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2.
PeerJ ; 12: e17203, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38618570

RESUMO

Background: Hypertension stands as the leading single contributor to the worldwide burden of mortality and disability. Limited evidence exists regarding the association between the combined healthy lifestyle score (HLS) and hypertension control in both treated and untreated hypertensive individuals. Therefore, we aimed to investigate the association between HLS and hypertension control among adults with treated and untreated hypertension. Methods: This cross-sectional study, including 311,994 hypertension patients, was conducted in Guangzhou using data from the National Basic Public Health Services Projects in China. The HLS was defined based on five low-risk lifestyle factors: healthy dietary habits, active physical activity, normal body mass index, never smoking, and no alcohol consumption. Controlled blood pressure was defined as systolic blood pressure <140 mmHg and diastolic blood pressure <90 mmHg. A multivariable logistic regression model was used to assess the association between HLS and hypertension control after adjusting for various confounders. Results: The HLS demonstrated an inverse association with hypertension control among hypertensive patients. In comparison to the low HLS group (scored 0-2), the adjusted odds ratios (95% confidence intervals) for hypertension were 0.76 (0.74, 0.78), 0.59 (0.57, 0.60), and 0.48 (0.46, 0.49) for the HLS groups scoring 3, 4, and 5, respectively (Ptrend < 0.001). Notably, an interaction was observed between HLS and antihypertensive medication in relation to hypertension control (Pinteraction < 0.001). When comparing the highest HLS (scored 5) with the lowest HLS (scored 0-2), adjusted odds ratios (95% confidence intervals) were 0.50 (0.48, 0.52, Ptrend < 0.001) among individuals who self-reported using antihypertensive medication and 0.41 (0.38, 0.44, Ptrend < 0.001) among those not using such medication. Hypertensive patients adhering to a healthy lifestyle without medication exhibited better blood pressure management than those using medication while following a healthy lifestyle. Conclusion: HLS was associated with a reduced risk of uncontrolled blood pressure.


Assuntos
Anti-Hipertensivos , Hipertensão , Adulto , Humanos , Anti-Hipertensivos/uso terapêutico , Estudos Transversais , Hipertensão/tratamento farmacológico , Pressão Sanguínea , Estilo de Vida Saudável
3.
Clin Teach ; : e13768, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38651678

RESUMO

INTRODUCTION: Physician educators are essential in training the next generation of physicians. However, physician educators' perspectives about what experiences they find beneficial to their teaching and the prevalence of these experiences remain unknown. Guided by social cognitive career theory (SCCT) and communities of practice (CoP), we explored what experiences physician educators perceive as beneficial in preparing them to teach. METHODS: In 2019, the Uniformed Services University School of Medicine in the United States surveyed its physician alumni to understand their education experiences during medical school, their current career path and what has contributed to their teaching role. Content analysis was applied to extract themes across the text response. Chi-square analysis was applied to examine if perceived contributing factors vary based on physician educators' gender, specialty and academic ranks. RESULTS: The five most prevalent contributing factors participants (n = 781) identified are (1) experiences gained during residency and fellowship (29.8%), (2) teaching as faculty member (28.9%) and (3) class experiences and peer interaction during medical school (26%). We organised three themes that reflected major avenues of how physician educators acquire teaching skills: reflection about quality teaching, journey as learners and learning by doing. Gender and clinical specialty were differentially associated with contributing factors such as faculty development and meta-reflection. CONCLUSION: The results are in line with theories of SCCT and CoP, in which we identified self-directed learning and regulation in shaping physician educators' teaching. The findings also revealed gaps and potential contexts for more formalised teaching practices to develop physician educators.

4.
Front Endocrinol (Lausanne) ; 15: 1302296, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38577567

RESUMO

Background: Cardiometabolic multimorbidity (CMM) has emerged as a prominent public health concern. Hypertensive patients are prone to develop comorbidities. Moreover, the accumulation of visceral adipose tissue is the main cause for the development of cardiometabolic diseases. The cardiometabolic index (CMI), lipid accumulation product (LAP), visceral adiposity index (VAI), and Chinese visceral adiposity index (CVAI) not only assess adipose tissue mass but also reflect adipose tissue dysfunction. So far, no study has been reported to evaluate the association of CMI, LAP, VAI, and CVAI with CMM risk in hypertensive patients. Therefore, this study aimed to assess the association between these adiposity indicators and the risk of CMM among Chinese hypertensive patients. Methods: In this cross-sectional study, a total of 229,287 hypertensive patients aged 35 years and older were included from the National Basic Public Health Service Project. All participants underwent a face-to-face questionnaire survey, physical examination, and the collection of fasting venous blood samples. Multivariable logistic regression models were performed to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Receiver operating characteristic curve was utilized to evaluate the identification ability for CMM. Results: After adjusting for confounders, each 1-standard deviation increase in CMI, LAP, VAI, and CVAI was associated with a 14%, 8%, 12%, and 54% increased risk of CMM, respectively. When comparing the highest quartile of these indicators with the lowest quartile, individuals in the highest quartile of CMM, LAP, VAI, and CVAI had a 1.39-fold (95% CI 1.30, 1.48), 1.28-fold (95% CI 1.19, 1.37), 1.37-fold (95% CI 1.29, 1.46), and 2.56-fold (95% CI 2.34, 2.79) increased risk of CMM after adjusting for potential confounders. Notably, a nonlinear association was observed for CMI, LAP, and VAI with the risk of CMM (all P nonlinearity < 0.001). CVAI exhibited the highest area under the receiver operating characteristic curve (AUC) among all the included adiposity indices in this analysis. Conclusion: This study indicated the significant positive association of CMI, LAP, VAI, and CVAI with the risk of CMM in hypertensive patients. Among these indicators, CVAI demonstrated the most robust performance in predicting CMM risk and may serve as a valuable tool for identifying CMM risk in Chinese hypertensive patients.


Assuntos
Adiposidade , Hipertensão , Humanos , Estudos Transversais , Multimorbidade , Índice de Massa Corporal , Obesidade , Hipertensão/epidemiologia , Obesidade Abdominal
5.
Heliyon ; 10(6): e27666, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38524594

RESUMO

Objective: To develop and test a post competency scale for traditional Chinese medicine (TCM) physicians undergoing standardized training to provide an applicable tool for scientific evaluation. Methods: Based on literature analysis, behavioral event interviews, and expert consultations, measurement questions were formulated and the initial scale was designed. A questionnaire survey was conducted from July 2022 to May 2023 among TCM physicians undergoing standardized training in China. The rationality of the scale was confirmed through item purification, factor analysis, and tests of reliability and validity. Results: The post competency scale consisted of three dimensions (TCM fundamentals and research abilities, TCM thinking and skill abilities, and personal traits and communication abilities) with 21 items. Exploratory factor analysis identified three common factors, accounting for a cumulative variance contribution rate of 62.165%. Confirmatory factor analysis demonstrated that the fit indices of the three-factor model fell within a relatively ideal level. The Cronbach's alpha coefficient of the scale was 0.885. Through convergent validity analysis, the standardized loading coefficients of the 21 items were >0.5, and the average extracted variance (AVE) of the three factors was also >0.5. Moreover, the square roots of the AVE values for each dimension exceeded the correlation coefficients between it and the other dimensions. Conclusions: The findings suggest that the post competency scale of TCM physicians undergoing standardized training can provide a reliable scientific basis for training and assessment within China.

6.
Int J Oral Sci ; 16(1): 27, 2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38548721

RESUMO

Uncovering the risk factors of pulmonary hypertension and its mechanisms is crucial for the prevention and treatment of the disease. In the current study, we showed that experimental periodontitis, which was established by ligation of molars followed by orally smearing subgingival plaques from patients with periodontitis, exacerbated hypoxia-induced pulmonary hypertension in mice. Mechanistically, periodontitis dysregulated the pulmonary microbiota by promoting ectopic colonization and enrichment of oral bacteria in the lungs, contributing to pulmonary infiltration of interferon gamma positive (IFNγ+) T cells and aggravating the progression of pulmonary hypertension. In addition, we identified Prevotella zoogleoformans as the critical periodontitis-associated bacterium driving the exacerbation of pulmonary hypertension by periodontitis, and the exacerbation was potently ameliorated by both cervical lymph node excision and IFNγ neutralizing antibodies. Our study suggests a proof of concept that the combined prevention and treatment of periodontitis and pulmonary hypertension are necessary.


Assuntos
Placa Dentária , Hipertensão Pulmonar , Periodontite , Humanos , Camundongos , Animais , Linfócitos T/patologia , Bactérias , Placa Dentária/microbiologia
7.
HLA ; 103(3): e15444, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38494882

RESUMO

HLA-DPB1*1550:01 differs from HLA-DPB1*02:02:01:01 by one nucleotide in exon 2.


Assuntos
Cadeias beta de HLA-DP , Nucleotídeos , Humanos , Alelos , Sequência de Bases , China
8.
Acad Med ; 2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38518095

RESUMO

PURPOSE: This study presents the steps taken to develop and collect initial validity evidence for the Shame Frequency Questionnaire in Medical Students. METHOD: The instrument was based on a 7-step survey design; validity evidence was collected from content, response process, internal structure, and relationship to other variables. A literature review and qualitative interviews led to the design of the initial 16-item scale. Expert review and cognitive interviewing led to minor modifications in the original structure. Initial pilot testing was conducted in August 2019 in Uniformed Services University (USU) medical students; reliability assessment and exploratory factor analysis were performed. The revised 12-item scale was tested in January 2022 in Duke University School of Medicine medical students; reliability assessment, exploratory factor analysis, and correlation analysis with depression, burnout, anxiety, emotional thriving, and emotional well-being were performed. RESULTS: A total of 336 of 678 USU students (50%) and 106 of 522 Duke students (20%) completed the survey. Initial exploratory factor analysis of the USU data revealed 1 factor (shame), and 4 items were dropped from the scale according to predefined rules. Subsequent exploratory factor analysis of the Duke data revealed 1 factor; no further items were removed according to predefined rules. Internal consistent reliability was 0.95, and all interitem correlations were less than 0.85 for USU and Duke samples. As predicted, mean shame scale scores were positively correlated with anxiety (r = 0.54, P < .001), burnout (r = 0.50, P < .001), and depression (r = 0.47, P < .001) and negatively correlated with emotional thriving (r = -0.46, P < .001) and emotional recovery (r = -0.46, P < .001). CONCLUSIONS: The Shame Frequency Questionnaire in Medical Students is a psychometrically sound instrument with strong internal reliability and multisource validity evidence, supporting its use in studying shame in medical students.

9.
Mater Today Bio ; 25: 100971, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38347936

RESUMO

Critical-size defects (CSDs) of the craniofacial bones cause aesthetic and functional complications that seriously impact the quality of life. The transplantation of human dental pulp stem cells (hDPSCs) is a promising strategy for bone tissue engineering. Chirality is commonly observed in natural biomolecules, yet its effect on stem cell differentiation is seldom studied, and little is known about the underlying mechanism. In this study, supramolecular chiral hydrogels were constructed using L/d-phenylalanine (L/D-Phe) derivatives. The results of alkaline phosphatase expression analysis, alizarin red S assay, as well as quantitative real-time polymerase chain reaction and western blot analyses suggest that right-handed D-Phe hydrogel fibers significantly promoted osteogenic differentiation of hDPSCs. A rat model of calvarial defects was created to investigate the regulation of chiral nanofibers on the osteogenic differentiation of hDPSCs in vivo. The results of the animal experiment demonstrated that the D-Phe group exhibited greater and faster bone formation on hDPSCs. The results of RNA sequencing, vinculin immunofluorescence staining, a calcium fluorescence probe assay, and western blot analysis indicated that L-Phe significantly promoted adhesion of hDPSCs, while D-Phe nanofibers enhanced osteogenic differentiation of hDPSCs by facilitating calcium entry into cells and activate the MAPK pathway. These results of chirality-dependent osteogenic differentiation offer a novel therapeutic strategy for the treatment of CSDs by optimising the differentiation of hDPSCs into chiral nanofibers.

10.
Carbohydr Polym ; 331: 121870, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38388058

RESUMO

Self-pumping wound scaffolds designed for directional biofluid transport are extensively investigated. They efficiently extract excessive biofluids from wounds, while maintaining an optimally humid wound environment, thus facilitating rapid wound healing. However, the existing designed scaffolds are insufficiently focused on stimulating the hydrophobic layer at the wound site, thereby exacerbating inflammation and impeding the wound healing process. Herein, we engineered and fabricated a hydrophilic-hydrophobic-hydrophilic sandwich-structured hydrogel-Janus nanofiber scaffold (NFS) employing a Layer-by-Layer (LbL) method. This scaffold comprises a hydrophilic carboxymethyl chitosan/silver (CMCS-Ag) hydrogel component in conjunction with a poly(caprolactone)/poly(caprolactone)-poly(citric acid)-co-ε-polylysine (PCL/PCL-PCE) Janus NFS. It is noteworthy that the hydrogel-Janus nanofiber scaffold not only demonstrates outstanding water absorption (202.2 %) and unidirectional biofluid transport capability but also possesses high breathability (308.663 m3/m2 h kPa), appropriate pore size (6.7-7.5 µm), excellent tensile performance (270 ± 10 %), and superior mechanical strength (26.36 ± 1.77 MPa). Moreover, in vitro experimentation has convincingly demonstrated the impeccable biocompatibility of hydrogel-Janus NFS. The inherent dual-antibacterial properties in CMCS-Ag and PCE significantly augment fibroblast proliferation and migration. In vivo studies further underscore its capability to expedite wound healing by absorption and expulsion of wound exudates, thereby fostering collagen deposition and vascularization. As such, this work potentially provides fresh insights into the design and fabrication of multifunctional biomimetic scaffolds, holding immense potential in the medical field for efficient wound healing.


Assuntos
Quitosana , Nanofibras , Hidrogéis/farmacologia , Hidrogéis/química , Quitosana/química , Nanofibras/química , Cicatrização , Antibacterianos , Drenagem
11.
Cell Metab ; 36(3): 557-574.e10, 2024 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-38237601

RESUMO

Augmented CD4+ T cell response in autoimmunity is characterized by extensive metabolic reprogramming. However, the epigenetic molecule that drives the metabolic adaptation of CD4+ T cells remains largely unknown. Here, we show that lysine acetyltransferase 6A (KAT6A), an epigenetic modulator that is clinically associated with autoimmunity, orchestrates the metabolic reprogramming of glucose in CD4+ T cells. KAT6A is required for the proliferation and differentiation of proinflammatory CD4+ T cell subsets in vitro, and mice with KAT6A-deficient CD4+ T cells are less susceptible to experimental autoimmune encephalomyelitis and colitis. Mechanistically, KAT6A orchestrates the abundance of histone acetylation at the chromatin where several glycolytic genes are located, thus affecting glucose metabolic reprogramming and subsequent CD4+ T cell responses. Treatment with KAT6A small-molecule inhibitors in mouse models shows high therapeutic value for targeting KAT6A in autoimmunity. Our study provides novel insights into the epigenetic programming of immunometabolism and suggests potential therapeutic targets for patients with autoimmunity.


Assuntos
Lisina Acetiltransferases , Linfócitos T , Animais , Humanos , Camundongos , Autoimunidade/genética , Linfócitos T CD4-Positivos/metabolismo , Epigênese Genética , Glucose/metabolismo , Histona Acetiltransferases/genética , Histona Acetiltransferases/metabolismo , Lisina Acetiltransferases/genética , Lisina Acetiltransferases/metabolismo , Linfócitos T/metabolismo
12.
Nat Commun ; 15(1): 807, 2024 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-38280848

RESUMO

Kupffer cells are liver resident macrophages and play critical role in fatty liver disease, yet the underlying mechanisms remain unclear. Here, we show that activation of G-protein coupled receptor 3 (GPR3) in Kupffer cells stimulates glycolysis and protects mice from obesity and fatty liver disease. GPR3 activation induces a rapid increase in glycolysis via formation of complexes between ß-arrestin2 and key glycolytic enzymes as well as sustained increase in glycolysis through transcription of glycolytic genes. In mice, GPR3 activation in Kupffer cells results in enhanced glycolysis, reduced inflammation and inhibition of high-fat diet induced obesity and liver pathogenesis. In human fatty liver biopsies, GPR3 activation increases expression of glycolytic genes and reduces expression of inflammatory genes in a population of disease-associated macrophages. These findings identify GPR3 activation as a pivotal mechanism for metabolic reprogramming of Kupffer cells and as a potential approach for treating fatty liver disease.


Assuntos
Células de Kupffer , Hepatopatia Gordurosa não Alcoólica , Humanos , Animais , Camundongos , Células de Kupffer/metabolismo , Fígado/metabolismo , Hepatopatia Gordurosa não Alcoólica/metabolismo , Glicólise , Obesidade/metabolismo , Camundongos Endogâmicos C57BL , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo
14.
ACS Appl Mater Interfaces ; 16(5): 5438-5450, 2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38112719

RESUMO

Flexible epidermal sensors hold significant potential in personalized healthcare and multifunctional electronic skins. Nonetheless, achieving both robust sensing performance and efficient antibacterial protection, especially in medical paradigms involving electrophysiological signals for wound healing and intelligent health monitoring, remains a substantial challenge. Herein, we introduce a novel flexible accelerated-wound-healing biomaterial based on a hydrogel-nanofiber scaffold (HNFS) via electrostatic spinning and gel cross-linking. We effectively engineer a multifunctional tissue nanoengineered skin scaffold for wound treatment and health monitoring. Key features of HNFS include high tensile strength (24.06 MPa) and elasticity (214.67%), flexibility, biodegradability, and antibacterial properties, enabling assembly into versatile sensors for monitoring human motion and electrophysiological signals. Moreover, in vitro and in vivo experiments demonstrate that HNFS significantly enhances cell proliferation and skin wound healing, provide a comprehensive therapeutic strategy for smart sensing and tissue repair, and guide the development of high-performance "wound healing-health monitoring" bioelectronic skin scaffolds. Therefore, this study provides insights into crafting flexible and repairable skin sensors, holding potential for multifunctional health diagnostics and intelligent medical applications in intelligent wearable health monitoring and next-generation artificial skin fields.


Assuntos
Nanofibras , Dispositivos Eletrônicos Vestíveis , Humanos , Hidrogéis/farmacologia , Cicatrização , Antibacterianos/farmacologia
15.
Front Endocrinol (Lausanne) ; 14: 1278619, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38027188

RESUMO

Background: Diabetes mellitus (DM) is associated with an increased risk of cardiovascular disease (CVD). Hence, early detection of cardiac changes by imaging is crucial to reducing cardiovascular complications. Purpose: Early detection of cardiac changes is crucial to reducing cardiovascular complications. The study aimed to detect the dynamic change in cardiac morphology, function, and diffuse myocardial fibrosis(DMF) associated with T1DM and T2DM mice models. Materials and methods: 4-week-old C57Bl/6J male mice were randomly divided into control (n=30), T1DM (n=30), and T2DM (n=30) groups. A longitudinal study was conducted every 4 weeks using serial 7.0T CMR and echocardiography imaging. Left ventricular ejection fraction (LV EF), tissue tracking parameters, and DMF were measured by cine CMR and extracellular volume fraction (ECV). Global peak circumferential strain (GCPS), peak systolic strain rate (GCPSSR) values were acquired by CMR feature tracking. LV diastolic function parameter (E/E') was acquired by echocardiography. The correlations between the ECV and cardiac function parameters were assessed by Pearson's test. Results: A total of 6 mice were included every 4 weeks in control, T1DM, and T2DM groups for analysis. Compared to control group, an increase was detected in the LV mass and E/E' ratio, while the values of GCPS, GCPSSR decreased mildly in DM. Compared to T2DM group, GCPS and GCPSSR decreased earlier in T1DM(GCPS 12W,P=0.004; GCPSSR 12W,P=0.04). ECV values showed a significant correlation with GCPS and GCPSSR in DM groups. Moreover, ECV values showed a strong positive correlation with E/E'(T1DM,r=0.757,P<0.001;T2DM, r=0.811,P<0.001). Conclusion: The combination of ECV and cardiac mechanical parameters provide imaging biomakers for pathophysiology, early diagnosis of cardiac morphology, function and early intervention in diabetic cardiomyopathy in the future.


Assuntos
Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Cardiomiopatias Diabéticas , Animais , Masculino , Camundongos , Diabetes Mellitus Experimental/diagnóstico por imagem , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/diagnóstico por imagem , Cardiomiopatias Diabéticas/diagnóstico por imagem , Cardiomiopatias Diabéticas/etiologia , Ecocardiografia , Fibrose , Estudos Longitudinais , Volume Sistólico/fisiologia , Função Ventricular Esquerda
16.
Mil Med ; 2023 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-37952196

RESUMO

INTRODUCTION: Military physicians must be prepared to lead health care teams across complex landscapes of war during future small- and large-scale combat operations. This preparation optimally begins in medical school so that early career physicians are fully ready for their first deployment. Past qualitative research has suggested that military physicians who attended civilian medical school are not as well prepared for the operational environment as physicians who attended the Uniformed Services University (USU), our nation's military medical school. However, there is a lack of larger-scale quantitative research comparing the readiness differences between the two medical school pathways. The purpose of this study, therefore, was to quantify any differences in first deployment preparation between students attending USU and civilian medical schools through the Health Professions Scholarship Program (HPSP). MATERIALS AND METHODS: We compared USU and HPSP graduates' first deployment experiences by distributing a 14-item Likert survey to active duty military physicians in the U.S. Army, U.S. Navy, and U.S. Air Force who graduated within the past 10 years from medical school (USU or civilian). RESULTS: The USU graduates rated themselves significantly higher than the HPSP graduates on their readiness for deployment (3.83 vs. 3.24; P < .001); ability to navigate the operational environment (3.59 vs. 2.99; P < .001); confidence in communicating with their commanding officer (3.59 vs. 2.99; P = .002); navigating the combined role as physician and officer (3.33 vs. 2.84; P = .004); leading a health care team (3.94 vs. 3.43; P = .001); preparation by a medical school (3.78 vs. 2.52; P < .001); and overall readiness compared to peers (4.20 vs. 3.49; P < .001). There was no significant difference between the two pathways regarding their stress level at the beginning of deployment (2.74 vs. 2.68; P = .683); clinical preparation (3.94 vs. 3.76; P = .202); and success of first deployment (3.87 vs. 3.91; P = .792). The largest effect size of the difference between the two pathways was noted on the question "How well did medical school prepare you for your first deployment" (Cohen's d = 1.02). CONCLUSIONS: While both groups believed that they were prepared for their first deployment, USU graduates consistently reported being more prepared by medical school for their first deployment than HPSP graduates. To close this readiness gap, supplemental military unique curricula may help to optimize HPSP students' readiness.

17.
J Agric Food Chem ; 71(49): 19551-19567, 2023 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-38032113

RESUMO

Liverworts provide valuable ecological services to improve the sustainability of agriculture, encompassing soil health maintenance and natural pest management. Some liverworts have potential applications in medicine and as food additives. Twenty-two novel diterpenoids (anajoerins A-V), of which anajoerins B-G are rearranged labdanes featuring an unprecedented 6/5 fused ring system, were isolated from the Chinese liverwort Anastrophyllum joergensenii Schiffn. The absolute configurations of all compounds were identified based on high-resolution electrospray ionization mass spectroscopy data, NMR spectra, and ECD calculations. Plausible biogenetic pathways for unprecedented rearranged labdanes were proposed. Seven diterpenoids exhibited anti-inflammatory activity by reducing nitric oxide production in LPS-stimulated RAW264.7 murine macrophages in a dose-dependent manner with IC50s between 9.71 and 56.56 µM. All tested compounds showed no cytotoxicity at the tested concentrations. Western blot analyses of NF-κB p65 downregulation showed that anajoerin L could inhibit the NF-κB signaling pathway. Furthermore, anajoerin L also suppressed the secretion of the ConA-induced proinflammatory cytokines IFN-γ, TNF-α, and IL-6.


Assuntos
Diterpenos , Hepatófitas , Animais , Camundongos , NF-kappa B/metabolismo , Hepatófitas/metabolismo , Células RAW 264.7 , Anti-Inflamatórios/farmacologia , Citocinas/metabolismo , China , Lipopolissacarídeos/farmacologia , Óxido Nítrico/metabolismo
18.
BMC Psychiatry ; 23(1): 805, 2023 11 03.
Artigo em Inglês | MEDLINE | ID: mdl-37924073

RESUMO

BACKGROUND: In Wilson's disease (WD) patients, network connections across the brain are disrupted, affecting multidomain function. However, the details of this neuropathophysiological mechanism remain unclear due to the rarity of WD. In this study, we aimed to investigate alterations in brain network connectivity at the whole-brain level (both intra- and inter-network) in WD patients through independent component analysis (ICA) and the relationship between alterations in these brain network functional connections (FCs) and clinical neuropsychiatric features to understand the underlying pathophysiological and central compensatory mechanisms. METHODS: Eighty-five patients with WD and age- and sex-matched 85 healthy control (HC) were recruited for resting-state functional magnetic resonance imaging (rs-fMRI) scanning. We extracted the resting-state networks (RSNs) using the ICA method, analyzed the changes of FC in these networks and the correlation between alterations in FCs and clinical neuropsychiatric features. RESULTS: Compared with HC, WD showed widespread lower connectivity within RSNs, involving default mode network (DMN), frontoparietal network (FPN), somatomotor network (SMN), dorsal attention network (DAN), especially in patients with abnormal UWDRS scores. Furthermore, the decreased FCs in the left medial prefrontal cortex (L_ MPFC), left anterior cingulate gyrus (L_ACC), precuneus (PCUN)within DMN were negatively correlated with the Unified Wilson's Disease Rating Scale-neurological characteristic examination (UWDRS-N), and the decreased FCs in the L_MPFC, PCUN within DMN were negatively correlated with the Unified Wilson's Disease Rating Scale-psychiatric symptoms examination (UWDRS-P). We additionally discovered that the patients with WD exhibited significantly stronger FC between the FPN and DMN, between the DAN and DMN, and between the FPN and DAN compared to HC. CONCLUSIONS: We have provided evidence that WD is a disease with widespread dysfunctional connectivity in resting networks in brain, leading to neurological features and psychiatric symptoms (e.g. higher-order cognitive control and motor control impairments). The alter intra- and inter-network in the brain may be the neural underpinnings for the neuropathological symptoms and the process of injury compensation in WD patients.


Assuntos
Degeneração Hepatolenticular , Humanos , Degeneração Hepatolenticular/complicações , Degeneração Hepatolenticular/diagnóstico por imagem , Mapeamento Encefálico/métodos , Encéfalo/diagnóstico por imagem , Lobo Parietal , Imageamento por Ressonância Magnética/métodos
19.
Perspect Med Educ ; 12(1): 385-398, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37840648

RESUMO

Introduction: Self-regulated learning is a cyclical process of forethought, performance, and self-reflection that has been used as an assessment tool in medical education. No prior studies have evaluated SRL processes for answering multiple-choice questions (MCQs) and most evaluated one or two iterations of a non-MCQ task. SRL assessment during MCQs may elucidate reasons why learners are successful or not on these questions that are encountered repeatedly during medical education. Methods: Internal medicine clerkship students at three institutions participated in a SRL microanalytic protocol that targeted strategic planning, metacognitive monitoring, causal attributions, and adaptive inferences across seven MCQs. Responses were transcribed and coded according to previously published methods for microanalytic protocols. Results: Forty-four students participated. In the forethought phase, students commonly endorsed prioritizing relevant features as their diagnostic strategy (n = 20, 45%) but few mentioned higher-order diagnostic reasoning processes such as integrating clinical information (n = 5, 11%) or comparing/contrasting diagnoses (n = 0, 0%). However, in the performance phase, students' metacognitive processes included high frequencies of integration (n = 38, 86%) and comparing/contrasting (n = 24, 55%). In the self-reflection phase, 93% (n = 41) of students faulted their management reasoning and 84% (n = 37) made negative references to their abilities. Less than 10% (n = 4) of students indicated that they would adapt their diagnostic reasoning process for these questions. Discussion: This study describes in detail student self-regulatory processes during MCQs. We found that students engaged in higher-order diagnostic reasoning processes but were not explicit about it and seldom reflected critically on these processes after selecting an incorrect answer. Self-reflections focused almost exclusively on management reasoning and negative references to abilities which may decrease self-efficacy. Encouraging students to identify and evaluate diagnostic reasoning processes and make attributions to controllable factors may improve performance.


Assuntos
Educação de Graduação em Medicina , Educação Médica , Estudantes de Medicina , Humanos , Estudantes de Medicina/psicologia , Educação de Graduação em Medicina/métodos , Aprendizagem , Avaliação Educacional/métodos
20.
Transplant Proc ; 55(9): 2232-2240, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37777366

RESUMO

The study aims to lessen the monetary burden on patients and society by decreasing the price of proprietary drugs used in leukemia therapy. Flow cytometry, reverse transcription polymerase chain reaction, western blot, and a patient-derived xenograft mouse model were used to confirm the therapeutic effect of Pinellia ternata extract on leukemia. Three types of leukemia cells (K562, HL-60, and C8166 cell lines) were found to undergo early apoptosis (P ≤ .05) after being exposed to P. ternata extract, as measured by flow cytometry. Reverse transcription polymerase chain reaction results showed that P. ternata extract at both middle (300 µg/mL) and high (500 µg/mL) concentrations was able to down-regulate Bcl-2 and upregulate mRNA expression of Bax and caspase-3. In the patient-derived xenograft mouse model formed by BALB/c-nu/nu nude mice, immunohistochemistry indicated that P. ternata extract effectively suppressed the proliferation of leukemia cells. Therefore, P. ternata extract at 300 µg/mL and 500 µg/mL could effectively inhibit myeloid and lymphocytic leukemia cell proliferation and promote leukemia cell apoptosis by regulating Bax/Bcl-2 and caspase-3.


Assuntos
Leucemia , Pinellia , Humanos , Camundongos , Animais , Caspase 3/genética , Caspase 3/metabolismo , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismo , Pinellia/metabolismo , Camundongos Nus , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/farmacologia , Apoptose , Leucemia/tratamento farmacológico , Proliferação de Células
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