Confined Crystallization Polyether-Based Flexible Phase Change Film for Thermal Management.

Phase change materials (PCMs) possess the potential to regulate temperature by utilizing their thermal properties to absorb and release heat. Nevertheless, the application of PCMs in thermal management is constrained by issues such as liquid leakage and limited flexibility. In this study, we propose a novel approach to address these challenges by incorporating a pore structure within nanofibers to confine the crystallization of phase change molecules, thereby enhancing the flexibility of the composite material. Additionally, inspired by the adaptive mechanisms observed in plants, we have developed a form stable PCM based on polyether, which effectively mitigates the issue of liquid leakage at higher temperatures. Despite being a solid-liquid PCM at its core, this material exhibits molecular-scale flow and macroscopic shape stability as a result of intermolecular forces. The composite film material possesses remarkable flexibility, efficient thermal management capabilities, adjustable phase transition temperature, and the ability to undergo repeated processing and utilization. Consequently, it holds promising potential for applications in personal thermal energy management.

Varenicline solution nasal spray for dry eye disease in Chinese patients: a randomized phase 3 trial.

Background: Dry eye disease has a high prevalence and exerts a significant negative effect on quality of life. In China, there are currently no available nasal sprays to promote natural tear production in patients with dry eye disease. We therefore evaluated the efficacy and safety of OC-01 (varenicline solution) nasal spray versus vehicle in Chinese patients with dry eye disease. Methods: This was a randomized, multicenter, double-masked, vehicle-controlled, phase 3 clinical trial conducted at ophthalmology departments in 20 hospitals across China (NCT05378945). Eligible patients had a diagnosis of dry eye disease based on patient symptoms, Eye Dryness Score (EDS), Schirmer's Test (with topical anesthesia) Score (STS), and corneal fluorescein staining (CFS) score. Participants were randomly assigned 1:1 using an Interactive Web Response System (IWRS) to receive OC-01 0.6 mg/mL twice daily (BID) or vehicle nasal spray. Participants, investigators, and sponsor were all masked to treatment assignment. The primary endpoint was the percentage of subjects in the intention-to-treat population achieving ≥10 mm improvement in STS from baseline at week 4. Findings: In total, 340 patients were randomized from 21 July 2022 to 04 April 2023, 78.8% were female. Patients in the OC-01 group (n = 176) had significantly higher achievement of ≥10 mm improvement in STS (35.8% [n = 63] versus 17.7% [n = 29], stratified odds ratio: 2.67, 95% CI: 1.570-4.533, p = 0.0002) and a significantly greater increase from baseline STS (least-squares mean difference [SE]: 3.87 [0.794], p < 0.0001) at week 4 versus the vehicle group (n = 164). In addition, OC-01 led to a numerically greater reduction in mean EDS from baseline at week 4 compared to the vehicle group (LS mean [SE] difference: -1.3 [2.20]; 95% CI: -5.64 to 2.99, p = 0.5467). The most common adverse event was mild, transient sneezing (78% of OC-01 administrations). No serious adverse events related to nasal administration occurred. Interpretation: OC-01 (varenicline solution) nasal spray BID has clinically meaningful efficacy for reducing the signs (as measured by STS) and may improve the symptoms (as measured by EDS) of dry eye disease, with an excellent safety and tolerability profile, in the Chinese population. Funding: Jixing Pharmaceutical Co. Ltd.

MiR-452-5p facilitates retinoblastoma cell growth and invasion via the SOCS3/JAK2/STAT3 pathway.

Retinoblastoma (RB) is an intraocular tumor in children. Accumulated evidence confirms that microRNAs (miRNAs) exert critical functions in RB. This research aimed to investigate the miR-452-5p function in RB. MiR-452-5p expressions in RB were tested with quantitative real-time polymerase chain reaction (PCR). MiR-452-5p functions in RB were evaluated via Cell Counting Kit-8, 5-Ethynyl-2'-deoxyuridine assay, flow cytometry, Western blot, and Transwell. MiR-452-5p mechanism in RB was assessed using bioinformatics software Starbase and dual-luciferase reporter gene assay. Meanwhile, miR-452-5p function in RB in vivo was examined by constructing tumor xenografts in nude mice, immunohistochemistry, and Western blot assays. MiR-452-5p was overexpressed in RB tissues and cells, and miR-452-5p expression was positively correlated with RB clinicopathology including the Largest tumor base (mm) and Differentiation. Functionally, miR-452-5p knockdown restrained RB cell proliferation, invasion, epithelial-mesenchymal transition (EMT), and facilitated cell apoptosis. Mechanistically, suppressors of cytokine signaling (SOCS3) knockdown restored the inhibitory effects of miR-452-5p knockdown on RB cells. Meanwhile, in vivo studies further corroborated that miR-452-5p knockdown reduced RB tumor growth, EMT, and accelerated apoptosis in vivo. Also, miR-452-5p knockdown increased SOCS3 protein levels, and decreased phosphorylated Janus kinase 2/Janus kinase 2 (JAK2), phosphorylated signal transducer and activator of transcription 3/signal transducer and activator of transcription 3 (STAT3) in vivo. MiR-452-5p accelerated RB cell growth and invasion by SOCS3/JAK2/STAT3.

Form-Stable Phase Change Material with Wood-Based Materials as Support.

Building shape-stable phase change materials (PCMs) are crucial for their practical applications. Particularly, it is vital to utilize renewable/recyclable biomass media as the support material of form-stable PCMs. In this review article, we summarized the recent developments for building form-stable PCMs consisting of wood as a supporting material, either carbonized wood or wood composites. Moreover, the electrothermal conversion and photothermal conversion of form-stable PCMs based on carbonized wood are also demonstrated. In addition, the current technical problems and future research developments of wood-based PCMs are discussed, especially the leakage problem of PCMs during the phase change transition process. All of this information will be helpful for the in-depth understanding and development of new PCMs suitable for wide application perspectives.

25-Gauge pars plana vitrectomy combined with air tamponade for primary rhegmatogenous retinal detachment.

OBJECTIVE: This study was performed to evaluate the outcomes of 25-gauge (25-G) pars plana vitrectomy (PPV) with air tamponade for primary rhegmatogenous retinal detachment (RRD). METHODS: This retrospective consecutive case series included 126 eyes of 125 patients with primary RRD who underwent 25-G PPV with air tamponade. The patients were followed up for at least 6 months following surgery. The main outcome measures were the primary and final anatomical success rates and postoperative complications. RESULTS: The mean age of the 125 patients (80 men and 45 women) was 53.7 ± 10.0 years. The mean follow-up period was 8.3 ± 2.2 months (range, 6-18 months). Twenty-four eyes (19.0%) presented with high myopia, and 13 eyes (10.3%) were pseudophakic. Of the 126 eyes, 37 (29.4%) had inferior breaks, 2 (1.6%) had choroidal detachment, and 86 (68.3%) had macular detachment. The single- and final-operation success rates were 96.0% and 100%, respectively. Postoperative complications included macular hole formation in two eyes. During follow-up, secondary cataract surgery was performed in 27 (23.9%) of the 113 phakic eyes. CONCLUSION: 25-G PPV with air tamponade is effective and safe in treating selected patients with primary RRD with a high anatomical success rate.

Lrpap1 deficiency leads to myopia through TGF-ß-induced apoptosis in zebrafish.

BACKGROUND: Frameshift mutations in LRPAP1 are responsible for autosomal recessive high myopia in human beings but its underlying mechanism remains elusive. This study aims to investigate the effect of LRPAP1 defect on ocular refractive development and its involved mechanism. METHODS: A lrpap1 mutant zebrafish line with homozygous frameshift mutation was generated by CRISPR/Cas9 technology and confirmed by Sanger sequencing. The ocular refractive phenotype was analyzed by calculating the relative refractive error (RRE) with vivo photography and histological analysis at different development stages, together with examining ocular structure change via transmission electron microscopy. Further, RNA sequencing and bioinformatics analysis were performed. The potentially involved signaling pathway as well as the interacted protein were investigated in vivo. RESULTS: The lrpap1 homozygous mutant zebrafish line showed myopic phenotype. Specifically, the mutant lines showed larger eye axial length-to-body length in one-month old individuals and a myopic shift with an RRE that changed after two months. Collagen fibers became thinning and disordered in the sclera. Further, RNA sequencing and bioinformatics analysis indicated that apoptosis signaling was activated in mutant line; this was further confirmed by acridine orange and TUNEL staining. Moreover, the expression of TGF-ß protein was elevated in the mutant lines. Finally, the treatment of wild-type embryos with a TGF-ß agonist aggravated the degree of eyeball apoptosis; conversely, the use of a TGF-ß inhibitor mitigated apoptosis in mutant embryos. CONCLUSION: The study provides functional evidence of a link between lrpap1 and myopia, suggesting that lrpap1 deficiency could lead to myopia through TGF-ß-induced apoptosis signaling. Video abstract.

Integrated Analysis of lncRNA-miRNA-mRNA ceRNA Network in Mixed Dry Eye Disease.

In order to investigate the relationship between inflammation and lncRNA in mixed dry eye disease (DED), this study establishes competitive endogenous RNA (ceRNA) network in mixed DED. Microarray analysis of cornea from mixed DED mice is performed to screen for differences in lncRNA and target genes, and miRNA bioinformatics were predicted based on the ceRNA hypothesis. The ceRNA network, which consists of 96 relationship pairs, is constructed using the top 10 upregulated lncRNAs and all upregulated mRNAs and two pairs of lncRNA-miRNA-mRNA pairs (NONMMUT047964.2-miR-671-5p-Egr-1andNONMMUT054540.2-miR-1934-5p-Grm2) are selected for RT-qRCR verification in mouse corneal epithelial cells under high osmotic pressure and the samples for microarray. Meanwhile, mouse corneal epithelial cell lines (MCECs), transfected siRNA of NONMMUT047964.2 under high osmotic pressure, shows a decrease in apoptosis rate and a decrease in expression of IL-1ß and IL-6. The experimental results show that the NONMMUT047964.2-miR-671-5p-Egr-1 axis may regulate the inflammation and promote the apoptosis of corneal epithelial cells under hypertonic condition.

Development and Validation of a Deep Learning Model to Predict the Occurrence and Severity of Retinopathy of Prematurity.

Importance: Retinopathy of prematurity (ROP) is the leading cause of childhood blindness worldwide. Prediction of ROP before onset holds great promise for reducing the risk of blindness. Objective: To develop and validate a deep learning (DL) system to predict the occurrence and severity of ROP before 45 weeks' postmenstrual age. Design, Setting, and Participants: This retrospective prognostic study included 7033 retinal photographs of 725 infants in the training set and 763 retinal photographs of 90 infants in the external validation set, along with 46 characteristics for each infant. All images of both eyes from the same infant taken at the first screening were labeled according to the final diagnosis made between the first screening and 45 weeks' postmenstrual age. The DL system was developed using retinal photographs from the first ROP screening and clinical characteristics before or at the first screening in infants born between June 3, 2017, and August 28, 2019. Exposures: Two models were specifically designed for predictions of the occurrence (occurrence network [OC-Net]) and severity (severity network [SE-Net]) of ROP. Five-fold cross-validation was applied for internal validation. Main Outcomes and Measures: Area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, and specificity to evaluate the performance in ROP prediction. Results: This study included 815 infants (450 [55.2%] boys) with mean birth weight of 1.91 kg (95% CI, 1.87-1.95 kg) and mean gestational age of 33.1 weeks (95% CI, 32.9-33.3 weeks). In internal validation, mean AUC, accuracy, sensitivity, and specificity were 0.90 (95% CI, 0.88-0.92), 52.8% (95% CI, 49.2%-56.4%), 100% (95% CI, 97.4%-100%), and 37.8% (95% CI, 33.7%-42.1%), respectively, for OC-Net to predict ROP occurrence and 0.87 (95% CI, 0.82-0.91), 68.0% (95% CI, 61.2%-74.8%), 100% (95% CI, 93.2%-100%), and 46.6% (95% CI, 37.3%-56.0%), respectively, for SE-Net to predict severe ROP. In external validation, the AUC, accuracy, sensitivity, and specificity were 0.94, 33.3%, 100%, and 7.5%, respectively, for OC-Net, and 0.88, 56.0%, 100%, and 35.3%, respectively, for SE-Net. Conclusions and Relevance: In this study, the DL system achieved promising accuracy in ROP prediction. This DL system is potentially useful in identifying infants with high risk of developing ROP.

Air Tamponade for Rhegmatogenous Retinal Detachment With Inferior Breaks After 25-Gauge Pars Plana Vitrectomy: Technique and Outcome.

To evaluate the outcomes of 25-guage (G) pars plana vitrectomy (PPV) with air tamponade for rhegmatogenous retinal detachment (RRD) with inferior breaks. This retrospective consecutive case series included fifty-two eyes of fifty-two RRD patients with inferior breaks who underwent 25-G PPV with air tamponade. These patients were followed up for at least 6 months following surgery. Primary and final anatomical success rates and postoperative complications were the main outcome measures. The mean age of the patients (39 men and 13 women) was 51.8 ± 11.8 years. There were 49 primary RRDs (94.2%) and three recurrent RRDs (5.8%). The mean follow-up period was 8.2 ± 1.6 months (range: 6-13 months). Sixteen eyes (30.8%) presented with high myopia, and six eyes (11.5%) were pseudophakic. Proliferative vitreous retinopathy grade was C1 in four eyes (7.7%). Of the 52 eyes, two (3.8%) were complicated with choroidal detachment, and forty (76.9%) had the macula detached. The single- and final-operation success rates were 96.2% and 100%, respectively. During follow-up, secondary cataract surgery was performed in eight eyes (17.4%) of the 46 phakic eyes. 25-G PPV with air tamponade is effective in treating selected RRD patients with inferior breaks. Patients can benefit from early visual recovery and less complications.

The association of demodex infestation with pediatric chalazia.

PURPOSE: This study aimed to investigate the association of Demodex infestation with pediatric chalazia. METHODS: In a prospective study, 446 children with chalazia and 50 children with non-inflammatory eye disease (controls) who underwent surgical treatment were enrolled from December 2018 to December 2019. Patient ages ranged from 7 months to 13 years old. All patients underwent eyelash sampling for light microscope examination, and statistical correlation analysis between Demodex infestation and chalazia, including the occurrence, recurrence, and course of disease, morphological characteristics, and meibomian gland dysfunction (MGD) in chalazia patients was performed. RESULTS: Demodex was found in 236 (52.91%) patients with chalazia and zero control patients. Demodicosis was significantly more prevalent in chalazia patients than the control group (P < 1 × 10- 14). Recurrent chalazia (P = 0.006) and skin surface involvement (P = 0.029) were highly correlated with Demodex infestation. Demodicosis was also associated with multiple chalazia (P = .023) and MGD(P = .024). However, Demodex infestation was comparable in the course of disease (P = 0.15), seasonal change (P = 0.68) and blepharitis subgroups (P = 0.15). Within the group of chalazia patients who underwent surgical removal of cysts, 4 (0.9%) patients with concurrent demodicosis experienced recurrence. CONCLUSIONS: Demodex infestation was more prevalent in pediatric chalazia patients than healthy children, and was associated with recurrent and multiple chalazia. Demodicosis should be considered as a risk factor of chalazia. In children with chalazia, Demodex examination and comprehensive treatment of Demodex mites should be applied to potentially prevent recurrence.

Retinal Nerve Fiber Layer Thickness and Associations With Cognitive Impairment in Parkinson's Disease.

OBJECTIVE: This study intended to investigate whether retinal nerve fiber layer (RNFL) thickness could become a potential marker in patients with Parkinson's disease with cognitive impairment (PD-CI). METHODS: Fifty-seven PD patients and 45 age-matched healthy controls (HCs) were recruited in our cross-sectional study and completed optical coherence tomography (OCT) evaluations. PD with normal cognition (PD-NC) and cognitive impairment (PD-CI) patients were divided following the 2015 Movement Disorder Society criteria. RNFL thickness was quantified in subfields of the 3.0-mm circle surrounding the optic disk; while a battery of neuropsychiatric assessments was conducted to estimate the Parkinsonism severity. General linear models and one-way ANOVA were adopted to assess RNFL thickness between subgroups with different cognitive statuses; logistic regression analyses were applied to determine the relation between RNFL and PD-CI cases. RESULTS: Compared with HCs, more thinning of the RNFL was observed in the inferior and temporal sectors in PD patients, especially in the PD-CI group. Inferior RNFL thickness was reduced in PD-CI compared with PD-NC patients. Logistic regression analysis found that inferior RNFL thickness was independently associated with PD-CI cases (odds ratio = 0.923, p = 0.014). Receiver operating characteristic analysis showed that the RNFL-involved combined model provided a high accuracy in screening cognitive deficiency in PD cases (area under the curve = 0.85, p < 0.001). CONCLUSION: Reduced RNFL thickness especially in the inferior sector is independently associated with PD-CI patients. Our study present new perspectives into verifying possible indicators for neuropathological processes or disease severity in Parkinsonians with cognitive dysfunction.

Non-coding RNAs and related molecules associated with form-deprivation myopia in mice.

The role of miRNAs and its regulatory mechanism in myopia are indeterminate. Our study aimed to investigate potential myopia-associated non-coding RNAs and related molecules by performing a comprehensive bioinformatic analysis of miRNA expression profile of mice with form-deprivation myopia (FDM). Differentially expressed miRNAs in two raw microarray data sets (GSE58124 and GSE84220) from Gene Expression Omnibus (GEO) database were comprehensively analysed using GEO2R. Target genes were predicted using miRDB and enriched with Metascape online tool. Protein-protein interaction (PPI) networks were constructed utilizing STRING and Cytoscape. Significant differentially expressed miRNAs were validated by real-time polymerase chain reaction (qRT-PCR) using RNA extracted from monocular FDM ocular tissues. As result, we identified three upregulated miRNAs (mmu-miR-1936, mmu-miR-338-5p, and mmu-miR-673-3p) significantly associated with myopia in the two microarray data sets (p < 0.05 and |Log (Fold Change) |>1). GO functional analysis suggested these three miRNAs were targeted in genes mostly enriched in morphogenesis and developmental growth of retinal tissues. Enrichment analysis revealed top eight transcription factors, including PAX6 and Smad3, related to myopia. Ten hub genes, including Rbx1, Fbxl3, Fbxo27, Fbxl7, Fbxo4, Cul3, Cul2, Klhl5, Fbxl16 and Klhl42, associated with ubiquitin conjugation were identified. qRT-PCR confirmed the increased expression of mmu-miR-1936 and mmu-miR-338-5p (p < 0.05), but no statistical difference was observed in mmu-miR-673-3p expression in myopic retinas. Our findings indicated mmu-miR-1936, mmu-miR-338-5p and mmu-miR-673-3p upregulation may be associated with myopia development via post-transcriptional gene regulation, and identified potential molecules that could be further explored in future studies of the mechanism in myopia.

Validation of the DIGIROP-birth model in a Chinese cohort.

BACKGROUND: We aimed to validate the predictive performance of the DIGIROP-Birth model for identifying treatment-requiring retinopathy of prematurity (TR-ROP) in Chinese preterm infants to evaluate its generalizability across countries and races. METHODS: We retrospectively reviewed the medical records of preterm infants who were screened for retinopathy of prematurity (ROP) in a single Chinese hospital between June 2015 and August 2020. The predictive performance of the model for TR-ROP was assessed through the construction of a receiver-operating characteristic (ROC) curve and calculating the areas under the ROC curve (AUC), sensitivity, specificity, and positive and negative predictive values. RESULTS: Four hundred and forty-two infants (mean (SD) gestational age = 28.8 (1.3) weeks; mean (SD) birth weight = 1237.0 (236.9) g; 64.7% males) were included in the study. Analyses showed that the DIGIROP-Birth model demonstrated less satisfactory performance than previously reported in identifying infants with TR-ROP, with an area under the receiver-operating characteristic curve of 0.634 (95% confidence interval = 0.564-0.705). With a cutoff value of 0.0084, the DIGIROP-Birth model showed a sensitivity of 48/93 (51.6%), which increased to 89/93 (95.7%) after modification with the addition of postnatal risk factors. In infants with a gestational age < 28 weeks or birth weight < 1000 g, the DIGIROP-Birth model exhibited sensitivities of 36/39 (92.3%) and 20/23 (87.0%), respectively. CONCLUSIONS: Although the predictive performance was less satisfactory in China than in developed countries, modification of the DIGIROP-Birth model with postnatal risk factors shows promise in improving its efficacy for TR-ROP. The model may also be effective in infants with a younger gestational age or with an extremely low birth weight.

Quantitative assessment and determinants of foveal avascular zone in healthy volunteers.

OBJECTIVES: To evaluate the foveal avascular zone (FAZ) area in healthy volunteers using optical coherence tomography angiography (OCTA) and identify factors that influence the FAZ. METHODS: This single-center cross-sectional study included 526 eyes of 263 healthy volunteers who underwent macular scanning by Zeiss OCTA. A linear mixed model was used to investigate the effects of systemic factors (age, sex, blood pressure, height, and weight) and ocular factors (intraocular pressure, biometric parameters, and central macular thickness) on FAZ. RESULTS: In total, 520 eyes of 262 healthy volunteers were included in the analysis. The mean volunteer age was 38.59 ± 22.03 years (range, 5-84 years); 124 volunteers were male (47.33%) and 138 volunteers were female (52.67%). The mean FAZ area was 0.30 ± 0.03 mm2 (95% confidence interval [CI], 0.29-0.31 mm2). Univariate analysis showed that FAZ area was associated with age (ß = 0.0011), anterior chamber depth (ß = -0.0513), and axial length (ß = -0.0202). Multivariate analysis showed that FAZ area was negatively correlated with axial length (ß = -0.0181). CONCLUSIONS: The mean FAZ area in healthy volunteers, measured using Zeiss OCTA, was 0.30 ± 0.03 mm2. Furthermore, FAZ area was negatively associated with axial length; this relationship should be considered in clinical practice.

Quantitative assessment and determinants of the papillary microvasculature in healthy subjects.

BACKGROUND: It is critical to monitor the optic disc's vessel density using Optical coherence tomography angiography (OCTA) and evaluate its determinants. In the current study, we investigate the superficial vessel density (VD) of the papillary microvasculature and its determinants in healthy subjects of Southern China. METHODS: This was a prospective, cross-sectional study. Superficial VD in healthy individuals' optic disc region was measured by OCTA. The factors associated with ocular and systemic parameters were analyzed using a generalized estimation equation (GEE) model. RESULTS: A total of 510 eyes of 260 healthy subjects were analyzed in the study. The total VD in the optic disc area was 17.21 ± 2.15 mm- 1 (95% CI, 17.02-17.40 mm- 1). The VD in the inner ring and the outer ring of the optic disc were significantly higher compared with the central ring, while the VD of the superior quadrant and inferior quadrant was significantly higher compared with the temporal and nasal quadrant. After adjusting for the ocular factors and systemic factors, AL (ß = - 0.4917, P = 0.0003), disc area (ß = - 0.3748, P = 0.0143), CMT (ß = - 0.0183, P = 0.0003) and SSI (ß = 1.0588, P < 0.001) were significantly associated with total VD of the optic disc. CONCLUSION: The mean total VD in the optic disc area was 17.21 ± 2.15 mm- 1 in healthy subjects, and the superior and inferior VD was significantly higher than the temporal and nasal VD. AL, disc area, CMT, and SSI may affect the total VD in the optic disc area and should be considered in clinical practice.

Nuclear translocation of ß-catenin induced by E-cadherin endocytosis causes recurrent erosion of diabetic cornea.

Recurrent epithelial erosion and refractory corneal ulcer are the clinical features of diabetic keratopathy (DK), which eventually lead to corneal scar and visual disturbance. In this study, we sought to determine the abnormalities of cell junction in diabetic corneal epithelial cells and the effect of high glucose on the ß-catenin/E-cadherin complex. Corneal histology showed that corneal epithelial cells of high glucose mice were loosely arranged, and the immunohistochemistry showed that the expression of E-cadherin decreased, the levels of ß-catenin increased in nuclear. High glucose-induced degradation and endocytosis of E-cadherin of corneal epithelial cells reduce the formation of ß-catenin/E-cadherin complex and promote the nuclear translocation of ß-catenin. Moreover, high glucose also activated the transcription and expression of matrix metallopeptidase and snail, which interfered with the adhesion of corneal epithelial cells to the basement membrane. These findings reveal that DK is associated with the dissociation of cell junctions. The maintenance of the stability of the ß-catenin/E-cadherin complex may be a potential therapeutic target of refractory corneal ulcers in patients with diabetes.

Efficacy of the WINROP algorithm for retinopathy of prematurity screening in Southern China.

AIM: To evaluate the predicting efficacy of severe retinopathy of prematurity (ROP) by the WINROP algorithm (http://winrop.com) in Southern China. METHODS: All preterm infants with the gestational age (GA) less than 32wk were included. Their ROP screening results and serial postnatal body weight were analysed retrospectively. Weekly body weight was entered into and measured by the WINROP system. The outcomes were analysed, and the sensitivity, specificity, positive predictive value and negative predictive value (NPV) were calculated. RESULTS: Totally 432 infants with a median GA of 30.0 (24.0-31.9)wk, and a median birth weight (BW) of 1360 (540-2700) g were included. Among these 432 infants, 50 were diagnosed as type 1 ROP but only 28 were identified by the WINROP algorithm. The sensitivity was 56% (28/50) and the NPV was 92% (252/274). However, for infants with BW <1000 g or GA <28wk, the sensitivity was 93.8% (15/16) and 93.3% (14/15), respectively. Meanwhile, with several postnatal complications added as additional risk factors, the sensitivity was increased to 96% (48/50). CONCLUSION: The sensitivity of the WINROP algorithm from the Southern Chinese cohort is not as high as that reported in developed countries. This algorithm is effective for detecting severe ROP from extremely small or preterm infants. Modification of the algorithm with additional risk factors could improve the predictive value for infants with a GA>28wk in China.

The role of soluble programmed death protein-1 (sPD-1) and soluble programmed death ligand-1 (sPD-L1) in rat corneal transplantation rejection.

BACKGROUND: Immunological rejection is one of the problems in corneal transplantation. Recently, some research found out that soluble programmed death protein-1 (sPD-1) and soluble programmed death ligand protein-1 (sPD-L1) play a significant role in immunologic suppression. OBJECTIVES: To explore expression of sPD-1 and sPD-L1 in a penetrative corneal transplantation model and its relationship with transplant rejection. MATERIAL AND METHODS: Autologous corneal transplantation rat models and allogeneic corneal transplantation rat models were used as the control group and the experimental group, respectively. Changes of the transplanted grafts were observed under a slit-lamp microscope. Hematoxylin-eosin (H&E) staining was applied to examine the histopathological features of the corneal grafts. Flow cytometry was used to analyze CD4+CD25+Treg in the serum and spleen. The sPD-1, sPD-L1, interleukin 10 (IL-10) and interleukin 4 (IL-4) levels in serum and the aqueous humor of the rats were detected using enzyme-linked immunosorbent assay (ELISA). RESULTS: After the operation, no transplant rejection occurred in the control group. Flow cytometry results showed that expressions of CD4+CD25+Treg in serum in the experimental group were lower than those in the control group (p < 0.05). The ELISA results showed that after the operation, sPD-1 and sPD-L1 expression levels in serum in the experimental group were higher than in the control group (all p < 0.05). After the operation, lL-10 and IL-4 content in serum in the experimental group was lower than in the control group (all p < 0.05). The sPD-1/sPD-L1 ratio in the experimental group was higher than in the control group. CONCLUSIONS: Increases of sPD-1 content and decreases of CD4+CD25+Treg, IL-10 and IL-4 levels may be involved in corneal allograft rejection. Dynamic detection of the content of sPD-1 and sPD-L1 in serum and aqueous humor after the operation would help in understanding the local immune response in a clinical setting and predicting the occurrence of corneal graft rejection.

The embryonic stem cell microenvironment inhibits mouse glioma cell proliferation by regulating the PI3K/AKT pathway.

BACKGROUND: Glioblastoma multiforme (GBM) is the most common malignant tumor of the central nervous system, accounting for 48.6% of malignant tumors. The current standard treatment plan includes the widest range of safe surgical resection, supplemented by local brain radiotherapy and temozolomide concurrent chemotherapy; this can cause serious side effects. Even so, the median survival time of GBM patients is only 8 months, and the 5-year survival rate is only 5.5%. It is imminent to find new treatments. Early studies have shown that chicken and zebrafish embryos can reprogram cancer cells into a non-tumorigenic phenotype through the embryonic microenvironment. However, the effect of embryonic stem cell microenvironment on GBM and its possible mechanism are not clear. METHODS: In this study, the glioblastoma cell line, U118, in the brain was investigated. There were four experimental groups: GB, GE, GA and GT. U118 cells were harvested after culturing for 72 hours. Cell proliferation, apoptosis, reactive oxygen species (ROS) were examined using vasculogenic mimicry assays, quantitative real-time polymerase chain reaction (QRT-PCR), western blotting (WB) and flow cytometry. The differences in the biological function of U118 cells and the PI3K/protein kinase B (AKT) signaling pathway were compared between the groups. RESULTS: Compared with the GB control group, the GE co-culture group and GT chemotherapy group showed reduced cell proliferation, increased apoptosis, increased ROS, as well as decreased or inhibited vasculogenic mimicry. Expressions of cyclin B1 and cyclin D1 were also notably reduced, while that of Bax, Bcl-2, p53, Caspase-3, GSK-3ß, p21, and p27 were significantly increased. Moreover, the expression of PI3K, AKT, and mTOR were markedly decreased, whereas expression of PTEN increased considerably. Also, the expression of positive regulatory factors significantly increased, however negative regulatory factors decreased in the GA group compared to the GE group. CONCLUSIONS: The ESC microenvironment reverses glioma malignancy, partially via inhibition of the PI3K signaling pathway. Our study may have a significant impact and important clinical implications for cell therapy in the treatment of glioma.

[DNMT1 protein promotes retinoblastoma proliferation by silencing MEG3 gene].

OBJECTIVE: To investigate whether DNMT1 protein induces retinoblastoma proliferation by silencing MEG3 gene. METHODS: Two retinoblastoma cell lines (HXO-RB44 and SO-RB50) and a normal human retinal pigment epithelial (RPE) cell line were transfected with the plasmid pcDNA-DNMT1 or si-DNMT1 for up-regulating or interference of DNMT1 expression, and with pcDNA-MEG3 or si-MEG3 for up-regulating or interference of MEG3 expression. Western blotting was used to detect the changes in the expression of DNMT1 protein in the transfected cells, and CCK-8 and EdU assays were used to detect the changes in cell proliferation. Real-time quantitative PCR (qRT-PCR) was performed to detect MEG3 expression in SO-RB50 and HXO-RB44 cells after transfection, and the methylation level of MEG3 gene promoter after interference of DNMT1 expression was detected using methylation-specific PCR. RESULTS: SO-RB50 and HXO-RB44 cells showed significantly increased expression of DNMT1 protein as compared with normal RPE cells (P < 0.05). In HXO-RB44 cells, transfection with pcDNADNMT1 resulted in significantly increased expression of DNMT1 protein, enhanced cell proliferation ability, and significantly reduced expression of MEG3 (P < 0.05). In SO-RB50 cells, transfection with si-DNMT1 significantly reduced the expression of DNMT1 protein, suppressed the cell proliferation, and increased MEG3 expression (P < 0.05). Interference of DNMT1 significantly reduced the methylation level of MEG3 gene promoter. After reversing the regulatory effect of DNMT1 on MEG3 gene, DNMT1 protein showed significantly weakened ability to regulate retinoblastoma cell proliferation (P < 0.05). CONCLUSIONS: In retinoblastoma cells, the up-regulation of DNMT1 protein induces promoter methylation and inactivation of MEG3 gene and eventually leads to abnormal cell proliferation.