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BACKGROUND AND AIMS: Heart failure (HF) is a leading cause of mortality worldwide and characterized by significant co-morbidities and dismal prognosis. Neutrophil extracellular traps (NETs) aggravate inflammation in various cardiovascular diseases; however, their function and mechanism of action in HF pathogenesis remain underexplored. This study aimed to investigate the involvement of a novel VWF-SLC44A2-NET axis in HF progression. METHODS: NET levels were examined in patients with HF and mouse models of transverse aortic constriction (TAC) HF. PAD4 knockout mice and NET inhibitors (GSK-484, DNase I, NEi) were used to evaluate the role of NETs in HF. RNA sequencing was used to investigate the downstream mechanisms. Recombinant human ADAMTS13 (rhADAMTS13), ADAMTS13, and SLC44A2 knockouts were used to identify novel upstream factors of NETs. RESULTS: Elevated NET levels were observed in patients with HF and TAC mouse models of HF. PAD4 knockout and NET inhibitors improved the cardiac function. Mechanistically, NETs induced mitochondrial dysfunction in cardiomyocytes, inhibiting mitochondrial biogenesis via the NE-TLR4-mediated suppression of PGC-1α. Furthermore, VWF/ADAMTS13 regulated NET formation via SLC44A2. Additionally, sacubitril/valsartan amplifies the cardioprotective effects of the VWF-SLC44A2-NET axis blockade. CONCLUSIONS: This study established the role of a novel VWF-SLC44A2-NET axis in regulating mitochondrial homeostasis and function, leading to cardiac apoptosis and contributing to HF pathogenesis. Targeting this axis may offer a potential therapeutic approach for HF treatment.
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Protein labeling through transient and repetitive hybridization of short, fluorophore-labeled DNA oligonucleotides has become widely applied in various optical super-resolution microscopy methods. The main advantages are multitarget imaging and molecular quantification. A challenge is the high background signal originating from the presence of unbound fluorophore-DNA labels in solution. Here, we report the self-quenching of fluorophore dimers conjugated to DNA oligonucleotides as a general concept to reduce the fluorescence background. Upon hybridization, the fluorescence signals of both fluorophores are restored. We expand the toolbox of fluorophores suitable for self-quenching and report their spectra and hybridization equilibria. We apply self-quenched fluorophore-DNA labels to stimulated emission depletion microscopy and single-molecule localization microscopy and report improved imaging performances.
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DNA , Corantes Fluorescentes , Microscopia de Fluorescência , Corantes Fluorescentes/química , DNA/química , Hibridização de Ácido Nucleico , Oligonucleotídeos/químicaRESUMO
Doxorubicin (DOX) is an effective anticancer agent, but its clinical utility is constrained by dose-dependent cardiotoxicity, partly due to cardiomyocyte ferroptosis. However, the progress of developing cardioprotective medications to counteract ferroptosis has encountered obstacles. Protosappanin A (PrA), an anti-inflammatory compound derived from hematoxylin, shows potential against DOX-induced cardiomyopathy (DIC). Here, it is reported that PrA alleviates myocardial damage and dysfunction by reducing DOX-induced ferroptosis and maintaining mitochondrial homeostasis. Subsequently, the molecular target of PrA through proteome microarray, molecular docking, and dynamics simulation is identified. Mechanistically, PrA physically binds with ferroptosis-related proteins acyl-CoA synthetase long-chain family member 4 (ACSL4) and ferritin heavy chain 1 (FTH1), ultimately inhibiting ACSL4 phosphorylation and subsequent phospholipid peroxidation, while also preventing FTH1 autophagic degradation and subsequent release of ferrous ions (Fe2+) release. Given the critical role of ferroptosis in the pathogenesis of ischemia-reperfusion (IR) injury, this further investigation posits that PrA can confer a protective effect against IR-induced cardiac damage by inhibiting ferroptosis. Overall, a novel pharmacological inhibitor is unveiled that targets ferroptosis and uncover a dual-regulated mechanism for cardiomyocyte ferroptosis in DIC, highlighting additional therapeutic options for chemodrug-induced cardiotoxicity and ferroptosis-triggered disorders.
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BACKGROUND/AIMS: The aim of this study was to develop and evaluate digital ray, based on preoperative and postoperative image pairs using style transfer generative adversarial networks (GANs), to enhance cataractous fundus images for improved retinopathy detection. METHODS: For eligible cataract patients, preoperative and postoperative colour fundus photographs (CFP) and ultra-wide field (UWF) images were captured. Then, both the original CycleGAN and a modified CycleGAN (C2ycleGAN) framework were adopted for image generation and quantitatively compared using Frechet Inception Distance (FID) and Kernel Inception Distance (KID). Additionally, CFP and UWF images from another cataract cohort were used to test model performances. Different panels of ophthalmologists evaluated the quality, authenticity and diagnostic efficacy of the generated images. RESULTS: A total of 959 CFP and 1009 UWF image pairs were included in model development. FID and KID indicated that images generated by C2ycleGAN presented significantly improved quality. Based on ophthalmologists' average ratings, the percentages of inadequate-quality images decreased from 32% to 18.8% for CFP, and from 18.7% to 14.7% for UWF. Only 24.8% and 13.8% of generated CFP and UWF images could be recognised as synthetic. The accuracy of retinopathy detection significantly increased from 78% to 91% for CFP and from 91% to 93% for UWF. For retinopathy subtype diagnosis, the accuracies also increased from 87%-94% to 91%-100% for CFP and from 87%-95% to 93%-97% for UWF. CONCLUSION: Digital ray could generate realistic postoperative CFP and UWF images with enhanced quality and accuracy for overall detection and subtype diagnosis of retinopathies, especially for CFP.\ TRIAL REGISTRATION NUMBER: This study was registered with ClinicalTrials.gov (NCT05491798).
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Utilization of digital technologies for cataract screening in primary care is a potential solution for addressing the dilemma between the growing aging population and unequally distributed resources. Here, we propose a digital technology-driven hierarchical screening (DH screening) pattern implemented in China to promote the equity and accessibility of healthcare. It consists of home-based mobile artificial intelligence (AI) screening, community-based AI diagnosis, and referral to hospitals. We utilize decision-analytic Markov models to evaluate the cost-effectiveness and cost-utility of different cataract screening strategies (no screening, telescreening, AI screening and DH screening). A simulated cohort of 100,000 individuals from age 50 is built through a total of 30 1-year Markov cycles. The primary outcomes are incremental cost-effectiveness ratio and incremental cost-utility ratio. The results show that DH screening dominates no screening, telescreening and AI screening in urban and rural China. Annual DH screening emerges as the most economically effective strategy with 341 (338 to 344) and 1326 (1312 to 1340) years of blindness avoided compared with telescreening, and 37 (35 to 39) and 140 (131 to 148) years compared with AI screening in urban and rural settings, respectively. The findings remain robust across all sensitivity analyses conducted. Here, we report that DH screening is cost-effective in urban and rural China, and the annual screening proves to be the most cost-effective option, providing an economic rationale for policymakers promoting public eye health in low- and middle-income countries.
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Catarata , Análise Custo-Benefício , Programas de Rastreamento , Humanos , China/epidemiologia , Catarata/economia , Catarata/diagnóstico , Catarata/epidemiologia , Pessoa de Meia-Idade , Programas de Rastreamento/economia , Programas de Rastreamento/métodos , Masculino , Tecnologia Digital/economia , Feminino , Cadeias de Markov , Idoso , Inteligência Artificial , Telemedicina/economia , Telemedicina/métodosRESUMO
The construction of a yield loss evaluation index for the cold vortex type light-temperature-water composite adversity during rice flowering period in Northeast China is important for elucidating the impacts of cold vortex type composite disasters on rice yield loss in middle and high latitude areas. Moreover, it can provide meteorological support to ensure safe production of high-quality japonica rice in China and contribute to regional disaster reduction and efficiency improvement. By combining growth period data, meteorological data, and yield data, we delineated and constructed the composite stress occurrence index of cold vortex type light-temperature-water at the flowering stage of japonica. We analyzed the relationship between factors causing disasters and yield structure, as well as the relationship between different yield structures and yield by employing BP neural network method. We further dissected the processes involved in the causation of combined disasters. Based on the K-means clustering method and historical typical disaster years, we quantified the critical thresholds and disaster grades, and established an evaluation index and model for assessing yield loss caused by combined stress from cold vortex type light-temperature-water. Finally, we examined the spatial and temporal variations of low temperature, abundant rainfall, and reduced sunlight during the flowering period in the three provinces of Northeast China. Results showed that the critical thresholds for light, temperature, and water stress index during the flowering stage of mild, moderate, and severe cold vortex types were [0, 0.21), [0.21, 0.32), and [0.32, 0.64], respectively. The rates of yield loss were [0, 0.03), [0.03, 0.08), and [0.08, 0.096], respectively. Based on the verification results of a total of 751 samples in 11 random years from 1961 to 2020, the percentage of stations for which the production reduction grade, as calculated by the composite index developed in this study, aligning with the actual production reduction grade was 63.7%, consistently exceeding 58.0% annually. Moreover, the proportion of sites with a similarity or difference level of 1 stood at 88.3%, surpassing 85.0% in each year. The index could effectively assess the extent of rice yield loss caused by cold vortex disasters in Northeast China.
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Temperatura Baixa , Flores , Oryza , Oryza/crescimento & desenvolvimento , China , Flores/crescimento & desenvolvimento , Estresse Fisiológico , Água/análise , Luz , DesastresRESUMO
PURPOSE: To explore the factors related to the diagnosis yield of syndromic congenital cataracts and describe the phenotype-genotype correlation in congenital cataract patients. DESIGN: Prospective cohort study. METHODS: Setting: the participants from underwent clinical examinations between 2021 and 2022. Facial and anterior eye segment photographs, pre- and postoperative ocular parameters, and medical and family histories were recorded. Bioinformatics analysis was performed using whole-exome sequencing data. Statistical and correlation analyses were performed using the basic characteristics, deep phenotype, and genotype data. PARTICIPANTS: 115 patients with unrelated congenital cataract. INTERVENTIONS: performing clinical examinations, whole-exome sequencing, and bioinformatics analysis for all participants. MAIN OUTCOMES AND MEASURES: factors related to the genetic diagnosis yield of syndromic congenital cataracts. RESULTS: Bilaterally asymmetrical cataracts were identified to be associated with syndromic congenital cataracts. The overall genetic diagnostic yield in the cohort was 72.2%. In total, 34.8% of the probands were early diagnosed with various syndromes with the help of genetic information. A phenotype-genotype correlation was detected for some genes and deep phenotypes. CONCLUSIONS: We highlight the importance of screening syndromic diseases in the patients with asymmetrical congenital cataracts. Application of whole-exome sequencing helps provide early diagnosis and treatment for the patients with syndromic congenital cataracts. This study also achieved a high genetic diagnostic yield, expanded the genotypic spectrum, and found phenotype-genotype correlations. A comprehensive analysis of cataract symmetricity, family history, and deep phenotypes makes the genotype prediction of some congenital cataract patients possible.
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Catarata , Diagnóstico Precoce , Sequenciamento do Exoma , Humanos , Catarata/congênito , Catarata/genética , Catarata/diagnóstico , Masculino , Feminino , Estudos Prospectivos , Pré-Escolar , Lactente , Criança , Estudos de Associação Genética , Fenótipo , Síndrome , Genótipo , Testes GenéticosRESUMO
BACKGROUND: Emerging three-dimensional digital visualization technology (DVT) provides more advantages than traditional microscopy in microsurgery; however, its impact on microsurgeons' visual and nervous systems and delicate microsurgery is still unclear, which hinders the wider implementation of DVT in digital visualization for microsurgery. METHODS AND MATERIAL: Forty-two microsurgeons from the Zhongshan Ophthalmic Center were enrolled in this prospective self-controlled study. Each microsurgeon consecutively performed 30 min conjunctival sutures using a three-dimensional digital display and a microscope, respectively. Visual function, autonomic nerve activity, and subjective symptoms were evaluated before and immediately after the operation. Visual functions, including accommodative lag, accommodative amplitude, near point of convergence and contrast sensitivity function (CSF), were measured by an expert optometrist. Heart rate variability was recorded by a wearable device for monitoring autonomic nervous activity. Subjective symptoms were evaluated by questionnaires. Microsurgical performance was assessed by the video-based Objective Structured Assessment of Technical Skill (OSATS) tool. RESULTS: Accommodative lag decreased from 0.63 (0.18) diopters (D) to 0.55 (0.16) D ( P =0.014), area under the log contrast sensitivity function increased from 1.49 (0.15) to 1.52 (0.14) ( P =0.037), and heart rate variability decreased from 36.00 (13.54) milliseconds (ms) to 32.26 (12.35) ms ( P =0.004) after using the DVT, but the changes showed no differences compared to traditional microscopy ( P >0.05). No statistical significance was observed for global OSATS scores between the two rounds of operations [mean difference, 0.05 (95% CI: -1.17 to 1.08) points; P =0.95]. Subjective symptoms were quite mild after using both techniques. CONCLUSIONS: The impact of DVT-based procedures on microsurgeons includes enhanced accommodation and sympathetic activity, but the changes and surgical performance are not significantly different from those of microscopy-based microsurgery. Our findings indicate that short-term use of DVT is reliable for microsurgery and the long-term effect of using DVT deserve more consideration.
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Microscopia , Dispositivos Eletrônicos Vestíveis , Humanos , Microcirurgia/métodos , Estudos Prospectivos , TecnologiaRESUMO
Age is closely related to human health and disease risks. However, chronologically defined age often disagrees with biological age, primarily due to genetic and environmental variables. Identifying effective indicators for biological age in clinical practice and self-monitoring is important but currently lacking. The human lens accumulates age-related changes that are amenable to rapid and objective assessment. Here, using lens photographs from 20 to 96-year-olds, we develop LensAge to reflect lens aging via deep learning. LensAge is closely correlated with chronological age of relatively healthy individuals (R2 > 0.80, mean absolute errors of 4.25 to 4.82 years). Among the general population, we calculate the LensAge index by contrasting LensAge and chronological age to reflect the aging rate relative to peers. The LensAge index effectively reveals the risks of age-related eye and systemic disease occurrence, as well as all-cause mortality. It outperforms chronological age in reflecting age-related disease risks (p < 0.001). More importantly, our models can conveniently work based on smartphone photographs, suggesting suitability for routine self-examination of aging status. Overall, our study demonstrates that the LensAge index may serve as an ideal quantitative indicator for clinically assessing and self-monitoring biological age in humans.
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Aprendizado Profundo , Cristalino , Humanos , Pré-Escolar , Envelhecimento/genéticaRESUMO
PURPOSE: To develop a multimodal artificial intelligence (AI) system, EE-Explorer, to triage eye emergencies and assist in primary diagnosis using metadata and ocular images. DESIGN: A diagnostic, cross-sectional, validity and reliability study. METHODS: EE-Explorer consists of 2 models. The triage model was developed from metadata (events, symptoms, and medical history) and ocular surface images via smartphones from 2038 patients presenting to Zhongshan Ophthalmic Center (ZOC) to output 3 classifications: urgent, semiurgent, and nonurgent. The primary diagnostic model was developed from the paired metadata and slitlamp images of 2405 patients from ZOC. Both models were externally tested on 103 participants from 4 other hospitals. A pilot test was conducted in Guangzhou to evaluate the hierarchical referral service pattern assisted by EE-Explorer for unspecialized health care facilities. RESULTS: A high overall accuracy, as indicated by an area under the receiver operating characteristic curve (AUC) of 0.982 (95% CI, 0.966-0.998), was obtained using the triage model, which outperformed the triage nurses (P < .001). In the primary diagnostic model, the diagnostic classification accuracy (CA) and Hamming loss (HL) in the internal testing were 0.808 (95% CI 0.776-0.840) and 0.016 (95% CI 0.006-0.026), respectively. In the external testing, model performance was robust for both triage (average AUC, 0.988, 95% CI 0.967-1.000) and primary diagnosis (CA, 0.718, 95% CI 0.644-0.792; and HL, 0.023, 95% CI 0.000-0.048). In the pilot test in the hierarchical referral settings, EE-explorer demonstrated consistently robust performance and broad participant acceptance. CONCLUSION: The EE-Explorer system showed robust performance in both triage and primary diagnosis for ophthalmic emergency patients. EE-Explorer can provide patients with acute ophthalmic symptoms access to remote self-triage and assist in primary diagnosis in unspecialized health care facilities to achieve rapid and effective treatment strategies.
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Inteligência Artificial , Triagem , Humanos , Triagem/métodos , Reprodutibilidade dos Testes , Estudos Transversais , Serviço Hospitalar de EmergênciaRESUMO
Warburg Micro syndrome (WARBM) is an autosomal recessive neuro-ophthalmologic syndrome characterized by microcephaly, microphthalmia, congenital cataracts, cortical dysplasia, corpus callosum hypoplasia, spasticity, and hypogonadism. WARBM is divided into four subtypes according to the causative genes, of which RAB3GAP1 (OMIM# 602536) accounts for the highest proportion. We collected detailed medical records and performed whole-exome sequencing (WES) for a congenital cataract patient. A novel heterozygous frameshift RAB3GAP1 variant was detected in a boy with a rare ocular phenotype of bilateral membranous cataracts accompanied by a persistent papillary membrane. Further copy number variation (CNV) analysis identified a novel deletion on chromosome 2q21.3 that removed 4 of the 24 exons of RAB3GAP1. The patient was diagnosed with WARBM following genetic testing. The present study expands the genotypic and phenotypic spectrum of WARBM. It suggests applying whole exome sequencing (WES) and CNV analysis for the early diagnosis of syndromic diseases in children with congenital cataracts.
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Catarata , Hipogonadismo , Microcefalia , Humanos , Catarata/congênito , Variações do Número de Cópias de DNA , Sequenciamento do Exoma , Hipogonadismo/genética , Hipogonadismo/diagnóstico , Microcefalia/genética , Mutação , Proteínas rab3 de Ligação ao GTP/genética , MasculinoRESUMO
BACKGROUND: Deep venipuncture catheterization is widely used in clinical anesthesia. However, it is worth thinking about how to improve the rate of successful catheter insertion, and relieve patients' discomfort. This paper aimed to compare the clinical advantages between trocar and steel needle. METHODS: Total 503 adult patients were recruited and randomly assigned. The control group was punctured with steel needle, and the experimental group was punctured with trocar needle. Clinical and followed-up information was recorded. Pearson's chi-squared and spearman test were performed to analyze the correlation between intervention and relative parameters. Univariate logistic regression was performed to verify the odds ratio of trocar needle compared with steel needle. RESULTS: Pearson's chi-square test and Spearman's correlation test showed a significant correlation between puncture success, puncture comfort, successful catheter insertion, puncture time, thrombosis, catheter fever, bleeding, infection and interventions (Pâ <â .05). Univariate logistic regression showed that there existed better puncture comfort (odds ratio [OR]â =â 6.548, 95% confidence interval [CI]: 4.320-9.925, Pâ <â .001), higher successful catheter insertion (ORâ =â 6.060, 95% CI: 3.278-11.204, Pâ <â .001), shorter puncture time (ORâ =â 0.147, 95% CI: 0.093-0.233, Pâ <â .001), lesser thrombosis (ORâ =â 0.194, 95% CI: 0.121-0.312, Pâ <â .001), lesser catheter fever (ORâ =â 0.263, 95% CI: 0.158-0.438, Pâ <â .001), lesser bleeding (ORâ =â 0.082, 95% CI: 0.045-0.150, Pâ <â .001) and lesser infection (ORâ =â 0.340, 95% CI: 0.202-0.571, Pâ <â .001) in trocar group compared with steel needle group. CONCLUSION: Trocar application in deep venipuncture catheterization can improve successful catheter insertion, relieve pain and discomfort of patients, reduce incidence of complications, and provide better security for patients.
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Cateterismo Venoso Central , Trombose , Humanos , Adulto , Flebotomia/efeitos adversos , Cateterismo Venoso Central/efeitos adversos , Aço , Hemorragia/etiologia , Trombose/etiologia , Instrumentos CirúrgicosRESUMO
Congenital cataracts (CCs) have significant genotypic and phenotypic heterogeneity. The major intrinsic protein (MIP) gene, one of the causative genes of CCs, plays a vital role in maintaining the homeostasis and transparency of the lens. In this study, we identified a unique phenotype of anterior umbilication of the lens in a four-generation pedigree with CCs. All patients in the observed family had nystagmus, nuclear cataracts, and elongated axial lengths compared with their healthy counterparts except for patient I:2, whose axial length was unavailable, and patientII:4, who had total cataracts. We confirmed, using Sanger sequencing based on whole-exon sequencing (WES) data, that all patients carried a heterozygous variant NM_012064.4:c.97C > T (NP_036196.1:p.R33C) in their MIP gene. To our knowledge, 29 variants of the human MIP gene and the relative phenotypes associated with CCs have been identified. Nevertheless, this is the first report on the anterior umbilication of the lens with nuclear or total opacity caused by the c.97C > T (p.R33C) variant in the MIP gene. These results also provide evidence that the elongated axial length might be associated with this variant. This study further confirms the phenotypic heterogeneity of CCs.
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Aquaporinas , Catarata , Humanos , Aquaporinas/genética , Povo Asiático , Catarata/genética , Catarata/congênito , Proteínas do Olho/genética , Mutação de Sentido IncorretoRESUMO
BACKGROUND: Inflammation resolution and cardiac repair initiation after myocardial infarction (MI) require timely activation of reparative signals. Histone lactylation confers macrophage homeostatic gene expression signatures via transcriptional regulation. However, the role of histone lactylation in the repair response post-MI remains unclear. We aimed to investigate whether histone lactylation induces reparative gene expression in monocytes early and remotely post-MI. METHODS: Single-cell transcriptome data indicated that reparative genes were activated early and remotely in bone marrow and circulating monocytes before cardiac recruitment. Western blotting and immunofluorescence staining revealed increases in histone lactylation levels, including the previously identified histone H3K18 lactylation in monocyte-macrophages early post-MI. Through joint CUT&Tag and RNA-sequencing analyses, we identified Lrg1, Vegf-a, and IL-10 as histone H3K18 lactylation target genes. The increased modification and expression levels of these target genes post-MI were verified by chromatin immunoprecipitation-qPCR and reverse transcription-qPCR. RESULTS: We demonstrated that histone lactylation regulates the anti-inflammatory and pro-angiogenic dual activities of monocyte-macrophages by facilitating reparative gene transcription and confirmed that histone lactylation favors a reparative environment and improves cardiac function post-MI. Furthermore, we explored the potential positive role of monocyte histone lactylation in reperfused MI. Mechanistically, we provided new evidence that monocytes undergo metabolic reprogramming in the early stage of MI and demonstrated that dysregulated glycolysis and MCT1 (monocarboxylate transporter 1)-mediated lactate transport promote histone lactylation. Finally, we revealed the catalytic effect of IL (interleukin)-1ß-dependent GCN5 (general control non-depressible 5) recruitment on histone H3K18 lactylation and elucidated its potential role as an upstream regulatory element in the regulation of monocyte histone lactylation and downstream reparative gene expression post-MI. CONCLUSIONS: Histone lactylation promotes early remote activation of the reparative transcriptional response in monocytes, which is essential for the establishment of immune homeostasis and timely activation of the cardiac repair process post-MI.
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Histonas , Infarto do Miocárdio , Humanos , Histonas/metabolismo , Ativação Transcricional , Infarto do Miocárdio/metabolismo , Macrófagos/metabolismo , Monócitos/metabolismoRESUMO
Investigating the interplay of cellular proteins with optical microscopy requires multitarget labeling. Spectral multiplexing using high-affinity or covalent labels is limited in the number of fluorophores that can be discriminated in a single imaging experiment. Advanced microscopy methods such as STED microscopy additionally demand balanced excitation, depletion, and emission wavelengths for all fluorophores, further reducing multiplexing capabilities. Noncovalent, weak-affinity labels bypass this "spectral barrier" through label exchange and sequential imaging of different targets. Here, we combine exchangeable HaloTag ligands, weak-affinity DNA hybridization, and hydrophophic and protein-peptide interactions to increase labeling flexibility and demonstrate six-target STED microscopy in single cells. We further show that exchangeable labels reduce photobleaching as well as facilitate long acquisition times and multicolor live-cell and high-fidelity 3D STED microscopy. The synergy of different types of exchangeable labels increases the multiplexing capabilities in fluorescence microscopy, and by that, the information content of microscopy images.
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Corantes Fluorescentes , Proteínas , Corantes Fluorescentes/química , Microscopia de Fluorescência/métodosRESUMO
Objective: To examine the poly (lactic-co-glycolic acid) and sodium alginate (SA) scaffolds produced by 3D printing technology, access the healing morphology of bones following PLGA/SA implantation within rat cartilage, and examine osteogenesis-related factors in rat serum to determine the efficacy of PLGA/SA scaffolds in healing animal cartilage injuries. To identify the potential of this material to repair a tissue engineering osteochondral injury. Methods: Polylactic acid-glycolic acid copolymer and sodium alginate were used as raw materials to create PLGA/SA scaffolds. We observed the scaffold's macrostructure and microstructure, and the scaffold's microstructure was observed through a scanning electron microscope (SEM). The mechanical toughness of a stent was assessed using a biomechanical device. Hematoxylin-eosin staining revealed immune rejection after embedding the scaffolds under the skin of SD rats. The CCK-8 cell proliferation test kit was used to measure cell proliferation. An experimental model of cartilage injury in the knee joint was created in rats. Rats were used to establish an experimental model of cartilage damage in the knee joint. 120 female rats aged 5 weeks were chosen at random from the pool and divided into the experimental and control groups. They were all completely anesthetized with an anesthetic before having the lateral skin of the knee articular cartilage incised. Implanted PLGA/SA scaffolds were not used in the control group and only in the experiment group. Both groups of rats had their muscles and skin sutured and covered in plaster bandages. On the third, seventh, fourteenth, twenty-first, twenty-eighth, and thirty-fifth days after the procedure, the two groups of rats were divided into groups. At various stages, bone tissue, blood samples, and cartilage were examined and evaluated. Immunohistochemistry was used to identify the local bone morphogenetic protein-2 (BMP2). Results: (1) PLGA/SA was successfully used to build an artificial cartilage scaffold. (2) Macroscopic and SEM observation results showed the material had increased density and numerous microvoids on the surface. (3) The result of the biomechanical test showed that the PLGA/SA scaffold had superior biomechanical characteristics. (4) The stent did not exhibit any noticeable immunological rejection, according to the results of the subcutaneous embedding experiment performed on rats. (5) The CCK-8 data demonstrated that as the cell development time rose, the number of cells gradually increased. However, there was not statistically significant difference between the growth of the cells in the scaffold extract and the control group (P > 0.05). (6) A successful rat model based on a cartilage defect of the medial knee joint has been built. (7) Observations of specimens revealed that the experimental group's bone tissue score was higher than that of the control group. (8) Using immunohistochemistry, it was found that the experimental group's BMP2 expression was higher on the 7th, 14th, and 28th days than it was in the control group (P < 0.05). Conclusion: Strong mechanical and biological properties are present in stable, biodegradable PLGA/SA scaffolds that mimic cartilage. We demonstrated that the cartilage biomimetic PLGA/SA scaffold may repair cartilage and prevent negative reactions such as osteoarthritis in rat knee cartilage, making it suitable as a cartilage scaffolding material for tissue engineering. The PLGA/SA scaffold was also able to promote BMP2 expression in the bone healing zone when inserted into a knee cartilage lesion. Improved cartilage damage is the outcome of BMP2's promotion of bone formation and restriction of bone resorption in the bone healing zone.
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The deletion of chromosome 11p13 involving the WT1 and PAX6 genes has been shown to cause WAGR syndrome (OMIM #194072), a rare genetic disorder that features Wilms' tumor, aniridia, genitourinary anomalies, as well as mental retardation. In this study, we expand the genotypic and phenotypic spectrum of WAGR syndrome by reporting on six patients from six unrelated families with different de novo deletions located on chromosome 11p13. Very rare phenotypes of lens automated absorption and lens thinning were detected in four of the six patients. We assessed the involvement of the ARL14EP gene in patients with and without severe lens abnormalities and found that its deletion may worsen the lens abnormalities in these patients.
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Aniridia , Neoplasias Renais , Síndrome WAGR , Tumor de Wilms , Aniridia/genética , Deleção Cromossômica , Humanos , Neoplasias Renais/genética , Fenótipo , Síndrome WAGR/genética , Síndrome WAGR/patologia , Tumor de Wilms/genética , Tumor de Wilms/patologiaRESUMO
OBJECTIVE: This is a single-center retrospective analysis of the clinical data of 516 patients with acute ischemic stroke who underwent intravenous thrombolysis. This study was conducted to compare the therapeutic efficacy of smokers and non-smokers. METHODS: Univariate analysis was used to analyze and compare the clinical data of smokers and non-smokers. Multivariate analysis was used to assess risk factors affecting the 90-day modified Rankin Scale (mRS) score. RESULTS: Among the 516 patients, 235 (45.5 %) were smokers. Univariate analysis showed that smokers have a better 90-day prognosis and a lower 90-day mRS score than non-smokers. Multivariate logistic regression analysis showed that smoking is not a protective factor affecting prognosis, while baseline National Institutes of Health Stroke Scale (NIHSS) score was an independent risk factor affecting the 90-day functional outcome. Subgroup analysis did not determine a relationship between the 90-day mRS score and the smoking intensity and duration. CONCLUSION: Smoking was not associated with a good 90-day prognosis after intravenous thrombolysis (IVT) treatment. The good clinical outcome of smokers in univariate analysis was bound up with their baseline characteristics. Baseline NIHSS score was the independent risk factor that affected the 90-day outcome of AIS patients undergoing IVT.