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With the development of modern societies and the ageing of the population, the treatment of menopausal dry eye disease (MDED) has become a thorny issue for the medical profession. Erxian Decoction (EXD) is a traditional Chinese medicine prescription, which has performed good clinical effect on dry eye disease. In this research, we purposed to investigate the molecular mechanisms of EXD for the treatment of MDED. A MDED rat model was established, the results indicated that high concentration of EXD could significantly improve the tear secretion and tear film stability of the animal model. Next, we found that EXD worked through the LFA-1/ICAM-1/STAT3 pathway in the body, and EXD could regulate IL-17, IL-10, CTLA-4 and TGF-ß1 to get Th17/Treg balance. In vitro experiments, the results indicated that EXD affected the differentiation of CD4+ T cells into Th17/Treg cells by inhibiting the expression and activation of LFA-1 on CD4+ T cells, thus exerting immunotherapy effect. Our research provided the experimental basis and associated mechanisms for the clinical application of EXD in dry eye disease.

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This study aimed to investigate the effect of Yiqi Jiedu (YQJD) formula on the repair of corneal lesions in mice with recurrent herpes simplex virus keratitis (HSK). Sixty female BALB/c mice were randomly divided into three groups: a normal control group (Naive), a recurrence model group (Re), and a YQJD group. After inducing recurrence by ultraviolet irradiation, the ocular surfaces of different groups of mice were observed using a slit lamp and photographed, and ocular surface scores were calculated. The abundance of CD4+CD25+Foxp3+ regulatory T (Treg) cells was determined by flow cytometry in peripheral blood and spleen cells. The CD4+Foxp3+ Tregs were assessed by immunofluorescence in the cornea. The levels of the cytokines IL-10 and TGF-ß in serum and splenocyte culture supernatants were detected by enzyme-linked immunosorbent assay. Furthermore, the activation status of the STAT5 signaling pathway was examined by protein blotting, and the effect of YQJD on Treg cells through inhibition of the STAT5 pathway was observed in vitro. YQJD alleviated corneal inflammation by enhancing the STAT5 signaling pathway, thereby promoting the differentiation of CD4+CD25+Foxp3+ Treg cells, increasing the levels of anti-inflammatory cytokines such as IL-10 and TGF-ß, and maintaining immune tolerance. YQJD increased the proportion of CD4+Foxp3+ Treg cells; also, in the cornea, YQJD inhibited the aggregation of macrophages and CD4+ cells and reduced the proportion of Th17 cells and other pro-inflammatory cells. Moreover, YQJD promoted the secretion of IL-4 to protect the cornea, leading to the mitigation of corneal immunopathological damage. YQJD reduced corneal lesions in recurrent HSK mice by stimulating Treg cells, inducing immune tolerance, and inhibiting corneal immunopathological responses via modulation of the STAT5 signaling pathway.

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BACKGROUND: Diabetic retinopathy (DR) is a common and serious microvascular complication of diabetes. Taohong Siwu decoction (THSWD), a famous traditional Chinese medicine (TCM) prescription, has been proved to have a good clinical effect on DR, whereas its molecular mechanism remains unclear. Our study aimed to uncover the core targets and signaling pathways of THSWD against DR. METHODS: First, the active ingredients of THSWD were searched from Traditional Chinese Medicine Systems Pharmacology (TCMSP) Database. Second, the targets of active ingredients were identified from ChemMapper and PharmMapper databases. Third, DR associated targets were searched from DisGeNET, DrugBank and Therapeutic Target Database (TTD). Subsequently, the common targets of active ingredients and DR were found and analyzed in STRING database. DAVID database and ClueGo plug-in software were used to carry out the gene ontology (GO) and KEGG enrichment analysis. The core signaling pathway network of "herb-ingredient-target" was constructed by the Cytoscape software. Finally, the key genes of THSWD against DR were validated by quantitative real-time PCR (qRT-PCR). RESULTS: A total of 2340 targets of 61 active ingredients in THSWD were obtained. Simultaneously, a total of 263 DR-associated targets were also obtained. Then, 67 common targets were found by overlapping them, and 23 core targets were identified from protein-protein interaction (PPI) network. Response to hypoxia was found as the top GO term of biological process, and HIF-1 signaling pathway was found as the top KEGG pathway. Among the key genes in HIF-1 pathway, the mRNA expression levels of VEGFA, SERPINE1 and NOS2 were significantly down-regulated by THSWD (P < 0.05), and NOS3 and HMOX1 were significantly up-regulated (P < 0.05). CONCLUSION: THSWD had a protective effect on DR via regulating HIF-1 signaling pathway and other important pathways. This study might provide a theoretical basis for the application of THSWD and the development of new drugs for the treatment of DR.

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Background: We aimed to identify the functional brain networks involved in the regulation of visual accommodation by contrasting the cortical functional areas evoked by foveal fixation to an "E" target, which were subservient to the accommodation responses to a -3/-6 diopter stimulus. Methods: Neural activity was assessed in healthy volunteers by changes in blood oxygen level-dependent (BOLD) signals measured with functional magnetic resonance imaging (fMRI). Twenty-five right-handed subjects viewed the "E" target presented in a hierarchical block design. They participated in two monocular tasks: (i) sustained foveal fixation upon an "E" target on a white background at 33 cm (-3.03D accommodative demand); and (ii) sustained fixation through an attached -3D concave lens (-6D accommodative demand) in front of the fixated eye; each condition cycled through a standard alternating 30-s eye open/30-s eye closed design to provide the BOLD contrast. The total sustained period was 480 s. Results: The contrast between the -3D and the rest condition revealed activation in the occipital lobe (Lingual gyrus, Cuneus, Calcarine_L, and Calcarine_R); cerebellum (Cerebellum_Crus1_L and Cerebellum_6_L); precentral lobe (Precentral_R); frontal lobe (Frontal_Inf_Oper_R and Frontal_Mid_R); and cingulate cortex (Cingulum_Ant_L). With the -3D concave lenses (-6D accommodative demand) in front of the fixated eye, the voxel size and peak intensity of activation in the occipital lobe and cerebellum were greater than with the -3D accommodative demand; emergent activated brain areas included the parietal lobe (bilateral precuneus gyrus and right supramarginal gyrus); the precentral lobe and cingulate cortex failed to reach the threshold in the -6D vs. rest contrast. In the -3D and -6D contrast comparison, the frontal lobe (Frontal_Sup_Medial_L) and parietal lobe (Precuneus_L and Precuneus_R) passed the significance threshold of cluster-level family-wise error (FWE) correction. The mean activation in the -3D and -6D contrast revealed an incremental summation of the activations than that found in the previous -3D vs. rest and -6D vs. rest comparisons. Conclusions: Neural circuits were selectively activated during the -3D/-6D accommodative response to blur cues. Cognitive-perceptual processing is involved in signal regulation of ocular accommodative functions.

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Purpose: Conjunctivochalasis (CCH) is a common ocular disease and has received extensive attention recently. However, its exact pathogenesis remains largely unknown. Owing to the high morbidity of CCH in older people, this study aimed to investigate whether cellular senescence contributes to CCH progression and the underlying mechanism. Methods: Loose conjunctival tissues from CCH patients (n = 13) and normal conjunctival tissues from age-matched persons (n = 12) were obtained and the fibroblasts were separately induced and obtained. Cellular senescence, and the expression of senescence-associated genes (p53 and p21) and p38 in CCH conjunctival tissues and normal controls, were determined by senescence-associated ß-galactosidase (SA-ß-Gal) staining and quantitative (q)RT-PCR, respectively. To explore the effects of p38 on cellular senescence in CCH fibroblasts, small interfering RNA (siRNA) targeting p38 (siP38) and p38-specific inhibitor SB203580 was performed in CCH fibroblasts. Then, cellular senescence, cell viability, reactive oxygen species (ROS) production, and gene expression were detected according to the corresponding methods. Results: CCH conjunctival tissues had significantly more senescent cells, evidenced by more SA-ß-Gal-positive cells, and higher expression of senescence-associated genes (p53 and p21) and p38. CCH fibroblasts transfected with siP38 or treated with SB203580 had obviously reduced numbers of senescent cells, decreased ROS production, and increased cell viability, as well as reduced expression of senescence-associated genes. Meanwhile, blocking p38 signaling decreased the expression of p53 and p21. Conclusions: Therefore, these findings indicate that cellular senescence might be a causative factor for CCH. P38 signaling might play an important role in the progress of cellular senescence in CCH fibroblasts via manipulation of p53/p21 signaling.

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BACKGROUND: With the aging of the population and the use of video terminals, the incidence of Conjunctivochalasis is getting higher, and related research is increasing. So our research aimed to use visualization software to display the research trends of Conjunctivochalasis. METHODS: Retrieved the document (from 1986 to 2017) of conjunctivochalasis in the web of science core collection, analyzed by Citespace V. RESULTS: The main language is English. Article is the key type of document. The average annual number of publications in the time period from 2008 to 2017 was 11.6, which was significantly higher than the period from 1994 to 2007, indicating that the total number of publications has been continuously developed. The law of frequency quoted showed an upward trend yearly. Furthermore, we can find out that Japan, USA, and People's Republic of China were the most productive countries, Kyoto Prefectural University of Medicine was the most prolific institution, Shanghai Jiaotong University is a key institution. The average IF of journals was 3.0508. Cornea and Canadian Journal of Ophthalmology are core journals. Tseng SCG is the most active scholar. All cited author contributed to 5 classifications. Di PMA paper is a classic literature. Huang YK paper can be regarded as the frontier document. All cited-reference dedicated to 7 categories. Conjunctivochalasis is the hot topic, related to observe indicators, risk factors, treatment, graded diagnosis of conjunctivochalasis, etc. In addition, fibroblast was research hotspot. At length, the cluster map of keyword was divided into 7 categories. CONCLUSION: This research will help relevant clinicians and researchers to accurately and quickly grasp the research trends in the field, and continue to conduct new research on the basis.

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Diabetic mellitus (DM), commonly referred to diabetes, is a worldwide metabolic disorder, which usually causes high morbidity and mortality rates. Especially, DM may result in serious macrovascular problems including cataract. To investigate the underlying molecular mechanism, here we for the first time employed gas chromatography-time-of-flight mass spectrometry (GC-TOF MS) for an untargeted metabolomics study. Totally 263 metabolites were determined in aqueous humor (AH) samples from 30 patients: 15 for the controls and 15 with DM. Both the heat map and principal component analysis (PCA) plot showed a significantly distinct metabolomics profiles between patients with DM and the controls. Moreover, 20 metabolites were determined to be significantly altered (P ≤ 0.05) in DM patients, some of which were associated with oxidative stress. Metabolic pathway analysis of these significantly different metabolites identified ten most relevant pathways in the group of DM patients when compared with the control group. Among them, three pathways including fatty acid biosynthesis, fatty acid metabolism, and linoleic acid metabolism were the three most significantly influenced pathways (P ≤ 0.05), which probably play key roles in the formation of DM and its complication, cataracts. Altogether, this work not only indicated a distinct AH metabolomic profile in association with DM, but presented novel insights into the molecular mechanisms of DM formation, as well as formation of cataracts.

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BACKGROUND: With the understanding of the immune inflammatory response in the pathogenesis of dry eyes, and the limitations of widely used artificial tears and numerous pharmaceuticals and methods to promote tear secretion, clinicians pay more attention to the therapies that can promote tear secretion actively. Acupuncture treatment for dry eye may meet this requirement. OBJECTIVE: To observe the clinical efficacy of acupuncture treatment on dry eye and the effects on duration, and to examine the mechanisms of acupuncture in treating patients with dye eyes. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: The study was performed at Department of Ophthalmology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine from August 2010 to May 2011. Patients with the primary diagnosis of dry eye were enrolled. Sixty-five patients were randomly divided into treatment group and control group, and were given 3 weeks of acupuncture treatment or artificial tear therapy respectively. MAIN OUTCOME MEASURES: The enzyme-linked immunosorbent assay was used to detect the lactoferrin content of the tears before and after treatment. In order to evaluate the efficacy of the treatment methods, the Schirmer I test and break-up time were also measured. RESULTS: Compared with before treatment, the lactoferrin content in the tears of patients in the treatment group increased, break-up time was prolonged and the result of the Schirmer I test showed improvement after 3 weeks of treatment. The indexes mentioned above did not change in the control group after treatment. There were no significant differences in tear lactoferrin and Schirmer I test between one week after treatment and after 3-week treatment in the treatment group, but break-up time was significantly shortened. The result of Schirmer I test in the treatment group was significantly higher than that in the control group one week after treatment. CONCLUSION: Acupuncture can increase tear lactoferrin level, extend tear film break-up time and promote tear secretion in patients with dry eye in a time-limited trial. With the end of treatment, the effect decreased.

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