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The present study examined the effect of wearing myopia glasses on eye movement and scleral blood supply. For this purpose, a total of 30 individuals were recruited for the present self-control study. Under the same fixation distance, the individuals wore 0.00 D and -10.00 D glasses. The amount of eye movement generated when shifting from gazing at a central point to a point light source located at the left or right was measured and compared between the two glasses. The results revealed that the range of eye movement was significantly reduced after wearing -10.00 D glasses. When gazing at the right point light source from the central point, the difference between the rotation distances of the right eye when wearing the 0.00 D glasses and the -10.0 D glasses was 0.73±0.45 mm (t=8.93, P<0.01) and that of the left eye was 0.73±0.43 mm (t=9.34, P<0.01). Similar results were obtained when the left point light source was viewed from a shift in gaze from the central point. On the whole, the present study demonstrates that wearing concave lenses limits eyeball movement. Restricted eyeball movement can affect vascular changes within the extraocular muscles and blood flow, thereby affecting the blood supply to the anterior segment and sclera of the eye, potentially accelerating the development of myopia.
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OBJECTIVE: To investigate the significance of endoscopic grading (Hill's classification) of gastroesophageal flap valve (GEFV) in the examination of patients with gastroesophageal reflux disease (GERD). METHODS: One hundred and sixty-two patients undergoing gastroscopy in the Department of Gastroenterology, Xingyi People's Hospital between Apr. 2022 and Sept. 2022 were selected by convenient sampling, and data such as GEFV grade, and findings of esophageal high-resolution manometry (HRM) and esophageal 24-h pH/impedance reflux monitoring, and Los Angeles (LA) classification of reflux esophagitis (RE) were collected and compared. RESULTS: Statistically significant differences in age (F = 9.711, P < 0.001) and hiatal hernia (χ = 35.729, P < 0.001) were observed in patients with different GEFV grades. The resting LES pressures were 12.12 ± 2.79, 10.73 ± 2.68, 9.70 ± 2.29, and 8.20 ± 2.77 mmHg (F = 4.571, P < 0.001) and LES lengths were 3.30 ± 0.70, 3.16 ± 0.68, 2.35 ± 0.83, and 2.45 ± 0.62 (F = 3.789, P = 0.011), respectively, in patients with GEFV grades I-IV. DeMeester score (Z = 5.452, P < 0.001), AET4 (Z = 5.614, P < 0.001), acid reflux score (upright) (Z = 7.452, P < 0.001), weak acid reflux score (upright) (Z = 3.121, P = 0.038), liquid reflux score (upright) (Z = 3.321, P = 0.031), acid reflux score (supine) (Z = 6.462, P < 0.001), mixed reflux score (supine) (Z = 3.324, P = 0.031), gas reflux score (supine) (Z = 3.521, P = 0.024) were different in patients with different GEFV grades, with statistically significant differences. Pearson correlation analysis revealed a positive correlation between RE grade and LA classification of GERD (r = 0.662, P < 0.001), and the severity of RE increased gradually with the increase of the Hill grades of GEFV. CONCLUSION: The Hill grade of GEFV is related to age, hiatal hernia, LES pressure, and the consequent development and severity of acid reflux and RE. Evaluation of esophageal motility and reflux based on the Hill grade of GEFV is of significance for the diagnosis and treatment of GERD.
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Nine new oligophenalenone dimers, adpressins A-G (1-9), together with nine known compounds (10-18), were isolated from the fungus Talaromyces adpressus. Their chemical structures were determined on the basis of spectroscopic and mass spectral analyses. Their relative and absolute configurations were identified by 1H and 13C NMR calculations followed by DP4+ analyses, electronic circular dichroism (ECD) calculations, and ECD spectra comparison with related compounds. Compound 1 is the first example of a duclauxin derivative featuring an unusual 6/6/6/5/6/6/6 ring system, while compounds 6 and 7 contained a novel pyrrolidine ring. Compounds 5, 9, and 18 exhibited moderate inhibition against LPS-induced B lymphocyte proliferation with IC50 values ranging from 1.6 to 8.6 µM. Additionally, compounds 9 and 18 exhibited moderate inhibition against Con A-induced T lymphocyte proliferation with IC50 values of 9.3 and 2.6 µM, respectively.
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Talaromyces , Talaromyces/química , Estrutura Molecular , Fenalenos/farmacologia , Fenalenos/química , Fenalenos/isolamento & purificação , Animais , Camundongos , Linfócitos T/efeitos dos fármacos , Linfócitos B/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacosRESUMO
Twelve previously undescribed ophiobolin-type sesterterpenoids, undobolins A-L (1-12), were isolated from Aspergillus undulatus, and their structures were elucidated by spectroscopic analysis, ECD calculations, and single-crystal X-ray diffraction experiments. Compound 1 was the second example of 20-nor-ophiobolin reported, while compounds 2-6 were notable for oxygenation of C-2, and compound 6 showed significant inhibitory activity against ConA-induced T lymphocyte proliferation with an IC50 value of 2.3 µM, which suggests a promising new direction in the quest for immunosuppressive agents.
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Aspergillus , Sesterterpenos , Sesterterpenos/farmacologia , Sesterterpenos/química , Sesterterpenos/isolamento & purificação , Aspergillus/química , Estrutura Molecular , Animais , Linfócitos T/efeitos dos fármacos , Cristalografia por Raios X , Imunossupressores/farmacologia , Imunossupressores/química , Imunossupressores/isolamento & purificação , Camundongos , Proliferação de Células/efeitos dos fármacosRESUMO
Spectasterols F-O (1-10), ten interesting ergosterols with an aromatized B ring, were obtained from Aspergillus spectabilis. Their structures and absolute configurations were determined using a combination of high-resolution electrospray ionization mass spectrometry (HR-ESI-MS), nuclear magnetic resonance (NMR) spectroscopy, single-crystal X-ray diffraction analyses, and electronic circular dichroism (ECD) calculations. Structurally, these aromatic ergosterols feature versatile side chains. Notably, compound aromatic ergosterols featured versatile side chains, and compound 4 is an unusual C23 ergosterol characterized by a shorter side chain due to oxidative cleavage between C-23 and C-24. All compounds were evaluated for their neuroprotective activities, with compound 8 showing a dose-dependent ability to reduce apoptosis and protect mitochondrial function in glutamate-induced SH-SY5Y cells.
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Aspergillus , Ergosterol , Fármacos Neuroprotetores , Aspergillus/química , Ergosterol/química , Ergosterol/farmacologia , Ergosterol/análogos & derivados , Humanos , Estrutura Molecular , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/química , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Espectroscopia de Ressonância MagnéticaRESUMO
DNA methylation is an epigenetic modification that plays a crucial role in various biological processes. Aberrant DNA methylation is closely associated with the onset of diseases, and the specific localization of methylation sites in the genome offers further insight into the connection between methylation and diseases. Currently, there are numerous methods available for site-specific methylation detection. Electrochemical biosensors have garnered significant attention due to their distinct advantages, such as rapidity, simplicity, high sensitivity, low cost, and the potential for miniaturization. In this paper, we present a systematic review of the primary sensing strategies utilized in the past decade for analyzing site-specific methylation and their applications in electrochemical sensors, from a novel perspective focusing on the localization analysis of site-specific methylation. These strategies include bisulfite treatment, restriction endonuclease treatment, other sensing strategies, and deamination without direct bisulfite treatment. We hope that this paper can offer ideas and references for establishing site-specific methylation electrochemical analysis in clinical practice.
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Técnicas Biossensoriais , Metilação de DNA , Técnicas Eletroquímicas , Técnicas Biossensoriais/métodos , Técnicas Eletroquímicas/métodos , Técnicas Eletroquímicas/instrumentação , Humanos , DNA/química , DNA/genética , DNA/análise , Sulfitos/químicaRESUMO
Background: To identify the decrease in estimated glomerular filtration rate (eGFR) as an independent risk factor associated with ventricular tachyarrhythmias (VTA). Methods: This retrospective file review collected information from patients diagnosed with acute myocardial infarction (AMI), with and without VTA, from January 2017 to December 2019. We first applied the chi-square test to assess 12 risk factors and one outcome variable (incident rate of VTA). Next, all the 12 risk factors were further adjusted using the propensity score matching (PSM) method to simulate the dataset as a randomized controlled cohort, which can reduce the defects derived from confounding factors and the imbalance in baseline characteristics. To investigate the relationship between eGFR and VTA, univariate logistic regression analysis was applied to the cohort before and after PSM analysis. Results: A total of 503 patients diagnosed as AMI were included in the study. There were eight of twelve risk factors in baseline characteristics with a p-value < 0.05, as determined by the chi-square test before PSM matching. The result of PSM analysis indicated that 86 of 91 patients with decreased eGFR were matched, and all the risk factors were not significantly different (p-value > 0.05). The incident rates of VTA in the two groups were still significantly different (p-value < 0.001) according to the Pearson chi-square test in the cohort after PSM analysis. The results of univariate (eGFR) logistic regression indicated that the odds ratio of the cohort was 6.442 (95% confidence interval = 3.770-11.05) and 3.654 (95% confidence interval = 1.764-7.993) before and after PSM analysis respectively. Conclusions: The decrease in eGFR ( < 60 mL/min/1.73 m 2 ) has been demonstrated as an independent risk factor for VTA after AMI.
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A new fusicoccane diterpenoid, harziaderma A (1), two novel harziane diterpenoids, harzianones G and H (2 and 3), one revised harziane diterpenoid (4), and two known diterpenoids (5 and 6) were isolated from the fungus Trichoderma harzianum and established via NMR, HRESIMS, Mo2(OAc)4-induced circular dichroism (ICD) and electronic circular dichroism (ECD) calculations. It is worth noting that compound 1 represents the first instance of a fusicoccane-type diterpenoid derived from T. harzianum. The structure of furanharzianone B was revised to 4 via careful spectroscopic analyses. Additionally, compounds 2 and 5 could suppress the overall growth of the foodborne bacterial pathogen Bacillus cereus. Compound 4 showed a moderate suppressive impact on NO generation in lipopolysaccharide (LPS)-treated RAW 264.7 cells. The discoveries from the current study not only expanded the structural variety of diterpenoids isolated from T. harzianum but also laid a robust foundation for the development of harziane diterpenoids as anti-foodborne pathogen agents.
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Antibacterianos , Diterpenos , Diterpenos/farmacologia , Diterpenos/química , Camundongos , Antibacterianos/farmacologia , Antibacterianos/química , Animais , Células RAW 264.7 , Estrutura Molecular , Bacillus cereus/efeitos dos fármacos , Hypocreales/químicaRESUMO
Lung cancer is the most common malignant disease and the leading cause of cancer death in China. Non-small cell lung cancer (NSCLC) accounts for over 80% of all lung cancers, and the probability of NSCLC gene mutations is high, with a wide variety of types. With the development of next-generation sequencing (NGS) detection technology, more and more patients with rare fusion gene mutations are detected. Neuregulin 1 (NRG1) gene is a rare oncogenic driver that can lead to activation of human epidermal growth factor receptor 3 (Her3/ErbB3) mediated pathway, resulting in tumor formation. In this article, we reported a case of mixed NSCLC with CRISPLD2-NRG1 fusion detected by RNA-based NGS, who responsed to Afatinib well after 1 month of treatment, and magnetic resonance imaging (MRI) showed shrinkage of intracranial lesions. Meanwhile, we also compiled previously reported NSCLC patients with NRG1 rare gene fusion mutation, in order to provide effective references for clinical diagnosis and treatment.â©.
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Afatinib , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Neuregulina-1 , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Neuregulina-1/genética , Afatinib/uso terapêutico , Proteínas de Fusão Oncogênica/genética , Pessoa de Meia-Idade , Masculino , Moléculas de Adesão Celular/genética , FemininoRESUMO
Four new p-terphenyl derivatives, talaroterphenyls A-D (1-4), together with three biosynthetically related known ones (5-7), were obtained from the mangrove sediment-derived Talaromyces sp. SCSIO 41412. Compounds 1-3 are rare p-terphenyls, which are completely substituted on the central benzene ring by oxygen atoms; this is the first report of their isolation from natural sources. Their structures were elucidated through NMR spectroscopy, HRESIMS, and X-ray diffraction. Genome sequence analysis revealed that 1-7 were biosynthesized from tyrosine and phenylalanine, involving four key biosynthetic genes (ttpB-ttpE). These p-terphenyls (1-7) and 36 marine-derived terphenyl analogues (8-43) were screened for phosphodiesterase 4 (PDE4) inhibitory activities, and 1-5, 14, 17, 23, and 26 showed notable activities with IC50 values of 0.40-16 µM. The binding pattern of p-terphenyl inhibitors 1-3 with PDE4 were explored by molecular docking analysis. Talaroterphenyl A (1), with a low cytotoxicity, showed obvious anti-inflammatory activity in LPS-stimulated RAW264.7 cells. Furthermore, in the TGF-ß1-induced medical research council cell strain-5 (MRC-5) pulmonary fibrosis model, 1 could down-regulate the expression levels of FN1, COL1, and α-SMA significantly at concentrations of 5-20 µM. This study suggests that the oxidized p-terphenyl 1, as a marine-derived PDE4 inhibitor, could be used as a promising antifibrotic agent.
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Inibidores da Fosfodiesterase 4 , Compostos de Terfenil , Inibidores da Fosfodiesterase 4/farmacologia , Inibidores da Fosfodiesterase 4/química , Inibidores da Fosfodiesterase 4/isolamento & purificação , Camundongos , Animais , Compostos de Terfenil/farmacologia , Compostos de Terfenil/química , Compostos de Terfenil/isolamento & purificação , Estrutura Molecular , Talaromyces/química , Células RAW 264.7 , Nucleotídeo Cíclico Fosfodiesterase do Tipo 4/metabolismo , Biologia MarinhaRESUMO
Background: The aim of this study is to develop a predictive model utilizing deep learning and machine learning techniques that will inform clinical decision-making by predicting the 1-year postoperative recovery of patients with lumbar disk herniation. Methods: The clinical data of 470 inpatients who underwent tubular microdiscectomy (TMD) between January 2018 and January 2021 were retrospectively analyzed as variables. The dataset was randomly divided into a training set (n = 329) and a test set (n = 141) using a 10-fold cross-validation technique. Various deep learning and machine learning algorithms including Random Forests, Extreme Gradient Boosting, Support Vector Machines, Extra Trees, K-Nearest Neighbors, Logistic Regression, Light Gradient Boosting Machine, and MLP (Artificial Neural Networks) were employed to develop predictive models for the recovery of patients with lumbar disk herniation 1 year after surgery. The cure rate score of lumbar JOA score 1 year after TMD was used as an outcome indicator. The primary evaluation metric was the area under the receiver operating characteristic curve (AUC), with additional measures including decision curve analysis (DCA), accuracy, sensitivity, specificity, and others. Results: The heat map of the correlation matrix revealed low inter-feature correlation. The predictive model employing both machine learning and deep learning algorithms was constructed using 15 variables after feature engineering. Among the eight algorithms utilized, the MLP algorithm demonstrated the best performance. Conclusion: Our study findings demonstrate that the MLP algorithm provides superior predictive performance for the recovery of patients with lumbar disk herniation 1 year after surgery.
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PURPOSE: Sarcopenia, characterized by loss of muscle mass index (SMI), serves as a diagnostic indicator for malnutrition and has been shown to influence cancer treatment outcomes. The objective of this study was to investigate the prognostic significance of sarcopenia on the locally advanced nasopharyngeal carcinoma (laNPC) patients. PATIENTS AND METHODS: 545 patients with stage III-IVa NPC were included in this retrospective study. Sarcopenia was defined using the skeletal muscle index (SMI) determined at the C3 level based on baseline MRI. The log-rank test and the Cox proportional hazards model were used to compare overall survival (OS) and progression-free survival (PFS). RESULTS: The results of the multivariate analysis revealed that sarcopenia group (HR = 2.82, 95% CI 1.96-4.06, P < 0.01), T4 stage (HR = 1.64, 95% CI 1.24-2.15, P < 0.01), N3 stage (HR = 1.91, 95% CI 1.52-2.40, P < 0.01), comorbidities (HR = 2.08, 95% CI 1.45-2.97, P < 0.01), and any adverse event grade 3-4 (HR = 1.48, 95% CI 1.04-2.01, P = 0.03) were identified as independent risk factors that significantly impacted the OS. Additionally, sarcopenia group (HR = 2.40, 95% CI 1.73-3.33, P < 0.01), T4 stage (HR = 1.50, 95% CI 1.17-1.92, P < 0.01), N3 stage (HR = 1.80, 95% CI 1.46-2.22, P < 0.01), sarcopenia group (HR = 2.40, 95% CI 1.73-3.33, P < 0.01), and any adverse event grade 3-4 (HR = 1.45, 95% CI 1.04-2.01, P = 0.03) were found to have a significant impact on PFS. CONCLUSION: Sarcopenia was identified as a prognostic factor for patients with laNPC. Furthermore, T stage, N stage, comorbidities, and any adverse event grade 3-4 were identified as independent prognostic factors for laNPC.
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BACKGROUND: Advancements in nasopharyngeal carcinoma (NPC) treatment have led to a focus on personalized treatment. Circulating tumor cells (CTCs) are important for liquid biopsies and personalized treatment but are not being fully utilized. This study examined how pre- and post-treatment CTC counts, EMT subtypes, clinical characteristics, and patient prognosis are related in order to support the use of liquid biopsy in managing NPC. METHODS: This retrospective study included 141 patients with locally advanced NPC. All patients underwent CanPatrol™ CTC detection pre- and post-treatment and were categorized into EMT subtypes: epithelial type, mixed type, and mesenchymal type. This study analyzed CTC enumeration, EMT subtypes, and their associations with clinical characteristics and survival outcomes. RESULTS: The results indicated a positive correlation between the pre-treatment detection rate of CTCs and N stage (P < 0.01), alongside a positive correlation with the TNM clinical stage (P = 0.02). Additionally, the detection rate of mesenchymal CTCs post-treatment is positively associated with the N stage (P = 0.02). The enumeration of CTCs pre- and post-treatment is negatively correlated with prognosis and has statistical significance. Additionally, an investigation into the EMT subtypes of CTCs revealed a significant association between the presence of mesenchymal CTCs pre- and post-treatment and decreased overall survival (OS) (P < 0.05). Furthermore, T stage, N stage, TNM clinical stage, and Epstein-Barr virus (EBV) DNA were also significantly correlated with OS. CONCLUSION: The study found that mesenchymal CTCs pre- and post-treatment, as well as the number of CTCs, were linked to a poor prognosis.
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OBJECTIVE: To study the efficacy of ultrasound-guided parasternal block (US-PSI) in pediatric patients undergoing auricular reconstruction surgery. METHODS: For this study, the authors recruited 60 children between the ages of 5 and 12 years who underwent auricular reconstruction with autologous costal cartilage (ACC) to correct microtia. They were randomized to receive either ultrasound-guided modified parasternal block or periprostatic local infiltration anesthesia (PLIA), with 30 cases in each group. Ultrasound-guided parasternal block was administered following anesthesia induction, whereas PLIA was administered after ACC harvest. Lastly, following surgery, all children were provided with patient-controlled intravenous analgesia with sufentanil, and the numeric pain rating scale (NRS) was used to assess the intensity of pain. Our primary outcomes were the resting NRS pain scores and the NRS scores upon coughing at 1, 6, 12, 24, and 48 hours postsurgery. Sufentanil consumption within the first 24 hours of surgery, the mean duration to first ambulation, and the usage of rescue analgesics were our secondary outcomes. The authors also recorded the occurrence of undesirable side effects as well as more serious side effects like pneumothorax. RESULTS: Pediatric patients who were administered US-PSI showed significantly reduced NRS chest pain scores at 6 and 12 hours postsurgery compared to those who received PLIA (P<0.05). In addition, sufentanil consumption within the first 24 hours postsurgery, duration to first ambulation, and use of rescue analgesics were significantly lower among patients in the US-PSI group when compared to those in the PLIA group (P<0.05). CONCLUSIONS: This study found that US-PSI was a highly efficacious and safe technique for postsurgical analgesia following auricular reconstruction with ACC in pediatric patients. LEVEL OF EVIDENCE: Level II, therapeutic study.
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INTRODUCTION: Drivers for remission, relapse and violence-related behaviour among patients with schizophrenia are the most complicated issue. METHODS AND ANALYSIS: This study aims to recruit a longitudinal cohort of patients with schizophrenia. Two suburban districts and two urban districts were randomly selected according to health service facilities, population, geographical region and socioeconomic status. Individuals (>18 years old) who received a diagnosis of schizophrenia following the International Classification of Diseases (10th edition) criteria within the past 3 years will be invited as participants. Assessments will be carried out in local community health centres. Data will be used to (1) establish a community-based schizophrenia cohort and biobank, (2) prospectively determine the course of multidimensional functional outcomes of patients with schizophrenia who are receiving community-based mental health treatment, and (3) map the trajectories of patients with schizophrenia and prospectively determine the course of multidimensional outcomes based on the differential impact of potentially modifiable moderators. ETHICS AND DISSEMINATION: The study has been reviewed and approved by the Human Research Ethics Committee of Shanghai Mental Health Center (2021-67). Results of the study will be disseminated through peer-reviewed journals. If effective, related educational materials will be released to the public.
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Saúde Mental , Esquizofrenia , Humanos , Adolescente , Esquizofrenia/terapia , ChinaRESUMO
OBJECTIVES: Bivalent COVID-19 mRNA vaccines, which contain two different components, were authorized to provide protection against both the original strain of SARS-CoV-2 and the Omicron variant as a measure to address the COVID-19 pandemic. Concerns regarding the risk of myocarditis/pericarditis associated with bivalent vaccination have been raised due to the observed superior neutralizing antibody responses. This study aimed to investigate the risk of myocarditis/pericarditis following bivalent COVID-19 mRNA vaccination compared to monovalent vaccination. METHODS: The CDC COVID Data Tracker and the Vaccines Adverse Event Reporting System (VAERS) were analyzed between December 13, 2020 to March 8, 2023. Reporting rates were determined by dividing the number of myocarditis/pericarditis cases by the total number of vaccine doses administered. Disproportionality patterns regarding myocarditis/pericarditis were evaluated for various COVID-19 mRNA vaccinations using reporting odds ratios (RORs). RESULTS: The reporting rate for myocarditis/pericarditis following original monovalent COVID-19 mRNA vaccination was 6.91 (95 % confidence interval [95 %CI] 6.71-7.12) per million doses, while the reporting rate for bivalent vaccination was significantly lower (1.24, 95%CI 0.96-1.58). Disproportionality analysis revealed a higher reporting of myocarditis/pericarditis following original vaccination with a ROR of 2.21 (95 %CI 2.00-2.43), while bivalent COVID-19 mRNA vaccination was associated with fewer reports of myocarditis/pericarditis (ROR 0.57, 95 %CI 0.45-0.72). Sub-analyses based on symptoms, sex, age and manufacturer further supported these findings. CONCLUSION: This population-based study provides evidence that bivalent COVID-19 mRNA vaccination is not associated with risk of myocarditis/pericarditis. These findings provide important insights into the safety profile of bivalent COVID-19 mRNA vaccines and support their continued use as updated boosters.
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Sistemas de Notificação de Reações Adversas a Medicamentos , Vacinas contra COVID-19 , COVID-19 , Miocardite , Pericardite , Farmacovigilância , SARS-CoV-2 , Vacinas de mRNA , Humanos , Miocardite/epidemiologia , Miocardite/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , Vacinas contra COVID-19/imunologia , COVID-19/prevenção & controle , Pericardite/epidemiologia , Feminino , Adulto , Masculino , Pessoa de Meia-Idade , SARS-CoV-2/imunologia , Adulto Jovem , Idoso , Adolescente , Vacinação/efeitos adversosRESUMO
An unprecedented di-seco-indole diterpenoid, peniditerpenoid A (1), and a rare N-oxide-containing indole diterpenoid derivative, peniditerpenoid B (2), together with three known ones (3-5), were obtained from the mangrove-sediment-derived fungus Penicillium sp. SCSIO 41411. Their structures were determined by the analysis of spectroscopic data, quantum chemical calculations, and X-ray diffraction analyses. Peniditerpenoid A (1) inhibited lipopolysaccharide-induced NF-κB with an IC50 value of 11 µM and further effectively prevented RANKL-induced osteoclast differentiation in bone marrow macrophages. In vitro studies demonstrated that 1 exerted significant inhibition of NF-κB activation in the classical pathway by preventing TAK1 activation, IκBα phosphorylation, and p65 translocation. Furthermore, 1 effectively reduced the level of NFATc1 activation, resulting in the attenuation of osteoclast differentiation. Our findings suggest that 1 holds promise as an inhibitor with significant potential for the treatment of diseases related to osteoporosis.
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Diferenciação Celular , Diterpenos , Indóis , NF-kappa B , Osteoclastos , Penicillium , Penicillium/química , Osteoclastos/efeitos dos fármacos , Diterpenos/farmacologia , Diterpenos/química , Diterpenos/isolamento & purificação , Animais , Camundongos , Diferenciação Celular/efeitos dos fármacos , Estrutura Molecular , NF-kappa B/antagonistas & inibidores , NF-kappa B/metabolismo , Indóis/farmacologia , Indóis/química , Ligante RANK/farmacologia , Lipopolissacarídeos/farmacologia , Macrófagos/efeitos dos fármacosRESUMO
OBJECTIVE: To investigate the diagnostic value of urine luteinizing hormone (ULH) after the triptorelin stimulation test detected by immunochemiluminometric assay (ICMA) in girls with central precocious puberty (CPP). METHODS: The girls with precocious puberty were included. The triptorelin stimulation test at 8:30 a.m. was performed. Two consecutive 12-hour urine samples were collected after the test, defined as the first 12-hour and second 12-hour urine, respectively. ICMA measured ULH. Urine creatinine (Cr) concentration was measured. CPP and peripheral precocious puberty (PPP) were diagnosed by the same pediatric endocrinologist based on clinical symptoms, signs, and progression of clinical development. RESULTS: A total of 97 cases (CPP n=69; PPP n=28) were included, with 12 cases not meeting the receiver operating characteristic analysis criteria. The first and second 12-hour ULH/Cr in the CPP group were higher than those in the PPP group. When the first 12-hour ULH/Cr was≥287.252 IU/mol, the sensitivity and specificity for diagnosing CPP were 87.3% and 90.9%, respectively. When the second 12-hour ULH/Cr was≥152.769 IU/mol, the sensitivity and specificity for diagnosing CPP were 92.1% and 90.9%, respectively. The area under the curve of the first and second 12-hour ULH/Cr were 0.933 and 0.954, respectively. CONCLUSION: The ULH detection method after the triptorelin stimulation test has clinical significance for diagnosing CPP in girls. When blood sampling compliance in girls with precocious puberty is poor, the first 12-hour ULH/Cr≥288 IU/mol (or second 12-hour≥153 IU/mol) after the triptorelin stimulation test can serve as a laboratory indicator for diagnosis of CPP.
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Hormônio Luteinizante , Puberdade Precoce , Pamoato de Triptorrelina , Humanos , Puberdade Precoce/urina , Puberdade Precoce/diagnóstico , Puberdade Precoce/sangue , Puberdade Precoce/tratamento farmacológico , Feminino , Pamoato de Triptorrelina/farmacologia , Criança , Hormônio Luteinizante/sangue , Hormônio Luteinizante/urina , Pré-Escolar , Sensibilidade e EspecificidadeRESUMO
BACKGROUND: Urinary incontinence is highly prevalent in women while pelvic floor muscle training is recommended as the first-line therapy. However, the exact treatment regimen is poorly understood. Also, patients with pelvic floor muscle damage may have decreased muscle proprioception and cannot contract their muscles properly. Other conservative treatments including electromagnetic stimulation are suggested by several guidelines. Thus, the present study aims to compare the effectiveness of electromagnetic stimulation combined with pelvic floor muscle training as a conjunct treatment for urinary incontinence and different treatment frequencies will be investigated. METHODS/DESIGN: This is a randomized, controlled clinical trial. We will include 165 patients with urinary incontinence from the outpatient center. Participants who meet the inclusion criteria will be randomly allocated to three groups: the pelvic floor muscle training group (active control group), the low-frequency electromagnetic stimulation group (group 1), and the high-frequency electromagnetic stimulation group (group 2). Both group 1 and group 2 will receive ten sessions of electromagnetic stimulation. Group 1 will be treated twice per week for 5 weeks while group 2 will receive 10 days of continuous treatment. The primary outcome is the change in International Consultation on Incontinence Questionnaire-Short Form cores after the ten sessions of the treatment, while the secondary outcomes include a 3-day bladder diary, pelvic floor muscle function, pelvic organ prolapse quantification, and quality of life assessed by SF-12. All the measurements will be assessed at baseline, after the intervention, and after 3 months of follow-up. DISCUSSION: The present trial is designed to investigate the effects of a conjunct physiotherapy program for urinary incontinence in women. We hypothesize that this strategy is more effective than pelvic floor muscle training alone, and high-frequency electromagnetic stimulation will be superior to the low-frequency magnetic stimulation group.
Assuntos
Magnetoterapia , Diafragma da Pelve , Incontinência Urinária , Humanos , Feminino , Incontinência Urinária/terapia , Incontinência Urinária/fisiopatologia , Magnetoterapia/métodos , Diafragma da Pelve/fisiopatologia , Resultado do Tratamento , Pessoa de Meia-Idade , Fatores de Tempo , Adulto , Ensaios Clínicos Controlados Aleatórios como Assunto , Terapia por Exercício/métodos , Inquéritos e Questionários , Recuperação de Função Fisiológica , Idoso , Qualidade de VidaRESUMO
Ten ergostane-type steroids, including seven undescribed ones named spectasteroids A-G, were obtained from Aspergillus spectabilis. Their structures and absolute configurations were determined based on HRESIMS, NMR, ECD calculations, and single-crystal X-ray diffraction analyses. Structurally, spectasteroid A was a unique example of aromatic ergostane-type steroid that featured a rare peroxide ring moiety; spectasteroid B contained a rare oxetane ring system formed between C-9 and C-14; and spectasteroid C was an unusual 3,4-seco-ergostane steroid with an extra lactone ring between C-3 and C-9. Spectasteroids F and G specifically showed inhibitory effects against concanavalin A-induced T lymphocyte proliferation and lipopolysaccharide-induced B lymphocyte proliferation, with IC50 values ranging from 2.33 to 4.22 µM. Spectasteroid F also showed excellent antimultidrug resistance activity, which remarkable enhanced the inhibitory activity of PTX on the colony formation of SW620/Ad300 cells.