Advances in targeting of miR­10­associated lncRNAs/circRNAs for the management of cancer (Review).

With advancements in sequencing technologies, an increasing number of aberrantly expressed long-non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) have been identified in various types of cancer. lncRNAs and circRNAs are now well-established tumor-influencing factors in cancer, driving not only tumor proliferation and invasion, but also cancer progression, drug resistance and metastatic recurrence. The majority of lncRNAs and circRNAs influence cancer progression by targeting microRNAs (miRNAs/miRs). miR-10a and miR-10b, key members of the miR-10 family, have been shown to play important regulatory roles in cell proliferation, differentiation to cancer progression, and development. Manual evaluation and grouping according to different types of competing endogenous RNA and tumor was performed. The review outlined the current state of knowledge on the regulation of miR-10 family-related lncRNAs and circRNAs. The involvement of lncRNAs and circRNAs in the biogenesis, maturation and function of malignant tumors through the miR-10 family, and the key gene targets and signaling cascades that lncRNAs and circRNAs regulate through the miR-10 family were summarized. Based on the findings of this review, it can be hypothesized that lncRNAs and circRNAs targeting the miR-10 family may serve as diagnostic/prognostic markers and/or therapeutic targets for the management of cancer.

Meta-Analysis of Long-Term Efficacy of Proliferative Diabetic Retinopathy Based on Intelligent Medical Treatment.

In order to solve some problems of subhealth and high chronic diseases, the diagnosis and treatment of value-added diabetic retinopathy are studied. In particular, diabetes, a high chronic disease, poses a great threat to people's health. With the continuous improvement of national health awareness, the medical field also begins to pay more attention to the diagnosis and treatment of value-added diabetic retinopathy. In order to improve the long-term treatment of value-added diabetic retinopathy through intelligent medical monitoring and systematic scientific efficacy analysis and evaluation, the purpose of this study is to explore how to effectively achieve the meta-analysis of long-term efficacy of proliferative diabetic retinopathy through intelligent medical treatment. Through the study of diabetic retinopathy, the system can help doctors to achieve unlimited further signs of parameter acquisition and transmission and build more mature after treatment of the results of the monitoring platform. At the same time, a conclusion based on vitrectomy was proposed to effectively improve the surgical efficacy of patients with proliferative diabetic retinopathy.

Down-regulation of LCN2 attenuates retinal vascular dysfunction and caspase-1-mediated pyroptosis in diabetes mellitus.

Background: Diabetic retinopathy (DR) is a diabetic microangiopathy with increasing incidence, which seriously threatens the quality of life of patients. This study investigated the molecular regulation mechanism of lipocalin-2 (LCN2) in DR by targeting the function of human retinal vascular endothelial cells (HRVECs). Methods: The expression of LCN2 in the retinal tissue of diabetic and high glucose (HG)-induced HRVECs was detected by reverse transcription quantitative polymerase chain reaction (RT-qPCR) analysis and western blotting assay. After intravitreal injection of adeno-associated virus (AAV)-NC or AAV-sh-LCN2, in vivo experiments, hematoxylin and eosin (H&E) staining, and retinal trypsin digestion experiments were performed to analyze the effect of LCN2 silencing on DR retinal tissue. Terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL) staining was used to evaluate apoptosis and immunohistochemical (IHC) staining was performed to detect the expressions of caspase-1. Western blot was used to detect the expressions of pyroptosis-associated proteins. After transfection of sh-NC and sh-LCN2, the function of HRVECs cells induced by HG was evaluated by wound healing assay, Transwell assay, and tube formation assay. Results: The expression of LCN2 was significantly up-regulated in diabetic retinal tissue and HG-induced HRVECs. In vivo experiments showed that LCN2 silencing can significantly reduce diabetic retinal injury. Cell function experiments also revealed that LCN2 silencing inhibited cell migration, invasion, and angiogenesis. Flow cytometry and immunofluorescence staining showed that downregulation of LCN2 could inhibit caspase-1 mediated pyroptosis in HG-induced HRVECs. Conclusions: Down-regulation of LCN2 can significantly inhibit cell migration, invasion, and angiopoiesis, and pyroptosis regulated by caspase-1, thus attenuating the progression of DR.

The better surgical timing and approach for orbital fracture: a systematic review and meta-analysis.

Background: A large number of empirical studies on the surgical timing and approach of orbital fracture have been published, but which surgical timing and approach is better is still a dispute. We use a systematic review and meta-analysis to solve this problem. Methods: We performed a systematic search in the databases of PubMed, Cochrane Clinical Trials Database, Embase, and Web of Science for relevant literature. The search terms included those concerning or describing orbital fracture, timing, and approach, which are based on population, intervention, control, outcome, and study (PICOS) framework. The statistical software packages RevMan 5.4 and Stata 14.0 were used for data analysis. We sought to evaluate postoperative complications, and results were expressed as odds ratio (OR) with 95% confidence interval (CI). Forest plots, sensitivity analysis, funnel plots, Egger's test, and risk bias analysis were also performed on the included articles by using the Newcastle-Ottawa scale (NOS). Results: A total of 7 trials involving 1,283 patients compared the surgical timing of ≤14 days versus >14 days, and another 14 trials involving 1,768 patients compared the surgical strategy of transconjunctival approach (TCA) with that of subciliary approach (SCA) for orbital fracture. The quality of all articles was higher than 7 points, which means all articles were at low risk of bias. Surgery conducted within 14 days significantly reduced the incidence of diplopia (OR: 0.53, 95% CI: 0.34 to 0.83, P=0.005) and enophthalmos (OR: 0.32, 95% CI: 0.12 to 0.83, P=0.02); TCA had a significantly lower incidence of ectropion (OR: 0.20, 95% CI: 0.10 to 0.38, P<0.00001), scleral show (OR: 0.22, 95% CI: 0.12 to 0.38, P<0.00001), and visible scar (OR: 0.15, 95% CI: 0.03 to 0.65, P=0.33) compared to SCA, but had a significantly higher incidence of entropion (OR: 5.41, 95% CI: 1.83 to 15.96, P=0.002). There was no significant publication bias among our included studies. Conclusions: The operation in ≤14 days is better than that in >14 days. However, regarding the choice of surgical approach, TCA and SCA have their advantages and disadvantages, the exploration of which requires further research.

The Efficacy of Glucocorticoids in the Treatment of Nonarteritic Anterior Ischemic Optic Neuropathy: A Systematic Review and Meta-Analysis.

Background: To evaluate the clinical effects and safety of glucocorticoids for patients with nonarteritic anterior ischemic optic neuropathy (NAION). Methods: The databases MEDLINE, Embase, PubMed, Cochrane Database, and Web of Science were used to search for the relevant studies, and full-text articles that reported on the evaluation of glucocorticoids vs. no-treatment or placebo for patients with NAION. Review Manager 5.4 was used to estimate the pooled effects of the results among selected studies. Forest plots, funnel plots, and Begg's rank correlation were also performed on the included articles. Results: A total of 983 patients were contained in the 9 studies that satisfied the eligibility criteria. The meta-analysis showed that, compared with the control group, the glucocorticoid group had significantly improved the VA (MD: -0.25, 95% CI [-0.45, -0.05], P = 0.02), VF (MD: -0.50, 95% CI [-0.94, -0.07], P = 0.02), and RNFL (MD: -14.10, 95% CI [-26.41, -1.79], P = 0.02) in NAION patients and had a high improvement rate of VA (RR 1.31, 95% CI [1.12, 1.52], P = 0.0005). No significant publication bias was observed in our study. Discussion. Our research preliminarily confirmed the effectiveness of glucocorticoids for NAION treatment, but more high-quality RCTs focusing on the hormone adverse reactions should be performed to verify our conclusions.

Can dorzolamide/timolol-fixed combination effectively treat primary open-angle glaucoma?: A protocol for systematic review and meta-analysis.

BACKGROUND: Primary open-angle glaucoma (POAG) is a very common disorder, and it is the second leading cause that results in blindness worldwide after cataracts. Previous studies have reported that dorzolamide/timolol-fixed combination (DTFC) can be used in treating POAG. However, there are still inconsistent results. Thus, this study will systematically investigate the efficacy and safety of DTFC on POAG. METHODS: A comprehensive search will be carried out in Cochrane Library, MEDLINE, EMBASE, CINAHI, ACMD, China National Knowledge Infrastructure, and WANGFANG database from origin to the present. There are no limitations related to the language and publication status. Only randomized controlled trials that assessed the efficacy and safety of DTFC for the treatment of POAG will be included. Two researchers will independently undertake record selection, data extraction, and study quality assessment. Any divisions will be solved by discussion with a third researcher. We will perform statistical analysis using RevMan 5.3 software RESULTS:: This study will summarize the present evidence to identify the efficacy and safety of DTFC in treating POAG through mean intraocular pressure, best corrected visual acuity, contrast sensitivity, bioelectric activity of the retina, rate of progression of glaucoma, quality of life, and adverse events. CONCLUSIONS: The results of this study will provide evidence of DTFC for the treatment of POAG. SYSTEMATIC REVIEW REGISTRATION: INPLASY202040120.

Efficacy of transconjunctival approach for the treatment of orbital fractures: A protocol for systematic review and meta-analysis.

BACKGROUND: This study aims to assess the efficacy of transconjunctival approach (TCA) for the treatment of orbital fractures (OF) comprehensively and systematically. METHODS: In this study, we plan to search electronic databases of Cochrane Library, MEDLINE, EMBASE, Web of Science, Allied and Complementary Medicine Database, Chinese Biomedical Literature Database, China National Knowledge Infrastructure and for relevant randomized controlled trials. All these databases will be searched from inception to the March 1, 2020 without limitations of language and publication status. Two independent authors will carry out study selection, data collection, and study quality assessment. Any disagreements will be resolved by discussion with another author if necessary. The study quality will be assessed using Cochrane risk of bias tool. Statistical analysis will be conducted using RevMan 5.3 software. RESULTS: This study will be the first 1 to exert direct evidence to evaluate the efficacy of TCA for the treatment of OF. CONCLUSIONS: The findings of this study will provide an exhaustive view of TCA for the treatment of OF. STUDY REGISTRATION NUMBER: INPLASY202040154.

Can neuroprotection effectively manage primary open-angle glaucoma? a protocol of systematic review and meta-analysis.

BACKGROUND: This study aims to assess the efficacy of neuroprotection (NP) for the management of patients with primary open-angle glaucoma (POAG). METHODS: A comprehensive search will be carried out from the beginning to the February 29, 2020 in the electronic databases: Scopus, Web of Science, PUBMED, EMBASE, Cochrane Library, Cumulative Index to Nursing and Allied Health Literature, WANGFANG, and China National Knowledge Infrastructure. There are no limitations related to the language and publication date. Two researchers will independently undertake study selection from searched literatures, extract data from included trials, and appraise study quality using Cochrane risk of bias tool. Any disagreements will be solved by a third researcher through consultation. RevMan 5.3 software will be employed for statistical analysis. RESULTS: This study will provide a high-quality synthesis of randomized controlled trials of NP for the management of patients with POAG. CONCLUSIONS: The results of this study will help to create proposals for the treatment of POAG using NP. SYSTEMATIC REVIEW REGISTRATION: INPLASY202040107.

Th17 cells in glaucoma patients promote Ig production in IL-17A and IL-21-dependent manner.

Elevated expression of autoantibodies is a hallmark of immune dysregulation in glaucoma and may cause retinal ganglion cell apoptosis and immune-mediated nerve damage, thus contributing to the development of blindness. The cause of autoantibody upregulation remains unclear. Th17 cells are shown to promote autoimmunity and Ig production. Here, we demonstrate that the serum levels of interleukin (IL)-17A and IL-21 are comparable between glaucoma patients and non-glaucoma controls. However, the levels of Th17-promoting cytokines, such as tumour necrosis factor (TNF) IL-6, are higher in glaucoma patients than in controls. Subsequently, we demonstrate that glaucoma patients present upregulated levels of Th17 cells that are quiescent directly ex vivo. Interestingly, compared to the Th17 cells from non-glaucoma subjects, the Th17 cells from glaucoma patients present similar IL-17A production capacity but significantly higher IL-21 production capacity. Given that IL-21 is also described as a specific cytokine of follicular helper T cells, the Ig production by B cells following co-incubation with circulating Th17 cells is investigated. Th17 cells from glaucoma patients present significantly enhanced potential to promote Ig production than the Th17 cells from controls. Both glaucoma patient Th17 cells and control Th17 cells require IL-17A and IL-21 for Ig production. Overall, results from this study suggest that Th17 cells from glaucoma patients present elevated capacity to stimulate Ig production.

Therapeutic effect of lutein supplement on non-proliferative diabetic retinopathy: A retrospective study.

This study retrospectively evaluated the effect of lutein supplement (LS) on patients with non-proliferative diabetic retinopathy (NPDR).A total of 72 patients with NPDR were included in this study. All patients received Zeaxanthin during the study period. In addition, 36 patients also received LS and were assigned to the treatment group, while the other 36 patients did not receive LS and were assigned to the control group. All patients were treated for a total of 4 months. The endpoints included visual acuity (VA), contrast sensitivity (CS), and glare sensitivity (GS). In addition, any adverse events were also assessed. All endpoints were measured before and after 4-month treatment.Before treatment, there were no significant differences in VA (P = .75), CS (P = .71), and GS (P = .73) between two groups. After 4-month treatment, there were still no significant differences in all endpoints of VA (P = .66), CS (P = .58), and GS (P = .61) between two groups. No adverse events were recorded in either group.The results of this retrospective study showed that LS may not benefit for patients with NPDR after 4-month treatment. More high quality randomized controlled trials should still be needed to warrant the results of this study.

Efficacy of ranibizumab for the treatment of diabetic retinopathy: A protocol for systematic review of randomized controlled trial.

BACKGROUND: Previous clinical trials have reported that ranibizumab can be used to treat diabetic retinopathy (DR) effectively. However, no study has been conducted to evaluate its efficacy for patients with DR systematically. Thus, this study will specifically and systematically assess the efficacy and safety of ranibizumab for DR. METHODS: Cochrane Library, EMBASE, PUBMED, Web of Science, Google Scholar, Cumulative Index to Nursing and Allied Health Literature, China National Knowledge Infrastructure, and Chinese Biomedical Literature Database will be searched from inceptions to the March 20, 2019 for studies related to the topic. This study will only consider publicly released randomized controlled trials for evaluating the effect and safety of ranibizumab for DR. No language restrictions will be imposed for all databases search. Methodological quality of each included trial will be assessed by Cochrane risk of bias tool. Statistical analysis will be performed by Stata 12.0 software. RESULTS: This study will provide recent summary evidence of ranibizumab for DR. Primary outcomes include percentages with retinopathy improvement, and cumulative probabilities for retinopathy worsening. Secondary outcome consist of visual function, best-corrected visual acuities, central subfield thickness, total macular volume, peripheral visual field loss, retinal neovascularization, and adverse events. CONCLUSION: The findings of this study may provide theoretical basis for clinical practice refer and may benefit more patients with DR.

Efficacy of fenofibrate for diabetic retinopathy: A systematic review protocol.

BACKGROUND: Numerous studies have reported the efficacy of fenofibrate for patients with diabetic retinopathy (DRP). No systematic review has, however, addressed its efficacy for DRP. Thus, this systematic review will firstly evaluate the efficacy and safety of fenofibrate for patients with DRP. METHODS: This study will search the following databases: PUMBED, EMBASE, CINAHI, ACMD, CENTRAL, CBM, CNKI, VIP, and WANGFANG, along with grey literature from inception to the present. We will accept randomized controlled trials on evaluating the efficacy and safety of fenofibrate for DRP. The primary outcome is the progression of DRP. The secondary outcomes are vision loss, development of diabetic macular edema, aggravation of hard exudates, quality of life, and any adverse events. Methodological quality of each included study will be assessed by using Cochrane Collaboration risk of bias tool. In addition, Grading of Recommendations Assessment, Development and Evaluation tool will also be used to evaluate the overall strength of the evidence. Two independent reviewers will conduct all procedures of study selection, data extraction, and methodological assessment. Any disagreements will be consulted with a third reviewer. RevMan 5.3 software will be used to pool data and to carry out the meta-analysis if it is possible. RESULTS: In present study, we anticipate to find a considerable number of published studies presenting evidence on efficacy and safety of fenofibrate for DRP. CONCLUSION: The findings of this systematic review will provide latest evidence of fenofibrate for patients with DRP. DISSEMINATION AND ETHICS: The findings of this scoping review will be disseminated in print, conferences, or by peer-reviewed journals. No ethical approval is needed for this systematic review, because it is a literature-based study. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42019121869.

[Effect of pyruvate on polyol pathway and lens epithelium apoptosis in diabetic rats].

OBJECTIVE: To investigate the effect of polyol pathway on the lens epithelium apoptosis and caspase-3 activity and its reversal by pyruvate in diabetic rats. METHODS: Two hundred and twenty Wistar rats were divided into 3 groups: control group (60 rats), experiment group (80 rats) and treatment group (80 rats). After streptozotocin (STZ) induced cataract, the treatment group received 2% pyruvate in the diet and drinking. Lens opacification was detected by microscope every 2 weeks. Amounts of glucose and sorbitol in the lens were quantified by high-performance liquid chromatography 4, 8 and 12 weeks after the treatment. The percentage of lens epithelium undergoing apoptosis was measured by Annexin V-PI staining. The activity of caspase-3 was analyzed by Western-blot. RESULTS: Present study showed that there was significant increase of glucose and sorbitol in the lens in the experiment group, the apoptosis rate and caspase-3 activity of lens epithelium were also gradually increased. Pyruvate treatment decreased the levels of sorbitol, glucose, lens epithelium apoptosis and caspase-3 activity. The progress of cataract was also significantly delayed. CONCLUSIONS: Activation of polyol pathway, possibly through regulation of the activity of caspase-3, can induce apoptosis of the lens epithelium. Pyruvate ingested orally can effectively inhibit diabetic cataractogenesis in rats through inhibit polyol pathway.

Effect of pyruvate on polyol pathway and lens epithelial cells apoptosis in diabetic rats.

PURPOSE: To investigate the effect of polyol pathway on lens epithelial cells apoptosis and the activity of caspase-3 and its reversal by pyruvate in diabetic rats. METHODS: 220 Wistar rats were divided into 3 groups: control group, model group and treatment group. After streptozotocin (STZ) induced cataract, the treatment group received 2% pyruvate in the diet and drinking. The opacification of lens was detected by microscope every 2 weeks. On 4W, 8W and 12W of the experiment, glucose and sorbitol in the lens were quantified by high-performance liquid chromatography. The percentage of lens epithelial cells undergoing apoptosis was measured by Annexin V/PI staining. The activity of caspase-3 was analyzed by Western-blot. RESULTS: Studies show that there was significant increase of glucose, sorbitol in lens of model group, the apoptosis rate and caspase-3 activity of lens epithelial cells were also gradually increase. Pyruvate treatment decreased the levels of sorbitol, glucose, lens epithelial cells apoptosis and caspase-3 activity. The progress of cataract was also significantly delayed. CONCLUSIONS: Polyol pathway, possibly through regulation of the activity of caspase-3, can induce apoptosis of lens epithelial cell. Pyruvate ingested orally can effective inhibit diabetic cataractogenesis in rats through inhibit polyol pathway.