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1.
Exp Eye Res ; : 108300, 2020 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-33065089

RESUMO

Diabetic retinopathy (DR) is the leading cause of visual impairment and acquired blindness among adults worldwide. Retinal microvascular pericyte deficiency is one of the earliest pathological changes associated with DR, and long noncoding RNA myocardial infarction-associated transcript (MIAT) has been implicated as a crucial regulator of microvascular dysfunction in DR. Pyroptosis is a caspase-1-dependent proinflammatory form of cell death, and in the present study, we investigated the potential pyroptosis of primary human retinal pericytes (HRPCs) and the mechanism by which MIAT is involved in this process. We applied advanced glycation end product modified bovine serum albumin (AGE-BSA) to simulate the DR environment. The results suggested that AGE-BSA induced the active cleavage of caspase-1 and gasdermin D, the release of IL-1ß, IL-18 and LDH, and reduced cell viability, which was prevented by the inhibition of caspase-1, indicating the occurrence of caspase-1-mediated pyroptosis in HRPCs. Immunofluorescence images revealed the phenotypic characteristics of pyroptosis, including pyknosis, swelling and hyperpermeability in plasmolemma. MIAT and CASP1 expression were substantially increased, while that of miR-342-3p was decreased in AGE-BSA-treated HRPCs. MIAT knockdown inhibited pyroptosis in HRPCs, which was reinforced by cotreatment with miR-342-3p mimic but relieved by cotreatment with miR-342-3p inhibitor. Furthermore, HRPC pyroptosis was inhibited by treatment with the miR-342-3p mimic alone but enhanced by the miR-342-3p inhibitor. Luciferase reporter assay results demonstrated binding between MIAT and miR-342-3p, as well as between miR-342-3p and CASP1. MIAT antagonized the effect of miR-342-3p on the depression of its target CASP1 and promoted AGE-BSA-induced pericyte pyroptosis. These findings may promote a better understanding of retinal pericyte depletion pathogenesis and the development of new therapeutic strategies for the treatment of diabetic retinopathy.

2.
Artigo em Inglês | MEDLINE | ID: mdl-32918210

RESUMO

OBJECTIVE: This systematic review and meta-analysis was conducted to identify if long-term bosentan is an effective and safe treatment for pulmonary arterial hypertension (PAH) regardless of type, including idiopathic PAH (IPAH), and PAH associated with congenital heart disease (APAH-CHD), connective tissue disease (APAH-CTD), and human immunodeficiency virus (APAH-HIV). METHODS: All relevant observations were systematically searched by two independent investigators and obtained from three databases, including PubMed, EMBASE and the Cochrane Library, from the inception of each database to February 2020. Currently, long-term administration was defined as no less than 12 months. A random-effects or fixed-effects model was selected according to outcomes of the heterogeneity test for meta-analysis, where standardized mean difference (SMD) with 95% confidence intervals (CIs) was used for continuous outcomes, in addition to the estimated effect (ES; 95% CI) for the synthesized survival rate. Furthermore, subgroup analysis was applied to analyze the differences of efficacy and survivals in each type of PAH cohort. RESULTS: Fifteen studies including a total of 659 subjects undergoing oral bosentan administration for at least 12 months were pooled in this quantitative review. Meta-analysis and subgroup analysis indicated that significant clinical benefits existed, including an improved 6-min walk distance (6MWD) and functional class (FC), in patients with APAH-CHD (6MWD: SMD 0.72, 95% CI 0.52-0.93, p < 0.0001; functional benefits: 50.4%, 95% CI 43.7-57.1%), APAH-HIV (6MWD: SMD 0.83, 95% CI 0.36-1.30, p = 0.001; functional benefits: 80.4%), and IPAH (SMD 0.54, 95% CI 0.28-0.80, p < 0.0001; functional benefits: 61.4%, 95% CI 54.2-68.5%), but a non-significant change in APAH-CTD (6MWD: SMD 0.18, 95% CI - 0.60 to 0.95, p = 0.656; functional benefits: 27.5%). Furthermore, among the hemodynamic parameters, long-term bosentan led to a significant decrease in mean pulmonary artery pressure (SMD - 0.86, p < 0.0001) in APAH-CTD, and a decrease in pulmonary vascular resistance (SMD - 0.65, p < 0.0001) and elevated oxygen saturation (SMD 0.30, p = 0.006) in APAH-CHD. Importantly, in all pooled studies, the overall survival indicated 1-, 2-, and 3-year survival rates of 94.3%, 88.8%, and 81.7%, respectively, in all-cause PAH, and subgroup analysis demonstrated a relative decreasing trend in patients with HIV, from a 2-year survival of 89.8% to a 3-year survival of 66.1%. Adverse drug reactions were relatively mild. CONCLUSION: In this systematic review and meta-analysis, long-term administration of oral bosentan has been identified as a well-tolerated and effective agent in different types of PAH. In addition, we conclude that long-term oral bosentan should be considered for patients with CTD to achieve a satisfactory exercise capacity, and for those with APAH-HIV to improve survivals, where more attention on adverse events is required.

3.
Pediatr Cardiol ; 41(7): 1445-1457, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32583199

RESUMO

A meta-analysis is performed for a comparison of outcomes between the modified one-patch repair (MPR) and two-patch repair (TPR) for complete atrioventricular septal defects (CAVSD). Electronic databases, including PubMed, Scopus, Embase, and Cochrane Library were searched systematically for the literature which aimed mainly at comparing the therapeutic effects for CAVSD administrated by MPR and TPR. Corresponding data sets were extracted and two reviewers independently assessed the risks of bias. Meta-analysis was performed using Revman 5.3 and Stata 12.0. Fifteen studies meeting the inclusion criteria were included, involving 2076 subjects in total. It was observed that MPR was associated with shorter cardiopulmonary bypass (CPB) and aortic cross-clamp (ACC) times, as compared with TPR. However, no statistical differences were found in terms of size of ventricular septal defects (VSD), reoperation, mortality, implantation of permanent pacemakers, and length of ventilation, hospital and intensive care unit stay. As compared with TPR, MPR is superior in terms of ACC and CPB. However, with regard to reoperation, mortality, length of ventilation, ICU and hospital stay and permanent pacemakers implantation, no significant differences are found between these two procedures. MPR is likely to apply to younger infants with faster completion of surgery. Surgery is recommended between 3 and 6 months of age.

4.
Cancer Manag Res ; 12: 1863-1874, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32210629

RESUMO

Introduction and Aim: Hepatocellular carcinoma (HCC) is a primary malignancy that occurs in the liver. Clinical cases have been recorded worldwide, particularly in the Saharan area and Asia. In the present work, we aimed to probe the characteristics of melatonin involved in human HCC development, especially in cisplatin resistance and glucose metabolism. Methods: Two HCC cells, HepG2 and Hep3B cells, were treated with melatonin. Cell cycle test was then used to define the role of melatonin in cell progression while Western blotting and qPCR assay were applied to determine the associated proteins in the treatment. Annexin V/PI staining and MTT assay was used to probe the involvement of melatonin in cisplatin-induced cell apoptosis process. Successively, we assessed glucose consumption in melatonin treated cells along with Western blotting for detection of GLUT-3 expression level. Yes-associated protein (YAP), a key regulator of Hippo signaling pathway, was further examined to characterize the function of melatonin on adjusting GLUT3 and Bcl-2 expression. Results: Melatonin enabled inhibition of HepG2 and Hep3B proliferation and cell cycle progression via affecting the cell cycle-associated proteins. Annexin V/PI staining and MTT assay results demonstrated that melatonin assisted cisplatin-induced apoptosis accompanied with upregulated caspase-3 and poly ADP-ribose polymerase (PARP) cleavage, as well as Bcl-2 expression. It revealed that melatonin inhibits glucose uptake and ATP production via downregulation of Glucose transporter 3 (GLUT3). In addition, YAP was downregulated by melatonin treatment. The YAP depletion in HepG2 and Hep3B cells suppressed mRNA and protein expression of Bcl-2 and GLUT3, whereas overexpression of YAP in melatonin treated cells partly reversed the melatonin-induced inhibition on proliferation, cisplatin-induced apoptosis, and GLUT3 and Bcl-2 expression. Conclusion: Melatonin hindered HCC proliferation and aided cisplatin resistance via regulating the Hippo signaling pathway.

5.
Diabetes Obes Metab ; 22(2): 158-166, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31512365

RESUMO

AIM: To investigate the effectiveness of metformin in delaying or preventing progression to diabetes in a Chinese population with impaired glucose regulation (IGR). MATERIALS AND METHODS: This multicentre, randomized, open-label, controlled study (NCT03441750) will assess the efficacy of metformin in preventing diabetes over ≥2 years. Eligible participants will be randomly assigned (1:1) to lifestyle intervention (LSI) or metformin plus LSI, with stratification based on blood pressure, anti-hypertensive medication use and isolated/non-isolated impaired fasting glucose. All participants will receive LSI advice. Participants in the metformin plus LSI group will receive metformin 850 mg once daily for the first 2 weeks, and twice daily thereafter, according to tolerability. RESULTS: The primary objective is to compare rates of newly diagnosed diabetes in the two intervention groups. Changes in glycaemia, blood pressure, body weight, insulin resistance, and safety outcomes will also be evaluated. CONCLUSIONS: This large clinical trial in a Chinese population with IGR aims to provide critical information to guide clinical decision-making in order to alleviate the current diabetes epidemic.

6.
Cell Biochem Funct ; 38(2): 222-230, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31879991

RESUMO

Type 2 diabetes mellitus (T2DM) is a growing burden in low-and middle-income countries. Changing lifestyles and lack of physical activity are some of the reasons contributing to this epidemic increase. Co-morbidities associated with T2DM are largely due to the complications which arise as a consequence of endothelial dysfunction. Platelet derived growth factor-alpha (PDGFRA) is a protein responsible for cell proliferation, angiogenesis, migration and invasion. Increased levels of PDGFRA have been reported in T2DM. This study assessed the epigenetic regulation of PDGFRA through microRNAs (miR-181a/b-5p).Using a bioinformatics-based approach, we assessed the binding of miR-181a/b-5p to PDGFRA. Experimentally, this binding was confirmed using a dual luciferase reporter assay. Further, we overexpressed miR-181a/b-5p in Human umbilical vein endothelial cells (HUVECs) and the influence of over-expression on cell proliferation, migration and angiogenesis was assessed using in-vitro approaches. The influence of miR-181a/b-5p over expression on cellular apoptosis was ascertained using a TUNEL assay with concomitant changes being observed in the levels of Bcl-2 and cleaved Caspase-3.In HUVECs, PDGFRA is a direct target for miR-181a/b-5p. Over expression of miR-181a/b-5p decreased cellular proliferation, migration, invasion, and tube formation-a surrogate marker for angiogenesis. miR-181a/b-5p may be used as a therapeutic intervention to restrict uncontrolled levels of PDGFRA and thereby rescue the phenotypes of increased cell proliferation, migration, invasion and tube formation. miR-181a/b negatively regulates PDGFRA levels. Significance of the study: T2DM and its associated complications emerge from endothelial dysfunction. The associated phenotypes are regulated by a number of proteins, one such member being, PDGFRA. PDGFRA is in turn regulated by miR-181a/b-5p. Complementation with miR-181a/b-5p resulted in reversion of phenotypes. Thus, miR-181a/b-5p-mediated suppression of PDGFRA may be used as a therapeutic intervention in the management of type 2 diabetes.

7.
Indian J Pediatr ; 87(1): 17-25, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31833040

RESUMO

OBJECTIVES: To evaluate the efficacy and safety of nitazoxanide in intestinal parasitic infections in children. METHODS: Four databases, PubMed, EMBASE, Web of Science and Cochrane Library, have been systematically searched from the inception of each database up to March 1st, 2019. The enrolled studies were limited to randomized clinical trials in children, comparing nitazoxanide with placebo or other antiparasitic drugs. The data extraction and quality assessment of pooled studies were conducted by two reviewers independently. For meta-analysis, Stata12.0 was used and a randomized effect model or a fixed effect model was selected according to the outcomes of heterogeneity test. RESULTS: A total of 1645 subjects in 13 randomized controlled trials (RCTs) were enrolled, including 768 cases in the trial group and 877 cases in the control group. The effect of nitazoxanide vs. placebo and other antiparasitic drugs on the excretion rate of pathogens was uncertain (OR = 2.06, 95%CI [1.01,4.20], P = 0.047; I2 = 84.7%; very low quality evidence). Compared with placebo, subgroup analysis suggested that nitazoxanide could significantly improve the excretion rate of pathogens (OR = 7.01, 95%CI [1.82,26.94], P = 0.005; I2 = 79.1%; moderate quality evidence), while it made little or no difference compared with antiparasitic drugs (OR = 0.72, 95%CI [0.47,1.09], P = 0.124; I2 = 33.1%; low quality evidence). Meanwhile, nitazoxanide might increase the remission rate of diarrhea with OR = 5.12, 95%CI [2.00,13.08], P = 0.001; I2 = 72.3%; low quality evidence). However, it might also increase the rate of adverse events (OR = 1.47, 95%CI [1.05,2.07], P = 0.026; I2 = 44.7%; low quality evidence). CONCLUSIONS: The authors are uncertain whether or not nitazoxanide could improve the excretion rate of pathogens. Based on low-certainty evidence, nitazoxanide may improve the remission rate of diarrhea in children with intestinal parasite infections, but it may be associated with an increased risk of adverse reactions. Hence, more RCTs with a low risk of bias are still needed to assess the efficacy and safety of nitazoxanide.


Assuntos
Doenças Parasitárias/tratamento farmacológico , Tiazóis/uso terapêutico , Criança , Bases de Dados Factuais , Diarreia/tratamento farmacológico , Humanos , Tiazóis/efeitos adversos
8.
J Interv Cardiol ; 2019: 5408618, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31772535

RESUMO

Objective: To evaluate the safety and efficacy of interventional care in pediatric hemoptysis for anomalous bronchial arteries (BAs) and to identify the potential factors resulting in hemoptysis recurrence. Methods: 20 children complained of hemoptysis were diagnosed with anomalous BAs. All patients received transcatheter plug occlusion in Department of Cardiology, Children's Hospital of Chongqing Medical University. The safety and efficacy were evaluated according to clinical symptoms and images monitoring of enrolled subjects grouped as recurrence group and nonrecurrence group. The potential factors causing hemoptysis recurrence were reviewed and summarized. Results: No deaths were recorded in a follow-up. Otherwise, hemoptysis recurrence was found in 8 subjects for 14 times, accounting for about 40%. Compared with nonrecurrence group, it indicated a statistical significance in hemoglobin levels (P=0.049), mycoplasma pneumonia particle assays (MP-PA) titers (P=0.030), and number of anomalous BAs (P=0.020). Meanwhile, 50% recurrent scenarios were associated with a respiratory infection by microbiological assessment before transcatheter plug occlusion. The repeat occlusion was applied for unclosed BAs leading to visual recurrent hemoptysis, the average interval time of which was 5.4 ± 3.6 mon. Conclusion: The data from this retrospective study have shown that transcatheter plug occlusion is a relatively safe procedure with a low mortality. The number of abnormal BAs has been identified as a highly significant predictor of recurrence, and the role of MP and other potential factors should be verified in a multicenter, larger sample size, and randomized controlled trial.


Assuntos
Artérias Brônquicas , Procedimentos Endovasculares , Hemoptise , Complicações Pós-Operatórias/epidemiologia , Malformações Vasculares , Angiografia/métodos , Artérias Brônquicas/anormalidades , Artérias Brônquicas/diagnóstico por imagem , Artérias Brônquicas/cirurgia , Criança , China/epidemiologia , Procedimentos Endovasculares/efeitos adversos , Procedimentos Endovasculares/instrumentação , Procedimentos Endovasculares/métodos , Feminino , Hemoptise/etiologia , Hemoptise/cirurgia , Humanos , Pulmão/irrigação sanguínea , Masculino , Recidiva , Estudos Retrospectivos , Resultado do Tratamento , Dispositivos de Oclusão Vascular , Malformações Vasculares/diagnóstico , Malformações Vasculares/epidemiologia , Malformações Vasculares/cirurgia
9.
Eur J Pharmacol ; 864: 172715, 2019 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-31593687

RESUMO

Non-alcoholic steatohepatitis (NASH) is a key step in the progression of non-alcoholic fatty liver disease (NAFLD), which causes serious health problems worldwide. The nucleotide-binding oligomerization domain, leucine-rich repeat-containing receptor-containing pyrin domain 3 (NLRP3) inflammasome and pyroptosis play crucial roles in the progression of NASH. Our team has provided clinical evidence of the effects of glucagon-like peptide-1 (GLP-1) on the improvement in liver function and histological resolution of NAFLD. Preliminary work has demonstrated that GLP-1 inhibited NLRP3 inflammasome activation in a mouse model of NAFLD. We further explored the potential molecular mechanisms underlying the anti-inflammatory effect of liraglutide, a long-acting GLP-1 analog, in the treatment of NASH. We established a HepG2 cell model of NASH using double stimulation with palmitic acid and lipopolysaccharide to assess NLRP3 inflammasome and pyroptotic cell activity and to evaluate mitochondrial function and mitophagy. Liraglutide reduced lipid accumulation, inhibited NLRP3 inflammasome and pyroptosis activation, attenuated mitochondrial dysfunction and reactive oxygen species generation, augmented mitophagy in hepatocytes. Mitophagy inhibition with 3-methyladenine/PINK1-directed siRNA weakened the liraglutide-mediated suppression of inflammatory injury. We propose that liraglutide suppresses NLRP3 inflammasome-induced hepatocyte pyroptosis via mitophagy to slow the progression of NASH.


Assuntos
Inflamassomos/metabolismo , Liraglutida/farmacologia , Mitofagia/efeitos dos fármacos , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/patologia , Piroptose/efeitos dos fármacos , Progressão da Doença , Células Hep G2 , Hepatócitos/efeitos dos fármacos , Hepatócitos/patologia , Humanos , Metabolismo dos Lipídeos/efeitos dos fármacos , Liraglutida/uso terapêutico , Mitocôndrias/efeitos dos fármacos , Hepatopatia Gordurosa não Alcoólica/metabolismo , Espécies Reativas de Oxigênio/metabolismo
10.
Metab Syndr Relat Disord ; 17(8): 416-422, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31355704

RESUMO

Background: A number of researches have reported that thyroid hormones are associated with obesity. However, the relationship of serum levels of thyroid hormones in the normal range with obesity and parameters of obesity in women of childbearing age remains controversial. The purpose of this study was to examine serum levels of thyroid hormones within the normal range in obese Chinese women of reproductive age and to investigate the relationship between concentration of thyroid hormones and indices of obesity, including body mass index (BMI), waist-to-hip ratio (WHR), insulin resistance, blood glucose, blood lipids, and blood pressure. Methods: One hundred fifty-one obese women of reproductive age and 160 nonobese women of reproductive age were enrolled in this study. Serum levels of thyroid-stimulating hormone (TSH) of all subjects were within the normal reference range (0.35-4.94 mIU/L). The serum levels of free triiodothyronine (FT3), free thyroxine (FT4), and TSH, height, body weight, BMI, waist and hip circumferences, WHR, fasting blood glucose (FBG), fasting insulin (FI), homeostasis model assessment of insulin resistance (HOMA-IR), total triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), systolic blood pressure (SBP), and diastolic blood pressure (DBP) were measured in all subjects. Quantile regression analysis was used to analyze the associations of serum levels of FT3, FT4, and TSH with values of BMI, WHR, FBG, FI, HOMA-IR, TG, TC, LDL-C, HDL-C, SBP, and DBP. Results: In the group of obese women, serum levels of FT4 were lower (P < 0.001) and serum levels of TSH were higher (P < 0.001) compared with nonobese controls. After adjusting for covariables, quantile regression analysis showed that serum levels of FT4 were inversely associated with BMI values between the quantile levels of 0.29 and 0.60 of BMI (i.e., BMI level of 22.49 and 28.31 kg/m2, respectively). Meanwhile, we found that serum levels of TSH positively correlated with BMI values after the quantile level of 0.51 (i.e., BMI level of 27.06 kg/m2), positively associated with TC after the quantile level of 0.6 (i.e., TC level of 4.86 mM), and positively associated with LDL-C after the quantile level of 0.39 (i.e., LDL level of 1.96 mM). No significant associations were found between serum levels of thyroid hormones and values of WHR, FBG, FI, HOMA-IR, TG, HDL-C, SBP, and DBP. Conclusions: FT4 and TSH play an important role in regulating the weight in women with normal thyroid function during their reproductive years. Women with decreased serum FT4 or increased serum TSH levels have a higher risk of developing obesity. Besides, TSH has a significant influence on metabolism of blood lipids. Women with higher serum levels of TSH have a higher risk of incidence of lipid metabolism disorders.


Assuntos
Obesidade/sangue , Obesidade/epidemiologia , Obesidade/etiologia , Testes de Função Tireóidea/normas , Hormônios Tireóideos/sangue , Adolescente , Adulto , Fatores Etários , Índice de Massa Corporal , Estudos de Casos e Controles , China/epidemiologia , Feminino , Indicadores Básicos de Saúde , Humanos , Resistência à Insulina , Lipídeos/sangue , Pessoa de Meia-Idade , Obesidade/diagnóstico , Valores de Referência , Reprodução/fisiologia , Fatores de Risco , Hormônios Tireóideos/normas , Adulto Jovem
12.
Medicine (Baltimore) ; 98(20): e15632, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31096477

RESUMO

BACKGROUND: It is commonly reported a limitation of therapeutic strategy in Eisenmenger syndrome (ES) historically. This qualitative systematic review is conducted to evaluate the safety and efficacy of pulmonary arterial hypertension-specific drug therapy (PAH-SDT) for ES patients for a clinical therapeutic strategy based on evidence. METHODS: PubMed, EMBASE, and the Cochrane Library databases have been systematically reviewed up to January 2019. Two reviewers independently conducted a literature search, quality evaluation, and data extraction. The occurrence of death, deterioration, and adverse events (AEs) has respectively been described as a count or percentage. Meta-analysis was conducted by Stata 15.1, and weighted mean differences (WMD) with 95% confidence intervals (CI) were recorded for continuous data. Randomized-effect model or fixed-effect model was applied according to the heterogeneity test. RESULTS: Fifteen citations recruiting 456 patients associated with ES were eventually pooled, which involved 4 RCTs, 6 prospective studies, and 5 retrospective studies. Within the first year, it indicated PAH-SDT significantly ameliorated exercise capacity in 6-minute walk distance (6MWD) (I = 60.5%; WMD: 53.86 m, 95% CI [36.59, 71.13], P < .001), functional class (FC) (WMD = -0.71, 95% CI [-0.98, -0.44], P < .001) and Borg dyspnea index (WMD = -1.28, 95% CI [-1.86, -0.70], P < .001), in addition to hemodynamics, especially mean pulmonary arterial pressure by 5.70 mmHg (WMD = -5.70 mmHg, 95% CI [-8.19, -3.22], P < .001) and pulmonary vascular resistance by 4.20 wood U (WMD: -4.20, 95% CI [-7.32, -1.09], P = .008), but unsatisfactory effects in oxygen saturation at exercise (P = .747). In a prolonged medication, bosentan, a dual ERA, has been proved acting an important role in improving exercise tolerance of patients with ES (6MWD: I = 47.5%; WMD: 88.68 m, 95% CI [54.05, 123.3], P < .001; FC: I = 0.0%; WMD = -0.65, 95% CI [-1.10, -0.19], P = .006). While a nonsignificant change of 6MWD was noted in a long-term therapy of ambrisentan (P = .385). There existed rare evidence about the efficacy and safety of macitentan, phosphodiesterase-5 inhibitors (PDE5i), and prostanoids in a prolonged medication. Most AEs were recorded as mild to moderate with PAH-SDT, but about 4.3% individuals treated with endothelin receptor antagonists (ERAs) suffered from serious ones, and 3.9% suffered from death. CONCLUSIONS: This systematic review and meta-analysis proved PAH-SDT as a safe and effective role in ES in an early stage. However, in a long-term treatment, bosentan has been supported for a lasting effect on exercise tolerance. A further multicenter research with a large sample about pharmacotherapy of ES is necessary.


Assuntos
Anti-Hipertensivos/uso terapêutico , Complexo de Eisenmenger/tratamento farmacológico , Antagonistas dos Receptores de Endotelina/uso terapêutico , Inibidores da Fosfodiesterase 5/uso terapêutico , Prostaglandinas/uso terapêutico , Anti-Hipertensivos/administração & dosagem , Anti-Hipertensivos/efeitos adversos , Bosentana/uso terapêutico , Antagonistas dos Receptores de Endotelina/administração & dosagem , Antagonistas dos Receptores de Endotelina/efeitos adversos , Tolerância ao Exercício/efeitos dos fármacos , Hemodinâmica , Humanos , Hipertensão Pulmonar/tratamento farmacológico , Oxigênio/sangue , Fenilpropionatos/uso terapêutico , Inibidores da Fosfodiesterase 5/administração & dosagem , Inibidores da Fosfodiesterase 5/efeitos adversos , Prostaglandinas/administração & dosagem , Prostaglandinas/efeitos adversos , Piridazinas/uso terapêutico , Pirimidinas/uso terapêutico , Sulfonamidas/uso terapêutico
13.
Diabetes Metab Res Rev ; 35(6): e3158, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-30908791

RESUMO

The prevalence of diabetes in China has increased rapidly from 0.67% in 1980 to 10.4% in 2013, with the aging of the population and westernization of lifestyle. Since its foundation in 1991, the Chinese Diabetes Society (CDS) has been dedicated to improving academic exchange and the academic level of diabetes research in China. From 2003 to 2014, four versions of Chinese diabetes care guidelines have been published. The guidelines have played an important role in standardizing clinical practice and improving the status quo of diabetes prevention and control in China. Since September 2016, the CDS has invited experts in cardiovascular diseases, psychiatric diseases, nutrition, and traditional Chinese medicine to work with endocrinologists from the CDS to review the new clinical research evidence related to diabetes over the previous 4 years. Over a year of careful revision, this has resulted in the present, new version of guidelines for prevention and care of type 2 diabetes in China. The main contents include epidemiology of type 2 diabetes in China; diagnosis and classification of diabetes; primary, secondary, and tertiary diabetes prevention; diabetes education and management support; blood glucose monitoring; integrated control targets for type 2 diabetes and treatments for hyperglycaemia; medical nutrition therapy; exercise therapy for type 2 diabetes; smoking cessation; pharmacologic therapy for hyperglycaemia; metabolic surgery for type 2 diabetes; prevention and treatment of cardiovascular and cerebrovascular diseases in patients with type 2 diabetes; hypoglycaemia; chronic diabetic complications; special types of diabetes; metabolic syndrome; and diabetes and traditional Chinese medicine.


Assuntos
Complicações do Diabetes/terapia , Diabetes Mellitus Tipo 2/terapia , Guias de Prática Clínica como Assunto/normas , Padrão de Cuidado , Automonitorização da Glicemia , China/epidemiologia , Complicações do Diabetes/etiologia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Humanos
14.
Diabetes Metab Res Rev ; 35(6): e3152, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-30884108

RESUMO

Blood glucose monitoring is an important part of diabetes management. Continuous glucose monitoring (CGM) technology has become an effective complement to conventional blood glucose monitoring methods and has been widely applied in clinical practice. The indications for its use, the accuracy of the generated data, the interpretation of the CGM results, and the application of the results must be standardized. In December 2009, the Chinese Diabetes Society (CDS) drafted and published the first Chinese Clinical Guideline for Continuous Glucose Monitoring (2009 edition), providing a basis for the standardization of CGM in clinical application. Based on the updates of international guidelines and the increasing evidence of domestic studies, it is necessary to revise the latest CGM guidelines in China so that the recent clinical evidence can be effectively translated into clinical benefit for diabetic patients. To this end, the CDS revised the Chinese Clinical Guideline for Continuous Glucose Monitoring (2012 Edition) based on the most recent evidence from international and domestic studies.


Assuntos
Automonitorização da Glicemia/normas , Glicemia/análise , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 2/sangue , Guias como Assunto , China/epidemiologia , Diabetes Mellitus Tipo 1/epidemiologia , Diabetes Mellitus Tipo 2/epidemiologia , Humanos , Prognóstico
15.
Am J Cardiovasc Drugs ; 19(4): 393-401, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30778875

RESUMO

BACKGROUND: This systematic review and meta-analysis was conducted to investigate the efficacy and safety of the chronic administration of aerosolized iloprost for pulmonary arterial hypertension (PAH). METHODS: All the relevant studies were obtained from three databases, namely, PubMed, Web of Science and the Cochrane Library, from the inception of each database to June 1, 2018. In our study, chronic treatment was defined as a period lasting at least 3 months. The rate of each event was analyzed by SPSS as a percentage with 95% confidence intervals (CIs). For the meta-analysis, a randomized effect model or a fixed effect model was applied according to the results of the heterogeneity test. RESULTS: Ten studies were included in this study, with a total of 370 patients treated with inhaled iloprost, including 214 in five randomized controlled trials and 156 in five prospective clinical trials. Among the patients who received inhaled iloprost, there was a significant improvement in the 6-min walk distance (6MWD) in the short-medium and prolonged treatment groups. Notably, the functionality improved by at least 1 class in 48.7% of the treated patients. In all the pooled studies, the estimated 3-month, 6-month, 1-year and 2-year event-free survival rates were 96.6%, 92.3%, 62.6% and 39.6%, respectively. In addition, there were eight adverse drug responses. CONCLUSION: In this systematic review and meta-analysis, inhaled iloprost has been shown to be a safe and well-tolerated agent for PAH in the first 3 months after diagnosis. If used for a prolonged period, aerosol iloprost monotherapy could contribute to an unsatisfactory improvement in vascular remodeling and even a decreased event-free survival rate.


Assuntos
Anti-Hipertensivos/uso terapêutico , Hipertensão Pulmonar/tratamento farmacológico , Iloprosta/administração & dosagem , Iloprosta/efeitos adversos , Inibidores da Agregação de Plaquetas/uso terapêutico , Animais , Humanos , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto
16.
Pediatr Cardiol ; 40(1): 29-37, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30121860

RESUMO

Long-term oral warfarin is recommended in pediatric Kawasaki disease patients with large coronary artery aneurysms; however, heterogeneity is considerable. This study aimed to determine variables affecting warfarin dosage in Kawasaki disease. The enrolled individuals (194 children) were divided into four groups: (1) Cases with severe coronary artery lesions (CAL) of IV to V degrees or thrombogenesis treated with oral warfarin were assigned to Group A; (2) Group B, CAL of I degrees; (3) Group C, CAL of II and III degrees cases with small or medium-sized CAL not treated with warfarin; (4) Group D, normal children without Kawasaki disease. The relevant genotypes of CYP2C9, VKORC1 (1173, - 1639, and 3730), and CYP4F2 were assessed. There were no statistically significant differences in CYP2C9, VKORC1, and CYP4F2 mutation frequencies among the 4 groups. In the 44 Group A patients, demographic features, clinical characteristics, and genotypes were recorded, and their associations with warfarin dose variability were assessed. Multivariate linear regression analysis revealed that height, VKORC1 1173, and CYP2C9 accounted for 61.2%, 7.9%, and 4.3% of dosing variability, respectively. Conclusions: Patient height is the main factor determining warfarin dosage, while genotype effects on warfarin dosage vary among studies. New formula should be defined using data obtained from children in cases with demonstrated efficacy.


Assuntos
Anticoagulantes/administração & dosagem , Estatura , Citocromo P-450 CYP2C9/genética , Síndrome de Linfonodos Mucocutâneos/tratamento farmacológico , Vitamina K Epóxido Redutases/genética , Varfarina/administração & dosagem , Adolescente , Estudos de Casos e Controles , Criança , Pré-Escolar , China , Relação Dose-Resposta a Droga , Feminino , Humanos , Lactente , Modelos Lineares , Masculino , Síndrome de Linfonodos Mucocutâneos/genética , Análise Multivariada , Mutação , Estudos Retrospectivos
17.
Pediatr Cardiol ; 40(5): 881-891, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30196381

RESUMO

A meta-analysis was performed for a comparison of outcomes between sutureless technique and conventional surgery for primary repair for total anomalous pulmonary venous connection (TAPVC). Electronic databases including PubMed, EMbase, Scopus, and Cochrane Library were searched systematically for the single-arm studies regarding sutureless repair or conventional surgery, and two-arm studies compared the outcomes of sutureless repair and conventional surgery for TAPVC. Corresponding data were extracted and the methodological quality was assessed by two reviewers independently. 26 studies were included, involving a total of 2702 patients. It was observed that compared with conventional surgery, sutureless technique was associated with a lower occurrence rate of post-operative pulmonary veins obstruction (PVO) (4.6% vs. 13.5%, OR 0.54 in favor of sutureless technique) and re-operations due to PVO (3.4% vs. 12.4%, 0.25 in favor of sutureless technique). However, meta-analyses of post-operative early (OR 0.57; 95% CI 0.27-1.19; P = 0.13), late (OR 0.37; 95% CI 0.13-1.06; P = 0.13), and overall (OR 0.61; 95% CI 0.36-1.03; P = 0.07) mortality showed no significant difference between sutureless technique and conventional surgery. Compared with conventional surgery, sutureless technique was associated with a lower occurrence rate of post-operative PVO and re-operations due to PVO. Meanwhile, post-operative early, late, and overall mortality were not statistically different between two surgical approaches. Sutureless technique is beneficial in the primary repair of TAPVC regarding post-operative PVO and re-operations due to PVO. However, the level of evidence was low and randomized controlled trials should be designed to evaluate the safety and effectiveness of sutureless technique for TAPVC.


Assuntos
Síndrome de Cimitarra/cirurgia , Procedimentos Cirúrgicos sem Sutura/efeitos adversos , Suturas/efeitos adversos , Procedimentos Cirúrgicos Cardíacos/métodos , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Complicações Pós-Operatórias/epidemiologia , Período Pós-Operatório , Veias Pulmonares/cirurgia , Reoperação/estatística & dados numéricos
18.
Hepatology ; 69(6): 2414-2426, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30341767

RESUMO

To investigate the effect of antidiabetic agents on nonalcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes mellitus (T2DM), 75 patients with T2DM and NAFLD under inadequate glycemic control by metformin were randomized (1:1:1) to receive add-on liraglutide, sitagliptin, or insulin glargine in this 26-week trial. The primary endpoint was the change in intrahepatic lipid (IHL) from baseline to week 26 as quantified by magnetic resonance imaging-estimated proton density fat fraction (MRI-PDFF). Secondary endpoints included changes in abdominal adiposity (subcutaneous adipose tissue [SAT] and visceral adipose tissue [VAT]), glycated hemoglobin, and body weight from baseline to week 26. We analysed data from intent-to-treat population. MRI-PDFF, VAT, and weight decreased significantly with liraglutide (15.4% ± 5.6% to 12.5% ± 6.4%, P < 0.001; 171.4 ± 27.8 to 150.5 ± 30.8, P = 0.003; 86.6 ± 12.9 kg to 82.9 ± 11.1 kg, P = 0.005, respectively) and sitagliptin (15.5% ± 5.6% to 11.7% ± 5.0%, P = 0.001; 153.4 ± 31.5 to 139.8 ± 27.3, P = 0.027; 88.2 ± 13.6 kg to 86.5 ± 13.2 kg, P = 0.005, respectively). No significant change in MRI-PDFF, VAT, or body weight was observed with insulin glargine. SAT decreased significantly in the liraglutide group (239.9 ± 69.0 to 211.3 ± 76.1; P = 0.020) but not in the sitagliptin and insulin glargine groups. Changes from baseline in MRI-PDFF, VAT, and body weight were significantly greater with liraglutide than insulin glargine but did not differ significantly between liraglutide and sitagliptin. Conclusion: Combined with metformin, both liraglutide and sitagliptin, but not insulin glargine, reduced body weight, IHL, and VAT in addition to improving glycemic control in patients with T2DM and NAFLD.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Insulina Glargina/uso terapêutico , Liraglutida/uso terapêutico , Metformina/uso terapêutico , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Fosfato de Sitagliptina/uso terapêutico , Adulto , Idoso , Glicemia/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Comorbidade , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiologia , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Humanos , Hipoglicemiantes/uso terapêutico , Modelos Lineares , Metabolismo dos Lipídeos/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Prognóstico , Estudos Prospectivos , Resultado do Tratamento
19.
Interact Cardiovasc Thorac Surg ; 28(2): 291-300, 2019 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30060099

RESUMO

A meta-analysis was performed to compare the outcomes between surgery and balloon angioplasty (BA) for native coarctation of the aorta in paediatric patients. Electronic databases, including PubMed, EMbase, Medline and Cochrane Library were searched systematically for literature aimed mainly at comparing the therapeutic effects for native coarctation of the aorta administered by surgery or BA. Corresponding data sets were extracted and 2 reviewers independently assessed the methodological quality. Ten studies meeting the inclusive criteria were identified involving a total of 723 subjects. Eventually, it was observed that compared with BA, surgery was significantly associated with a lower incidence of recoarctation, repeat intervention due to recoarctation and residual transcoarctation gradient in mid- to long-term follow-up. However, BA was significantly associated with a shorter hospitalization time. Incidence of aneurysm formation, perioperative mortality, complications and immediate transcoarctation residual gradient were not statistically different between surgery and BA. The overall level of evidence for our study was low and randomized controlled trials should be designed to evaluate and compare the safety and effectiveness of both approaches for native coarctation of the aorta.


Assuntos
Angioplastia com Balão , Coartação Aórtica/terapia , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino
20.
Medicine (Baltimore) ; 97(42): e12869, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30335000

RESUMO

RATIONALE: Familial hypercholesterolemia (FH) is a common inherited cause of coronary heart disease (CHD) and premature death in an early age. Nevertheless, an ischemic heart failure (IHF) associated with FH seems to be rare, and an early diagnosis and therapy could influence the prognosis. PATIENT CONCERNS: In this 13-year-old girl, multiple xanthomas began to develop from the first day of birth. Until June, 2017, she was admitted to our center due to edema, oliguria, and dyspnea during exertion, which was attributed to a recent respiratory infection. DIAGNOSIS: Homozygous FH (HoFH), CHD, and IHF. INTERVENTIONS: The patient has been treated with statin, ezetimibe, aspirin, and traditional heart failure (HF) medications. In addition, the beta-blocker was simultaneously administered. OUTCOMES: Genotypes of this proband indicated homozygous mutations of low-density lipoprotein receptor (LDLR) and some co-segregated mutations, such as von Willebrand factor (VWF) and fibroblast growth factor receptors. At 6-month follow-up, we found a decreased level of plasma lipid profile, in addition to a significant improvement in 6-minute walk distance and functional class. Echocardiography indicated nonsignificant improvements in the structure and function of the heart. LESSONS: This case report indicates that HoFH can lead to dramatically progressive endothelial damages and ventricular remodeling, severe atherosclerosis, even IHF. Genetic outcomes indicate IHF with HoFH could possibly result from LDLR mutations and some co-segregated mutations influencing endothelial function and cardiovascular remodeling. In a short-term follow-up, a combination of statins, ezetimibe, aspirin, and traditional HF agents is safe and effective for IHF with HoFH, and there is a need for further identification of drugs to ameliorate endothelial function and cardiovascular remodeling which may play an important role in long-term treatment.


Assuntos
Doença das Coronárias/congênito , Insuficiência Cardíaca/congênito , Hiperlipoproteinemia Tipo II/complicações , Isquemia Miocárdica/congênito , Xantogranuloma Juvenil/congênito , Adolescente , Anticolesterolemiantes/uso terapêutico , Aspirina/uso terapêutico , Doença das Coronárias/tratamento farmacológico , Ezetimiba/uso terapêutico , Feminino , Insuficiência Cardíaca/tratamento farmacológico , Homozigoto , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hiperlipoproteinemia Tipo II/tratamento farmacológico , Mutação , Isquemia Miocárdica/tratamento farmacológico , Inibidores da Agregação de Plaquetas/uso terapêutico , Receptores de LDL/genética , Xantogranuloma Juvenil/tratamento farmacológico
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