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1.
Cell ; 186(10): 2193-2207.e19, 2023 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-37098343

RESUMO

Somatic hypermutation (SHM), initiated by activation-induced cytidine deaminase (AID), generates mutations in the antibody-coding sequence to allow affinity maturation. Why these mutations intrinsically focus on the three nonconsecutive complementarity-determining regions (CDRs) remains enigmatic. Here, we found that predisposition mutagenesis depends on the single-strand (ss) DNA substrate flexibility determined by the mesoscale sequence surrounding AID deaminase motifs. Mesoscale DNA sequences containing flexible pyrimidine-pyrimidine bases bind effectively to the positively charged surface patches of AID, resulting in preferential deamination activities. The CDR hypermutability is mimicable in in vitro deaminase assays and is evolutionarily conserved among species using SHM as a major diversification strategy. We demonstrated that mesoscale sequence alterations tune the in vivo mutability and promote mutations in an otherwise cold region in mice. Our results show a non-coding role of antibody-coding sequence in directing hypermutation, paving the way for the synthetic design of humanized animal models for optimal antibody discovery and explaining the AID mutagenesis pattern in lymphoma.


Assuntos
Citidina Desaminase , Hipermutação Somática de Imunoglobulina , Animais , Camundongos , Anticorpos/genética , Citidina Desaminase/genética , Citidina Desaminase/metabolismo , DNA/genética , DNA de Cadeia Simples , Mutação , Evolução Molecular , Regiões Determinantes de Complementaridade/genética , Motivos de Nucleotídeos
2.
EMBO J ; 41(11): e109324, 2022 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-35471583

RESUMO

In activated B cells, activation-induced cytidine deaminase (AID) generates programmed DNA lesions required for antibody class switch recombination (CSR), which may also threaten genome integrity. AID dynamically shuttles between cytoplasm and nucleus, and the majority stays in the cytoplasm due to active nuclear export mediated by its C-terminal peptide. In immunodeficient-patient cells expressing mutant AID lacking its C-terminus, a catalytically active AID-delC protein accumulates in the nucleus but nevertheless fails to support CSR. To resolve this apparent paradox, we dissected the function of AID-delC proteins in the CSR process and found that they cannot efficiently target antibody genes. We demonstrate that AID-delC proteins form condensates both in vivo and in vitro, dependent on its N-terminus and on a surface arginine-rich patch. Co-expression of AID-delC and wild-type AID leads to an unbalanced nuclear AID-delC/AID ratio, with AID-delC proteins able to trap wild-type AID in condensates, resulting in a dominant-negative phenotype that could contribute to immunodeficiency. The co-condensation model of mutant and wild-type proteins could be an alternative explanation for the dominant-negative effect in genetic disorders.


Assuntos
Citidina Desaminase , Switching de Imunoglobulina , Linfócitos B , Citidina Desaminase/genética , Citidina Desaminase/metabolismo , DNA/metabolismo , Humanos , Switching de Imunoglobulina/genética
3.
J Transl Med ; 22(1): 98, 2024 01 23.
Artigo em Inglês | MEDLINE | ID: mdl-38263117

RESUMO

BACKGROUND: Interindividual variation characterizes the relief experienced by constipation-predominant irritable bowel syndrome (IBS-C) patients following linaclotide treatment. Complex bidirectional interactions occur between the gut microbiota and various clinical drugs. To date, no established evidence has elucidated the interactions between the gut microbiota and linaclotide. We aimed to explore the impact of linaclotide on the gut microbiota and identify critical bacterial genera that might participate in linaclotide efficacy. METHODS: IBS-C patients were administered a daily linaclotide dose of 290 µg over six weeks, and their symptoms were then recorded during a four-week posttreatment observational period. Pre- and posttreatment fecal samples were collected for 16S rRNA sequencing to assess alterations in the gut microbiota composition. Additionally, targeted metabolomics analysis was performed for the measurement of short-chain fatty acid (SCFA) concentrations. RESULTS: Approximately 43.3% of patients met the FDA responder endpoint after taking linaclotide for 6 weeks, and 85% of patients reported some relief from abdominal pain and constipation. Linaclotide considerably modified the gut microbiome and SCFA metabolism. Notably, the higher efficacy of linaclotide was associated with enrichment of the Blautia genus, and the abundance of Blautia after linaclotide treatment was higher than that in healthy volunteers. Intriguingly, a positive correlation was found for the Blautia abundance and SCFA concentrations with improvements in clinical symptoms among IBS-C patients. CONCLUSION: The gut microbiota, especially the genus Blautia, may serve as a significant predictive microbe for symptom relief in IBS-C patients receiving linaclotide treatment. TRIAL REGISTRATION: This trial was registered with the Chinese Clinical Trial Registry (Chictr.org.cn, ChiCTR1900027934).


Assuntos
Microbioma Gastrointestinal , Síndrome do Intestino Irritável , Peptídeos , Humanos , Estudos Prospectivos , RNA Ribossômico 16S , Constipação Intestinal
4.
Gastrointest Endosc ; 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38851456

RESUMO

BACKGROUND AND AIMS: Despite the benefits of artificial intelligence in small-bowel (SB) capsule endoscopy (CE) image reading, information on its application in the stomach and SB CE is lacking. METHODS: In this multicenter, retrospective diagnostic study, gastric imaging data were added to the deep learning-based SmartScan (SS), which has been described previously. A total of 1069 magnetically controlled GI CE examinations (comprising 2,672,542 gastric images) were used in the training phase for recognizing gastric pathologies, producing a new artificial intelligence algorithm named SS Plus. A total of 342 fully automated, magnetically controlled CE examinations were included in the validation phase. The performance of both senior and junior endoscopists with both the SS Plus-assisted reading (SSP-AR) and conventional reading (CR) modes was assessed. RESULTS: SS Plus was designed to recognize 5 types of gastric lesions and 17 types of SB lesions. SS Plus reduced the number of CE images required for review to 873.90 (median, 1000; interquartile range [IQR], 814.50-1000) versus 44,322.73 (median, 42,393; IQR, 31,722.75-54,971.25) for CR. Furthermore, with SSP-AR, endoscopists took 9.54 minutes (median, 8.51; IQR, 6.05-13.13) to complete the CE video reading. In the 342 CE videos, SS Plus identified 411 gastric and 422 SB lesions, whereas 400 gastric and 368 intestinal lesions were detected with CR. Moreover, junior endoscopists remarkably improved their CE image reading ability with SSP-AR. CONCLUSIONS: Our study shows that the newly upgraded deep learning-based algorithm SS Plus can detect GI lesions and help improve the diagnostic performance of junior endoscopists in interpreting CE videos.

5.
Br J Nutr ; 132(2): 162-168, 2024 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-38679919

RESUMO

Inflammation is involved in the pathogenesis of stroke and depression. We aimed to investigate the association between the dietary inflammatory index (DII) and depression in American adults with stroke. Adults with stroke were enrolled in the National Health and Nutrition Examination Survey between 2005 and 2018 in the USA. The DII was obtained from a 24-h dietary recall interview for each individual. Multivariate regression and restricted cubic spline analyses were conducted to evaluate the association between DII and depression in adults with stroke. The mean age of the 1239 participants was 63·85 years (50·20 % women), and the prevalence of depression was 18·26 %. DII showed a linear and positive association with severe depression in adults with stroke (OR 1·359; 95 % CI 1·021, 1·810; P for non-linearity = 0·493). Compared with those in the lowest tertile of the DII, adults with stroke in the third tertile of the DII had a 3·222-fold higher risk of severe depression (OR 3·222; 95 % CI 1·150, 9·026). In the stratified analyses, the association between DII score and severe depression was more significant in older adults (P for interaction = 0·010) but NS with respect to sex (P for interaction = 0·184) or smoking status (P for interaction = 0·396). No significant association was found between DII and moderate-to-moderately severe depression in adults with stroke. In conclusion, an increase in DII score was associated with a higher likelihood of severe depression in older adults with stroke.


Assuntos
Depressão , Dieta , Inflamação , Inquéritos Nutricionais , Acidente Vascular Cerebral , Humanos , Feminino , Masculino , Estudos Transversais , Idoso , Acidente Vascular Cerebral/complicações , Pessoa de Meia-Idade , Fatores de Risco , Estados Unidos/epidemiologia , Prevalência
6.
Acta Pharmacol Sin ; 45(7): 1366-1380, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38538717

RESUMO

Parkinson's disease (PD) is the second most common neurodegenerative disease, and its prevalence is increasing. Currently, no effective therapies for PD exist. Marine-derived natural compounds are considered important resources for the discovery of new drugs due to their distinctive structures and diverse activities. In this study, tetrahydroauroglaucin (TAG), a polyketide isolated from a marine sponge, was found to have notable neuroprotective effects on MPTP/MPP+-induced neurotoxicity. RNA sequencing analysis and metabolomics revealed that TAG significantly improved lipid metabolism disorder in PD models. Further investigation indicated that TAG markedly decreased the accumulation of lipid droplets (LDs), downregulated the expression of RUBCN, and promoted autophagic flux. Moreover, conditional knockdown of Rubcn notably attenuated PD-like symptoms and the accumulation of LDs, accompanied by blockade of the neuroprotective effect of TAG. Collectively, our results first indicated that TAG, a promising PD therapeutic candidate, could suppress the accumulation of LDs through the RUBCN-autophagy pathway, which highlighted a novel and effective strategy for PD treatment.


Assuntos
Metabolismo dos Lipídeos , Fármacos Neuroprotetores , Animais , Metabolismo dos Lipídeos/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Homeostase/efeitos dos fármacos , Poríferos/química , Camundongos , Camundongos Endogâmicos C57BL , Autofagia/efeitos dos fármacos , Masculino , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/metabolismo , Policetídeos/farmacologia , Humanos
7.
Int Rev Psychiatry ; 36(1-2): 69-79, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38557343

RESUMO

A common challenge people face in today's cross-cultural world is how to solve a series of adaptation problems caused by cultural conflict. Exploring Bruce Lee's successful cross-cultural experiences through psychobiography offers some inspiration and thoughts. How did Bruce Lee successfully integrate martial arts, symbolising the Eastern culture, with films representing the Western culture, finally propelling kung fu films onto the international stage? Numerous publicly available materials about Bruce Lee were collected for this study, and the research data were evaluated using thematic analysis. Bruce Lee's success benefitted from reconstructing cultural environment information and exercising his initiative to shape a new cultural environment. His life experiences reflect individual cognition behaviour and social and cultural environments as two aspects of a dynamic circulation system and show that the two have reached internal and spiralling harmony through mutual integration. In the context of the Oriental collectivism culture's family narrative, Chinese adults' personality development features the unique theme of 'inheritance and innovation'. Dealing with the relationship between self-actualisation and familism is another important and challenging task in developing the Chinese personality.


Assuntos
Comparação Transcultural , Personalidade , Adulto , Humanos , Povo Asiático , Motivação , Desenvolvimento da Personalidade
8.
BMC Nurs ; 23(1): 364, 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38822273

RESUMO

BACKGROUNDS: Personal growth initiative (PGI) is regarded as a meaningful concept with potential value at both the individual and organizational levels, but little is known about the factors that contribute to nurses' PGI. This study aimed to explore how proactive personality and hospital work environment affect PGI of clinical nurses. METHODS: A cross-sectional study was conducted between September and October 2022 among 4414 nurses from 10 tertiary general hospitals in 10 cities in Sichuan, China, using a two-stage sampling method. Self-reported anonymous online questionnaires, such as sociodemographic information survey, personal growth initiative scale II, the 10-item proactive personality scale, and practice environment scale-nursing work index were used to collect data. Multiple hierarchical regression analyses were performed to examine research hypotheses. RESULTS: Among the control variables in this study, nurses' self-perceptions of general health status and professional title positively predicted PGI (ß = 0.462, 95%CI = 0.272-0.653; ß = 1.078, 95%CI = 0.508-1.648). After adding control variables, both proactive personality (ß = 1.143, 95%CI = 1.096-1.190) and work environment (ß = 3.391, 95%CI = 2.904-3.879) positively predicted PGI. The work environment positively moderated the association between proactive personality and PGI (ß = 0.108, 95%CI = 0.025-0.191). These predictors jointly explained 50.3% of the variance in PGI. CONCLUSIONS: Nurses with a greater tendency to have a typical proactive personality have higher levels of personal growth initiative, and this positive effect will be better highlighted in a healthier work environment. Nursing managers should prioritize the employment of people with proactive personality traits, focus on the development and stimulation of proactive personality traits in nurses, and establish a supportive work environment to maximize the personal growth initiative of nurses.

9.
Clin Endocrinol (Oxf) ; 99(4): 361-369, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37528510

RESUMO

OBJECTIVE: To explore the efficacy and safety of the 'Walk with you' application for titrating basal insulin (BI) doses in type-2 diabetes mellitus (T2DM) hospitalised patients. METHODS: This was a randomised, single-centre, open-label, controlled clinical trial to compare the changes in fasting blood glucose (FBG) and postprandial blood glucose (PBG), time to reach target FBG (FBG-TRT), incidence of hypoglycaemia events and FBG coefficient of variation in the application group (weight-based titration of BI dose regimen) and control group (typical adjustment regimen). PATIENTS: This study selected 173 patients with T2DM using basal-prandial insulin therapy who were admitted to Binhaiwan Central Hospital of Dongguan between December 2021 and December 2022. Patients were randomised to the control group or the application group (App group) and then titrated to achieve an FBG concentration of less than 7.0 mmol/L. RESULTS: There were 86 patients in the control group and 87 patients in the App group. The FBG concentrations in the control and App groups were decreased by 6.77 ± 4.75 and 5.95 ± 4.06 mmol/L, respectively. The FBG-TRTs in the control and App groups were 3.80 ± 1.52 and 2.82 ± 1.34 days, respectively (p < .001). Fewer patients in the control group reached the FBG-TRT within 3 days than in the App group, with 46.5% and 71.3% of patients reaching that target, respectively. There was no significant between-group difference in hypoglycaemia incidence. CONCLUSION: The use of this weight-based insulin dose titration protocol for BI app is effective and safe for achieving the target FBG in noncritically ill patients with T2DM and is free, easy to use and user friendly.


Assuntos
Diabetes Mellitus Tipo 2 , Hipoglicemia , Insulina , Smartphone , Humanos , Glicemia , Jejum , Hipoglicemia/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Insulina/administração & dosagem , Resultado do Tratamento
10.
Epidemiol Infect ; 151: e128, 2023 05 19.
Artigo em Inglês | MEDLINE | ID: mdl-37202367

RESUMO

To develop a machine learning model and nomogram to predict the probability of persistent virus shedding (PVS) in hospitalized patients with coronavirus disease 2019 (COVID-19), the clinical symptoms and signs, laboratory parameters, cytokines, and immune cell data of 429 patients with nonsevere COVID-19 were retrospectively reviewed. Two models were developed using the Akaike information criterion (AIC). The performance of these two models was analyzed and compared by the receiver operating characteristic (ROC) curve, calibration curve, net reclassification index (NRI), and integrated discrimination improvement (IDI). The final model included the following independent predictors of PVS: sex, C-reactive protein (CRP) level, interleukin-6 (IL-6) level, the neutrophil-lymphocyte ratio (NLR), monocyte count (MC), albumin (ALB) level, and serum potassium level. The model performed well in both the internal validation (corrected C-statistic = 0.748, corrected Brier score = 0.201) and external validation datasets (corrected C-statistic = 0.793, corrected Brier score = 0.190). The internal calibration was very good (corrected slope = 0.910). The model developed in this study showed high discriminant performance in predicting PVS in nonsevere COVID-19 patients. Because of the availability and accessibility of the model, the nomogram designed in this study could provide a useful prognostic tool for clinicians and medical decision-makers.


Assuntos
COVID-19 , Pacientes Internados , Humanos , Aprendizado de Máquina , Nomogramas , Regras de Decisão Clínica
11.
Nurs Crit Care ; 28(6): 893-901, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37644760

RESUMO

BACKGROUND: With the aging population and the ongoing pandemic, older persons account for a large proportion of ICU admissions. Despite numerous studies on the impact of COVID-19 on older persons, there has been a small body of research investigating nursing practice with critically ill older patients admitted to ICU for COVID-19. AIMS: To explore current challenges in the nursing care of older persons with severe COVID-19 through the experience of frontline nurses. STUDY DESIGN: A qualitative descriptive design was used. In-depth and semi-structured interviews with 18 ICU nurses were conducted to explore the experience of providing care for older persons with severe COVID-19 in the Omicron wave. A content analysis approach was adopted to analyse qualitative data. FINDINGS: Three themes emerged as follows: (1) no plan survives first contact with the enemy, (2) expectations versus Reality and (3) difficulty in providing holistic care. CONCLUSIONS: Challenges could be encountered in different stages of providing care for older persons with severe COVID-19, including the preparation and training of knowledge and skills in the early stage, the challenges posed by old age in the diagnostic and treatment stage and the challenges of psychological care and rehabilitation care. RELEVANCE TO CLINICAL PRACTICE: With the regular prevention and control of COVID-19, our study provides guidance for establishing measures (training courses of ICU nurses) to improve the nursing quality of older persons with severe COVID-19.


Assuntos
COVID-19 , Cuidados de Enfermagem , Humanos , Idoso , Idoso de 80 Anos ou mais , COVID-19/epidemiologia , Unidades de Terapia Intensiva , Envelhecimento , Hospitalização , Pesquisa Qualitativa
12.
BMC Public Health ; 22(1): 1679, 2022 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-36064340

RESUMO

BACKGROUND: Health promotion behaviors are key determinant of health and well-being, and also play an important role in promoting successful aging. This study investigated levels of engagement in health promotion behaviors among Chinese rural older adults, and explored effects of perceived health competence, health education activities experience and sociodemographic variables on health promotion behavior in this population. METHODS: A multicenter cross-sectional survey was performed. Participants were recruited by a multistage, stratified, cluster-sampling procedure from Nanbu County, Sichuan Province, China. All participants completed four paper questionnaires: sociodemographic characteristics and health care status survey, the Chinese version of the health promoting lifestyle profile-II (HPLP-II), perceived health competence scale and Lubben social network scale. Data were collected from July to August 2021. Stepwise multiple linear regression analysis was performed to analyze the effects of different factors on health promotion behaviors. RESULTS: A total of 425 rural older adults with an average age of 72.7 years were included in analysis. The overall average score of HPLP-II was 101.6. The stepwise multiple linear regression analysis results showed that those who had higher perceived health competence (ß = 0.66, P < 0.001), experienced health education activities (ß = 0.254, P < 0.001), had physical examination (ß = 0.107, P < 0.001), was married (ß = 0.189, P < 0.001), had primary school education or above (ß = 0.189, P < 0.001), and had a per capita monthly household income of more than 1000¥ (ß = 0.085, P = 0.007), have higher levels of engagement in health promotion behaviors; while the level of health promotion behaviors of the older adults living alone was lower than that of living with their spouse or others (ß = -0.192, P < 0.001). Combination of the above variables accounted for a total of 69.1% of the variance in health promotion behaviors. CONCLUSIONS: The level of health promotion behaviors among Chinese rural older adults is low. Perceived health competence and health education activities experience are two strong determinants of health promotion behaviors. Comprehensive health promotion programs aimed at improving perceived health competences and health literacy through health education activities may be an important part of optimizing the level of health promotion behaviors among rural older adults.


Assuntos
Educação em Saúde , Estilo de Vida Saudável , Idoso , Estudos Transversais , Promoção da Saúde , Nível de Saúde , Humanos , Inquéritos e Questionários
13.
Psychogeriatrics ; 22(3): 308-316, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35104921

RESUMO

BACKGROUND: Identification of cognition status and its associated factors permit targeted interventions. This study aimed to: (i) investigate cognitive function of Chinese older adults using a large, nationally representative cohort; and (ii) explore its associated factors from aspects of socio-demographic, health behaviour, physical and mental health. METHODS: Data on 2665 adults aged 65 and older from the China Health and Retirement Longitudinal Study wave 4 in 2018 were analyzed. Information on self-reported cognition status, socio-demographic characteristics, health behaviour, physical and mental health status were obtained. Hierarchical regression analyses were conducted to explore associated factors. RESULTS: The cognition score was 24.8, with 41.1% of Chinese older adults identified as cognitively impaired. Better cognition was associated with being married, more education, living in a city/town or urban-rural integration zone, moderate night-time sleep (5-9 h) and post-lunch napping (less than 90 min), moderate/light physical activity for 30 min to 2 h every day, socially active and good health status; while worse cognition was associated with older age, intensive physical activity every day and more than 4 h a day, greater dependency in activities of daily living and depression. CONCLUSIONS: Cognitive impairment is a common health problem in Chinese older adults. Its associated factors are multifaceted, including socio-demographic characteristics, health behaviour and physical and mental health status. Developing interventions focused on these factors may be an important part of optimising cognition in these populations.


Assuntos
Disfunção Cognitiva , Aposentadoria , Atividades Cotidianas , Idoso , China/epidemiologia , Cognição , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/epidemiologia , Humanos , Estudos Longitudinais
14.
Dig Dis Sci ; 66(6): 1928-1939, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-32648079

RESUMO

BACKGROUND: The hyper-accumulation of extracellular matrix (ECM) is the leading cause of hepatic fibrosis, and TGF-ß-induced activation of hepatic stellate cells (HSCs) is the central event of hepatic fibrosis pathogenesis. The deregulation and dysfunction of miRNAs in hepatic fibrosis have been reported previously. AIMS: To identify miRNA(s) playing a role in HSC activation and the underlying mechanism. METHODS: We analyzed online microarray expression datasets from Gene Expression Omnibus (GEO) for differentially expressed miRNAs in hepatic fibrosis-related disease liver tissues, examined the specific effects of the candidate miRNA on TGF-ß-induced HSC activation, and screened for the targets of the candidate miRNA in the TGF-ß/SMAD signaling. Then, the predicted miRNA-mRNA binding, the specific effects of the target mRNA, and the dynamic effects of miRNA and mRNA on TGF-ß-induced HSC activation were investigated. RESULTS: The miR-503 expression was upregulated in TGF-ß-activated HSCs. miR-503 overexpression enhanced, while miR-503 inhibition attenuated TGF-ß-induced HSC proliferation and ECM accumulation in HSCs. miR-503 targeted SMAD7 to inhibit SMAD7 expression. SMAD7 knockdown also aggravated TGF-ß-induced HSC proliferation and ECM accumulation in HSCs. The effects of miR-503 overexpression on TGF-ß-induced HSC activation were partially reversed by SMAD7 overexpression. In CCl4-induced hepatic fibrosis model in rats, miR-503 overexpression aggravated, whereas SMAD7 overexpression improved CCl4-induced fibrotic changes in rats' liver tissues. The effects of miR-503 overexpression on CCl4-induced fibrotic changes were partially reversed by SMAD7 overexpression. CONCLUSION: miR-503 acts on HSC activation and hepatic fibrosis through SMAD7. The miR-503/SMAD7 axis enhances HSC activation and hepatic fibrosis through the TGF-ß/SMAD pathway.


Assuntos
Células Estreladas do Fígado/metabolismo , Cirrose Hepática/metabolismo , MicroRNAs/biossíntese , Proteína Smad7/biossíntese , Animais , Tetracloreto de Carbono/toxicidade , Células Estreladas do Fígado/patologia , Humanos , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/genética , Cirrose Hepática/patologia , MicroRNAs/genética , Ratos , Ratos Sprague-Dawley , Proteína Smad7/genética
15.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 43(6): 886-891, 2021 Dec 30.
Artigo em Zh | MEDLINE | ID: mdl-34980327

RESUMO

Objective To explore the feasibility of using ultrasound to evaluate stent placement for managing graft stenosis after Meso-rex bypass for cavernous transformation of the portal vein in adults. Methods This study enrolled the patients who underwent Meso-rex bypass due to cavernous transformation of the portal vein,were diagnosed graft stenosis by postoperative ultrasound,and then underwent percutaneous portal vein puncture portography and stent placement.We then compared the ultrasonic measurement indicators and sonographic manifestations before and after stent placement,and evaluated the alleviation of portal hypertension symptoms after stent placement and related clinical indexes. Results Finally,8 patients were enrolled in this study,including 5 males and 3 females,with an average age of(32.4±14.7)years.The median duration of follow-up was 26 months after stent placement.The mean diameter of graft stenosis was(2.74±0.23)mm after Meso-rex bypass and became wider[(7.23±0.68)mm]after stent placement(P=0.000).The mean maximum velocity at graft stenosis was(195.88±30.83)cm/s after Meso-rex bypass and became lower[(72.75±29.94)cm/s]after stent placement(P=0.000).The color Doppler flow imaging at graft stenosis presented colorful blood flow,and presented regular near laminar flow within the stent and characteristic reverse flow within the left portal vein after stent placement.No gastrointestinal bleeding or ascites occurred after interventional therapy,and the mean thickness of spleen decreased from 6.0 cm before stent placement to 5.4 cm(P=0.018).After stent placement,the platelet count increased from(51.57±18.83)×109/L to(149.00±58.96)×109/L(P=0.002),and the serum ammonia level decreased from(66.25±21.78)µmol/L to(44.88±10.60)µmol/L(P=0.012). Conclusions Ultrasound can accurately assess graft patency before and after stent placement in patients with stenosis after Meso-rex bypass,and effectively monitor the hemodynamic changes in the portal venous system.The clinical symptoms can be relieved after interventional therapy.


Assuntos
Hipertensão Portal , Derivação Portossistêmica Cirúrgica , Adolescente , Adulto , Constrição Patológica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Veia Porta/diagnóstico por imagem , Veia Porta/cirurgia , Stents , Resultado do Tratamento , Adulto Jovem
16.
J Neuroinflammation ; 17(1): 105, 2020 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-32252767

RESUMO

BACKGROUND: Senescent astrocytes have been implicated in the aging brain and neurodegenerative disorders, including Parkinson's disease (PD). Astragaloside IV (AS-IV) is an antioxidant derivative from a traditional Chinese herbal medicine Astragalus membraneaceus Bunge and exerts anti-inflammatory and longevity effects and neuroprotective activities. However, its effect on astrocyte senescence in PD remains to be defined. METHODS: Long culture-induced replicative senescence model and lipopolysaccharide/1-methyl-4-phenylpyridinium (LPS/MPP+)-induced premature senescence model and a mouse model of PD were used to investigate the effect of AS-IV on astrocyte senescence in vivo and in vitro. Immunocytochemistry, qPCR, subcellular fractionation, flow cytometric analyses, and immunohistochemistry were subsequently conducted to determine the effects of AS-IV on senescence markers. RESULTS: We found that AS-IV inhibited the astrocyte replicative senescence and LPS/MPP+-induced premature senescence, evidenced by decreased senescence-associated ß-galactosidase activity and expression of senescence marker p16, and increased nuclear level of lamin B1, and reduced pro-inflammatory senescence-associated secretory phenotype. More importantly, we showed that AS-IV protected against the loss of dopamine neurons and behavioral deficits in the mouse model of PD, which companied by reduced accumulation of senescent astrocytes in substantia nigra compacta. Mechanistically, AS-IV promoted mitophagy, which reduced damaged mitochondria accumulation and mitochondrial reactive oxygen species generation and then contributed to the suppression of astrocyte senescence. The inhibition of autophagy abolished the suppressive effects of AS-IV on astrocyte senescence. CONCLUSIONS: Our findings reveal that AS-IV prevents dopaminergic neurodegeneration in PD via inhibition of astrocyte senescence through promoting mitophagy and suggest that AS-IV is a promising therapeutic strategy for the treatment of age-associated neurodegenerative diseases such as PD.


Assuntos
Astrócitos/efeitos dos fármacos , Senescência Celular/efeitos dos fármacos , Neurônios Dopaminérgicos/efeitos dos fármacos , Transtornos Parkinsonianos/patologia , Saponinas/farmacologia , Triterpenos/farmacologia , Animais , Astrócitos/patologia , Neurônios Dopaminérgicos/patologia , Masculino , Camundongos , Degeneração Neural/patologia , Fármacos Neuroprotetores/farmacologia
17.
J Adv Nurs ; 76(5): 1172-1181, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32026506

RESUMO

AIMS: To examine the effects of a tailored telehealth educational intervention on medication adherence and disease activity in discharged patients with rheumatoid arthritis (RA). DESIGN: An un-blinded randomized controlled trial. METHODS: A total of 92 eligible patients were recruited from January 2015-December 2015. Participants were randomly assigned to either the intervention (N = 46) or control group (N = 46). The intervention group received four educational sessions delivered through a telephone across a 12-week intervention. The content of the education mainly included: subject's knowledge about disease; treatment goals; the importance of taking medication correctly; side effect management; remembering to take medication. The control group received only standard care including discharge instructions. Outcome measures included medication adherence and disease activity. RESULTS: The intervention group had significantly higher medication adherence compared with the control group at 12th and 24th week. There was no significant difference between two groups in disease activity at 12th and 24th week. CONCLUSIONS: The telephone-delivered tailored educational intervention effectively improved medication adherence among discharged patients with rheumatoid arthritis. However, no significant benefits of the intervention on disease activity were detected. IMPACT: Good medication adherence in rheumatoid arthritis patients contributes to controlling symptom and inflammation, preventing the progressive structural damage. This study demonstrated that the telehealth educational intervention could improve patients' medication adherence but did not have a direct impact on clinical condition in the short-term. The intervention for discharged patients with rheumatoid arthritis can be integrated into the clinical setting by the nursing staff as follow-up care. TRIAL REGISTRATION NUMBER: ChiCTR-IPR-14005722.


Assuntos
Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/fisiopatologia , Adesão à Medicação/psicologia , Adesão à Medicação/estatística & dados numéricos , Educação de Pacientes como Assunto/métodos , Telemedicina/métodos , Adulto , Idoso , China , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Telefone
19.
Gastrointest Endosc ; 88(3): 543-546, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29704471

RESUMO

BACKGROUND AND AIMS: Esophageal stricture is a common adverse event after endoscopic submucosal dissection (ESD) when it involves the entire circumference of the esophagus. We aimed to assess the effectiveness and safety of endoscopic transplantation of autologous esophageal mucosa in preventing stricture formation after circumferential ESD. METHODS: Nine patients who underwent circumferential ESD for early esophageal cancer were enrolled. After the patients underwent ESD, autologous esophageal mucosal patches were attached to the ulcer surface by using hemoclips and were then fixed with a covered metal mesh stent. The stent was removed 7 days after the procedure. The patients were followed up with endoscopy at scheduled times. RESULTS: Epithelialization occurred within a median of 7.1 days, with a graft survival rate of 96.5%. Strictures occurred at a mean of 24.7 days (range 18-34 days) after the procedure. The median number of endoscopic balloon dilatation sessions was 2.7 (range 0-6). CONCLUSIONS: Transplantation of autologous esophageal mucosa could be a safe way of relieving the severity of esophageal stricture after circumferential ESD.


Assuntos
Ressecção Endoscópica de Mucosa/efeitos adversos , Mucosa Esofágica/transplante , Neoplasias Esofágicas/cirurgia , Estenose Esofágica/prevenção & controle , Transplante Autólogo , Adulto , Idoso , Idoso de 80 Anos ou mais , Dilatação , Neoplasias Esofágicas/patologia , Estenose Esofágica/etiologia , Estenose Esofágica/terapia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reepitelização , Stents , Telas Cirúrgicas
20.
Am J Emerg Med ; 36(9): 1627-1630, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29502976

RESUMO

BACKGROUND: Real-time ultrasound elastography (RTE) is used to examine liver fibrosis and benign and malignant lesions, but its use for the diagnosis of liver trauma has not been examined. The purpose of this study was to examine the use of RTE for the evaluation of differential penetrating liver trauma in a rabbit model. MATERIAL AND METHODS: Eighty New Zealand rabbits were divided into 2 groups. In one group, a single incision (type "-" lesion) was made, and in the other group a hash mark incision (type "#" lesion) was made (about 0.5cm in depth; 1.0-2.0cm in length). RTE was performed at 10, 30, and 60min after injury. RESULTS: There were no differences in mean RTE scores between the 2 types of lesions at 10 and 30min. However, the mean values for the 2 types of lesions increased from 10min to 60min (type '-' lesion: 0.88±0.32 to 2.06±0.88; type '#' lesion: 0.89±0.34 to 2.63±1.16). At 60min, the mean elasticity score in the type '#' lesion group was significantly higher than in the type '-' lesion group (P<.001). Strain ratios were not different between the groups at each time point, but in each group the values decreased from the 10min time point to the 60min time point (P-value for the trends, <.001). CONCLUSIONS: RTE may be able to distinguish mild or severe penetrating liver trauma at 60min or more after injury.


Assuntos
Técnicas de Imagem por Elasticidade/métodos , Fígado/lesões , Ferimentos Penetrantes/diagnóstico por imagem , Animais , Masculino , Coelhos , Estresse Mecânico , Fatores de Tempo , Vasodilatação/fisiologia , Ferimentos Penetrantes/fisiopatologia
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