Identification and validation of a CCL18-related signature for prediction of overall survival in patients with uveal melanoma.

Uveal melanoma (UM), the most frequent primary intraocular tumor in adults, has poor prognosis. High C-C motif chemokine ligand 18 (CCL18) has been detected in various tumors and is closely correlated with patients' clinicopathological characteristics. However, the essential role of CCL18 in UM remains unclear. Therefore, this study aimed to explore the prognostic value of CCL18 in UM. Uveal melanoma cells (M17) were transfected with pcDNA3.1-CCL18 si-RNA using Lipofectamine™ 2000. Cell growth and invasion abilities were measured through Cell Counting Kit-8 assay and invasion assay. RNA expression data and clinical and histopathological details were downloaded from the UM in The Cancer Genome Atlas (TCGA-UM) and GSE22138 datasets, which were defined as the training and validation cohorts, respectively. Univariate and multivariate Cox regression analyses were performed to identify significant prognostic biomarkers. The coefficients of these significant biomarkers generated by multivariate Cox proportional hazard regression analysis were used to establish a risk score formula. Functional enrichment analyses were also carried out. We found that downregulated CCL18 inhibits M17 cell growth and invasion in vitro. CCL18 may affect UM progression by altering C-C motif receptor 8 related pathways. Higher CCL18 expression was associated with worse clinical outcomes and tumor-specific death in the TCGA-UM dataset. Based on the coefficients obtained from the Cox proportional hazard regression analysis, a CCL18-related prognostic signature formula was constructed as follows: risk score = 0.05590 × age +2.43437 × chromosome 3 status +0.39496 × ExpressionCCL18. Notably, in this formula, the normal chromosome 3 was coded as 0, whereas the chromosome 3 loss was coded as 1. Each patient was assigned to either low-risk or high-risk groups using the median cut-off in the training cohort. High-risk patients survived for a shorter time than low-risk patients. The time-dependent and multivariate receiver operating characteristic curves showed promising diagnostic efficacy. Multivariate Cox regression analysis demonstrated the potential of this CCL18-related signature as an independent prognostic indicator. These results were validated using the GSE22138 dataset. In addition, in both TCGA-UM and GSE22138 datasets, stratification of clinical correlations and survival analyses based on this signature indicated the involvement of clinical progression and survival outcome in UM. In the high-risk group, Gene Ontology analyses mainly indicated the enrichment of immune response pathways, such as the T cell activation, response to interferon-gamma, antigen processing and presentation, interferon-gamma-mediated signaling pathway, MHC protein complex, MHC class II protein complex, antigen binding, and cytokine binding. Meanwhile, Kyoto Encyclopedia of Genes and Genomes analyses showed enrichments of pathways in cancer, cell adhesion, cytokine-cytokine receptor interaction, chemokine signaling pathway, Th1 and Th2 cell differentiation, and chemokine signaling pathway. Moreover, single-sample gene set enrichment analysis demonstrated the enrichment of almost all immune cells and immune functions in the high-risk group. In summary, a new prognostic CCL18-related signature was successfully established using the TCGA-UM dataset and validated using the GSE22138 dataset with meaningful predictive and diagnostic efficacies. This signature could serve as an independent and promising prognostic biomarker for patients with UM.

Identification of a prognostic six-immune-gene signature and a nomogram model for uveal melanoma.

BACKGROUND: To identify an immune-related prognostic signature and find potential therapeutic targets for uveal melanoma. METHODS: The RNA-sequencing data obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets. The prognostic six-immune-gene signature was constructed through least absolute shrinkage and selection operator and multi-variate Cox regression analyses. Functional enrichment analysis and single sample GSEA were carried out. In addition, a nomogram model established by integrating clinical variables and this signature risk score was also constructed and evaluated. RESULTS: We obtained 130 prognostic immune genes, and six of them were selected to construct a prognostic signature in the TCGA uveal melanoma dataset. Patients were classified into high-risk and low-risk groups according to a median risk score of this signature. High-risk group patients had poorer overall survival in comparison to the patients in the low-risk group (p < 0.001). These findings were further validated in two external GEO datasets. A nomogram model proved to be a good classifier for uveal melanoma by combining this signature. Both functional enrichment analysis and single sample GSEA analysis verified that this signature was truly correlated with immune system. In addition, in vitro cell experiments results demonstrated the consistent trend of our computational findings. CONCLUSION: Our newly identified six-immune-gene signature and a nomogram model could be used as meaningful prognostic biomarkers, which might provide uveal melanoma patients with individualized clinical prognosis prediction and potential novel treatment targets.

[Prediction of postoperative visual acuity in cataract patients with idiopathic macular epiretinal membrane by hand-held retinal optometer and optical coherence tomography].

OBJECTIVE: To investigate the value of hand-held retinal optometer and optical coherence tomography (OCT) in predicting postoperative visual acuity in patients with age-related cataract and idiopathic macular epiretinal membrane. METHODS: We retrospectively analyzed the data of patients undergoing phacoemulsification combined with intraocular lens implantation for age-related cataract in our hospital from January, 2019 to April, 2020.Preoperative examination detected idiopathic macular epiretinal membrane in 45 of the patients (52 eyes) with lens opacity grade C2N2P1 according to LOCSⅡ lens opacity classification criteria.Based on the thickness of the macular fovea, the eyes were divided into group A (9 eyes) with macular thickness < 300 µm by OCT examination, group B (25 eyes) with macular thickness of 300 to 400 µm, and group C (18 eyes) with macular thickness >400 µm.The best corrected visual acuity and retinal visual acuity before operation and the best corrected visual acuity on the first day and at 3 months after the surgery were compared among the 3 groups.The consistency between the preoperative retinal vision and the best corrected vision at 3 months after the surgery was analyzed. RESULTS: The best corrected visual acuity at one day and 3 months after the surgery differed significantly from that before the surgery in all the 3 groups (P < 0.05).The best corrected visual acuity recovered to 0.3-0.5 in most of the patients in the 3 groups. Thirty-one (91.18%) of the patients with a macular thickness less than 400 µm had a visual acuity≥0.3 after cataract surgery, as compared with only 14 patients (77.78%) among those with a macular thickness >400 µm.There was a positive linear correlation between preoperative retinal visual acuity and best corrected visual acuity at 3 months after the surgery (r=0.830, P < 0.05). CONCLUSIONS: For patients with cataract and idiopathic macular epiretinal membrane, phacoemulsification combined with intraocular lens implantation can improve postoperative vision.Hand-held retinal optometer can accurately assess postoperative vision in patients with stage C2N2P1 cataract.Patients with a macular thickness >400 µm caused by idiopathic macular epiretinal membrane are likely to have poor postoperative visual outcomes.

Efficacy and safety of cinobufacini injection combined with vinorelbine and cisplatin regimen chemotherapy for stage III/IV non-small cell lung cancer: A protocol for systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: The main component of cinobufacini injection is dry toad skin, which is used as adjuvant therapy for stage III/IV non-small cell lung cancer patients in long-term combination with vinorelbine and cisplatin. However, the efficacy and safety of this combination therapy remain unclear. METHODS: A systematic review and meta-analysis will be conducted following the preferred reported items for systematic review and meta-analysis guidelines. Two independent reviewers (LRL and ZLN) will carry out a comprehensive search of the PubMed, Web of Science, Cochrane Library, EMBASE, the Chinese Science and Technology Periodical Database, China National Knowledge Infrastructure, Wanfang Databases, China Biology Medicine. The last search date will be July 30, 2020. Reference list of all selected articles will independently screened to identify additional studies left out in the initial search. The Cochrane Risk of Bias Tool will be used to evaluate the risk of bias of the randomized controlled trials. Outcome index: The main efficacy indicators were based on the objective efficacy evaluation criteria of the World Health Organization antineoplastic drugs or the objective efficacy evaluation criteria of solid tumors established by RECIST. Secondary criteria Karnofsky performance scale (KPS) score, pain efficacy criteria, side effects of chemotherapy such as myelosuppression and gastrointestinal symptoms. Assessment of risk of bias and data synthesis will be conducted using Review Manager V5.3 software. RESULTS: This study will systematically evaluate the efficacy and safety of cinobufacini combined with vinorelbine and cisplatin in the treatment of stage III/IV non-small cell lung cancer. The results of this systematic review will be published in peer-reviewed scientific journals. ETHICS: The ethical approval is not required since systematic review is based on published studies. INPLASY REGISTRATION NUMBER: INPLASY202060091.

Fabrication of a Micellar Supramolecular Hydrogel for Ocular Drug Delivery.

In this paper, we describe a simple method for constructing a micellar supramolecular hydrogel, composed of a low-molecular-weight methoxy poly(ethylene glycol) (Mn = 2000 Da) block polymer and α-cyclodextrin (α-CD), for topical ocular drug delivery. Adding aqueous block polymer micelles into an α-CD aqueous solution resulted in the formation of a micellar supramolecular hydrogel through host-guest inclusion. The effects of the drug payload, block polymer, and α-CD concentrations as well as the block polymer structure on gelation time were investigated. The resultant micellar supramolecular hydrogels were thoroughly characterized by X-ray diffraction, rheological studies, and scanning electron microscopy. The hydrogels exhibited thixotropic properties, which are beneficial to ocular drug delivery. In vitro release studies indicated that the α-CD concentration strongly influenced the release rate of diclofenac (DIC) from supramolecular hydrogel. The hydrogels showed relatively low cytotoxicity toward L-929 and HCEC cells and did not significantly affect the migration of the latter after 24 h incubation. The hydrogel was nonirritant toward the rabbit eye, as indicated by the Draize test, fluorescein staining, and histological observation. Nile Red-labeled micellar supramolecular hydrogel showed that it could significantly extend the retention time on the corneal surface in rabbits, compared with a plain micellar formulation. In vivo pharmacokinetics indicated that the hydrogel could greatly improve ocular drug bioavailability, compared with that of micellar formulation. Our results suggest that the micellar supramolecular hydrogel is a promising system for ocular drug delivery.

Chitosan grafted methoxy poly(ethylene glycol)-poly(ε-caprolactone) nanosuspension for ocular delivery of hydrophobic diclofenac.

This study aimed to develop a cationic nanosuspension of chitosan (CS) and methoxy poly(ethylene glycol)-poly(ε-caprolactone) (MPEG-PCL) for ocular delivery of diclofenac (DIC). MPEG-PCL-CS block polymer was synthesized by covalent coupling of MPEG-PCL with CS. The critical micelle concentration of the MPEG-PCL-CS block polymer was 0.000692 g/L. DIC/MPEG-PCL-CS nanosuspension (mean particle size = 105 nm, zeta potential = 8 mV) was prepared and characterized by Fourier transform infrared spectroscopy, X-ray diffraction, and differential scanning calorimetry. The nanosuspension was very stable without apparent physical property changes after storage at 4 °C or 25 °C for 20 days, but it was unstable in the aqueous humor solution after 24 h incubation. Sustained release of the encapsulated DIC from the nanosuspension occurred over 8 h. Neither a blank MPEG-PCL-CS nanosuspension nor a 0.1% (mass fraction) DIC/MPEG-PCL-CS nanosuspension caused ocular irritation after 24 h of instillation. Enhanced penetration and retention in corneal tissue was achieved with a Nile red/MPEG-PCL-CS nanosuspension compared with a Nile red aqueous solution. In vivo pharmacokinetics studies showed enhanced pre-corneal retention and penetration of the DIC/MPEG-PCL-CS nanosuspension, which resulted in a higher concentration of DIC (Cmax) in the aqueous humor and better bioavailability compared with commercial DIC eye drops (P < 0.01).

MoO3 nanowires as electrochemical pseudocapacitor materials.

MoO(3) nanowires synthesized using a biomolecule-assisted hydrothermal approach showed excellent adsorption ability for the removal of RhB and were also shown to be excellent pseudocapacitor materials.