation of rADSCs and that the PFM substrate had stronger osteoinductivity than PLGA and the control, as indicated by the significant upregulation of osteogenesis-related genes, proteins and calcium mineralization in vitro. Next, PFM was combined with rADSCs to repair a critical-sized calvarial defect in rats. Compared to the PLGA scaffold, the PFM scaffold significantly promoted new bone formation and exhibited excellent effects in repairing rat calvarial defects. In conclusion, PFM possesses strong osteoinductivity, which could markedly enhance bone regeneration, suggesting that PFM could serve as a promising and effective optimization method for traditional scaffolds in bone regeneration.

Tailored treatment for the management of scleral necrosis following pterygium excision.

The present study aimed to investigate the efficacy of tailored treatment for the management of scleral necrosis following pterygium surgery. A series of nine cases of scleral necrosis following pterygium excision between September 2009 and September 2012 were included. In cases where ischemia was the cause of scleral necrosis, Tenon's membrane covering (TMC) surgery was performed. For cases with surgically-induced necrotizing scleritis (SINS), systemic immunosuppressive therapy following surgical repair of the scleral defect was administered in the form of oral prednisolone (starting dose, 30-60 mg/day). Five patients with ischemic scleral necrosis received TMC postoperatively. Four patients with SINS received various doses of oral prednisolone according to their systematic immune state. All patients had successful postoperative results except one with rheumatoid arthritis, who postoperatively developed scleral patch graft melting within 2 weeks. Following aggressive immunosuppressive treatment, the scleral patch graft was saved. In conclusion, patients achieved positive results using tailored treatment according to the pathogenesis of their scleral necrosis.

The Long Non-Coding RNA RHPN1-AS1 Promotes Uveal Melanoma Progression.

Increasing evidence suggests that aberrant long non-coding RNAs (lncRNAs) are significantly correlated with the pathogenesis, development and metastasis of cancers. RHPN1 antisense RNA 1 (RHPN1-AS1) is a 2030-bp transcript originating from human chromosome 8q24. However, the role of RHPN1-AS1 in uveal melanoma (UM) remains to be clarified. In this study, we aimed to elucidate the molecular function of RHPN1-AS1 in UM. The RNA levels of RHPN1-AS1 in UM cell lines were examined using the quantitative real-time polymerase chain reaction (qRT-PCR). Short interfering RNAs (siRNAs) were designed to quench RHPN1-AS1 expression, and UM cells stably expressing short hairpin (sh) RHPN1-AS1 were established. Next, the cell proliferation and migration abilities were determined using a colony formation assay and a transwell migration/invasion assay. A tumor xenograft model in nude mice was established to confirm the function of RHPN1-AS1 in vivo. RHPN1-AS1 was significantly upregulated in a number of UM cell lines compared with the normal human retinal pigment epithelium (RPE) cell line. RHPN1-AS1 knockdown significantly inhibited UM cell proliferation and migration in vitro and in vivo. Our data suggest that RHPN1-AS1 could be an oncoRNA in UM, which may serve as a candidate prognostic biomarker and target for new therapies in malignant UM.