RESUMO
BACKGROUND: Stroke survivors are at high risk of coping with cognitive problems after stroke. In recent decades, the relationship between socioeconomic status (SES) and health-related outcomes has been a topic of considerable interest. Learning more about the potential impact of SES on poststroke cognitive dysfunction is of great importance. OBJECTIVE: The purpose of this systematic review and meta-analysis was to summarize the association between SES and poststroke cognitive function by quantifying the effect sizes of the existing studies. METHOD: We searched studies from PubMed, Ovid, Embase, Cochrane, Scopus, and PsychINFO up to January 30th 2024 and the references of relevant reviews. Studies reporting the risk of poststroke cognitive dysfunction as assessed by categorized SES indicators were included. The Newcastle-Ottawa scale and the Agency for Healthcare Research and Quality were used to evaluate the study quality. Meta-analyses using fixed-effect models or random-effect models based on study heterogeneity were performed to estimate the influence of SES on cognitive function after stroke, followed by subgroup analyses stratified by study characteristics. RESULTS: Thirty-four studies were eligible for this systematic review and meta-analysis. Of which, 19 studies reported poststroke cognitive impairment (PSCI) as the outcome, 13 reported poststroke dementia (PSD), one reported both PSCI and PSD, and one reported vascular cognitive impairment no dementia. The findings showed that individuals with lower SES levels had a higher risk of combined poststroke cognitive dysfunction (odds ratio (OR) = 1.91, 95% confidence interval (CI) = 1.59-2.29), PSCI (OR = 2.09, 95% CI = 1.57-2.78), and PSD (OR = 1.95, 95% CI = 1.48-2.57). Subgroup analyses stratified by SES indicators demonstrated the protective effects of education and occupation against the diagnoses of combined poststroke cognitive dysfunction, PSCI, and PSD. CONCLUSIONS: Stroke survivors belonging to a low SES are at high risk of poststroke cognitive dysfunction. Our findings add evidence for public health strategies to reduce the risk of poststroke cognitive dysfunction by reducing SES inequalities.
Assuntos
Disfunção Cognitiva , Classe Social , Acidente Vascular Cerebral , Humanos , Acidente Vascular Cerebral/psicologia , Acidente Vascular Cerebral/complicações , Disfunção Cognitiva/etiologia , Cognição/fisiologia , Demência/psicologiaRESUMO
OBJECTIVE: The study aims to compare the efficacies of the immunosuppressants most commonly prescribed for patients with neuromyelitis optica spectrum disorder (NMOSD). The predictors, which might be associated with relapse and disability in NMOSD, were also analyzed. METHODS: This retrospective study included NMOSD patients treated with azathioprine (AZA), mycophenolate mofetil (MMF), and rituximab (RTX). The annual relapse rate (ARR) and the incidence rates of adverse events were compared. Cox proportional-hazards model calculated the potential predictors of NMOSD relapse and disability. RESULTS: A total of 83 patients were included. The median treatment time of AZA group (n = 34), MMF group (n = 20), and RTX group (n = 29) were 19.5, 15.5, and 12 months, respectively. ARR of the three groups reduced significantly after treatment. In the three groups, 55.9%, 50%, and 79.3% of patients, respectively, were free from relapse. However, the difference among the three groups was of no statistical significance, possibly due to the small sample size. During the treatment, 32.4%, 15%, and 24.1% of patients experienced adverse events in the AZA group, MMF group, and RTX group, respectively. Additionally, the multivariate Cox analyses indicated that history of a severe attack and disease duration were associated with the risk of relapse after immunotherapy. Late-onset (≥ 50 years old) NMOSD patients were probably more susceptible to motor disability, and those with optic neuritis at onset were more likely to develop visual disability. CONCLUSIONS: AZA, MMF, and low-dose RTX were all effective in reducing the relapse rate in NMOSD. The age at onset, disease duration, history of severe attacks, and primary syndromes might be significant prognostic predictors in NMOSD.
Assuntos
Pessoas com Deficiência , Imunossupressores/uso terapêutico , Transtornos Motores , Neuromielite Óptica , Azatioprina/uso terapêutico , Humanos , Pessoa de Meia-Idade , Ácido Micofenólico/uso terapêutico , Neuromielite Óptica/tratamento farmacológico , Prognóstico , Estudos Retrospectivos , Rituximab/efeitos adversosRESUMO
Five pomelo cultivars (i.e., Citrus grandis cv. Shatianyou, Citrus grandis cv. Guanximiyou, Citrus grandis cv. Yuhuanyou, Citrus grandis cv. Duweiwendanyou and Citrus grandis cv. Liangpingyou) from different origins in China were selected to analyze their components by using supercritical CO2 fluid extraction coupled with ultra-high-performance liquid chromatography-tandem mass spectrometry. A total of 45 compounds were identified in the supercritical CO2 fluid extracts of the pomelo peels from the five cultivars. These compounds included eight flavonoids, 18 coumarins, four organic acids, three aldehydes, and 12 other compounds, which were identified using the obtained MS data and by comparison with commercial standards, orbitrap Chinese Traditional Medicine Library, and previous literature. Twenty-five of the identified compounds were detected for the first time in the pomelo peel extracts. Results suggested that the pomelo peels of C. grandis cv. Shatianyou contained the most natural chemical compositions. The pooled result may offer scientific evidence for further development and utilization of pomelo peels and a route for screening appropriate varieties for various demands.
Assuntos
Citrus , Dióxido de Carbono , Cromatografia Líquida de Alta Pressão/métodos , Citrus/química , Frutas/química , Extratos Vegetais/química , Espectrometria de Massas em TandemRESUMO
BACKGROUND: To evaluate the efficacy and safety of pomalidomide in combination treatment of relapsed/refractory multiple myeloma (RRMM). METHODS: Published clinical trials were searched in the Cochrane Library, PubMed, EMBASE to February 2023. The literature was screened and evaluated according to the inclusion criteria, and the data were analyzed by a random effect model. Overall response rate (ORR), overall survival (OS), progression-free survival (PFS) and full grade or ≥ 3 adverse events (AEs) were the outcomes. RESULTS: This study included 31 clinical trials, which included 4776 patients. The pooled ORR of the doublet regimens was 33.3% (95%CI: 27-39%) and the triplet regimens was 66% (95%CI: 58-74%). Among the 25 included studies, the median PFS was 8.29 months (95%CI: 7.27-9.31), and nine studies reported median OS of 19.43 months (95%CI: 14.56-24.30). In terms of safety, the most common hematologic AEs of grade ≥ 3 were neutropenia (41%) and anemia (20%); Non-hematologic AEs were pneumonia (14%) and infection/febrile neutropenia (14%). CONCLUSIONS: Pomalidomide combined treatment regimens have shown good clinical efficacy, especially in pomalidomide + dexamethasone combined with other drugs. In terms of safety, it's important to pay attention to the likelihood of hematological adverse events when used clinically. SYSTEMATIC REVIEW REGISTRATION: PROSPERO: CRD42023420644.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Dexametasona , Mieloma Múltiplo , Talidomida , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/mortalidade , Humanos , Talidomida/análogos & derivados , Talidomida/uso terapêutico , Talidomida/administração & dosagem , Talidomida/efeitos adversos , Dexametasona/uso terapêutico , Dexametasona/administração & dosagem , Dexametasona/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Recidiva , Resultado do TratamentoRESUMO
BACKGROUND: N1-Methyladenosine (m1A) is an abundant modification of transcripts regulating mRNA structure and translation efficiency. However, the characteristics and biological functions of mRNA m1A modification in adult hippocampal neurogenesis remain enigmatic. RESULTS: We found that m1A demethylase Alkbh3 was dramatically enriched in neurons and neuronal genesis. Functionally, depletion of Alkbh3 in neural stem cells (NSCs) significantly decreased m1A modification, neuronal differentiation and proliferation coupling with increasing gliogenesis, whereas overexpressing Alkbh3 facilitated neuronal differentiation and proliferation. Mechanistically, the m1A demethylation of Mmp15 mRNA by Alkbh3 improved its RNA stability and translational efficacy, which promoted neurogenesis. Therapeutically, the silencing of Alkbh3 reduced hippocampal neurogenesis and impaired spatial memory in the adult mice. CONCLUSIONS: We reveal a novel function of m1A demethylation on Mmp15 mRNA in Alkbh3-mediated neurogenesis, which shed light on advancing Alkbh3 regulation of neurogenesis as a novel neurotherapeutic strategy.
RESUMO
Ovarian tumor domain-containing protease 1 (OTUD1) is a critical negative regulator that promotes innate immune homeostasis and is extensively involved in the pathogenesis of sepsis. In this study, we performed a powerful integration of multiomics analysis and an experimental mechanistic investigation to elucidate the immunoregulatory role of OTUD1 in sepsis at the clinical, animal and cellular levels. Our study revealed the upregulation of OTUD1 expression and the related distinctive alterations observed via multiomics profiling in clinical and experimental sepsis. Importantly, in vivo and in vitro, OTUD1 was shown to negatively regulate inflammatory responses and play a protective role in sepsis-induced pathological lung injury by mechanistically inhibiting the activation of the transforming growth factor-beta-activated kinase 1 (TAK1)-mediated mitogen-activated protein kinase (MAPK) and nuclear factor kappa-B (NF-κB) signaling pathways in the present study. Subsequently, we probed the molecular mechanisms underlying OTUD1's regulation of NF-κB and MAPK pathways by pinpointing the target proteins that OTUD1 can deubiquitinate. Drawing upon prior research conducted in our laboratory, it has been demonstrated that tumor necrosis factor-α-induced protein 8-like 2 (TIPE2) performs a protective function in septic lung injury and septic encephalopathy by suppressing the NF-κB and MAPK pathways. Hence, we hypothesized that TIPE2 might be a target protein of OTUD1. Additional experiments, including Co-IP, immunofluorescence co-localization, and Western blotting, revealed that OTUD1 indeed has the ability to deubiquitinate TIPE2. In summary, OTUD1 holds potential as an immunoregulatory and inflammatory checkpoint agent, and could serve as a promising therapeutic target for sepsis-induced lung injury.
Assuntos
Peptídeos e Proteínas de Sinalização Intracelular , MAP Quinase Quinase Quinases , Camundongos Endogâmicos C57BL , NF-kappa B , Sepse , Proteases Específicas de Ubiquitina , Animais , Sepse/metabolismo , MAP Quinase Quinase Quinases/metabolismo , MAP Quinase Quinase Quinases/genética , NF-kappa B/metabolismo , Camundongos , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/genética , Masculino , Humanos , Proteases Específicas de Ubiquitina/metabolismo , Proteases Específicas de Ubiquitina/genética , Transdução de Sinais/fisiologia , Ubiquitinação , Lesão Pulmonar/metabolismo , Lesão Pulmonar/etiologia , Lesão Pulmonar/prevenção & controle , Sistema de Sinalização das MAP Quinases/fisiologiaRESUMO
BACKGROUND AND OBJECTIVE: GB221 is a recombinant humanized anti-HER2 monoclonal antibody. The purpose of this study was to evaluate the pharmacokinetic, safety, and immunogenicity of GB221 in healthy Chinese adults in comparison to trastuzumab (Herceptin®). METHODS: In this randomized, double-blind, parallel-group phase I clinical trial, 88 subjects were randomized 1:1 to receive a single intravenous infusion (90-100 min) of GB221 or trastuzumab (6 mg/kg). The primary pharmacokinetic parameters-maximum observed serum concentration (Cmax), area under the serum concentration-time curve from zero to the last quantifiable concentration at time t (AUC0-t), and area under the serum concentration-time curve from time zero to infinity (AUC0-∞)-of GB221 and trastuzumab were compared to establish whether the 90% confidence interval (CI) attained the 80-125% bioequivalence standard. Safety and immunogenicity were also evaluated. RESULTS: The GB221 group (n = 43) and the trastuzumab group (n = 44) showed similar pharmacokinetic characteristics. The geometric mean ratios (90% CI) of Cmax, AUC0-t, and AUC0-∞ between the two groups were 107.53% (102.25-113.07%), 108.31% (103.57-113.26%), and 108.34% (103.57-113.33%), respectively. The incidence of treatment-emergent adverse events (TEAEs) was 83.7% (36/43) of the subjects in the GB221 group and 95.5% (42/44) of the subjects in the trastuzumab group. No subjects withdrew from the trial due to TEAEs, and there were no occurrences of serious adverse events. All subjects tested negative for antidrug antibodies (ADA). CONCLUSION: GB221 demonstrated similar pharmacokinetics to trastuzumab and comparable safety and immunogenicity in healthy Chinese adults.
Assuntos
Antineoplásicos Imunológicos , Área Sob a Curva , Equivalência Terapêutica , Trastuzumab , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Antineoplásicos Imunológicos/farmacocinética , Antineoplásicos Imunológicos/administração & dosagem , Antineoplásicos Imunológicos/efeitos adversos , Povo Asiático , Método Duplo-Cego , População do Leste Asiático , Voluntários Saudáveis , Infusões Intravenosas , Receptor ErbB-2/imunologia , Trastuzumab/farmacocinética , Trastuzumab/administração & dosagem , Trastuzumab/efeitos adversosRESUMO
OBJECTIVE: To investigate the association between income and post-stroke cognition at 3 months, and the underlying neuroanatomical mechanism. METHODS: Patients with first-ever ischemic stroke were enrolled and analyzed. Baseline information on income and neuroimaging measurements with predictive values for post-stroke cognitive impairment (PSCI) were collected within 7 days of the admission. Three months after the index stroke, all participants underwent a detailed neuropsychological test battery. The associations between income and PSCI and between income and brain structural measurements were investigated. RESULTS: A total of 294 patients were recruited for this study. Lower income was independently associated with poor cognitive performance on Stroop tests, Clinical Dementia Rating, Boston Naming Test, and Verbal Fluency Test. Regarding neuroimaging parameters, lower income was associated with a lower total brain volume (TBV)/total intracranial volume (TICV) ratio (p = 0.004). CONCLUSIONS: Lower income is associated with an increased chance of post-stroke cognitive decline, particularly in executive function and language domains. Since global brain atrophy (measured by TBV/TICV ratio) is a strong predictor for PSCI, its correlation with income may help explain the neuroanatomical mechanism between income and post-stroke cognition.
RESUMO
BACKGROUND: Osteoid osteoma is a benign osteogenic tumor that occurs mostly in the femoral stem, while osteoid osteoma occurring in the lumbar vertebral body is a relatively rare case. To minimize treatment-related complications, a computer-assisted navigation fully visualized spinal endoscopy was used. Ultimately, the pathology was diagnosed as osteoid osteoma. CASE PRESENTATION: We report a 19-year-old adult male with low back pain that worsened at night and CT, MRI imaging showed an abnormal signal shadow at the posterior margin of the lumbar vertebral body. Due to the proximity of the lesion to the spinal canal and adjacent to the nerve roots, it was difficult to precisely localize the lesion by purely endoscopic or open procedures, and if necessary, the resection of surrounding tissues had to be expanded, causing unnecessary damage to the surrounding tissues. Therefore, we choose computer-assisted navigation fully visualized spinal endoscopy to perform the treatment. CONCLUSION: In this case, we report an osteoid osteoma that occurs less frequently in the lumbar vertebral body. Using computer-assisted navigation with fully visualized spinal endoscopy, we successfully resected the osteoid osteoma at the posterior margin of the L3 vertebral body preoperatively by computer-planned path with intraoperative visualization endoscopy, minimizing the damage to spinal stability. Computer-assisted navigation with visualization endoscopy provides a more precise and minimally invasive approach to the treatment of osteoid osteoma of the spine.
Assuntos
Osteoma Osteoide , Neoplasias da Coluna Vertebral , Cirurgia Assistida por Computador , Adulto , Humanos , Masculino , Adulto Jovem , Osteoma Osteoide/diagnóstico por imagem , Osteoma Osteoide/cirurgia , Neoplasias da Coluna Vertebral/diagnóstico por imagem , Neoplasias da Coluna Vertebral/cirurgia , Resultado do Tratamento , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/cirurgia , Vértebras Lombares/patologia , Endoscopia , Cirurgia Assistida por Computador/métodosRESUMO
The volatile and nonvolatile phytochemicals in peels of 5 major pomelo cultivars (including Citrus grandis cv. Yuhuanyou, C. grandis cv. Liangpingyou, C. grandis cv. Guanximiyou, C. grandis cv. Duweiwendanyou, and C. grandis cv. Shatianyou) from 11 places in China were characterized. First, 194 volatile compounds in pomelo peels were identified by gas chromatography-mass spectrometry (GC-MS). Of these, 20 major volatile compounds were subjected to cluster analysis. The heatmap indicated that the volatile compounds in peels of C. grandis cv. Shatianyou and C. grandis cv. Liangpingyou were different from those in other varieties, while there was no difference among C. grandis cv. Guanximiyou, C. grandis cv. Yuhuanyou, and C. grandis cv. Duweiwendanyou from different origins. Second, 53 nonvolatile compounds were identified in pomelo peels by ultraperformance liquid chromatography-Q-exactive orbitrap tandem MS (UPLC-Q-exactive orbitrap-MS), of which 11 components were detected for the first time. Third, six major nonvolatile compounds were quantitatively analyzed with high-performance LC-photodiode array detection (HPLC-PDA). Combining the results of HPLC-PDA and the heatmap, 6 nonvolatile compounds in 12 batches of pomelo peel were well separated among varieties. Comprehensive analysis and identification of chemical components in pomelo peels are of great significance for their further development and utilization.
RESUMO
BACKGROUND: GB223 is a novel, fully-humanized monoclonal antibody against the receptor activator of nuclear factor-kappa B ligand (RANKL). In this phase I study, the safety, tolerability, pharmacokinetics, pharmacodynamics, and immunogenicity of GB223 were investigated. PATIENTS AND METHODS: This was a randomized, double-blinded, placebo-controlled, single-dose escalation study conducted in 44 healthy Chinese adults. Participants were randomly assigned to receive a single subcutaneous injection dose of 7, 21, 63, 119, or 140 mg of GB223 (n = 34) or placebo (n = 10) and were followed up for 140-252 days. RESULTS: The results of noncompartmental analysis showed that GB223 was slowly absorbed after dosing, with a time to reach maximum concentration (Tmax) ranging from 5 to 11 days. Serum GB223 concentrations decreased slowly, with a long half-life ranging from 7.91 to 19.60 days. A two-compartment Michaelis-Menten model was found to best describe the pharmacokinetics of GB223, and the absorption rate of GB223 differed between males (0.0146 h-1) and females (0.0081 h-1). Serum C-terminal telopeptide of type I collagen decreased significantly postdose, and the inhibition lasted 42-168 days. No deaths or drug-related serious adverse events occurred. The most frequent adverse events were blood parathyroid hormone increased (94.1%), blood phosphorus decreased (67.6%) and blood calcium decreased (58.8%). In the GB223 group, 44.1% (15/34) of subjects were antidrug antibody positive after dosing. CONCLUSION: In this study, we demonstrated for the first time that a single subcutaneous injection of GB223, from 7 to 140 mg, is safe and well tolerated in healthy Chinese subjects. GB223 has a nonlinear pharmacokinetic profile, and sex was a potential covariate that may affect the absorption rate of GB223. CLINICAL TRIAL REGISTRATION: NCT04178044 and ChiCTR1800020338.
Assuntos
Anticorpos Monoclonais Humanizados , Ligante RANK , Adulto , Feminino , Humanos , Masculino , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/farmacocinética , Relação Dose-Resposta a Droga , Método Duplo-Cego , População do Leste Asiático , Voluntários SaudáveisRESUMO
Content analysis is a common and flexible technique to quantify and make sense of qualitative data in psychological research. However, the practical implementation of content analysis is extremely labor-intensive and subject to human coder errors. Applying natural language processing (NLP) techniques can help address these limitations. We explain and illustrate these techniques to psychological researchers. For this purpose, we first present a study exploring the creation of psychometrically meaningful predictions of human content codes. Using an existing database of human content codes, we build an NLP algorithm to validly predict those codes, at generally acceptable standards. We then conduct a Monte-Carlo simulation to model how four dataset characteristics (i.e., sample size, unlabeled proportion of cases, classification base rate, and human coder reliability) influence content classification performance. The simulation indicated that the influence of sample size and unlabeled proportion on model classification performance tended to be curvilinear. In addition, base rate and human coder reliability had a strong effect on classification performance. Finally, using these results, we offer practical recommendations to psychologists on the necessary dataset characteristics to achieve valid prediction of content codes to guide researchers on the use of NLP models to replace human coders in content analysis research. (PsycInfo Database Record (c) 2022 APA, all rights reserved).
RESUMO
Ultra-high-performance liquid chromatography-Q-Exactive Orbitrap-mass spectrometry (MS) and gas chromatography (GC)-MS were performed for the qualitative and quantitative analyses of Citri Sarcodactylis Fructus (CSF) from different origins. The contents of eight major CSF components, namely 5,7-dimethoxycoumarin, scopoletin, hesperidin, tangeretin, nobiletin, limonin, nomilin, and stachydrine, were quantitatively analyzed. Clustering analysis and principal component analysis (PCA) were, respectively, performed to classify and compare the 10 CSF batches. One hundred and two volatile components were identified accordingly by comparing retention times, reference standards, parent peaks, fragment peaks, and findings from relevant literature. Moreover, high content of 5,7-dimethoxycoumarin and stachydrine was detected in all the CSFs, especially in CSF-Zhe. Therefore, the high content component coumarin "5,7-dimethoxycoumarin" was suggested to be quality analysis component rather than hesperidin. Additionally, characteristic compounds were found to distinguish different CSFs. This work was a comprehensive study about the components of various CSF. It distinguished the basic differences in the compositions of CSF from different origins. Eventually, it provided experimental and systematic bases for the quality control analysis of CSF, which has potential application in the further research.
RESUMO
Pattern-recognition receptors (PRRs) have been shown to promote tumour metastasis via sensing tumour cell-derived small extracellular vesicles (EVs). Nucleotide-binding oligomerisation domain 1 (NOD1), a cytoplasmic PRR, plays a role in colorectal cancer (CRC) by detecting bacterial products. However, the precise mechanisms underlying the effects of NOD1, following identification of CRC cell-derived EVs (CRC-EVs), to potentiate CRC liver metastasis (CRC-LM), remain poorly understood. Here, we demonstrate that CRC-EVs activate NOD1 in macrophages to initiate secretion of inflammatory cytokines and chemokines. NOD1-activated macrophages also promote CRC cell migration, while in a murine model of liver metastasis (LM), NOD1-deficient mice exhibit reduced metastasis following CRC-EV treatment. Furthermore, cell division cycle 42 (CDC42), a small Rho guanosine-5'-triphosphate (GTP)ase, is delivered by CRC-EVs into macrophages where it activates NOD1. In addition, EVs from the plasma of patients with CRC-LM mediate NOD1 activation in human peripheral blood mononuclear cells. Moreover, high NOD1 expression in tumour tissues is associated with poor prognosis of CRC-LM. Our findings suggest that CRC-EVs activate NOD1 to promote tumour metastasis, thus, NOD1 may serve as a potential target in the diagnosis and treatment of CRC-LM.
Assuntos
Neoplasias Colorretais , Vesículas Extracelulares , Neoplasias Hepáticas , Animais , Vesículas Extracelulares/metabolismo , Humanos , Leucócitos Mononucleares/metabolismo , Neoplasias Hepáticas/metabolismo , Camundongos , Proteína Adaptadora de Sinalização NOD1/metabolismo , Transdução de SinaisRESUMO
By virtue of α-allenols as innovative three-carbon annulation components, the Rh(III)-catalyzed redox-neutral C-H coupling of N-phenoxyacetamides with α-allenols has been realized for the assembly of 4-alkylidene chroman-2-ol frameworks via an unusual [3+3] annulation. This transformation features good functional group tolerance, specific regio-/chemoselectivity and potential synthetic utility. Mechanistic studies reveal that synergistic coordination modes between the dual directing groups (-ONHAc and -OH) and the rhodium metal center account for the observed exclusive selectivity.
RESUMO
To systematically analyze the chemical constituents of Citri Sarcodactylis Fructus (CSF) from different origins, an efficient approach based on ultraperformance liquid chromatography plus Q-Exactive Orbitrap tandem mass spectrometry (UPLC-Q-Exactive Orbitrap/MS) detection for the discrimination of chemical components from of 15 batches of CSF from four main origins was used in this research. Through parent peaks, fragment peaks, fragmentation characteristics, and comparative analysis with the literature and reference standards, a total of 77 components from the methanol extracts including 18 coumarins, 24 flavonoids, seven organic acids, three limonoids, and 25 other compounds were detected and identified. Among them, 15 components have not been reported previously in the CSF. Notably, the stachydrine peak initially showed a higher content in the total ion current chromatogram. Overall, CSF produced in the Zhejiang province contained a richer variety of chemical compositions. These observations provided a theoretical basis for the further quality assessment and application of CSF.
RESUMO
INTRODUCTION: The purpose of this study was to characterize the at-risk diabetes and prediabetes patient population visiting emergency department (ED) and urgent care (UC) centers in upstate South Carolina. METHODS: We conducted this retrospective study at the largest non-profit healthcare system in South Carolina, using electronic health record (EHR) data of patients who had an ED or UC visit between February 2, 2016-July 31, 2018. Key variables including International Classification of Diseases, 10th Revision codes, laboratory test results, family history, medication, and demographic characteristics were used to classify the patients as healthy, having prediabetes, having diabetes, being at-risk for prediabetes, or being at-risk for diabetes. Patients who were known to have diabetes were classified further as having controlled diabetes, management challenged, or uncontrolled diabetes. Population analysis was stratified by the patient's annual number of ED/UC visits. RESULTS: The risk stratification revealed 4.58% unique patients with unrecognized diabetes and 10.34% of the known patients with diabetes considered to be suboptimally controlled. Patients identified as diabetes management challenged had more ED/UC visits. Of note, 33.95% of the patients had unrecognized prediabetes/diabetes risk factors identified during their ED/UC with 87.95% having some form of healthcare insurance. CONCLUSION: This study supports the idea that a single ED/UC unscheduled visit can identify individuals with unrecognized diabetes and an at-risk prediabetes population using EHR data. A patient's ED/UC visit, regardless of their primary reason for seeking care, may be an opportunity to provide early identification and diabetes disease management enrollment to augment the medical care of our community.
Assuntos
Diabetes Mellitus/diagnóstico , Serviço Hospitalar de Emergência/estatística & dados numéricos , Adulto , Idoso , Idoso de 80 Anos ou mais , Técnicas de Apoio para a Decisão , Diabetes Mellitus/classificação , Diabetes Mellitus/epidemiologia , Registros Eletrônicos de Saúde/normas , Serviço Hospitalar de Emergência/organização & administração , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudo de Prova de Conceito , Estudos Retrospectivos , Medição de Risco , Adulto JovemRESUMO
Nucleotide-binding oligomerization domain-containing protein 1 and 2 (NOD1/2) receptors are potential immune checkpoints. In this article, a quinazolinone derivative (36b) as a NOD1/2 dual antagonist was identified that significantly sensitizes B16 tumor-bearing mice to paclitaxel treatment by inhibiting both nuclear factor κB (NF-κB) and mitogen-activated protein kinase inflammatory signaling that mediated by NOD1/2.
Assuntos
Proteína Adaptadora de Sinalização NOD1/antagonistas & inibidores , Proteína Adaptadora de Sinalização NOD2/antagonistas & inibidores , Quinazolinonas/química , Quinazolinonas/farmacologia , Animais , Linhagem Celular , Descoberta de Drogas , Humanos , Masculino , Melanoma Experimental/tratamento farmacológico , Melanoma Experimental/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , NF-kappa B/metabolismo , Proteína Adaptadora de Sinalização NOD1/metabolismo , Proteína Adaptadora de Sinalização NOD2/metabolismo , Nucleotídeos/metabolismoRESUMO
To thoroughly evaluate the quality of Citri Sarcodactylis Fructus (CSF) and acquire knowledge of the lipophilic components of CSF from different origins, a simple and efficient approach based on supercritical fluid extraction (SFE) combined with ultraperformance liquid chromatography plus Q-Exactive Orbitrap tandem mass spectrometry (UPLC-Q-Exactive Orbitrap/MS) detection for the discrimination of components from CSF was set up for the first time in this work. Eight batches of CSF samples from five main producing areas were extracted by SFE under optimized conditions, and then SFE extracts were dissected via UPLC-Q-Exactive Orbitrap/MS. The results indicated that 39 lipophilic compounds were successfully separated and unambiguously or tentatively identified, where 4 coumarins, 6 polymethoxyflavones, 3 phthalides, 6 terpenes, and 4 phenolics were not reported formerly. It was illustrated that CSF may be abundant in polymethoxyflavones, as in coumarins. Moreover, there were significant differences in the components of CSF from different origins. Especially, coumarin, dehydrocostus lactone, atractylenolide II, and atractylenolide I were exclusively found in CSF from the Guangdong province; isopsoralen was almost exclusively found in CSF from the Guangxi province; and ferulic acid was exclusively found in CSF from the Zhejiang province. These observations indicated that SFE joint with UPLC-Q-Exactive Orbitrap/MS owing to the potential of characterizing the lipophilic components could be used to promote quality assessment and chemotaxonomic investigation in phytology sciences of CSF.
RESUMO
Nucleotide-binding oligomerization domain-containing proteins 1 and 2 play important roles in immune system activation. Recently, a shift has occurred due to the emerging knowledge that preventing nucleotide-binding oligomerization domains (NODs) signaling could facilitate the treatment of some cancers, which warrants the search for dual antagonists of NOD1 and NOD2. Herein, we undertook the synthesis and identification of a new class of derivatives of dual NOD1/NOD2 antagonists with novel benzofused five-membered sultams. Compound 14k was finally demonstrated to be the most potent molecule that inhibits both NOD1-and NOD2-stimulated NF-κB and MAPK signaling in vitro and in vivo.