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OBJECTIVES: This study aimed to monitor blood-brain barrier permeability within 24 h and during the delayed cerebral ischemia (DCI) time window (DCITW) spanning 4-14 days after aneurysmal subarachnoid hemorrhage (aSAH) and to investigate its correlation with both DCI occurrence and outcomes at three months. METHODS: A total of 128 patients were stratified based on the DCI occurrence and three-month modified Rankin scale scores. Comparison of Ktrans at admission (admission Ktrans) and during DCITW (DCITW Ktrans) was conducted between DCI and non-DCI groups, as well as between groups with good and poor outcomes. Changes in Ktrans were also analyzed. Multivariate logistic regression analysis was performed to identify independent predictors of DCI and poor outcomes. RESULTS: Admission Ktrans (0.58 ± 0.18 vs 0.47 ± 0.12, p = 0.002) and DCITW Ktrans (0.54 ± 0.19 vs 0.41 ± 0.14, p < 0.001) were significantly higher in the DCI group compared with the non-DCI group. Although both were higher in the poor outcome group than the good outcome group, the difference was not statistically significant at admission (0.53 ± 0.18 vs 0.49 ± 0.14, p = 0.198). Ktrans in the non-DCI group (0.47 ± 0.12 vs 0.41 ± 0.14, p = 0.004) and good outcome group (0.49 ± 0.14 vs 0.41 ± 0.14, p < 0.001) decreased significantly from the admission to DCITW. Multivariate analysis identified DCITW Ktrans and admission Ktrans as independent predictors of poor outcomes (OR = 1.73, 95%CI: 1.24-2.43, p = 0.001) and DCI (OR = 1.75, 95%CI: 1.25-2.44, p = 0.001), respectively. CONCLUSION: Elevated Ktrans at admission is associated with the occurrence of DCI. Continuous monitoring of Ktrans from admission to DCITW can accurately identify reversible and irreversible changes and can predict outcomes at 3 months. CLINICAL RELEVANCE STATEMENT: Ktrans measured with CT perfusion is a valuable tool for predicting both delayed cerebral ischemia and three-month outcomes following aneurysmal subarachnoid hemorrhage. Monitoring changes in Ktrans from admission to time window of delayed cerebral ischemia can guide treatment and management decisions for aneurysmal subarachnoid hemorrhage patients. KEY POINTS: ⢠Ktrans measured at admission and during the delayed cerebral ischemia time window (4-14 days) holds distinct clinical significance following aneurysmal subarachnoid hemorrhage. ⢠Admission Ktrans serves as a predictor for delayed cerebral ischemia, while continuous assessment of Ktrans from admission to the delayed cerebral ischemia time window can predict three-month outcomes. ⢠Monitoring Ktrans at different stages improves instrumental in enhancing decision-making and treatment planning for patients with aneurysmal subarachnoid hemorrhage.
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Barreira Hematoencefálica , Isquemia Encefálica , Hemorragia Subaracnóidea , Humanos , Hemorragia Subaracnóidea/diagnóstico por imagem , Hemorragia Subaracnóidea/complicações , Masculino , Feminino , Barreira Hematoencefálica/diagnóstico por imagem , Pessoa de Meia-Idade , Isquemia Encefálica/diagnóstico por imagem , Isquemia Encefálica/etiologia , Idoso , Fatores de Tempo , Permeabilidade , Adulto , Prognóstico , Valor Preditivo dos Testes , Estudos RetrospectivosRESUMO
Seventeen C20-O-alkyl/benzyl oxime derivatives were synthesized by a concise and effective method. Most of these derivatives showed tens to several hundred nanomolar IC50 values against HT-29 colorectal, HGC-27 gastric and MDA-MB-231 breast cancer cells, whose antiproliferative activity is 15-240 fold better than that of salinomycin. The C20-oxime etherified derivatives can coordinate potassium ions, and further adjust the cytosolic Ca2+ concentrations in HT-29 cells. The significant improvement of the potency should be attributed to the better ion binding and transport ability of the modified derivatives. In addition, the C20-O-alkyl/benzyl oxime derivatives showed much better selectivity indexes (SI) than salinomycin, indicating that they present lower neurotoxic risk.
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Antineoplásicos/farmacologia , Oximas/farmacologia , Piranos/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Modelos Moleculares , Conformação Molecular , Oximas/síntese química , Oximas/química , Piranos/síntese química , Piranos/químicaRESUMO
BACKGROUND: Previous studies suggest that retirement, a major life event, affects overall healthcare utilization. We examine, the effects of retirement on inpatient healthcare utilization, including effect heterogeneity by gender, disease category, and type of health service. METHODS: We used routine health insurance claims data (N = 87,087) spanning the period 2021 - September 2013 from the Urban Employee Basic Medical Insurance (UEBMI), a mandatory social health insurance for working and retired employees in urban China. We applied a non-parametric fuzzy regression discontinuity design using the statutory retirement age in urban China as an exogenous instrument to measure the causal effect of retirement on six measures of inpatient healthcare utilization. RESULTS: Retirement reduced total hospital costs (-84.71 Chinese Yuan (CNY), 95% confidence interval (CI) -172.03 - 2.61), shortened length of hospital stays (-44.59, 95% CI -70.50 - -18.68), and increased hospital readmissions (0.06, 95% CI 0.00 - 0.12) and primary hospital visits (0.06, 95% CI 0.02 - 0.09) among women. Retirement did not significantly change inpatient healthcare utilization among men. The retirement effects among women varied by disease category. Specifically, retirement substantially increased hospitalizations for non-communicable diseases (NCDs), yet had only modest or no effect on hospitalizations for communicable diseases or injuries. Retirement effects among women also varied by the type of services. For relatively inexpensive services, such as nonoperative treatment, there were surges in the extensive margin (hospital readmission). For relatively expensive and invasive services, such as surgeries, retirement reduced the intensive margin (out-of-pocket expenditures and length of stay). CONCLUSIONS: Retirement decreases overall use of inpatient healthcare for women. The examination on the disease-related heterogeneous effects helps with the introduction and implementation of integrated healthcare delivery and appropriate incentive schemes to encourage better use of healthcare resources among older adults.
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Pacientes Internados , Aposentadoria , Idoso , China/epidemiologia , Atenção à Saúde , Feminino , Humanos , Seguro Saúde , Masculino , Aceitação pelo Paciente de Cuidados de SaúdeRESUMO
PURPOSE: To evaluate the changes of blood-brain barrier permeability (BBBP) after aneurysmal subarachnoid hemorrhage (aSAH) and find out whether BBBP within 24 h after onset can further improve prediction of delayed cerebral ischemia (DCI). METHODS: CT perfusion (CTP) was performed within 24 h after onset and in the DCI time window (DCITW). Whole brain average values of flow extraction product (mKtrans), qualitative and quantitative CTP parameters, and clinical data were compared between DCI and non-DCI groups. The changes of mKtrans were analysed using a Paired t test. Multivariate logistic regression analysis and ROC analyses were performed to identify predictors of DCI and evaluate the predictive performance. RESULTS: One hundred and forty of 179 consecutive patients were included, 45 of whom (32%) developed DCI. mKtrans was higher in the DCI group both on admission and in the DCITW (P<0.001). mKtrans decreased significantly in the non-DCI group (P=0.003), but not in DCI group (P=0.285). Multivariate logistic regression analysis showed that mKtrans (OR=1.07, 95%CI: 1.03-1.11, P<0.001), World Federation of Neurosurgery Scale (OR=6.73, 95%CI: 1.09-41.41, P=0.040), Hunt-Hess grade (OR=0.16, 95%CI: 0.02-1.19, P=0.073), modified Fisher Score (OR=3.74, 95%CI: 1.30-10.75, P=0.014), and qualitative CTP (OR=4.31, 95%CI: 1.49-12.47, P=0.007) were independent predictors of DCI. The model with Ktrans produced a larger AUC of 0.88 (95%CI: 0.81-0.95), with corresponding sensitivity and specificity of 84% and 86%, respectively. CONCLUSION: BBBP measurement within 24 h after onset can improve the prediction of DCI. Early moderate BBB disruption may be reversible, whereas severe BBBP disruption indicates the risk of DCI.
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Isquemia Encefálica , Hemorragia Subaracnóidea , Encéfalo , Isquemia Encefálica/diagnóstico por imagem , Isquemia Encefálica/etiologia , Infarto Cerebral , Humanos , Permeabilidade , Hemorragia Subaracnóidea/diagnóstico , Hemorragia Subaracnóidea/diagnóstico por imagemRESUMO
BACKGROUND: Extensive research has explored disparities in access to health care between people with and without disabilities, but much less is understood about disparities and associated factors within the disabled population. OBJECTIVE: The aim of this study was to examine differences in the prevalence of unmet health-care needs by residential status (hukou status) and disability type among people with disabilities. METHODS: Our data were from the National Survey on Basic Public Service Delivery of Persons with Disabilities. The analysis sample included a nationally representative sample of 9 642 112 adults (aged 16+ years) with disabilities. Associated factors were obtained at both individual level and community level. Cross-sectional multivariable logistic regression analyses were conducted to compare unmet medical, care, rehabilitation and accessibility needs among people with different residential statuses and different types of disabilities. RESULTS: The estimated prevalence of unmet medical, care, rehabilitation and accessibility needs is 15.4%, 10.2%, 45.6% and 13.7%, respectively. Rural hukou was associated with an important 13-40% increase in unmet health-care needs for people with disabilities in China. These rural-urban disparities in unmet health service needs can be partly explained by community-level factors, including access to facilities, social participation and health professionals. Disparities across the type of disability were smaller, but on average, people with multiple disabilities appeared to have the highest rates of unmet care, medical and accessibility needs, whereas those with physical disability had the highest unmet rehabilitation need. CONCLUSIONS: Differences by residential status and impairment type were evident in all types of unmet health service needs. Targeted policy designs that meet the needs for justice and equality of people with disabilities are advisable. Public health and policy efforts are required to improve access to health service and meet the needs of people with disabilities, especially in rural practices and for particular disability groups.
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Pessoas com Deficiência , Acessibilidade aos Serviços de Saúde , Adulto , China , Estudos Transversais , Serviços de Saúde , Necessidades e Demandas de Serviços de Saúde , Disparidades em Assistência à Saúde , HumanosRESUMO
This study examines the shear-induced formation of fibrillar form II crystals and subsequent form II to I transformation of an isotactic polybutene-1 sample through a combination of rheology, polarized optical microscopy (POM), and small- and wide-angle X-ray scattering (SAXS and WAXS) measurements. Strong shear flow was applied using a strain-controlled rheometer with parallel plate geometry, for which the shear rate increases linearly from the center to the perimeter. Highly oriented crystals were created by the shear flow, leading to the birefringent region shown in the POM images, which propagated from the perimeter to the center with increasing applied shear rate. The form II to I transformation, traced by WAXS, was greatly accelerated with increasing shear rate. This trend is explained as being due to the formation of fibrillar crystals and accordingly a large amount of highly oriented chains tethered between the crystal lamellae. The stress sustained by these tethered chains facilitates the nucleation of form I thereby accelerating the form II to I transformation.
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BACKGROUND: Some bereaved parents experience a decreasing trajectory of grief, while others fail to adapt over the long term and persistently suffer from negative health consequences. This study investigates the mediating role of social integration in the relationship between losing an only child and parental health in a family-oriented society. METHOD: A sample of 1828 bereaved parents and 4739 non-bereaved parents was drawn from a 10-city survey in China. Regression methods were used to examine the impact of child loss on parental health, and Sobel test was applied to examine the mediating role of social integration. RESULTS: Bereaved parents who lost their only child have worse self-rated health and more negative affect than the non-bereaved parents, which lasted for years after the death of the only child. The Sobel test shows that 24.8% of the total effects on self-rated health and 6.7% of the total effects on negative affect can be explained via decreased social integration. The gender of parents and child as well as fertility intentions are important sources of heterogeneity in the Chinese culture. LIMITATION: The results based on cross-sectional data may only reveal correlation rather than causality. The data was retrieved from self-reported questionnaires and there is a lack of objective measures of parental health. Moreover, the detailed mechanisms behind how child loss resulted in less social integration should be further explored. CONCLUSIONS: Significant disparities in health outcomes and social integration were found for bereaved parents relative to the non-bereaved parents. Future work is needed to assess the health of bereaved parents, identify the vulnerable and disadvantaged groups, and design inclusive intervention programs.
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Luto , Pesar , Pais/psicologia , Qualidade de Vida , Integração Social , Estudos de Casos e Controles , Criança , China , Estudos Transversais , Família , Feminino , Nível de Saúde , Humanos , Masculino , Inquéritos e QuestionáriosRESUMO
Competitive endogenous RNAs (ceRNAs) regulate RNA transcripts by competing for shared miRNAs and play critical roles in disease development. Psoriasis is a long-lasting, recurring chronic inflammatory skin disease characterized by hyperproliferation of keratinocytes. The keratinocyte response is triggered by the activation of inflammatory cytokines, like interleukin-22 (IL-22). We used lncRNA array analysis to detect differentially expressed lncRNAs in skin (HaCaT) cells treated with or without IL-22. We used hematoxylin and eosin (H&E) staining to determine the pathological changes in skin cells and immunohistochemistry to evaluate the expression of S100A7. We used qRT-PCR and Western blotting to detect the expression levels of MSX2P1 and S100A7. We down-regulated the expression of MSX2P1 by infecting with lentiviral-vector shRNA. We measured cell proliferation, cell cycle status, and apoptosis by the CCK-8 assay, flow cytometry, and Annexin â ¤-FITC/PI staining, respectively. In addition, we used the luciferase reporter gene assay to determine the relationships between MSX2P1 or miR-6731-5p and S100A7, respectively. LncRNA array analysis revealed that 103 lncRNAs were up-regulated and 51 were down-regulated. Furthermore, qRT-PCR showed that the mRNAs levels of MSX2P1 was significantly altered in HaCaT cells treated with IL-22, compared with control cells; and MSX2P1 was mainly in the cytoplasm. Based on the IL-22-stimulated lncRNA-associated ceRNA network, we selected MSX2P1-miR-6731-5p-S100A7 for further study. H&E staining exhibited characteristic features specific to psoriatic lesions. Immunohistochemistry demonstrated significantly increased expression levels of S100A7 in psoriatic lesions, compared with normal skin tissue. We observed a positive correlation between lncRNA-MSX2P1 expression and S100A7 expression. In addition, miR-6731-5p suppressed proliferation, accelerated apoptosis in IL-22-stimulated keratinocytes, and decreased the expressions of S100A7, IL-12ß, IL-23, HLA-C, CCHCR1, TNF-α, and NF-κB proteins. Our data demonstrated that MSX2P1 facilitate the progression and growth of IL-22-stimulated keratinocytes by inhibiting miR-6731-5p and activating S100A7. We speculate that the biological network of MSX2P1-miR-6731-5p-S100A7 is a potential novel therapeutic target for the future treatment of psoriasis.
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Interleucinas/farmacologia , Queratinócitos/efeitos dos fármacos , MicroRNAs/genética , RNA Longo não Codificante/genética , Proteína A7 Ligante de Cálcio S100/metabolismo , Ciclo Celular/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Proteínas de Homeodomínio/metabolismo , Humanos , Queratinócitos/metabolismo , Interleucina 22RESUMO
BACKGROUND: The treatment of vitiligo is still one of the most difficult dermatological challenges, although there are many therapeutic options. Narrow band ultraviolet B (NB-UVB) phototherapy is considered to be a very important modality for generalized vitiligo. OBJECTIVE: The aim of this study was to explore whether a combination of NB-UVB and topical agents would be superior to NB-UVB alone for treating vitiligo. METHODS: We searched the electronic databases such as PUBMED, EMBASE, Cochrane Library, and Web of Science. The primary outcome was the proportion of ≥50% repigmentation (a clinical significance), and secondary outcome was the proportion of ≥75% repigmentation (an excellent response). RESULTS: Seven randomized controlled trials (RCTs) involving 240 patients (413 lesions) were included in this meta-analysis. The study showed no significant difference between NB-UVB combination therapy (NB-UVB and topical calcineurin inhibitor or vitamin D analogs) and NB-UVB monotherapy in the outcomes of ≥50% repigmentation and ≥75% repigmentation. However, lesions located on the face and neck had better results in ≥50% repigmentation (RR = 1.40, 95% CI 1.08-1.81) and ≥75% repigmentation (RR = 1.88, 95% CI 1.10-3.20) with NB-UVB and topical calcineurin inhibitor combination therapy vs. NB-UVB monotherapy. CONCLUSIONS: The meta-analysis suggested that adding neither topical calcineurin inhibitors nor topical vitamin-D3 analogs on NB-UVB can yield significantly superior outcomes than NB-UVB monotherapy for treatment of vitiligo. However, addition of topical calcineurin inhibitors to NB-UVB may increase treatment outcomes in vitiligo affecting face and neck.
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Inibidores de Calcineurina/administração & dosagem , Terapia Ultravioleta/métodos , Vitamina D/análogos & derivados , Vitiligo/tratamento farmacológico , Vitiligo/radioterapia , Administração Cutânea , Calcitriol/administração & dosagem , Calcitriol/análogos & derivados , Quimiorradioterapia , Fármacos Dermatológicos/administração & dosagem , Di-Hidroxicolecalciferóis/administração & dosagem , Dermatoses Faciais/tratamento farmacológico , Dermatoses Faciais/radioterapia , Humanos , Pescoço , Ensaios Clínicos Controlados Aleatórios como Assunto , Pigmentação da Pele/efeitos dos fármacos , Pigmentação da Pele/efeitos da radiação , Tacrolimo/administração & dosagem , Tacrolimo/análogos & derivadosRESUMO
PURPOSE: The optimal treatment modalities of ruptured middle cerebral artery aneurysm are still controversial. The objective of this study is to analyze the outcomes of patients with ruptured middle cerebral artery aneurysms treated by endovascular coiling. MATERIALS AND METHODS: From October 2011 to October 2015, 67 patients with 71 ruptured middle cerebral artery aneurysms received endovascular coiling in our hospital. We retrospectively reviewed the clinical, radiologic records and outcomes. RESULTS: Of all the 71 aneurysms (67 patients), 42 were treated by coil embolization merely, 27 by stent-assisted coiling and 2 unruptured aneurysms in patients with bilateral middle cerebral artery aneurysms without receiving treatment. Complete occlusion was achieved in 82.6% (57/69) of all the procedures. Each of incomplete and partial occlusion rates was 8.7% (6/69). Intraoperative rupture of aneurysms occurred in two procedures (2.9%). Thrombogenesis occurred in eight procedures (11.6%). Brain infarction occurred in eight patients (11.9%). Post-operative rebleeding occurred in seven patients (10.4%). Sixty-three patients were followed at a mean follow-up of 8.24 ± 7.16 months. The mortality and good outcome rate were 3.2% and 90.5%, respectively. Aneurysm recurrence occurred in 6 (13.3%) of the 45 aneurysms at a mean follow-up of 8.44 ± 7.83 months. CONCLUSIONS: Endovascular coiling is effective for patients with ruptured middle cerebral artery aneurysms. Individualized treatment should be assessed by experienced specialist. It is essential to perform randomized large trials to confirm the efficiency of endovascular coiling.
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Aneurisma Roto/cirurgia , Procedimentos Endovasculares/métodos , Aneurisma Intracraniano/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Aneurisma Roto/complicações , Aneurisma Roto/diagnóstico por imagem , Angiografia Cerebral , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Aneurisma Intracraniano/complicações , Aneurisma Intracraniano/diagnóstico por imagem , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Artéria Cerebral Média , Estudos Retrospectivos , Índice de Gravidade de Doença , Stents , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Adulto JovemRESUMO
Analysis of noncovalent interactions between natural products and proteins is important for rapid screening of active ingredients and understanding their pharmacological activities. In this work, the intensity fading MALDI-TOF mass spectrometry (IF-MALDI-MS) method with improved reproducibility was implemented to investigate the binding interactions between saponins from Panax notoginseng and lysozyme. The benchmark IF-MALDI-MS experiment was established using N,N',Nâ³-triacetylchitotriose-lysozyme as a model system. The reproducibility of ion intensities in IF-MALDI-MS was improved by scanning the whole sample deposition with a focused laser beam. The relative standard deviation (RSD) of deposition scanning IF-MALDI-MS is 5.7%. Similar decay trends of the relative intensities of notoginseng saponins against increasing amounts of lysozyme were observed for all six notoginseng saponins. The half-maximal fading concentration (FC50) was calculated to quantitatively characterize the binding affinity of each ligand based on the decay curve. According to the FC50 values obtained, the binding affinities of the six notoginseng saponins were evaluated in the following order: notoginsenoside S > notoginsenoside Fc > ginsenoside Rb1 > ginsenoside Rd > notoginsenoside Ft1 > ginsenoside Rg1. The binding order was in accordance with molecular docking studies, which showed hydrogen bonding might play a key role in stabilizing the binding interaction. Our results demonstrated that deposition scanning IF-MALDI-MS can provide valuable information on the noncovalent interactions between ligands and proteins.
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Muramidase , Panax notoginseng , Saponinas , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Muramidase/química , Muramidase/metabolismo , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Saponinas/química , Saponinas/análise , Saponinas/metabolismo , Panax notoginseng/química , Ligação Proteica , Simulação de Acoplamento Molecular , Reprodutibilidade dos Testes , Animais , TrissacarídeosRESUMO
Though deep learning-based surgical smoke removal methods have shown significant improvements in effectiveness and efficiency, the lack of paired smoke and smoke-free images in real surgical scenarios limits the performance of these methods. Therefore, methods that can achieve good generalization performance without paired in-vivo data are in high demand. In this work, we propose a smoke veil prior regularized two-stage smoke removal framework based on the physical model of smoke image formation. More precisely, in the first stage, we leverage a reconstruction loss, a consistency loss and a smoke veil prior-based regularization term to perform fully supervised training on a synthetic paired image dataset. Then a self-supervised training stage is deployed on the real smoke images, where only the consistency loss and the smoke veil prior-based loss are minimized. Experiments show that the proposed method outperforms the state-of-the-art ones on synthetic dataset. The average PSNR, SSIM and RMSE values are 21.99±2.34, 0.9001±0.0252 and 0.2151±0.0643, respectively. The qualitative visual inspection on real dataset further demonstrates the effectiveness of the proposed method.
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Processamento de Imagem Assistida por Computador , Exame FísicoRESUMO
BACKGROUND: Apoptosis and pyroptosis are two types of programmed cell death related to the neuroinflammatory reaction after subarachnoid hemorrhage (SAH). Research indicates that triggering receptor expressed on myeloid cells 2 (TREM2) can regulate the SAH-induced inflammatory response. However, whether TREM2 regulates programmed cell death (apoptosis and pyroptosis) remains to be clarified. The purpose of the present study was to investigate the effects of TREM2 on cell death in SAH. METHODS: SAH was induced in adult male C57BL/6J mice by endovascular perforation. An in-vitro cellular model of SAH was established by treating cocultured BV2 microglia and HT22 neuronal cells with oxyhemoglobin. TREM2 overexpression or knockdown was carried out by intraventricular lentivirus injection at 7 d before SAH induction in mice or lentiviral transfection, respectively. Neurobehavioral tests as well as western blot, reverse transcription-quantitative polymerase chain reaction (RT-qPCR), immunofluorescence, Evans blue (EB) staining, Nissl staining, and flow cytometry assays were performed to investigate the neuroprotective role of TREM2 after SAH. RESULTS: After SAH, the TREM2 mRNA and protein levels were elevated in SAH mice, exhibiting a peak at 72 h. TREM2 overexpression improved the SAH-induced neurological deficits in mice, while TREM2 knockdown worsened them. In the brains of mice with TREM2 overexpression, less neuronal death and more neuronal survival were detected at 72 h post SAH. Meanwhile, TREM2 overexpression showed an inhibitory effect on microglial activation, neutrophil infiltration, and the expression of cell death marker proteins. Consistent results were obtained in vitro. CONCLUSIONS: Our research indicates the important role of TREM2 on cell death after SAH, suggesting that targeting TREM2 might be an effective approach for treating SAH.
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Lesões Encefálicas , Hemorragia Subaracnóidea , Animais , Masculino , Camundongos , Ratos , Apoptose , Camundongos Endogâmicos C57BL , Doenças Neuroinflamatórias , Ratos Sprague-Dawley , Transdução de Sinais , Hemorragia Subaracnóidea/genéticaRESUMO
Background: Artesunate (ART), a natural compound derived from Artemisia annua, has shown promising clinical potentials in the treatment of various tumors, but the exact mechanism is unclear. Choroidal melanoma (CM) is a major malignant ocular tumor in adults, known for its significant malignancy and poor prognosis, with limited efficacy in current treatments. This study explored the anti-CM effects and mechanisms of ART using a combination of network pharmacology, molecular docking and experimental validation. Methods: Potential targets of ART were screened in PubChem, Swiss Target Prediction and Traditional Chinese Medicine Systems Pharmacology (TCMSP) Database Analysis Platform databases, while target genes related to CM prognosis were selected from Online Mendelian Inheritance in Man (OMIM), GeneCards and DisGeNET databases. The intersection of these two groups of datasets yielded the target genes of ART involved in CM. Protein-protein interaction (PPI) network analysis of the intersecting targets, as well as Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, were conducted to identify core targets and critical pathways. Molecular docking methods were performed to predict the binding interactions between ART and core targets. The effects of ART on CM were evaluated through CCK8, colony formation, transwell, as well as flow cytometry assays to detect apoptosis, cell cycle, reactive oxygen species (ROS). Western blot (WB) assays were conducted to investigate the impact of ART on key proteins and pathways associated with CM. Finally, in vivo assays were conducted to further validate the effects of ART on subcutaneous tumors in nude mice. Results: Research has shown that key pathways and core targets for ART in treating CM were identified through a network pharmacology approach. Molecular docking results verified the strong binding affinity between ART and these core targets. The analysis and predicted results indicated that ART primarily exerted its effects on CM through various tumor-related pathways like apoptosis. The assays in vitro confirmed that ART significantly inhibited the proliferation and migration of CM cells. This was achieved by promoting apoptosis through activation of the p53 signaling pathway, causing cell cycle arrest at the G0/G1 phase by inhibiting the PI3K/AKT/mTOR signaling pathway and increasing the intracellular level of ROS by activating the NRF2/HO-1 signaling pathway. Additionally, the assays in vivo further validated the significant proliferation-inhibitory effect of ART on CM. Conclusion: This study, making the initial exploration, illustrated through network pharmacology combined with molecular docking and in vitro/in vivo assays, confirmed that ART exerted potential anti-cancer effects on CM by promoting apoptosis, inducing cell cycle arrest and increasing intracellular levels of ROS. These findings suggested that ART held significant therapeutic potential for CM.
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Objective: To explore the relationship between childhood maltreatment, growth mindset, beliefs about adversity and learning engagement among high school students. Methods: Research participants were selected by random cluster sampling.652 high school students (50.2% male and 49.8% female) from five high schools were investigated using paper-pencil survey versions of Child Trauma Questionnaire, The Utrecht Work Engagement Scale-student, Growth Mindset Scale, and The Beliefs About Adversity Scale. Results: Childhood maltreatment had a significant negative effect on high school students' learning engagement. Childhood maltreatment directly predicted high school students' learning engagement and also had an indirect negative predictive effect on learning engagement via growth mindset. Conclusion: Growth mindset plays a mediating role between childhood maltreatment and learning engagement. The beliefs about adversity moderated the relationship between childhood maltreatment and growth mindset, as well as the relationship between childhood maltreatment and learning engagement. This study has empirical implications for helping high school students who have experienced childhood maltreatment to develop growth mindset and teaching students to adopt positive adversity beliefs in response to trauma during psychological interventions, thereby increasing high school students' engagement in learning.
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China's flower industry is developing rapidly, and the size of the retail market is increasing year by year. Studying the factors influencing residents' flower purchasing behavior and understanding their flower needs can help promote the sustainable development of the flower industry. Based on customer satisfaction theory, this paper uses 838 consumer research questionnaires from 15 districts in Shanghai to analyze the influence of customer satisfaction on residents' flower purchasing behavior by conducting a binary logit model and to investigate the moderating effect of flower purchasing purpose on the influence of satisfaction. The results show that price satisfaction and satisfaction with promotional methods have a significant negative effect on flower purchasing behavior, service satisfaction has a significant positive effect on purchasing behavior, and different customer purchase purposes lead to different intensities of the effect of satisfaction on purchasing behavior. According to the conclusion of the study, three countermeasures are proposed: to popularize the knowledge of flower culture, guide the concept of flower consumption, and promote the transformation of flower consumption to daily consumption; to conduct regular research on consumers by flower merchants to clarify consumers' needs and improve their satisfaction; to clarify consumers' purchase intention, increase the investment in the research and development and cultivation of flower products, and improve the supply level of flowers.
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Comportamento do Consumidor , Intenção , China , Marketing , Satisfação PessoalRESUMO
The bacterial ATP-competitive GyrB/ParE subunits of type II topoisomerase are important anti-bacterial targets to treat super drug-resistant bacterial infections. Herein we discovered novel pyrrolamide-type GyrB/ParE inhibitors based on the structural modifications of the candidate AZD5099 that was withdrawn from the clinical trials due to safety liabilities such as mitochondrial toxicity. The hydroxyisopropyl pyridazine compound 28 had a significant inhibitory effect on Gyrase (GyrB, IC50 = 49 nmol/L) and a modest inhibitory effect on Topo IV (ParE, IC50 = 1.513 µmol/L) of Staphylococcus aureus. It also had significant antibacterial activities on susceptible and resistant Gram-positive bacteria with a minimum inhibitory concentration (MIC) of less than 0.03 µg/mL, which showed a time-dependent bactericidal effect and low frequencies of spontaneous resistance against S. aureus. Compound 28 had better protective effects than the positive control drugs such as DS-2969 (5) and AZD5099 (6) in mouse models of sepsis induced by methicillin-resistant Staphylococcus aureus (MRSA) infection. It also showed better bactericidal activities than clinically used vancomycin in the mouse thigh MRSA infection models. Moreover, compound 28 has much lower mitochondrial toxicity than AZD5099 (6) as well as excellent therapeutic indexes and pharmacokinetic properties. At present, compound 28 has been evaluated as a pre-clinical drug candidate for the treatment of drug-resistant Gram-positive bacterial infection. On the other hand, compound 28 also has good inhibitory activities against stubborn Gram-negative bacteria such as Escherichia coli (MIC = 1 µg/mL), which is comparable with the most potent pyrrolamide-type GyrB/ParE inhibitors reported recently. In addition, the structure-activity relationships of the compounds were also studied.
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Intervertebral discdegeneration (IDD) is the most common cause of lower back pain, but the exact molecular mechanism of IDD is still unknown. Recently, studies have shown that circular RNAs (circRNAs) regulate diverse biological procedures such as cell metastasis, growth, metabolism, migration, apoptosis, and invasion. We demonstrated that IL-1ß and TNF-α induced circ_0005918 expression in the NP cell, and circ_0005918 was overexpressed in the IDD group compared with the control group. Moreover, the upregulated expression of circ_0005918 was associated with disc degeneration degree. The elevated expression of circ_0005918 promoted cell growth and ECM degradation, and it induced secretion of inflammatory cytokines including IL-1ß, IL-6, and TNF-α. Moreover, we found that circ_0005918 sponged miR-622 in the NP cell. In addition, the exposure to IL-1ß and TNF-α suppressed the expression of miR-622, which was downregulated in the IDD group compared with the control group. Furthermore, the downregulated expression of miR-622 was associated with disc degeneration degree. The expression level of miR-622 was negatively associated with circ_0005918 expression in the IDD group. In conclusion, circ_0005918 regulated cell growth, ECM degradation, and secretion of inflammatory cytokines by regulating miR-622 expression. These data suggested that circ_0005918 played important roles in the development of IDD via sponging miR-622.
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Objective: To examine the relationship among childhood trauma, acceptance, positive reappraisal and post-traumatic growth (PTG) among college students. Methods: Research participants were selected by random cluster sampling. 1,028 college students (62.6% female, 30.5% only-children) from 8 universities were investigated using manuscript-pencil survey versions of Childhood Trauma Questionnaire-Short Form (CTQ-SF), Cognitive emotion regulation questionnaire-Chinese version (CERQ-C) and Post traumatic Growth Inventory (PTGI). Results: Traumatic childhood experience significantly negatively predicts post traumatic growth in college students. Exposure to traumatic experiences in childhood can directly negatively predict post-traumatic growth and indirectly positively predict post traumatic growth via acceptance. Conclusion: Acceptance plays a mediating role between childhood traumatic experience and post traumatic growth. The mediating effect of acceptance is moderated by the positive reappraisal. When individuals have a lower level of positive reappraisal, the mediating effect between traumatic experience and post traumatic growth is significant. Several clinical implications for clinical psychology and psychological intervention are highlighted. Starting with changing individual cognition and helping individuals adopt positive cognitive emotion regulation strategies can help individuals actively reevaluate traumatic experience, so as to gain better and faster counseling results.
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Objective: To evaluate the safety and effectiveness of the double microcatheter technique in the treatment of ruptured aneurysms of the anterior cerebral circulation. Methods: Between 2012 and 2019, 113 patients with ruptured aneurysms of the anterior cerebral circulation were treated using the double microcatheter technique. Clinical records, angiographic results, and procedure-related complications were reviewed. Clinical and angiographic follow-up was performed. Results: Complete occlusion, neck remnant, and partial occlusion were, respectively, recorded in 56.6, 38.9, and 4.4% of the total cases. For all patients, the incidence of intraoperative complications was 5.3% (6/113), and the overall rate of morbidity was 10.6% (12/113). Before discharge, three patients (2.7%) died. There was no procedure-related mortality. At discharge, favorable outcomes were observed in 79.6% (90/113) of the patients. High Hunt-Hess grades and receiving a craniotomy or external ventricular drainage were risk factors for clinical outcomes at discharge. Clinical follow-up was performed in 91 patients at a mean interval of 14.07 ± 11.68 months. At follow-up, favorable outcomes were observed in 92.3% (84/91) of the patients. Angiographic follow-up was performed in 66 patients at an average of 11.53 ± 11.13 months. The recurrence rate was 37.9%. Of these patients, 13 (19.7%) received retreatment. Conclusion: The double microcatheter technique can be performed in ruptured aneurysms with high technical success and low morbidity/mortality. However, recurrence remains a problem, and patients should be followed up regularly.