RESUMO
OBJECTIVE: Early identification of modifiable risk factors is crucial for the prevention of constipation. This study systematically investigated the relationship between genetically predicted modifiable risk factors and constipation. METHODS: The inverse variance weighting (IVW) method was employed as the primary analytical approach. For similar exposure indicators, the multivariate Mendelian randomization (MVMR) method was used to adjust for potential biases in univariate MR analysis. The robustness of the results was further evaluated using the MR-Egger intercept test, Cochran's Q test, and leave-one-out analysis. Bonferroni correction was applied to reduce the false positive rate in the results. RESULTS: The IVW analysis indicated a significant causal association between genetically predicted gastroesophageal reflux disease [OR (95% CI) = 1.192 (1.079-1.315), P = 0.0005], atorvastatin use [OR (95% CI) = 16.995 (3.327-86.816), P = 0.0007], and constipation. Additionally, there was a potential causal association between education level [OR (95% CI) = 0.859 (0.767-0.964), P = 0.009], major depressive disorder [OR (95% CI) = 1.206 (1.041-1.399), P = 0.013], hypothyroidism [OR (95% CI) = 2.299 (1.327-3.985), P = 0.003], and aspirin use [OR (95% CI) = 4.872 (1.174-20.221), P = 0.029] with constipation. No causal associations were found for the other included indicators. Sensitivity analysis demonstrated the absence of evidence for heterogeneity and pleiotropy in any positive results. CONCLUSION: This study identified several risk factors that could be targeted for the prevention of constipation, offering valuable insights for public health policies.
Assuntos
Constipação Intestinal , Análise da Randomização Mendeliana , Humanos , Constipação Intestinal/epidemiologia , Fatores de Risco , Refluxo Gastroesofágico/complicações , Refluxo Gastroesofágico/genética , Polimorfismo de Nucleotídeo Único , Escolaridade , Predisposição Genética para DoençaRESUMO
Toxoplasma gondii (T. gondii), an obligate intracellular protozoan parasite, is increasingly recognized for its role in various human diseases, including periodontal diseases. Periodontal diseases comprise a wide range of inflammatory conditions that not only affect the supporting structures of the teeth and oral health but also contribute to systemic diseases. The parasite's ability to modulate the host's immune response and induce chronic inflammation within the periodontium is a key factor in periodontal tissue damage. Through its virulence factors, T. gondii disrupts the balance of inflammatory cytokines, leading to dysregulated immune responses, and exacerbates oxidative stress in periodontal tissues. And T. gondii invasion could affect specific proteins in host cells including HSP70, BAGs, MICs, ROPs, SAGs, and GRAs leading to periodontal tissue damage. The indirect role of the host immune response to T. gondii via natural killer cells, monocytes, macrophages, neutrophils, dendritic cells, T cells, and B cells also contributes to periodontal diseases. Understanding these complex interactions of T. gondii with host cells could unravel disease mechanisms and therapeutic targets for periodontal diseases. This review delves into the pathogenic mechanisms of T. gondii in periodontal diseases, offering a detailed exploration of both direct and indirect pathways of its impact on periodontal health.
Assuntos
Doenças Periodontais , Toxoplasma , Toxoplasmose , Humanos , Toxoplasma/imunologia , Doenças Periodontais/parasitologia , Doenças Periodontais/imunologia , Toxoplasmose/imunologia , Toxoplasmose/parasitologia , Toxoplasmose/metabolismo , Animais , Interações Hospedeiro-Parasita/imunologia , Citocinas/metabolismo , Citocinas/imunologiaRESUMO
Compared with silicon, gallium nitride, silicon carbide, and other traditional semiconductors, gallium oxide (Ga2O3) who possesses, an ultrawide bandgap of approximately 5.0 eV and a higher breakdown field strength of approximately 8 MV/cm has attracted increasing attention from researchers, especially for the potential application in power devices. Moreover, Ga2O3 material has natural ultraviolet detection ability for photodetectors due to its ultrawide bandgap. These future commercial applications put forward an urgent require for high-quality epitaxial Ga2O3 material in an efficient growth method at a lower cost. Although there are some conventional methods for single crystal Ga2O3 film epitaxial growth such as MBE and MOCVD, these methods always need a vacuum growth environment and expensive equipment. As a fast-growing method, Mist-CVD gives the growth of Ga2O3 in a vacuum-free, process-simple, and low-cost method, which will greatly reduce the cost and facilitate the development of Ga2O3. This review has summarizes the Mist-CVD epitaxy growth mechanism of Ga2O3, recent progress in the Ga2O3 film epitaxial growth, and various device properties based on the Mist-CVD method. Our work aims to provide help for the development of Ga2O3 material growth and device applications.
RESUMO
The ubiquitination or SUMOylation of hematopoietic related factors plays pivotal roles in hematopoiesis. RNF111, known as a ubiquitin ligase (Ubl), is a newly discovered SUMO-targeted ubiquitin ligase (STUbl) involved in multiple signaling pathways mediated by TGF-ß family members. However, its role in hematopoiesis remains unclear. Herein, a heritable Rnf111 mutant zebrafish line was generated by CRISPR/Cas9-mediated genome editing. Impaired hematopoietic stem and progenitor cells (HSPC) of definitive hematopoiesis was found in Rnf111 deficient mutants. Ablation of Rnf111 resulted in decreased phosphorylation of Smad2/3 in HSPC. Definitive endoderm 2 inducer (IDE2), which specifically activates TGF-ß signaling and downstream Smad2 phosphorylation, can restore the definitive hematopoiesis in Rnf111-deficient embryos. Further molecular mechanism studies revealed that Gcsfr/NO signaling was an important target pathway of Smad2/3 involved in Rnf111-mediated HSPC development. In conclusion, our study demonstrated that Rnf111 contributes to the development of HSPC by maintaining Smad2/3 phosphorylation and the Gcsfr/NO signaling pathway activation. Keywords: Rnf111, Ubiquitin ligase (UbL), HSPC, Smad2/3, Gcsfr/NO.
RESUMO
INTRODUCTION: Pyroptosis, inflammatory necrosis of cells, is a programmed cell death involved in the pathological process of diseases. Endoplasmic reticulum stress (ERS), as a protective stress response of cell, decreases the unfold protein concentration to inhibit the unfold protein agglutination. Whereas the relationship between endoplasmic reticulum stress and pyroptosis in pulmonary hypertension (PH) remain unknown. Previous evident indicated that circular RNA (circRNA) can participate in several biological process, including cell pyroptosis. However, the mechanism of circRNA regulate pyroptosis of pulmonary artery smooth muscle cells through endoplasmic reticulum stress still unclear. Here, we proved that circSSR1 was down-regulate expression during hypoxia in pulmonary artery smooth muscle cells, and over-expression of circSSR1 inhibit pyroptosis both in vitro and in vivo under hypoxic. Our experiments have indicated that circSSR1 could promote host gene SSR1 translation via m6A to activate ERS leading to pulmonary artery smooth muscle cell pyroptosis. In addition, our results showed that G3BP1 as upstream regulator mediate the expression of circSSR1 under hypoxia. These results highlight a new regulatory mechanism for pyroptosis and provide a potential therapy target for pulmonary hypertension. METHODS: RNA-FISH and qRT-PCR were showed the location of circSSR1 and expression change. RNA pull-down and RIP verify the circSSR1 combine with YTHDF1. Western blotting, PI staining and LDH release were used to explore the role of circSSR1 in PASMCs pyroptosis. RESULTS: CircSSR1 was markedly downregulated in hypoxic PASMCs. Knockdown CircSSR1 inhibited hypoxia induced PASMCs pyroptosis in vivo and in vitro. Mechanistically, circSSR1 combine with YTHDF1 to promote SSR1 protein translation rely on m6A, activating pyroptosis via endoplasmic reticulum stress. Furthermore, G3BP1 induce circSSR1 degradation under hypoxic. CONCLUSION: Our findings clarify the role of circSSR1 up-regulated parental protein SSR1 expression mediate endoplasmic reticulum stress leading to pyroptosis in PASMCs, ultimately promoting the development of pulmonary hypertension.
Assuntos
Estresse do Retículo Endoplasmático , Miócitos de Músculo Liso , Artéria Pulmonar , Piroptose , Estresse do Retículo Endoplasmático/fisiologia , Piroptose/fisiologia , Artéria Pulmonar/metabolismo , Artéria Pulmonar/patologia , Animais , Camundongos , Miócitos de Músculo Liso/metabolismo , Miócitos de Músculo Liso/patologia , RNA Circular/metabolismo , RNA Circular/genética , Masculino , Células Cultivadas , Camundongos Endogâmicos C57BL , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/patologia , Hipertensão Pulmonar/metabolismo , Hipertensão Pulmonar/patologia , Hipertensão Pulmonar/genética , Proteínas de MembranaRESUMO
PURPOSE: To explore the diagnostic characteristics of cystitis glandularis (CG) using magnetic resonance imaging (MRI). MATERIALS AND METHODS: A retrospective study was conducted on pathologically confirmed patients who underwent bladder MRI examination between January 2019 and November 2023. Image analysis was jointly conducted, with emphasis on lesion location, morphology, size, signal intensity, and pattern of enhancement, by two genitourinary radiologists with 22 and 15 years of experience, respectively. RESULTS: A total of 27 patients with 27 lesions were included (median age 47 years, 24 males). The lesions were mostly located in the bladder trigone area (18/27). The lesions could be categorized as focal thickening (17/27), nodular (8/27), and diffuse thickening of the entire bladder (2/27) in morphological terms. On T2-weighted imaging (T2WI), 15 of 17 focal thickening lesions appeared as a slightly hyperintense thickened inner layer, with a higher signal in the center of the thickened inner layer, resembling a sandwich sign, and 6 of 8 nodular lesions were slightly hyperintense. On T1-weighted imaging (T1WI), 19 patients showed slight hypointensity. The lesions on DWI showed mainly high (5/27) and slightly high signal (21/27), with an average mean apparent diffusion coefficient (mADC) value of 2.171 ± 0.052 × 10-3mm2/s. Among the 23 patients who underwent dynamic contrast-enhanced (DCE) scanning, 18 lesions showed mild enhancement in the arterial phase (average 1.7 times comparing to unenhanced phase), and the degree of enhancement gradually increased in the venous and delayed phases (average 2.2 and 2.3 times compared to the unenhanced phase, respectively), showing a progressive enhancement pattern. CONCLUSION: On MRI, the majority of CG manifest as focal thickening or nodules in the bladder trigone area, showing slight hyperintensity on T2WI, slight hypointensity on T1WI, and a progressive enhancement pattern, without significant restriction on DWI. Focal thickening lesions may exhibit a special sandwich sign.
RESUMO
PEG-enzyme nanocomplexes are prepared and stabilized in an oil-in-water-type emulsion for Pickering interfacial biocatalysis, and these nanocomplexes function as catalysts and emulsifiers at the emulsion interface. The nanocomplexes are self-assembled by cross-linking mPEG-ALD with lipase, without complicated synthesis steps, toxic chemical reagents, and external carriers. Moreover, the mild cross-linking process preserves the original structure of the enzyme, the retention rate of enzyme activity is 82.1%, and the nanocomplexes are used to emulsify biphasic aqueous-organic solution into Pickering emulsion. The system exhibits excellent reusability, with enzyme activity remaining at 86.05% after five cycles, providing a desirable eco-friendly platform for carrier-free Pickering interfacial biocatalysis.
Assuntos
Biocatálise , Materiais Biocompatíveis , Lipase , Teste de Materiais , Tamanho da Partícula , Polietilenoglicóis , Polietilenoglicóis/química , Lipase/metabolismo , Lipase/química , Materiais Biocompatíveis/química , Materiais Biocompatíveis/síntese química , Materiais Biocompatíveis/metabolismo , Emulsões/químicaRESUMO
The abnormal expression of circular RNAs (circRNAs) is emerging as a critical cause in regulation of pathological changes of hypoxic pulmonary hypertension (PH), in which ferroptosis is a new pathological change reported recently. However, how circRNAs regulate ferroptosis remains unclear. Here, we proved a significant decrease in circMyst4 expression in hypoxia. In vitro assays revealed that circMyst4 alleviated hypoxic pulmonary artery smooth muscle cell (PASMC) ferroptosis through directly combing with DDX5 in the nucleus to promote GPX4 mRNA processing and inhibiting the formation of the Eef1a1/ACSL4 complex in the cytoplasm. Additionally, superenhancer (SE) was verified to drive the generation of circMyst4. In vivo assays revealed that circMyst4 inhibited the progression of hypoxic PH. Overall, SE-driven circMyst4 may be a new potential therapeutic target for mediating PASMC ferroptosis through promoting DDX5-regulated GPX4 mRNA processing and inhibiting the binding between Eef1a1 and ACSL4.
RESUMO
Background: Restricting salt, caffeine, and alcohol intake is commonly recommended as a first-line treatment for patients with Ménière's disease (MD). However, it remains unclear whether these interventions effectively improve symptoms of MD. Therefore, we conducted a bidirectional two-sample Mendelian randomization (MR) analysis to evaluate the relationship between these dietary modifications and MD. Methods: Summary statistics for salt added to food, alcohol consumption, coffee consumption, and MD were sourced from the United Kingdom Biobank, GSCAN, and the FinnGen study, involving up to 941,280 participants. The main analyses were performed using the random-effects inverse-variance weighted (IVW) approach and were complemented by four additional methods. Multiple sensitivity analyses were performed to validate the findings, and both forward and reverse MR analyses were employed to address potential reverse causality bias. Results: The primary MR results using the IVW method revealed that salt added to food (OR = 0.719, 95% CI: 0.429-1.206; p = 0.211), alcohol consumption (OR = 0.834, 95% CI: 0.427-1.628; p = 0.595), and coffee consumption (OR = 0.852, 95% CI: 0.555-1.306; p = 0.461) were not significantly correlated with MD. In reverse analysis, no evidence of significant effect was found from MD to salt added to food (OR = 1.000, 95% CI: 0.993-1.007; p = 0.957), alcohol consumption (OR = 0.998, 95% CI: 0.987-1.008; p = 0.682), and coffee consumption (OR = 0.998, 95% CI: 0.985-1.011; p = 0.72). Conclusion: This MR analysis did not identify convincing evidence to support the idea that restricting salt, caffeine, and alcohol intake is beneficial for the treatment of MD.
RESUMO
BACKGROUND: This systematic review and meta-analysis aims to detecting performance of muscular ultrasound for intensive care unit (ICU)-acquired weakness (ICUAW). METHODS: We searched PubMed, Web of Science, Embase, Cochrane library, CNKI, VIP, and Wanfang databases for articles published before July 2024. A random-effects model was utilized to derive the summary estimates of sensitivity, specificity, and diagnostic odds ratio (DOR) with 95% confidence interval (CI). Additionally, the sources of heterogeneity were explored by subgroup analysis and meta-regression. RESULTS: This meta-analysis comprised ten prospective studies involving 561 participants, of whom 241 (42.96%) were diagnosed as ICUAW. Overall, muscular ultrasound exhibited good performance for detecting ICUAW, with the area of SROC curve of 0.85 (95%CI 0.82-0.88), sensitivity of 0.76 (95%CI 0.70-0.81), specificity of 0.80 (95%CI 0.74-0.84), and DOR of 12.43 (95%CI 7.98-19.38). Upon pre-defined subgroup analysis, the rectus femoris exhibited significantly superior discriminatory ability in identifying ICUAW than the non-rectus femoris, with higher SROC (0.88 [95%CI 0.85-0.91] vs. 0.76 [95%CI 0.72-0.79], p < 0.01). Moreover, cross-sectional area was more effective than thickness, with higher specificity (0.86 [95%CI 0.80-0.91] vs. 0.74 [95%CI 0.68-0.79], p = 0.02) and SROC (0.89 [95%CI 0.86-0.92] vs. 0.76 [95%CI 0.72-0.80], p < 0.01). Furthermore, integrated analysis of these two indicators revealed that the cross-sectional area of rectus femoris was statistically superior to the thickness of rectus femoris, with higher sensitivity (0.82 [95%CI 0.74-0.87] vs. 0.75 [95%CI 0.65-0.83], p < 0.05) and AUC (0.91 [95%CI 0.88-0.93] vs. 0.80 [95%CI 0.76-0.83], p < 0.01). CONCLUSIONS: Muscular ultrasound could be a reliable tool for ICUAW detection. Compared with alternative indices, the cross-sectional area of the rectus femoris exhibits superior detection efficacy and may be considered as a valuable parameter for clinical application.
RESUMO
Flow-diverter devices (FDs) are effective in treating intracranial aneurysms (IAs) but carry substantial periprocedural risks, particularly ischemic complications. This study aimed to determine if elevated Systemic Immune-Inflammation Index (SII) can independently predict these risks and assess the impact of age and dual antiplatelet therapy on this association. We conducted a retrospective analysis of patients treated with FDs between February 2016 and August 2023, using blood samples taken within six days before surgery to calculate SII. Logistic regression and decision tree analyses assessed the link between SII and periprocedural complications, with subgroups exploring influencing factors. Multivariable analysis identified high SII as an independent predictor of periprocedural complications (OR = 5.306, 95% CI: 1.367-18.455; P = 0.009). The decision tree model confirmed SII > 0.437 as a critical threshold. Subgroup analysis showed a pronounced association of SII with periprocedural complications in patients ≥ 65 years (OR = 36.979, 95% CI: 2.103-650.134; P = 0.014) and in those on clopidogrel plus aspirin therapy (OR = 16.921, 95% CI: 2.733-104.746; P = 0.002). An elevated Systemic Immune-Inflammation Index (SII) > 0.437 significantly correlates with increased periprocedural complications (6.5% vs. 1.8%, P = 0.017). Although not statistically significant, higher SII is associated with a greater rate of ischemic events (3.9% vs. 0.9%). Elevated preoperative SII independently predicts periprocedural complications, particularly ischemic events, in patients undergoing FDs treatment for intracranial aneurysms. This association is particularly pronounced in older patients (> 65 years) and those receiving dual therapy with clopidogrel plus aspirin. Trial Registration: ClinicalTrials.gov (NCT06446778). Registered on May 22, 2024.
Assuntos
Inflamação , Aneurisma Intracraniano , Inibidores da Agregação Plaquetária , Complicações Pós-Operatórias , Humanos , Aneurisma Intracraniano/cirurgia , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Estudos Retrospectivos , Complicações Pós-Operatórias/epidemiologia , Adulto , Inibidores da Agregação Plaquetária/uso terapêutico , Aspirina/uso terapêutico , Valor Preditivo dos Testes , Procedimentos Endovasculares/métodos , Procedimentos Endovasculares/efeitos adversos , Clopidogrel/uso terapêuticoRESUMO
DJ-1 is a vital enzyme involved in the maintenance of mitochondrial health, and its mutation has been associated with an increased risk of Parkinson's disease (PD). Effective regulation of DJ-1 activity is essential for the well-being of mitochondria, and DJ-1 is thus a potential target for PD drug development. In this study, two peptides (15EEMETIIPVDVMRRA29 and 47SRDVVICPDA56) were utilized with the aim of enhancing the activity of DJ-1. The mechanisms underlying the activity enhancement by these two peptides were investigated using hydrogen/deuterium exchange mass spectrometry (HDXMS). The HDXMS results revealed distinct mechanisms. Peptide 1 obstructs the access of solvent to the dimer interface and stabilizes the α/ß hydrolase structure, facilitating substrate binding to a stabilized active site. Conversely, peptide 2 induces a destabilization of the α/ß hydrolase core, enhancing substrate accessibility and subsequently increasing DJ-1 activity. The binding of these two peptides optimizes the activity site within the dimeric structure. These findings offer valuable insights into the mechanisms underlying the activity enhancement of DJ-1 by the two peptides, potentially aiding the development of new drugs that can enhance the activity of DJ-1 and, consequently, advance PD treatment.
Assuntos
Peptídeos , Proteína Desglicase DJ-1 , Proteína Desglicase DJ-1/metabolismo , Proteína Desglicase DJ-1/química , Proteína Desglicase DJ-1/genética , Humanos , Peptídeos/química , Peptídeos/metabolismo , Peptídeos/farmacologia , Domínio Catalítico , Doença de Parkinson/metabolismo , Doença de Parkinson/tratamento farmacológico , Espectrometria de Massa com Troca Hidrogênio-Deutério , Ligação Proteica , Modelos Moleculares , Multimerização ProteicaRESUMO
BACKGROUND: Abdominal obesity, a significant risk factor for the progression of diabetic retinopathy (DR), may lead to improved visual outcomes through early assessment. This study aims to evaluate any potential associations between DR and novel lipid metabolism markers, including the Atherogenic Index of Plasma (AIP), Visceral Adiposity Index (VAI), and Lipid Accumulation Product (LAP). METHODS: This study aimed to elucidate the association between various lipid markers and DR by screening the National Health and Nutrition Examination Survey (NHANES) database in the United States from 2005 to 2008. To examine the correlation, multifactor logistic regression analysis, subgroup analysis, threshold effect analysis, interaction test, and smooth curve fitting were used. RESULTS: Among the 2591 participants included, the incidence of DR was 13.6% and the mean age was 59.55 ± 12.26 years. After adjusting for important confounding covariates, logistic regression studies suggested a possible positive association between LAP, VAI, AIP, and DR occurrence (odds ratio [OR] = 1.004; 95% confidence interval [CI]: 1.002, 1.006; P < 0.0001; [OR] = 1.090; 95% [CI]: 1.037, 1.146; P = 0.0007; [OR] = 1.802; 95% [CI]: 1.240, 2.618; P = 0.0020). The nonlinear association between LAP and DR was further illustrated using an S-shaped curve by smoothing curve fitting, with the inflection point of the curve located at 63.4. Subgroup analyses and interaction tests were performed with full variable adjustment (P > 0.05 for all interactions). CONCLUSION: Studies have shown that elevated levels of LAP, VAI, and AIP increase the likelihood of DR, suggesting that they have the potential to be predictive markers of DR, emphasizing their potential utility in risk assessment and prevention strategies, and advocating for early intervention to mitigate the likelihood of DR.
Assuntos
Aterosclerose , Retinopatia Diabética , Produto da Acumulação Lipídica , Inquéritos Nutricionais , Obesidade Abdominal , Humanos , Pessoa de Meia-Idade , Masculino , Feminino , Retinopatia Diabética/sangue , Retinopatia Diabética/epidemiologia , Obesidade Abdominal/sangue , Obesidade Abdominal/complicações , Obesidade Abdominal/epidemiologia , Idoso , Aterosclerose/sangue , Aterosclerose/epidemiologia , Fatores de Risco , Estados Unidos/epidemiologia , Modelos Logísticos , Biomarcadores/sangueRESUMO
Parkinson's disease (PD) affects movement; however, most patients with PD also develop nonmotor symptoms, such as hyposmia, sleep disorder, and depression. Dopamine levels in the brain have a critical influence on movement control, but other neurotransmitters are also involved in the progression of PD. This study analyzed the fluctuation of neurotransmitters in PC12 cells during neurogenesis and neurodegeneration by performing mass spectrometry. We found that the dopaminergic metabolism pathway of PC12 cells developed vigorously during the neuron differentiation process and that the neurotransmitters were metabolized into 3-methoxytyramine, which was released from the cells. The regulation of the intracellular and extracellular concentrations of adenosine indicated that adenine nucleotides were actively utilized in neural differentiation. Moreover, we exposed the differentiated PC12 cells to rotenone, which is a suitable material for modeling PD. The cells exposed to rotenone in the early stage of differentiation exhibited stimulated serotoninergic metabolism, and the contents of the serotoninergic neurotransmitters returned to their normal levels in the late stage of differentiation. Interestingly, the nondifferentiated cells can resist the toxicant rotenone and produce normal dopaminergic metabolites. However, when differentiated neuron cells were exposed to rotenone, they were seriously damaged, leading to a failure to produce dopaminergic neurotransmitters. In the low-dosage damage process, the amino acids that functioned as dopaminergic pathway precursors could not be absorbed by the cells, and dopamine and L-dopa were secreted and unable to be reuptaken to trigger the cell damage.
Assuntos
Diferenciação Celular , Neurogênese , Neurotransmissores , Rotenona , Células PC12 , Animais , Ratos , Neurogênese/efeitos dos fármacos , Neurotransmissores/metabolismo , Rotenona/farmacologia , Espectrometria de Massas , Doença de Parkinson/metabolismo , Doença de Parkinson/patologia , Dopamina/metabolismo , Adenosina/análogos & derivados , Adenosina/metabolismoRESUMO
Introduction: Early identification of high-risk traumatic brain injury (TBI) patients is crucial for optimizing treatment strategies and improving outcomes. The C-reactive protein-to-lymphocyte ratio (CLR) reflects systemic immunology and inflammation function and serves as a new biomarker for patient stratification. This study aimed to assess the predictive value of the CLR for mortality in patients with isolated moderate to severe TBI. Methods: A retrospective analysis of trauma registry data from 2009 to 2022 was conducted, including 1641 adult patients with isolated moderate to severe TBI. Patient demographics, the CLR, injury characteristics, and outcomes were compared between deceased and surviving patients. Univariate and multivariate analyses were performed to identify mortality risk factors. The optimal CLR cut-off value for predicting mortality was determined using receiver operating characteristic (ROC) curve analysis. Results: The CLR was significantly higher in deceased patients compared to survivors (60.1 vs. 33.9, p < 0.001). The optimal CLR cut-off value for predicting mortality was 54.5, with a sensitivity of 0.328 and a specificity of 0.812. The area under the ROC curve was 0.566, indicating poor discriminative ability. In the multivariate analysis, the CLR was not a significant independent predictor of mortality (OR 1.03, p = 0.051). After propensity score matching to attenuate the difference in baseline characteristics, including sex, age, comorbidities, conscious level, and injury severity, the high-CLR group (CLR ≥ 54.5) did not have significantly higher mortality compared to the low-CLR group (CLR < 54.5). Conclusion: While the CLR was associated with mortality in TBI patients, it demonstrated poor discriminative ability as a standalone predictor. The association between a high CLR and worse outcomes may be primarily due to other baseline patient and injury characteristics, rather than the CLR itself.
RESUMO
In recent years, research on attribute-based encryption (ABE) has expanded into the quantum domain. Because a traditional single authority can cause the potential single point of failure, an improved lattice-based quantum-resistant identity authentication and policy attribute encryption scheme is proposed, in which the generation of random values is optimized by adjusting parameters in the Gaussian sampling algorithm to improve overall performance. Additionally, in the key generation phase, attributes are processed according to their shared nature, which reduces the computational overhead of the authorization authority. In the decryption phase, the basis transformation of the Lenstra-Lenstra-Lovász (LLL) lattice reduction algorithm is utilized to rapidly convert shared matrices into the shortest vector form, which can reduce the computational cost of linear space checks. The experimental results demonstrate that the proposed method not only improves efficiency but also enhances security compared with related schemes.
RESUMO
PROBLEM: No studies have been conducted to examine the relationships between perceived stress, positive/negative dyadic coping, and prenatal depression symptoms in Chinese couples with gestational diabetes mellitus (GDM). BACKGROUND: GDM is a stressful event for pregnant women and their partners, which may result in clinically significant prenatal depression symptoms in couples. AIM: This study aims to examine the relationships and differences in perceived stress, positive/negative dyadic coping, and prenatal depression symptoms between Chinese pregnant women with GDM and their partners and to explore the mediating role of positive/negative dyadic coping. METHODS: A cross-sectional study was conducted in Guangzhou, China, from January to October 2021. 402 pairs of GDM couples completed the questionnaires, including the Edinburgh Postnatal Depression Scale, the Chinese version of the Dyadic Coping Inventory, and the Perceived Stress Scale. Dyadic data was analyzed using the actor-partner interdependence mediation model. FINDINGS: 37.6 % of pregnant women with GDM and 24.6 % of their partners experienced clinically significant prenatal depression symptoms. Depression symptoms in couples mutually influence each other. Perceived stress was directly or indirectly related to their and partners' prenatal depression symptoms in GDM couples, with negative dyadic coping acting as a mediator. Maternal negative dyadic coping was also a partner-mediator. DISCUSSION: The findings of the present study may provide healthcare professionals with a better understanding of the effect of the interpersonal interaction between the couples as a dyad on prenatal depression symptoms in Chinese context. CONCLUSION: There were intrapersonal and interpersonal associations among perceived stress, negative dyadic coping, and prenatal depression symptoms in pregnant women with GDM and their partners. It suggests a need for screening clinically significant prenatal depression symptoms and decreasing perceived stress and negative dyadic coping among couples with GDM with a focus on pregnant women with GDM.
RESUMO
Inflammatory bowel disease (IBD) is a chronic non-specific intestinal inflammatory disease that affects millions of people worldwide, and current treatment methods have certain limitations. This study aimed to explore the therapeutic potential and mechanism of action of lemairamin (Wgx-50) in inflammatory bowel disease (IBD). We used dextran sulfate sodium (DSS)-treated zebrafish as an inflammatory bowel disease model, and observed the effect of Wgx-50 on DSS-induced colitis inflammation. The results of the study showed that Wgx-50 could reduce the expression of pro-inflammatory cytokines induced by DSS and inhibit the recruitment of neutrophils to the site of intestinal injury. Further experiments revealed that Wgx-50 exerted its anti-inflammatory effect by regulating the activation of the Akt pathway. These research findings indicate that Wgx-50 possesses anti-inflammatory activity.
Assuntos
Anti-Inflamatórios , Colite , Sulfato de Dextrana , Modelos Animais de Doenças , Peixe-Zebra , Animais , Sulfato de Dextrana/efeitos adversos , Anti-Inflamatórios/farmacologia , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite/metabolismo , Colite/patologia , Citocinas/metabolismo , Neutrófilos/efeitos dos fármacos , Neutrófilos/metabolismo , Transdução de Sinais/efeitos dos fármacos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/induzido quimicamente , Doenças Inflamatórias Intestinais/patologia , Doenças Inflamatórias Intestinais/metabolismo , Intestinos/efeitos dos fármacos , Intestinos/patologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Inflamação/tratamento farmacológico , Inflamação/patologia , Inflamação/induzido quimicamente , Inflamação/metabolismoRESUMO
Cytokine-induced apoptosis inhibitor 1 (CIAPIN1) is a protein that regulates apoptosis and programmed cell death. This research aims to evaluate its potential role in inhibiting breast cancer cell proliferation, migration, and glycolysis and uncover its underlying molecular mechanism. We collected breast cancer tissue samples from eight patients between January 2019 and June 2023 in our Hospital to analyse CIAPIN1 expression. We transfected human breast cancer cell lines (MCF7, MDA-MB-231, MDA-MB-453, and MDA-MB-468) with siRNA of CIAPIN1. Finally, we determined protein expression using RT-qPCR and Western blotting. CIAPIN1 expression was elevated in both breast cancer tissue and serum. Overexpression of CIAPIN1 detected in the breast cancer cell lines MCF7 and MDA-MB-468. In addition, CIAPIN1 overexpression increased cell proliferation and migration rate. CIAPIN1 downregulation suppressed cell proliferation while elevated cellular apoptosis, reactive oxygen species (ROS) production and oxidative stress in breast cancer cells. Moreover, CIAPIN1 inhibition remarkably suppressed pyruvate, lactate and adenosine triphosphate (ATP) production and reduced the pyruvate kinase M2 (PKM2) protein expression and phosphorylation of signal transducer and activator of transcription 3 (STAT3) in breast cancer cells. Downregulation of CIAPIN1 suppresses cell proliferation, migration and glycolysis capacity in breast cancer cells by inhibiting the STAT3/PKM2 pathway.