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1.
JAMA Cardiol ; 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32236489

RESUMO

Importance: Idiopathic pulmonary arterial hypertension (IPAH) is a fatal disease with high heritability; however, the bone morphogenetic protein receptor 2 (BMPR2) gene only accounts for 17% of IPAH. The genetic basis of IPAH needs further investigation. Objective: To identify novel IPAH susceptibility genes other than BMPR2. Design, Setting, and Participants: This 2-stage, case-control genetic association study enrolled 230 patients with IPAH from 2 referral pulmonary hypertension centers in China. Eligible patients had no BMPR2 variants and were compared with 968 healthy control participants. Data were collected from January 1, 2000, to July 31, 2015, and analyzed from August 1, 2015, to May 30, 2018. Exposures: PTGIS rare variants. Main Outcomes and Measures: Whole-genome sequencing was performed to identify putative IPAH genes in a discovery cohort, with validation in an independent referral cohort. Correlation of genotype and hemodynamic characteristics was then evaluated at baseline and after pulmonary vasodilator testing. Functional assessments were conducted to analyze the effects of identified genetic variants on transcript splicing, enzymatic activity, and endothelial cell phenotypes. Results: Among 230 patients with IPAH (164 female [71.3%]; mean [SD] age, 34 [18] years), an enrichment of rare variants in a gene encoding prostacyclin synthase (PTGIS) was identified in the discovery cohort. The association of PTGIS rare variants with IPAH was confirmed in the replication cohort. In the combined data set, PTGIS rare variants were found in 14 of 230 cases (6.1%) and 8 of 968 controls (0.8%) (odds ratio, 7.8; 95% CI, 3.2-18.8; P = 5 × 10-6, logistic regression). Compared with patients without PTGIS variants, inhaled iloprost induced a more significant decrease of pulmonary vascular resistance (difference in the least square mean, -21.7%; 95% CI, -31.4% to -12.0%; P < .001, linear regression model) and an increase of cardiac index (difference in the least square mean, 18.3%; 95% CI, 8.8%-27.8%; P < .001, linear regression model) in patients with PTGIS variants. The minigene assay indicated that the c.521 + 1G>A variant resulted in aberrant messenger RNA transcripts. The functional studies showed that the 2 missense rare variants (R252Q and A447T) resulted in a decrease in prostacyclin production and increased cell death of pulmonary microvascular endothelial cells. Conclusions and Relevance: This study identified 3 rare loss-of-function variants in the PTGIS gene from 2 independent cohorts with IPAH. The genetic variants of PTGIS predispose pulmonary vascular responses to the iloprost stimulation. These findings suggest that PTGIS variants may be involved in the pathogenesis of IPAH.

2.
Int J Cancer ; 146(1): 272-280, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31162842

RESUMO

Epstein-Barr virus (EBV)-associated gastric carcinomas (EBVaGCs) may account for 8-9% of all gastric cancer (GC) patients. All previous reports on EBVaGC were retrospective. Prospective study is warranted to evaluate the exact role of EBV status in predicting the prognosis of GC. It is of special interest to figure out whether dynamic detection of plasma EBV-DNA load could be a feasible biomarker for the monitor of EBVaGC. From October 2014 to September 2017, we consecutively collected GC patients (n = 2,760) from Sun Yat-sen University Cancer Center for EBER examination. We detected EBV-DNA load in plasma and tissue samples of EBVaGC patients at baseline. Subsequently, plasma EBV-DNA load was dynamically monitored in EBVaGC patients. The overall prevalence of EBVaGC is 5.1% (140/2,760). The incidence rate of EBVaGC decreased with advanced AJCC 7th TNM stage (p < 0.001), with the corresponding percentages of 9.3, 9.9, 6.7 and 1.4% for Stage I, II, III and IV patients. EBVaGC patients were predominately young males with better histologic differentiation and earlier TNM stage than EBV-negative GC (EBVnGC) patients. EBVaGC patients were confirmed to had a favorable 3-year survival rate (EBVaGC vs. EBVnGC: 76.8% vs. 58.2%, p = 0.0001). Though only 52.1% (73/140) EBVaGC patients gained detectable EBV-DNA and 43.6% (61/140) reached a positive cutoff of 100 copies/ml, we found the plasma EBV-DNA load in EBVaGC decreased when patients got response, while it increased when disease progressed. Our results suggested that plasma EBV-DNA is a good marker in predicting recurrence and chemotherapy response for EBVaGC patients.


Assuntos
DNA Viral/sangue , Herpesvirus Humano 4/isolamento & purificação , Neoplasias Gástricas/virologia , Carga Viral , Idoso , Feminino , Herpesvirus Humano 4/genética , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
3.
Arterioscler Thromb Vasc Biol ; 39(6): 1055-1071, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30943771

RESUMO

Objective- Vascular adventitia encompasses progenitors and is getting recognized as the major site of inflammation in early stage of atherosclerosis. However, the cellular atlas of the heterogeneous adventitial cells, the intercellular communication, the cellular response of adventitia to hyperlipidemia, and its contribution to atherosclerosis have been elusive. Approach and Results- Single-cell RNA sequencing was applied to wt (wild type) and ApoE (apolipoprotein E)-deficient aortic adventitia from 12-week-old C57BL/6J mice fed on normal laboratory diet with early stage of atherosclerosis. Unbiased clustering analysis revealed that the landscape of adventitial cells encompassed adventitial mesenchyme cells, immune cells (macrophages, T cells, and B cells), and some types of rare cells, for example, neuron, lymphatic endothelial cells, and innate lymphoid cells. Seurat clustering analysis singled out 6 nonimmune clusters with distinct transcriptomic profiles, in which there predominantly were stem/progenitor cell-like and proinflammatory population (Mesen II). In ApoE-deficient adventitia, resident macrophages were activated and related to increased myeloid cell infiltration in the adventitia. Cell communication analysis further elucidated enhanced interaction between a mesenchyme cluster and inflammatory macrophages in ApoE-deficient adventitia. In vitro transwell assay confirmed the proinflammatory role of SCA1+ (stem cell antigen 1 positive) Mesen II population with increased CCL2 (chemokine [C-C motif] ligand 2) secretion and thus increased capacity to attract immune cells in ApoE-deficient adventitia. Conclusions- Cell atlas defined by single-cell RNA sequencing depicted the heterogeneous cellular landscape of the adventitia and uncovered several types of cell populations. Furthermore, resident cell interaction with immune cells appears crucial at the early stage of atherosclerosis.


Assuntos
Túnica Adventícia/metabolismo , Apolipoproteínas E/genética , Aterosclerose/genética , Células Endoteliais/metabolismo , Hiperlipidemias/genética , Túnica Adventícia/citologia , Animais , Aterosclerose/fisiopatologia , Células Cultivadas , Análise por Conglomerados , Modelos Animais de Doenças , Células Endoteliais/citologia , Linfócitos/metabolismo , Macrófagos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Pericitos/metabolismo , Distribuição Aleatória , Valores de Referência , Análise de Sequência de RNA/métodos
4.
Immunotherapy ; 11(4): 311-320, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30678553

RESUMO

AIM: To estimate efficacy of checkpoint inhibitors and rank treatment effects in non-small-cell lung cancer. MATERIALS & METHODS: Prospective randomized trials were included. p-score was used to rank treatment effects. RESULTS: A total of nine trials were identified, involving 5504 patients and three checkpoint inhibitors. Pembrolizumab plus chemotherapy had the highest p-score of 0.95 among all the treatments, and was superior to pembrolizumab alone (hazard ratio: 0.87; 95% CI: 0.79-0.95). Combination therapy had more grade 3-5 adverse events; but toxicity-related discontinuation and treatment-related death did not increase. CONCLUSION: Pembrolizumab plus chemotherapy was likely to be the most effective treatment for patients with wild-type advanced NSCLC.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Imunoterapia/métodos , Neoplasias Pulmonares/tratamento farmacológico , Nivolumabe/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Humanos , Neoplasias Pulmonares/mortalidade , Estadiamento de Neoplasias , Metanálise em Rede , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Ensaios Clínicos Controlados Aleatórios como Assunto , Análise de Sobrevida
5.
Eur Respir J ; 53(3)2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30578397

RESUMO

BACKGROUND: Idiopathic pulmonary arterial hypertension (IPAH) is a rare disease with high heritability. Although several predisposing genes have been linked to IPAH, the genetic aetiology remains unknown for a large number of IPAH cases. METHODS: We conducted an exome-wide gene-based burden analysis on two independent case-control studies, including a total of 331 IPAH cases and 10 508 controls. Functional assessments were conducted to analyse the effects of genetic mutations on protein biosynthesis and function. RESULTS: The gene encoding human bone morphogenetic protein 9 (BMP9) was identified as a novel genetic locus displaying exome-wide association with IPAH in the discovery cohort (OR 18.8; p=1.9×10-11). This association was authenticated in the independent replication cohort (p=1.0×10-5). Collectively, the rare coding mutations in BMP9 occurred in 6.7% of cases, ranking this gene second to BMPR2, comprising a combined significance of 2.7×10-19 (OR 21.2). Intriguingly, the patients with BMP9 mutations had lower plasma levels of BMP9 than those without. Functional studies showed that the BMP9 mutations led to reduced BMP9 secretion and impaired anti-apoptosis ability in pulmonary arterial endothelial cells. CONCLUSION: We identify BMP9 as an IPAH culprit gene.

6.
Water Sci Technol ; 80(8): 1571-1580, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31961819

RESUMO

Rhodamine B (RhB), widely used as an industrial dye, is a toxic organic that is hazardous to human health and can cause water pollution. In this study, the removal rate of RhB was investigated by the following methods: hydrodynamic cavitation (HC) operated individually, and HC combined with oxidants H2O2 or ClO2. The effect of different operating parameters including pressure (2-6 bar) and initial pH (2-8) on the extent of degradation was investigated using an orifice plate as the cavitation device to achieve maximum removal of RhB. Under the parameters of HC, the effect of different loadings was investigated: H2O2 (n(RhB):n(H2O2) was varied from 1:17.60 to 1:211.28) and ClO2 (n(RhB):n(ClO2) was varied from 1:8.87 to 1:177.53). A combination of cavitation and H2O2 or ClO2 resulted in degradations of 80.6% and 95.3%. The results indicated that the combination of HC and oxidants was better than the individual HC process for the degradation of RhB. When combining HC with H2O2 or ClO2, the synergistic coefficients of 62.54 and 74.79 were obtained. The combination of HC and ClO2 was proven to be more effective for the removal of RhB compared to HC alone and the hybrid process of HC and H2O2.


Assuntos
Hidrodinâmica , Peróxido de Hidrogênio , Rodaminas
7.
J Exp Med ; 215(8): 2175-2195, 2018 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-29970474

RESUMO

Pulmonary arterial hypertension (PAH) is a life-threatening disease characterized by progressive pulmonary artery (PA) remodeling. T helper 2 cell (Th2) immune response is involved in PA remodeling during PAH progression. Here, we found that CRTH2 (chemoattractant receptor homologous molecule expressed on Th2 cell) expression was up-regulated in circulating CD3+CD4+ T cells in patients with idiopathic PAH and in rodent PAH models. CRTH2 disruption dramatically ameliorated PA remodeling and pulmonary hypertension in different PAH mouse models. CRTH2 deficiency suppressed Th2 activation, including IL-4 and IL-13 secretion. Both CRTH2+/+ bone marrow reconstitution and CRTH2+/+ CD4+ T cell adoptive transfer deteriorated hypoxia + ovalbumin-induced PAH in CRTH2-/- mice, which was reversed by dual neutralization of IL-4 and IL-13. CRTH2 inhibition alleviated established PAH in mice by repressing Th2 activity. In culture, CRTH2 activation in Th2 cells promoted pulmonary arterial smooth muscle cell proliferation through activation of STAT6. These results demonstrate the critical role of CRTH2-mediated Th2 response in PAH pathogenesis and highlight the CRTH2 receptor as a potential therapeutic target for PAH.


Assuntos
Hipertensão Pulmonar/imunologia , Ativação Linfocitária/imunologia , Receptores Imunológicos/metabolismo , Receptores de Prostaglandina/metabolismo , Células Th2/imunologia , Transferência Adotiva , Adulto , Animais , Anticorpos/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Medula Óssea/efeitos dos fármacos , Medula Óssea/metabolismo , Proliferação de Células/efeitos dos fármacos , Quimera , Doença Crônica , Modelos Animais de Doenças , Feminino , Deleção de Genes , Humanos , Hipertensão Pulmonar/fisiopatologia , Hipóxia/complicações , Hipóxia/fisiopatologia , Imunidade/efeitos dos fármacos , Indóis , Pulmão/efeitos dos fármacos , Pulmão/patologia , Pulmão/fisiopatologia , Masculino , Camundongos , Ovalbumina , Artéria Pulmonar/efeitos dos fármacos , Artéria Pulmonar/patologia , Artéria Pulmonar/fisiopatologia , Pirróis , Receptores Imunológicos/deficiência , Receptores de Prostaglandina/deficiência , Fator de Transcrição STAT6/metabolismo , Regulação para Cima/efeitos dos fármacos
8.
Respir Res ; 19(1): 94, 2018 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-29751839

RESUMO

BACKGROUND: Pulmonary arterial hypertension (PAH) is a rare systemic disorder associated with considerable metabolic dysfunction. Although enormous metabolomic studies on PAH have been emerging, research remains lacking on metabolic reprogramming in experimental PAH models. We aim to evaluate the metabolic changes in PAH and provide new insight into endogenous metabolic disorders of PAH. METHOD: A single subcutaneous injection of monocrotaline (MCT) (60 mg kg- 1) was used for rats to establish PAH model. Hemodynamics and right ventricular hypertrophy were adopted to evaluate the successful establishment of PAH model. Plasma samples were assessed through targeted metabolomic profiling platform to quantify 126 endogenous metabolites. Orthogonal partial least squares discriminant analysis (OPLS-DA) was used to discriminate between MCT-treated model and control groups. Metabolite Set Enrichment Analysis was adapted to exploit the most disturbed metabolic pathways. RESULTS: Endogenous metabolites of MCT treated PAH model and control group were well profiled using this platform. A total of 13 plasma metabolites were significantly altered between the two groups. Metabolite Set Enrichment Analysis highlighted that a disruption in the urea cycle pathway may contribute to PAH onset. Moreover, five novel potential biomarkers in the urea cycle, adenosine monophosphate, urea, 4-hydroxy-proline, ornithine, N-acetylornithine, and two candidate biomarkers, namely, O-acetylcarnitine and betaine, were found to be highly correlated with PAH. CONCLUSION: The present study suggests a new role of urea cycle disruption in the pathogenesis of PAH. We also found five urea cycle related biomarkers and another two candidate biomarkers to facilitate early diagnosis of PAH in metabolomic profile.


Assuntos
Hipertensão Pulmonar/induzido quimicamente , Hipertensão Pulmonar/metabolismo , Metabolômica/métodos , Monocrotalina/toxicidade , Transdução de Sinais/fisiologia , Ureia/metabolismo , Animais , Hipertensão Pulmonar/patologia , Masculino , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley
9.
J Int Med Res ; 46(2): 802-810, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29231776

RESUMO

Objective To evaluate the efficacy and safety of using the Ilizarov invasive distraction technique combined with limited surgical operations in the treatment of relapsed talipes equinovarus in children. Methods This retrospective study analysed the outcomes of paediatric patients with relapsed talipes equinovarus who were treated with the Ilizarov technique with moderate open limited soft tissue or bony operations. The International Clubfoot Study Group (ICFSG) classification system score was used to evaluate the deformities before and after surgery. Results The study evaluated 16 feet in 14 patients (nine boys). The correction time ranged from 6 to 12 weeks. The mean duration of frame application was 5.9 months. The gait was improved significantly in all patients. At final follow-up, the mean ankle dorsiflexion and plantarflexion ranges were 8.3° and 34.6°, respectively. The talocalcaneal angle improved from 10.0° preoperatively to 28.3° postoperatively in the anteroposterior plane; and from 4.1° preoperatively to 42.1° postoperatively in the lateral plane. The differences in the angle of plantarflexion, dorsiflexion, range of motion of the ankle joint and talocalcaneal angles pre- and postoperation were significant. Conclusions These current findings suggest that the Ilizarov technique combined with limited surgery effectively corrects relapsed talipes equinovarus in children.


Assuntos
Pé Torto Equinovaro/cirurgia , Técnica de Ilizarov/reabilitação , Amplitude de Movimento Articular/fisiologia , Procedimentos Cirúrgicos Reconstrutivos/métodos , Recuperação de Função Fisiológica , Adolescente , Criança , Pré-Escolar , Pé Torto Equinovaro/patologia , Feminino , Marcha/fisiologia , Humanos , Masculino , Recidiva , Estudos Retrospectivos , Resultado do Tratamento
10.
Chin J Traumatol ; 20(6): 347-351, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29198718

RESUMO

PURPOSE: To compare the efficacy of quadratus femoris muscle pedicle bone flap transplantation combined with hollow compression screw fixation versus AO hollow compression screw fixation in the treatment of femoral neck fracture for Chinese young and middle-aged patients. METHODS: Case-controlled studies (CCTs) were used to compare the two operative methods in the treatment of femoral neck fractures. Data were retrieved from the Cochrane Library, Pubmed Database, CNKI, Chinese Biomedical Database. Wanfang Data published during the period of January 2005 to December 2014. Methodological quality of the trials was critically assessed, and relevant data were extracted. Statistical Software Revman 5.0 was used for data-analysis. RESULTS: Eight articles were included in the meta-analysis. The results showed that there was statistical significance in the rate of fracture healing [OR = 5.43, 95% CI (2.89, 10.20), p < 0.05], the rate of good function of hip joint [OR = 5.12, 95% CI (3.21, 8.17), p < 0.05], the rate of femoral head necrosis [OR = 4.21, 95% CI (2.02, 8.76), p < 0.05], the time of fracture healing [WMD = -46.85, 95% CI (-65.13, -28.56), p < 0.05] between the two groups. CONCLUSIONS: For the treatment of femoral neck fractures, the transplantation of quadratus femoris muscle pedicle bone flap combined with hollow compression screw; fixation is superior to the AO hollow compression screw fixation in terms of the rate; of fracture healing, the rate of good function of hip joint, the rate of femoral head; necrosis and the time of fracture healing.


Assuntos
Fraturas do Colo Femoral/cirurgia , Retalhos Cirúrgicos , Adulto , Estudos de Casos e Controles , Fêmur/patologia , Necrose da Cabeça do Fêmur , Fixação Interna de Fraturas/métodos , Consolidação da Fratura , Humanos , Pessoa de Meia-Idade , Músculo Esquelético
11.
ANZ J Surg ; 87(10): 815-819, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28815843

RESUMO

BACKGROUND: The objective of this study was to evaluate the efficacy and safety of using Ilizarov invasive distraction technique combined with limited surgical operations in the treatment of post-traumatic talipes equinovarus in children. METHODS: Eighteen cases of post-traumatic deformed feet in 15 patients who received the treatment of Ilizarov frame application, limited soft-tissue release or osteotomy were selected in this study. After removal of the frame, an ankle-foot orthosis was used continuously for another 6-12 months. Pre- and post-operatively, the International Clubfoot Study Group (ICFSG) score was employed to evaluate the gait and range of motion of the ankle joint. Radiographical assessment was also conducted. RESULTS: Patients were followed up for 22 (17-32) months. Ilizarov frame was applied for a mean duration of 5.5 (4-9) months. When it was removed, the gait was improved significantly in all the patients. The correction time was 6-8 weeks for patients who underwent soft-tissue release and 8-12 weeks for those with bone osteotomy. At the last follow-up assessment, the differences between pre- and post-operative plantar-flexion angle, dorsiflexion, motion of ankle joint and talocalcaneal angle were significant (all P < 0.05). The observed complications included wire-hole infection in one foot, toe contracture in one, residual deformity in three, recurrence of deformity in two and spastic ischaemia in one foot. CONCLUSION: Our findings suggest that Ilizarov technique combined with limited surgical operation can be considered as an efficient and successful method for correction of post-traumatic talipes equinovarus in children.


Assuntos
Pé Torto Equinovaro/cirurgia , Pé Torto Equinovaro/terapia , Técnica de Ilizarov/estatística & dados numéricos , Procedimentos Ortopédicos/métodos , Osteotomia/métodos , Ferimentos e Lesões/complicações , Adolescente , Assistência ao Convalescente , Articulação do Tornozelo/diagnóstico por imagem , Articulação do Tornozelo/fisiologia , Criança , Pré-Escolar , Pé Torto Equinovaro/etiologia , Feminino , Humanos , Masculino , Aparelhos Ortopédicos/estatística & dados numéricos , Amplitude de Movimento Articular/fisiologia , Recuperação de Função Fisiológica , Articulação Talocalcânea/fisiologia , Resultado do Tratamento , Ferimentos e Lesões/patologia
12.
Chin J Traumatol ; 20(4): 229-234, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28709737

RESUMO

PURPOSE: To compare the efficacy and safety of open reduction and internal fixation through ilioinguinal approach and Stoppa approach for the treatment of displaced acetabular fractures. METHODS: Case-controlled trials (CCTs) published from January 2010 to August 2015 that compared the ilioinguinal approach and Stoppa approach in the management of displaced acetabular fractures were retrieved from the databases of Cochrane Library, Pubmed, CNKI, and so on. Methodological quality of the trials was critically assessed. Statistical software RevMan 5.0 was used for data analysis. RESULTS: Eight articles were included in the meta-analysis. Through comparing the efficacy and safety of ilioinguinal approach and Stoppa approach in the treatment of displaced acetabular fracture, statistical significance was found in the average operation time [WMD = 68.29, 95% CI (10.52, 126.05), p < 0.05] and the median intraoperative blood loss [WMD = 142.26, 95% CI (9.30, 275.23), p < 0.05]. However, there existed no statistical significance in the fracture end reset satisfaction rate [RR = 0.63, 95% CI (0.17, 2.37), p > 0.05], the early complications rate [RR = 0.89, 95% CI (0.33, 2.40), p > 0.05], the late complications rate [RR = 0.91, 95% CI (0.27, 3.01), p > 0.05], and Harris hip score good function rate [RR = 0.52, 95% CI (0.25, 1.10), p > 0.05]. CONCLUSION: Though both techniques can obtain satisfactory clinical functions in the treatment of displaced acetabular fractures, Stoppa approach is superior to the ilioinguinal approach in terms of operation time and intraoperative blood loss.


Assuntos
Acetábulo/lesões , Fixação Interna de Fraturas/métodos , Fraturas Ósseas/cirurgia , Redução Aberta/métodos , Fixação Interna de Fraturas/efeitos adversos , Humanos , Redução Aberta/efeitos adversos , Complicações Pós-Operatórias/epidemiologia
13.
Sci Rep ; 7(1): 743, 2017 04 07.
Artigo em Inglês | MEDLINE | ID: mdl-28389663

RESUMO

We evaluated how metabolic disorders affected antihypertension therapy. 2,912 rural Chinese patients with hypertension who provided blood samples, demographic and clinical data at baseline and after 1 year of antihypertension therapy were evaluated. At baseline, 1,515 patients (52.0%) were already receiving drug therapy and 11.4% of them had controlled blood pressure (BP). After 1 year, all 2,912 patients were receiving antihypertension therapy that was administered by community physicians, and 59.42% of them had controlled BP. Central obesity and abnormal triglyceride, high-density lipoprotein cholesterol, and glucose were associated with 15-70% higher risks of uncontrolled hypertension. Metabolic syndrome using the JIS criteria was associated with poor BP control (odds ratio: 1.71 and 1.54 for the baseline and follow-up datasets, respectively). The risk of uncontrolled hypertension increased with the number of metabolic disorders (p for trend <0.01). The presence of ≥3 metabolic disorder factors was associated with higher risks of poor BP control. The associations of metabolic factors and uncontrolled hypertension were stronger for the standard and modified ATP III criteria, compared to the IDF and JIS criteria. Metabolic factors were associated with less effective antihypertension therapy, and all definitions of metabolic syndrome helped identify patients with elevated risks of uncontrolled hypertension.


Assuntos
Hipertensão/complicações , Hipertensão/epidemiologia , Síndrome Metabólica/complicações , Síndrome Metabólica/epidemiologia , Adolescente , Adulto , Idoso , Anti-Hipertensivos/farmacologia , Anti-Hipertensivos/uso terapêutico , Biomarcadores , Feminino , Humanos , Hipertensão/diagnóstico , Hipertensão/tratamento farmacológico , Estilo de Vida , Masculino , Pessoa de Meia-Idade , Vigilância da População , Fatores de Risco , Índice de Gravidade de Doença , Inquéritos e Questionários , Falha de Tratamento , Resultado do Tratamento , Adulto Jovem
15.
Sci Rep ; 6: 38089, 2016 11 30.
Artigo em Inglês | MEDLINE | ID: mdl-27901076

RESUMO

The prevalence of metabolic syndrome (MS) varies worldwide due to genetic and environmental factors. A population-based cross-sectional study, with 37,582 participants recruited in Nantong, China in 2007-2008 (stage I) and 2013 (stage II). Socio-demographic, lifestyle factors, disease history and fasting blood sample were collected. The prevalence of MS was much higher in 2013 (42.6%) than that in 2007-2008 (21.6%), which was significantly higher in older people in both stages. Participants with two or more familial history of diseases were associated with a higher MS prevalence compared to those who didn't have familial history of diseases. Total physical activity (PA) was associated with 24 and 19% decreased risk of MS in men and women. Occupational PA in moderate and vigorous intensity was associated with a 25%-45% decreased risk of MS. Female smokers who smoked more than 10 cigarettes per day or over 25 years were associated with 96 and 74% increased MS risk, respectively. The highest quartile of rice wine consumption was associated with a lower risk of MS with OR of 0.63 in women, compared with female non-drinkers. These findings indicated that PA and rice wine are two protective factors in MS prevention in rural areas of East China.


Assuntos
Síndrome Metabólica/epidemiologia , População Rural , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Consumo de Bebidas Alcoólicas , China/epidemiologia , Exercício Físico , Feminino , Humanos , Masculino , Síndrome Metabólica/fisiopatologia , Pessoa de Meia-Idade , Prevalência
16.
Eur Respir J ; 48(5): 1386-1395, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27660508

RESUMO

Intact nitric oxide (NO) signalling is critical to maintaining appropriate pulmonary vascular tone. NO bioavailability is reduced in patients with pulmonary arterial hypertension. This study aimed to examine the impact of NO plasma metabolites (NOx) relative to haemodynamic dysfunction and mortality in patients with idiopathic pulmonary arterial hypertension (IPAH).A total of 104 consecutive adult IPAH patients who had undergone genetic counselling when first diagnosed were enrolled in this prospective study.The median concentration of NOx (µmol·L-1) was significantly lower in IPAH patients compared with healthy subjects, and was decreased further in 19 carriers of the bone morphogenetic protein-receptor type-2 (BMPR2) mutation compared to non-carriers. Reduced concentrations of NOx were correlated with mean pulmonary arterial pressure (mPAP), pulmonary vascular resistance (PVR) and cardiac output. Compared with higher baseline NOx concentrations, patients with a NOx concentration of ≤10 µmol·L-1 had a markedly worse survival. After adjustment for clinical features, a BMPR2 mutation and haemodynamics, a lower NOx level remained an increased risk of mortality.Patients with IPAH had lower levels of plasma NOx, which correlated inversely with mPAP, PVR and survival. Plasma NOx may be an important biomarker and prognostic indicator, suggesting that reduced NO synthesis contributes to the pathogenesis of IPAH.


Assuntos
Hipertensão Pulmonar Primária Familiar/metabolismo , Óxido Nítrico/metabolismo , Adulto , Biomarcadores/metabolismo , Pressão Sanguínea , Receptores de Proteínas Morfogenéticas Ósseas Tipo II/genética , Cateterismo Cardíaco , Débito Cardíaco , Hipertensão Pulmonar Primária Familiar/fisiopatologia , Feminino , Aconselhamento Genético , Hemodinâmica , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Pressão , Prognóstico , Estudos Prospectivos , Artéria Pulmonar/patologia , Risco , Resistência Vascular , Adulto Jovem
17.
Int J Cardiol ; 222: 368-374, 2016 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-27500766

RESUMO

BACKGROUND: Aberrant transforming growth factor (TGF)-ß signaling is involved in the pathogenesis of pulmonary arterial hypertension (PAH). We aimed to investigate the predictive value of the upstream ligand of TGF-ß signaling (TGF-ß1) on long-term mortality and the clinical characteristics of patients with idiopathic pulmonary arterial hypertension (IPAH) and heritable PAH (HPAH). METHODS AND RESULTS: Plasma TGF-ß1 levels were measured in 151 IPAH and 65 HPAH patients retrospectively enrolled between January 2008 and March 2013, and compared to 61 healthy subjects. Data for mortality over time were obtained from hospital databases and from telephone follow-ups. The main outcome was all-cause death. Plasma TGF-ß1 was significantly higher in IPAH/HPAH patients compared to control subjects (4.74 vs. 2.61ng/mL, respectively; P<0.001). Mean follow-up time was 3.4±1.8years, during which 86 patients died. ROC curves were utilized to determine TGF-ß1 cutoff values. Compared to patients with TGF-ß1 of <3.74ng/mL, heart function was significantly impaired (percentage of patients with WHO functional class III/IV, 51.4% vs. 65.5%, P=0.043) and mortality risk was elevated (P=0.009) for patients with TGF-ß1>3.74ng/mL. However, the difference in mortality rate between patients with higher and lower TGF-ß1 levels was only statistically significant for female patients (P=0.004), despite a similar trend for male patients. Multivariate analyses revealed that TGF-ß1 (HR after log transformation base of 10: 2.623; 95%CI: 1.228-5.603; P=0.013) emerged as the independent predictor for all-cause mortality. CONCLUSION: High circulating levels of TGF-ß1 were an independent predictor of a poor outcome for IPAH/HPAH patients.


Assuntos
Hipertensão Pulmonar Primária Familiar/sangue , Hipertensão Pulmonar Primária Familiar/diagnóstico , Fator de Crescimento Transformador beta1/sangue , Adulto , Biomarcadores/sangue , Feminino , Seguimentos , Humanos , Masculino , Estudos Retrospectivos , Adulto Jovem
18.
Hypertens Res ; 39(5): 302-11, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26763846

RESUMO

Most patients with pulmonary arterial hypertension die from right ventricular failure (RVF). Right ventricular (RV) myocardial apoptosis has an important role in RVF and is regulated by the mitochondria. Dichloroacetate (DCA) can improve cardiac function in RVF, but whether it can regulate myocardial apoptosis via mitochondria is still unknown. In this study, we investigated the effects of DCA on myocardial mitochondria, the mitochondrial apoptosis and other aspects of RV remodeling, including fibrosis and capillary rarefaction. RVF was induced in rats by a single s.c. injection of monocrotaline. After 4 weeks, DCA treatment was started with i.p. injection of 50, 150 or 2007 mg kg(-1) per day during 14 days. Compared with saline-treated RVF animals, treatment with DCA resulted in decreased mean pulmonary arterial pressure and total pulmonary resistance (TPR), and increased cardiac output. The expression of pyruvate dehydrogenase kinase was suppressed, while pyruvate dehydrogenase expression was upregulated with DCA application. DCA treatment was also associated with restored RV mitochondrial function and a reduction in RV hypertrophy, fibrosis, capillary rarefaction and apoptosis. Mitochondria-dependent apoptosis was involved in DCA regulation of RV. The absent correlation between TPR and main parameters in RV suggests that the effects of DCA in the two organ systems are independent. We conclude that DCA improves cardiac function in experimental RVF partly by reversing RV remodeling, restoring mitochondrial function and regulating mitochondria-dependent apoptosis. The study shows that a fear for increased RV apoptosis with DCA treatment is unnecessary and suggests a potential role of DCA in the treatment of RVF.


Assuntos
Apoptose/efeitos dos fármacos , Ácido Dicloroacético/farmacologia , Ventrículos do Coração/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Remodelação Ventricular/efeitos dos fármacos , Animais , Pressão Arterial/efeitos dos fármacos , Modelos Animais de Doenças , Ventrículos do Coração/metabolismo , Hemodinâmica/efeitos dos fármacos , Masculino , Mitocôndrias/metabolismo , Monocrotalina/farmacologia , Ratos , Ratos Sprague-Dawley , Remodelação Ventricular/fisiologia
19.
Lancet Respir Med ; 4(2): 129-37, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26795434

RESUMO

BACKGROUND: Mutations in the gene encoding the bone morphogenetic protein receptor type II (BMPR2) are the commonest genetic cause of pulmonary arterial hypertension (PAH). However, the effect of BMPR2 mutations on clinical phenotype and outcomes remains uncertain. METHODS: We analysed individual participant data of 1550 patients with idiopathic, heritable, and anorexigen-associated PAH from eight cohorts that had been systematically tested for BMPR2 mutations. The primary outcome was the composite of death or lung transplantation. All-cause mortality was the secondary outcome. Hazard ratios (HRs) for death or transplantation and all-cause mortality associated with the presence of BMPR2 mutation were calculated using Cox proportional hazards models stratified by cohort. FINDINGS: Overall, 448 (29%) of 1550 patients had a BMPR2 mutation. Mutation carriers were younger at diagnosis (mean age 35·4 [SD 14·8] vs 42·0 [17·8] years), had a higher mean pulmonary artery pressure (60·5 [13·8] vs 56·4 [15·3] mm Hg) and pulmonary vascular resistance (16·6 [8·3] vs 12·9 [8·3] Wood units), and lower cardiac index (2·11 [0·69] vs 2·51 [0·92] L/min per m(2); all p<0·0001). Patients with BMPR2 mutations were less likely to respond to acute vasodilator testing (3% [10 of 380] vs 16% [147 of 907]; p<0·0001). Among the 1164 individuals with available survival data, age-adjusted and sex-adjusted HRs comparing BMPR2 mutation carriers with non-carriers were 1·42 (95% CI 1·15-1·75; p=0·0011) for the composite of death or lung transplantation and 1·27 (1·00-1·60; p=0·046) for all-cause mortality. These HRs were attenuated after adjustment for potential mediators including pulmonary vascular resistance, cardiac index, and vasoreactivity. HRs for death or transplantation and all-cause mortality associated with BMPR2 mutation were similar in men and women, but higher in patients with a younger age at diagnosis (p=0·0030 for death or transplantation, p=0·011 for all-cause mortality). INTERPRETATION: Patients with PAH and BMPR2 mutations present at a younger age with more severe disease, and are at increased risk of death, and death or transplantation, compared with those without BMPR2 mutations. FUNDING: Cambridge NIHR Biomedical Research Centre, Medical Research Council, British Heart Foundation, Assistance Publique-Hôpitaux de Paris, INSERM, Université Paris-Sud, Intermountain Research and Medical Foundation, Vanderbilt University, National Center for Advancing Translational Sciences, National Institutes of Health, National Natural Science Foundation of China, and Beijing Natural Science Foundation.


Assuntos
Receptores de Proteínas Morfogenéticas Ósseas Tipo II/genética , Hipertensão Pulmonar/genética , Transplante de Pulmão/estatística & dados numéricos , Adulto , Hipertensão Pulmonar Primária Familiar/genética , Hipertensão Pulmonar Primária Familiar/mortalidade , Hipertensão Pulmonar Primária Familiar/cirurgia , Feminino , Humanos , Hipertensão Pulmonar/mortalidade , Hipertensão Pulmonar/cirurgia , Masculino , Pessoa de Meia-Idade , Mutação , Prognóstico , Modelos de Riscos Proporcionais , Taxa de Sobrevida , Adulto Jovem
20.
Chin J Traumatol ; 19(6): 362-367, 2016 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-28088943

RESUMO

PURPOSE: To compare the efficacy of percutaneous poking reduction and fixationwith open reduction and fixation in the treatment of displaced calcaneal fractures. METHODS: Reports of studies using case-controlled trials (CCT) to compare the percutaneous poking reduction and fixation with the open reduction and fixation in the management of calcaneal fractures were retrieved from the Cochrane Library, PubMed Database, CNKI, Chinese Biomedical Database, Wanfang Data (from January of 2005 to August of 2015). Methodological quality of the trials was critically assessed, and relevant data were extracted. Statistical software Revman 5.0 was used for data-analysis. RESULTS: Fifteen articles were included in the meta-analysis. Comparison of the efficacy of percutaneous poking reduction and fixation with open reduction and fixation in the treatment of calcaneal fractures revealed statistical significance in the incidence of complications after operation [RR = 0.32, 95% CI (0.20, 0.5), p < 0.05]. However, there were neither statistical significance in the degrees of recovery for calcaneal Bohler angle [WMD = -1.65, 95% CI (-3.43, 0.14), p > 0.05] and calcaneal Gissane angle [WMD = -3.21, 95% CI (-6.75, 0.33), p > 0.05], nor statistical significance in the rate of good foot function after operation [RR= 0.95, 95% CI (0.90, 1.00), p > 0.05]. CONCLUSION: For the treatment of calcaneal fractures, percutaneous poking reduction and fixation is su- perior to open reduction and fixation in terms of the incidence of postoperative complications. But both techniques can obtain satisfactory clinical function.


Assuntos
Calcâneo/lesões , Fixação Interna de Fraturas/métodos , Fraturas Ósseas/cirurgia , Redução Aberta/métodos , Calcâneo/cirurgia , Fixação Interna de Fraturas/efeitos adversos , Humanos , Redução Aberta/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Viés de Publicação
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