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1.
Diabetes Obes Metab ; 26(5): 1897-1907, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38379430

RESUMO

AIM: The objective of this study is to evaluate the mean body mass index (BMI), general obesity and abdominal obesity in adults aged ≥40 years residing in China in 2020, and to analyse variations in these factors across different geographic areas and subpopulations. METHODS: We utilized data from the National Stroke High-Risk Population Screening programme to calculate and compare the mean BMI and prevalence of obesity across various demographics, including sex, age, urban-rural locality, geographical region (province) and ethnicity status. RESULTS: In our study, we found that the standardized mean BMI level was 24.65 kg/m2 [95% confidence interval (CI): 24.50-22.84] in men and 24.31 kg/m2 (95% CI: 24.15-24.45) in women. Using the criteria from China, we found that the standardized prevalence of general obesity and abdominal obesity was 13.13% (95% CI: 13.05-13.21%) and 33.03% (95 CI: 32.92-33.14%), respectively. Our study also identified significant effects of age, sex, urban-rural locality, province and ethnicity status on the prevalence of obesity. Overall, our study estimated that in 2020, approximately 91.1 million adults aged ≥40 years in China were obese (46.5 million men and 44.6 million women), while 229.2 million adults (110.4 million men and 118.8 million women) were diagnosed with abdominal obesity. CONCLUSION: Our research has revealed compelling new evidence about the obesity epidemic among Chinese adults aged ≥40 years, particularly at the provincial and ethnic levels. As a result, more targeted and effective prevention strategies should be developed to alleviate the burden of obesity.


Assuntos
Etnicidade , Obesidade Abdominal , Adulto , Idoso , Pessoa de Meia-Idade , Masculino , Humanos , Feminino , Obesidade Abdominal/epidemiologia , Prevalência , Obesidade/epidemiologia , Índice de Massa Corporal , China/epidemiologia
2.
Chin Med Sci J ; 39(2): 144-148, 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-38915216

RESUMO

Peking Union Medical College (PUMC) launched the "4+4" Medical Doctor (MD) pilot program in 2018, admitting students with non-medical backgrounds from top universities, aligning with national medical talent training policies to foster diverse and eager learners in medicine. On the occasion of the graduation of the first class of the "4+4" MD pilot class at PUMC in 2023, we reviewed the teaching reform in the pilot program and carried out a systematic survey and interviews with students, faculties, and management staff of the pilot class. This article reports on the measures taken by the pilot class at PUMC in enrollment and curriculum setting, and demonstrates the achievements of the pilot class in terms of student academic background structure, knowledge acquisition and skill learning, scientific research ability, and course evaluation. The results indicated that the pilot class had met the national demand for the "Medicine + X" talent training model. More specifically, with a diverse academic backgrounds, the pilot class graduates had academic levels comparable to the eight-year medical education graduates, and their scientific research abilities were satisfactory. The pilot program at PUMC will optimize the curriculum setting, strengthen the construction of faculty, learning resources, and teaching facilities, and reform the academic evaluation methods, thus deepening the reform of medical education and improving the "4+4" MD program as a novel medical education model.


Assuntos
Currículo , Humanos , Projetos Piloto , Educação Médica , Estudantes de Medicina , Médicos , Faculdades de Medicina/organização & administração
3.
J Nat Prod ; 86(10): 2348-2359, 2023 10 27.
Artigo em Inglês | MEDLINE | ID: mdl-37737089

RESUMO

Eleven diterpenoids, wulfenioidins D-N (1-11), classified into five distinct carbon skeletons with one unreported framework, and four modified abietane diterpenoids were isolated from the whole plant of Orthosiphon wulfenioides. The structures and absolute configurations were characterized by spectroscopic methods, single-crystal X-ray diffraction, and electronic circular dichroism analyses. Compounds 3 and 5 exhibited activity against Zika virus (ZIKV) with EC50 values of 8.07 and 8.50 µM, respectively, and showed no significant cytotoxicity toward Vero cells at 100 µM. Western blot and immunofluorescence experiments showed that compounds 3 and 5 interfered with the replication of the ZIKV by inhibiting the expression of the ZIKV envelope (E) protein.


Assuntos
Diterpenos , Orthosiphon , Infecção por Zika virus , Zika virus , Animais , Chlorocebus aethiops , Células Vero , Diterpenos/química , Estrutura Molecular
4.
Bioorg Chem ; 136: 106534, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37068364

RESUMO

Wulfenioidones A - K (1-11) were abietane diterpenoids with highly oxidized 6/6/6 aromatic tricyclic skeleton isolated from the whole plant of Orthosiphon wulfenioides, and their planar structures and absolute configurations were elucidated by spectroscopic data interpretation, electronic circular dichroism calculation as well as X-ray crystallography analysis. Bioactivity screening indicated that compounds 1-4, 6 and 8 exhibited lactate dehydrogenase (LDH) inhibition effect with IC50 values ranging from 0.23 to 3.43 µM by preventing the mononuclear macrophage cell pyroptosis induced by double signal stimulation of LPS and nigericin. Western Blot analyses of Caspase-1 and IL-1ß down-regulation exhibited that compound 1 could selectively inhibit NLRP3 inflammasome, and the cell morphological observation further supported that compound 1 prevented macrophage cell pyroptosis.


Assuntos
Inflamassomos , Orthosiphon , Proteína 3 que Contém Domínio de Pirina da Família NLR , Abietanos/farmacologia , Abietanos/química , Macrófagos
5.
Chem Biodivers ; 20(12): e202301676, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37971960

RESUMO

Three new compounds callicarpenoids A-C (1-3), were isolated from the stems of Callicarpa arborea Roxb together with fifteen known compounds (4-18). The structures of these compounds were elucidated using advanced spectroscopic techniques, including 1D and 2D NMR, UV, IR, HR-ESI-MS, ECD, ORD, and quantum chemical calculations. Compound 3, a rare rearranged diterpenoid with a fused 5/6-ring system demonstrated strong potential as an inhibitor of the NLRP3 inflammasome activation with an IC50 value of 3.153 µM. It effectively reduced GSDMD-NT production, inhibited caspase-1 activation, and suppressed IL-1ß secretion, thereby mitigating NLRP3 inflammasome-induced pyroptosis in J774A.1 cells. These findings suggest that compound 3 warrants further research and development as a promising NLRP3 inflammasome inhibitor.


Assuntos
Callicarpa , Diterpenos Clerodânicos , Inflamassomos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Diterpenos Clerodânicos/farmacologia , Callicarpa/química , Espectroscopia de Ressonância Magnética
6.
Chem Biodivers ; 20(12): e202301628, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37964626

RESUMO

Two new prostaglandin-like compounds callicarboric acids A-B (1-2), along with six known compounds (3-8) were isolated from the stems of Callicarpa arborea Roxb. Their structures were determined with the help of modern spectroscopic techniques such as NMR, UV, IR, HR-ESI-MS, ECD, and ORD with the assistance of quantum chemical calculations. Compound 1 exhibited remarkable anti-NLRP3 inflammasome activation potential, demonstrating an IC50 value of 0.74 µM. Additionally, by reducing GSDMD-NT production, inhibiting caspase-1 activation, and suppressing IL-1ß secretion, it effectively mitigated NLRP3 inflammasome-induced pyroptosis in J774A.1 cells. These findings indicate that compound 1 possesses the capability to be a valuable candidate for further research and development as an NLRP3 inflammasome inhibitor.


Assuntos
Callicarpa , Inflamassomos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Prostaglandinas/farmacologia , Piroptose
7.
Hum Mol Genet ; 29(11): 1784-1796, 2020 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-31261376

RESUMO

The neuromuscular junction (NMJ) is a synapse between motoneurons and skeletal muscles to control motor behavior. Acetylcholine receptors (AChRs) are restricted at the synaptic region for proper neurotransmission. Mutations in the mitochondrial CHCHD10 protein have been identified in multiple neuromuscular disorders; however, the physiological roles of CHCHD10 at NMJs remain elusive. Here, we report that CHCHD10 is highly expressed at the postsynapse of NMJs in skeletal muscles. Muscle conditional knockout CHCHD10 mice showed motor defects, abnormal neuromuscular transmission and NMJ structure. Mechanistically, we found that mitochondrial CHCHD10 is required for ATP production, which facilitates AChR expression and promotes agrin-induced AChR clustering. Importantly, ATP could effectively rescue the reduction of AChR clusters in the CHCHD10-ablated muscles. Our study elucidates a novel physiological role of CHCHD10 at the peripheral synapse. It suggests that mitochondria dysfunction contributes to neuromuscular pathogenesis.


Assuntos
Proteínas Mitocondriais/genética , Músculo Esquelético/metabolismo , Doenças da Junção Neuromuscular/genética , Receptores Colinérgicos/genética , Agrina/farmacologia , Animais , Modelos Animais de Doenças , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Camundongos , Camundongos Knockout , Mitocôndrias/genética , Neurônios Motores/metabolismo , Músculo Esquelético/patologia , Junção Neuromuscular/efeitos dos fármacos , Junção Neuromuscular/genética , Sinapses/genética , Transmissão Sináptica/genética
8.
Neurol Sci ; 43(1): 677-682, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34480243

RESUMO

OBJECTIVE: To evaluate whether shorter door-to-needle times (DNT) with intravenous tissue plasminogen activator (tPA) for acute ischemic stroke are associated with improved 1-year outcomes in Chinese patients. METHODS: From August to September 2019, all first-ever ischemic stroke patients who were treated with intravenous tPA within 4.5 h of the time they were last known to be well from 232 hospitals in China were included. Patients were divided into four groups according to DNT time (≤ 45 min; 45-60 min; 60-90 min; > 90 min). All discharged patients would receive a telephone follow-up at 12-month after admission. Death and disability events were recorded. RESULTS: Finally, 2370 patients were analyzed. The median age was 65 years, 66.6% were male, and 2.4% were of ethnic minorities. In the 1-year follow-up, 211 patients died (8.9%; 95%CI: 7.8-10.0%). The patients (53.1%) had DNT times of longer than 45 min, compared with those treated within 45 min, did not have significantly higher 1-year mortality (8.9% vs 8.9% [absolute difference, 0.03% {95% CI, - 0.05% to - 0.10%}, odd ratio {OR}, 1.00 {95% CI, 0.75 to 1.33}]). In addition, 385 patients (16.2%; 14.8-17.3%) out of those survivors had disability events. The patients had DNT times of longer than 45 min, compared with those treated within 45 min, did not have significantly higher 1-year disability rate (18.9% vs 16.7% [absolute difference, 1.9% {95% CI, 1.1% to 3.0%}, odd ratio {OR}, 1.22 {95% CI, 0.89 to 1.43}]). CONCLUSIONS: The results did not show that shorter DNT for tPA administration was significantly associated with better 1-year outcomes.


Assuntos
Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Idoso , Isquemia Encefálica/complicações , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/epidemiologia , Minorias Étnicas e Raciais , Fibrinolíticos/uso terapêutico , Humanos , Masculino , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/epidemiologia , Terapia Trombolítica , Tempo para o Tratamento , Ativador de Plasminogênio Tecidual/uso terapêutico , Resultado do Tratamento
9.
Aging Clin Exp Res ; 34(5): 1159-1163, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-34727357

RESUMO

China is undergoing great social changes, and its demographic makeup is shifting every year along with those changes. China released key indicators from the seventh national population census on 12 May 2021. The total population of China's mainland increased to 1.41178 billion in 2020 from 1.33972 billion in 2010 (sixth national population census) with an average annual growth rate of 0.53%. In the past 10 years, the share of the population aged above 60 and 65 years increased by 5.44% (from 13.26% in 2010 to 18.70% in 2020) and 4.6% (from 8.9 to 13.5%), respectively. The share of the population with a college education or above rose from 8.93% in 2010 to 15.47% in 2020, and the illiteracy rate dropped from 4.08% in 2010 to 2.67% in 2020. In the next decade, China is likely to face many changes, including the increasing proportion of older adults in the population, declining births, and economic transformation. In an effort to respond to the changed demographic landscape, the authorities should adopt new laws and strategies to improve government services for older adults and consider ways to support women and families and make childbearing more attractive to and feasible for women.


Assuntos
Censos , Países em Desenvolvimento , Idoso , Envelhecimento , China , Demografia , Feminino , Humanos , Dinâmica Populacional
10.
Liver Int ; 41(5): 956-968, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33346937

RESUMO

BACKGROUND & AIMS: Differentiation antagonizing non-protein coding RNA is associated with various types of neoplasms. Hepatitis C virus-related hepatocellular carcinoma has a high risk of recurrence. Here we determined the role of differentiation antagonizing non-protein coding RNA in hepatitis C virus-related hepatocarcinogenesis and identified potential therapeutic targets and non-invasive prognostic markers for long-term outcome of hepatitis C virus-related hepatocellular carcinoma after surgical resection. METHODS: Differentiation antagonizing non-protein coding RNAs relevant to hepatitis C virus-related hepatocellular carcinoma were identified through comparative RNA-sequencing of tumour and adjacent non-tumour (ANT) tissues in a screening set, and were validated using real-time polymerase chain reaction. Target long non-coding RNAs (lncRNAs) in tissues and serum exosomes were used to predict the recurrence of hepatitis C virus-related hepatocellular carcinoma after curative surgical resection in a large application cohort from 2005 to 2012. RESULTS: We confirmed that differentiation antagonizing non-protein coding RNA was upregulated following hepatitis C virus infection and identified as the lncRNA most relevant to hepatitis C virus-related hepatocellular carcinoma in tumour tissues as compared to that in ANT tissues. In 183 hepatitis C virus-related hepatocellular carcinoma patients followed for 10 years after curative HCC resection, the expression level of circulating exosomal differentiation antagonizing non-protein coding RNA was positively associated with HCC recurrence and was the most predictive factor associated with HCC recurrence and mortality (hazard ratio/95% confidence intervals: 7.0/4.3-11.6 and 2.7/1.5-5.1 respectively). CONCLUSIONS: Differentiation antagonizing non-protein coding RNA is highly relevant to disease progression of hepatitis C virus-related hepatocellular carcinoma. Our finding indicated that circulating exosomal differentiation antagonizing non-protein coding RNA might serve as a non-invasive prognostic biomarker for hepatitis C virus-related hepatocellular carcinoma.


Assuntos
Carcinoma Hepatocelular , Exossomos , Neoplasias Hepáticas , RNA Longo não Codificante , Carcinoma Hepatocelular/genética , Exossomos/genética , Regulação Neoplásica da Expressão Gênica , Hepacivirus/genética , Humanos , Neoplasias Hepáticas/genética , Recidiva Local de Neoplasia , RNA Longo não Codificante/genética
11.
Zhongguo Dang Dai Er Ke Za Zhi ; 23(6): 593-598, 2021 Jun.
Artigo em Zh | MEDLINE | ID: mdl-34130781

RESUMO

OBJECTIVE: To evaluate the clinical features of preterm infants with a birth weight less than 1 500 g undergoing different intensities of resuscitation. METHODS: A retrospective analysis was performed for the preterm infants with a birth weight less than 1 500 g and a gestational age less than 32 weeks who were treated in the neonatal intensive care unit of 20 hospitals in Jiangsu, China from January 2018 to December 2019. According to the intensity of resuscitation in the delivery room, the infants were divided into three groups:non-tracheal intubation (n=1 184), tracheal intubation (n=166), and extensive cardiopulmonary resuscitation (ECPR; n=116). The three groups were compared in terms of general information and clinical outcomes. RESULTS: Compared with the non-tracheal intubation group, the tracheal intubation and ECPR groups had significantly lower rates of cesarean section and use of antenatal corticosteroid (P < 0.05). As the intensity of resuscitation increased, the Apgar scores at 1 minute and 5 minutes gradually decreased (P < 0.05), and the proportion of infants with Apgar scores of 0 to 3 at 1 minute and 5 minutes gradually increased (P < 0.05). Compared with the non-tracheal intubation group, the tracheal intubation and ECPR groups had significantly higher mortality rate and incidence rates of moderate-severe bronchopulmonary dysplasia and serious complications (P < 0.05). The incidence rates of grade Ⅲ-Ⅳ intracranial hemorrhage and retinopathy of prematurity (stage Ⅲ or above) in the tracheal intubation group were significantly higher than those in the non-tracheal intubation group (P < 0.05). CONCLUSIONS: For preterm infants with a birth weight less than 1 500 g, the higher intensity of resuscitation in the delivery room is related to lower rate of antenatal corticosteroid therapy, lower gestational age, and lower birth weight. The infants undergoing tracheal intubation or ECRP in the delivery room have an increased incidence rate of adverse clinical outcomes. This suggests that it is important to improve the quality of perinatal management and delivery room resuscitation to improve the prognosis of the infants.


Assuntos
Cesárea , Recém-Nascido Prematuro , Peso ao Nascer , China , Feminino , Idade Gestacional , Humanos , Lactente , Recém-Nascido , Gravidez , Estudos Retrospectivos
12.
Clin Infect Dis ; 71(15): 748-755, 2020 07 28.
Artigo em Inglês | MEDLINE | ID: mdl-32239127

RESUMO

BACKGROUND: In December 2019, a series of pneumonia cases of unknown cause emerged in Wuhan, Hubei, China. In this study, we investigate the clinical and laboratory features and short-term outcomes of patients with coronavirus disease 2019 (COVID-19). METHODS: All patients with COVID-19 admitted to Wuhan University Zhongnan Hospital in Wuhan, China, between 3 January and 1 February 2020 were included. All those patients were with laboratory-confirmed infections. Epidemiological, clinical, and radiological characteristics; underlying diseases; laboratory tests; treatments; complications; and outcomes data were collected. Outcomes were followed up at discharge until 15 February 2020. RESULTS: The study cohort included 102 adult patients. The median age was 54 years (interquartile ranger, 37-67 years), and 48.0% were female. A total of 34 patients (33.3%) were exposed to a source of transmission in the hospital setting (as health-care workers, patients, or visitors) and 10 patients (9.8%) had a familial cluster. There were 18 patients (17.6%) who were admitted to the intensive care unit (ICU), and 17 patients died (mortality, 16.7%; 95% confidence interval, 9.4-23.9%). Those patients who survived were younger, were more likely to be health-care workers, and were less likely to suffer from comorbidities. They were also less likely to suffer from complications. There was no difference in drug treatment rates between the survival and nonsurvival groups. Those patients who survived were less likely to require admission to the ICU (14.1% vs 35.3% of those admitted). Chest imaging examinations showed that patients who died were more likely to have ground-glass opacity (41.2% vs 12.9% in survivors). CONCLUSIONS: The mortality rate was high among the COVID-19 patients described in our cohort who met our criteria for inclusion in this analysis. The patient characteristics seen more frequently in those who died were the development of systemic complications following onset of the illness and a severity of disease requiring admission to the ICU. Our data support those described by others indicating that COVID-19 infection results from human-to-human transmission, including familial clustering of cases, and from nosocomial transmission. There were no differences in mortality among those who did or did not receive antimicrobial or glucocorticoid drug treatments.


Assuntos
Infecções por Coronavirus/mortalidade , Pneumonia Viral/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Antivirais/uso terapêutico , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/patogenicidade , COVID-19 , China , Estudos de Coortes , Comorbidade , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/transmissão , Feminino , Hospitalização , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/transmissão , SARS-CoV-2
13.
BMC Immunol ; 21(1): 22, 2020 04 21.
Artigo em Inglês | MEDLINE | ID: mdl-32316916

RESUMO

BACKGROUND: Cancer cells subvert natural immunosuppression by upregulating the expression of checkpoint proteins and their ligands. For example, tumor cells expressing programmed death-ligand 1 (PD-L1) induce immune cell tolerance to cancers, thereby facilitating tumor progression. The recent clinical success of immunotherapy, particularly checkpoint blockade, represents a significant advance in cancer therapy. However, many cancers develop resistance to immunotherapies, and the underlying mechanisms and how these might be exploited to overcome resistance still need to be determined. METHODS: T cell dysfunction, in part caused by chronic T cell receptor stimulation, diminishes the capacity for durable responses to checkpoint blockade. Furthermore, T cell populations are phenotypically and functionally heterogeneous, resulting in varying responses to checkpoint blockade. Recent molecular studies of T cell heterogeneity have shown that checkpoint blockade on its own does not alter the epigenetic landscape of T cells, despite epigenetic changes governing T cell phenotype. CONCLUSION: Here we argue that epigenetic modifiers can be used to prime and sensitize T cells to immunotherapy. Administering epitherapy in conjunction with checkpoint blockade could decrease T cell exhaustion and immunotherapy resistance in many cancer types.


Assuntos
Epigênese Genética/imunologia , Inibidores de Checkpoint Imunológico/imunologia , Linfócitos T/imunologia , Animais , Antígeno B7-H1/imunologia , Humanos , Imunoterapia/métodos , Neoplasias/imunologia , Neoplasias/terapia
14.
J Virol ; 93(10)2019 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-30814289

RESUMO

Infection by enteroviruses can cause severe neurological complications in humans. The interactions between the enteroviral and host proteins may facilitate the virus replication and be involved in the pathogenicity of infected individuals. It has been shown that human enteroviruses possess various mechanisms to suppress host innate immune responses in infected cells. Previous studies showed that infection by enterovirus 71 (EV71) causes the degradation of MDA5, which is a critical cytoplasmic pathogen sensor in the recognition of picornaviruses for initiating transcription of type I interferons. In the present study, we demonstrated that the RNA-dependent RNA polymerase (RdRP; also denoted 3Dpol) encoded by EV71 interacts with the caspase activation and recruitment domains (CARDs) of MDA5 and plays a role in the inhibition of MDA5-mediated beta interferon (IFN-ß) promoter activation and mRNA expression. In addition, we found that the 3Dpol protein encoded by coxsackievirus B3 also interacted with MDA5 and downregulated the antiviral signaling initiated by MDA5. These findings indicate that enteroviral RdRP may function as an antagonist against the host antiviral innate immune response.IMPORTANCE Infection by enteroviruses causes severe neurological complications in humans. Human enteroviruses possess various mechanisms to suppress the host type I interferon (IFN) response in infected cells to establish viral replication. In the present study, we found that the enteroviral 3Dpol protein (or RdRP), which is a viral RNA-dependent RNA polymerase for replicating viral RNA, plays a role in the inhibition of MDA5-mediated beta interferon (IFN-ß) promoter activation. We further demonstrated that enteroviral 3Dpol protein interacts with the caspase activation and recruitment domains (CARDs) of MDA5. These findings indicate that enteroviral RdRP functions as an antagonist against the host antiviral response.


Assuntos
Enterovirus Humano A/metabolismo , Helicase IFIH1 Induzida por Interferon/metabolismo , RNA Polimerase Dependente de RNA/metabolismo , Domínio de Ativação e Recrutamento de Caspases/genética , Domínio de Ativação e Recrutamento de Caspases/fisiologia , Enterovirus/genética , Enterovirus/metabolismo , Enterovirus Humano A/genética , Enterovirus Humano B/metabolismo , Infecções por Enterovirus/virologia , Células HEK293 , Interações Hospedeiro-Patógeno , Humanos , Imunidade Inata , Interferon Tipo I/metabolismo , Helicase IFIH1 Induzida por Interferon/genética , Interferon beta/metabolismo , Interferons/metabolismo , Interferons/fisiologia , RNA Viral/genética , RNA Polimerase Dependente de RNA/genética , Transdução de Sinais , Replicação Viral
15.
Cardiovasc Diabetol ; 19(1): 125, 2020 08 08.
Artigo em Inglês | MEDLINE | ID: mdl-32771014

RESUMO

BACKGROUND: Adiponectin plays role in multiple metabolic pathways. Previous studies in cardiovascular disease evaluated the association between adiponectin and clinical outcomes, yielding conflicting results. The aim of this study was to investigate the association of adiponectin with major adverse cardiovascular and cerebrovascular events (MACCE) and mortality in Chinese patients with first-ever acute ischemic stroke (AIS). METHODS: This was a prospective, multicenter cohort study. From September 2009 through October 2015, all patients with AIS from 3 stroke centers in Shandong were included. Serum levels of adiponectin at admission were tested. The prognostic role of adiponectin to predict the MACCE and mortality within 3 years was evaluated by multivariable-adjusted Cox proportional hazards models. RESULTS: This study included 4274 patients (median age 68 years [interquartile ranges {IQR}: 61-76]; 53.2% men). There were 794 deaths and 899 MACCE events. Higher serum levels of adiponectin on admission were found in patients with MACCE events and nonsurvivors (P < 0.001 and P < 0.001). In multivariable models adjusted for factors that confirmed in the univariate model, elevated serum levels of adiponectin were associated with a higher risk of MACCE (Quartile[Q]4 vs. Q1, Hazard ratio[HR] = 4.95 [95% confidence interval {CI}: 3.03-7.06]) and mortality (Q4 vs. Q1, HR = 5.63 [95% CI 3.15-7.99]). Adiponectin improved the prognostic value of the National Institutes of Health Stroke Scale (NIHSS) to predict MACCE (combined areas under the curve [AUC], 0.76; 95% CI 0.68-0.88; P = 0.001) and mortality (0.78[0.69-0.91]; P < 0.01). Subgroups analysis indicated that the prognostic role of adiponectin was more pronounced in women and patients with high levels of N-terminal-pro B-type natriuretic peptide(NT-pro BNP) (P < 0.001 and P < 0.001). CONCLUSIONS: Elevated serum levels of adiponectin were associated with a higher risk of MACCE and mortality independent of traditional risk factors in ischemic stroke patients.


Assuntos
Adiponectina/sangue , AVC Isquêmico/sangue , Idoso , Biomarcadores/sangue , Causas de Morte , China/epidemiologia , Progressão da Doença , Feminino , Humanos , AVC Isquêmico/diagnóstico , AVC Isquêmico/mortalidade , Masculino , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/sangue , Admissão do Paciente , Fragmentos de Peptídeos/sangue , Prognóstico , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Regulação para Cima
16.
PLoS Genet ; 13(4): e1006744, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-28426667

RESUMO

Degeneration and loss of lower motor neurons is the major pathological hallmark of spinal muscular atrophy (SMA), resulting from low levels of ubiquitously-expressed survival motor neuron (SMN) protein. One remarkable, yet unresolved, feature of SMA is that not all motor neurons are equally affected, with some populations displaying a robust resistance to the disease. Here, we demonstrate that selective vulnerability of distinct motor neuron pools arises from fundamental modifications to their basal molecular profiles. Comparative gene expression profiling of motor neurons innervating the extensor digitorum longus (disease-resistant), gastrocnemius (intermediate vulnerability), and tibialis anterior (vulnerable) muscles in mice revealed that disease susceptibility correlates strongly with a modified bioenergetic profile. Targeting of identified bioenergetic pathways by enhancing mitochondrial biogenesis rescued motor axon defects in SMA zebrafish. Moreover, targeting of a single bioenergetic protein, phosphoglycerate kinase 1 (Pgk1), was found to modulate motor neuron vulnerability in vivo. Knockdown of pgk1 alone was sufficient to partially mimic the SMA phenotype in wild-type zebrafish. Conversely, Pgk1 overexpression, or treatment with terazosin (an FDA-approved small molecule that binds and activates Pgk1), rescued motor axon phenotypes in SMA zebrafish. We conclude that global bioenergetics pathways can be therapeutically manipulated to ameliorate SMA motor neuron phenotypes in vivo.


Assuntos
Neurônios Motores/metabolismo , Atrofia Muscular Espinal/metabolismo , Fosfoglicerato Quinase/genética , Medula Espinal/metabolismo , Proteína 1 de Sobrevivência do Neurônio Motor/genética , Trifosfato de Adenosina/metabolismo , Animais , Axônios/metabolismo , Axônios/patologia , Modelos Animais de Doenças , Suscetibilidade a Doenças , Metabolismo Energético , Regulação da Expressão Gênica no Desenvolvimento , Humanos , Camundongos , Mitocôndrias/metabolismo , Neurônios Motores/efeitos dos fármacos , Músculo Esquelético/metabolismo , Músculo Esquelético/patologia , Atrofia Muscular Espinal/genética , Atrofia Muscular Espinal/fisiopatologia , Fosfoglicerato Quinase/antagonistas & inibidores , Prazosina/administração & dosagem , Prazosina/análogos & derivados , Medula Espinal/crescimento & desenvolvimento , Medula Espinal/patologia , Proteína 1 de Sobrevivência do Neurônio Motor/metabolismo , Peixe-Zebra/genética , Peixe-Zebra/crescimento & desenvolvimento
17.
Pain Med ; 20(12): 2459-2471, 2019 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-30953590

RESUMO

Objectives The aim of our study was to ascertain the underlying role of microRNAs (miRNAs) in human intervertebral disc degeneration (IDD). Design Bioinformatic analysis from multiple databases. Methods Studies of the association of miRNAs and IDD were identified in multiple electronic databases. All potential studies were assessed by the same inclusion and exclusion criteria. We recorded whether miRNA expression was commonly increased or suppressed in the intervertebral disc tissues and cells of IDD subjects. We used String to identify biological process and cellular component pathways of differentially expressed genes. Results We included fifty-seven articles from 1,277 records in this study. This report identified 40 different dysregulated miRNAs in 53 studies, including studies examining cell apoptosis (26 studies, 49.06%), cell proliferation (15 studies, 28.3%), extracellular matrix (ECM) degradation (10 studies, 18.86%), and inflammation (five studies, 9.43%) in IDD patients. Three upregulated miRNAs (miR-19b, miR-32, miR-130b) and three downregulated miRNAs (miR-31, miR-124a, miR-127-5p) were considered common miRNAs in IDD tissues. The top three biological process pathways for upregulated miRNAs were positive regulation of biological process, nervous system development, and negative regulation of biological process, and the top three biological process pathways for downregulated miRNAs were negative regulation of gene expression, intracellular signal transduction, and negative regulation of biological process. Conclusions This study revealed that miRNAs could be novel targets for preventing IDD and treating patients with IDD by regulating their target genes. These results provide valuable information for medical professionals, IDD patients, and health care policy makers.


Assuntos
Degeneração do Disco Intervertebral/genética , MicroRNAs/genética , Apoptose/genética , Proliferação de Células/genética , Biologia Computacional , Regulação para Baixo , Matriz Extracelular/metabolismo , Regulação da Expressão Gênica/genética , Humanos , Inflamação/genética , Transdução de Sinais , Regulação para Cima
18.
BMC Anesthesiol ; 19(1): 7, 2019 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-30630421

RESUMO

BACKGROUND: This study aimed at developing and validating a scoring model to stratify critically ill patients after cardiac surgery based on risk for dysphagia, a common but often neglected complication. METHODS: Data were prospectively collected and analyzed from January 2016 to June 2017 from 395 consecutive post cardiac surgery patients at the cardiac care unit (CCU) at a single center; 103 (26.1%) developed dysphagia. Univariate and multivariate logistic analyses were used to identify independent predictors for dysphagia. The survival nomogram was developed on the basis of a multivariable Cox model, which allowed us to obtain survival probability estimations. The predictive performance of the nomogram was verified for discrimination and calibration. Areas under receiver operating characteristic curve analysis were used to illustrate and evaluate the diagnostic performance of the novel model. RESULTS: The final novel scoring model, named SSG-OD, consists of three independent factors: gastric intubation (OR = 1.024, 95% CI 1.015-1.033), sedative drug use duration (OR = 1.031, 95% CI 1.001-1.063) and stroke or not (OR = 6.182, 95% CI 3.028-12.617). SSG-OD identified patients at risk for dysphagia with sensitivity of 68.5% and specificity of 89.0% (OR = 0.833, 95% CI: 0.782-0.884). The positive and negative likelihood ratios were 6.22 and 0.35. CONCLUSIONS: The novel SSG-OD scoring system to risk stratify CCU patients for dysphagia is an easy-to-use bedside prognostication aid with good predictive performance and the potential to reduce aspiration incidence and accelerate recovery.


Assuntos
Procedimentos Cirúrgicos Cardíacos/métodos , Estado Terminal , Transtornos de Deglutição/epidemiologia , Complicações Pós-Operatórias/epidemiologia , Idoso , Estudos de Coortes , Transtornos de Deglutição/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nomogramas , Valor Preditivo dos Testes , Estudos Prospectivos , Sensibilidade e Especificidade
19.
Emerg Infect Dis ; 24(6): 1147-1149, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29774853

RESUMO

A highly pathogenic avian influenza A(H5N6) virus of clade 2.3.4.4 was detected in a domestic duck found dead in Taiwan during February 2017. The endemic situation and continued evolution of various reassortant highly pathogenic avian influenza viruses in Taiwan warrant concern about further reassortment and a fifth wave of intercontinental spread.


Assuntos
Genótipo , Vírus da Influenza A/classificação , Vírus da Influenza A/genética , Influenza Aviária/epidemiologia , Influenza Aviária/virologia , Influenza Humana/epidemiologia , Influenza Humana/virologia , Vírus Reordenados , Animais , Aves , História do Século XXI , Humanos , Vírus da Influenza A/patogenicidade , Influenza Humana/história , RNA Viral , Taiwan/epidemiologia
20.
Emerg Infect Dis ; 24(4): 782-785, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29553328

RESUMO

A putative new lyssavirus was found in 2 Japanese pipistrelles (Pipistrellus abramus) in Taiwan in 2016 and 2017. The concatenated coding regions of the virus showed 62.9%-75.1% nucleotide identities to the other 16 species of lyssavirus, suggesting that it may be representative of a new species of this virus.


Assuntos
Lyssavirus , Infecções por Rhabdoviridae/epidemiologia , Infecções por Rhabdoviridae/virologia , Genes Virais , Genoma Viral , Humanos , Lyssavirus/classificação , Lyssavirus/genética , Lyssavirus/isolamento & purificação , Filogenia , Taiwan/epidemiologia
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