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1.
BMC Med ; 22(1): 303, 2024 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-39026251

RESUMO

BACKGROUND: To systematically analyze differences in atherosclerotic cardiovascular disease (ASCVD) burden between young and older adults. METHODS: We estimated the prevalence, mortality, and disability-adjusted life years (DALYs) of ASCVD, including ischemic heart disease (IHD), ischemic stroke (IS), and peripheral artery disease (PAD), in individuals aged 20-54 and > 55 years from 1990-2019, utilizing data from the 2019 Global Burden of Disease Study. The annual percentage changes (EAPCs) for age-specific prevalence, mortality, or DALY rates were calculated to quantify the temporal trends of ASCVD burden. We also analyzed population attribution fractions (PAF) of premature ASCVD mortality and DALYs for different risk factors and compared the burden of extremely premature, premature, and non-premature ASCVD cases based on clinical classifications. RESULTS: From 1990-2019, the global prevalence rates of IHD, IS, and PAD in the 20-54 years age group increased by 20.55% (from 694.74 to 837.49 per 100,000 population), 11.50% (from 439.48 to 490.03 per 100,000 population), and 7.38% (from 384.24 to 412.59 per 100,000 population), respectively. Conversely, the ASCVD prevalence in > 55years age group decreased. Adverse outcome burdens, including mortality and DALYs, varied among ASCVD subtypes. The decrease in the mortality/DALY burden of IHD and IS was lower in the 20-54 years group than in the > 55 years group. For PAD, DALYs among those aged 20-54 increased but decreased among those aged > 55 years. When grouped according to socio-demographic index (SDI) values, lower SDI regions exhibited a higher proportion of young ASCVD burden. The prevalence of young IHD, IS, and PAD in low SDI regions reached 20.70%, 40.05%, and 19.31% in 2019, respectively, compared with 12.14%, 16.32%, and 9.54%, respectively, in high SDI regions. Metabolic risks were the primary contributors to the ASCVD burden in both age groups. Increased susceptibility to ambient particulate matter pollution and inadequate control of high body-mass index and high fasting plasma glucose in young individuals may partially explain the differing temporal trends between young and older individuals. CONCLUSIONS: The ASCVD burden in young individuals may become a growing global health concern, especially in areas with lower socioeconomic development levels that require more effective primary prevention strategies.


Assuntos
Aterosclerose , Carga Global da Doença , Humanos , Pessoa de Meia-Idade , Adulto , Feminino , Masculino , Adulto Jovem , Prevalência , Carga Global da Doença/tendências , Aterosclerose/epidemiologia , Idoso , Fatores de Risco , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/mortalidade , Fatores Etários , Anos de Vida Ajustados por Deficiência/tendências , Doença Arterial Periférica/epidemiologia
2.
Diabetes Obes Metab ; 26(2): 548-556, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37860884

RESUMO

AIMS: To evaluate the impact of a dual glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist tirzepatide (TZP), and its potential dose-response effect, on heart rate. METHODS: Articles were searched from PubMed, Web of Science, Embase, Cochrane Library, and clinical trials registries (ClinicalTrials.gov) databases. Randomized controlled trials (RCTs) comparing TZP at doses of 5, 10 and 15 mg in adults with type 2 diabetes were included. Six study arms were summarized from original research (TZP 5, 10 and 15 mg, GLP-1 receptor agonists [GLP-1RAs], insulin, placebo). The GLP-1RA and non-GLP-1RA groups were combined to form a control group. Two reviewers independently extracted data and assessed the quality of each study. Mean differences (MDs) were calculated as effect estimates for continuous outcomes. Pairwise meta-analyses and network meta-analyses were conducted. The study protocol was prospectively registered (PROSPERO ID: CRD42023418551). RESULTS: Eight articles were included in this systematic review and meta-analysis. The mean baseline heart rate ranged from 65.2 to 75.7 beats per minute. Pairwise meta-analysis showed that, compared with combined the control group, there were significantly greater increases in heart rates in the TZP group (MD 1.82, 95% confidence interval [CI] 0.75, 2.89). Similar significant rises were identified when comparing TZP with GLP-1RAs and non-GLP-1RAs (GLP-1 RAs: MD 2.29, 95% CI 1.00, 3.59; non-GLP-1RAs: MD 1.58, 95% CI 0.26, 2.91). TZP 5 mg was associated with smaller increases in heart rates compared to TZP 10 mg and TZP 15 mg (TZP 10 mg: MD -0.97, 95% CI -1.79, -0.14; TZP 15 mg: MD -2.57, 95% CI -3.79, -1.35). TZP 10 mg increased heart rate less than TZP 15 mg (MD -1.5, 95% CI -2.38, -0.82). Network meta-analysis indicated that TZP 15 mg was associated with significant increases in heart rate compared with TZP 5 mg (MD 2.53, 95% CI 1.43, 3.62), TZP 10 mg (MD 1.44, 95% CI 0.35, 2.53), GLP-1RAs (MD 3.46, 95% CI 1.67, 5.25), insulin (MD 2.86, 95% CI 1.32, 4.41) and placebo (MD 2.96, 95% CI 1.36, 4.57). CONCLUSIONS: Our study showed not only that there was a greater increase in heart rate in the TZP group than in the control, GLP-1RA and non-GLP-1RA groups, but also that the 15-mg dose of TZP had the strongest impact on increasing heart rates compared with the other five inventions, with a TZP dose-response impact on heart rate. Further research on the effects of TZP treatment-related increases in heart rate is required.


Assuntos
Diabetes Mellitus Tipo 2 , Polipeptídeo Inibidor Gástrico , Adulto , Humanos , Diabetes Mellitus Tipo 2/complicações , Polipeptídeo Inibidor Gástrico/agonistas , Peptídeo 1 Semelhante ao Glucagon/agonistas , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Agonistas do Receptor do Peptídeo 1 Semelhante ao Glucagon/farmacologia , Frequência Cardíaca/efeitos dos fármacos , Insulina/uso terapêutico , Metanálise em Rede
3.
Nutr Metab Cardiovasc Dis ; 34(1): 230-234, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38000989

RESUMO

BACKGROUND AND AIMS: Leukocyte telomere length (LTL) has been correlated with uric acid levels, although results are inconsistent, and prospective studies are lacking. In this longitudinal, prospective cohort study, we aimed to assess whether a shorter LTL predicts the risk of hyperuricemia. METHODS AND RESULTS: We conducted a longitudinal study in a Chinese cohort of 599 participants. Of these, 266 participants completed a 5.9-year follow-up from June 2014 to December 2021. LTL was assessed at baseline using real-time polymerase chain reaction. Hyperuricemia was defined as serum uric acid ≥420 mmol/L according to Chinese guidelines for diagnosis and treatment of hyperuricemia and gout. Participants who had developed hyperuricemia during follow-up (n = 17) had shorter LTL at baseline. Baseline LTL was independently associated with the development of hyperuricemia at follow-up after adjusting for conventional hyperuricemia risk factors (odds ratio [OR] 2.347 [95% confidence interval [CI] 1.123, 4.906]; P = 0.023). After grouping according to LTL tertiles, the incidence of hyperuricemia was 18.334-fold higher for the first than for the third tertile (OR 18.334 [95%CI 1.786, 191.272]; P = 0.014, P for trend = 0.050). CONCLUSION: Our findings in a prospective cohort suggest that LTL could predict hyperuricemia risk, which might inform the timely prevention and treatment of hyperuricemia.


Assuntos
Hiperuricemia , Ácido Úrico , Humanos , Estudos Longitudinais , Estudos Prospectivos , Hiperuricemia/diagnóstico , Hiperuricemia/epidemiologia , Hiperuricemia/genética , Leucócitos , Telômero/genética
4.
Environ Toxicol ; 2024 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-38881217

RESUMO

The prolonged exposure to arsenic results in intestinal barrier dysfunction, which is strongly concerned with detrimental processes such as oxidative stress and the inflammatory response. Ferulic acid (FA), as a phenolic acid, possesses the capability to mitigate arsenic-induced liver damage and cardiotoxic effects dependent on inhibition of oxidative stress and inflammatory responses. FA can mitigate testicular tissue damage and alveolar epithelial dysfunction, the mechanism of which may rely on nuclear factor erythroid 2-related factor 2/heme oxygenase 1 (Nrf2/HO-1) activation and nuclear factor-kappa B (NF-κB) pathway blocking. Based on the antioxidant and anti-inflammatory properties of FA, we speculated that FA might have the potential to inhibit arsenic-induced intestinal damage. To confirm this scientific hypothesis, mice exposed to sodium arsenite were treated with FA to observe colonic histopathology and TJ protein levels, and oxidative stress and TJ protein levels in Caco-2 cells exposed to sodium arsenite were assessed after FA intervention. In addition, molecular levels of NF-κB and Nrf2/HO-1 pathway in colon and Caco-2 cells were also detected. As shown in our data, FA inhibited arsenic-induced colon injury, which was reflected in the improvement of mucosal integrity, the decrease of down-regulated expression of tight junction (TJ) proteins (Claudin-1, Occludin, and ZO-1) and the inhibition of oxidative stress. Similarly, treatment with FA attenuated the inhibitory effect of arsenic on TJ protein expression in Caco-2 cells. In addition to suppressing the activation of NF-κB pathway, FA retrieved the activation of Nrf2/HO-1 pathway in colon and intestinal epithelial cells induced by arsenic. In summary, our findings propose that FA has the potential to mitigate arsenic-induced intestinal damage by preserving the integrity of intestinal epithelial TJs and suppressing oxidative stress. These results lay the groundwork for the potential use of FA in treating colon injuries caused by arsenic.

5.
J Am Chem Soc ; 145(8): 4871-4881, 2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36795897

RESUMO

The Catellani reaction, i.e., the Pd/norbornene (NBE) catalysis, has been evolved into a versatile approach to multisubstituted arenes via the ortho-functionalization/ipso-termination process of a haloarene. Despite significant advances over the past 25 years, this reaction still suffered from an intrinsic limitation in the substitution pattern of haloarene, referred to as "ortho-constraint". When an ortho substituent is absent, the substrate often fails to undergo an effective mono ortho-functionalization process, and either ortho-difunctionalization products or NBE-embedded byproducts predominate. To tackle this challenge, structurally modified NBEs (smNBEs) have been developed, which were proved effective for the mono ortho-aminative, -acylative, and -arylative Catellani reactions of ortho-unsubstituted haloarenes. However, this strategy is incompetent for solving the ortho-constraint in Catellani reactions with ortho-alkylation, and to date there lacks a general solution to this challenging but synthetically useful transformation. Recently, our group developed the Pd/olefin catalysis, in which an unstrained cycloolefin ligand served as a covalent catalytic module to enable the ortho-alkylative Catellani reaction without NBE. In this work, we show that this chemistry could afford a new solution to ortho-constraint in the Catellani reaction. A functionalized cycloolefin ligand bearing an amide group as the internal base was designed, which allowed for mono ortho-alkylative Catellani reaction of iodoarenes suffering from ortho-constraint before. Mechanistic study revealed that this ligand is capable of both accelerating the C-H activation and inhibiting side reactions, which accounts for its superior performance. The present work showcased the uniqueness of the Pd/olefin catalysis as well as the power of rational ligand design in metal catalysis.

6.
Int J Med Sci ; 20(12): 1592-1599, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37859695

RESUMO

Aim/hypothesis: The relationship between peripheral blood leukocyte telomere length (LTL) and kidney dysfunction, especially in people with hypertension, remains unclear. No clinical study has explored the role of inflammation and oxidative stress in the relationship between LTL and kidney dysfunction. Therefore, we examined the relationship between baseline LTL and albuminuria progression and/or rapid renal function decline in Chinese patients with or without hypertension and investigated whether inflammation and oxidative stress played a mediating role in this relationship. Methods: We conducted a prospective study including 262 patients in a 7-year follow-up period from 2014 to 2021. Data on LTL, inflammation, oxidative markers, renal function, and urine protein levels were assessed. Kidney dysfunction was defined as either albuminuria progression, rapid decline in renal function, or the composite endpoint (albuminuria progression and rapid decline in renal function). Logistic regression and simple mediation models were used for the analysis. Results: In this cohort (mean age, 54.3±9.7 years; follow-up period, 5.9±1.1 years), 42(16.0%), 21(8.0%), and 59(22.5%) patients developed albuminuria progression, rapid eGFR decline, and the composite endpoint of kidney dysfunction, respectively. Logistic regression analysis showed that each standard deviation decrease of baseline LTL and the lower quartile (Q) of baseline LTL were significantly correlated with an increased risk of rapid decline in renal function (OR=1.83 [95% CI 1.07, 3.27] per 1SD, P=0.03; OR=7.57 [95% CI 1.25, 145.88] for Q1 vs. Q4, P for trend=0.031); and the composite endpoint of kidney dysfunction (OR=1.37 [95% CI 0.97, 1.96] per 1SD, borderline positive P=0.072; OR=2.96[95% CI 1.15, 8.2] for Q1 vs. Q4, P for trend=0.036). The mediating analysis showed that tumor necrosis factor (TNF)-a partly mediated the relationship between LTL and rapid decline in renal function (direct effect: ß=0.046 95%CI [0.006, 0.090],P=0.02; indirect effect: ß=0.013 95%CI [0.003, 0.020]), and the mediating proportion was 22.4%.In subgroup analyses, LTL was inversely associated with rapid decline in renal function or the composite endpoint of kidney dysfunction only in patients with hypertension (OR=49.07[3.72,211.12] vs.1.32[0.69,2.58] per 1SD, P for interaction=0.045;OR=3.10 [1.48, 7.52] vs.1.08[0.92,1.63] per 1SD, P for interaction=0.036). Conclusion: Baseline LTL could independently predict kidney dysfunction at follow-up, especially in participants with hypertension. TNF-a partially mediated the negative association between LTL and kidney dysfunction.


Assuntos
Hipertensão , Fator de Necrose Tumoral alfa , Humanos , Adulto , Pessoa de Meia-Idade , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , Estudos Prospectivos , Albuminúria/genética , Inflamação/patologia , Hipertensão/genética , Rim , Telômero/genética , Leucócitos/metabolismo , Leucócitos/patologia
7.
Mediators Inflamm ; 2023: 8974960, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36756089

RESUMO

Liraglutide has been extensively applied in the treatment of type 2 diabetes mellitus and also has hepatoprotective effects. However, the role of liraglutide treatment on liver injury in a mouse model of type 1 diabetes mellitus (T1DM) induced by streptozotocin (STZ) and its underlying mechanisms remain to be elucidated. In the present study, diabetes was initiated in experimental animals by single-dose intraperitoneal inoculation of STZ. Forty female C57BL/6J mice were equally assigned into five groups: diabetic group, insulin+diabetic group, liraglutide+diabetic group, insulin+liraglutide+diabetic group, and control group for eight weeks. Diabetic mice exhibited a significantly elevated blood glucose level and decreased body weight, and morphological changes of increased steatosis and apoptosis were observed in the liver compared with the control. Furthermore, a significant increase in the levels of malondialdehyde and inflammatory markers such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin 1ß (IL-1ß) and the proapoptotic proteins caspase-3 and Bax were observed in the livers of diabetic mice, together with marked increases in antioxidants superoxide dismutase (SOD) and glutathione peroxidase (GPX) as well as antiapoptotic protein Bcl-2, all of which were significantly mitigated by treatment with liraglutide, insulin, and their combinations. Interestingly, liraglutide monotherapy showed better efficacy in ameliorating liver injury in T1DM mice than insulin monotherapy, similar to the combined drug therapy. Furthermore, the expression of Wnt/ß-catenin signaling pathway-associated molecules was upregulated in the liver of mice treated with liraglutide or insulin. The results of the present study suggested that liraglutide improves T1DM-induced liver injury and may have important implications for the treatment of nonalcoholic fatty liver disease (NAFLD) in patients with T1DM.


Assuntos
Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Feminino , Camundongos , Animais , Liraglutida/uso terapêutico , Estreptozocina , Hipoglicemiantes/uso terapêutico , Diabetes Mellitus Tipo 2/metabolismo , Via de Sinalização Wnt , Diabetes Mellitus Experimental/metabolismo , Camundongos Endogâmicos C57BL , Fígado/metabolismo , Inflamação/metabolismo , Estresse Oxidativo , Insulina/metabolismo , Apoptose
8.
BMC Med Educ ; 23(1): 878, 2023 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-37978373

RESUMO

BACKGROUND: Shared decision-making (SDM) may influence the clinical outcomes of patients with endocrine disorders. There are few studies describing perspectives towards SDM among endocrinologists in China. METHODS: In the first stage, we conducted a national survey using an online questionnaire about SDM among endocrinologists in China. The national survey focused on attitude and propensity, potential barriers, and the effectiveness of SDM implementation strategies. In the second stage, survey participants were further recruited to participate in a prospective cohort study in the online continuing medical education (CME) program of Peking Union Medical College Hospital in Beijing. The Shared Decision-Making Questionnaire (SDM-Q-Doc) was employed to assess the effects of online CME on physicians' perspectives during the process of SDM, which was conducted before and after the CME course was provided. RESULTS: In the national survey, 280 endocrinologists (75.7% female, mean age 38.0 ± 4.5 years, 62.5% with a duration of practice of more than ten years) completed the questionnaire. Participants had a generally positive attitude towards SDM in clinical practice. The main perceived barriers included time consumption, information inequality between doctors and patients, and a lack of technical support and training for SDM. The main uncertainties of implementation steps included inviting patients to participate in SDM (16.3%), assisting in decision-making (15.3%), facilitating deliberation and decision-making (13.7%), and providing information on benefits and risks (12.6%). Of the physicians who participated in the national survey, 84 registered for the eight-day online CME course. The SDM-Q-Doc score increased from 87.3 ± 18.2 at baseline to 93.0 ± 9.3 at the end of the 8-day online CME training (p = 0.003, paired t test). The participants' age, sex, education level, practice duration, the annual number of patients with rare endocrine diseases, and the annual number of patients requiring MDT or CME were not significantly related to increased SDM-Q-Doc scores after online CME (all p > 0.05). CONCLUSIONS: Chinese endocrinologists had a generally positive attitude towards SDM in clinical practice. There were also several uncertainties in the implementation steps of SDM. Regardless of a physician's educational background or prior professional experience, CME may help to improve their perspectives regarding SDM.


Assuntos
Tomada de Decisões , Endocrinologistas , Humanos , Feminino , Adulto , Masculino , Educação Médica Continuada , Estudos Prospectivos , População do Leste Asiático , Participação do Paciente
9.
J Org Chem ; 86(9): 6983-6993, 2021 05 07.
Artigo em Inglês | MEDLINE | ID: mdl-33852316

RESUMO

The straightforward synthesis of α-fluoro-ß-arylalkenyl sulfones under transition-metal- and base-free conditions has been described, which displays broad functional group compatibility and high stereoselectivity. In particular, the strategy is also applied to the late-stage modification of complex natural products and drugs.


Assuntos
Preparações Farmacêuticas , Sulfonas , Íons , Estrutura Molecular , Sódio
10.
Endocr Pract ; 27(4): 348-353, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34024343

RESUMO

OBJECTIVE: To compare metastatic pheochromocytoma/paraganglioma (MPP) patients with germline SDHB mutations (SDHB MPP) and without SDHB mutations (non-SDHB MPP) in terms of baseline clinical manifestations, tumor characteristics, and outcomes. METHODS: Clinical data were retrospectively reviewed in 101 MPP patients, including 34 SDHB MPP patients and 61 non-SDHB MPP patients. RESULTS: SDHB MPP patients presented at a younger age at onset, diagnosis, or metastasis (25 ± 16 vs 36 ± 14, 28 ± 17 vs 38 ± 15, and 31 ± 17 vs 44 ± 14 years old, respectively, P < .01 for all) than non-SDHB patients. Compared with their non-SDHB counterparts, SDHB patients were more likely to have paragangliomas (83% vs 47%, P < .05), synchronous metastases (44% vs 23%, P < .05), bone metastases (80% vs 48%, P < .01), and a shorter progression-free survival (3 years vs 5 years, P < .01). The Ki-67 index was higher in SDHB tumors (P < .05). The 5- and 10-year survival rates were 79% and 74%, respectively, in all patients. Seventeen patients died from MPP, and the time from metastasis to death in patients who had received systemic therapy was significantly longer than in those who had not (3.1 ± 1.5 vs 1.4 ± 0.7 years, P < .01). CONCLUSION: Compared with MPP patients without SDHB mutations, MPP patients with SDHB mutations were younger at onset, diagnosis, or metastasis; had a higher incidence of synchronous metastases, higher ratio of paraganglioma, and higher Ki-67 index; had a shorter postoperative progression-free survival; and were more likely to develop bone metastasis or sole liver metastasis. Our results suggest that patients with SDHB mutations should be identified early and monitored regularly to achieve optimal clinical outcomes.


Assuntos
Neoplasias das Glândulas Suprarrenais , Paraganglioma , Feocromocitoma , Adolescente , Neoplasias das Glândulas Suprarrenais/genética , Adulto , Criança , Mutação em Linhagem Germinativa , Humanos , Pessoa de Meia-Idade , Mutação , Paraganglioma/genética , Feocromocitoma/genética , Prognóstico , Estudos Retrospectivos , Succinato Desidrogenase/genética , Adulto Jovem
11.
Endocr Pract ; 27(8): 776-782, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33991656

RESUMO

OBJECTIVE: Genetic detection for the diagnosis of maturity-onset diabetes of the young (MODY) in China has low sensitivity and specificity. Better gene detection is urgently needed to distinguish testing subjects. We proposed to use numerous and weighted clinical traits as key indicators for reasonable genetic testing to predict the probability of MODY in the Chinese population. METHODS: We created a prediction model based on data from 306 patients, including 140 patients with MODY, 84 patients with type 1 diabetes (T1D), and 82 patients with type 2 diabetes (T2D). This model was evaluated using receiver operating characteristic curves. RESULTS: Compared with patients with T1D, patients with MODY had higher C-peptide levels and negative antibodies, and most patients with MODY had a family history of diabetes. Different from T2D, MODY was characterized by lower body mass index and younger diagnostic age. A clinical prediction model was established to define the comprehensive probability of MODY by a weighted consolidation of the most distinguishing features, and the model showed excellent discrimination (areas under the curve of 0.916 in MODY vs T1D and 0.942 in MODY vs T2D). Further, high-sensitivity C-reactive protein, glycated hemoglobin A1c, 2-h postprandial glucose, and triglyceride were used as indicators for glucokinase-MODY, while triglyceride, high-sensitivity C-reactive protein, and hepatocellular adenoma were used as indicators for hepatocyte nuclear factor 1-α MODY. CONCLUSION: We developed a practical prediction model that could predict the probability of MODY and provide information to identify glucokinase-MODY and hepatocyte nuclear factor 1-α MODY. These results provide an advanced and more reasonable process to identify the most appropriate patients for genetic testing.


Assuntos
Diabetes Mellitus Tipo 2 , China/epidemiologia , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/genética , Fator 1-alfa Nuclear de Hepatócito/genética , Humanos , Modelos Estatísticos , Mutação , Prognóstico
12.
Med Educ ; 55(3): 293-308, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-32881047

RESUMO

CONTEXT: Synchronous distance education (SDE) has been widely used for health science students in recent years. This study examined the effectiveness and acceptance of SDE compared with traditional education for health science students and explored the potential moderators that could impact the pooled results. METHODS: A systematic review and meta-analysis was conducted of randomised controlled trials (RCTs) from January 2000 to March 2020 searched on nine electronic databases, including Web of Science, PubMed, Cochrane Library, Scopus, EMBASE, CINAHL, ERIC, PsycINFO, and ProQuest Dissertations and Theses. The outcomes measured were knowledge, skills with objective assessments and overall satisfaction with subjective evaluations. The pooled results were calculated using random-model effects, and moderators were explored through meta-regression. RESULTS: A total of seven RCTs with 594 participants were included. At the post-test level, the pooled effect size of knowledge acquisitions (SMD 0.12, 95% CI -0.07-0.32) showed insignificant difference between the SDE and traditional education groups (P = .207), with low heterogeneity (I2  = 17.6%). Subgroup analyses observed no factors that significantly impacted the pooled results of knowledge acquisition at the post-test levels (P for interaction > 0.05). Knowledge gains from pretest to post-test in SDE groups also did not differ significantly between groups (SMD 0.15, 95% CI -0.22-0.53; P = .428). The pooled effect size of skills (SMD 0.02, 95% CI -0.24-0.28; P = .735) was similarly insignificant. The pooled effect size of overall satisfaction (SMD 0.60, 95% CI 0.38-0.83; P < .001) significantly favoured SDE over traditional education. Incorporating two-group studies without randomisations did not significantly change the overall results of knowledge acquisition at the post-test level (SMD -0.002, 95% CI -0.11-0.10; P = .994), with moderate heterogeneity (I2  = 61.9%). CONCLUSIONS: Synchronous distance education was not significantly different from traditional education in effectiveness and had higher satisfaction ratings. Our findings might provide indications for adoptions of online remote education in health science education centres.


Assuntos
Educação a Distância , Educação Médica , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudantes de Ciências da Saúde , COVID-19 , Humanos
13.
Angew Chem Int Ed Engl ; 60(25): 13871-13876, 2021 06 14.
Artigo em Inglês | MEDLINE | ID: mdl-33851763

RESUMO

Palladium-catalyzed direct C-H activation of indole benzenoid moiety has been achieved in the past decade. However, palladium-catalyzed remote C-H activation of indoles is rare. Herein, we report a challenging palladium-catalyzed remote C4-H phosphonylation of indoles by a radical approach. The method provides access to a series of C4-phosphonylated indoles, including tryptophan and tryptophan-containing dipeptides, which are typically inaccessible by direct C4-H activation due to its heavy reliance on C3 directing groups. Notably, unexpected C6-phosphonylated indoles were obtained through blocking of the C4 position. The preliminary mechanistic studies indicated that the reactions may proceed via a C7-palladacycle/remote-activation process. Based on the strategy, examples of remote C4-H difluoromethylation with BrCF2 COOEt are also presented, suggesting that the strategy may offer a general blueprint for other cross-couplings.

14.
Gerontology ; 66(5): 439-446, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32663832

RESUMO

BACKGROUND: With the shortening of leukocyte telomere length (LTL) and decrease in the copy number of mitochondrial DNA, mitochondrial dysfunction and oxidative stress are considered important drivers of the aging process. Although previous experimental studies report that caloric intake is associated with age-related renal dysfunction through the changes in mitochondrial function, there are insufficient epidemiological data to establish this association. OBJECTIVE: We aimed to explore the association between caloric intake and renal function and to investigate whether mitochondrial DNA copy number (mtDNAcn) mediated this association by cross-sectional analysis. METHODS: A total of 403 individuals from a Chinese rural cohort (women = 66.50%; mean age = 53.94 ± 10.27 years) with an estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2 and with differences in the glucose tolerance status (diabetes, n = 106; prediabetes, n = 125; normal glucose tolerance, n = 172) were included. Dietary data were obtained by a 24-h food recall, and caloric intake was normalized by ideal body weight. The mtDNAcn and LTL were detected using real-time PCR assay. The associations between caloric intake, aging markers, and renal function were analyzed by partial correlation analysis and multiple linear regression analysis. Mediation analysis was applied to examine the role of mtDNAcn in the association between caloric intake and eGFR. RESULTS: Caloric intake was higher while age-adjusted mtDNAcn was lower in individuals with eGFR <90 mL/min/1.73 m2 (n = 140) than in those with eGFR ≥90 mL/min/1.73 m2 (n = 263). After adjusting for multiple factors, linear regression analysis revealed that caloric intake was negatively associated with eGFR and mtDNAcn, while mtDNAcn was positively associated with eGFR. Moreover, mediation analysis indicated that the indirect effect of caloric intake on eGFR through mtDNAcn was significant (ß = -0.0505, 95% confidence interval -0.0931 to -0.0190). CONCLUSIONS: Caloric intake was negatively associated with eGFR in a Chinese population, and the association was partly mediated by decreased mtDNAcn.


Assuntos
Ingestão de Energia/fisiologia , Taxa de Filtração Glomerular/fisiologia , Mitocôndrias/metabolismo , Adulto , Idoso , Envelhecimento/fisiologia , Povo Asiático , Biomarcadores , China , Estudos de Coortes , Estudos Transversais , Variações do Número de Cópias de DNA , DNA Mitocondrial , Diabetes Mellitus/metabolismo , Feminino , Humanos , Leucócitos/metabolismo , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo , Telômero/metabolismo
15.
Lipids Health Dis ; 19(1): 121, 2020 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-32487177

RESUMO

BACKGROUND: Previous studies on the effects of lipotoxicity and oxidative stress on islet beta cell function mainly focused on patients with diabetes, whereas studies on normal glucose tolerance (NGT) are few. The aim of this study was to explore the relationships among triglyceride (TG), high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c), oxidative stress indicators, insulin resistance, and beta cell function in populations with different glucose and lipid metabolism states. METHODS: A total of 517 individuals were recruited from a rural community in Beijing, China. Glucose metabolism status was defined according to the results of a 75-g oral glucose tolerance test (OGTT). Dyslipidemia was defined as abnormal TG, HDL-c, or LDL-c levels. The population was divided into four groups: individuals with normal glucose and lipid levels (group A, n = 62); those with dyslipidemia alone (group B, n = 82); those with dysglycemia alone (group C, n = 121); and those with dysglycemia and dyslipidemia (group D, n = 247). Oxidative stress indicators, including superoxide dismutase (SOD), glutathione reductase (GR) and 8-hydroxydeoxyguanosine (8-OHdG), were measured. Homeostasis model assessment of insulin resistance (HOMA-IR) and glucose disposition index (DI30, DI120) were calculated to assess insulin resistance and islet beta cell function, respectively. Stratified multiple linear regression analysis was used to explore relationships between TG, HDL-c, LDL-c, oxidative stress indicators, and insulin resistance (natural log transformation of HOMA-IR, LnHOMA-IR) and beta cell function (natural log transformation of DI30, Ln DI30). RESULTS: Compared with the control group, populations with dyslipidemia and/or dysglycemia showed significantly increased insulin resistance. Dyslipidemia aggravated insulin resistance and beta cell dysfunction in individuals with dysglycemia. Stratified regression analysis showed that TG positively correlated with LnHOMA-IR in individuals with normal glucose levels (beta = 0.321, 0.327, P = 0.011, 0.003 in groups A and B, respectively) and negatively correlated with LnDI30 in participants with dyslipidemia (beta = - 0.225, - 0.122, P = 0.035, 0.048 in groups B and D, respectively). Reduced serum SOD levels in individuals with dysglycemia plus dyslipidemia were observed, and a negative association between TG and SOD levels was found (r = - 0.461, P < 0.001). CONCLUSION: TG correlated with both insulin resistance and beta cell function in individuals with dyslipidemia alone. SOD negatively correlated with TG, indicating a close relationship between oxidative stress and glucose-lipid metabolism. Due to the adverse effect of hypertriglyceridemia on insulin sensitivity and islet beta cell function, more attention should be paid to the detection and management of hypertriglyceridemia.


Assuntos
Diabetes Mellitus/genética , Resistência à Insulina/genética , Metabolismo dos Lipídeos/genética , Triglicerídeos/sangue , Idoso , Glicemia/genética , China/epidemiologia , Diabetes Mellitus/sangue , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/patologia , Dislipidemias/sangue , Dislipidemias/epidemiologia , Dislipidemias/genética , Dislipidemias/patologia , Feminino , Glucose/genética , Humanos , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo/genética
16.
Mediators Inflamm ; 2020: 7610436, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32565730

RESUMO

OBJECTIVES: In this study, we assessed the effects of dietary magnesium on leukocyte telomere length (LTL). DESIGNS: The current cross-sectional analysis was based on data collected within a type 2 diabetes project. Settings. Dietary magnesium intake is associated with peripheral blood leukocyte telomere length (LTL). However, few epidemiological studies have evaluated the effects of magnesium on LTL in the clinical setting. Participants. This cross-sectional analysis included 467 participants (34.8% men). Measurements. Serum blood lipid profile, HbA1c, oxidative stress, and proinflammatory mediator levels were measured. Detailed dietary data were obtained using a 24 h food recall. LTL was assessed using a real-time PCR assay. Regression models and simple regulatory models were used for data analysis. RESULTS: There was an inverse relationship between dietary magnesium and LTL (P < 0.001), with a between-extreme-quarter difference of -0.55. Conversely, there was a positive relationship between dietary magnesium and serum tumor necrosis factor (TNF) α, with an interquarter difference of 3.79 pmol/mL (P for trend = 0.006). Multivariate regression analysis revealed that the odds ratios (ORs) for shorter LTL and higher serum TNFα increased with magnesium intake, and the ORs of the differences between extreme quartiles were 2.60 (95% confidence interval (CI): 1.31-5.36; P = 0.003) and 1.98 (95% CI: 1.09-3.59; P = 0.008). There was a direct negative effect of dietary magnesium intake on LTL (B = -0.002; P = 0.001), which appeared to be indirectly influenced by TNFα (-0.002 to -0.0005). CONCLUSIONS: Dietary magnesium intake may be a critical component of the cellular aging process, and its effect could be partly mediated by TNFα.


Assuntos
Leucócitos/metabolismo , Magnésio/metabolismo , Telômero/metabolismo , Fator de Necrose Tumoral alfa/sangue , Adulto , Idoso , Antropometria , Glicemia/metabolismo , Estudos Transversais , Diabetes Mellitus Tipo 2/sangue , Dieta , Feminino , Hemoglobinas Glicadas/metabolismo , Humanos , Inflamação , Masculino , Pessoa de Meia-Idade , Razão de Chances , Estresse Oxidativo , Reação em Cadeia da Polimerase em Tempo Real , Análise de Regressão
18.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 42(5): 702-705, 2020 Oct.
Artigo em Zh | MEDLINE | ID: mdl-33131528

RESUMO

This article summarizes the clinical features and follow-up findings of insulin autoimmune syndrome in two patients with type 2 diabetes after the use of lipoic acid,along with literature review,with an attempt to increase the awareness of lipoic acid-induced insulin autoimmune syndrome among clinicians and improve its diagnosis and treatment.


Assuntos
Doenças Autoimunes , Diabetes Mellitus Tipo 2 , Doenças Autoimunes/induzido quimicamente , Doenças Autoimunes/complicações , Doenças Autoimunes/tratamento farmacológico , Doenças Autoimunes/patologia , Diabetes Mellitus Tipo 2/complicações , Humanos , Ácido Tióctico/efeitos adversos
19.
Langmuir ; 35(36): 11829-11835, 2019 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-31414811

RESUMO

Silver nanowires (AgNWs) with the diameter down to 16 nm have been synthesized by using tetrabutyl ammonium dibromochloride (TBADBC) as the organic auxiliary. Moderate dosage of TBADBC was proven to be favorable for the in situ growth of Ag pentahedral seeds on the surface of small AgClBr2 particles and have a passivation effect on the Ag{100} crystal facet during the growth of AgNWs, eventually resulting in the formation of thin AgNWs. Furthermore, the transparent conductive film fabricated by using the obtained AgNWs exhibited excellent photoelectric properties, which has a transmittance of 90.60%, a haze of 0.95%, and a sheet resistance of 110.8 Ω/sq, indicating large potential for application in flexible transparent conductors.

20.
BMC Endocr Disord ; 19(1): 119, 2019 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-31690291

RESUMO

BACKGROUND: The shape of the glucose response curve during an oral glucose tolerance test (OGTT) can predict ß-cell function and insulin resistance. However, there have been few studies conducted on Chinese people. Thus, we aimed to verify the usefulness of the glucose response curve in a large Chinese population. METHODS: A total of 9059 OGTT (3-h tests) were categorized into either a monophasic or a multiphasic group based on the shape of the glucose response. Homeostasis model assessments of fasting insulin resistance, the Matsuda Index, the insulinogenic index, and the disposition index were assessed by plasma glucose and serum insulin concentration obtained at fasting or during an OGTT. RESULTS: The shape of the OGTT glucose response curve was monophasic in 87.3% and multiphasic in 12.7% of participants. Individuals in the multiphasic group were younger compared to those in the monophasic group (38.6 ± 13.6 vs. 35.4 ± 13.5, P < 0.001). Individuals in the monophasic group had significantly higher fasting plasma glucose (FPG 5.6 ± 13.5 vs. 5.2 ± 0.6, P < 0.001), fasting insulin (FINS 14.8 ± 8.7 vs. 13.5 ± 7.9, P < 0.01), and homeostasis model assessment of insulin resistance (HOMA-IR 3.8 ± 2.6 vs. 3.1 ± 2.0, P < 0.001) and impaired ß-cell function (disposition index 12.7 ± 14.1 vs. 16.6 ± 17.8, P < 0.001) compared to those in the multiphasic group. CONCLUSION: The monophasic OGTT glucose response curve could reflect impaired ß-cell function in a large Chinese population.


Assuntos
Biomarcadores/sangue , Glicemia/análise , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/patologia , Teste de Tolerância a Glucose/métodos , Células Secretoras de Insulina/patologia , Insulina/sangue , Adulto , China/epidemiologia , Diabetes Mellitus Tipo 2/metabolismo , Feminino , Seguimentos , Humanos , Resistência à Insulina , Células Secretoras de Insulina/metabolismo , Masculino , Prognóstico
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