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.

Fixed-time angle of attack constrained control for aircraft considering dynamic icing process.

Aircraft icing deteriorates aerodynamic performance and reduces stall angle of attack, the fast convergence rate of tracking error is required to stabilize the aircraft when aircraft icing occurs. The state-of-the-art control methods for icing aircraft mostly assume that the icing of aircraft is instantaneous. Aiming at these issues, a fixed-time angle of attack-constrained control strategy is designed considering dynamic icing process. In order to explore the variation of aerodynamic coefficients in the process of dynamic icing, an ice wind tunnel experiment is implemented, and the relationship between lift coefficient, drag coefficient and pitching moment coefficient with angle of attack and icing intensity is obtained by fitting method. In order to prevent the stalling problem caused by the decrease of the stalling angle of attack in the process of dynamic icing, a method to determine the stalling angle of attack based on deep neural network is proposed. Considering the asymmetric and time-varying angle of attack constraint, a fixed-time convergent angle of attack-constrained robust control method is designed. The ice wind tunnel experiment shows the process of dynamic icing of the airfoil, and the simulation results verify the effectiveness of the proposed control method.

24-Hour efficacy of single primary selective laser trabeculoplasty versus latanoprost eye drops for Naïve primary open-angle glaucoma and ocular hypertension patients.

This prospective, observer-masked, randomized clinical trial was conducted between December 2018 and June 2021 at Eye Hospital, China Academy of Chinese Medical Sciences. A total of 45 glaucoma patients from Beijing, China, were enrolled in this clinical trial to compare the short-term efficacy of primary single-selective laser trabeculoplasty (SLT) to 0.005% latanoprost eye drops for the treatment of 24-h intraocular pressure (IOP) in patients with newly diagnosed primary open angle glaucoma (POAG) and ocular hypertension (OHT). Both SLT and latanoprost significantly decreased mean 24-h IOP and peak IOP, although the latanoprost group effect was more potent when compared to the SLT group (both Ps < 0.05). Compared with the SLT group, the latanoprost group had a significant and stable decrease in IOP after treatment. The latanoprost group had a more pronounced reduction in IOP at weeks 4 and 12 (P < 0.05) but had no difference at week 1 (P = 0.097). As a first-line treatment, both SLT and latanoprost eye drops are effective in newly diagnosed POAG and OHT patients. However, the latanoprost eye drops may be better in decreasing mean and peak 24-h IOP and thus controlling 24-h IOP fluctuation compared to SLT.

Qing-Zhi-Tiao-Gan-Tang (QZTGT) prevents nonalcoholic steatohepatitis (NASH) by expression pattern correction.

ETHNOPHARMACOLOGICAL RELEVANCE: Qing-Zhi-Tiao-Gan-Tang or Qing-Zhi-Tiao-Gan Decoction (QZTGT) is based on the compatibility theory of traditional Chinese medicine (TCM), that is a combination of three classical formulae for the treatment of nonalcoholic fatty liver disease (NAFLD). Its pharmacodynamic material basis is made up of quinones, flavanones, and terpenoids. AIM OF THE STUDY: This study aimed to look for a promising recipe for treating nonalcoholic steatohepatitis (NASH), a more advanced form of NAFLD, and to use a transcriptome-based multi-scale network pharmacological platform (TMNP) to find its therapy targets. MATERIALS AND METHODS: A classical dietary model of NASH was established using MCD (Methionine- and choline-deficient) diet-fed mice. Liver coefficients like ALT, AST, serum TC, and TG levels were tested following QZTGT administration. A transcriptome-based multi-scale network pharmacological platform (TMNP) was used to further analyze the liver gene expression profile. RESULTS: The composition of QZTGT was analyzed by HPLC-Q-TOF/MS, a total of 89 compounds were separated and detected and 31 of them were found in rat plasma. QZTGT improved liver morphology, inflammation and fibrosis in a classical NASH model. Transcriptomic analysis of liver samples from NASH animal model revealed that QZTGT was able to correct gene expression. We used transcriptome-based multi-scale network pharmacological platform (TMNP) to predicted molecular pathways regulated by QZTGT to improve NASH. Further validation indicated that "fatty acid degradation", "bile secretion" and "steroid biosynthesis" pathways were involved in the improvement of NASH phenotype by QZTGT. CONCLUSIONS: Using HPLC-Q-TOF/MS, the compound composition of QZTGT, a Traditional Chinese prescription, was separated, analyzed and identified systematically. QZTGT mitigated NASH symptoms in a classical dietary model of NASH. Transcriptomic and network pharmacology analysis predicted the potential QZTGT regulated pathways. These pathways could be used as therapeutic targets for NASH.

Dose-dependent pharmacokinetics of midazolam in rats: influence of hepatic first-pass metabolism.

To characterise the dose-dependent pharmacokinetics of midazolam and evaluate the intestinal and hepatic first-pass effects on midazolam in Sprague-Dawley rats, the concentrations and area under the concentration-time curve (AUC) of midazolam in the portal and systemic plasma were simultaneously determined with a double cannulation method.It was found that about 75% of the dose was left in the portal blood with different oral administration doses, while the bioavailability in the liver was 37.86% at 20 mg/kg, significantly higher than 9.16% at 2 mg/kg.The disproportional increase in AUC of midazolam and significant decrease in exposure of metabolites were observed in systemic plasma after hepatic portal vein administration. And in the in vitro study, the formation rate of the metabolites of midazolam significantly decreased when midazolam was at 300 µM compared with 100 µM.These results indicated that not only the saturation of first-pass metabolism but also the inhibition of hepatic metabolism is responsible for the nonlinear PK of midazolam. Thus, a rational dose should be chosen when midazolam is used as a probe in the drug-drug interaction study, particularly for orally administered drugs that undergo hepatic first-pass metabolism.

Comprehensive Evaluation of Metabolism and the Contribution of the Hepatic First-Pass Effect in the Bioavailability of Glabridin in Rats.

Glabridin is a bioactive isoflavan, which has a wide range of biological properties and is widely used in the market of health products and dietary supplements. However, the transformation pathway of glabridin in vivo is unclear, and the bioavailability is controversial among different studies. Therefore, a new HPLC-Q-TOF method was developed to analyze and identify the prototype and metabolites of glabridin in rats. A total of 63 compounds were identified, including hydroxylation, demethylation, acetylation, demethylation to carboxylation, glucuronidation, and sulfate conjugation, and 43 of which were new metabolites that had not been reported. Additionally, our study verified that the oral bioavailability of glabridin was 6.63 ± 2.29% in rats. Furthermore, we found that the hepatic first-pass effect was 62.12 ± 15.7% for glabridin. These results indicated that a high hepatic first-pass effect and extensive metabolism of glabridin in vivo may lead to its limited oral bioavailability.

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.

The optimization method of wing ice shape regulation based on flight dynamics characteristics.

Ice on aircraft wing changes the aircraft aerodynamic shape, and has negative effects on flight dynamic characteristics, seriously threatening flight safety. Plasma ice shape regulation is a new de-icing method. Plasma actuator produces an apparent thermal effect, which is designed to dissolve the continuous ice into intermittent ice pieces. How to achieve the optimal regulation ice shape to improve the flight dynamics characteristics under icing conditions is a technical problem restricting the application of this method. A simulation ice shape based on previous ice tunnel experiments and a scale model of swept wing were established. The aerodynamic parameters of no ice, full ice, and two regulation ice schemes were obtained based on wind tunnel. Six degrees of freedom flight dynamics model was established, and flight simulation had been carried out. As the analysis of trim characteristics, dynamic stability, and maneuverability, flight dynamics characteristics were better improved when the ratio of ice width to the mean aerodynamic chord was 0.15. The evaluation method of plasma ice shape regulation schemes was proposed. The proposed method, which can compare and optimize the arrangement of plasma actuators, realized the optimal regulation ice shape on the premise of balancing flight safety and energy consumption.

Optical coherence tomography angiography in retinitis pigmentosa: A narrative review.

Retinitis pigmentosa (RP) is a group of inherited retinal disorders characterized by progressive rod and cone photoreceptor degeneration. Changes in retinal vasculature have long been associated with RP. Optical coherence tomography angiography (OCTA) is a novel imaging technology that enables noninvasive visualization of the retinal and choroidal microvasculature. OCTA enables quantification of microvascular changes in the retinal capillary plexus and choriocapillaris, in addition to qualitative feature description. Therefore, OCTA has the potential to become an important tool for better understanding, early detection, progression, and treatment of RP. In this review, we focus on the applications of OCTA in clinical research on RP. We also discuss future improvements in the OCTA technology for RP management. We believe that the advancement of the OCTA technique will ultimately lead to a better understanding of RP and aid in the prevention of visual impairment.

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.

In depth understanding of retinitis pigmentosa pathogenesis through optical coherence tomography angiography analysis: a narrative review.

Retinitis pigmentosa (RP) is the most recognized inherited retinal disorder involving progressive photoreceptors degeneration which eventually causes blindness. However, the pathogenesis of RP is still unclear, making it difficult to establish satisfying treatments. Evidence have been found to support the theory that vascular dysfunction is associated with the progression of RP. Optical coherence tomography angiography (OCTA) is a newly developed technology that enables visualization as well as quantitative assessment of retinal and choroidal vasculature non-invasively. Advances in OCTA have opened a window for in-depth understanding of RP pathogenesis. Here, we propose a hypothesis of RP pathogenesis based on the current OCTA findings in RP, which includes four stages and two important key factors, vascular dysfunction and microglia activation. Further, we discuss the future animal experiments needed and how advanced OCTA technology can help to further verity the hypothesis. The final goal is to explore potential treatment options with enhanced understanding of RP pathogenesis.

Effects of biochar derived from sewage sludge and sewage sludge/cotton stalks on the immobilization and phytoavailability of Pb, Cu, and Zn in sandy loam soil.

Co-pyrolysis of sewage sludge and straws has been used to improve the pore structure and reduce the ecological risks of heavy metals in sewage sludge-derived biochars. However, to date, no study has focused on the effects of biochar derived from sewage sludge/straws on the immobilization and phytoavailability of heavy metals in soil. Here, we studied the effects of biochar derived from sewage sludge/cotton stalks (SCB) and that derived from sewage sludge alone (SSB) on the remediation of sandy loam soil contaminated by Pb, Cu, and Zn. SCB amendment decreased the bioavailable forms of Pb, Cu, and Zn in the soil by 19.0%, 34.9%, and 18.2%, respectively, and reduced their accumulation in ryegrass by 28.6%, 50.1%, and 30.0%, respectively, compared with those by SSB amendment. Furthermore, SCB amendment transformed more metals from the acid-soluble fraction to the oxidizable fraction than SSB amendment, indicating that complexation played a more critical role in SCB amendment than in SSB amendment. Both biochar amendments effectively improved soil water holding capacity, increased the supply of available P, N, and K, and promoted ryegrass growth. The findings of this study show the benefits of SCB over SSB for the remediation of heavy metal-contaminated soil.

Identification of the absorbed ingredients and metabolites in rats after an intravenous administration of Tanreqing injection using high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry.

The metabolic profiles of Tanreqing injection, which is a traditional Chinese medicine recommended for complementary administration to treat a novel coronavirus, have remained unclear, which inhibit the understanding of the effective chemical compounds of Tanreqing injection. In this study, a sensitive high-performance liquid chromatography quadrupole time-of-flight mass spectrometry method was used to identify the compounds and metabolites in various biosamples, including plasma, bile, liver, lung, kidney, urine, and feces, following the intravenous administration of Tanreqing injection in rats. A total of 89 compounds were characterized in the biosamples of Tanreqing injection-treated rats including 25 precursor constituents and 64 metabolites. Nine flavonoid compounds, twelve phenolic acids, and four iridoid glycosides were identified in the rats. Their metabolites were mainly produced by glucuronidation, deglucuronidation, glycosylation, deglycosylation, methylation, demethylation, N-heterocyclisation, sulphation, dehydroxylation, decarboxylation, dehydration, hydroxylation, and corresponding recombination reactions. This study was the first to comprehensively investigate the metabolic profile of Tanreqing injection and provides a scientific basis to further elucidate the pharmacodynamic material basis and therapeutic mechanism of Tanreqing injection.

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.

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.

Systematic investigation on the chemical basis of anti-NAFLD Qushi Huayu Fang. Part 1: A study of metabolic profiles in vivo and in vitro by high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry.

Qushi Huayu Fang (QHF) is a clinic-empirical prescription for treating non-alcoholic fatty liver disease (NAFLD) in China, which is composed of five herbs. However, the bioactive constituents responsible for the efficacy of QHF remain unclear. Thus, a high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry method was established and adopted to identify the constituents of QHF, and profile its metabolism in vivo and in vitro. Among the 66 constituents in QHF, only 14 compounds of six structural types were absorbed, and 34 metabolites were generated through eight metabolic pathways. A total of 20 metabolites were first reported, including four organic acids, one iridoid, two flavones, five naphthols, three anthraquinones, and five stilbenes. Glucuronidation and sulfation were the main metabolic pathways, and the intestinal metabolism played an important role in the biotransformation of QHF. Many compounds, especially those detected in the liver, the target organ of QHF, were reported to display the anti-NAFLD activity. This is the first study to explore the constituents of QHF and its metabolism in vivo and in vitro, thus realizing the first step to clarify the chemical basis of QHF qualitatively, and laying the foundation for further research on the anti-NAFLD mechanism of QHF.