Optical coherence tomography angiography characteristics and correlated factors with visual acuity in retinal arterial occlusion.

PURPOSE: To reveal the characteristics of vascular changes in retinal arterial occlusion (RAO) using optical coherence tomography angiography (OCTA) and determine the correlated factors with best-corrected visual acuity (BCVA). METHODS: This retrospective study recruited 54 RAO patients and 27 healthy individuals. Ophthalmic examinations including BCVA and OCTA were performed in all the patients and individuals. The OCTA outcomes were analyzed using SPSS software, and the characteristics of vascular changes and BCVA-related factors were summarized. RESULTS: The vessel density in all areas except fovea of both superficial capillary plexus (SCP) and deep capillary plexus (DCP) was significantly reduced in RAO eyes compared with the fellow eyes and normal control eyes (P < 0.05). The vessel density of DCP in all areas except fovea was significantly reduced in the fellow eyes compared with that in the normal control eyes as well (P < 0.05). The retinal thickness in fovea was significantly increased in RAO eyes compared with that in the fellow eyes and normal control eyes (P < 0.05), without any differences in other areas between the RAO eyes and the other two groups (P > 0.05). The retinal thickness in whole area and retinal thickness in fovea were correlated with BCVA, respectively (whole area: r = 0.295, P = 0.030; fovea: r = 0.322, P = 0.018). CONCLUSIONS: OCTA is a fast, noninvasive, and effective examination means for RAO that can display the vascular density and retinal thickness quantitatively and distinctly. RAO patients had reduced vascular density in both eyes and increased foveal retinal thickness in RAO eyes, showing a correlation with BCVA.

An explanation for fluctuations of icariin content in Epimedium production process.

Epimedium has beneficial effects in nourishing and building up the body and is widely used in practical production of Epimedium preparations. As one of the major active compounds in Epimedium preparations, icariin is be used as a quality control index of industrial manufacture. However, content of icariin was observed to increase to uncertain extent in pharmaceutical production, which might bring difficulties in quality control. The content fluctuation mainly occurred in high-temperature extraction process. The aim of this study is to investigate what happen to flavonol-glycosides in Epimedium under heating treatment. Ultra-Performance Liquid Chromatography-Linear Ion Trap Mass Spectrometer was applied to profile the transformation rule of flavonol-glycosides in Epimedium and search for an explanation for the increase in icariin content under heating treatment. 56 compounds were found to have significantly changed and their structures were identified, among which 15 flavonol-glycosides were proposed to play a role in icariin content variation. Further studies were conducted based on 8 flavonol-glycosides standard substances to obtain more credible data. Finally, Baohuoside II, 2"-o-rhamnosylicariside II, Epimedin A1, Epimedin A, Epimedin B, Epimedin C, Baohuoside I and Anhydroicaritin were found to transform into icariin during the heating process. This study provides an evidence for the quality control study of Epimedium preparation, as well as reference for chemical researches in natural pharmacy.

Inhibition of Hypoxia-Induced Retinal Angiogenesis by Specnuezhenide, an Effective Constituent of Ligustrum lucidum Ait., through Suppression of the HIF-1α/VEGF Signaling Pathway.

Specnuezhenide (SPN), one of the main ingredients of Chinese medicine "Nü-zhen-zi", has anti-angiogenic and vision improvement effects. However, studies of its effect on retinal neovascularization are limited so far. In the present study, we established a vascular endothelial growth factor A (VEGFA) secretion model of human acute retinal pigment epithelial-19 (ARPE-19) cells by exposure of 150 µM CoCl2 to the cells and determined the VEGFA concentrations, the mRNA expressions of VEGFA, hypoxia inducible factor-1α (HIF-1α) & prolyl hydroxylases 2 (PHD-2), and the protein expressions of HIF-1α and PHD-2 after treatment of 3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole (YC-1, 1.0 µg/mL) or SPN (0.2, 1.0 and 5.0 µg/mL). Furthermore, rat pups with retinopathy were treated with SPN (5.0 and 10.0 mg/kg) in an 80% oxygen atmosphere and the retinal avascular areas were assessed through visualization using infusion of ADPase and H&E stains. The results showed that SPN inhibited VEGFA secretion by ARPE-19 cells under hypoxia condition, down-regulated the mRNA expressions of VEGFA and PHD-2 slightly, and the protein expressions of VEGFA, HIF-1α and PHD-2 significantly in vitro. SPN also prevented hypoxia-induced retinal neovascularization in a rat model of oxygen-induced retinopathy in vivo. These results indicate that SPN ameliorates retinal neovascularization through inhibition of HIF-1α/VEGF signaling pathway. Therefore, SPN has the potential to be developed as an agent for the prevention and treatment of diabetic retinopathy.

[Relationship between selection of Pinus massoniana families and Folium Pini].

Based on variation of Pinus massoniana families, heritablility and correlation analysis, the contents of shikimic acid and procyanidine (heritability 0.90, 0.70), dry weight of single branch (heritability 0.60) and and leaf length (heritability 0.46) were screened out as quality, yield and harvest cost traits of Folium Pini, respectively. For the different medicinal application of Folium Pini, varied methods were chosen to estimate weight and construct index equation. Weight adjustment based.on equal emphasis were used as economic weight determining method to select the best families, and the index (accuracy 0. 936 4 and heritability 0. 881 6) obtained was a little better than that obtained by equal emphasis, and much better than that by restricted index. The superior families selected with adjustment weight and equal emphasis were No. 46, 43 and 28. Partial regression were used as economic weight determining method to select the best families,and the index obtained had the highest accuracy (0.941 5) , index heritability (0. 889 9) and the genetic gain of shikimic acid content. The superior families selected with this method were No. 46, 27 and 47. No. 46 was the best families with maximal economic benefit. Our study indicated that suitable method for estimate weight and construct index equation can be applied for better accuracy of superior families selection of P. massoniana.

Effects of dietary selenium on the pathological changes and oxidative stress in loach (Paramisgurnus dabryanus).

In this study, loach (Paramisgurnus dabryanus) were fed artificial diets containing 0.31 (control), 0.39, 0.48, 0.50 and 0.62 mg kg(-1) of selenium (Se) for 60 days, respectively. Liver histopathology, hepatocyte ultrastructure, blood indices, biochemical parameters of liver functions and oxidative stress in the Se-treated loach were then assayed. The results showed the following: histopathological and ultrastructural lesions in liver were only observed in loach fed the 0.62 mg Se kg(-1) diet; Haemoglobin and total protein were significantly increased in the 0.50 mg Se kg(-1) group; albumin and high-density lipoprotein were increased significantly in the 0.48-0.50 mg Se kg(-1) groups. However, white blood cell count was significantly decreased in the 0.48 mg Se kg(-1) group; alanine aminotransferase, aspartate aminotransferase and lactate dehydrogenase were decreased in the 0.39-0.50 mg Se kg(-1) groups. In liver tissue, the content of hydrogen peroxide was lower than that of controls in the 0.48-0.50 mg Se kg(-1) groups, and the malondialdehyde level was lowest in the 0.48 mg Se kg(-1) group. The activities of superoxide dismutase and glutathione peroxidase were significantly increased in the 0.50 mg Se kg(-1) group; catalase and total antioxidant capacity were markedly increased in the 0.48-0.50 mg Se kg(-1) group. These present results indicated that the dietary Se requirement for loach is 0.48-0.50 mg Se kg(-1) diet.

Lightweight reinforced wood beams through compression of its surface layers combined with the removal of lignin and hemicellulose.

When wood is used as a stressed component of building materials, the parts most prone to failure are the upper and lower surfaces which can be called the weak structure. In a hydrothermal environment, lignin and hemicellulose in wood readily soften and dissolve, thus leading to their designation as the weak structure. The weak structures results in the wood having a low strength. In this paper, the sandwich beam material can be obtained by two steps from the skin self-reinforcement method, whereby the weak structure of the wood surface was removed by the delignification, and then the wood surface was densified. The authenticity of the sandwich structure is proved by a scanning electron microscope (SEM) and density profile analysis. When the moisture content (MC) is 10 %-12 % and the mass loss ratio is 23.04 %, the optimal resilience of the sandwich beam is only 1 %, the maximum modulus of rupture (MOR) and modulus of elasticity (MOE) are 1.42 and 2.1 times greater than those of natural wood, respectively. This finding shows that our method strengthens the weak structure of natural wood, which has good flexural performance and springback ratio.

Predicting the Potential Distribution of Hypericum perforatum under Climate Change Scenarios Using a Maximum Entropy Model.

H. perforatum, as one of the Traditional Chinese Medicinal materials, possesses a variety of pharmacological activities and high medicinal value. However, in recent years, the wild resources of H. perforatum have been severely depleted due to global climate change and human activities, and artificial cultivation faces problems such as unstable yield and active ingredient content. This poses a serious obstacle to the development and utilization of its resources. Therefore, this experiment took H. perforatum as the research object and used 894 distribution records of H. perforatum and 36 climatic environmental factors, using the MaxEnt model and GIS technology to explore the main climatic factors affecting the distribution of H. perforatum. Additionally, by utilizing the principles of ecological niche theory, the potential suitable distribution regions of H. perforatum across past, present, and future timelines were predicted, which can ascertain the dynamics of its spatial distribution patterns and the trend of centroid migration. The results indicate that the main environmental factors affecting the geographical distribution of H. perforatum are solar radiation in April (Srad4), solar radiation in September (Srad9), mean temperature of driest quarter (Bio9), solar radiation in November (Srad11), annual mean temperature (Bio1), and annual precipitation (Bio12). Under future climate scenarios, there is a remarkable trend of expansion in the suitable distribution areas of H. perforatum. The centroid migration indicates a trend of migration towards the northwest direction and high-altitude areas. These results can provide a scientific basis for formulating conservation and sustainable use management strategies for H. perforatum resources.

Computational Retinal Microvascular Biomarkers from an OCTA Image in Clinical Investigation.

Retinal structural and functional changes in humans can be manifestations of different physiological or pathological conditions. Retinal imaging is the only way to directly inspect blood vessels and their pathological changes throughout the whole body non-invasively. Various quantitative analysis metrics have been used to measure the abnormalities of retinal microvasculature in the context of different retinal, cerebral and systemic disorders. Recently developed optical coherence tomography angiography (OCTA) is a non-invasive imaging tool that allows high-resolution three-dimensional mapping of the retinal microvasculature. The identification of retinal biomarkers from OCTA images could facilitate clinical investigation in various scenarios. We provide a framework for extracting computational retinal microvasculature biomarkers (CRMBs) from OCTA images through a knowledge-driven computerized automatic analytical system. Our method allows for improved identification of the foveal avascular zone (FAZ) and introduces a novel definition of vessel dispersion in the macular region. Furthermore, retinal large vessels and capillaries of the superficial and deep plexus can be differentiated, correlating with retinal pathology. The diagnostic value of OCTA CRMBs was demonstrated by a cross-sectional study with 30 healthy subjects and 43 retinal vein occlusion (RVO) patients, which identified strong correlations between OCTA CRMBs and retinal function in RVO patients. These OCTA CRMBs generated through this "all-in-one" pipeline may provide clinicians with insights about disease severity, treatment response and prognosis, aiding in the management and early detection of various disorders.

Pharmacokinetics of a long-lasting anti-VEGF fusion protein in rabbit.

Conbercept(KH902), a recombinant fusion protein in clinical trial II/III, shows good potential to treat the neovascular age-related macular degeneration (AMD). This investigation evaluated its ocular pharmacokinetics and pharmacodynamic profile in rabbits following intravitreal administration (IVT). Rabbits (n = 120) received single bilateral conbercept IVT administration or single IV administration. Conbercept concentrations in ocular tissues and serum were measured after dosing. VEGF concentration was also measured simultaneously. The results showed that conbercept rapidly distributed from vitreous into targeted tissues and lasted over 81 days. Clearance in ocular tissues was parallel and exhibited a terminal half of 2.5-4.2 days. The drug exposure in the retina was 1/4 to 1/5 of that in vitreous. Serum conbercept concentrations after IVT dosing were low and bioavailability was approximately 44%. And single intravitreal injection induced that ocular VEGF concentration declined over 60 days and serum VEGF concentration decreased for a short time but rebounded to higher level than baseline later. All these indicated conbercept good pharmacokinetic profile in rabbits, with good ocular tropism and systemic tolerance. Combined with the efficacy data from our earlier in vitro and in vivo studies, it should have a promising clinical application for AMD treatment.

Association of Abnormal Renal Profiles with Subretinal Fluid in Diabetic Macular Edema.

Purpose: To investigate the risk factors for subretinal fluid (SRF) in diabetic macular edema (DME). Methods: We reviewed the records of 66 patients with DME. Systemic parameters, including hypertension, glycosylated hemoglobin, serum fasting glucose, total cholesterol, triglycerides, and diabetic kidney disease, were evaluated. Renal parameters for diabetic kidney disease included serum albumin, serum creatinine, albuminuria, and estimated glomerular filtration rate. Ocular factors included visual acuity and diabetic retinopathy, and the following parameters are evaluated through optical coherence tomography examination: disorganization of the retinal inner layers, loss of ellipsoid zone, central subretinal fluid thickness, central macular thickness, and presence of SRF. Results: Higher albuminuria (odds ratio, 3.431; 95% confidence interval, 1.039-11.334; P=0.043) was associated with the presence of SRF in patients with DME. Lower serum albumin levels (beta = -14.028, se = 6.646, P=0.044) were associated with increased SRF thickness. Conclusions: Poor kidney function was associated with the presence of SRF in DME. Screening for SRF in DME in patients with higher albuminuria and lower serum albumin levels should be routinely performed.

Superconductivity in CeBeH8and CeBH8at moderate pressures.

High-pressure structural searches of superhydrides CeBeH8and CeBH8were performed under ambient pressure up to 300 GPa. We identifyFm3‾m-CeBeH8with a superconducting transition temperatureTcof 56 K at 10 GPa. Two more phases with spacegroupR3‾mandC2/m, were investigated within the increasing pressures. CeBH8shows a similar phase transition process as CeBeH8but with higher transition pressures and higherTc.Fm3‾m-CeBH8is predicted to be superconducting above 120 GPa with a maximumTcof 118 K at 150 GPa.R3‾m-CeBH8andC2/m-CeBH8are dynamically stable above 120 GPa and 100 GPa, respectively. The maximumTcis 123 K at 195 GPa forR3‾m-CeBH8, and 115 K at 350 GPa forC2/m-CeBH8. Our work enriches the family of ternary hydrides and may provide a useful guideline for further search for superconducting hydrides at low and moderate pressures.

Traditional Chinese medicine Xiaosheng Powder for dry eye disease: A protocol for systematic review and meta analysis.

BACKGROUND: Dry eye disease (DED) has shown a significant increase in recent years, which seriously affects people's work and life. Xiaosheng Powder, a traditional Chinese medicine decoction, has been widely used in treating DED. However, there is no systematic review of the results of the study on this therapeutic effect. The purpose of this review is to evaluate the effectiveness and safety of Xiaosheng Powder in the treatment of DED. METHODS AND ANALYSIS: The electronic databases to be searched will include MEDLINE (PubMed), Cochrane Central Register of Controlled Trials in the Cochrane Library, Excerpta Medica Database, China National Knowledge Infrastructure, China Scientific Journal Database, Wanfang Database and Chinese Biomedical Literature Database. Papers in English or Chinese published from inception to 2020 will be included without any restrictions. Improvement in Ocular Surface Disease Index will be assessed as the primary outcomes. Tear break-up time, Schirmer I test, fluorescent, adverse events, and the recurrence rate after at least 3 months of the treatment will be evaluated as secondary outcomes. We will conduct a meta-analysis of randomized controlled trial if possible. The methodological qualities, including the risk of bias, will be evaluated using the Cochrane risk of bias assessment tool, while confidence in the cumulative evidence will be evaluated using the Grading of Recommendations Assessment, Development, and Evaluation approach. ETHICS AND DISSEMINATION: It is not necessary for a formal ethical approval because the data is not individualized. The results of this review will offer implications for the use of Xiaosheng Powder as a treatment for DED. This knowledge will inform recommendations by ophthalmologist and researchers who are interested in the treatment of DED. The findings of this systematic review will be disseminated through peer-reviewed publications and conference presentations. TRAIL REGISTRATION NUMBER: PROSPERO CRD42020147709.

Study on the potential effective ingredients of Xiaosheng prescription for dry eye disease.

Xiaosheng prescription (XSP) has been used for dry eye disease (DED) for more than 10 years in Eye Hospital of China Academy of Chinese Medicine Sciences. However, the effective ingredients involved have remained unclear, which was investigated in this study by the correlation of ingredient and therapeutic activity. Human corneal epithelial cells (HCEC) cultured with 110 mM NaCl solution in vitro and C57BL/6 mice injected subcutaneously with scopolamine hydrobromide were used to establish dry eye models, and the therapeutic effect of XSP extract 1 was better than that of XSP extract 2 significantly. Then, UPLC-Q-TOF/MS and data analysis program Progenesis QI and Makerlynx XS were used to analyze the potential effective ingredients of XSP, and 4 compounds were speculated and identified, in which Schisandrin and 1 µM of Schisantherin A could obviously increase the cell survival rate of injured cells on the cell model. It can be indicated that Schisandrin and Schisantherin A are probably the potential effective ingredients in XSP for DED.

A Network Pharmacology to Explore the Mechanism of Astragalus Membranaceus in the Treatment of Diabetic Retinopathy.

BACKGROUND: Diabetic retinopathy (DR) includes a series of typical lesions affected by retinal microvascular damage caused by diabetes mellitus (DM), which not only seriously damages the vision, affecting the life's quality of patients, but also brings a considerable burden to the family and society. Astragalus Membranaceus (AM) is a commonly used medicine in clinical therapy of eye disorders in traditional Chinese medicine (TCM). In recent years, it is also used for treating DR, but the specific mechanism is unclear. Therefore, this study explores the potential mechanism of AM in DR treatment by using network pharmacology. METHODS: Based on the oral bioavailability (OB) and drug likeness (DL) of two ADME (absorption, distribution, metabolism, excretion) parameters, Traditional Chinese Medicine Systems Pharmacology Database (TCMSP), Swiss Target Prediction platform, GeneCards, and OMIM database were used to predict and screen the active compounds of AM, the core targets of AM in DR treatment. The Metascape data platform was used to perform Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis on the core targets. RESULTS: 24 active compounds were obtained, such as quercetin, kaempferol, and astragaloside IV. There were 169 effective targets of AM in DR treatment, and the targets were further screened and finally, 38 core targets were obtained, such as VEGFA, AKT1, and IL-6. EGFR tyrosine kinase inhibitor resistance, AGE-RAGE signaling pathway in diabetic complications, PI3K-Akt signaling pathway, and other metabolic pathways participated in oxidative stress, cell apoptosis, angiogenesis signal transduction, inflammation, and other biological processes. CONCLUSION: AM treats DR through multiple compounds, multiple targets, and multiple pathways. AM may play a role in the treatment of DR by targeting VEGFA, AKT1, and IL-6 and participating in oxidative stress, angiogenesis, and inflammation.

Rac1 activates HIF-1 in retinal pigment epithelium cells under hypoxia.

BACKGROUND: Upregulation of vascular endothelial growth factor (VEGF) in hypoxic retinal pigment epithelium (RPE) cells, mediated by hypoxia-inducible factor-1 (HIF-1) is responsible for choroidal neovascularization (CNV). HIF-1alpha is the inducible subunit of HIF-1, but the underlying mechanisms by which RPE cells sense a decrease in oxygen concentration and transduce this signal to HIF-1alpha are largely unknown. Rho family small GTPase Rac1, as a potential intermediate, possibly plays a pivotal role in activating HIF-1alpha in RPE cells under hypoxia. AIMS: To further define Rac1 playing an essential role in the induction of HIF-1alpha expression in RPE cells under hypoxia. METHODS: In this study, we examined the expression of HIF-1alpha and Rac1 in human RPE cells under hypoxia for 0, 1, 2, 4, 8, 12 and 24 h by RT-PCR and Western blot. To elucidate whether Rac1 is responsible for activating the expression of hypoxia-induced HIF-1alpha, human RPE cells were treated with Rac1 inhibitor NSC23766 under hypoxia for 0, 1, 2, 4, 8, 12 and 24 h, and expression of HIF-1alpha and Rac1 measured by RT-PCR and Western blot. RESULTS: The mRNA expression of HIF-1alpha and Rac1 in RPE cells significantly increased in a time-dependent manner, reaching the maximum at 4 h, and thereafter slowly declined. HIF-1alpha protein induction in human RPE cells was found after 1 h of hypoxia, reaching the maximum at 8 h, and then slowly declined. In response to hypoxia, the levels of Rac1 protein significantly increased, reaching the maximum at 4 h, and then slowly declined. After treatment with NSC23766, both HIF-1alpha and Rac1 expression were significantly inhibited in hypoxic RPE cells. CONCLUSIONS: Rac1 is crucial to activate HIF-1 in RPE cells under hypoxia, which may be a novel target other than VEGF and HIF-1 in developing CNV inhibitors.

Intervention of artemisinin in macular edema associated with retinal vein occlusion: A protocol for a systematic review and meta-analysis.

BACKGROUND: Artemisinin was discovered to be highly effective antimalarial drugs shortly after the isolation of the parent artemisinin in 1971 in China. It is derived from extracts of sweet wormwood (Artemisia annua) and are well established for the treatment of malaria. Recently, artemisinin has been shown that it might have therapeutic value for several other diseases. The purpose of this review is to assess the efficacy of artemisinin as a treatment for macular edema associated with retinal vein occlusion. METHODS AND ANALYSIS: A systematic literature search will be performed in all available databases to quantitatively review eligible studies and identify all relevant data. We will include randomized controlled trials assessing efficacy of artemisinin as a treatment for macular edema associated with retinal vein occlusion. The methodological qualities, including the risk of bias, will be evaluated using the Cochrane risk of bias assessment tool, while confidence in the cumulative evidence will be evaluated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. ETHICS AND DISSEMINATION: Ethical approval is not required, as this study is based on the review of published research. This review will be published in a peer-reviewed journal and disseminated both electronically and in print. PROSPERO REGISTRATION NUMBER: The protocol for this systematic review has been registered on PROSPERO under the number CRD42019131408.

Formononetin, an active compound of Astragalus membranaceus (Fisch) Bunge, inhibits hypoxia-induced retinal neovascularization via the HIF-1α/VEGF signaling pathway.

BACKGROUND: It has been reported that formononetin (FMN), one of the main ingredients from famous traditional Chinese medicine "Huang-qi" (Astragalus membranaceus [Fisch] Bunge) for Qi-tonifying, exhibits the effects of immunomodulation and tumor growth inhibition via antiangiogenesis. Furthermore, A. membranaceus may alleviate the retinal neovascularization (NV) of diabetic retinopathy. However, the information of FMN on retinal NV is limited so far. In the present study, we investigated the effects of FMN on the hypoxia-induced retinal NV and the possible related mechanisms. MATERIALS AND METHODS: The VEGF secretion model of acute retinal pigment epithelial-19 (ARPE-19) cells under chemical hypoxia was established by the exposure of cells to 150 µM CoCl2 and then cells were treated with 3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole (YC-1, a potent HIF-1α inhibitor, 1.0 µg/mL) or different concentrations of FMN (0.2 µg/mL, 1.0 µg/mL, and 5.0 µg/mL). The supernatants of cells were collected 48 hours later to measure the VEGF concentrations, following the manufacturer's instruction. The mRNA expressions of VEGF, HIF-1α, PHD-2, and ß-actin were analyzed by quantitative reverse transcription polymerase chain reaction, and the protein expressions of HIF-1α and PHD-2 were determined by Western blot analysis. Furthermore, the rats with retinopathy were treated by intraperitoneal administration of conbercept injection (1.0 mg/kg) or FMN (5.0 mg/kg and 10.0 mg/kg) in an 80% oxygen atmosphere. The retinal avascular areas were assessed through visualization of the retinal vasculature by adenosine diphosphatase staining and hematoxylin and eosin staining. RESULTS: FMN can indeed inhibit the VEGF secretion of ARPE-19 cells under hypoxia, downregulate the mRNA expression of VEGFA and PHD-2, and decrease the protein expression of VEGF, HIF-1α, and PHD-2 in vitro. Furthermore, FMN can prevent hypoxia-induced retinal NV in vivo. CONCLUSION: FMN can ameliorate retinal NV via the HIF-1α/VEGF signaling pathway, and it may become a potential drug for the prevention and treatment of diabetic retinopathy.