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Breast cancer is a malignant tumor, with various subtypes showing different behaviors. Endogenous H2O2 is an important marker of tumor progression, which makes it important to study the relationship between breast cancer subtypes and H2O2 for pathogenesis and treatment strategies, but this has rarely been reported so far. In this work, we constructed a three-dimensional (3D) electrochemiluminescence (ECL) sensing platform for the detection of H2O2 released from two typical subtypes of breast cancer cells (MCF-7 cells for luminal A-type and MDA-MB-231 cells for three negative breast cancers, TNBCs). To adequately replicate the tumor microenvironment, the peptide hydrogel was introduced as a scaffold for 3D cell culture. The titanium foam (TF) was used as a 3D electrode to better match the 3D culture substrate. N-(4-Aminobutyl)-N-ethylisoluminol (ABEI) was selected as the ECL emitter and assembled into the peptide hydrogel by hydrogen bonding and π-stacking, which resulted in a stable and homogeneous distribution of ABEI along the hydrogel fibers. Furthermore, basic amino acids were introduced to provide alkaline microenvironment for ABEI. Therefore, ABEI exhibited high ECL efficiency, resulting in a high sensitivity with an ultralow detection limit of 0.023 nM (S/N = 3) for H2O2 of the proposed ECL biosensor. MCF-7 and MDA-MB-231 cells were cultured in a 3D peptide hydrogel/ABEI/TF electrode, respectively, and endogenous H2O2 was successfully monitored. A notably significant difference of H2O2 released between MDA-MB-231 cells and MCF-7 cells without stimulation but similar extra release with stimulation were observed. These findings may help understand the physiological mechanisms behind the various subtypes and reactive oxygen species (ROS)-related treatment for breast cancer.
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Neoplasias de la Mama , Técnicas Electroquímicas , Hidrogeles , Peróxido de Hidrógeno , Péptidos , Humanos , Peróxido de Hidrógeno/análisis , Peróxido de Hidrógeno/química , Neoplasias de la Mama/patología , Neoplasias de la Mama/metabolismo , Péptidos/química , Hidrogeles/química , Mediciones Luminiscentes , Femenino , Línea Celular Tumoral , Células MCF-7 , Técnicas BiosensiblesRESUMEN
OBJECTIVE: Delayed cerebral ischemia (DCI)-induced cerebral infarction is a major cause of adverse neurological outcomes following aneurysmal subarachnoid hemorrhage (aSAH). This study aimed to investigate the relationship between postoperative serum electrolyte levels and DCI in patients with aSAH. MATERIALS AND METHODS: We analyzed the data of patients with aSAH between 2015 and 2022. The patients were classified into two groups according to whether they experienced DCI. Electrolyte levels were categorized into three groups based on the normal ranges for electrolytes. Logistic regression models were used to study the relationship between electrolyte levels and DCI. Another logistic regression analysis was conducted to explore the relationship between the different severity levels of statistically significant indicators and DCI. A restrictive cubic spline model was adopted to assess the potential linear relationship between electrolytes and DCI. Subsequently, sensitivity analysis was performed to assess the impact of collinearity among ions. Finally, subgroup analysis was performed. RESULTS: This study included 1,099 patients. Patients with hyperchloremia were more prone to DCI than those with normal chloride levels. Subsequently, excluding the population with hypochloremia, both mild and severe hyperchloremia were found to be associated with an increased risk of DCI compared with normal chloride levels. Within the framework of a restrictive cubic spline, our findings revealed an increased incidence of DCI (P for nonlinear = 0.735) as chloride levels increased. Sensitivity analysis revealed that patients with severe hyperchloremia were more susceptible to DCI. CONCLUSIONS: This study found that patients with aSAH and postoperative hyperchloremia are more prone to developing DCI.
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Isquemia Encefálica , Hemorragia Subaracnoidea , Humanos , Hemorragia Subaracnoidea/complicaciones , Hemorragia Subaracnoidea/diagnóstico , Estudios Retrospectivos , Cloruros , Infarto Cerebral/etiología , Infarto Cerebral/complicaciones , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/etiologíaRESUMEN
Mpox (formerly monkeypox) is a zoonotic disease caused by monkeypox virus (MPXV), which, like smallpox, is characterised by skin rashes. While the world is currently grappling with the coronavirus disease 2019 pandemic, the appearance of MPXV has presented a global threat and raised concerns worldwide. Since May 2022, MPXV has spread rapidly in non-endemic mpox areas. As of 27 June 2023, the virus has spread to more than 112 countries and regions, with over 88,060 laboratory-confirmed cases and 147 deaths. Thus, measures to control the mpox epidemic are urgently needed. As the principal methods for identifying and monitoring mpox, laboratory detection techniques play an important role in mpox diagnosis. This review summarises the currently-used laboratory techniques for MPXV detection, discusses progress in improving these methods, and compares the benefits and limitations of various diagnostic detection methods. Currently, nucleic acid amplification tests, such as the polymerase chain reaction, are the most commonly used. Immunological methods have also been applied to diagnose the disease, which can help us discover new features of MPXV, improve diagnostic accuracy, track epidemic trends, and guide future prevention and control strategies, which are also vital for controlling mpox epidemics. This review provides a resource for the scientific community and should stimulate more research and development in alternative diagnostics to be applied to this and future public health crises.
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COVID-19 , Mpox , Animales , COVID-19/diagnóstico , COVID-19/epidemiología , Mpox/diagnóstico , Mpox/epidemiología , Pandemias , Reacción en Cadena de la Polimerasa , ZoonosisRESUMEN
PURPOSE: To observe the clinical efficacy of the small incision lenticule extraction (SMILE)-derived lenticule patch graft in therapeutic keratoplasty, especially for the treatment of corneal microperforation or partial-thickness corneal defects. METHODS: Corneal lenticule obtained from SMILE surgery with diameter greater than 6.5 mm and thickness greater than 100 µm was preserved in a balanced salt solution (Alcon Laboratories, Fort Worth, TX) containing 50 mg/mL penicillin, 50 mg/mL streptomycin, 100 mg/mL neomycin, and 2.5 mg/mL amphotericin for at least 3 months. Preoperatively, anterior segment optical coherence tomography was used to assess the depth of the ulcer and to decide the thickness of the lenticule. Patients were followed up on day 1 and then at 1, 3, and 6 months postoperatively. RESULTS: Corneal perforation or defects were successfully patched in all 17 eyes; 8 eyes (47%) exhibited improvement postoperative corrected distance visual acuity. During the follow-up period of 6 months, there was no evidence of infection, relapse, or perforation detected in all eyes. Lenticule grafts were attached by graft beds very well and remain clear through to the last follow-up checkup in all eyes treated. CONCLUSIONS: The lenticule patch graft seems to serve as a safe, feasible, and inexpensive surgical option for the treatment of keratohelcosis or partial-thickness corneal defects, especially in small perforation and defects. There are hopeful signs that SMILE-derived lenticule becomes a potential graft for therapeutic keratoplasty.
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Sustancia Propia/cirugía , Cirugía Laser de Córnea/métodos , Trasplante de Córnea/métodos , Láseres de Excímeros/uso terapéutico , Miopía/cirugía , Agudeza Visual , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Sustancia Propia/patología , Topografía de la Córnea/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Miopía/diagnóstico , Miopía/fisiopatología , Tomografía de Coherencia Óptica/métodos , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND/AIMS: Pterygium is a common ocular surface disease with an unknown etiology and threatens vision as it invades into the cornea. Circular RNAs (circRNAs) are a novel class of RNA transcripts that participate in several physiological and pathological processes. However, the role of circRNAs in pathogenesis of pterygium remains largely unknown. METHODS: Genome-wide circRNA expression profiling was performed to identify pterygium -related circRNAs. GO analysis, pathway analysis, and miRNA response elements analysis was performed to predict the function of differentially expressed circRNAs in pterygium. MTT assays, Ki67 staining, Transwell assay, Hoechst 33342 staining, and Calcein-AM/PI staining were performed to determine the effect of circRNA silencing on pterygium fibroblast and epithelial cell function. RESULTS: Approximately 669 circRNAs were identified to be abnormally expressed in pterygium tissues. GO analysis demonstrated that the host genes of differentially expressed circRNAs were targeted to extracellular matrix organization (ontology: biological process), cytoplasm (ontology: cellular component), and protein binding (ontology: molecular function). Pathway analysis showed that dysregulated circRNAs-mediated regulatory networks were mostly enriched in focal adhesion signaling pathway. Notably, circ_0085020 (circ-LAPTM4B) was shown as a potential biomarker for pterygium. circ_0085020 (circ-LAPTM4B) silencing affected the viability, proliferation, migration, and apoptosis of pterygium fibroblast and epithelial cells in vitro. CONCLUSIONS: This study provides evidence that circRNAs are involved in the pathogenesis of pterygium and might constitute promising targets for the therapeutic intervention of pterygium.
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Células Epiteliales , Fibroblastos , Estudio de Asociación del Genoma Completo , Pterigion , ARN , Biomarcadores/metabolismo , Células Epiteliales/metabolismo , Células Epiteliales/patología , Fibroblastos/metabolismo , Fibroblastos/patología , Humanos , Pterigion/genética , Pterigion/metabolismo , Pterigion/patología , ARN/biosíntesis , ARN/genéticaRESUMEN
Excessive light exposure leads to retinal degeneration and accelerates the progression and severity of several ocular diseases, such as age-related macular degeneration (AMD) and retinitis pigmentosa. Long non-coding RNAs (LncRNAs) have emerged as important regulators of photoreceptor development and ocular diseases. In this study, we investigated the role of lncRNA-MEG3 in light-induced retinal degeneration. MEG3 expression was significantly up-regulated after light insult in vivo and in vitro. MEG3 silencing protected against light-induced retinal degeneration in vivo and light-induced photoreceptor cell apoptosis in vitro. Mechanistically, MEG3 regulated retinal photoreceptor cell function by acting as p53 decoy. MEG3 silencing decreased caspase 3/7 activity, up-regulated anti-apoptotic protein (Bcl-2) expression, and down-regulated pro-apoptotic protein (Bax) expression. Taken together, this study provides a promising method of MEG3 silencing for treating light-induced retinal degeneration.
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Terapia Genética/métodos , ARN Largo no Codificante/genética , Traumatismos Experimentales por Radiación/genética , Traumatismos Experimentales por Radiación/prevención & control , Degeneración Retiniana/genética , Degeneración Retiniana/prevención & control , Animales , Silenciador del Gen , Luz/efectos adversos , Masculino , Ratones , Ratones Endogámicos C57BL , Traumatismos Experimentales por Radiación/patología , Degeneración Retiniana/patología , Resultado del TratamientoRESUMEN
Sperm motility is an important standard to measure the fertility of male. In our previous study, we found that the diploid spermatozoa from allotetraploid hybrid (4nAT) had longer durations of rapid and slow progressive motility than haploid spermatozoa from common carp (COC). In this study, to explore sperm motility-related molecular mechanisms, we compared the testis tissues transcriptomes from 2-year-old male COC and 4nAT. The RNA-seq data revealed that 2985 genes were differentially expressed between COC and 4nAT, including 2216 upregulated and 769 downregulated genes in 4nAT. Some differentially expressed genes, such as tubulin genes, dynein, axonemal, heavy chain(dnah) genes, mitogen-activated protein kinase(mapk) genes, tektin 4, FOX transcription factors, proteasome genes, and ubiquitin carboxyl-terminal hydrolase(uchl) genes, are involved in the regulation of cell division, flagellar and ciliary motility, gene transcription, cytoskeleton, energy metabolism, and the ubiquitin-proteasome system, suggesting that these genes were related to sperm motility of the 4nAT. We confirmed the differential expression of 12 such genes in 4nAT by quantitative PCR. By western blotting, we also confirmed increased expression of Uchl3 in 4nAT testis. In addition, we identified 1915 and 2551 predicted long noncoding RNA (lncRNA) transcripts from testis tissue transcriptomes of COC and 4nAT, respectively. Of these, 1575 lncRNAs were specifically expressed in 4nAT and 939 were specifically expressed in COC. This study provides insights into the transcriptome profile of testis tissues from diploid and tetraploid, which are useful for research on regulatory mechanisms behind sperm motility in male polyploidy.
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Cyprinidae/genética , Cyprinidae/fisiología , Regulación de la Expresión Génica/fisiología , Ploidias , Motilidad Espermática/fisiología , Testículo/metabolismo , Animales , Masculino , EspermatozoidesRESUMEN
Epithelial-mesenchymal transition (EMT) promotes tumor cell infiltration and metastasis. Tracking the progression of EMT could potentially indicate early cancer metastasis. A key characteristic of EMT is the dynamic alteration in the molecular levels of E-cadherin and N-cadherin. Traditional assays have limited sensitivity and multiplexing capabilities, relying heavily on cell lysis. Here, we developed a multiplex electrochemical biosensor to concurrently track the upregulation of N-cadherin expression and reduction of E-cadherin in breast cancer cells undergoing EMT. Small-sized gold nanoparticles (Au NPs) tagged with redox probes (thionin or amino ferrocene) and bound to two types of antibodies were used as distinguishable signal tags. These tags specifically recognized E-cadherin and N-cadherin proteins on the tumor cell surface without cross-reactivity. The diphenylalanine dipeptide (FF)/chitosan (CS)/Au NPs (FF-CS@Au) composites with high surface area and good biocompatibility were used as the sensing platforms for efficiently fixing cells and recording the dynamic changes in electrochemical signals of surface proteins. The electrochemical immunosensor allowed for simultaneous monitoring of E- and N-cadherins on breast cancer cell surfaces in a single run, enabling tracking of the EMT dynamic process for up to 60 h. Furthermore, the electrochemical detection results are consistent with Western blot analysis, confirming the reliability of the methodology. This present work provides an effective, rapid, and low-cost approach for tracking the EMT process, as well as valuable insights into early tumor metastasis.
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Técnicas Biosensibles , Neoplasias de la Mama , Técnicas Electroquímicas , Transición Epitelial-Mesenquimal , Oro , Nanopartículas del Metal , Humanos , Técnicas Biosensibles/métodos , Neoplasias de la Mama/patología , Oro/química , Femenino , Nanopartículas del Metal/química , Técnicas Electroquímicas/métodos , Cadherinas , Línea Celular Tumoral , Inmunoensayo/métodos , Quitosano/químicaRESUMEN
Rapid drug clearance and off-target effects of therapeutic drugs can induce low bioavailability and systemic side effects and gravely restrict the therapeutic effects of inflammatory bowel diseases (IBDs). Here, we propose an amplifying targeting strategy based on orally administered gallium (Ga)-based liquid metal (LM) nano-agents to efficiently eliminate reactive oxygen and nitrogen species (RONS) and modulate the dysregulated microbiome for remission of IBDs. Taking advantage of the favorable adhesive activity and coordination ability of polyphenol structure, epigallocatechin gallate (EGCG) is applied to encapsulate LM to construct the formulations (LM-EGCG). After adhering to the inflamed tissue, EGCG not only eliminates RONS but also captures the dissociated Ga to form EGCG-Ga complexes for enhancive accumulation. The detained composites protect the intestinal barrier and modulate gut microbiota for restoring the disordered enteral microenvironment, thereby relieving IBDs. Unexpectedly, LM-EGCG markedly decreases the Escherichia_Shigella populations while augmenting the abundance of Akkermansia and Bifidobacterium, resulting in favorable therapeutic effects against the dextran sulfate sodium-induced colitis.
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Microbioma Gastrointestinal , Enfermedades Inflamatorias del Intestino , Animales , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Administración Oral , Microbioma Gastrointestinal/efectos de los fármacos , Ratones , Catequina/análogos & derivados , Catequina/química , Catequina/administración & dosificación , Catequina/farmacología , Galio/química , Galio/farmacología , Modelos Animales de Enfermedad , Inflamación/tratamiento farmacológico , Especies Reactivas de Oxígeno/metabolismo , Colitis/tratamiento farmacológico , Humanos , Especies de Nitrógeno Reactivo/metabolismoRESUMEN
Type 2 diabetes (T2D) is a global health concern with increasing prevalence. Comorbid hypothyroidism (HT) exacerbates kidney, cardiac, neurological and other complications of T2D; these risks can be mitigated pharmacologically upon detecting HT. The current HT standard of care (SOC) screening in T2D is infrequent, delaying HT diagnosis and treatment. We present a first-to-date machine learning algorithm (MLA) clinical decision tool to classify patients as low vs. high risk for developing HT comorbid with T2D; the MLA was developed using readily available patient data from harmonized multinational datasets. The MLA was trained on data from NIH All of US (AoU) and UK Biobank (UKBB) (Combined dataset) and achieved a high negative predictive value (NPV) of 0.989 and an AUROC of 0.762 in the Combined dataset, exceeding AUROCs for the models trained on AoU or UKBB alone (0.666 and 0.622, respectively), indicating that increasing dataset diversity for MLA training improves performance. This high-NPV automated tool can supplement SOC screening and rule out T2D patients with low HT risk, allowing for the prioritization of lab-based testing for at-risk patients. Conversely, an MLA output that designates a patient to be at risk of developing HT allows for tailored clinical management and thereby promotes improved patient outcomes.
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Fusarium wilt of banana caused by Fusarium oxysporum f. sp. cubense, Tropical Race 4 (TR4) is a soil-borne disease, and it is devastating. At present, the biological control using antagonistic microorganisms to mitigate TR4 is one of the best strategies as a safe and green way. Yunnan has abundant and diverse microbial resources. Using the dual-culture method, the antagonistic endophytic fungi against TR4 were isolated and screened from the root nodule of Dolichos lablab. The effect of the highest antagonistic activity strain on the morphology of the TR4 mycelium was observed using the scanning electron microscope. According to morphological characteristics and sequence analysis, the strain was identified. The biocontrol effect and plant growth promotion were investigated by greenhouse pot experiment. Using the confocal laser scanning microscope and the real-time fluorescence quantitative PCR, the dynamics of TR4 infestation and the TR4 content in banana plant roots and corms would also be detected. In this study, 18 native endophytic fungi were isolated from a root nodule sample of Dolichos lablab in the mulch for banana fields in Yuxi, Yunnan Province, China. The YNF2217 strain showed a high antagonistic activity against TR4 in plate confrontation experiments, and the inhibition rate of YNF2217 is 77.63%. After TR4 culture with YNF2217 for 7 days in plate confrontation experiments, the morphology of the TR4 mycelium appeared deformed and swollen when observed under a scanning electron microscope. According to morphological characteristics and sequence analysis, the strain YNF2217 was identified as Pochonia chlamydosporia. In the greenhouse pot experiment, the biocontrol effect of YNF2217 fermentation solution on TR4 was 70.97% and 96.87% on banana plant leaves and corms, respectively. Furthermore, YNF2217 significantly promoted the growth of banana plants, such as plant height, leaf length, leaf width, leaf number, pseudostem girth, and both the aboveground and underground fresh weight. Observations of TR4 infestation dynamics in banana roots and corms, along with real-time fluorescence quantitative PCR, verified that YNF2217 inoculation could significantly reduce the TR4 content. Therefore, YNF2217 as P. chlamydosporia, which was found first time in China and reported here, is expected to be an important new fungal resource for the green control of Fusarium wilt of banana in the future.
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Tables are a ubiquitous data format for insight communication. However, transforming data into consumable tabular views remains a challenging and time-consuming task. To lower the barrier of such a task, research efforts have been devoted to developing interactive approaches for data transformation, but many approaches still presume that their users have considerable knowledge of various data transformation concepts and functions. In this study, we leverage natural language (NL) as the primary interaction modality to improve the accessibility of average users to performing complex data transformation and facilitate intuitive table generation and editing. Designing an NL-driven data transformation approach introduces two challenges: a) NL-driven synthesis of interpretable pipelines and b) incremental refinement of synthesized tables. To address these challenges, we present NL2Rigel, an interactive tool that assists users in synthesizing and improving tables from semi-structured text with NL instructions. Based on a large language model and prompting techniques, NL2Rigel can interpret the given NL instructions into a table synthesis pipeline corresponding to Rigel specifications, a declarative language for tabular data transformation. An intuitive interface is designed to visualize the synthesis pipeline and the generated tables, helping users understand the transformation process and refine the results efficiently with targeted NL instructions. The comprehensiveness of NL2Rigel is demonstrated with an example gallery, and we further confirmed NL2Rigel's usability with a comparative user study by showing that the task completion time with NL2Rigel is significantly shorter than that with the original version of Rigel with comparable completion rates.
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Macrophages/microglia are immune system defense and homeostatic cells that develop from bone marrow progenitor cells. According to the different phenotypes and immune responses of macrophages (Th1 and Th2), the two primary categories of polarized macrophages/microglia are those conventionally activated (M1) and alternatively activated (M2). Macrophage/microglial polarization is a key regulating factor in the development of inflammatory disorders, cancers, metabolic disturbances, and neural degeneration. Macrophage/microglial polarization is involved in inflammation, oxidative stress, pathological angiogenesis, and tissue healing processes in ocular diseases, particularly in diabetic retinopathy (DR). The functional phenotypes of macrophages/microglia affect disease progression and prognosis, and thus regulate the polarization or functional phenotype of microglia at different DR stages, which may offer new concepts for individualized therapy of DR. This review summarizes the involvement of macrophage/microglia polarization in physiological situations and in the pathological process of DR, and discusses the promising role of polarization in personalized treatment of DR.
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Diabetes Mellitus , Retinopatía Diabética , Humanos , Microglía/metabolismo , Retinopatía Diabética/metabolismo , Macrófagos/metabolismo , Inflamación/metabolismo , Activación de Macrófagos , Diabetes Mellitus/metabolismoRESUMEN
Indirect bypass surgery is an effective treatment for moyamoya disease (MMD), but the success of the surgery depends on the formation of spontaneous collateral vessels, which cannot be accurately predicted before surgery. Developing a prediction nomogram model for neoangiogenesis in patients after indirect revascularization surgery can aid surgeons in identifying suitable candidates for indirect revascularization surgery. This retrospective observational study enrolled patients with MMD who underwent indirect bypass surgery from a multicenter cohort between December 2010 and December 2018. Data including potential clinical and radiological predictors were obtained from hospital records. A nomogram was generated based on a multivariate logistic regression analysis identifying potential predictors of good neoangiogenesis. A total of 263 hemispheres of 241 patients (mean ± SD age 24.38 ± 15.78 years, range 1-61 years) were reviewed, including 168 (63.9%) hemispheres with good postoperative collateral formation and 95 (36.1%) with poor postoperative collateral formation. Based on multivariate analysis, a nomogram was formulated incorporating four predictors, including age at operation, abundance of ICA moyamoya vessels, onset type, and Suzuki stage. The C-index for this nomogram was 0.80. Calibration curve and decision-making analysis validated the fitness and clinical application value of this nomogram. The nomogram developed in this study exhibits high accuracy in predicting good neoangiogenesis after indirect revascularization surgery in MMD patients. This model can be very helpful for clinicians when making decisions about surgical strategies for MMD patients in clinical practice.
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Purpose: Systemic inflammation plays an important role in the pathophysiology and progression of aneurysmal subarachnoid hemorrhage (aSAH). In this study, we aimed to investigate the association between a new biomarker, the inflammatory burden index (IBI) and the prognosis as well as in-hospital complications of aSAH patients. Patients and Methods: We analyzed data from patients with aSAH between January 2019 and September 2022 who were included in the LongTEAM (Long-term Prognosis of Emergency Aneurysmal Subarachnoid Hemorrhage) registry study. The IBI was formulated as C-reactive protein × neutrophils/lymphocytes. The unfavorable functional prognosis was assessed by the modified Rankin Scale (mRS). Receiver operating characteristic (ROC) curve analysis was conducted to determine the optimal cut-off values for IBI to distinguish the unfavorable functional prognosis. Multivariate logistic regression was applied to investigate the association between IBI and in-hospital complications. Propensity score matching was adjusted for imbalances in baseline characteristics to assess the effect of IBI on prognosis. Results: A total of 408 consecutive patients with aSAH enrolled in the study, of which 235 (57.6%) were female patients and the mean age was 55.28 years old. An IBI equal to 138.03 was identified as the best cut-off threshold to distinguish the unfavorable prognosis at 3 months (area under the curve [AUC] [95% CI] 0.637 [0.568-0.706]). ln IBI was independently associated with 3-month functional prognosis (OR [95% CI] 1.362 [1.148-1.615]; P<0.001), pneumonia (OR [95% CI] 1.427 [1.227-1.659]; P<0.001) and deep venous thrombosis (DVT). (OR [95% CI] 1.326 [1.124-1.564]; P=0.001). After propensity score matching (57:57), an increased proportion of patients with IBI ≥138.03 had a poor functional prognosis at 3 months and in-hospital complications including developed pneumonia and DVT. Conclusion: In patients with aSAH, high IBI level at admission was associated with unfavorable functional prognosis as well as pneumonia and deep vein thrombosis.
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Background: Stress-related gastrointestinal bleeding (SRGB) is one of the major complications after aneurysmal subarachnoid hemorrhage (aSAH), and it can present challenges in patient care and treatment. The aim of this study was to explore the clinical significance of the caudate Hounsfield unit (HU) value in the Alberta Stroke Program Early CT (ASPECT) score for predicting SRGB in patients with aSAH. Methods: We retrospectively analyzed the data of 531 aSAH patients admitted to our institution between 2019 and 2022. Potential predictors of SRGB were identified using multivariate Cox regression analysis. We used a restricted cubic spline (RCS) to evaluate whether there is a nonlinear relationship between the right caudate HU value and SRGB. MaxStat analysis (titled as maximally selected rank statistics) was performed to identify the optimal cutoff point for the right caudate HU value. Another Kaplan-Meier method with the log-rank test was used to analyze the right caudate HU value in predicting the occurrence of SRGB. Results: The incidence rate of SRGB was 17.9%. In the multivariate Cox regression analysis, the right caudate HU value was an independent predictor of SRGB [Hazard ratio (HR) = 0.913; 95% confidence interval (CI): 0.847-0.983, and p = 0.016]. The RCS indicated that the incidence of developing SRGB reduces with increasing right caudate HU values (nonlinear p = 0.78). The optimal cut-off value of the right caudate HU was 25.1. Conclusion: Among aSAH patients, lower right caudate HU values indicated a higher risk of developing SRGB. Our findings provide further evidence for the relationship between the gastrointestinal system and the brain.
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Contact lens sensors provide a noninvasive approach for intraocular pressure (IOP) monitoring in patients with glaucoma. Accurate measurement of this imperceptible pressure variation requires highly sensitive sensors in the absence of simultaneously amplifying IOP signal and blinking-induced noise. However, current noise-reduction methods rely on external filter circuits, which thicken contact lenses and reduce signal quality. Here, we introduce a contact lens strain sensor with an anti-jamming ability by utilizing a self-lubricating layer to reduce the coefficient of friction (COF) to remove the interference from the tangential force. The sensor achieves exceptionally high sensitivity due to the strain concentration layout and the confined occurrence of sympatric microcracks. The animal tests prove our lens can accurately detect IOP safely and reliably.
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Lentes de Contacto , Glaucoma , Animales , Presión Intraocular , Tonometría Ocular/métodos , Glaucoma/diagnósticoRESUMEN
OBJECTIVE: Our study aims to investigate the association between the Hounsfield unit (Hu) value of the insular cortex (IC) during emergency admission and the subsequent occurrence of post-operative neurocardiogenic injury (NCI) among patients afflicted with aneurysmal subarachnoid hemorrhage (aSAH). METHODS: Patients baseline characteristics were juxtaposed between those with and without NCI. The significant variables were incorporated into a multivariable stepwise logistic regression model. Receiver operating characteristic (ROC) curves were drafted for each significant variable, yielding cutoff values and the area under the curve (AUC). Subgroup and sensitivity analyses were performed to assess the predictive performance across various cohorts and ascertain result stability. Propensity score matching (PSM) was ultimately employed to redress any baseline characteristic disparities. RESULTS: Patients displaying a right IC Hu value surpassing 28.65 exhibited an escalated risk of postoperative NCI upon confounder adjustment (p < 0.001). The ROC curve eloquently manifested the predictive capacity of right IC Hu in relation to NCI (AUC = 0.650, 95%CI, 0.591-0.709, p < 0.001). Further subgroup analysis revealed significant interactions between right IC Hu and factors such as age, history of heart disease, and Graeb 5-12 score. Sensitivity analysis further upheld the results' significant (p = 0.002). The discrepancy in NCI incidence between the two groups, both prior (p < 0.002) and post (p = 0.039) PSM, exhibited statistical significance. After PSM implementation, the likelihood of NCI displayed an ascending trend with increasing right IC Hu values, from the Hu1 cohort onward, receding post the Hu4 cohort. CONCLUSION: This study definitively establishes an elevated right IC Hu value in the early stages of emergency admission as an autonomous predictor for ensuing NCI subsequent to aSAH.
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Hemorragia Subaracnoidea , Humanos , Hemorragia Subaracnoidea/complicaciones , Hemorragia Subaracnoidea/diagnóstico por imagen , Corteza InsularRESUMEN
BACKGROUND: Downregulation of epithelial markers and upregulation of mesenchymal markers are the characteristics of the epithelial to mesenchymal transition (EMT) program, which provides the metastatic advantage of breast cancer. However, the mechanism underlying the switch of EMT markers remains poorly understood. METHODS: In this study, we used the affinity purification and mass spectrometry coupled approach to identify the interactome of Slug. CoIP, GST-pulldown, ChIP, Re-ChIP, qPCR and Immunoblot were used to investigate the underlying mechanism of Slug-PRMT5-LSD1 complex. The role of PRMT5 and LSD1 in breast cancer progression was evaluated both in vivo and in vitro. RESULTS: Here we found that the transcription factor Slug associates with PRMT5 and LSD1 in a complex and facilitates the breast cancer invasion in vitro. Mechanistically, PRMT5 and LSD1 work with Slug to exert dual transcriptional activities to inhibit E-cadherin expression by PRMT5-catalyzed H4R3me2s and LSD1-mediated demethylation of H3K4me2 on the E-cadherin (CDH1) promoter, and activate vimentin (VIM) expression via PRMT5-driven H3R2me2s and LSD1-mediated removal of H3K9me2. Importantly, PRMT5 and LSD1 are coordinately expressed in breast cancer patients and pharmacologic perturbation of both PRMT5 and LSD1 shows a synergetic effect on the inhibition of breast tumor growth and metastasis in vivo. CONCLUSIONS: Our study suggests that PRMT5 and LSD1 function as a dual epigenetic modifier to promote Slug induced EMT program, suggesting that the inhibition of PRMT5 and LSD1 presents a potential therapeutic strategy against cancer metastasis.
Asunto(s)
Neoplasias de la Mama , Gastrópodos , Animales , Neoplasias de la Mama/genética , Cadherinas , Transición Epitelial-Mesenquimal/genética , Femenino , Histona Demetilasas/genética , Humanos , Proteína-Arginina N-Metiltransferasas/genéticaRESUMEN
RATIONALE: Internal limiting membrane (ILM) peeling and gas tamponade are the standardized treatments for macular holes (MHs). However, the close rate is low, and postoperative vision is unsatisfactory in large, chronic MHs. Currently, various modifications of the ILM flap techniques are being gradually applied for large MHs in the hope of obtaining better postoperative effects. This study described 2 successful cases achieved by "Sandwich-type" modified ILM flap covering technique in patients with large, chronic MHs. PATIENT CONCERNS: A 62-year-old woman presented with decreased vision and visual distortion of the left eye for 18âmonths. Optical coherence tomography (OCT) showed the absence of full-thickness neuroepithelial tissue in the central fovea, with a minimum MH diameter of 742âµm and a base diameter of 1630âµm. A 57-year-old man experienced decreased visual acuity for 8âmonths. OCT showed the absence of full-thickness neuroepithelial tissue in the central fovea, with a minimum MH diameter of 713âµm and a basal diameter of 939âµm. DIAGNOSES: Two patients were diagnosed with large, chronic MH based on the OCT results and duration of the hole. INTERVENTIONS: The 2 patients were treated with the "sandwich-type" modified ILM flap covering technique. OUTCOMES: Large, chronic MH closure was observed using SD-OCT, and the BCVA improved. The patients were very satisfied with the postoperative results. LESSONS: "Sandwich-type" modified ILM flap covering technique may be a safe, effective way for large, chronic MH.