Aflibercept combined with triamcinolone acetonide in the treatment of diabetic macular edema: optical coherence tomography and optical coherence tomography angiography.

AIM: To analyze the relationship between optical coherence tomography (OCT) and OCT angiography (OCTA) imaging in patients with diabetic macular edema (DME) who are treated with a combination of aflibercept and triamcinolone acetonide (TA). METHODS: A total of 76 eyes newly diagnosed DME were included in this study. They were randomly assigned to receive either aflibercept or a combination of aflibercept and TA. Injections once a month for a total of three injections. Central macular thickness (CMT), number of hyperreflective foci (HRF), height of subretinal fluid (SRF), and area of foveal avascular zone (FAZ) were evaluated using OCT and OCTA at baseline and after each monthly treatment. RESULTS: Both groups showed improvement in best corrected visual acuity (BCVA) and reduction in macular edema after treatment, and the difference in BCVA between the two groups was statistically significant after each treatment (P<0.05). The difference in CMT between the two groups was statistically significant after the first two injections (P<0.01), but not after the third injection (P=0.875). The number of HRF (1mo: 7.41±8.25 vs 10.86±7.22, P=0.027; 2mo: 5.33±6.13 vs 9.12±8.61, P=0.034; 3mo: 3.58±3.00 vs 6.37±5.97, P=0.007) and height of SRF (1mo: 82.39±39.12 vs 105.77±42.26 µm, P=0.011; 2mo: 36.84±10.02 vs 83.59±37.78 µm, P<0.01; 3mo: 11.57±3.29 vs 45.43±12.60 µm, P<0.01) in combined group were statistically significant less than aflibercept group after each injection, while the area of FAZ showed no significant change before and after treatment in both groups. CONCLUSION: The combination therapy of aflibercept and TA shows more significant effects on DME eyes with decreased HRF and SRF. However, both aflibercept and combination therapy show no significant change in the area of FAZ.

Exploring correlations between soy sauce components and the formation of thermal contaminants during low-salt solid-state fermentation.

Soy sauce is a traditional seasoning in Asia and provides a unique flavor to food. However, some harmful Maillard reaction products (MRPs) were inevitably formed during the manufacturing process. Fermentation is a critical step of soy sauce manufacturing and has a significant impact on MRPs formation. Therefore, this study investigated the formation of some characteristic MRPs (e.g., furan, carboxymethyl lysine (CML), 5-hydroxymethylfurfural (5-HMF), α-dicarbonyl compounds) and their correlation with major quality indicators (e.g., free amino acids, reducing sugar, total acid, ammonia nitrogen, total nitrogen, non-salt soluble solids) in low-salt solid-state fermentation soy sauce (LSFSS). The result showed that the levels of furan, CML, and 5-HMF continue to increase during the fermentation process, reaching a maximum after sterilization. Further testing using Person correlation showed that the formation of furan, CML, and 5-HMF in LSFSS was positively correlated with glucose, fructose, α-dicarbonyl compounds, and most of the amino acids, while it was negatively correlated with sucrose and methionine. Among them, the contribution of lysine, valine, isoleucine, leucine, and arginine to furan formation has rarely been reported. Our results provide a good theoretical basis for the control of MRPs during LSFSS fermentation.

Effect of aflibercept combined with triamcinolone acetonide on aqueous humor growth factor and inflammatory mediators in diabetic macular edema.

AIM: To investigate the efficacy of aflibercept combined with sub-tenon injection of triamcinolone acetonide (TA) in treating diabetic macular edema (DME) and to examine changes in growth factors and inflammatory mediator levels in aqueous humor after injection. METHODS: Totally 67 DME patients (67 eyes) and 30 cataract patients (32 eyes) were enrolled as the DME group and the control group, respectively. The DME group was divided into the aflibercept group (34 cases) and the aflibercept combined with TA group (combined group, 33 cases). The aqueous humor of both groups was collected during the study period. The aqueous levels of vascular endothelial growth factor (VEGF), monocyte chemoattractant protein-1 (MCP-1), interleukin-6 (IL-6), interleukin-8 (IL-8), and interleukin-1ß (IL-1ß) were detected using a microsphere suspension array technology (Luminex 200TM). Aqueous cytokines, best-corrected visual acuity (BCVA), central macular thickness (CMT), and complications before and after treatment were compared between the aflibercept group and combined group. RESULTS: The concentrations of VEGF, MCP-1, IL-6, and IL-8 in the aqueous humor were significantly higher in the DME group than those of the control group (all P<0.01). After 1mo of surgery, the concentrations of VEGF, MCP-1, IL-6, and IL-8 in the aqueous humor were significantly lower in the combined group than those of the aflibercept group (all P<0.01). The BCVA and CMT values of the two groups were statistically different after 1 and 2mo of treatment (P<0.01). However, the difference was not statistically significant after 3mo of treatment (P>0.05). CONCLUSION: The cytokines VEGF, MCP-1, IL-6, and IL-8 in the aqueous humor of DME patients are significantly increased. Aflibercept and aflibercept combined with TA have good efficacy in DME patients, can effectively reduce CMT, improve the patient's vision, and have high safety. Aflibercept combined with TA can quickly down-regulate the aqueous humor cytokines and help to relieve macular edema rapidly. However, the long-term efficacy is comparable to that of aflibercept alone.

Targeting ZIP8 mediated ferroptosis as a novel strategy to protect against the retinal pigment epithelial degeneration.

The degeneration of retinal pigment epithelium (RPE) plays an important role in the development of age-related macular degeneration (AMD). However, the underlying mechanism remains elusive. In this study, we identified that ZIP8, a metal-ion transporter, plays a crucial role in the degeneration of RPE cells mediated by ferroptosis. ZIP8 was found to be upregulated in patients with AMD through transcriptome analysis. Upregulated ZIP8 was also observed in both oxidative-stressed RPE cells and AMD mouse model. Importantly, knockdown of ZIP8 significantly inhibited ferroptosis in RPE cells induced by sodium iodate-induced oxidative stress. Blocking ZIP8 with specific antibodies reversed RPE degeneration and restored retinal function, improving visual loss in a mouse model of NaIO3-induced. Interestingly, the modification of the N-glycosylation sites N40, N72 and N88, but not N273, was essential for the intracellular iron accumulation mediated by ZIP8, which further led to increased lipid peroxidation and RPE death. These findings highlight the critical role of ZIP8 in RPE ferroptosis and provide a potential target for the treatment of diseases associated with retinal degeneration, including AMD.

Ferroptosis as a potential therapeutic target for age-related macular degeneration.

Cell death plays a crucial part in the process of age-related macular degeneration (AMD), but its mechanisms remain elusive. Accumulating evidence suggests that ferroptosis, a novel form of regulatory cell death characterized by iron-dependent accumulation of lipid hydroperoxides, has a crucial role in the pathogenesis of AMD. Numerous studies have suggested that ferroptosis participates in the degradation of retinal cells and accelerates the progression of AMD. Furthermore, inhibitors of ferroptosis exhibit notable protective effects in AMD, underscoring the significance of ferroptosis as a pivotal mechanism in the death of retinal cells during the process of AMD. This review aims to summarize the molecular mechanisms of ferroptosis in AMD, enumerate potential inhibitors and discuss the challenges and future opportunities associated with targeting ferroptosis as a therapeutic strategy, providing important information references and insights for the prevention and treatment of AMD.

Symmetrical femtosecond laser arc incision in correcting corneal astigmatism in cataract patients.

AIM: To evaluate the effect of symmetrical arc incision correcting corneal astigmatism in femtosecond laser-assisted phacoemulsification (FLACS). METHODS: This study enrolled patients with cataract combined with regular corneal astigmatism of >0.75 D, who underwent FLACS. Symmetrical arc incision was set at 8 mm diameter and 85% depth. The follow-up time was 3-24mo (4.92±3.49mo). Pentacam recorded the corneal astigmatism and higher-order aberration at pre-operation and post-operation. The changes in corneal astigmatism were analyzed by Alpins method. The correlation of astigmatism type, age, corneal horizontal diameter, corneal thickness, arc incision length, and correction index (CI) was analyzed, and the residual corneal astigmatism was compared with the residual whole eye astigmatism. RESULTS: Totally 79 patients (102 eyes) were enrolled, 10 patients had corneal epithelial injury, 1 patient occurred corneal epithelial hyperplasia. The corneal astigmatism was 1.23±0.38 D pre-operation, and decreased to 0.76±0.39 D post-operation (t=10.146, P=0.000). Corneal high-order aberration was 0.17±0.08 µm pre-operation and 0.24±0.11 µm post-operation (t=-5.186, P=0.000). The residual corneal astigmatism and residual whole eye astigmatism were no significant difference (t=-0.347, P=0.729). Using Alpin's method, the following were determined: target-induced astigmatism (TIA) =1.23±0.38 D, surgery-induced astigmatism (SIA) =0.77±0.45 D, difference vector (DV)=0.77±0.39 D, and CI=0.54±0.28. Age, astigmatism size, corneal horizontal diameter, corneal thickness, and arc incision length were not correlated with CI. The CI for against the rule astigmatism (ATR) was better than that for with the rule astigmatism (WTR; P=0.001). CONCLUSION: Femtosecond laser-assisted astigmatic keratotomy has better CI of ATR, but increase higher-order corneal aberration. CI is not ideal, it's not a perfect choice if we pursue ideal correction effect.

Sealing mechanism study of laryngeal mask airways via 3D modelling and finite element analysis.

Proper sealing of laryngeal mask airways (LMAs) is critical for airway management in clinical use. Understanding the sealing mechanism can significantly help front-line anaesthetists to reduce the incidence of adverse events. However, anaesthetists, who may not have the most substantial engineering backgrounds, lack intuitive ways to develop an understanding of the LMA sealing mechanism effectively. The paper aims to study the LMA-pharynx sealing mechanisms from the perspective of front-line anaesthetists. We use a computer-aided 3D modelling technique to visualise the LMA-pharynx interactions, which helps anaesthetists identify the critical areas of complications. Furthermore, we conduct a quantitative pressure distribution analysis of the LMA-pharynx contacting surface using the finite element analysis technique, which helps further understand the sealing mechanics in those areas. We present two cases studies based on one male volunteer, aged 50, inserted with a ProSeal LMA. In the first case, a relatively low cuff pressure (CP) was applied to simulate the clinical circumstances in which complications related to air leakage are most likely to happen; in the second case, we increase the CP to a relatively high value to simulate the scenarios with an increased risk of complications related to high mucosal pressure. The experiments suggest the follows: (1) Sore throat complications related to high mucosal pressure is most likely to occur in the hypopharynx with a high CP setting, particularly in the areas where the cricoid cartilage presses the mucosa. (2) The narrow hyoid bone super horn width likely causes LMA insertion difficulties. (3) Insufficient CP will significantly increase the risk of air leakage in the oropharynx. A complete sealing pressure line in the contacting surface will be formed with sufficient CP, thereby preventing the air leakage into the oral.

Electrochemiluminescence from a biocatalysis accelerated N-(aminobutyl)-N-(ethylisoluminol)/dissolved O2 system for microRNA detection.

A kind of biocatalyst, laccase, has been employed as a biocompatible coreactant accelerator to efficiently catalyze coreactant (dissolved O2) for generating high local concentration of superoxide radical (O2•-), acquiring high-intense electrochemiluminescence (ECL) emission of ABEI (N-(aminobutyl)-N-(ethylisoluminol))/dissolved O2 system. Furthermore, a modified strand displacement reaction with excellent amplification efficiency was constructed by replacing traditional single strand DNA to the hairpin DNA as template for triggering the immobilization of more signal probes. As a result, the biosensor for microRNA-21 determination has preeminent selectivity and favorable sensitivity with detection limit down to 80.8 aM. Significantly, the devised strategy has blazed a new path for seeking more coreaction accelerators with splendid biocompatibility thus promoting the application of ternary ECL systems in biological analysis and clinical diagnosis.

The effects of on hemodynamics, oxygen saturation, peak airway pressure and adverse events during anesthesia for thyroid surgery: tracheal intubation Vs. ProSeal laryngeal mask airway.

OBJECTIVE: To investigate the effect of tracheal intubation and ProSeal laryngeal mask airway (PLMA) on hemodynamics, oxygen saturation, peak airway pressure and adverse events during anesthesia for thyroid surgery. METHODS: 65 patients who underwent luminal thyroid surgery under general anesthesia were enrolled as the study subjects, and were divided into control group (30 patients, tracheal intubation) and experimental group (35 patients, PLMA) using random number table. The time to establishment of artificial airway and success rate, hemodynamics, oxygen saturation, peak airway pressure and adverse effects were observed in the two groups. RESULTS: The SBP, DBP, and HR levels of patients in the experimental group were significantly lower than those of control group (P < 0.05), and there were no significant changes in SBP, DBP, and HR levels during the insertion and removal of the laryngeal mask, and the patients were hemodynamically stable. SpO2 and Ppeak values remained stable at 5 min, 30 min, and 60 min after the start and the end of surgery in both groups, and showed no significant difference between the two groups (P > 0.05). A surgical airway was quickly established in both groups, and the time to airway establishment was shorter in the experimental group than in the control group. The incidence of adverse reactions during extubation was lower in the experimental group than in the control group, and the incidence of hoarseness, choking and cough differed significantly between the two groups (P < 0.05), and the adverse reactions in both groups were relieved or disappeared 24 h after the operation. CONCLUSION: With LMPA, patients are more hemodynamically stable during insertion and removal of the mask, have a lower incidence of adverse events, and experience less throat irritation, with safety.

Comparative study of the oxidation of cold-pressed and commercial refined camellia oil during storage with 1H and 31P NMR spectroscopy.

The oxidation of cold-pressed and commercial refined camellia oil stored at room temperature for one year was comparatively studied by 1H and 31P NMR spectroscopy. The oxidation of extra virgin olive oil (EVOO) under the same conditions was further compared. The 1H NMR showed that no aldehydes were formed in the studied period. Coupled with the changes of unsaturated acyl groups, the oxidation degrees of the three oils could be obtained follow the order: commercial refined camellia oil > cold-pressed camellia oil > EVOO. The 31P NMR showed that the evolution of diacylglycerols (DGs) and ratio D in commercial refined camellia oil was fairly different from other two oils. Besides, the kinetics curves of unsaturated acyl groups and ratio D both fit to an exponential equation with high coefficients which indicated that the oxidation of the studied oils progressed in an exponential way with storage time at room temperature.

Determination of the Oxidative Stability of Camellia Oils Using a Chemometrics Tool Based on 1H NMR Spectra and α-Tocopherol Content.

This study, for the first time, predicts oxidative stability in camellia oils by partial least squares (PLS) built with proton nuclear magnetic resonance (1H NMR) and α-tocopherol content. The prediction models were established by the PLS method. Outlier detection, latent variables optimization, data pretreatment, and important variables selection were applied for models optimization. All the developed models exhibited good performance as indicated by R2 > 0.895 and root mean square error of estimation and root mean square error of prediction less than 0.322 and 0.307. For verification of the contribution of 1H NMR spectra and α-tocopherol for prediction performance, a PLS model with fatty acids composition instead of 1H NMR spectra and one with only 1H NMR spectra as input variables were developed, respectively. The results showed that the model based on 1H NMR data was more accurate and precise than that based on fatty acid composition data. And the performance of the models was significantly degraded without α-tocopherol as input variables.

Novel ABEI/Dissolved O2/Ag3BiO3 Nanocrystals ECL Ternary System with High Luminous Efficiency for Ultrasensitive Determination of MicroRNA.

Herein, a ternary electrochemiluminescence (ECL) sensing platform with high luminous efficiency was established for ultrasensitive bioanalysis of the microRNA-21 (miR-21) from cancer cell based on N-(aminobutyl)-N-(ethylisoluminol) (ABEI) as ECL emitter, dissolved O2 as coreactant, and silver bismuth oxide nanocrystals (Ag3BiO3 NCs) as coreaction accelerator. Specifically, a novel coreaction accelerator Ag3BiO3 NCs was introduced into the ABEI/dissolved O2 system to form an ECL ternary system, which could promote the reduction of dissolved O2 to generate great deal of superoxide anion radical (O2•-), reacting with the ABEI to dramatically enhance the ECL performance. Simultaneously, a small amount of target miR-21 could trigger a one-step DNA self-assembly to form the DNA nanonet for embedding abundance ABEI with the assistance of doxorubicin hydrochloride (Dox), realizing the high-intense ECL response. Furthermore, owing to the thin-layer and porous structure, the obtained DNA nanonet could shorten the electron-transfer path of the ternary ECL system to reduce the energy loss, further improving the sensitivity of the sensing platform. As expected, the developed ECL sensing platform of miR-21 detection manifested prominent sensitivity with a low detection limit of 7.1 aM in the concentration of miR-21 range from 10 aM to 100 pM. Satisfactorily, the proposed sensing platform was triumphantly applied to detect miRNA in tumor cell lysates. Consequently, the designed strategy broadened the application of ABEI in biological analysis and hewed out a new path to establish the ECL ternary system with high luminous efficiency.

Therapeutic effects of various therapeutic strategies on non-exudative age-related macular degeneration: A PRISMA-compliant network meta-analysis of randomized controlled trials.

PURPOSE: Age-related macular degeneration (AMD) is a chronic progressive central retinal disease. Geographic atrophy (GA) is a late stage of dry AMD (DAMD) and is a slowly but inexorably progressive disease that causes irreversible blindness over time. We aimed to assess various therapeutic strategies for DAMD and GA treatment by network meta-analysis. METHODS: We searched PubMed, Embase, and the Cochrane Library to identify randomized controlled trials (RCTs) of atrophic AMD treatments published prior to December 16, 2017. Best-corrected visual acuity (BCVA) and change in GA area were evaluated to reflect therapeutic effects. A random-effects network meta-analysis, with a frequentist framework, was used to assess the effectiveness of therapeutic strategies for DAMD treatment. RESULTS: We included 22 articles that assessed 16 types of regimens and 2482 patients in our meta-analysis. The network meta-analysis results showed that zinc-monocysteine (98.1%) was the most likely to improve BCVA (logMAR), followed by alprostadil (84.0%), eculizumab (70.5%), and rheohemapheresis (67.3%). In BCVA (letters) outcomes, rheohemapheresis (99.6%), lampalizumab (69.5%), and the antioxidant complex (67.9%) showed marked benefits in visual function recovery. Regarding the outcome of GA area change, isopropyl unoprostone (IU) (88.6%) might have the best GA area reduction; however, there was no significant difference between IU and the blank control. CONCLUSIONS: Zinc-monocysteine and rheohemapheresis showed significantly better effects on BCVA (logMAR) improvement, and compared with the blank control, rheohemapheresis and the antioxidant complex showed better effects on BCVA (letters) improvement. Other treatments have potential effects on DAMD, including alprostadil, eculizumab, and lampalizumab. However, there is no effective treatment for GA area reduction.

An ultrasensitive electrochemiluminescence biosensor for detection of MicroRNA by in-situ electrochemically generated copper nanoclusters as luminophore and TiO2 as coreaction accelerator.

Herein, we constructed an ultrasensitive electrochemiluminescence (ECL) biosensor for detecting microRNA-21 (miR-21) based on in-situ generation of copper nanoclusters (Cu NCs) as luminophore and titanium dioxide (TiO2) as coreaction accelerator. First, numerous AT-rich double-stranded DNA (dsDNA) was produced from the conversion of a small amount of target miR-21 via the combination of exonuclease III (Exo III)-assisted amplification and hybridization chain reaction (HCR), which could reduce the aggregation-caused self-etching effect of Cu NCs and improve the emitting of Cu NCs. Simultaneously, the introduction of TiO2 in the sensing interface not just acted as the immobilizer of dsDNA-stabilized Cu NCs, more than acted as the coreaction accelerator to accelerate the reduction of the coreaction reagent (S2O82-) for significantly enhancing the ECL efficiency of Cu NCs. The biosensor showed an excellent linear relationship in the concentration range from 100 aM to 100 pM with the detection limit of 19.05 aM Impressively, the strategy not only opened up a novel and efficient preparation method for the Cu NCs, but expanded the application of Cu NCs in ultrasensitive biodetection owing to the addition of coreaction accelerator.