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Purpose. To investigate the hyperreflective foci (HRF) as an inflammatory biomarker using optical coherence tomography angiography (OCTA) in neovascular age-related macular degeneration (AMD) patients after antivascular endothelial growth factor (anti-VEGF) treatment and its association with the retinal microcapillary density. Methods. Twenty-five eyes from 25 patients with neovascular AMD were included in the study. All eyes were imaged with OCTA at baseline (M0) and after 3 consecutive injections (M3; injection performed each month) of anti-VEGF. The number of HRF in the superficial capillary plexus (SCP), deep capillary plexus (DCP), and outer retina was counted. The vascular density of the fovea, parafovea, and the whole macula, as well as the area of the foveal avascular zone (FAZ), was measured. Results. The mean interval between baseline and follow-up with OCTA was 93.08 ± 5.00 (range, 85-101) days. Compared with the baseline, the number of HRF significantly decreased in DCP ( 7.52 ± 3.06 vs. 3.76 ± 1.48 , P < 0.01 ) and outer retina ( 12.04 ± 4.91 vs. 5.88 ± 3.32 , P < 0.01 ) after treatment. There was no significant difference for HRF number in the SCP, the vascular density (containing foveal, parafoveal, and whole macular), and FAZ area before and after treatments. Conclusion. The number of HRF in DCP and outer retina might serve as an inflammatory biomarker in patients with neovascular AMD. The reduced HRF possibly represents the alleviation of inflammation after anti-VEGF treatment in patients with AMD.

The pathophysiology of diabetic retinopathy (DR) was complex. Under hyperglycemic conditions, the release of proinflammatory cytokines and the adhesion of leukocytes to retinal capillaries contribute to endothelial damage and the subsequent increase in vascular permeability resulting in macular edema. Melatonin, produced in the retina to regulate redox reactions and dopamine metabolism, plays protective roles against inflammation and oxidative stress. Considering its anti-inflammatory and antioxidative properties, melatonin was speculated to exert beneficial effects in DR. In this study, we characterized the protective effects of melatonin on the inner blood-retinal barrier (iBRB), as well as the possible mechanisms in experimental DR. Results showed that in diabetic rat retinas, the leakage of iBRB and the expression of inflammatory factors (VEGF, TNF-α, IL-1β, ICAM-1, and MMP9) increased dramatically, while the expression of tight junction proteins (ZO-1, occludin, JAM-A, and claudin-5) decreased significantly. The above changes were largely ameliorated by melatonin. The in vivo data were confirmed in vitro. In addition, the protein expressions of p38 MAPK, NF-κB, and TXNIP were upregulated significantly in diabetes and were downregulated following melatonin treatment. Melatonin could maintain the iBRB integrity by upregulating the expression of tight junction proteins via inhibiting p38/TXNIP/NF-κB pathway, thus decreasing the production of inflammatory factors. This study may shed light on the development of melatonin-based DR therapy.

Background Angiogenesis is an important parameter in the development of diabetic retinopathy (DR), and it is indicative of an early stage evolving into a late phase. Therefore, examining the role of angiogenic factors in early DR is crucial to understanding the mechanism of neovascularization. Methods The present study identified hub genes and pathways associated with angiogenesis in early DR using bioinformatics analysis. Genes from published literature and Gene Expression Omnibus (GEO) were collected and analysed. Results We collected 73 genes from 70 published studies in PubMed, which were referred to as DR-related gene set 1 (DRgset1). The gene expression profile of GSE12610 was downloaded, and 578 differentially expressed genes (DEGs) between diabetic and normal samples were identified. DEGs and DRgset1 were further combined to create DR-related gene set 2 (DRgset2). After an enrichment analysis, we identified 12 GO terms and 2 pathways associated with neovascularization in DRgset1, and 8 GO terms and 2 pathways in DRgset2. We found 39 new genes associated with angiogenesis and verified 8 candidate angiogenesis-related genes in DR cells using real-time PCR: PIK3CB, ALDH3A1, ITGA7, FGF23, THBS1, COL1A1, MAPK13, and AIF1. We identified 10 hub genes associated with neovascularization by constructing a protein-protein interaction (PPI) network: TNF, VEGFA, PIK3CB, TGFB1, EDN1, MMP9, TLR4, PDGFB, MMP2, and THBS1. Conclusions The present study analysed angiogenesis-related genes and pathways in early DR in a comprehensive and systematic manner. PIK3CB, ALDH3A1, ITGA7, FGF23, THBS1, COL1A1, MAPK13, and AIF1 may be the candidate genes to further explore the mechanisms of angiogenesis in early DR. TNF, PIK3CB, TGFB1, EDN1, MMP9, TLR4, PDGFB, MMP2, and THBS1 may be new targets for early neovascularization therapy in the future.

Histone deacetylase inhibitors (HDACis) have displayed neuroprotective effects in animal models of retinal ischemia/reperfusion (I/R) injury. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is a redox-sensitive transcription factor responds to oxidative damage. We investigated the role of Nrf2 in retinal I/R injury, and further explored the mechanisms underlying Nrf2-mediated neuroprotection exerted by HDACi. High intraocular pressure was used to establish retinal I/R model in wild type (WT) and Nrf2 knockout (KO) mice. Nrf2 KO mice displayed more severe retinal damage after I/R. Trichostatin A (TSA) was administered to both WT and Nrf2 KO mice with retinal I/R damage. TSA significantly diminished the retinal ganglion cell degeneration in WT mice but offered no notable protection in Nrf2 KO mice. TSA markedly promoted Nrf2 nuclear translocation and its acetylation. In addition, TSA upregulated Nrf2 downstream proteins, such as Ho-1 and Nqo1, in retinal tissues. In the retinal neuronal cell line 661W, TSA reduced the expression of proinflammatory cytokines, Il-1β, Il-6, Tnf-α and Mmp-9, and it upregulated Bdnf under oxidative stress. However, this trend was not continued after silencing Nrf2. Chromatin immunoprecipitation assay demonstrated that Nrf2 at the Ho-1 promoter significantly increased transcriptional activity after oxidative stress induction. Nrf2, which is dispensable in HDACi-mediated neuroprotection, plays a major neuroprotective role in retinal I/R injury.

This study was conducted to explore the proper time required to achieve stabilization in digestibility, serum metabolism, and rumen fermentation characteristics when different diets shift, thus providing decision-making of practical sampling frequency for basal nutritional research. For these purposes, 12 Holstein steers (body weight 467 ± 34 kg, age 14 ± 0.5 months) were equally assigned to two dietary treatments: high-density (metabolizable energy (ME) = 2.53 Mcal/kg and crude protein (CP) = 119 g/kg, both ME and CP were expressed on a dry matter basis) or low-density (ME = 2.35 Mcal/kg and CP = 105 g/kg). The samples of feces, serum, and rumen contents were collected with a 30-day interval. All data involved in this study were analyzed using the repeated measures in mixed model of SPSS. Results showed that nutrient apparent digestibility and serum metabolic parameters were stable across each monthly collection, while most rumen fermentation characteristics, namely concentrations of acetate, propionate, isobutyrate, and valerate, were affected by the interaction effects between collection period and dietary density. These findings indicate that rumen fermentation characteristics require more time to stabilize when diet shifts. It is recommended to collect ruminal digesta monthly to evaluate rumen fermentation characteristics, while unnecessary to sample monthly for digestion trials and blood tests in the long-term fattening of Holstein steers. This study may provide insights into exploring the associations between detected parameters and stabilization time, and between diet type and stabilization time when diet shifts.

The objectives of this study were to investigate the effects of age and dietary straw levels on growth performance, carcass and meat traits, as well as tissue antioxidant status of Yiling cull cows. Twenty-four Yiling cull cows were arranged in a 2 × 2 factorial design: two age classes consisting of younger cull cows (YCC, appearing with three or four pairs of permanent teeth) and older cull cows (OCC, worn out teeth), two dietary treatments consisting of lower and higher rice straw levels (LRS and HRS, providing 0.7 kg/d and 1.2 kg/d rice straw per head based on air-dry basis, respectively). Cows were fed twice a day. Straw was offered at half of the predetermined weight each meal, concentrate was separately supplied ad libitum. After 300 d of feeding, final body weight (BW), total BW gain, average daily gain and gain:feed intake were higher (p &lt, 0.01) in the YCC group than in the OCC group. Total dry matter intake was higher (p = 0.03) in the HRS group than in the LRS group, but neutral detergent fiber apparent digestibility was negatively affected (p = 0.01) by increased straw levels. Decreased C15:0, C17:0, C20:5n3c, and saturated fatty acids (SFAs) proportion as well as increased C18:1n9c and monounsaturated fatty acids (MUFAs) proportion in meat from YCC with HRS diet were observed as compared to that in meat from YCC with LRS diet (p &lt, 0.05). Meat from HRS group had higher (p = 0.04) C18:3n3c proportion than meat from LRS group. No significant differences (p &gt, 0.05) were found for meat quality attributes except for cooking loss, which was higher (p = 0.02) in the HRS group than in the LRS group. Both YCC group and HRS group had higher (p &lt, 0.05) cold carcass weight compared to OCC group and LRS group. Moreover, catalase activity of liver tissue was higher (p = 0.045) in YCC than in OCC, while superoxide dismutase activity of muscle tissue was higher (p = 0.01) in LRS than in HRS. Based on results, we concluded that younger age and feeding high-level straw can improve the finishing performance of Yiling cull cows.

The dietary energy level can affect ruminal microbiota, and further can affect rumen fermentation and fatty acid (FA) synthesis. In this study, we investigated the correlations between rumen bacteria and rumen fermentation parameters and intramuscular fat (IMF) FA profiles of Holstein bulls fed different energy diets via using 16S rRNA high-throughput sequencing and gas chromatography. The results showed that the improved dietary energy increased propionate, isobutyrate and isovalerate concentrations, and decreased acetate concentration and the acetate/propionate ratio. Increased dietary energy improved beef IMF content and had no effects on cooking loss, Warner-Bratzler shear force, water holding capacity, or drip loss. Increase dietary energy also decreased C18:0, C18:1 trans, C22:0, C20:3n-3, C22:6n-3, and saturated fatty acids, and increased C18:1 cis-9, C18:2n-6 trans, and monounsaturated fatty acids. 16S rRNA high-throughput sequencing analysis revealed that dietary energy had no impact on alpha diversity or the relative abundance of most of the major phyla and genera in rumen. In all dietary treatment groups, the dominant microbial phyla were Bacteroidetes (54.91%) and Firmicutes (33.60%), and the major microbial genus was Prevotella_1 (21.75%). Improved dietary energy decreased the abundances of Firmicutes and Tenericutes and increased that of Proteobacteria at the phylum level, while decreasing those of RC9_gut_group, and increased Prevotellaceae_UCG-004, Phocaeicola, Acetitomaculum, Lachnoclostridium_1, Prevotellaceae_UCG-003, and Anaerovibrio at the genus level. Spearman correlation analysis showed high correlations between rumen bacteria and fermentation parameters/IMF FA profiles. Collectively, our data indicated that dietary energy affects the ruminal microbiota, and further affects ruminal fermentation and IMF FA composition.

The aim of this study was to investigate the impact of dietary crude protein (CP) levels and calcium salts of long-chain fatty acids (CSFA) on the nutrient intake and digestibility, nitrogen deposition, rumen fermentation characteristic and microbiota, plasma biochemical indexes and fatty acid composition in the Holstein bulls. Eight Holstein bulls was used in a 4 × 4 Latin Square design with 2 × 2 factorial diets, including two levels of CP (133 or 112 g/kg dry matter), and with or without 2.32 g/kg CSFA. The high CP level diets increased the CP intake and the CP apparent digestibility and the urinary nitrogen excretion (P = 0.001). Dietary supplementation with CSFA promoted the apparent digestibility of organic matter (P = 0.012). The diets of CSFA and high CP level raised the rumen ammonia nitrogen concentration (P = 0.009), and enhanced the isovalerate and valerate concentrations, respectively. The high CP diets improved the abundance of Butyrivibrio fibrisolvens (P = 0.037) and Megasphaera elsdenii (P = 0.023), while the CSFA reduced the abundance of methanogens (P = 0.047). High CP increased urea concentration (P = 0.008). Dietary supplementation with CSFA increased the cholesterol and the low-density lipoprotein cholesterol concentration in the plasma, and the proportion of C16:0, C18:1n9c and Δ9 desaturase C18, while it reduced the ratio of C21:1 and C22:0. The low CP diets reduced the protein waste and environmental pollution in the final stage of fattening Holstein bulls. Further study needs to be done to investigate the effect of CSFA on the CH4 emission in terms of microbial mechanism in the rumen.

The rumen anaerobic fermentation has been exploited as a molecular platform for producing fermentative biogas and organic acids. The aim of this study was to select more efficient rumen fermentation bacteria by comparing the nutrient degradation rate, rumen fermentation characteristics and bacterial flora between the bulls and heifers. The rumen fluid from bulls and heifers was inoculated to wheat straw for anaerobic fermentation to produce organic acids and biogas. The results showed that the bulls had higher degradation rate of dietary total solids and acid detergent fiber, and had higher concentration of acetate, butyrate, ammoniacal nitrogen, total volatile fatty acids and total fungi in rumen compared with the heifers (P

Immune thrombocytopenia is a common complication in patients in a minimally conscious state (MCS). MCS patients are prone to pulmonary infection for the reasons of long-term bed rest and tracheotomy etc., which leads to frequent immune thrombocytopenia. At present, there is no specific treatment for immune thrombocytopenia. Moreover, the cost of routine treatment is high, and clinicians need to consider different drug combinations, side effects, and the risk of drug dependence when selecting treatments. Here, we report a case of a patient in a MCS who developed immune thrombocytopenia after tracheotomy and long-term bed laying in October 2015. The patient's platelet count declined continuously, and by December 2015, she was in a critical condition, with a platelet count of less than 20×109/L. The patient firstly received routine treatment, however, this could only temporarily prevent the drop in platelets. Following a series of explorations, the patient was treated with a combination of traditional Chinese and Western medicine, which included treatment and preventive measures. For treatment, the patient was given roxithromycin dispersible administration tablets and a self-made preparation of peanut red skin, which could quickly cure the immune thrombocytopenia. Preventive measures included the addition of ursodeoxycholic acid capsules, silybin capsules, and a traditional Chinese medicine preparation. As shown by laboratory examination results, the patient's platelet count has stayed around a normal level since March 2016, and she now has normal liver and kidney function. This outcome evidence that combined traditional Chinese and Western medicine could effectively cure immune thrombocytopenia and prevent its recurrence. Moreover, the cost of the treatment was lower and there were fewer side effects than routine treatment, and at the same time, the method of treatment was simple and convenient. Our practical experience may provide a valuable clue for the treatment of immune thrombocytopenia.

High-altitude retinopathy (HAR) is an ocular manifestation of acute oxygen deficiency at high altitudes. Although the pathophysiology of HAR has been revealed by many studies in recent years, the molecular mechanism is not yet clear. Our study aimed to systematically identify the genes and microRNA (miRNA) and explore the potential biomarkers associated with HAR by integrated bioinformatics analysis. The mRNA and miRNA expression profiles were obtained from the Gene Expression Omnibus database. We performed Gene Ontology functional annotations and Kyoto Encyclopedia of Genes and Genomes pathway analysis. Potential target gene analysis and miRNA–mRNA network analysis were also conducted. Quantitative RT-PCR (qRT-PCR) was used to validate the results of the bioinformatics analysis. Through a series of bioinformatics analyses and experiments, we selected 16 differentially expressed miRNAs (DE-miRNAs) and 157 differentially expressed genes related to acute mountain sickness (AMS) and constructed a miRNA–mRNA network containing 240 relationship pairs. The hub genes were filtered from the protein-protein interaction network: IL7R, FOS, IL10, FCGR2A, DDX3X, CDK1, BCL11B and HNRNPH1, which were all down-regulated in the AMS group. Then, nine up-regulated DE-miRNAs and eight hub genes were verified by qRT-PCR in our hypoxia-induced HAR cell model. The expression of miR-3177-3p, miR-369-3p, miR-603, miR-495, miR-4791, miR-424-5p, FOS, IL10 and IL7R was consistent with our bioinformatics results. In conclusion, FOS, IL10, IL-7R and 7 DE-miRNAs may participate in the development of HAR. Our findings will contribute to the identification of biomarkers and promote the effective prevention and treatment of HAR in the future.

The aim of this study is to track the dynamic alterations in nutrient intake and digestion, rumen fermentation and plasma metabolic characteristics, and rumen bacterial community of Holstein finishing steers in response to three nutrient density diets as fattening phases advanced. A total of eighteen Holstein steers were randomly allocated into three nutrient density groups and steers in each group were fed under a three-phase fattening strategy, with nutrient density increased in each group when fattening phase advanced. Results showed that both fattening phase and dietary nutrient density significantly influenced the nutrient digestion, most of the rumen fermentation parameters, and part of bacteria at phylum and genus levels. Individually, dietary nutrient density affected the concentrations of plasma alanine aminotransferase and urea N, bacterial richness and evenness. All determined nutrient intake and plasma biochemical parameters, except for alanine aminotransferase and triglyceride, differed among fattening phases. Spearman correlation analysis revealed strong correlations between fiber intake and bacterial richness and evenness, rumen fermentation characteristics and certain bacteria. Moreover, Patescibacteria abundance was positively correlated with ambient temperature and plasma total protein. These results indicate that rumen fermentation and nutrient digestion were influenced by both dietary nutrient density and fattening phase, and these influences were regulated by certain rumen bacterial community and ruminal bacteria may be affected simultaneously by ambient temperature. This study may provide insights into diet optimization and potentially adaptive mechanism of rumen bacterial community in response to fattening phases and gradually climatic change.

PURPOSE To compare structural and functional improvements in patients with vitreous haemorrhage (VH) with different IOPs re-established at the end of pars plana vitrectomy (PPV). METHODS It is a prospective, randomized, comparative, interventional study. Ninety-five patients with nonclearing VH were randomized to receive PPV with normalized IOPs of 15 mmHg (Group I: 32 eyes), 25 mmHg (Group II: 32 eyes) and 35 mmHg (Group III: 31 eyes) at the end of surgery. The grade of vitreous opacity and best-corrected visual acuity (BCVA) on postoperative day 1, week 1, month 1 and month 3 were compared with a mixed model for repeated measures analysis. RESULTS All 3 groups achieved significant improvement on postoperatively in BCVA (p

Purpose To elucidate the mechanism whereby miR-590-3p regulates pyroptosis in diabetic retinopathy (DR). Methods Human retinal microvascular endothelial cells (HRMECs) incubated with high glucose (HG) were used to establish cell models, and the expression levels of miR-590-3p, caspase-1, IL-1β, NLRP1, NOX4, TXNIP, NLRP3, and ROS were determined. Additionally, miR-590-3p was altered using a mimic or an inhibitor, and siRNAs targeting NLRP1 and NOX4 were applied to explore the regulatory mechanism of miR-590-3p in DR. The relationships between miR-590-3p and NLRP1/NOX4 also were investigated using a luciferase reporter assay. Furthermore, vitreous tissue samples were collected to confirm pyroptosis in clinical DR. Results Downregulated miR-590-3p and upregulated NLRP1/NOX4 levels were observed in a cell culture model of DR. Inhibiting miR-590-3p upregulated NLRP1, the NOX4/ROS/TXNIP/NLRP3 pathway, and caspase-1. NLRP1 and NOX4 were confirmed as direct target genes of miR-590-3p. The overexpression of miR-590-3p or knockdown of NLRP1 and NOX4 increased cell activity and suppressed pyroptosis. Intriguingly, the upregulation of IL-1β induced the downregulation of miR-590-3p by lowering the DNA promoter activity of pri-miR-590. Conclusions HG induced pyroptosis in a cell culture model of DR, and the downregulation of miR-590-3p promoted pyroptotic death by targeting NLRP1 and activating the NOX4/ROS/TXNIP/NLRP3 pathway via an IL-1β-mediated positive feedback loop.

The objective of this study was to explore whether collecting rumen samples of finishing steers at monthly intervals differed, and whether this difference or similarity varied with diets. For these purposes, 12 Chinese Holstein steers were equally divided into two groups. The dietary treatments were either standard energy and standard protein (C) or low energy and low protein (L). Rumen samples were obtained on day 30, day 60 and day 90 from both dietary treatments and were analyzed by using 16S rRNA gene sequencing. The results showed that monthly intervals had no effect on the richness and evenness of the rumen bacterial community in the two diets. However, taxonomic difference analysis (relative abundance &gt, 0.5%) revealed that the relative abundance of three phyla (Proteobacteria, Fibrobacteres and Cyanobacteria) and six genera (Rikenellaceae_RC9_gut_group, Ruminococcaceae_NK4A214_group, Fibrobacter, Eubacterium_coprostanoligenes_group, Ruminococcaceae_UCG-010 and Ruminobacter) were significantly different between monthly sampling intervals, and the difference was prominent between sampling in the first month and the subsequent two months. Moreover, the differences in abundances of phyla and genera between monthly sampling intervals were affected by diets. Analysis of similarity (ANOSIM) showed no significant differences between monthly sampling intervals in the C diet. However, ANOSIM results revealed that significant differences between the first month and second month and between the first month and third month were present in the L diet. These results indicated that temporal dynamics in rumen bacterial community composition did occur even after an adaptation period of three months. This study tracked the changes in rumen bacterial populations of finishing cattle after a shift in diet with the passage of time. This study may provide insight into bacterial adaptation time to dietary transition in finishing steers.

Twenty-eight male, weaned Chinese Holstein calves ((156.8±33.4) kg) were used to investigate the effects of dietary forage to concentrate ratio (F:C) and forage length on nutrient digestibility, plasma metabolites, ruminal fermentation, and fecal microflora. Animals were randomly allocated to four treatments in a 2×2 factorial arrangement: whole-length forage (WL) with low F:C (50:50); WL with high F:C (65:35); short-length forage (SL) with high F:C (65:35); and SL with low F:C (50:50). Chinese wildrye was used as the only forage source in this trial. The grass in the SL treatments was chopped using a chaff cutter to achieve small particle size (∼50% particles >19 mm). Dry matter intake (DMI) and organic matter (OM) intake was increased by increasing both F:C (P0.05). Microflora similarity was 50–73% among the different treatments. It is concluded that the WL with high F:C (65:35) diet is suitable for weaned calves.

The purpose of this study was to assess the effects of calcium salt of long-chain fatty acids (CSFA) and alfalfa on beef cattle in the late fattening. 48 Holstein bulls were selected and randomly divided into 4 groups, feeding four dietary that Leymus chinensis with (LC) or with no (LN) 2.4% CSFA, and alfalfa replaced 50% Leymus chinensis with (AC) or with no (AN) 2.4% CSFA. The results indicated that alfalfa improved the feed conversion rate (P < 0.05). CSFA increased serum low density lipoprotein cholesterol, and reduced the cooking loss of Longissimus muscle (P < 0.05). CSFA and alfalfa reduced Acetate/Propionate. Alfalfa and CASF had significant additive effects on the apparent digestibility of dry matter, crude protein, neutral detergent fiber, acid detergent fiber, organic matter and rumen fermentation for acetate, isobutyrate, butyrate, isovalerate, total volatile fatty acids (P < 0.05). CSFA increased microbial diversity index when compared with alfalfa (P < 0.05), but no significant differences were detected in bacterial genera abundances among diets. The relative abundances of rumen bacterial genera have significant correlation with apparent digestibility of nutrients, rumen fermentation characteristics and serum biochemical parameters (P < 0.05). These results comprehensively evaluated the additive effects of alfalfa and CSFA on the application in Holstein bulls.

The purpose of this study is to compare the efficacy of intraoperative 360° and localized laser retinopexy in 23-gauge pars plana vitrectomy (PPV) for rhegmatogenous retinal detachments (RRD) with undetected retinal breaks intraoperatively. This is a retrospective, comparative, interventional study. Medical records of 48 consecutive eyes with RRD of intraoperative undetected retinal breaks were reviewed. Nineteen patients (group I) received 360° laser retinopexy in PPV, while the remaining 29 patients (group II) underwent localized laser retinopexy. In group I, a triple row of confluent medium-white laser burns were placed posterior to the ora serrata. Anatomical and visual outcomes of the two groups were compared. The mean follow-up period was 13.46 ± 3.02 months. No significant difference was identified in baseline characteristics. A single-operation reattachment rate of 89.47% was achieved in group I, which was significantly higher than that of group II (55.17%, p = 0.01), and this trend was not weakened after adjustment for the confounding factor (odds ratio 0.15, p = 0.03). Moreover, greater improvement of postoperative best-corrected visual acuity was observed in group I. Significant complications sufficient to require further operation included proliferative vitreoretinopathy in 2 (4.17%) eyes and epiretinal membrane in 4 (8.33%) eyes. Three hundred sixty-degree laser retinopexy was associated with better anatomic and visual outcomes in RRD patients with unseen breaks intraoperatively, when compared with localized laser retinopexy in PPV.

Backgrounds. Age-related macular degeneration is closely related to lipid oxidation, while relationship between OX-LDL and choroidal neovascularization is unclear. Recently, cylindromatosis is proved to regulate angiogenesis. However, its role in CNV progression remained unclear. Salvianolic acid A is widely used in vascular diseases. We investigated the relationship between OX-LDL and CNV and explore antineovascularization mechanism of Sal A. Methods. C57BL6/J mice were randomized into four groups and injected with PBS or OX-LDL, together with Sal A for one week. CNV was induced by laser; CNV severity was analyzed by fundus fluorescein angiography, H&E staining, and choroid flat mount after 1 week. In in vitro experiments, ARPE-19 and HUVECs were cultured with OX-LDL (with or without Sal A) for 48 hours. Angiogenic proteins, cell junction integrity, and tube formation were measured. CYLD siRNA and specific inhibitors were used to explore mechanisms of CYLD in promoting OX-LDL-induced CNV progression. Results. OX-LDL promoted laser-induced CNV volume by increasing VEGF, PDGF, and CYLD levels. Sal A antagonized OX-LDL effects and restrained CNV progression by decreasing VEGF/PDGF/CYLD, increasing antiangiostatin levels, and promoting P62-CYLD-TRAF6 interaction. Conclusions. We demonstrated oxidation damage exacerbates CNV progression, and Sal A could be a clinical therapeutic reagent to exudative AMD.

Background Ocular fundus angiography is an indispensable component of the tests utilized for fundus diseases. Dynamic angiography results can provide additional information; however, many difficulties remain. In this study, we introduce a modified method, time-lapse angiography (TLA), to dynamically present imaging results. Methods TLA, combining time-lapse photography and fundus angiography (using Heidelberg retina angiography II, Germany), includes pre-photographing and post- photosynthesis and ultimately produces a video that is approximately 15 s in length. Results Four typical videos in the article showed the characteristics of TLA, including a short and rapid but continuous and integral presentation, highly valid information, high definition, etc. Conclusions TLA is beneficial for the diagnosis of diseases and the assessment of progression and is convenient for peer communication, patient interpretation, and student education. The application of time-lapse photography in ocular fundus angiography is a monumental and innovative attempt.

Background: We sought to verify the efficacy and safety of transconjunctival 23-gauge pars plana vitrectomy (PPV) alone by our bimanual technique for the removal of dense posteriorly dislocated crystalline lens. Methods: A retrospective, noncomparative, interventional study of 31 consecutive cases of patients who underwent 23-gauge PPV alone for the removal of dense posteriorly dislocated crystalline lens following complicated cataract surgeries using our bimanual technique was conducted. The main outcomes measured included best-corrected visual acuity (BCVA), preoperative intraocular pressure (IOP), postoperative IOP and postoperative complications. Results: In all 31 cases included in this study, those dense posteriorly dislocated crystalline lenses were successfully removed. The enrolled patients consisted of 17 males and 14 females with a mean age of (75.84 ± 6.17) years (range 59 - 90). The mean follow-up length was (7.61 ± 1.87) months with a range of 6 months to 1 year. The mean preoperative BCVA was 0.22 ± 0.11 logMAR system, and the postoperative BCVA was 0.33 ± 0.07 logMAR system after 6 months of follow-up. The mean operative time was 46.32 ± 4.80 minutes with a range of 38.00 to 57.00 minutes. All of the conjunctival incisions self-closed within the first week with no wound leakage or hemorrhage. The postoperative complications were relatively rare. Conclusions: The removal of dense posteriorly dislocated crystalline lens might be a challenge for micro-incision vitrectomy. Our bimanual technique was proved to be an effective and safe method for those particular dense lenses using 23-gauge alone.

Rhegmatogenous retinal detachment (RRD) is an important cause of vision loss worldwide, with an annual incidence rate of 6.3 to 18.9 per 100,000 individuals.1–3 The main treatment modality for RRD is surgical reattachment of the retina, which includes pneumatic retinopexy (PR), scleral buckling (SB), and vitrectomy. Generally, vitrectomy is indicated for relatively complicated RRD.4 However, vitrectomy may be more frequently associated with cataract aggravation, secondary glaucoma, and a high economic burden to poor patients in developing countries.5–7 PR has long been used for the management of RRD because it is convenient and less invasive.8–11 SB cures RRD by releasing vitreous traction, closing the retinal breaks, and bringing the retina and retinal pigment epithelium (RPE) closer to each other.12 Both PR and SB preserve the vitreous. However, they are usually indicated for relatively simple RRD. Prior studies have indicated that low intraocular pressure (IOP), persistent intraoperative detachment at the buckle, macular-off status, and posterior retinal breaks are risk factors for surgical failure of SB.13–15 Meanwhile, inferior breaks and visible vitreous traction on a tear often predict failure of PR.16,17 Nonetheless, PR and SB can complement each other. Early in 1985, Gilbert and McLeod18 and Stanford and Chignell19 introduced a technique involving sequential subretinal fluid (SRF) drainage (D), intravitreal injection of air (A), trans-scleral cryopexy (C), and episcleral explant (E) (DACE) for selected patients with bullous retinal detachment (RD). The primary operation success rates were 90%18 and 96%,19 respectively. However, after including more complicated cases (e.g., RRD with unseen retinal breaks, macular holes [MHs], or some degree of proliferative vitreoretinopathy [PVR]), the single-operation success rate decreased to 67%.20 Even after reoperation, the reattachment rate was only 81%.20 In a subsequent study, Cheng et al.21 performed short-term external SB combined with PR in patients with RRD with inferior breaks and reported a single-operation reattachment rate of 87.9%. Consistent with our clinical experience, a single PR with external drainage of SRF rarely achieves complete retinal reattachment in relatively complicated RRD because of the deep SRF, static vitreoretinal tractions on a tear, and deep locations of retinal breaks. The use of a small gas bubble in prior studies was largely ineffective for complete release of the vitreoretinal traction. In the past few years, maximal PR has been developed in our practice. Maximal PR involves injection of an adequately large non-expansile gas bubble into the vitreous to achieve thorough release of the vitreoretinal traction. We have performed maximal PR and SRF drainage combined with SB for treatment of relatively complicated RRD, such as those involving tractional tears, vitreous hemorrhage, unseen retinal breaks, and posterior holes (including MHs) with combined peripheral retinal breaks, and favorable results were achieved. The purpose of the present study was to introduce and evaluate the efficacy of maximal PR and SRF drainage together with SB for the management of relatively complicated RRD.

The aim of this systematic review was to determine the anatomical outcome—macular hole (MH) closure rate—and functional outcome—visual acuity (VA) improvement rate—of the inverted internal limiting membrane (ILM) flap technique for large MH. We searched for articles on large MH (> 400 μm) treated with inverted ILM flap technique in databases as of December 1, 2017. And single-arm meta-analysis was performed for the primary outcome of MH closure rate and the secondary outcome of VA improvement rate. In addition, we searched and pooled studies treating large MH with indocyanine green (ICG)-assisted ILM peeling as the reference. R software (version 2.15.2) was used for analysis. This review includes eight studies that used inverted ILM flap technique to treat large MH (> 400 μm). Based on the single-arm meta-analysis performed in R 2.15.2, the pooled MH closure rate and VA improvement rate following inverted ILM flap technique were 95% (95% CI, 88 to 98%) and 75% (95% CI, 62 to 85%), respectively, in fixed-effect models. There was no substantial methodological heterogeneity. In addition, we selected four studies on large MH treated with ICG-assisted ILM peeling as the reference. The fixed-model pooled MH closure rate and VA improvement rate were 87% (95% CI, 79 to 92%) and 57% (95% CI, 46 to 68%), respectively. Inverted ILM flap technique should be an effective and safe method for treating large MH, with high closure rates and good VA improvement. However, further studies in large randomized controlled trials on minimizing surgical complications and understanding the mechanism of this technique are necessary.

This study presented the effects of alfalfa and calcium salts of long-chain fatty acids (CSFA) on feed intake, apparent digestibility, rumen fermentation, microbial community, plasma biochemical parameters, and fatty acid profile in Holstein freemartin heifers. Eight Holstein freemartin heifers were randomly divided into a 4 × 4 Latin Square experiment with 2 × 2 factorial diets, with or without alfalfa or CSFA. Dietary supplementation of CSFA significantly increased the apparent digestibility of dry matter, crude protein, neutral detergent fiber, organic matter, and significantly reduced N retention (P < 0.05). CSFA increased the concentration of ammonia nitrogen in the ruminal fluid (P < 0.05), but alfalfa increased the concentration of valerate and isovalerate (P < 0.05). CSFA increased the concentration of ammonia nitrogen and the relative population of Streptococcus bovis in the rumen (P < 0.05) and inhibited the relative population of Ruminococcus flavefaciens, methanogens, and protozoa (P < 0.05). Alfalfa instead of Leymus chinensis increased the relative population of Butyrivibrio fibrisolvens and Ruminobacter amylophilus in the rumen (P < 0.05) and reduced the relative population of the Ruminococcus albus and Megasphaera elsdenii (P < 0.05). Supplemental CSFA increased the concentration of cholesterol and low-density lipoprotein cholesterol in the plasma (P < 0.05). And it also altered the composition of fatty acids in the plasma, which was expressed in reducing saturated fatty acid (ΣSFA) ratio and C14-C17 fatty acids proportion except C16:0 (P < 0.05) and increasing the proportion of polyunsaturated fatty acid (ΣPUFA) and unsaturated fatty acid (ΣUFA) (P < 0.05). The results showed that alfalfa and CSFA had interaction effect on the apparent digestibility of ether extracts, plasma triglyceride concentration, isobutyrate concentration, and Ruminococcus albus relative abundance in the rumen. It was concluded that alfalfa substituting Leymus chinensis did not change the apparent digestibility of nutrients in the final stage of fattening Holstein freemartin heifers, while CSFA increased the cholesterol and the proportion of unsaturated fatty acids in plasma. Alfalfa and CSFA had mutual interaction effect on fat digestion and plasma triglycerides.

Twelve Holstein bulls were used in a 4 × 4 Latin square design to investigate the effects of using whole-crop wheat hay (WCWH) as a substitute for Leymus chinensis (LC) on apparent digestibility, plasma parameters, ruminal fermentation, and microbial communities. Experimental treatments were four proportions of WCWH, 0, 33, 67, and 100%, as a substitute for LC (WCWH0, WCWH33, WCWH67, and WCWH100, respectively). The WCWH100 group showed a higher nutritional intake of crude protein (CP) and higher apparent digestibility of organic matter (OM), CP, and ether extract (EE) than the WCWH0 group (P P

Chronic low-grade inflammation occurs in diabetic retinopathy (DR), but the underlying mechanism(s) remains (remain) unclear. NLRP3 inflammasome activation is involved in several other inflammatory diseases. Thus, we investigated the role of the NLRP3 inflammasome signaling pathway in the pathogenesis of DR. Diabetes was induced in rats by streptozotocin treatment for 8 weeks. They were treated with NLRP3 shRNA or minocycline during the last 4 weeks. High glucose-exposed human retinal microvascular endothelial cells (HRMECs) were co-incubated with antioxidants or subjected to TXNIP or NLRP3 shRNA interference. In high glucose-exposed HRMECs and retinas of diabetic rats, mRNA and protein expression of NLRP3, ASC, and proinflammatory cytokines were induced significantly by hyperglycemia. Upregulated interleukin (IL)-1β maturation, IL-18 secretion, and caspase-1 cleavage were also observed with increased cell apoptosis and retinal vascular permeability, compared with the control group. NLRP3 silencing blocked these effects in the rat model and HRMECs, confirming that inflammasome activation contributed to inflammation in DR. TXNIP expression was increased by reactive oxygen species (ROS) overproduction in animal and cell models, whereas antioxidant addition or TXNIP silencing blocked IL-1β and IL-18 secretion in high glucose-exposed HRMECs, indicating that the ROS–TXNIP pathway mediates NLRP3 inflammasome activation. Minocycline significantly downregulated ROS generation and reduced TXNIP expression, subsequently inhibited NLRP3 activation, and further decreased inflammatory factors, which were associated with a decrease in retinal vascular permeability and cell apoptosis. Together, our data suggest that the TXNIP/NLRP3 pathway is a potential therapeutic target for the treatment of DR, and the use of minocycline specifically for such therapy may be a new avenue of investigation in inflammatory disease.

Background Freemartinism generally occurs in female offspring of dizygotic twins in a mixed-sex pregnancy. Most bovine heterosexual twin females are freemartins. However, about 10% of bovine heterosexual twin females are fertile. Farmers mostly cull bovine fertile heterosexual twin females due to the lack of a practical diagnostic approach. Culling of such animals results in economic and genetic-material losses both for dairy and beef industry. Methods In this study, a comparative test, including qualitative detection of SRY gene by polymerase chain reaction (PCR), quantitative detection of relative content of SRY by real-time quantitative polymerase chain reaction (qPCR), and quantitative detection of H-Y antigen, was performed to establish the most accurate diagnosis for freemartin. Twelve Holstein heterosexual twin females were used in this study, while three normal Holstein bulls and three normal Holstein cows were used as a positive and negative control, respectively. Results Polymerase chain reaction results revealed that SRY gene were absent in three heterosexual twin females and only two of them were verified as fertile in later age. The qPCR results showed that relative content of SRY was more than 14.2% in freemartins and below 0.41% in fertile heterosexual twin females. The H-Y antigen test showed no significant numerical difference between freemartin and fertile heterosexual twin female. Discussion Our results show that relative content of SRY quantified by qPCR is a better detection method for diagnosis of freemartin in Holstein cattle as compare to qualitative detection of SRY gene by PCR or quantitative detection of H-Y antigen. To the authors’ knowledge, this is the first time we applied qPCR to diagnosing freemartin by quantifying SRY gene and got relative SRY content of each freemartin and fertile heterosexual twin female. We concluded that low-level of SRY would not influence fertility of bovine heterosexual twin female.

The mechanisms underlying the cellular metabolic memory induced by high glucose remain unclear. Here, we sought to determine the effects of microRNAs (miRNAs) on metabolic memory in diabetic retinopathy. The miRNA microarray was used to examine human retinal endothelial cells (HRECs) following exposure to normal glucose (N) or high glucose (H) for 1 week or transient H for 2 days followed by N for another 5 days (H→N). Levels of sirtuin 1 (SIRT1) and acetylated-nuclear factor κB (Ac-NF-κB) were examined following transfection with miR-23b-3p inhibitor or with SIRT1 small interfering (si)RNA in the H→N group, and the apoptotic HRECs were determined by flow cytometry. Retinal tissues from diabetic rats were similarly studied following intravitreal injection of miR-23b-3p inhibitor. Chromatin immunoprecipitation (ChIP) analysis was performed to detect binding of NF-κB p65 to the potential binding site of the miR-23b-27b-24-1 gene promoter in HRECs. High glucose increased miR-23b-3p expression, even after the return to normal glucose. Luciferase assays identified SIRT1 as a target mRNA of miR-23b-3p. Reduced miR-23b-3p expression inhibited Ac-NF-κB expression by rescuing SIRT1 expression and also relieved the effect of metabolic memory induced by high glucose in HRECs. The results were confirmed in the retina using a diabetic rat model of metabolic memory. High glucose facilitated the recruitment of NF-κB p65 and promoted transcription of the miR-23b-27b-24-1 gene, which can be suppressed by decreasing miR-23b-3p expression. These studies identify a novel mechanism whereby miR-23b-3p regulates high-glucose-induced cellular metabolic memory in diabetic retinopathy through a SIRT1-dependent signalling pathway.