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BACKGROUND: Dyslipidemia is prominently associated with adverse outcomes in patients with coronary artery disease (CAD). The non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) is a novel comprehensive lipid index. However, limited evidence exists on the relationship of the NHHR with the risk of adverse outcomes in patients with CAD. This study aimed to explore the associations between the NHHR and adverse outcomes and identify the optimal NHHR ranges linked to the lowest adverse outcome risk in patients with CAD undergoing percutaneous coronary intervention (PCI). METHODS: Among 2253 patients with CAD undergoing PCI, 2251 with available total cholesterol and HDL-C levels were analyzed. Furthermore, all patients were classified into quintiles based on the NHHR. The primary outcome was the incidence of MACCEs, comprising cardiac mortality, acute myocardial infarction, stroke, and repeat revascularization. Multivariable logistic regression analysis was used to assess the relationship between the NHHR and MACCEs. Moreover, restricted cubic spline (RCS) analysis was performed to quantify nonlinearity. Lastly, the consistency between these associations was confirmed by conducting subgroup and interaction analyses. RESULTS: A total of 270 patients experienced MACCEs over a median follow-up of 29.8 months (interquartile range, 25.6-34 months). After adjustment for confounding variables, the adjusted ORs (95% CIs) of the patients in quintiles 2, 3, 4, and 5 were 0.79 (0.52-1.20), 0.64 (0.42-0.99), 1.00 (0.67-1.48), and 1.17 (0.74-1.64), respectively (reference group: quintile 1). Additionally, RCS analysis demonstrated a U-shaped relationship between the NHHR and MACCEs, with an inflection point at an NHHR of 3.119 using a two-piecewise regression model. This relationship was consistent across the various subgroups, while significant interactions were not observed in these associations.The ORs and 95% CIs to the left and right of the inflection point were 0.734 (0.551-0.978) and 1.231 (1.038-1.460), respectively. CONCLUSIONS: This study reveals a U-shaped association between baseline NHHR and MACCE incidence in patients with CAD undergoing PCI.
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HDL-Colesterol , Doença da Artéria Coronariana , Intervenção Coronária Percutânea , Humanos , Intervenção Coronária Percutânea/efeitos adversos , Masculino , Feminino , HDL-Colesterol/sangue , Pessoa de Meia-Idade , Idoso , Estudos Retrospectivos , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/cirurgia , Fatores de Risco , Infarto do Miocárdio/sangue , Infarto do Miocárdio/epidemiologia , LDL-Colesterol/sangue , Colesterol/sangue , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/epidemiologia , Resultado do TratamentoRESUMO
PURPOSE: Lung adenocarcinoma (LUAD) significantly contributes to cancer-related mortality worldwide. The heterogeneity of the tumor immune microenvironment in LUAD results in varied prognoses and responses to immunotherapy among patients. Consequently, a clinical stratification algorithm is necessary and inevitable to effectively differentiate molecular features and tumor microenvironments, facilitating personalized treatment approaches. METHODS: We constructed a comprehensive single-cell transcriptional atlas using single-cell RNA sequencing data to reveal the cellular diversity of malignant epithelial cells of LUAD and identified a novel signature through a computational framework coupled with 10 machine learning algorithms. Our study further investigates the immunological characteristics and therapeutic responses associated with this prognostic signature and validates the predictive efficacy of the model across multiple independent cohorts. RESULTS: We developed a six-gene prognostic model (MYO1E, FEN1, NMI, ZNF506, ALDOA, and MLLT6) using the TCGA-LUAD dataset, categorizing patients into high- and low-risk groups. This model demonstrates robust performance in predicting survival across various LUAD cohorts. We observed distinct molecular patterns and biological processes in different risk groups. Additionally, analysis of two immunotherapy cohorts (N = 317) showed that patients with a high-risk signature responded more favorably to immunotherapy compared to those in the low-risk group. Experimental validation further confirmed that MYO1E enhances the proliferation and migration of LUAD cells. CONCLUSION: We have identified malignant cell-associated ligand-receptor subtypes in LUAD cells and developed a robust prognostic signature by thoroughly analyzing genomic, transcriptomic, and immunologic data. This study presents a novel method to assess the prognosis of patients with LUAD and provides insights into developing more effective immunotherapies.
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Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Microambiente Tumoral , Humanos , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/patologia , Adenocarcinoma de Pulmão/mortalidade , Adenocarcinoma de Pulmão/imunologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/mortalidade , Prognóstico , Microambiente Tumoral/genética , Microambiente Tumoral/imunologia , Biomarcadores Tumorais/genética , Imunoterapia , Regulação Neoplásica da Expressão Gênica , Perfilação da Expressão Gênica , Feminino , Análise de Célula Única/métodos , Masculino , Transcriptoma , Aprendizado de Máquina , MultiômicaRESUMO
Background: Foreign body-induced cancer is a traditional way of understanding cancer development. The induction of cancers by exogenous foreign bodies has been identified in many organs. However, small bowel adenocarcinoma induced by foreign bodies has not been reported in the literature, although the incidence of small bowel adenocarcinoma is increasing globally. Case Presentation: A 70-year-old man was hospitalized for persistent right-sided abdominal pain for 3 months. Abdominal computed tomography revealed localized thickening and clustering of the small bowel wall in the right abdominal cavity. A comminuted fracture of the right 11th rib protruding into the abdominal cavity was observed, with a bone fragment located within the intestinal mass. Exploratory laparotomy was performed, and extensive adhesions were noted among the greater omentum, small bowel, mesentery, and right abdominal wall. Radical resection and lymph node dissection of the affected small bowel and appendix were performed. We also excised the rib end and repaired the abdominal wall to prevent further irritation. The patient was discharged 12 days post-surgery and follow-up assessments revealed no reported discomfort. Conclusion: We first report a case of small bowel adenocarcinoma induced by self-bone tissue, along with successful radical tumor excision and thorough foreign body removal. This case highlights the significant role of chronic inflammation in carcinogenesis.
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BACKGROUND: Postoperative delirium (POD) is a common, transient postoperative cognitive dysfunction in elderly patients. The relationship between POD and intraoperative hypotension remains unclear. This study aims to determine if intraoperative hypotension predicts POD in elderly male patients undergoing laryngectomy. METHODS: This study included male patients over 65 years old who underwent laryngectomy between April 2018 and January 2022. The Confusion Assessment Method (CAM) was used to diagnose delirium. Intraoperative hypotension was defined as a Mean Arterial Pressure (MAP) during surgery that was less than 30% of the preoperative level for at least 30 minutes. The relationship between intraoperative hypotension and POD incidence was adjusted for patient demographics and surgery-related factors. RESULTS: Out of 428 male patients, 77 (18.0%) developed POD, and 166 (38.8%) experienced intraoperative hypotension. Surgery duration ≥ 300 minutes (OR = 1.873, 95% CI 1.041-3.241, p = 0.036), intraoperative hypotension (OR = 1.739, 95% CI 1.039-2.912, p = 0.035), and schooling (OR = 2.655, 95% CI 1.338-5.268) were independent risk factors for POD. The association between intraoperative hypotension and POD was significantly influenced by surgery duration (p for interaction = 0.008), with a stronger association in prolonged surgeries (adjusted OR = 4.902; 95% CI 1.816-13.230). CONCLUSIONS: Intraoperative hypotension and low education level are associated with an increased risk of POD in elderly male patients undergoing laryngectomy, especially with prolonged surgery duration.
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OBJECTIVES: To identify risk factors correlated with atrioventricular block (AVB) in the general population. METHODS: Participants in the Atherosclerosis Risk in Communities study (ARIC) and the Cardiovascular Health study (CHS) were enrolled. The presence of AVB was confirmed at an electrocardiogram (ECG) reading center using Minnesota ECG Classification. Cox proportional hazards models were performed to investigate potential risk factors of AVB, after adjustment for age, sex, race and traditional cardiovascular risk factors. RESULTS: During the 17 years of follow-up, a total of 731 high-degree AVB cases were identified. Age and sex-standardized rate of AVB was 2.79 and 2.35 per 1000 person-years in the white and the black population, respectively. With the increase of the geriatric population, the incidence of high-degree AVB will increase from 378,816 in 2020 to 535,076 in 2060, and most increment would occur among the elderly. Older age, male sex, the white race, overweight, comorbidities, declined forced vital capacity (FVC), elevated inflammation biomarkers, left bundle branch block and bifascicular block were independently associated with the incidence of high-degree AVB. CONCLUSION: To conclude, older age, male sex, white population, overweight, combined diabetes or chronic kidney disease, impaired FVC, elevated inflammation biomarkers, left bundle branch block and bifascicular block were independent predictors for high-degree AVB. The next 40 years would witness a dramatic increase in the incidence of high-degree AVB.
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Bloqueio Atrioventricular , Humanos , Masculino , Feminino , Bloqueio Atrioventricular/epidemiologia , Bloqueio Atrioventricular/fisiopatologia , Bloqueio Atrioventricular/diagnóstico , Incidência , Idoso , Pessoa de Meia-Idade , Estados Unidos/epidemiologia , Medição de Risco , Fatores Etários , Fatores de Tempo , Fatores Sexuais , Comorbidade , Fatores de Risco , Fatores de Risco de Doenças Cardíacas , Eletrocardiografia , Estudos Prospectivos , População Branca , Idoso de 80 Anos ou maisRESUMO
The hydration heat generated during the concreting of cast-in-place piles causes thermal disturbance to the surrounding permafrost, leading to its thawing. This further affects the stability of the pile foundation and degrades the construction progress. To explore the influence mechanisms of the concrete hydration heat on the permafrost temperature field around the pile, as well as that of different construction seasons on the pile-side boundary conditions and permafrost temperature field, monitoring results of on-site tests and numerical simulation were used to analyze the distribution law of the pile soil temperature field in space and time, and the pile-side boundary conditions and permafrost temperature field during construction seasons. The results show that the temperature trend of the pile foundation can be divided into three stages: a rapid rise phase (0â¼2 d), a rapid decline phase (2â¼10 d), and a slow decline and stabilization phase (10â¼90 d). As the radial distance from the pile center decreases, there occur a corresponding acceleration in temperature increase and an elevated maximum temperature rise (MTR). The influence range of the molding temperature and the hydration heat is about 1â¼2 times the pile diameter and less than 1.5 m in the depth direction. Compared to the atmospheric temperature, there is a lag in the change in the permafrost temperature caused by accumulation of ground temperature, and the significant difference between the two leads to an increased rate of heat exchange at the boundary condition. Conducting drilling operation and cast-in-place pile construction in the cold seasons is conducive to reducing the thermal disturbance to the permafrost around the pile in permafrost areas.
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Methylotrophic yeast Ogataea polymorpha has become a promising cell factory due to its efficient utilization of methanol to produce high value-added chemicals. However, the low homologous recombination (HR) efficiency in O. polymorpha greatly hinders extensive metabolic engineering for industrial applications. Overexpression of HR-related genes successfully improved HR efficiency, which however brought cellular stress and reduced chemical production due to constitutive expression of the HR-related gene. Here, we engineered an HR repair pathway using the dynamically regulated gene ScRAD51 under the control of the l-rhamnose-induced promoter PLRA3 based on the previously constructed CRISPR-Cas9 system in O. polymorpha. Under the optimal inducible conditions, the appropriate expression level of ScRAD51 achieved up to 60% of HR rates without any detectable influence on cell growth in methanol, which was 10-fold higher than that of the wild-type strain. While adopting as the chassis strain for bioproductions, the dynamically regulated recombination system had 50% higher titers of fatty alcohols than that static regulation system. Therefore, this study provided a feasible platform in O. polymorpha for convenient genetic manipulation without perturbing cellular fitness.
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Sistemas CRISPR-Cas , Edição de Genes , Recombinação Homóloga , Engenharia Metabólica , Metanol , Saccharomycetales , Edição de Genes/métodos , Sistemas CRISPR-Cas/genética , Saccharomycetales/genética , Engenharia Metabólica/métodos , Metanol/metabolismo , Regiões Promotoras Genéticas/genética , Ramnose/metabolismo , Álcoois Graxos/metabolismo , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismoRESUMO
Spatial deposition and patterning of microparticles are crucial in chemistry, medicine, and biology. Existing technologies like electric force manipulation, despite precise trajectory control, struggle with complex and personalized patterns. Key challenges include adjusting the quantity of particles deposited in different areas and accurately depositing particles in non-continuous patterns. Here, we present a rational process termed combinatory electric-field-guided deposition (CED) for achieving spatially regulated microparticle deposition on insulative substrates. This process involves coating the substrates with insulating materials like PVP and positioning it on a relief-patterned negative electrode. The negative electric field generated by the electrode attracts microparticles, while the positive surface charges on the substrates repel microparticles, resulting in the formation of a potential well over the electrode area. Consequently, this configuration enables precise control over microparticle deposition without the need for direct contact with the substrate's surface, simplifying the process of switching masks to meet varying microparticle deposition requirements. Furthermore, we demonstrate the customization of patterned microparticles on superhydrophobic coatings to regulate cell distribution, as well as the successful loading of drug-laden microparticles onto antibacterial bandages to match the areas of skin lesions. These applications underscore the versatility of CED across chemical, medical, and bioengineering domains.
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Glycosylation is an important post-modification reaction in plant secondary metabolism, and contributes to structural diversity of bioactive natural products. In plants, glycosylation is usually catalyzed by UDP-glycosyltransferases. Flavonoid 2'-O-glycosides are rare glycosides. However, no UGTs have been reported, thus far, to specifically catalyze 2'-O-glycosylation of flavonoids. In this work, UGT71AP2 was identified from the medicinal plant Scutellaria baicalensis as the first flavonoid 2'-O-glycosyltransferase. It could preferentially transfer a glycosyl moiety to 2'-hydroxy of at least nine flavonoids to yield six new compounds. Some of the 2'-O-glycosides showed noticeable inhibitory activities against cyclooxygenase 2. The crystal structure of UGT71AP2 (2.15 Å) was solved, and mechanisms of its regio-selectivity was interpreted by pK a calculations, molecular docking, MD simulation, MM/GBSA binding free energy, QM/MM, and hydrogenâdeuterium exchange mass spectrometry analysis. Through structure-guided rational design, we obtained the L138T/V179D/M180T mutant with remarkably enhanced regio-selectivity (the ratio of 7-O-glycosylation byproducts decreased from 48% to 4%) and catalytic efficiency of 2'-O-glycosylation (k cat/K m, 0.23 L/(s·µmol), 12-fold higher than the native). Moreover, UGT71AP2 also possesses moderate UDP-dependent de-glycosylation activity, and is a dual function glycosyltransferase. This work provides an efficient biocatalyst and sets a good example for protein engineering to optimize enzyme catalytic features through rational design.
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Five previously undescribed protopanaxatriol-type saponins, notoginsenosides Ta-Te (1-5), together with eighteen known triterpenoid saponins (6-23) were isolated from the roots of Panax notoginseng. The structures of new compounds were determined by HRESIMS and NMR spectroscopic analyses and chemical methods. Compounds 1 and 2 were the first examples of ginsenosides featuring a 6-deoxy-ß-d-glucose moiety from Panax species. Compounds 1-4, 7, 10, 12, 21-22 showed protective effects on L02 cells against the injury of acetaminophen (APAP). Among them, notoginsenoside R1 (12), ginsenoside Rg1 (21), and ginsenoside Re (22) were the most potent ones, with cell viabilities >80%. Moreover, compounds 12 and 22 remarkably alleviated APAP-induced liver injury in mice. These saponins are potential hepatoprotective agents.
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Acetaminofen , Doença Hepática Induzida por Substâncias e Drogas , Ginsenosídeos , Panax notoginseng , Raízes de Plantas , Saponinas , Animais , Panax notoginseng/química , Raízes de Plantas/química , Camundongos , Estrutura Molecular , Saponinas/farmacologia , Saponinas/isolamento & purificação , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Masculino , Ginsenosídeos/farmacologia , Ginsenosídeos/isolamento & purificação , Humanos , Triterpenos/farmacologia , Triterpenos/isolamento & purificação , Substâncias Protetoras/farmacologia , Substâncias Protetoras/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/isolamento & purificação , Linhagem Celular , ChinaRESUMO
[2,3-diamino-N-(4-(benzo[d]thiazol-2-yl)phenyl)propanamide], named as ETN101, is a novel therapeutic agent for hepatocellular carcinoma. In vitro studies examined ETN101 metabolites in human, mouse, rat, dog, and monkey hepatocytes and identified the drug-metabolizing enzymes involved using cDNA-expressed human recombinant cytochrome P450s (CYPs), carboxylesterases (CESs), N-acetyltransferase (NAT) 1, and human liver cytosol. ETN101 showed similar metabolic stability across hepatocytes from five species, with particularly comparable stability in humans, rats, and monkeys. Its half-life was 75.0 min in humans, 68.9 in rats, 73.1 in monkeys, 120.4 in mice, and 112.7 in dogs. Thirty-four ETN101 metabolites, including the major metabolite M1, were identified using liquid chromatography-high-resolution mass spectrometry. ETN101 was primarily metabolized to M1 and CYP1A2 is exclusively responsible for M1 metabolism. Both NAT1 and NAT2 were responsible for the N-acetylation of M1 to M2. ETN101 remained stable in human CESs. In conclusion, this study provides comprehensive insights into the metabolic characteristics of ETN101, valuable for its toxicological and clinical development.
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Methanol, a rich one-carbon feedstock, can be massively produced from CO2 by the liquid sunshine route, which is helpful to realize carbon neutrality. ß-Farnesene is widely used in the production of polymers, surfactants, lubricants, and also serves as a suitable substitute for jet fuel. Constructing an efficient cell factory is a feasible approach for ß-farnesene production through methanol biotransformation. Here, we extensively engineered the methylotrophic yeast Ogataea polymorpha for the efficient bio-production of ß-farnesene using methanol as the sole carbon source. Our study demonstrated that sufficient supply of precursor acetyl-CoA and cofactor NADPH in an excellent yeast chassis had a 1.3-fold higher ß-farnesene production than that of wild-type background strain. Further optimization of the mevalonate pathway and enhancement of acetyl-CoA supply led to a 7-fold increase in ß-farnesene accumulation, achieving the highest reported sesquiterpenoids production (14.7 g/L with a yield of 46 mg/g methanol) from one-carbon feedstock under fed-batch fermentation in bioreactor. This study demonstrates the great potential of engineering O. polymorpha for high-level terpenoid production from methanol.
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Engenharia Metabólica , Metanol , Sesquiterpenos , Metanol/metabolismo , Sesquiterpenos/metabolismoRESUMO
OBJECTIVE: To investigate pantothenate kinases 1 (PANK1) expression in kidney renal clear cell carcinoma (KIRC) tissues, analyze its correlation with clinicopathological features and prognosis, and explore its impact on invasion, migration, and apoptosis in KIRC cells. METHODS: GEPIA (gene expression profiling interactive analysis), UALCAN and LinkedOmics, were employed to analyze PANK1 expression in KIRC tissues and its correlation with clinical characteristics. Comparative analyses were performed between KIRC (Caki-1 and 786-O) and noncancerous renal cells (HK-2 and RPTEC). Transfection with PANK1 activation particles was conducted, followed by Wound healing, Transwell assay, Annexin V-fluorescein isothiocyanate/propidium iodide (Annexin V-FITC/PI) staining, quantitative reverse-transcription polymerase chain reaction (qRT-PCR), and Western blotting. RESULTS: PANK1 was down-regulated in KIRC tissues and cells compared to normal tissues and noncancerous cells. Correlation analyses linked PANK1 expression with clinicopathological features in KIRC, with high PANK1 expression associated with a favorable outcome. High PANK1 expression correlated positively with E-cadherin (CDH1), tight junction protein 1 (TJP1), Fas cell surface death receptor (FAS), caspase-8 (CASP8), and CASP9, while showing a negative correlation with vimentin (VIM), snail family transcriptional repressor 1 (SNAIL1), twist family BHLH transcription factor 1 (TWIST1), and TWIST2. PANK1 overexpression increased CDH1, TJP1, FAS, CASP8, and CASP9 while downregulating SNAIL1, VIM, TWIST1, and TWIST2, inhibiting invasion and migration, and promoting apoptosis in KIRC cells. CONCLUSION: PANK1 down-regulation in KIRC tissues correlated with clinicopathological features and prognosis. Its overexpression modulated epithelial-mesenchymal transition (EMT)-related gene, inhibited invasion, promoted apoptosis in KIRC cells, highlighting its role in disease progression and therapeutic potential.
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Astragaloside IV is a significant chemical component derived from the medicinal plant Astragalus membranaceus. Despite the characterization of several glycosyltransferases from A. membranaceus, the complete biosynthetic pathway of astragaloside IV has not been fully elucidated. In this study, we propose a biosynthetic pathway for astragaloside IV that involves a sequence of oxidation-reduction reactions. The biosynthesis pathway from cycloastragenol to astragaloside IV encompasses four key steps: C-3 oxidation, 6-O-glucosylation, C-3 reduction, and 3-O-xylosylation. We identified a hydroxysteroid dehydrogenase AmHSD1 from A. membranaceus. AmHSD1 catalyzes the C-3 oxidation of cycloastragenol, yielding cycloastragenol-3-one, and the C-3 reduction of cycloastragenol-3-one-6-O-glucoside, resulting in cycloastragenol-6-O-glucoside. Additionally, the glycosyltransferases AmGT8 and AmGT1, previously reported by our groups, were identified as catalyzing the 6-O-glucosylation and 3-O-xylosylation steps, respectively. Astragaloside IV was successfully synthesized in transient expression in Nicotiana benthamiana using the combination of AmHSD1, AmGT8 and AmGT1. These results support the proposed four-step biosynthetic pathway and suggest that AmHSD1 probably plays a crucial role in the biosynthesis of astragaloside IV within A. membranaceus.
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The objective of this study was to enhance the microbial inactivation efficacy of sesame seeds through the utilization of a pilot-scale IPL device, while also identifying the process variables that influence the microbial inactivation effect. Three different types of IPL processes were employed, each with a distinct arrangement, to treat sesame seeds. The total fluences applied ranged from 1.33 to 53.94 J/cm2. Total aerobic bacteria and fungi exhibited a maximum reduction of 2.27 and 2.77 log, respectively. The curved pathway of the sample flow effectively extended the duration of exposure to the IPL emitted by the lamps. The arrangement of the IPL process using two lamps in parallel but at different locations proved the most efficient for microbial inactivation. The application of IPL was found to be effective in reducing the presence of indigenous microbes in sesame seeds while having no significant impact on the physicochemical properties of the seeds.
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Background: Type 2 diabetes mellitus (T2DM) is widely acknowledged as a vital warning sign contributing to cognitive dysfunction. However, there is still a lack of consensus on whether hypoglycemic events resulting from poor glycemic control increase the risk of cognitive dysfunction in people with diabetes, and the potential dose-response correlation between hypoglycemic events and cognitive dysfunction remains unexplored. The primary objective of the current study was to assess the contribution of hypoglycemic events to cognitive dysfunction in T2DM patients and the dose-response correlation between the two. Methods: A comprehensive search of nine major databases was executed from inception to May 2023. We screened all observational studies examining the connection between hypoglycemia and cognitive dysfunction. The DerSimonian-Laird method was used to compute the combined risk ratio (RR) and its 95% confidence interval (CI). Additionally, dose-response analysis was employed to investigate the correlation between the frequency of hypoglycemia and the likelihood of cognitive dysfunction. Results: A total of 30 studies of different levels in 17 articles with 3,961,352 participants were included in this review. The pooled RR for the connection of hypoglycemia and the likelihood of cognitive dysfunction was 1.47 (95% CI: 1.35-1.60). Subgroup analyses showed that the pooled RR for the likelihood of cognitive dysfunction was 1.20 (95% CI: 1.11-1.31) for one episode of hypoglycemia, 1.41 (95% CI: 1.05-1.88) for two episodes of hypoglycemia, and 1.62 (95% CI: 1.20-2.91) for three or more episodes of hypoglycemia. Dose-response analysis showed a linear dose-response relationship between hypoglycemia and the likelihood of cognitive dysfunction (exp (b) = 1.178694, z = 7.12, p < 0.001). Conclusion: Our investigations demonstrated a 47% heightened likelihood of cognitive dysfunction in individuals with hypoglycemia compared to those without. Furthermore, the likelihood of cognitive dysfunction climbed by 17.87% for every subsequent episode of hypoglycemia. Therefore, long-term monitoring of blood glucose, periodic screening of cognitive function, and moderate health education should be encouraged, which will be beneficial for people with diabetes to prevent hypoglycemic events and cognitive dysfunction. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, CRD42023432352.
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PURPOSE: Recent studies have increasingly linked Ephrin receptor B2 (EPHB2) to cancer progression. However, comprehensive investigations into the immunological roles and prognostic significance of EPHB2 across various cancers remain lacking. METHODS: We employed various databases and bioinformatics tools to investigate the impact of EPHB2 on prognosis, immune infiltration, genome instability, and response to immunotherapy. Validation of the correlation between EPHB2 expression and M2 macrophages included analyses using bulk and single-cell transcriptomic datasets, spatial transcriptomics, and multi-fluorescence staining. Moreover, we performed cMap web tool to screen for EPHB2-targeted compounds and assessed their potential through molecular docking and dynamics simulations. Additionally, in vitro validation using lung adenocarcinoma (LUAD) cell lines was conducted to confirm the bioinformatics predictions about EPHB2. RESULTS: EPHB2 dysregulation was observed across multiple cancer types, where it demonstrated significant diagnostic and prognostic value. Gene Set Enrichment Analysis (GSEA) indicated that EPHB2 is involved in enhancing cellular proliferation, invasiveness of cancer cells, and modulation of the anti-cancer immune response. Furthermore, it is emerged as a pan-cancer marker for M2 macrophage infiltration, supported by integrated analyses of transcriptomics and multiple fluorescence staining. In LUAD cells, knockdown of EPHB2 expression led to a decrease in both cell proliferation and migratory activity. CONCLUSION: EPHB2 expression may serve as a pivotal indicator of M2 macrophage infiltration, offering vital insights into tumor dynamics and progression across various cancers, including lung adenocarcinoma, highlighting its significant prognostic and therapeutic potential for further exploration.
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Biomarcadores Tumorais , Imunoterapia , Receptor EphB2 , Humanos , Receptor EphB2/genética , Receptor EphB2/metabolismo , Prognóstico , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Imunoterapia/métodos , Linhagem Celular Tumoral , Biologia Computacional/métodos , Neoplasias/genética , Neoplasias/imunologia , Neoplasias/terapia , Regulação Neoplásica da Expressão Gênica , Proliferação de Células , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/metabolismo , Perfilação da Expressão Gênica , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/imunologia , Adenocarcinoma de Pulmão/patologia , Adenocarcinoma de Pulmão/metabolismo , Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/terapia , Movimento Celular , Simulação de Acoplamento MolecularRESUMO
BACKGROUND: In recent years, immune checkpoint inhibitors (ICIs) have demonstrated remarkable efficacy across diverse malignancies. Notably, in patients with advanced gastric cancer, the use of programmed death 1 (PD-1) blockade has significantly prolonged overall survival, marking a pivotal advancement comparable to the impact of Herceptin over the past two decades. While the therapeutic benefits of ICIs are evident, the increasing use of immunotherapy has led to an increase in immune-related adverse events. CASE SUMMARY: This article presents the case of a patient with advanced gastric cancer and chronic plaque psoriasis. Following sintilimab therapy, the patient developed severe rashes accompanied by cytokine release syndrome (CRS). Fortunately, effective management was achieved through the administration of glucocorticoid, tocilizumab, and acitretin, which resulted in favorable outcomes. CONCLUSION: Glucocorticoid and tocilizumab therapy was effective in managing CRS after PD-1 blockade therapy for gastric cancer in a patient with chronic plaque psoriasis.
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OBJECTIVES: To analyze the rules of acupoint selection in treatment of cancer-related insomnia with acupuncture and moxibustion by data mining technology. METHODS: The articles of cancer-related insomnia treated with acupuncture and moxibustion were searched from CNKI, Wanfang, VIP, SinoMed, PubMed, WOS, Cochrane, and Embase databases, from the inception of each database to January 5, 2024. The prescription database of acupuncture and moxibustion for cancer-related insomnia was established. The descriptive analysis was conducted on the use frequency, meridian tropism and distribution of acupoints. Using SPSS Modeler 18.0 Apriori algorithm, the association rules of acupoint prescriptions were analyzed. With Cytoscape3.9.1 software used, the complex network diagram was plotted, and the cluster analysis of high-frequency acupoints was performed by SPSS26.0 software. RESULTS: Forty-one articles were included, and 67 prescriptions were extracted with 89 acupoints involved, and the total use frequency was 447 times. The top 4 acupoints of the high use frequency were Baihui (GV20), Sanyinjiao (SP6), Shenmen (HT7) and Shenting (GV24). The included meridians were the governor vessel, the spleen meridian, the bladder meridian, the conception vessel, the heart meridian and the stomach meridian. The selected acupoints were mostly distributed on the head, the neck and and the upper and lower limbs. The special acupoints of the high use frequency included the five-Shu points, the crossing points and yuan-primordial points. Regarding acupoint combination, GV24, SP6, HT7, and GV20 were highly correlated. The three effective clusters were categorized among the top 12 acupoints of the high use frequency. CONCLUSIONS: In treatment of cancer-related insomnia with acupuncture and moxibustion, the principle focuses on supporting the healthy qi, eliminating pathogens, regulating yin and yang, promoting the circulation of the governor vessel for regulating the spirit, and tranquilizing the mind. The core acupoint prescription may includes GV24, SP6, HT7 and GV20ï¼combined with Zusanli (ST36) and Yintang (GV4+) to enhance the therapeutic effect.
Assuntos
Pontos de Acupuntura , Terapia por Acupuntura , Mineração de Dados , Moxibustão , Neoplasias , Distúrbios do Início e da Manutenção do Sono , Humanos , Distúrbios do Início e da Manutenção do Sono/terapia , Distúrbios do Início e da Manutenção do Sono/etiologia , Neoplasias/complicações , Neoplasias/terapiaRESUMO
Fine tuning of the metal site coordination environment of a single-atom catalyst (SAC) to boost its catalytic activity for oxygen reduction reaction (ORR) is of significance but challenging. Herein, we report a new SAC bearing Fe-N3C-N sites with asymmetric in-plane coordinated Fe-N3C and axial coordinated N atom for ORR, which was obtained by pyrolysis of an iron isoporphyrin on polyvinylimidazole (PVI) coated carbon black. The C@PVI-(NCTPP)Fe-800 catalyst exhibited significantly improved ORR activity (E1/2 = 0.89 V vs RHE) than the counterpart SAC with Fe-N4-N sites in 0.1 M KOH. Significantly, the Zn-air batteries equipped with the C@PVI-(NCTPP)Fe-800 catalyst demonstrated an open-circuit voltage (OCV) of 1.45 V and a peak power density (Pmax) of 130 mW/cm2, outperforming the commercial Pt/C catalyst (OCV = 1.42 V; Pmax = 119 mW/cm2). The density functional theory (DFT) calculations revealed that the d-band center of the asymmetric Fe-N3C-N structure shifted upward, which enhances its electron-donating ability, favors O2 adsorption, and supports O-O bond activation, thus leading to significantly promoted catalytic activity. This research presents an intriguing strategy for the designing of the active site architecture in metal SACs with a structure-function controlled approach, significantly enhancing their catalytic efficiency for the ORR and offering promising prospects in energy-conversion technologies.