Recurrence of macular edema in patients with branch retinal vein occlusion: a proteomic study.

BACKGROUND: Branch retinal vein occlusion (BRVO) is a common retinal vascular disease leading to severe vision loss and blindness. This study aimed to investigate and reveal the pathophysiological mechanisms underlying macular edema (ME) recurrence in patients with BRVO through a proteomic approach. METHODS: We detected proteins in the aqueous humor of 14 untreated, four refractory, and four post-operative patients with BRVO-ME and 12 age-matched cataract controls using four-dimensional label-free proteomic and bioinformatics analyses. RESULTS: In total, 84 proteins exhibited significant differential expression between the BRVO and control samples (fold change [FC] ≥ 1.2 and adjusted p-value < 0.05). Compared to the control group, 43 and 41 proteins were upregulated and downregulated, respectively, in the BRVO group. These proteins were involved in cell adhesion, visual perception, retina homeostasis, and platelet activation. Several significantly enriched signaling pathways included complement and coagulation cascades and platelet activation. In the protein-protein interaction networks generated using the search tool for retrieval of interacting genes (STRING), the fibrinogen alpha chain and fibrinogen beta chain constituted a tightly connected cluster. Many common protein expression trends, such as the fibrinogen alpha chain and fibrinogen beta chain, were observed in both the recurrent and refractory groups. Differentially expressed proteins in the two groups were involved in complement activation, acute-phase response, platelet activation, and platelet aggregation. Important signaling pathways include the complement and coagulation cascades, and platelet activation. Protein-protein interaction analysis suggested that the fibrinogen alpha chain and fibrinogen beta chain constituted a tightly connected cluster. The expression of some differentially expressed proteins shared by the BRVO and the recurrent and refractory groups was reversed in the post-operative group. CONCLUSIONS: Our study is the first to analyze the proteomics of recurrent, refractory, and post-operative groups treated for BRVO-ME, and may potentially provide novel therapeutic interventions for the recurrence of ME.

Higher incidence of meibomian gland dysfunction in postmenopausal women with primary acquired nasolacrimal duct obstruction.

PURPOSE: This study aimed to investigate the incidence of meibomian gland dysfunction (MGD) in postmenopausal women with primary acquired nasolacrimal duct obstruction (PANDO) and enables ophthalmologists to pay attention to ocular surface damage before surgery. METHODS: 165 postmenopausal women with PANDO and 115 postmenopausal women with a normal lacrimal drainage system were enrolled in this prospective study. Based on the results of lacrimal duct irrigation and age, the participants were further subdivided. The incidence of different severities of MGD in different groups was calculated and analyzed by the chi-squared test. RESULTS: The incidence of MGD in the PANDO group was 81.21%, and in the control group, it was 46.96%, which was significantly higher in the presence of PANDO (p < 0.001). The incidence of severe MGD in the complete and incomplete PANDO groups was higher than that in the control group (all p < 0.05), and no significant differences were observed between the complete and incomplete PANDO groups. The incidence of moderate MGD was significantly higher in the complete PANDO group than in the control group (p < 0.001). When age was considered an independent variable, the results revealed a significant value for patients aged < 70 years (p < 0.001). CONCLUSIONS: Our study revealed a prodominantly high incidence of MGD in postmenopausal women with PANDO, especially in a complete PANDO or aged < 70 years. Ophthalmologists need to pay close attention to MGD in postmenopausal women with PANDO.

Identification of Prognostic Factors in Cholangiocarcinoma Based on Integrated ceRNA Network Analysis.

This study is aimed at screening prognostic biomarkers in cholangiocarcinoma (CHOL) based on competitive endogenous RNA (ceRNA) regulatory network analysis. Microarray data for lncRNAs, mRNA, and miRNAs were downloaded from the GEO and TCGA databases. Differentially expressed RNAs (DERs) were identified in CHOL and normal liver tissue samples. WGCNA was used to identify disease-related gene modules. By integrating the information from the starBase and DIANA-LncBasev2 databases, we constructed a ceRNA network. Survival analysis was performed, and a prognostic gene-based prognostic score (PS) model was generated. The correlation between gene expression and immune cell infiltration or immune-related feature genes was analyzed using TIMER. Finally, real-time quantitative PCR (RT-qPCR) was used to verify the expression of the 10 DERs with independent prognosis. A large cohort of DERs was identified in the CHOL and control samples. The ceRNA network consisted of 6 lncRNAs, 2 miRNAs, 90 mRNAs, and 98 nodes. Ten genes were identified as prognosis-related genes, and a ten-gene signature PS model was constructed, which exhibited a good prognosis predictive ability for risk assessment of CHOL patients (AUC value = 0.975). Four genes, ELF4, AGXT, ABCG2, and LDHD, were associated with immune cell infiltration and closely correlated with immune-related feature genes (CD14, CD163, CD33, etc.) in CHOL. Additionally, the consistency rate of the RT-qPCR results and bioinformatics analysis was 80%, implying a relatively high reliability of the bioinformatic analysis results. Our findings suggest that the ten-signature gene PS model has significant prognostic predictive value for patients with CHOL. These four immune-related DERs are involved in the progression of CHOL and may be useful prognostic biomarkers for CHOLs.

Serum Cytokines and FeNO in School-Aged Children with Mycoplasma pneumoniae Pneumonia.

BACKGROUND Mycoplasma pneumoniae is a major cause of community-acquired pneumonia (CAP) that is particularly prevalent in school-aged children. This study explored the potential involvement of cytokines in children with Mycoplasma pneumoniae pneumonia (MPP) infection. MATERIAL AND METHODS Children aged 3-7 years who were hospitalized due to CAP infection were enrolled and divided into 2 groups: an MPP group (n=33) and a NMPP group (n=38), along with 21 age-matched healthy controls. Clinical characteristics and laboratory data were recorded. Serum levels of IL-18, IL-33, IFN-γ, IL-5, IL-6, IL-8, and IL-13 were assessed using Luminex xMAP technology. Correlation analysis and ROC curves analysis were also performed to further explore the role of these detected cytokines in CAP. RESULTS Compared with the healthy controls, the serum expression of IL-18, IL-33, IFN-γ, IL-5, IL-6, IL-8, and IL-13 were significantly higher in the MPP and NMPP groups. Furthermore, serum IL-18 expression was found to be significantly correlated with lgE, FeNO, IL-5, IL-8, and IL-13 concentrations. Significant differences were also observed between the MPP group and NMPP group patients in levels of IL-18, IL-5, and IL-6, and further ROC analysis showed that the area under the curve (AUC) of IL-18 and IL-5 were 0.813 (95% CI: 0.710-0.917; P<0.01) and 0.844 (95% CI: 0.756-0.933; P<0.01), respectively. CONCLUSIONS IL-18, IL-33, IFN-γ, IL-5, IL-6, IL-8, and IL-13 serum levels showed significant differences in children with CAP. IL-18 and IL-5 were much higher in the MPP group compared to the NMPP group patients, whereas IL-6 levels were significantly lower in these 2 groups.

Sorafenib-Loaded Long-Circulating Nanoliposomes for Liver Cancer Therapy.

A type of sorafenib- (SOR-) loaded long-circulating nanoliposome was constructed, and the targeting performance and antitumor effects of the prepared liposome were evaluated in the present study. Polyethylene glycol- (PEG-) modified long-circulating nanoliposomes (LC-NPs) were designed and prepared using reverse evaporation, and the LC-NPs were used for delivering sorafenib (LC-PEG-SOR-NPs). Then, the anti-VEGFR antibody as a targeting moiety was chemically coupled with LC-PEG-SOR-NPs to form liver cancer-targeted nanoliposomes (anti-VEGFR-LC-PEG-SOR-NPs). The drug entrapment and loading efficiency were measured. And the cancer-targeting performance and therapeutic efficiency were evaluated both in vitro and in vivo. The anti-VEGFR-LC-PEG-SOR-NPs with an average of 119.8 ± 4.2 nm showed a uniform spherical structure. The drug entrapment and loading efficiency were 92.5% and 18.5%, respectively. The killing efficiency of anti-VEGFR-LC-PEG-SOR-NPs was up to 18% after incubating with liver cancer cells for 72 h. Furthermore, the anti-VEGFR-LC-PEG-SOR-NPs could actively target at the tumor region and could efficiently inhibit tumor growth with negligible side effects. This newly designed nanoliposomes had desirable dispersibility, high drug entrapment efficiency, tumor targeting and therapeutic efficiency, and good safety. As a biocompatible nanocomposite, it was promising to become a novel and useful tumor-targeting nanodrug for liver cancer therapy.

ABCB1 Polymorphisms and Childhood Acute Lymphoblastic Leukemia Risk: A Meta-Analysis.

The association between ATP-binding cassette subfamily B member 1 (ABCB1) C3435T and C1236T polymorphisms and the risk for childhood acute lymphoblastic leukemia (ALL) is inconclusive. We conducted a meta-analysis of all published studies to determine the association of ABCB1 C3435T and C1236T polymorphisms and pediatric ALL risk. A systematic retrieval of relevant publications from the PubMed and Web of Science databases was performed. Data were calculated and statistical analysis was performed using STATA version 12.0 software. Metaanalysis results showed no significant association between C3435T polymorphism and pediatric ALL risk (TT vs. CC: odds ratio [OR] = 1.20, 95% confidence interval [CI] = 0.95-1.52; CT vs. CC: OR = 1.00, 95% CI = 0.82-1.23; the dominant model: OR = 1.07, 95% CI = 0.89-1.29; the recessive model: OR = 1.17, 95% CI = 0.84-1.62). Similarly, there was no association found for the C1236T polymorphism (TT vs. CC: OR = 1.18, 95% CI= 0.82-1.70; CT vs. CC: OR = 1.08, 95% CI = 0.80-1.45; the dominant model: OR = 1.10, 95% CI= 0.83-1.46; the recessive model: OR = 0.98, 95% CI = 0.61-1.58). Similar results were observed in the subgroup analyses on ethnicity and Hardy-Weinberg equilibrium. The present meta-analysis found no evidence for ABCB1 C3435T and C1236T polymorphisms as risk factors for pediatric ALL.