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BACKGROUND: Our objective was to elucidate the pivotal roles of BCAR1 in unfolded protein response (UPR), autophagy and vasculogenic mimicry (VM) formation, processes that essential for the metastasis of lung adenocarcinoma (LUAD) cells. METHODS: The morphological assessment of endoplasmic reticulum (ER) status and autolysosomes in H1975 and H1299 LUAD cells following BCAR1 knockout (KO) was conducted using transmission electron microscope. The expression of markers and cellular functions related to the UPR, autophagy, and VM formation were examined in LUAD cells tissues. Additionally, proteomic analysis of LUAD cells was performed via mass spectrometry, and the pertinent signaling pathways were analyzed using bioinformatics tools. RESULTS: BCAR1-KO inhibited autophagy and UPR induced triggered starvation in LUAD cells. Cleaved-ATF6a-mediated UPR and subsequent autophagy, enhanced by BCAR1, were confirmed using the UPR stimulator and blocker. High BCAR1 expression, along with elevated UPR and autophagy, predicts poor prognosis in LUAD patients. BCAR1-KO reduced tube formation and VM markers expressions in LUAD cells. Additionally, BCAR1 expression positively correlated with VM formation in BALB/c-nu mice xenografts and LUAD patient tissues. CONCLUSION: BCAR1 promotes LUAD metastasis by enhancing cancer cell survival in nutrient-poor environments through ATF6-mediated UPR activation and autophagy. As BCAR1 induces VM formation, metastatic lesions eventually colonize. Thus, BCAR1 is a promising anti-metastasis target.
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BACKGROUND: Reducing exposure to risk factors and screening represent 2 major approaches to gastric cancer (GC) prevention, but public knowledge GC risk factors and screening behaviour remain unknown. We aimed to investigate public awareness of GC risk factors, adherence to screening, and barriers hindering screening practices in China. METHODS: This community-based household survey was conducted within Shijiazhuang, China, and 1490 residents were recruited through a multistage stratified cluster random sampling approach. A self-administered questionnaire was completed which consisted of three sections: demographics, awareness of GC risk factors, and personal screening behaviours. Factors associated with knowledge of risk factors and screening behaviours were evaluated using binary logistic regression analysis. RESULTS: The mean risk factor awareness score of 12 (7, 15) revealed insufficient knowledge in 51.1% of participants. Dietary lifestyle factors were better understood than physical activity and weight-related factors. Marital status (OR 1.967; 95% CI 1.415 to 2.734), higher income (OR 1.197; 95% CI 1.010 to 1.418), and a history of upper gastrointestinal problems (OR 0.048; 95% CI 1.002 to 1.311) were associated with higher awareness. Merely 21.5% underwent GC screening, with higher rates linked to older age (OR 1.642; 95% CI 1.418 to 1.902), higher education (OR 1.398; 95% CI 1.176 to 1.662), a history of upper gastrointestinal problems (OR 3.842; 95% CI 2.833 to 5.209), and moderate (OR 2.077; 95% CI 1.352 to 3.191) and high (OR 2.529; 95% CI 1.311 to 4.878) perceived GC risk. Notably, participants commonly refused gastroscopy due to the absence of symptoms or signs. CONCLUSIONS: In Shijiazhuang, more than half of participants demonstrated inadequate knowledge of GC risk factors, and screening participation rates were remarkably low. This emphasizes the need for targeted interventions to enhance GC awareness and significantly improve screening rates.
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Detección Precoz del Cáncer , Conocimientos, Actitudes y Práctica en Salud , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/epidemiología , Neoplasias Gástricas/prevención & control , Masculino , China/epidemiología , Femenino , Persona de Mediana Edad , Factores de Riesgo , Adulto , Anciano , Encuestas y Cuestionarios , Detección Precoz del Cáncer/estadística & datos numéricos , Detección Precoz del Cáncer/psicología , Tamizaje Masivo , Adulto JovenRESUMEN
Water is essential to the formation of intracontinental granites, but its origin remains elusive. Here we address this scientific problem by analyzing D/H isotopes of apatites, hydrous minerals in Jurassic and Early Cretaceous granites and basalts from eastern North China Craton, where water was previously interpreted as derived from subducting slab. Results reveal extremely low δD values in pristine Early Cretaceous granitic (-203 to -127) and basaltic (-197 to -107) apatites, contrasting with relatively high δD values (-137 to -47) in Jurassic granites. Given the depth-dependent D/H isotopic fractionation during slab dehydration and high-water contents in coeval primitive mafic magmas, the Early Cretaceous magma water is attributed to the stagnant slab within the mantle transition zone. Secular change in the depth of water aligns with steepening of subducting Paleo-Pacific plate from Jurassic to Early Cretaceous, demonstrating the potential of apatite H isotopes in tracing water origin in granites and basalts.
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Krüppel-like factors (KLFs) are a family of basic transcription factors with three conserved Cys2/His2 zinc finger domains located in their C-terminal regions. It is acknowledged that KLFs exert complicated effects on cell proliferation, differentiation, survival, and responses to stimuli. Dysregulation of KLFs is associated with a range of diseases including cardiovascular disorders, metabolic diseases, autoimmune conditions, cancer, and neurodegenerative diseases. Their multidimensional roles in modulating critical pathways underscore the significance in both physiological and pathological contexts. Recent research also emphasizes their crucial involvement and complex interplay in the skeletal system. Despite the substantial progress in understanding KLFs and their roles in various cellular processes, several research gaps remain. Here, we elucidated the multifaceted capabilities of KLFs on body health and diseases via various compliable signaling pathways. The associations between KLFs and cellular energy metabolism and epigenetic modification during bone reconstruction have also been summarized. This review helps us better understand the coupling effects and their pivotal functions in multiple systems and detailed mechanisms of bone remodeling and develop potential therapeutic strategies for the clinical treatment of pathological diseases by targeting the KLF family.
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BACKGROUND: Poor glucose control might deteriorate the impaired pulmonary function, which can ultimately lead to mortality. However, few studies have examined the effect modification of glucose control on the association between pulmonary function and mortality. This study aimed to examine the association of pulmonary function with mortality and determine the effect modification of glycemic level on the association of pulmonary function with mortality in persons with type 2 diabetes (T2DM). METHODS: A retrospective cohort study included 3846 persons with T2DM with pulmonary function testing in Taiwan during 2002-2020. Expiratory volume in 1 s (FEV1) was measured as pulmonary function. Cox proportional hazards models were used and the effect modification of pulmonary function parameters and glucose control was assessed by their product terms. RESULTS: There were 733 deaths during an average follow-up of 7.83 years. Significant associations of FEV1 and mortality were found (hazards ratio [HR] for FEV1 Z-scores of <0 to -1, <-1 to -2 and <-2: 1.47 [1.20, 1.80], 2.48 [1.95, 3.14] and 3.07 [1.74, 5.44] compared with participants with Z-score ≥0, respectively. All p for trend<0.001). Significant effect modifications were found and the association between FEV1 and mortality was stronger in persons with good glycemic control compared with poor glycemic control (FEV1-FPG effect modification, P = 0.01; FEV1-HbA1c effect modification, P = 0.03). CONCLUSION: Pulmonary function, measured by FEV1, is significantly associated with mortality in persons with T2DM. Significant effect modification of glucose control on the association between pulmonary function parameters and mortality was found.
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To explore the changes in water status and protein characteristics of Tibetan pork (TP) under modified atmosphere packaging (MAP) with different oxygen concentrations compared to Duroc×Landrace×Yorkshire pork (DLY), the water holding capacity (WHC), water distribution, protein oxidation, and conformation of both types were determined. Results indicate that under MAP, TP pork and DLY pork exhibited higher water retention and lower protein oxidation compared to air packaging. However, with increased oxygen concentration in the MAP, protein oxidation intensified, leading to reduced WHC in the pork. Compared to DLY pork, TP pork in different packaging conditions maintained the integrity of protein secondary and tertiary structures, reducing protein cross-linking aggregation. The lower content of P 3 in the two-dimensional relaxation spectra, shorter T 1 and T 2 relaxation times, and higher proton density suggest better water retention properties in Tibetan pork. These findings support the development of long-distance preservation and transportation technologies for TP pork.
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Histamine is a biogenic amine that is critical in various physiological and pathophysiological processes, including but not limited to allergic reactions, wakefulness, gastric acid secretion and neurotransmission. Here, we determine 9 cryo-electron microscopy (cryo-EM) structures of the 4 histamine receptors in complex with four different G protein subtypes, with endogenous or synthetic agonists bound. Inside the ligand pocket, we identify key motifs for the recognition of histamine, the distinct binding orientations of histamine and three subpockets that facilitate the design of specific ligands. In addition, we also identify key residues responsible for the selectivity of immethridine. Moreover, we reveal distinct structural features as determinants of Gq vs. Gs or Gs vs. Gi coupling differences among the histamine receptors. Our study provides a structural framework for understanding the ligand recognition and G protein coupling of all 4 histamine receptors, which may facilitate the rational design of ligands targeting these receptors.
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Microscopía por Crioelectrón , Histamina , Receptores Histamínicos , Ligandos , Humanos , Histamina/metabolismo , Histamina/química , Receptores Histamínicos/metabolismo , Receptores Histamínicos/química , Células HEK293 , Unión Proteica , Sitios de Unión , Agonistas de los Receptores Histamínicos/química , Agonistas de los Receptores Histamínicos/metabolismo , Agonistas de los Receptores Histamínicos/farmacología , Modelos MolecularesRESUMEN
RATIONALE: This article reports a case of coronavirus disease (COVID-19)-associated autoimmune encephalitis (AE) and reviews the relevant literature to investigate the clinical manifestations, auxiliary inspection, diagnosis and treatment, and prognosis of AE associated with COVID-19. PATIENT CONCERNS: A 68-year-old female with fatigue developed altered consciousness after 2 days of fever, thereafter testing positive for COVID-19. The protein levels in the lumbar puncture cerebrospinal fluid were elevated, and cranial magnetic resonance imaging (MRI) scan indicated T2-weighted hyperintensity in the temporal lobe. DIAGNOSES: The patient was diagnosed with COVID-19-associated AE. INTERVENTIONS: After admission, the patient received pulse steroid therapy with methylprednisolone. Additionally, gastric protection, blood glucose control, nutritional support, and other treatments were administered. OUTCOMES: The symptoms were significantly relieved by steroid pulse therapy. At the 3-month follow-up, the patient had recovered completely without any obvious discomfort. LESSONS: The possibility of AE should be considered if neurological symptoms occur a few days after infection with COVID-19, with early diagnosis and immediate steroid pulse therapy resulting in better outcomes.
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COVID-19 , Encefalitis , Metilprednisolona , Anciano , Femenino , Humanos , COVID-19/complicaciones , COVID-19/inmunología , Encefalitis/diagnóstico , Encefalitis/tratamiento farmacológico , Encefalitis/inmunología , Glucocorticoides/uso terapéutico , Imagen por Resonancia Magnética , Metilprednisolona/uso terapéutico , Metilprednisolona/administración & dosificación , SARS-CoV-2/inmunologíaRESUMEN
Background: Dementia poses a growing global mental health impact, with variations in prevalence by gender, possibly influenced by reproductive factors. Ectopic pregnancy (EP), known for its association with cardiovascular diseases and depression, which are also predictors of dementia, prompted an exploration of their interplay. Methods: Using Taiwan's National Health Insurance Research Database, this nationwide cohort study examined 53,096 individuals to investigate the link between EP and dementia. Covariates included age, insured premiums, comorbidity by Charlson Comorbidity Index revised by excluding dementia, level of care, and residence. Surgical approaches, number of EP episodes, and dementia subtypes were considered in outcomes analysis using Cox regression. Results: Among 13,274 women diagnosed with EP, 791 developed dementia over a 15-year follow-up, particularly vascular dementia. Adjusting for the covariates, the adjusted sub-distribution Hazard Ratio (asHR) with competing risks was 1.644 (95% CI, 1.394-2.053; p < 0.001). For patients with more than one episode, it was even higher (asHR=1.670 [95% CI, 1.419-2.092; p < 0.001]). Post-ectopic depression, prevalent in 62.2% within four weeks, was associated with a greater dementia risk compared to those without (asHR=1.702 [95% CI, 1.444-2.125; p<0.001] vs. asHR=1.551 [95%CI, 1.310-1.937; p<0.001]). Antidepressant treatments showed a partial protective effect, reducing the increased risk by 14.7%. Conclusion: An EP history is linked to an earlier onset and a higher risk of overall dementia, VaD in particular, in a dose dependent manner, regardless of surgical intervention and stroke. Post-ectopic depression exacerbates dementia risk, while antidepressants offer partial protection. These findings underscore the potential benefit of screening and treating depression in women following EPs.
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In order to explore the application prospects of static magnetic field (SMF) combined with supercooling in meat preservation, this study proposed a novel method of supercooling assisted by a stationary magnetic field (SMF + supercooling) for the preservation of chilled pork, evaluating its cooling rate and quality changes (e.g., water holding capacity, color, pH, and TVB-N), as well as the evolution trend of the microbiota. The results showed that SMF + supercooling significantly (P < 0.05) improved the cooling rate of pork. Compared to chilling and supercooling, SMF + supercooling significantly delayed the increase of TVB-N and TVC on the 12th day of storage (P < 0.05). SMF + supercooling treatment achieves the maintenance of pork water-holding capacity by inhibiting water migration, reducing drip loss, cooking loss, and centrifugal loss of pork. The 16S rDNA bacteria flora analysis demonstrated that SMF + supercooling treatment reduced the relative abundance of spoilage bacteria such as Acinetobacter, Streptococcus, and Pseudomonas, delaying the deterioration of pork quality caused by microbial growth. The SMF + supercooling treatment can be considered a novel refrigeration preservation method that delays the deterioration of pork quality and extends its shelf life.
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Frío , Almacenamiento de Alimentos , Campos Magnéticos , Animales , Porcinos , Almacenamiento de Alimentos/métodos , Conservación de Alimentos/métodos , Microbiología de Alimentos , Microbiota , Carne de Cerdo/microbiología , Carne de Cerdo/análisis , Bacterias/crecimiento & desarrollo , Bacterias/clasificación , Calidad de los Alimentos , Refrigeración , Concentración de Iones de Hidrógeno , AguaRESUMEN
Meat quality (MQ) is unstable during cold chain logistics (CCL). Different technologies have been developed to enhance MQ during the CCL process, while most of them cannot cover all the links of the cold chain because of complex environment (especially transportation and distribution), compatibility issues, and their single effect. Electric fields (EFs) have been explored as a novel treatment for different food processing. The effects and potential advantages of EFs for biological cryopreservation have been reported in many publications and some commercial applications in CCL have been realized. However, there is still a lack of a systematic review on the effects of EFs on their quality attributes in meat and its applications in CCL. In this review, the potential mechanisms of EFs on meat physicochemical properties (heat and mass transfer and ice formation and melting) and MQ attributes during different CCL links (freezing, thawing, and refrigeration processes) were summarized. The current applications and limitations of EFs for cryopreserving meat were also discussed. Although high intensity EFs have some detrimental effects on the quality attributes in meat due to electroporation and electro-breakdown effect, EFs present good applicability opportunities in most CCL scenes that have been realized in some commercial applications. Future studies should focus on the biochemical reactions of meat to the different EFs parameters, and break the limitations on equipment, so as to make EFs techniques closer to usability in the production environment and realize cost-effective large-scale application of EFs on CCL.
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Criopreservación , Carne , Refrigeración , Carne/análisis , Animales , Criopreservación/métodos , Conservación de Alimentos/métodos , Electricidad , Congelación , Calidad de los Alimentos , Manipulación de Alimentos/métodos , Almacenamiento de Alimentos/métodos , FríoRESUMEN
Purpose: To investigate the clinical value of adding Jin-gu-lian (JGL) capsules into rheumatoid arthritis (RA) treatment by examining its impact on disease activity and quality of life (QoL) through a real-world study (RWS). Patients and methods: RWS was conducted to compare the inflammatory markers, including IgM-RF, ESR, and CRP, between RA patients treated with only Western medicine (reference group) and Western medicine plus JGL (study group) during one-year follow-up. The clinical data was acquired from the hospital information system (HIS). Telephone call-based follow-up on QoL (SF-36) and accompanying symptoms, including gastrointestinal complaints, attacks of pneumonia, herpes zoster, URTIs, UTIs, and LTBIs. Finally, the anti-rheumatic drugs given to both groups were also compared. RWS was further validated for its feasibility by performing studies with hydroxychloroquine (HCQ) treatment, which is a commonly used anti-rheumatic drug for RA with mild effect. Results: The study group failed to show a significant effect on inflammatory markers, especially on the CRP levels, indicating no additional clinical value of supplementing with JGL. Similarly, at the endpoint, no significant differences between the two groups on QoL and related symptoms were observed. Our study suggests that the patients in the study group might need more anti-rheumatic drugs to fill the treatment insufficiency, and the application ratio of NSAIDs would be significantly higher than the reference group. By conducting this study on HCQ treatment, the positive aspects of controlling disease activity and reducing NSAIDs application were found, which demonstrates the utility of performing the RWS to evaluate the effect of JGL. Conclusion: Adding JGL did not significantly improve the clinical efficacy of RA treatment by this RWS. Folk herbal prescriptions such as JGL are suggested to underwent strict clinical trials before application.
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OBJECTIVES: To investigate the clinical characteristics of Ureaplasma urealyticum (UU) infection and colonization in extremely preterm infants and its impact on the incidence of bronchopulmonary dysplasia (BPD). METHODS: A retrospective analysis was conducted on 258 extremely preterm infants who were admitted to the Department of Neonatology, Shenzhen Maternity and Child Healthcare Hospital, from September 2018 to September 2022. According to the results of UU nucleic acid testing and the evaluation criteria for UU infection and colonization, the subjects were divided into three groups: UU-negative group (155 infants), UU infection group (70 infants), and UU colonization group (33 infants). The three groups were compared in terms of general information and primary and secondary clinical outcomes. RESULTS: Compared with the UU-negative group, the UU infection group had significant increases in the incidence rate of BPD, total oxygen supply time, and the length of hospital stay (P<0.05), while there were no significant differences in the incidence rates of BPD and moderate/severe BPD between the UU colonization group and the UU-negative group (P>0.05). CONCLUSIONS: The impact of UU on the incidence of BPD in extremely preterm infants is associated with the pathogenic state of UU (i.e., infection or colonization), and there are significant increases in the incidence rate of BPD, total oxygen supply time, and the length of hospital stay in extremely preterm infants with UU infection. UU colonization is not associated with the incidence of BPD and moderate/severe BPD in extremely preterm infants.
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Displasia Broncopulmonar , Recien Nacido Extremadamente Prematuro , Infecciones por Ureaplasma , Ureaplasma urealyticum , Humanos , Infecciones por Ureaplasma/epidemiología , Infecciones por Ureaplasma/complicaciones , Ureaplasma urealyticum/aislamiento & purificación , Recién Nacido , Estudios Retrospectivos , Femenino , Masculino , Displasia Broncopulmonar/epidemiología , Displasia Broncopulmonar/microbiología , Displasia Broncopulmonar/etiología , Tiempo de InternaciónRESUMEN
RATIONALE: Ethylene oxide (EO) sterilization is commonly employed for the sterilization of medical devices and has a very high market share. However, EO and its metabolite ethylene chlorohydrin (ECH) are toxic to humans. In compliance with the classification and residue limits of medical devices defined by ISO 10993-7, our study established two extraction methods for the testing of EO and ECH. METHODS: The first method involves simulated-use extraction using water as the extraction solvent. While the second, exhaustive extraction, directly extracts sample through headspace sampling analysis. Gas chromatography-tandem mass spectrometry in multiple reaction monitoring mode was utilized, requiring only 16 min. Then, the developed method was applied to assess 10 commercially available medical devices sterilized by EO. RESULTS: In simulated-use extraction, calibration curves were evaluated in the range of 1-100 and 5-500 µg for EO and ECH, respectively (r > 0.999). Inter-day recoveries ranged from 85.0% to 95.2% and from 94.8% to 102.4%. In exhaustive extraction, calibration curves spanned 0.5-50 and 2-200 µg for EO and ECH, respectively (r > 0.999). Inter-day recoveries ranged from 101.6% to 102.1% for EO and from 98.1% to 102.2% for ECH. After analysis of the 10 commercially available medical devices, two cotton swabs were found to have ECH of 35.1 and 28.4 µg per device, and four medical devices were found to have EO with concentration below the limit of quantification. Meanwhile, we found that the EO internal standard (propylene oxide) recommended by ISO 10993-7 had interference problems with other similar substances and was not suitable as an internal standard for EO. CONCLUSIONS: This study offers a sensitive and straightforward analytical approach to EO and ECH residues in a variety of medical devices. In addition, the results show that the EO or ECH content of these types of medical devices in our study falls below the regulatory limits, therefore instilling confidence among consumers regarding their safe use.
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Óxido de Etileno , Cromatografía de Gases y Espectrometría de Masas , Espectrometría de Masas en Tándem , Óxido de Etileno/análisis , Óxido de Etileno/química , Espectrometría de Masas en Tándem/métodos , Cromatografía de Gases y Espectrometría de Masas/métodos , Equipos y Suministros , Límite de Detección , Etilenos/análisis , Etilenos/química , Reproducibilidad de los Resultados , Contaminación de Equipos , Esterilización/métodosRESUMEN
With the continuous advancement of wearable technology and advanced medical monitoring, there is an increasing demand for electronic devices that can adapt to complex environments and have high perceptual sensitivity. Here, a novel artificial injury perception device based on an Ag/HfOx/ITO/PET flexible memristor is designed to address the limitations of current technologies in multimodal perception and environmental adaptability. The memristor exhibits excellent resistive switching (RS) performance and mechanical flexibility under different bending angles (BAs), temperatures, humid environment, and repetitive folding conditions. Further, the device demonstrates the multimodal perception and conversion capabilities toward voltage, mechanical, and thermal stimuli through current response tests under different conditions, enabling not only the simulation of artificial injury perception but also holds promise for monitoring and controlling the movement of robotic arms. Moreover, the logical operation capability of the memristor-based reconfigurable logic (MRL) gates is also demonstrated, proving the device has great potential applications with sensing, storage, and memory functions. Overall, this study not only provides a direction for the development of the next-generation flexible multimodal sensors, but also has significant implications for technological advancements in many fields such as robotic arms, electronic skin (e-skin), and medical monitoring.
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BACKGROUND: The main goal of this study was to examine how diabetes, cardiovascular calcification characteristics and other risk factors affect mortality in end-stage renal disease (ESRD) patients in the early stages of hemodialysis. METHODS: A total of 285 ESRD patients in the early stages of hemodialysis were enrolled in this research, including 101 patients with diabetes. Survival time was monitored, and general data, biochemical results, cardiac ultrasound calcification of valvular tissue, and thoracic CT calcification of the coronary artery and thoracic aorta were recorded. Subgroup analysis and logistic regression were applied to investigate the association between diabetes and calcification. Cox regression analysis and survival between calcification, diabetes, and all-cause mortality. Additionally, the nomogram model was used to estimate the probability of survival for these individuals, and its performance was evaluated using risk stratification, receiver operating characteristic, decision, and calibration curves. RESULTS: Cardiovascular calcification was found in 81.2% of diabetic patients (82/101) and 33.7% of nondiabetic patients (62/184). Diabetic patients had lower phosphorus, calcium, calcium-phosphorus product, plasma PTH levels and lower albumin levels (p < 0.001). People with diabetes were more likely to have calcification than people without diabetes (OR 5.66, 95% CI 1.96-16.36; p < 0.001). The overall mortality rate was 14.7% (42/285). The risk of death was notably greater in patients with both diabetes and calcification (29.27%, 24/82). Diabetes and calcification, along with other factors, collectively predict the risk of death in these patients. The nomogram model demonstrated excellent discriminatory power (area under the curve (AUC) = 0.975 at 5 years), outstanding calibration at low to high-risk levels and provided the greatest net benefit across a wide range of clinical decision thresholds. CONCLUSIONS: In patients with ESRD during the early period of haemodialysis, diabetes significantly increases the risk of cardiovascular calcification, particularly multisite calcification, which is correlated with a higher mortality rate. The risk scores and nomograms developed in this study can assist clinicians in predicting the risk of death and providing individualised treatment plans to lower mortality rates in the early stages of hemodialysis.
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Causas de Muerte , Fallo Renal Crónico , Nomogramas , Diálisis Renal , Calcificación Vascular , Humanos , Masculino , Persona de Mediana Edad , Femenino , Estudios Retrospectivos , Calcificación Vascular/mortalidad , Calcificación Vascular/diagnóstico por imagen , Fallo Renal Crónico/mortalidad , Fallo Renal Crónico/terapia , Fallo Renal Crónico/diagnóstico , Fallo Renal Crónico/sangre , Fallo Renal Crónico/complicaciones , Diálisis Renal/mortalidad , Medición de Riesgo , Factores de Tiempo , Anciano , Factores de Riesgo , Resultado del Tratamiento , Diabetes Mellitus/mortalidad , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/sangre , Adulto , Valor Predictivo de las Pruebas , Nefropatías Diabéticas/mortalidad , Nefropatías Diabéticas/diagnóstico , Nefropatías Diabéticas/terapia , Nefropatías Diabéticas/sangre , Técnicas de Apoyo para la Decisión , Enfermedad de la Arteria Coronaria/mortalidad , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/diagnóstico , Enfermedad de la Arteria Coronaria/terapiaRESUMEN
BACKGROUND: The aim of this study was to investigate the associations of blood phosphorus levels with the risk of developing medial arterial calcification (MAC) in lower-limb arteries and diabetic foot (DF) in diabetes patients. We sought to enhance the understanding of the pathophysiology of diabetic complications and develop strategies to mitigate diabetes-related risks. METHODS: We conducted a retrospective analysis of 701 diabetic patients from the Department of Endocrinology at Sun Yat-Sen Memorial Hospital (2019-2023). We utilized multimodel-adjusted logistic regression to investigate the associations of serum phosphorus levels and the risk of developing MAC and DF. Restricted cubic spline plots were employed to model the relationships, and threshold analysis was used to identify inflection points. Subgroup analyses were performed to explore variations across different demographics. The diagnostic utility of phosphorus concentrations was assessed via the C index, net reclassification improvement (NRI), and integrated discrimination improvement (IDI). RESULTS: Of the 701 patients (mean age 63.9 years; 401 (57.20%) were male), 333 (47.50%) had MAC, and 329 (46.93%) had DF. After controlling for numerous confounding variables, each one-unit increase in phosphorus concentrations was associated with an increased risk of developing MAC (OR 2.65, 95% CI 1.97-3.57, p < 0.001) and DF (OR 1.54, 95% CI 1.09-2.18, p = 0.014). Phosphorus levels demonstrated a linear risk association, with risk not being uniform on either side of the inflection point, which was approximately 3.28 mg/dL for MAC and varied for DF (3.26 to 3.81 mg/dL). Adding the phosphorus as an independent component to the diagnostic model for MAC and DF increased the C index, NRI, and IDI to varying degrees. CONCLUSIONS: Elevated serum phosphorus levels are significantly associated with an increased risk of developing MAC and DF among diabetic people. These findings suggest that phosphorus management could be integrated into routine diagnostic processes to improve the identification and management of lower-extremity diabetic complications.
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Biomarcadores , Pie Diabético , Enfermedad Arterial Periférica , Fósforo , Calcificación Vascular , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Femenino , Estudios Transversales , Fósforo/sangre , Calcificación Vascular/sangre , Calcificación Vascular/epidemiología , Calcificación Vascular/diagnóstico por imagen , Calcificación Vascular/diagnóstico , Anciano , Factores de Riesgo , Enfermedad Arterial Periférica/diagnóstico , Enfermedad Arterial Periférica/sangre , Enfermedad Arterial Periférica/epidemiología , Pie Diabético/diagnóstico , Pie Diabético/sangre , Pie Diabético/epidemiología , Medición de Riesgo , Biomarcadores/sangre , Pronóstico , Extremidad Inferior/irrigación sanguíneaRESUMEN
PERK/CHOP pathway-mediated excessive endoplasmic reticulum (ER) stress is closely linked to aging-related cognitive impairment (ARCD). Zerumbone (ZB), a naturally occurring sesquiterpene molecule obtained from dietary bitter ginger, has garnered significant interest due to its diverse range of biological properties. It is unclear, though, if ZB can reduce ARCD by preventing ER stress that is dependent on the PERK/CHOP pathway. Here, the PERK-CHOP ER stress pathway was the main focus of an evaluation of the effects and mechanisms of ZB for attenuating ARCD in D-galactose (D-gal)-induced aging mice and SH-SY5Y cells. According to our findings, ZB not only greatly decreased neuronal impairment both in vitro and in vivo, but also significantly alleviated learning and memory failure in vivo. ZB significantly reduced the activation of the PERK/CHOP pathway and neuronal apoptosis in vitro and in vivo, exhibiting the down-regulation of GRP78, p-PREK/PERK, and CHOP expression levels, in addition to suppressing oxidative damage (MDA drop and SOD rise). Comparable outcomes were noted in SH-SY5Y cells subjected to severe ER stress caused by TM. On the other hand, 4-PBA, an ER stress inhibitor, considerably reversed these modifications. Remarkably, CCT020312 (a PERK activator) dramatically overrode the inhibitory effects of ZB on the PERK/CHOP pathway and neuronal death in D-gal-induced SH-SY5Y cells. In contrast, GSK2606414 (a PERK inhibitor) significantly increased these effects of ZB. In summary, our results suggested that ZB prevented D-gal-induced cognitive deficits by blocking the PERK/CHOP-dependent ER stress pathway and apoptosis, suggesting that ZB might be a natural sesquiterpene molecule that relieves ARCD.
Asunto(s)
Envejecimiento , Chaperón BiP del Retículo Endoplásmico , Estrés del Retículo Endoplásmico , Memoria , Sesquiterpenos , Factor de Transcripción CHOP , Zingiber officinale , eIF-2 Quinasa , Estrés del Retículo Endoplásmico/efectos de los fármacos , Sesquiterpenos/farmacología , Animales , eIF-2 Quinasa/metabolismo , Ratones , Factor de Transcripción CHOP/metabolismo , Envejecimiento/efectos de los fármacos , Humanos , Masculino , Zingiber officinale/química , Memoria/efectos de los fármacos , Disfunción Cognitiva/tratamiento farmacológico , Apoptosis/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Extractos Vegetales/farmacología , Línea Celular TumoralRESUMEN
This present study investigated how heat treatment affects the mechanical properties of 3D-printed black carbon fiber HTPLA by manipulating two parameters: heating temperature and holding time. The mechanical properties of 3D-printed black carbon fiber HTPLA components are crucial for assessing their structural integrity and performance. The shrinkage and dimensional accuracy of the 3D-printed parts were also explored using a vernier caliper. The microstructure of both heat-treated and non-heat-treated HTPLA black carbon fiber 3D-printed parts was examined using scanning electron microscopy. Samples were prepared, printed, heat-treated, and mechanically tested, and their microstructure was observed and recorded. The results showed that heat treatment improved the material's strength, hardness, and crystallinity, leading to better mechanical properties. However, statistical analysis indicates no clear evidence that the two factors, optimum heating temperature and holding time, affect the mechanical properties of heat-treated printed parts. Nonetheless, further study suggests that these factors might be important in optimizing the heat treatment process.