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.

Changes in the meibomian glands in postmenopausal women with primary acquired nasolacrimal duct obstruction: a prospective study.

BACKGROUND: Primary acquired nasolacrimal duct obstruction (PANDO) is frequently encountered in perimenopausal women, causing tear flow stagnation and resulting in a variety of ocular discomfort symptoms. However, little is known about the alterations in the meibomian gland in postmenopausal women with PANDO. Hence, this study investigated the changes in the meibomian gland and ocular surface in postmenopausal women with PANDO. METHODS: This prospective study included 60 eyes of 60 postmenopausal women with PANDO (PANDO group) and 30 eyes of 30 postmenopausal women without PANDO (control group). The PANDO group was further subdivided into incomplete and complete PANDO groups, based on the degree of nasolacrimal duct obstruction. The patients' symptoms were evaluated using the ocular surface disease index questionnaire. The meibomian gland and ocular surface were assessed using the Keratograph 5 M. Other ophthalmologic examinations included the tear break-up time, corneal fluorescein staining, meibomian gland expression, and Schirmer I test. The correlations between the degree of nasolacrimal duct obstruction and other metrics were analyzed. RESULTS: The loss ratio of the upper eyelid was greater in the incomplete PANDO group than in the control group (p = 0.023). Meibomian gland distortion of the upper eyelid was more severe in the control group than in the complete PANDO group (p = 0.022). The non-invasive tear meniscus height was greater, whereas the intensity of corneal fluorescein staining was lower in the PANDO group than in the control group (all p < 0.05). The degree of nasolacrimal duct obstruction was positively associated with the non-invasive tear meniscus height and ocular surface disease index scores (p < 0.001 and p < 0.001, respectively). Corneal fluorescein staining and meibomian gland distortion of the upper eyelid were negatively correlated with the degree of nasolacrimal duct obstruction (p = 0.01 and p = 0.007, respectively). CONCLUSION: Postmenopausal women with PANDO exhibit significant morphological changes in the meibomian gland. More attention should be paid to meibomian gland loss in postmenopausal women with incomplete PANDO, as it is crucial for identifying meibomian gland impairments in patients with PANDO.

MDSCs Aggravate the Asthmatic Progression in Children and OVA-Allergic Mice by Regulating the Th1/Th2/Th17 Responses.

Background: Asthma is a chronic inflammatory disease of respiratory with serious risks for children. This study explored myeloid-derived suppressor cells (MDSCs) on the pathogenesis of asthmatic children and mice. Methods: The clinical study enrolled 30 asthma, 20 pneumonia, and 20 control participants. The MDSCs, Th17 and Th1 cells percentage, and IL-4, IL-12, IL-10, and IFN-γ levels were detected by flow cytometry and ELISA. In experimental asthma, mice were divided into control, ovalbumin (OVA), and OVA + MDSCs groups. The changes in inflammatory cell count and the levels of IL-5, IL-12, and IL-10 in mice BALF and the levels of inflammatory factors, IgE, and IFN-γ in mice were detected by ELISA. The amount of ROS generation and pathological changes and the levels of caspase 1 and caspase 3 were tested by flow cytometry, HE and PAS staining, and immunohistochemistry. The expression of cleaved caspase 1/caspase 1 and cleaved caspase 3/caspase 3 was detected by western blot. Results: In clinical trials, the levels of IL-12, IFN-γ, and Th1 percentage decreased in pneumonia and asthma children's peripheral blood, while the levels of IL-4 and IL-10 and the percentages MDSCs and Th17 increased. In asthma mice, pathological staining showed that asthma caused lung inflammation and damage, while the OVA + MDSC group was severer. Moreover, the percentages of eosinophils, neutrophils, lymphocytes, and the levels of inflammatory factors, IgE, ROS production, caspase 1, caspase 3, cleaved caspase 1/caspase 1, and cleaved caspase 3/caspase 3 increased in OVA + MDSC group, while the percentage of macrophages, IL-12, and IFN-γ levels reduced, illustrating that MDSCs exacerbated asthma. Conclusion: Our study indicated that MDSCs could aggravate asthma by regulating the Th1/Th2/Th17 response.

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.

Angiotensin-converting enzyme insertion/deletion polymorphism and susceptibility to pediatric asthma: A meta-analysis.

OBJECTIVE: The correlation of the angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism with pediatric asthma risk was assessed in this meta-analysis. METHODS: PubMed, Web of Science, Embase and CNKI databases were systematically searched for relevant literature, followed by application of odds ratios (OR) along with 95% confidence interval (CI) for determining the strength of relationship. RESULTS: Seven articles with 802 cases and 632 controls fulfilled the inclusion criteria. As a result, the ACE I/D polymorphism was related to elevated pediatric asthma risk (D vs I: OR = 1.87, 95% CI = 1.59-2.20; dominant model: OR =1.53, 95% CI = 1.28-1.81; recessive model: OR =1.54, 95% CI = 1.28-1.85; DD vs II: OR =2.95, 95% CI = 2.19-3.98; DI vs II: OR = 0.96, 95% CI = 0.78-1.19). Subgroup analysis stratified by race revealed significant interrelation in Asians. CONCLUSION: This meta-analysis demonstrated that the ACE I/D polymorphism might be related to the risk of pediatric asthma.

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.

[Study on negative expiratory pressure technique in children with bronchial asthma].

OBJECTIVE: To investigate the clinical significance of children bronchial asthma detection by using negative expiratory pressure (NEP) technique. METHODS: The children with bronchial asthma admitted to Department of Pediatrics of Zhejiang Provincial Integrated Traditional Chinese and Western Medicine Hospital from March 2016 to March 2018 were enrolled. They were divided into mild group (0-4 scores) and severe group (5-12 scores) according to asthma clinical scoring criteria. The children undergoing physical examination at the same period were served as healthy control group. NEP technique and tidal volume (VT) were detected by the pulmonary function instrument. Respiratory flow-volume curves (F-V curves) without NEP were compared with tidal F-V curves after NEP application to assess expiratory flow limitation (EFL). EFL index was calculated according to the percentage of expiratory VT after EFL and expiratory VT when NEP was not used. Pearson correlation method was used to analyze the relationship between EFL index and severity of bronchial asthma. Receiver operating characteristic (ROC) curve was plotted to analyze the value of EFL index in evaluating the severity of bronchial asthma in children. RESULTS: A total of 86 children with bronchial asthma were enrolled in the study, and 84 patients completed the test and 2 children withdrew due to other diseases. Finally, 84 patients were included in the final analysis, including 41 mild and 43 severe children. Forty-two healthy children in the same period were served as healthy control group. There was no significant difference in gender or age among the groups, and no adverse reactions occurred during the test. The EFL index of children with bronchial asthma was significantly higher than that of the healthy control group, and it was increased with the severity of the disease [mild group compared with healthy control group: (30.60±6.03)% vs. (6.64±2.37)%, severe group compared with healthy control group: (33.70±5.41)% vs. (6.64±2.37)%, both P < 0.05]. There was no significant difference in respiratory rate (RR) or VT between mild group or severe group and healthy control group [RR (times/min): 31.45±4.18, 32.81±4.07 vs. 31.97±4.01, VT (mL/kg): 6.29±1.14, 5.96±0.90 vs. 6.30±1.20, all P > 0.05]. It was shown by the correlation analysis that EFL index was positively correlated with the severity of asthma (r = 0.836, P = 0.000). It was shown by ROC curve analysis that the area under ROC curve (AUC) of EFL index for predicting the severity of bronchial asthma in children was 0.801 [95% confidence interval (95%CI) = 0.725-0.878]; when the best cut-off value of EFL index was 29.21%, the sensitivity was 85.7%, the specificity was 69.2%, the positive predictive value was 75.1%, and the negative predictive value was 60.2%. CONCLUSIONS: The EFL index measured by NEP technology was closely related to the severity of bronchial asthma. The higher the EFL index, the more serious of the condition. The severity of bronchial asthma could be early judged by EFL index, which provided a basis for the evaluation and treatment of bronchial asthma.

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.

A new acylphloroglucinol glycoside from Solidago altissima L.

A new acylphloroglucinol glycoside was isolated from the leaves of Solidago altissima L. The chemical structure of the glycoside, which has a phloroglucinol moiety with a butyryl side chain, was elucidated based on the analysis of spectroscopic data.