A chronotherapeutics-applicable multi-target therapeutics based on AI: Example of therapeutic hypothermia.

Nowadays, the complexity of disease mechanisms and the inadequacy of single-target therapies in restoring the biological system have inevitably instigated the strategy of multi-target therapeutics with the analysis of each target individually. However, it is not suitable for dealing with the conflicts between targets or between drugs. With the release of high-precision protein structure prediction artificial intelligence, large-scale high-precision protein structure prediction and docking have become possible. In this article, we propose a multi-target drug discovery method by the example of therapeutic hypothermia (TH). First, we performed protein structure prediction for all protein targets of each group by AlphaFold2 and RoseTTAFold. Then, QuickVina 2 is used for molecular docking between the proteins and drugs. After docking, we use PageRank to rank single drugs and drug combinations of each group. The ePharmaLib was used for predicting the side effect targets. Given the differences in the weights of different targets, the method can effectively avoid inhibiting beneficial proteins while inhibiting harmful proteins. So it could minimize the conflicts between different doses and be friendly to chronotherapeutics. Besides, this method also has potential in precision medicine for its high compatibility with bioinformatics and promotes the development of pharmacogenomics and bioinfo-pharmacology.

CD93 regulates breast cancer growth and vasculogenic mimicry through the PI3K/AKT/SP2 signaling pathway activated by integrin ß1.

In women, breast cancer (BC) accounts for 7%-10% of all cancer cases and is one of the most common cancers. To identify a new method for treating BC, the role of CD93 and its underlying mechanism were explored. MDA-MB-231 cells were used in this study and transfected with si-CD93, si-MMRN2, oe-CD93, si-integrin ß1, or oe-SP2 lentivirus. After MDA-MB-231 cells were transfected with si-NC or si-CD93, they were injected into nude mice by subcutaneous injection at a dose of 5 × 106/mouse to construct a BC animal model. The expression of genes and proteins and cell migration, invasion and vasculogenic mimicry were detected by RT‒qPCR, western blot, immunohistochemistry, immunofluorescence, Transwell, and angiogenesis assays. In pathological samples and BC cell lines, CD93 was highly expressed. Functionally, CD93 promoted the proliferation, migration, and vasculogenic mimicry of MDA-MB-231 cells. Moreover, CD93 interacts with MMRN2 and integrin ß1. Knockdown of CD93 and MMRN2 can inhibit the activation of integrin ß1, thereby inhibiting the PI3K/AKT/SP2 signaling pathway and inhibiting BC growth and vasculogenic mimicry. In conclusion, the binding of CD93 to MMRN2 can activate integrin ß1, thereby activating the PI3K/AKT/SP2 signaling pathway and subsequently promoting BC growth and vasculogenic mimicry.

Differences between young and elderly polypoidal choroidal vasculopathy patients with and without pachychoroid phenotypes.

PURPOSE: To investigate the distinct characteristics between young and elderly polypoidal choroidal vasculopathy (PCV) patients based on the pachy- or non-pachychoroid phenotypes. METHODS: PCV patients treated with intravitreal injections of Conbercept based on the 3 + PRN regimen from 27 centers of China PCV Research Alliance were included. Patients were categorized into the young and the elderly aged group based on the cut-off point determined using the Youden method according to the pachychoroid phenotypes. The characteristics of past medical history, lifestyle factors, fundus manifestations, and treatment response between the subgroups were analyzed. RESULTS: Three hundred eight eligible patients were included. Multivariate logistic regression showed a significant association between age and PCV subtype classification (OR = 0.921, P = 0.002). A cutoff age of 64.5 effectively distinguished between pachychoroid PCV and non-pachychoroid PCV (P < 0.001). Elderly PCV patients had a higher incidence of hypertension history (P = 0.044) but a lower incidence of diabetes history (P = 0.027). In terms of lifestyle, smoking history (P = 0.015) and staying up late (P = 0.004) were more significant in the young group of PCV patients. For clinical characteristics, the proportion of hemorrhagic PCV in the young group was significantly higher (P = 0.038), with a higher proportion of sharp-peaked PED (P = 0.049), thicker choroid (P < 0.001) but a lower portion of double-layer sign (P = 0.023) in OCT. Both groups showed significant anatomical changes compared to baseline in each follow-up period (P < 0.05), with the young group having a higher proportion of good anatomical response after the first injection (P = 0.009). CONCLUSION: PCV patients stratified by subtype exhibit distinct characteristics between the young and elderly groups.

Evaluation of the First-Dose Anti-VEGF Anatomical Response in Polypoidal Choroidal Vasculopathy Patients: Correlation with the Third-Dose Response and Risk Factor Analysis.

INTRODUCTION: The aims of the study were to investigate whether first-dose efficacy can predict third-dose anatomical response and analyze the risk factors for first-dose response of polypoidal choroidal vasculopathy (PCV) patients. METHODS: We retrospectively reviewed patients' medical records from 27 centers of China PCV Research Alliance. PCV patients treated with intravitreal injections of conbercept (IVC) based on the 3+ pro re nata regimen (three initial monthly injections, followed by injections as needed) with complete 3-month injection data were included. Response correlations, risk factor associations, changes in central macular thickness (CMT) or best-corrected visual acuity (BCVA), and number of injections in the first year of follow-up were evaluated separately in the pachy-PCV and non-pachy-PCV phenotypes. RESULTS: Overall, 165 eligible patients were included. There was a significant correlation between first-dose and third-dose anatomical response in pachy-PCV or non-pachy-PCV patients (rs = 0.611, p < 0.001; rs = 0.638, p < 0.001). Multivariate analysis revealed associations of good first-dose anatomical response in pachy-PCV patients with baseline CMT with a predicted area under the curve (AUC) of 0.847, while a good response in non-pachy-PCV patients was associated with baseline BCVA, baseline CMT, pigment epithelial detachment (PED) height, higher proportion of intraretinal fluid, and lower PED minimum diameter with a predicted AUC of 0.940. CMT in the good first-dose response group was significantly decreased from baseline at all first-year follow-up visits in both groups (p < 0.001), and mean BCVA was improved in the good versus poor first-dose anatomical response group (5.4 vs. 1.6 ETDRS letters in pachy-PCV, 10.6 vs. 7.4 letters in non-pachy-PCV) after the third injection. No significant difference was observed in the number of injections in the first year of follow-up between different response groups. CONCLUSION: In PCV patients receiving IVC, the first- and third-dose responses are significantly correlated, and different factors influence the first-dose response in different subtypes of PCV.

Gut microbiome variations in Rhinopithecus roxellanae caused by changes in the environment.

BACKGROUND: The snub-nosed monkey (Rhinopithecus roxellanae) is an endangered animal species mainly distributed in China and needs to be protected. Gut microbiome is an important determinant of animal health and population survival as it affects the adaptation of the animals to different foods and environments under kinetic changes of intrinsic and extrinsic factors. Therefore, this study aimed to elucidate gut fecal microbiome profiles of snub-nosed monkeys affected by several extrinsic and intrinsic factors, including raising patterns (captive vs. wild), age, sex, and diarrheal status to provide a reference for making protection strategies. RESULTS: The 16S rRNA gene sequencing was firstly used to pre-check clustering of 38 fecal samples from the monkeys including 30 wild and 8 captive (5 healthy and 3 diarrheal) from three Regions of Shennongjia Nature Reserve, Hubei Province, China. Then the 24 samples with high-quality DNA from 18 wild and 6 captive (4 healthy and 2 diarrheal) monkeys were subjected to shotgun metagenomic sequencing to characterize bacterial gut microbial communities. We discovered that the raising pattern (captive and wild) rather than age and sex was the predominant factor attributed to gut microbiome structure and proportionality. Wild monkeys had significantly higher bacterial diversity and lower Bacteroidetes/Firmicutes ratios than captive animals. Moreover, the gut microbiomes in wild healthy monkeys were enriched for the genes involved in fatty acid production, while in captive animals, genes were enriched for vitamin biosynthesis and metabolism and amino acid biosynthesis from carbohydrate intermediates. Additionally, a total of 37 antibiotic resistant genes (ARG) types were detected. Unlike the microbiome diversity, the captive monkeys have a higher diversity of ARG than the wild animals. CONCLUSION: Taken together, we highlight the importance of self-reprogramed metabolism in the snub-nosed monkey gut microbiome to help captive and wild monkeys adapt to different intrinsic and extrinsic environmental change.

Relationship between mental health literacy and professional psychological help-seeking attitudes in China: a chain mediation model.

BACKGROUND: Mental health literacy is considered an important factor in promoting professional psychological help-seeking attitudes. However, it is important to clarify the emotional and behavioral factors that underlie this association. Drawing from the ABC model of attitudes and the Health Disclosure Decision-Making Model, this study aimed to examine the mediating role of psychological help-seeking stigma and distress disclosure in the relationship between mental health literacy and professional psychological help-seeking attitudes. METHODS: We collected data from 827 participants in seven regions of China (597 female; Mage = 26.019, SD = 5.592 years old) using self-report measures, including the Mental Health Literacy Scale, Questionnaire of Stigma for Seeking Professional Psychological Help, Distress Disclosure Index, and Attitudes Toward Seeking Professional Psychological Help-Short Form. A chain mediation model was built to examine the relationships among mental health literacy, psychological help-seeking stigma, distress disclosure, and professional psychological help-seeking attitudes. RESULTS: The results of the analyses showed a positive association between mental health literacy and professional psychological help-seeking attitudes, with psychological help-seeking stigma and distress disclosure playing mediating roles in this relationship. Furthermore, even after controlling for participants' age, gender, and education, the chain mediation effect of psychological help-seeking stigma and distress disclosure on the relationship between mental health literacy and professional psychological help-seeking attitudes was observed among the Chinese population. CONCLUSIONS: These findings underscore the significance of mental health literacy in shaping professional psychological help-seeking attitudes, while emphasizing the need to account for psychological help-seeking stigma and distress disclosure when examining this association. Additionally, the model proposed in this study provides a valuable framework for promoting the utilization of professional mental health services.

THERAPEUTIC EFFECT OF USING AUTOLOGOUS PLATELET CONCENTRATE IN VITRECTOMY FOR MACULAR HOLE: A Systematic Review and Meta-Analysis.

PURPOSE: To summarize the current evidence regarding the therapeutic effect of using autologous platelet concentrate (APC) in vitrectomy for macular hole (MH). METHODS: The PubMed, Web of Science, and Embase databases were searched according to the PROSPERO protocol (CRD42022366202). Controlled trials comparing whether APC was used in the vitrectomy of MH were included. The primary outcome was the closure rate of MH and postoperative best-corrected visual acuity, and the secondary outcome was the incidence of different types of complications. RESULTS: Seven studies that included 634 eyes were eligible. For the primary outcome, the usage of APC significantly improved the closure rate of MH in vitrectomy (odds ratio [OR] = 5.34, 95% confidence interval, 2.83-10.07, P < 0.001). Postoperative visual acuity did not significantly differ between the APC group and similar baseline controls (SMD = -0.07, 95% confidence interval, -0.35 to 0.22, P = 0.644). For the secondary outcome, using APC did not result in additional complications regarding postoperative retinal detachment or the recurrence of MH. CONCLUSION: The use of APC in vitrectomy was associated with a superior closure rate of the hole and no additional complications; therefore, it is effective and safe in MH surgery.

Gender and socioeconomic disparities in global burden of chronic kidney disease due to glomerulonephritis: A global analysis.

AIM: To investigate the gender and socioeconomic disparities in the global burden of chronic kidney disease (CKD) due to glomerulonephritis from 1990 to 2019. METHODS: Data were extracted from the global burden of diseases (GBD) 2019 study, including incidence, prevalence and disability-adjusted life-years (DALYs). Estimated annual percentage changes (EAPCs) were calculated to quantify the temporal trends in age-standardized rate (ASR) of CKD due to glomerulonephritis. Paired t-test, paired Wilcoxon signed-rank test and Spearman correlation were performed to analyse the association and gender disparity in CKD due to glomerulonephritis. RESULTS: Globally, incident cases of CKD due to glomerulonephritis increased 81% from 9 557 397 in 1990 to 17 308 071 in 2019. The age-standardized incidence rate increased by 1.47 compared with 1990 and DALYs increased by 1.35 compared with 1990 (per 100 000). The number of patients with CKD due to glomerulonephritis in low-middle SDI (3829917) and middle SDI (6268817) regions accounts for more than 55% of the total cases. CKD due to glomerulonephritis caused a higher burden including the incidence rate (p < .0001) and DALY rate (p < .0001) in men compared to women. The age-standardized DALY rate was negatively correlated with SDI (ρ = -0.64, p < .001). In the analysis of risk factors for DALYs, male individuals had a larger burden of hypertension, high BMI and high sodium diet in the DALY rates than female subjects. CONCLUSION: The burden of CKD due to glomerulonephritis was more skewed towards developing and less developed economies and differed by gender, so certain nations should implement far more focused and targeted policies.

Graph Multi-Scale Permutation Entropy for Bearing Fault Diagnosis.

Bearing faults are one kind of primary failure in rotatory machines. To avoid economic loss and casualties, it is important to diagnose bearing faults accurately. Vibration-based monitoring technology is widely used to detect bearing faults. Graph signal processing methods promising for the extraction of the fault features of bearings. In this work, graph multi-scale permutation entropy (MPEG) is proposed for bearing fault diagnosis. In the proposed method, the vibration signal is first transformed into a visibility graph. Secondly, a graph coarsening method is used to generate coarse graphs with different reduced sizes. Thirdly, the graph's permutation entropy is calculated to obtain bearing fault features. Finally, a support vector machine (SVM) is applied for fault feature classification. To verify the effectiveness of the proposed method, open-source and laboratory data are used to compare conventional entropies and other graph entropies. Experimental results show that the proposed method has higher accuracy and better robustness and de-noising ability.

Diradicaloid Boron-Doped Molecular Carbons Achieved by Pentagon-Fusion.

Molecular carbons (MCs) are molecular cutouts of carbon materials. Doping with heteroatoms and constructing open-shell structures are two powerful approaches to achieve unexpected and unique properties of MCs. Herein, we disclose a new strategy to design open-shell boron-doped MCs (BMCs), namely by pentagon-fusion of an organoborane π-system. We synthesized two diradicaloid BMC molecules that feature C24 B and C38 B π-skeletons containing a pentagonal ring. A thorough investigation reveals that such pentagon-fusion not only leads to their local antiaromaticity, but also incorporates an internal quinoidal substructure and thereby induces open-shell singlet diradical states. Moreover, their fully fused structures enable efficient π conjugation, which is expanded over the whole frameworks. Consequently, some intriguing physical properties are achieved, such as narrow energy gaps, very broad light absorptions, and superior photothermal capability, along with excellent photostability. Notably, the solid of the C38 B molecule exhibits absorption that covers the range of 300-1200 nm and an efficiency of 93.5 % for solar-driven water evaporation, thus demonstrating the potential of diradicaloid BMCs as high-performance organic photothermal materials.

A pilot study to investigate the alteration of gut microbial profile in Dip2a knockout mice.

Accumulating evidence has pointed out that the gut-brain axis plays important roles in the etiology of autism spectrum disorder (ASD). Gut dysbiosis was reported in both ASD human patients and animal models. Dip2a was identified as a human ASD candidate gene. Deletion of Dip2a led to dendritic spine dysfunction and autistic-like behaviors in mice. To further investigate if Dip2a deletion leads to gut dysbiosis, we used 16S rDNA sequencing to study the gut microbiota in Dip2a KO mice. In both co-housed and separated breeding conditions, deletion of Dip2a could affect the gut microbiome composition. The probiotic bacteria, Lactobacillus and Bifidobacterium, became less abundant, while some potentially harmful bacteria, Alistipes, Lachnospiraceae_NK4A136_group, Clostridium, Desulfovibrio, and Enterorhabdus, became more abundant. We further found that probiotic treatment could help to reconstitute the gut microbiome composition in Dip2a KO mice. Altogether, these data showed DIP2A is required for the proper composition of gut microbiota, and the probiotics have potential roles in rectifying the gut microbiota in Dip2a KO mice.

Transition of fluctuations from Gaussian state to turbulent state.

Variation of the statistical properties of an incompressible velocity, passive vector and passive scalar in isotropic turbulence was studied using direct numerical simulation. The structure functions of the gradients, and the moments of the dissipation rates, began to increase at about [Formula: see text] from the Gaussian state and grew rapidly at [Formula: see text] in the turbulent state. A contour map of the probability density functions (PDFs) indicated that PDF expansion of the gradients of the passive vector and passive scalar begins at around [Formula: see text], whereas that of the longitudinal velocity gradient PDF is more gradual. The left tails of the dissipation rate PDF were found to follow a power law with an exponent of 3/2 for the incompressible velocity and passive vector dissipation rates, and 1/2 for the scalar dissipation rate and the enstrophy; they remained constant for all Reynolds numbers, indicating the universality of the left tail. The analytical PDFs of the dissipation rates and enstrophy of the Gaussian state were obtained and found to be the Gamma distribution. It was shown that the number of terms contributing to the dissipation rates and the enstrophy determines the decay rates of the two PDFs for low to moderate amplitudes. This article is part of the theme issue 'Scaling the turbulence edifice (part 1)'.

Sex Differences in the Association between Different Obesity Parameters and Cognitive Function in Older Adults: A Cross-Sectional Study in Rural China.

BACKGROUND: Early identification of risk factors for cognition decline may contribute to the interventions for Alzheimer's disease. Obesity is a common modifiable risk factor for chronic diseases. The association between obesity and cognition in older adults is limited, and sex differences in this area have not been well recognized. OBJECTIVE: The aim of the study was to observe the sex differences in the relationship between obesity and cognition in a rural community-dwelling older population of Guizhou, China. METHODS: Data were gathered from the baseline survey of a cohort study of older people in rural areas of Guizhou, China. Demographic and behavioral data (sex, age, education, household income, smoking history, drinking history, history of head injury, diet, and level of physical exercise time) were collected. The Mini-Mental State Examination (MMSE) was used to assess cognitive function. Body mass index (BMI), waist circumference (WC), hip circumference (HC), and waist-to-hip ratio (WHR) were used as different measures of obesity. Comparisons between the groups were made by the Wilcoxon rank-sum test or Kruskal-Wallis H test. Restricted cubic spline regression was used to examine a dose-response relationship between obesity indicators and cognitive function. Linear relationships were performed by the multivariable linear regression model. RESULTS: A total of 1,654 participants including 964 women and 690 men were enrolled in this study. After adjustment, BMI showed a nonlinear relationship with MMSE scores in women. There was a significant trend toward increasing MMSE scores at the low end of BMI (13.52-20.10 kg/m2, p = 0.014). The multivariable linear regression model showed that MMSE increased by 0.631 (p < 0.001) for every one standard deviation increase in HC in women. No association was found between obesity parameters and cognitive function in men. CONCLUSION: Our results suggest that there are significant sex differences in some obesity parameters and cognition in an older Chinese population. BMI and HC are positively associated with cognitive function in women. No association was found between obesity measures and cognitive function in men.

THREE-DIMENSIONAL HEAD-UP DISPLAY VERSUS STANDARD OPERATING MICROSCOPE FOR VITRECTOMY SURGERY: A Systematic Review and Meta-analysis.

PURPOSE: To evaluate the effects of vitrectomy with three-dimensional head-up display (3D HUD) versus standard operating microscopy (SOM) for retinal diseases. METHODS: The PubMed, Cochrane Library, and Embase databases were comprehensively searched to identify studies that compared 3D HUD versus SOM in vitrectomy for retinal diseases (PROSPERO protocol CRD42021265827). The primary outcomes are duration of surgical time, postoperative best-corrected visual acuity, endoillumination levels, and intraoperative complications. The secondary outcomes are reattachment rate of rhegmatogenous retinal detachment, macular hole closure rate, and the like. RESULTS: Fifteen studies of 2,889 eyes were included. Compared with SOM, 3D HUD vitrectomy took a longer surgical time (weighted mean difference = 1.48; 95% confidence interval, 0.13-2.82), but it needed lower endoillumination levels (weighted mean difference = -16.04, 95% confidence interval, -18.33 to -13.75) than SOM. There were no significant differences in the postoperative best-corrected visual acuity, intraoperative complications, reattachment rate of rhegmatogenous retinal detachment, or closure rate of macular hole. CONCLUSION: Our results suggested that 3D HUD provides lower retinal illumine toxicities but with a longer surgical time. The surgical results and complications of vitrectomy were equally comparable for 3D HUD and SOM.

Acoustic Sensor-Based Soundscape Analysis and Acoustic Assessment of Bird Species Richness in Shennongjia National Park, China.

Passive acoustic sensor-based soundscape analysis has become an increasingly important ecological method for evaluation of ecosystem conditions using acoustic indices. Understanding the soundscape composition and correlations between acoustic indices and species richness of birds, the most important sound source in the ecosystem, are of great importance for measuring biodiversity and the level of anthropogenic disturbance. In this study, based on yearlong sound data obtained from five acoustic sensors deployed in Dalongtan, Shennongjia National Park, we analyzed the soundscape composition by comparing the distributions of the soundscape power in different frequency ranges, and examined the correlations between acoustic indices and bird species richness by means of the Spearman rank correlation coefficient method. The diurnal dynamic characteristics of acoustic indices in different seasons were also described. Results showed that the majority of sounds were in the frequency of 2-8 kHz, in which over 50% sounds were in 2-6 kHz, commonly considered the bioacoustic frequency range. The Acoustics Complexity Index, Bioacoustic Index, and Normalized Difference Soundscape Index were significantly correlated with bird species richness, suggesting that these indices can be used for evaluation of bird species richness; Apparent diurnal dynamic patterns of bird acoustic activities were observed in spring, summer, and autumn; however, the intensity and duration of bird acoustic activities in summer is larger/longer than in spring and autumn.

Interaction between arteriosclerosis and the APOE4 gene in cognitive decline in older adults: a cross-sectional study in rural minority areas in western China.

BACKGROUND: Numerous studies have confirmed that the apolipoprotein E4 allele (APOE4) gene and arteriosclerosis (AS) have a combined effect on the occurrence of cognitive function impairment, and dyslipidaemia levels are significantly correlated with APOE4 levels and AS. Few studies have focused on the combined effect of the APOE4 gene and AS on cognitive function. Therefore, this study aimed to investigate the effect of APOE4 gene and AS acting together on cognitive function through dyslipidaemia levels, which could provide certain scientific research value for future studies. METHODS: A multi-stage cluster sampling method was used to investigate older adults aged 60 years and above in rural areas of Guizhou, China. The demographic sociological characteristics were collected, and laboratory tests, blood lipid measurements, and physical examinations were performed. Mini-Mental State Examination (MMSE) was used to determine cognitive function. Analysis of variance with two-factor factorial design was used to analyse the interaction between the APOE4 gene and AS on cognitive function and its domains. RESULTS: A total of 549 elderly subjects were eligible for this study. The result of the factorial design analysis revealed there was a significant interaction between the APOE4 gene and AS in terms of attention and numeracy (F = 6.878, P = 0.009). CONCLUSIONS: The combination of the APOE4 gene and AS leads to a decrease in the level of attention and numeracy domains, and certain attention should be focused on such populations in the future.

Progress of artificial intelligence in diabetic retinopathy screening.

Diabetic retinopathy (DR) is one of the leading causes of blindness worldwide, and the limited availability of qualified ophthalmologists restricts its early diagnosis. For the past few years, artificial intelligence technology has developed rapidly and has been applied in DR screening. The upcoming technology provides support on DR screening and improves the identification of DR lesions with a high sensitivity and specificity. This review aims to summarize the progress on automatic detection and classification models for the diagnosis of DR.

Deep learning-based detection and stage grading for optimising diagnosis of diabetic retinopathy.

AIMS: To establish an automated method for identifying referable diabetic retinopathy (DR), defined as moderate nonproliferative DR and above, using deep learning-based lesion detection and stage grading. MATERIALS AND METHODS: A set of 12,252 eligible fundus images of diabetic patients were manually annotated by 45 licenced ophthalmologists and were randomly split into training, validation, and internal test sets (ratio of 7:1:2). Another set of 565 eligible consecutive clinical fundus images was established as an external test set. For automated referable DR identification, four deep learning models were programmed based on whether two factors were included: DR-related lesions and DR stages. Sensitivity, specificity and the area under the receiver operating characteristic curve (AUC) were reported for referable DR identification, while precision and recall were reported for lesion detection. RESULTS: Adding lesion information to the five-stage grading model improved the AUC (0.943 vs. 0.938), sensitivity (90.6% vs. 90.5%) and specificity (80.7% vs. 78.5%) of the model for identifying referable DR in the internal test set. Adding stage information to the lesion-based model increased the AUC (0.943 vs. 0.936) and sensitivity (90.6% vs. 76.7%) of the model for identifying referable DR in the internal test set. Similar trends were also seen in the external test set. DR lesion types with high precision results were preretinal haemorrhage, hard exudate, vitreous haemorrhage, neovascularisation, cotton wool spots and fibrous proliferation. CONCLUSIONS: The herein described automated model employed DR lesions and stage information to identify referable DR and displayed better diagnostic value than models built without this information.

Oncogenic role of ALX3 in cervical cancer cells through KDM2B-mediated histone demethylation of CDC25A.

BACKGROUND: Cell division cycle 25A (CDC25A) is a well-recognized regulator of cell cycle progression and is involved in cancer development. This work focused on the function of CDC25A in cervical cancer cell growth and the molecules involved. METHODS: A GEO dataset GSE63514 comprising data of cervical squamous cell carcinoma (CSCC) tissues was used to screen the aberrantly expressed genes in cervical cancer. The CDC25A expression in cancer and normal tissues was predicted in the GEPIA database and that in CSCC and normal cells was determined by RT-qPCR and western blot assays. Downregulation of CDC25A was introduced in CSCC cells to explore its function in cell growth and the cell cycle progression. The potential regulators of CDC25A activity and the possible involved signaling were explored. RESULTS: CDC25A was predicted to be overexpressed in CSCC, and high expression of CDC25A was observed in CSCC cells. Downregulation of CDC25A in ME180 and C33A cells reduced cell proliferation and blocked cell cycle progression, and it increased cell apoptosis. ALX3 was a positive regulator of CDC25A through transcription promotion. It recruited a histone demethylase, lysine demethylase 2B (KDM2B), to the CDC25A promoter, which enhanced CDC25A expression through demethylation of H3k4me3. Overexpression of ALX3 in cells blocked the inhibitory effects of CDC25A silencing. CDC25A was found as a positive regulator of the PI3K/Akt signaling pathway. CONCLUSION: This study suggested that the ALX3 increased CDC25A expression through KDM2B-mediated demethylation of H3K4me3, which induced proliferation and cell cycle progression of cervical cancer cells.

FOVEA-SPARING VERSUS COMPLETE INTERNAL LIMITING MEMBRANE PEELING IN VITRECTOMY FOR VITREOMACULAR INTERFACE DISEASES: A Systematic Review and Meta-Analysis.

PURPOSE: To evaluate fovea-sparing internal limiting membrane (ILM) peeling in vitrectomy compared with traditional complete ILM peeling in vitreomacular interface diseases, including macular hole (MH), epiretinal membrane, macular foveoschisis, myopic traction maculopathy, and the like. METHODS: PubMed, EMBASE, Cochrane, CNKI Databases, and the ClinicalTrials.gov website (PROSPERO number CRD42020187401) were searched. Controlled trials comparing fovea-sparing with complete ILM peeling were included. Postoperative changes in best-corrected visual acuity, central retinal thickness in vitreomacular interface diseases, the incidence of MH closure in MH cases, full-thickness macular hole development in non-MH cases, and retinal reattachment in retinoschisis cases were extracted. RESULTS: Fourteen studies (487 eyes) were eligible. Compared with complete ILM peeling, the fovea-sparing technique revealed significant improvement in best-corrected visual acuity ( logarithm of the minimum angle of resolution; weighted mean difference = -0.70; 95% confidence interval, -1.11 to -0.30), and a reduced incidence of full-thickness macular hole was noted in non-MH cases (risk ratios = 0.25; 95% confidence interval, 0.08-0.76). However, no significant differences in mean change in central retinal thickness, incidence of MH closure in MH cases, and retinal reattachment in retinoschisis cases were noted. CONCLUSION: Based on current evidence, fovea-sparing ILM peeling significantly improve visual outcomes and decrease complications of full-thickness macular hole development in vitreomacular interface diseases.