Oriented cellulose hydrogel: Directed tissue regeneration for reducing corneal leukoplakia and managing fungal corneal ulcers.

Fungal corneal ulcer is one of the leading causes of corneal blindness in developing countries. Corneal scars such as leukoplakia are formed due to inflammation, oxidative stress and non-directed repair, which seriously affect the patients' subsequent visual and life quality. In this study, drawing inspiration from the oriented structure of collagen fibers within the corneal stroma, we first proposed the directional arrangement of CuTA-CMHT hydrogel system at micro and macro scales based on the 3D printing extrusion method combined with secondary patterning. It played an antifungal role and induced oriented repair in therapy of fungal corneal ulcer. The results showed that it effectively inhibited Candida albicans, Aspergillus Niger, Fusarium sapropelum, which mainly affects TNF, NF-kappa B, and HIF-1 signaling pathways, achieving effective antifungal functions. More importantly, the fibroblasts interacted with extracellular matrix (ECM) of corneal stroma through formation of focal adhesions, promoted the proliferation and directional migration of cells in vitro, induced the directional alignment of collagen fibers and corneal stromal orthogonally oriented repair in vivo. This process is mainly associated with MYLK, MYL9, and ITGA3 molecules. Furthermore, the downregulation the growth factors TGF-ß and PDGF-ß inhibits myofibroblast development and reduces scar-type ECM production, thereby reducing corneal leukoplakia. It also activates the PI3K-AKT signaling pathway, promoting corneal healing. In conclusion, the oriented CuTA-CMHT hydrogel system mimics the orthogonal arrangement of collagen fibers, inhibits inflammation, eliminates reactive oxygen species, and reduces corneal leukoplakia, which is of great significance in the treatment of fungal corneal ulcer and is expected to write a new chapter in corneal tissue engineering.

Seasonal migration patterns of Siberian Rubythroat (Calliope calliope) facing the Qinghai-Tibet Plateau.

BACKGROUND: Small songbirds respond and adapt to various geographical barriers during their annual migration. Global flyways reveal the diverse migration strategies in response to different geographical barriers, among which are high-elevation plateaus. However, few studies have been focused on the largest and highest plateau in the world, the Qinghai-Tibet Plateau (QTP) which poses a significant barrier to migratory passerines. The present study explored the annual migration routes and strategies of a population of Siberian Rubythroats (Calliope calliope) that breed on the north-eastern edge of the QTP. METHODS: Over the period from 2021 to 2023, we applied light-level geolocators (13 deployed, seven recollected), archival GPS tags (45 deployed, 17 recollected), and CAnMove multi-sensor loggers (with barometer, accelerometer, thermometer, and light sensor, 20 deployed, six recollected) to adult males from the breeding population of Siberian Rubythroat on the QTP. Here we describe the migratory routes and phenology extracted or inferred from the GPS and multi-sensor logger data, and used a combination of accelerometric and barometric data to describe the elevational migration pattern, flight altitude, and flight duration. All light-level geolocators failed to collect suitable data. RESULTS: Both GPS locations and positions derived from pressure-based inference revealed that during autumn, the migration route detoured from the bee-line between breeding and wintering grounds, leading to a gradual elevational decrease. The spring route was more direct, with more flights over mountainous areas in western China. This different migration route during spring probably reflects a strategy for faster migration, which corresponds with more frequent long nocturnal migration flights and shorter stopovers during spring migration than in autumn. The average flight altitude (1856 ± 781 m above sea level) was correlated with ground elevation but did not differ between the seasons. CONCLUSIONS: Our finding indicates strong, season-dependent impact of the Qinghai-Tibet Plateau on shaping passerine migration strategies. We hereby call for more attention to the unexplored central-China flyway to extend our knowledge on the environment-migration interaction among small passerines.

Exploitation of enhanced prime editing for blocking aberrant angiogenesis.

INTRODUCTION: Aberrant angiogenesis plays an important part in the development of a variety of human diseases including proliferative diabetic retinopathy, with which there are still numerous patients remaining a therapeutically challenging condition. Prime editing (PE) is a versatile gene editing approach, which offers a novel opportunity to genetically correct challenging disorders. OBJECTIVES: The goal of this study was to create a dominant-negative (DN) vascular endothelial growth factor receptor (VEGFR) 2 by editing genomic DNA with an advanced PE system to block aberrant retinal angiogenesis in a mouse model of oxygen-induced retinopathy. METHODS: An advanced PE system (referred to as PE6x) was established within two lentiviral vectors, with one carrying an enhanced PE guide RNA and a canonical Cas9 nickase fused with an optimized reversal transcriptase, and the other conveying a nicking guide RNA and a DN-MLH1 to improve PE efficiency. Dual non-integrating lentiviruses (NILVs) produced with the two lentiviral PE6x vectors were then employed to create a mutation of VEGFR2 T17967A by editing the Mus musculus VEGFR2 locus in vitro and in vivo, leading to generation of a premature stop codon (TAG, K796stop) to produce DN-VEGFR2, to interfere with the wild type VEGFR2 which is essential for angiogenesis. RESULTS: NILVs targeting VEGFR2 delivered into cultured murine vascular endothelial cells led to 51.06 % VEGFR2 T17967A in the genome analyzed by next generation sequencing and the production of DN-VEGFR2, which was found to hamper VEGF-induced VEGFR2 phosphorylation, as demonstrated by Western blot analysis. Intravitreally injection of the dual NILVs into postnatal day 12 mice in a model of oxygen-induced retinopathy, led to production of retinal DN-VEGFR2 in postnatal day 17 mice which blocked retinal VEGFR2 expression and activation as well as abnormal retinal angiogenesis without interfering with retinal structure and function, as assessed by electroretinography, optical coherence tomography, fundus fluorescein angiography and histology. CONCLUSION: DN-VEGFR2 resulted from editing genomic VEGFR2 using the PE6x system can be harnessed to treat intraocular pathological angiogenesis.

Multi-risk factors joint prediction model for risk prediction of retinopathy of prematurity.

Purpose: Retinopathy of prematurity (ROP) is a retinal vascular proliferative disease common in low birth weight and premature infants and is one of the main causes of blindness in children.In the context of predictive, preventive and personalized medicine (PPPM/3PM), early screening, identification and treatment of ROP will directly contribute to improve patients' long-term visual prognosis and reduce the risk of blindness. Thus, our objective is to establish an artificial intelligence (AI) algorithm combined with clinical demographics to create a risk model for ROP including treatment-requiring retinopathy of prematurity (TR-ROP) infants. Methods: A total of 22,569 infants who underwent routine ROP screening in Shenzhen Eye Hospital from March 2003 to September 2023 were collected, including 3335 infants with ROP and 1234 infants with TR-ROP among ROP infants. Two machine learning methods of logistic regression and decision tree and a deep learning method of multi-layer perceptron were trained by using the relevant combination of risk factors such as birth weight (BW), gestational age (GA), gender, whether multiple births (MB) and mode of delivery (MD) to achieve the risk prediction of ROP and TR-ROP. We used five evaluation metrics to evaluate the performance of the risk prediction model. The area under the receiver operating characteristic curve (AUC) and the area under the precision-recall curve (AUCPR) were the main measurement metrics. Results: In the risk prediction for ROP, the BW + GA demonstrated the optimal performance (mean ± SD, AUCPR: 0.4849 ± 0.0175, AUC: 0.8124 ± 0.0033). In the risk prediction of TR-ROP, reasonable performance can be achieved by using GA + BW + Gender + MD + MB (AUCPR: 0.2713 ± 0.0214, AUC: 0.8328 ± 0.0088). Conclusions: Combining risk factors with AI in screening programs for ROP could achieve risk prediction of ROP and TR-ROP, detect TR-ROP earlier and reduce the number of ROP examinations and unnecessary physiological stress in low-risk infants. Therefore, combining ROP-related biometric information with AI is a cost-effective strategy for predictive diagnostic, targeted prevention, and personalization of medical services in early screening and treatment of ROP.

Protocol for performing deep learning-based fundus fluorescein angiography image analysis with classification and segmentation tasks.

Fundus fluorescein angiography (FFA) examinations are widely used in the evaluation of fundus disease conditions to facilitate further treatment suggestions. Here, we present a protocol for performing deep learning-based FFA image analytics with classification and segmentation tasks. We describe steps for data preparation, model implementation, statistical analysis, and heatmap visualization. The protocol is applicable in Python using customized data and can achieve the whole process from diagnosis to treatment suggestion of ischemic retinal diseases. For complete details on the use and execution of this protocol, please refer to Zhao et al.1.

Microbiota and metabolite alterations in pancreatic head and body/tail cancer patients.

Pancreatic head cancer (PHC) and pancreatic body/tail cancer (PBTC) have distinct clinical and biological behaviors. The microbial and metabolic differences in PHC and PBTC have not been studied. The pancreatic microbiota and metabolome of 15 PHC and 8 PBTC tissues and their matched nontumor tissues were characterized using 16S rRNA amplicon sequencing and untargeted metabolomics. At the genus level, Bradyrhizobium was increased while Corynebacterium and Ruminococcus were decreased in the PHC tissues (Head T) compared with the matched nontumor tissues (Head N) significantly. Shuttleworthia, Bacillus, and Bifidobacterium were significantly decreased in the PBTC tissues (Body/Tail T) compared with the matched nontumor tissues (Body/Tail N). Significantly, Ileibacterium was increased whereas Pseudoxanthomonas was decreased in Head T and Body/Tail T, and Lactobacillus was increased in Head T but decreased in Body/Tail T. A total of 102 discriminative metabolites were identified between Head T and Head N, which were scattered through linoleic acid metabolism and purine metabolism pathways. However, there were only four discriminative metabolites between Body/Tail T and Body/Tail N, which were related to glycerophospholipid metabolism and autophagy pathways. The differential metabolites in PHC and PBTC were commonly enriched in alpha-linolenic acid metabolism and choline metabolism in cancer pathways. Eubacterium decreased in Head T was positively correlated with decreased linoleic acid while negatively correlated with increased arachidyl carnitine and stearoylcarnitine. Bacillus decreased in Body/Tail T was negatively correlated with increased L-carnitine. These microbiota and metabolites deserve further investigations to reveal their roles in the pathogenesis of PHC and PBTC, providing clues for future treatments.

A fundus image dataset for intelligent retinopathy of prematurity system.

Image-based artificial intelligence (AI) systems stand as the major modality for evaluating ophthalmic conditions. However, most of the currently available AI systems are designed for experimental research using single-central datasets. Most of them fell short of application in real-world clinical settings. In this study, we collected a dataset of 1,099 fundus images in both normal and pathologic eyes from 483 premature infants for intelligent retinopathy of prematurity (ROP) system development and validation. Dataset diversity was visualized with a spatial scatter plot. Image classification was conducted by three annotators. To the best of our knowledge, this is one of the largest fundus datasets on ROP, and we believe it is conducive to the real-world application of AI systems.

Spatiotemporal distribution and lag effect of extreme temperature exposure on mortality of residents in Jiangsu, China.

Background: With the ever-increasing occurrence of extreme weather events as a result of global climate change, the impact of extreme temperatures on human health has become a critical area of concern. Specifically, it is imperative to investigate the impact of extreme weather conditions on the health of residents. Methods: In this study, we analyze the daily death data from 13 prefecture-level cities in Jiangsu Province from January 2014 to September 2022, using the distributed lag nonlinear model (DLNM) to comprehensively account for factors such as relative humidity, atmospheric pressure, air pollutants, and other factors to evaluate the lag and cumulative effects of extreme low temperature and high temperature on the death of residents across different age groups. Additionally, we utilize the Geographical Detector to analyze the effects of various meteorological and environmental factors on the distribution of resident death in Jiangsu Province. This provides valuable insights that can guide health authorities in decision-making and in the protection of residents. Results: The experimental results indicate that both extreme low and high temperatures increase the mortality of residents. We observe that the impact of extreme low temperatures has a delayed effect, peaking after 3-5 days and lasting up to 11-21 days. In contrast, the impact of extreme high temperature is greatest on the first day, and lasts only 2-4 days. Conclusion: Both extreme high and low temperatures increase the mortality of residents, with the former being more transient and stronger and the latter being more persistent and slower. Furthermore, residents over 75 years of age are more vulnerable to the effects of extreme temperatures. Finally, we note that the spatial distribution of resident deaths is most closely associated consistent with the spatial distribution of daily mean temperature, and there is significant spatial heterogeneity in deaths among residents in Jiangsu Province.

Effectiveness and safety of early lens extraction during par plana vitrectomy for proliferative diabetes retinopathy with mild cataract: a randomized clinical trial.

AIM: To evaluate the effectiveness and safety of early lens extraction during pars plana vitrectomy (PPV) for proliferative diabetic retinopathy (PDR) compared to those of PPV with subsequent cataract surgery. METHODS: This multicenter randomized controlled trial was conducted in three Chinese hospitals on patients with PDR, aged >45y, with mild cataracts. The participants were randomly assigned to the combined (PPV combined with simultaneously cataract surgery, i.e., phacovitrectomy) or subsequent (PPV with subsequent cataract surgery 6mo later) group and followed up for 12mo. The primary outcome was the change in best-corrected visual acuity (BCVA) from baseline to 6mo, and the secondary outcomes included complication rates and medical expenses. RESULTS: In total, 129 patients with PDR were recruited and equally randomized (66 and 63 in the combined and subsequent groups respectively). The change in BCVA in the combined group [mean, 36.90 letters; 95% confidence interval (CI), 30.35-43.45] was significantly better (adjusted difference, 16.43; 95%CI, 8.77-24.08; P<0.001) than in the subsequent group (mean, 22.40 letters; 95%CI, 15.55-29.24) 6mo after the PPV, with no significant difference between the two groups at 12mo. The overall surgical risk of two sequential surgeries was significantly higher than that of the combined surgery for neovascular glaucoma (17.65% vs 3.77%, P=0.005). No significant differences were found in the photocoagulation spots, surgical time, and economic expenses between two groups. In the subsequent group, the duration of work incapacity (22.54±9.11d) was significantly longer (P<0.001) than that of the combined group (12.44±6.48d). CONCLUSION: PDR patients aged over 45y with mild cataract can also benefit from early lens extraction during PPV with gratifying effectiveness, safety and convenience, compared to sequential surgeries.

Strain-Controlled Formation Energy and Migration of Nitrogen Vacancy in Al1-xScxN: A First-Principles Study.

The impact of strain on the formation energy and migration behavior of nitrogen vacancies (VNs) in Al1-xScxN has been investigated by first-principles calculations. The formation energy of VNs is obtained by total energy calculations. The migration barrier calculation utilizes the climbing nudged elastic band method. It is found that the formation energy of VNs is highly tunable with respect to the strain. The formation energy of VNs increases with the tensile strain increasing to +4% and decreases with the increasing compressive strain to -4%. A minimum formation energy of 4.11 eV is obtained when -4% strain is applied. Furthermore, the migration behavior of VNs is studied by calculating the migration barriers. Calculation results show that the migration barrier is strongly affected by strain. When the strain is -4%, the barrier is 2.46 eV while the barrier is increased to 2.71 eV under +4% strain. Therefore, a tensile strain can prevent the formation and migration of VNs. These findings suggest that strain engineering may serve as a tool for regulating VNs behavior in Al1-xScxN, potentially alleviating the ferroelectric degradations associated with VNs.

Short-Term Effects of Extreme Meteorological Factors on Hand, Foot, and Mouth Disease Infection During 2010-2017 in Jiangsu, China: A Distributed Lag Non-Linear Analysis.

Hand, Foot, and Mouth Disease (HFMD) is an infectious disease that primarily affects young children. In densely populated Jiangsu Province in China, the impact of extreme meteorological factors on HFMD is a concern. We aimed to examine the association between extreme meteorological variables and HFMD infection risk using daily HFMD infections and meteorological data from 2010 to 2017 in Jiangsu Province. We used distributed lag non-linear model (DLNM) to analyze the data, which can effectively capture the nuanced non-linear dynamics and lag effects in the relationship between HFMD and extreme meteorological factors. Comparing the 10th and 90th percentiles of meteorological variables with their respective median values, our results showed that extremely low temperatures and high humidity were significantly associated with increased HFMD infection risk. The greatest effect of extremely low temperatures was observed at a lag of 1-2 days, elevating the risk by 18 âˆ¼ 33% (RR = 1.18 âˆ¼ 1.33). Extremely high humidity was found to increase the risk of infection, starting at a lag of 4 days. In contrast, extremely high temperatures, low humidity, and high wind speed were associated with reduced risk of infection at lag of 0-12 days, with the range of RR values being 0.60-0.98 for extremely high temperatures, 0.69-0.89 for extremely low humidity, and 0.84-0.98 for extremely high wind speed respectively. Our findings suggest that extreme meteorological factors can significantly impact the incidence of HFMD in Jiangsu Province, and highlight the need for effective public health protection measures during the periods of extreme meteorological condition, particularly for vulnerable populations.

Long-term follow-up of the cognitive function in children after intravitreal ranibizumab for retinopathy of prematurity.

PURPOSE: To evaluate the long-term cognitive function in children treated with intravitreal ranibizumab (IVR) for retinopathy of prematurity(ROP), and the impact of IVR on the growth and ocular development. METHODS: In this retrospective study, the premature children aged 4 to 9 years who received monotherapy of IVR (IVR group, n = 25) or monotherapy of laser photocoagulation (LP) (LP group, n = 33) for ROP, and the same age premature children with no ROP (Control group, n = 26) were enrolled from 2020 to 2022 in the pediatric fundus clinic of Shenzhen Eye Hospital. Main outcome measures were full-scale intelligence quotient (FSIQ) and index score using the Chinese version of the Wechsler intelligence scale for children-fourth edition (WISC-IV) and Wechsler preschool and primary scale of intelligence-fourth edition (WPPSI-IV). All children were examined and analyzed for growth and ocular development by recording the height, weight, head circumference, spherical equivalent (SE), best corrected visual acuity (BCVA) and axial length (AL). RESULTS: There were 17 children in IVR group, 17 in LP group, and 11 in Control group who received the WISC-IV assessment. There were no significant differences in FSIQ, verbal comprehension index, perceptual reasoning index, working memory index, processing speed index, general ability index and cognitive efficiency index among the three groups. There were 8 children in IVR group, 16 in LP group, and 15 in Control group who received the WPPSI-IV assessment. There were no significant differences in FSIQ, verbal comprehension index, visuospatial index, fluid reasoning index, working memory index, non-verbal index, general ability index and cognitive efficiency index among the three groups. There was no significant difference in BCVA among the three groups (P = 0.74), however, there is an increase for AL in IVR group when compared with LP group (22.60 ± 0.58 vs. 22.13 ± 0.84, P = 0.003), and the ROP patients of IVR group have a significant increase in the AL compared to the Control group(22.60 ± 0.58 vs. 22.03 ± 0.71, P < 0.0001). CONCLUSIONS: Children with a history of IVR have a similar cognitive function outcomes compared to those with a history of LP or were premature without ROP. ROP children with a history of IVR has longer AL than those treated with LP.

Thermosensitive hydrogel containing ethosuximide-loaded multivesicular liposomes attenuates age-related hearing loss in C57BL/6J mice.

Ethosuximide is the first drug reported to protect against age-related hearing loss, but its benefits are hampered by the pronounced side effects generated through systemic administration. We prepared a thermosensitive hydrogel containing ethosuximide-encapsulated multivesicular liposomes (ethosuximide-loaded MVLs-Gel) and evaluated its functional and histological effects on age-related hearing loss in C57BL/6J mice. The MVLs-Gel showed slow sustained-release characteristics up to over 120 h. After 8 weeks of treatment, compared to the oral systemic administration of ethosuximide, intratympanic ethosuximide-loaded MVLs-Gel injection dramatically reduced the loss of age-related spiral ganglion neurons in the apical turns of the mice (low-frequency regions, p < 0.05). Correspondingly, compared to the oral systemic administration group, the intratympanic ethosuximide-loaded MVLs-Gel injection group showed significantly lower auditory brainstem response threshold shifts at stimulus frequencies of 4, 8, and 16 kHz (low-and middle-frequency regions, p < 0.05). In conclusion, intratympanic ethosuximide-loaded MVLs-Gel injection can reach the apical turn of the cochlea, which is extremely difficult with oral systemic administration of the drug. The ethosuximide-loaded MVLs-Gel, as a novel intratympanic sustained-release drug delivery system, attenuated age-related hearing loss in C57BL/6J mice.

Automated detection of nine infantile fundus diseases and conditions in retinal images using a deep learning system.

Purpose: We developed an Infant Retinal Intelligent Diagnosis System (IRIDS), an automated system to aid early diagnosis and monitoring of infantile fundus diseases and health conditions to satisfy urgent needs of ophthalmologists. Methods: We developed IRIDS by combining convolutional neural networks and transformer structures, using a dataset of 7697 retinal images (1089 infants) from four hospitals. It identifies nine fundus diseases and conditions, namely, retinopathy of prematurity (ROP) (mild ROP, moderate ROP, and severe ROP), retinoblastoma (RB), retinitis pigmentosa (RP), Coats disease, coloboma of the choroid, congenital retinal fold (CRF), and normal. IRIDS also includes depth attention modules, ResNet-18 (Res-18), and Multi-Axis Vision Transformer (MaxViT). Performance was compared to that of ophthalmologists using 450 retinal images. The IRIDS employed a five-fold cross-validation approach to generate the classification results. Results: Several baseline models achieved the following metrics: accuracy, precision, recall, F1-score (F1), kappa, and area under the receiver operating characteristic curve (AUC) with best values of 94.62% (95% CI, 94.34%-94.90%), 94.07% (95% CI, 93.32%-94.82%), 90.56% (95% CI, 88.64%-92.48%), 92.34% (95% CI, 91.87%-92.81%), 91.15% (95% CI, 90.37%-91.93%), and 99.08% (95% CI, 99.07%-99.09%), respectively. In comparison, IRIDS showed promising results compared to ophthalmologists, demonstrating an average accuracy, precision, recall, F1, kappa, and AUC of 96.45% (95% CI, 96.37%-96.53%), 95.86% (95% CI, 94.56%-97.16%), 94.37% (95% CI, 93.95%-94.79%), 95.03% (95% CI, 94.45%-95.61%), 94.43% (95% CI, 93.96%-94.90%), and 99.51% (95% CI, 99.51%-99.51%), respectively, in multi-label classification on the test dataset, utilizing the Res-18 and MaxViT models. These results suggest that, particularly in terms of AUC, IRIDS achieved performance that warrants further investigation for the detection of retinal abnormalities. Conclusions: IRIDS identifies nine infantile fundus diseases and conditions accurately. It may aid non-ophthalmologist personnel in underserved areas in infantile fundus disease screening. Thus, preventing severe complications. The IRIDS serves as an example of artificial intelligence integration into ophthalmology to achieve better outcomes in predictive, preventive, and personalized medicine (PPPM / 3PM) in the treatment of infantile fundus diseases. Supplementary Information: The online version contains supplementary material available at 10.1007/s13167-024-00350-y.

Morphologic and Functional Assessment of Photoreceptors in Laser-Induced Retinopathy Using Adaptive Optics Scanning Laser Ophthalmoscopy and Microperimetry.

PURPOSE: To assess the cone photoreceptors' morphology and associated retinal sensitivity in laser-induced retinopathy (LIR) using adaptive optics scanning laser ophthalmoscopy (AO-SLO) and microperimetry (MP). DESIGN: Cohort study. METHODS: This study included 13 patients (15 eyes) with LIR and 38 age-matched healthy volunteers (38 eyes). Participants underwent comprehensive evaluations including AO-SLO, MP, and spectral-domain OCT. Lesion morphology, cone density, dispersion, and regularity in AO-SLO were assessed and correlated with visual function. RESULTS: In AO-SLO images, LIR lesions were predominantly characterized by hyporeflective regions, suggesting potential cone loss at the fovea, accompanied by the presence of sizable clumps of hyperreflective material within these lesions. The average size of lesions in affected eyes was 97,128±107,478 µm², ranging from 6705 to 673,348 µm². Compared with the healthy contralateral eye and control group, LIR demonstrated significantly reduced cone density, increased cone dispersion, and notably decreased cone regularity in all 4 quadrants at 3° eccentricity (all P values < .05). Lesion morphology in AO-SLO correlated with ellipsoid zone defects observed in OCT, showing a positive correlation in size (r = 0.84, P < .001) but not with retinal sensitivities (P = .09). Similarly, cone density at 3° eccentricity did not correlate with retinal sensitivities (P = .13). CONCLUSIONS AND RELEVANCE: The study provides crucial insights into the morphologic and functional impacts of LIR on cone photoreceptors, revealing significant morphologic changes in cones that do not consistently align with functional outcomes. This research highlights the need for continued exploration into the relationship between retinal structure and function in LIR, and the importance of heightened public awareness and preventive strategies to mitigate the risk of LIR.

Diagnostic value of Procalcitonin, C-reactive protein-to-lymphocyte ratio (CLR), C-reactive protein and neutrophil-to-lymphocyte ratio (NLR) for predicting patients with Bacteraemia in the intensive care unit.

BACKGROUND: To explore the diagnostic value of procalcitonin (PCT), C-reactive protein-to-lymphocyte ratio (CLR), C-reactive protein (CRP) and neutrophil-to-lymphocyte ratio (NLR) for predicting patients with bacteremia in the intensive care unit (ICU). METHODS: This case-control study included 359 patients with suspected bacteremia were divided into a bacteremia group (n = 152) and a control group (n = 207) from September 2018 to April 2023. Patient data were collected using a laboratory information system (LIS). ROC curves for PCT, CLR, CRP, and NLR in predicting patients with bacteremia. RESULTS: For PCT, CLR, CRP and NLR to predict patients with bacteremia in the ICU, the AUCs were 0.991(95%CI: 0.974-0.998), 0.960(95%CI: 0.935-0.978), 0.955(95%CI: 0.928-0.974), and 0.898(95%CI:0.862-0.927), respectively; the optimal thresholds were 0.248 ng/mL, 47.52 mg/109, 48.32 mg/L, and 6.51, respectively; the sensitivities were 95.4(95%CI: 90.7-98.1), 88.2(95%CI: 81.9-92.8), 87.5(95%CI: 81.2-92.3), and 86.8(95%CI:80.4-91.8), respectively; and the specificities were 95.7(95%CI: 91.9-98.0), 90.8(95%CI: 86.0-94.4), 90.3(95%CI: 85.5-94.0), and 85.0(95%CI:79.4-89.6), respectively. The sensitivities of PCT, CLR, CRP and NLR for predicting bacteremia due to E. coli infection are as high as over 90%, the specificity of PCT is 100, and the sensitivity of NLR is 100. The sensitivity of CRP for predicting bacteremia due to non-Enterobacer infection is 100. CONCLUSIONS: Compared with those in the control group, PCT, CLR, CRP and NLR were significantly greater in the bacteremia group. The PCT, CLR, CRP, and NLR can all predict the occurrence of bacteremia. The PCT had the highest sensitivity and specificity in predicting bacteremia in ICU patients.

A Novel LDLC Equation is Superior to the NIH LDLC Equation and the Friedewald Equation.

Background: LDLC equations have varying levels of underestimation for the calculated LDLC. Therefore, underestimating LDLC should be avoided as much as possible. We need to establish LDLC equations that underestimate LDLC as little as possible. Methods: We established the equations with a healthy cohort from Shuyang Hospital and validated the equations with an unselected patient cohort from The Second People's Hospital of Lianyungang. We established the novel LDLC equations by using the regression equation. The relationship between two markers was analysed using Pearson's approach. The 95% limits of measuring agreement within ±2 SD for the LDLC equations was performed using Bland‒Altman analysis. ROC curve analysis was used to predict LDLC levels and the accuracy of the LDLC equation for determining the direct LDLC levels at LDLC cut-offs was assessed. Results: We obtained two novel LDLC equations (LDL_nonHDLC equation=-0.899+1.195*nonHDLC-0.00347*nonHDLC2 and LDL_TC(total cholesterol) equation=-2.775+1.29*TC -0.00990* TC 2). The correlation coefficient between the novel LDLC equation and the direct LDLC measurements is not lower than that between the LDL_NIH equation and the direct LDLC measurements. The AUCs of our novel LDLC equations were greater than those of the LDL_NIH equation and the LDL_F equation at the LDLC cut-offs for clinical decision-making. The measuring agreement in the methods of the LDL_nonHDL equation is superior to that of the LDL_NIH equation. Conclusion: LDLC calculated by the novel LDL_nonHDL equation exhibited superiority over the LDL_NIH equation. Combining the LDL_NIH equation and our novel LDLC equation may improve accuracy and avoid undertreatment of high LDLC levels.

Revealing new insights: Two-center evidence of microplastics in human vitreous humor and their implications for ocular health.

Microplastics (MPs), an emerging environmental contaminant, have raised growing health apprehension due to their detection in various human biospecimens. Despite extensive research into their prevalence in the environment and the human body, the ramifications of their existence within the enclosed confines of the human eye remain largely unexplored. Herein, we assembled a cohort of 49 patients with four ocular diseases (macular hole, macular epiretinal membrane, retinopathy and rhegmatogenous retinal detachment) from two medical centers. After processing the samples with an optimized method, we utilized Laser Direct Infrared (LD-IR) spectroscopy and Pyrolysis Gas Chromatography/Mass Spectrometry (Py-GC/MS) to analyze 49 vitreous samples, evaluating the characteristics of MPs within the internal environment of the human eye. Our results showed that LD-IR scanned a total of 8543 particles in the composite sample from 49 individual vitreous humor samples, identifying 1745 as plastic particles, predominantly below 50 µm. Concurrently, Py-GC/MS analysis of the 49 individual samples corroborated these findings, with nylon 66 exhibiting the highest content, followed by polyvinyl chloride, and detection of polystyrene. Notably, correlations were observed between MP levels and key ocular health parameters, particularly intraocular pressure and the presence of aqueous humor opacities. Intriguingly, individuals afflicted with retinopathy demonstrated heightened ocular health risks associated with MPs. In summary, this research provides significant insights into infiltration of MP pollutants within the human eye, shedding light on their potential implications for ocular health and advocating for further exploration of this emerging health risk.

Müller cells under hydrostatic pressure modulate retinal cell survival via TRPV1/PLCγ1 complex-mediated calcium influx in experimental glaucoma.

Glaucoma, an irreversible blinding eye disease, is currently unclear whose pathological mechanism is. This study investigated how transient receptor potential cation channel subfamily V member 1 (TRPV1), 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 (PLCγ1), and P2X purinoceptor 7 (P2X7) modulate the levels of intracellular calcium ions (Ca2+) and adenosine triphosphate (ATP) in Müller cells and retinal ganglion cells (RGCs) under conditions of elevated intraocular pressure (IOP). Müller cells were maintained at hydrostatic pressure (HP). TRPV1- and PLCG1-silenced Müller cells and P2X7-silenced RGCs were constructed by transfection with short interfering RNA (siRNAs). RGCs were cultured with the conditioned media of Müller cells under HP. A mouse model of chronic ocular hypertension (COH) was established and used to investigate the role of TRPV1 in RGCs in vivo. Müller cells and RGCs were analyzed by ATP release assays, intracellular calcium assays, CCK-8 assays, EdU (5-ethynyl-2'-deoxyuridine) staining, TUNEL staining, flow cytometry, and transmission electron microscopy. In vivo changes in inner retinal function were evaluated by hematoxylin and eosin (H&E) staining and TUNEL staining. Western blot analyses were performed to measure the levels of related proteins. Our data showed that HP increased the levels of ATP and Ca2+ influx in Müller cells, and those increases were accompanied by the upregulation of TRPV1 and p-PLCγ1 expression. Suppression of TRPV1 or PLCG1 expression in Müller cells significantly decreased the ATP levels and intracellular Ca2+ accumulation induced by HP. Knockdown of TRPV1, PLCG1, or P2X7 significantly decreased apoptosis and autophagy in RGCs cultured in the conditioned media of HP-treated Müller cells. Moreover, TRPV1 silencing decreased RGC apoptosis and autophagy in the in vivo model of COH. Collectively, inhibition of TRPV1/PLCγ1 and P2X7 expression may be a useful therapeutic strategy for managing RGC death in glaucoma.

Multiplatform tear proteomic profiling reveals novel non-invasive biomarkers for diabetic retinopathy.

OBJECTIVES: To investigate a comprehensive proteomic profile of the tear fluid in patients with diabetic retinopathy (DR) and further define non-invasive biomarkers. METHODS: A cross-sectional, multicentre study that includes 46 patients with DR, 28 patients with diabetes mellitus (DM), and 30 healthy controls (HC). Tear samples were collected with Schirmer strips. As for the discovery set, data-independent acquisition mass spectrometry was used to characterize the tear proteomic profile. Differentially expressed proteins between groups were identified, with gene ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes enrichment analysis further developed. Classifying performance of biomarkers for distinguishing DR from DM was compared by the combination of three machine-learning algorithms. The selected biomarker panel was tested in the validation cohort using parallel reaction monitoring mass spectrometry. RESULTS: Among 3364 proteins quantified, 235 and 88 differentially expressed proteins were identified for DR when compared to HC and DM, respectively, which were fundamentally related to retina homeostasis, inflammation and immunity, oxidative stress, angiogenesis and coagulation, metabolism, and cellular adhesion processes. The biomarker panel consisting of NAD-dependent protein deacetylase sirtuin-2 (SIR2), amine oxidase [flavin-containing] B (AOFB), and U8 snoRNA-decapping enzyme (NUD16) exhibited the best diagnostic performance in discriminating DR from DM, with AUCs of 0.933 and 0.881 in the discovery and validation set, respectively. CONCLUSIONS: Tear protein dysregulation is comprehensively revealed to be associated with DR onset. The combination of tear SIR2, AOFB, and NUD16 can be a novel potential approach for non-invasive detection or pre-screening of DR. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Registry Identifier: ChiCTR2100054263. https://www.chictr.org.cn/showproj.html?proj=143177 . Date of registration: 2021/12/12.