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1.
Health Qual Life Outcomes ; 19(1): 140, 2021 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-33962617

RESUMO

BACKGROUND: Health Related Quality of Life (HRQL) is a multi-dimensional construct that can comprehensively evaluate the patient's health status, including physical, emotional, mental and social well-being. In this study, we aimed to evaluate the impact of non-alcoholic fatty liver disease (NAFLD) on HRQL in a Chinese population. METHODS: In this national multicenter cross-sectional survey, patients with NAFLD were enrolled. Chronic Liver Disease Questionnaire (CLDQ)-NAFLD was used to qualify HRQL. Univariate and multivariate analysis were used to identify independent risk factors of HRQL. RESULTS: A total of 5181 patients with NAFLD from 90 centers were enrolled in this study (mean age, 43.8 ± 13.3 years; male, 65.8%). The overall CLDQ score was 5.66 ± 0.89. Multivariate logistic regression analysis showed that body mass index (BMI: HR, 1.642; 95% CI, 1.330-2.026), alanine transaminase (ALT: HR, 1.006; 95% CI, 1.001-1.011), triglyceride (HR, 1.184; 95% CI, 1.074-1.305), disease severity (HR, 3.203; 95% CI, 1.418-7.232) and cardiovascular disease (HR, 4.305; 95% CI, 2.074-8.939) were independent risk factors for overall CLDQ score. In the logistic analyses of individual domain, BMI and triglyceride were independent risk factors of all domains. ALT, disease severity, diabetes, depression and cardiovascular disease were influencing factors for the CLDQ score of several domains. CONCLUSIONS: This national multicenter cross-sectional survey in China indicated that the HRQL in patients with NAFLD was impaired. HRQL was found to be significantly associated with sociodemographic and clinical factors. Attention should be paid to the optimally managing care of patients with NAFLD to improve their HRQL.


Assuntos
Grupo com Ancestrais do Continente Asiático/psicologia , Grupo com Ancestrais do Continente Asiático/estatística & dados numéricos , Nível de Saúde , Hepatopatia Gordurosa não Alcoólica/psicologia , Qualidade de Vida/psicologia , Índice de Gravidade de Doença , Inquéritos e Questionários/normas , Adolescente , Adulto , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Adulto Jovem
2.
Eur Respir J ; 56(5)2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32513782

RESUMO

Pathological mechanisms of pulmonary arterial hypertension (PAH) remain largely unexplored. Effective treatment of PAH remains a challenge. The aim of this study was to discover the underlying mechanism of PAH through functional metabolomics and to help develop new strategies for prevention and treatment of PAH.Metabolomic profiling of plasma in patients with idiopathic PAH was evaluated through high-performance liquid chromatography mass spectrometry, with spermine identified to be the most significant and validated in another independent cohort. The roles of spermine and spermine synthase were examined in pulmonary arterial smooth muscle cells (PASMCs) and rodent models of pulmonary hypertension.Using targeted metabolomics, plasma spermine levels were found to be higher in patients with idiopathic PAH compared to healthy controls. Spermine administration promoted proliferation and migration of PASMCs and exacerbated vascular remodelling in rodent models of pulmonary hypertension. The spermine-mediated deteriorative effect can be attributed to a corresponding upregulation of its synthase in the pathological process. Inhibition of spermine synthase in vitro suppressed platelet-derived growth factor-BB-mediated proliferation of PASMCs, and in vivo attenuated monocrotaline-mediated pulmonary hypertension in rats.Plasma spermine promotes pulmonary vascular remodelling. Inhibiting spermine synthesis could be a therapeutic strategy for PAH.


Assuntos
Hipertensão Arterial Pulmonar , Animais , Proliferação de Células , Modelos Animais de Doenças , Glicogênio Sintase , Humanos , Miócitos de Músculo Liso , Artéria Pulmonar , Ratos , Espermina , Remodelação Vascular
3.
Life Sci ; 252: 117649, 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32275936

RESUMO

Chronic obstructive pulmonary disease (COPD) with cardiovascular complications is very common. Due to fear of exacerbating airway spasm, ß-blockers are rarely used in such patients. Many observational studies suggest that ß-blockers can reduce the disease progression and the risk of mortality in patients with COPD, but lack of confirmation from randomized controlled trials. This article reviews the application of ß-blockers in patients with COPD based on the results of the latest published randomized controlled trials.


Assuntos
Antagonistas Adrenérgicos beta/administração & dosagem , Doenças Cardiovasculares/prevenção & controle , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Antagonistas Adrenérgicos beta/efeitos adversos , Progressão da Doença , Humanos , Doença Pulmonar Obstrutiva Crônica/mortalidade , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Ensaios Clínicos Controlados Aleatórios como Assunto
4.
J Dig Dis ; 21(1): 3-11, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31682309

RESUMO

The development of new drugs for nonalcoholic steatohepatitis (NASH) is a current focus of research in the management of liver disease. Here we provided an overview of NASH drug pipelines and the challenges faced in conducting phases II and III clinical trials. These challenges include the selection and definition of research populations, rational selection of study end-points, choice of noninvasive diagnostic indicators, accounting for confounding factors and safety assessments. Furthermore, we discussed how to establish guidelines for study design and end-points in complex clinical trials of anti-NASH drugs.


Assuntos
Anti-Inflamatórios/uso terapêutico , Biomarcadores/sangue , Ensaios Clínicos como Assunto , Desenvolvimento de Medicamentos , Quimioterapia Combinada , Fibrose/tratamento farmacológico , Fibrose/etiologia , Fibrose/prevenção & controle , Humanos , Inflamação/tratamento farmacológico , Inflamação/etiologia , Intestinos/efeitos dos fármacos , Hepatopatia Gordurosa não Alcoólica/sangue , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Hepatopatia Gordurosa não Alcoólica/metabolismo , Estresse Oxidativo/efeitos dos fármacos
5.
Eur Respir J ; 53(3)2019 03.
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.


Assuntos
Receptores de Proteínas Morfogenéticas Ósseas Tipo II/genética , Hipertensão Pulmonar Primária Familiar/genética , Mutação em Linhagem Germinativa , Adolescente , Adulto , Estudos de Casos e Controles , Células Endoteliais/metabolismo , Exoma , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Adulto Jovem
6.
J Dig Dis ; 19(3): 144-154, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29389068

RESUMO

OBJECTIVE: To evaluate tolvaptan as a novel therapeutic option for Chinese patients with liver cirrhosis-associated ascites in a phase 2 clinical trial. METHODS: This randomized, double-blind, placebo-controlled, multicenter trial was conducted in patients with insufficient responses to combination therapies of an oral loop diuretic and an aldosterone antagonist. Reduction in body weight and abdominal circumference, increase in 24-h cumulative urine volume and improvement in serum sodium level from baseline to the end of treatment in the tolvaptan groups (15 mg/day or 30 mg/day orally) were compared with those in the placebo group. Drug safety was also assessed. RESULTS: Sixty-two patients were allocated to the placebo group, 56 to the tolvaptan 15-mg group and 63 to the tolvaptan 30-mg group. Their mean changes in body weight were -0.5 ± 1.6 kg, -2.1 ± 2.0 kg and -1.9 ± 2.0 kg, respectively. Body weight reductions in both tolvaptan groups were significantly greater than that in the placebo group (difference -1.6, 95% confidence interval [CI] -2.5 to -0.8, and difference -1.4, 95% CI, -2.2 to -0.7, both P < 0.0001). The administration of tolvaptan also significantly reduced the abdominal circumference, increased 24-h cumulative urine volume and serum sodium level compared with placebo. The most common adverse events in the tolvaptan groups were constipation, diarrhea, dry mouth and thirst, with no severe adverse events observed. CONCLUSION: Tolvaptan at 15 mg/day significantly reduced the body weight and abdominal circumference in patients with liver cirrhosis-associated ascites, which needs to be confirmed in a phase 3 trial.


Assuntos
Antagonistas dos Receptores de Hormônios Antidiuréticos/administração & dosagem , Ascite/tratamento farmacológico , Benzazepinas/administração & dosagem , Cirrose Hepática/tratamento farmacológico , Abdome/patologia , Adolescente , Adulto , Idoso , Antagonistas dos Receptores de Hormônios Antidiuréticos/efeitos adversos , Antagonistas dos Receptores de Hormônios Antidiuréticos/farmacologia , Ascite/patologia , Ascite/fisiopatologia , Benzazepinas/efeitos adversos , Benzazepinas/farmacologia , Peso Corporal/efeitos dos fármacos , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Humanos , Cirrose Hepática/patologia , Cirrose Hepática/fisiopatologia , Masculino , Pessoa de Meia-Idade , Sódio/sangue , Tolvaptan , Urina , Adulto Jovem
7.
J Dig Dis ; 18(11): 607-617, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29106066

RESUMO

Pharmacotherapy for nonalcoholic fatty liver disease (NAFLD) has not yet been approved by the US Food and Drug Administration. Over the past decade, a large number of clinical studies have explored the safety and efficacy of different drugs in treating nonalcoholic steatohepatitis (NASH), including diet pills, antioxidants, insulin sensitizers, lipid-lowering agents, anti-inflammatory cytokines, cytoprotective agents and intestinal probiotics. Based on the evidence from randomized controlled trials a number of academic groups have developed guidelines for the diagnosis and management of NAFLD and NASH. In this article, we discussed the current situation of NASH pharmacotherapy.


Assuntos
Antioxidantes/uso terapêutico , Hipoglicemiantes/uso terapêutico , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Tiazolidinedionas/uso terapêutico , Vitamina E/uso terapêutico , Quimioterapia Combinada , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Pentoxifilina/uso terapêutico , Pioglitazona , Guias de Prática Clínica como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto
8.
Life Sci ; 188: 17-25, 2017 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-28864224

RESUMO

AIMS: Catheter-directed therapy (CDT) is included in the guidelines for diagnosing and treating massive pulmonary embolism. However, few studies have evaluated the efficacy of CDT as a treatment for submassive pulmonary embolism (SPE). Therefore, we used evidence-based medicine to evaluate the effectiveness and safety of CDT in treating SPE. METHODS: Search terms describing CDT in SPE and patients with intermediate pulmonary embolism were entered into the PubMed, Embase and Cochrane Library databases to identify relevant articles without language restrictions published between January 1990 and December 2016. A quality assessment and data extraction were performed by two investigators. The clinical efficacy of and major complications associated with treatment were analysed using a fixed effects model. KEY FINDINGS: A total of 552 patients in 16 studies were included in this meta-analysis. The clinical success rate in CDT was approximately 100% (95% confidence interval (CI): 99%, 100%), the primary bleeding rate was 0.02% (95% CI: 0%, 0.05%), and mortality during hospitalization was approximately 0% (95% CI: 0%, 0.01%). The mean decrease in pulmonary artery systolic pressure after treatment was -14.9% (95% CI: -19.25%, -10.55%), and the mean post-treatment change in the ratio of the right to the left ventricle (RV/LV) was -0.35% (95% CI: -0.48%, -0.22%). SIGNIFICANCE: CDT is effective and safe as a treatment for SPE and could be a first-line treatment for SPE under specific conditions.


Assuntos
Cateterismo de Swan-Ganz , Embolia Pulmonar/terapia , Pressão Sanguínea/fisiologia , Cateterismo de Swan-Ganz/efeitos adversos , Humanos , Embolia Pulmonar/fisiopatologia , Resultado do Tratamento
9.
Lipids Health Dis ; 16(1): 153, 2017 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-28807032

RESUMO

BACKGROUND: Acetaminophen (APAP) overdose is one of the most common causes of acute liver failure in many countries. The aim of the study was to describe the profiling of phosphatidylcholine (PC) and phosphatidylethanolamine (PE) in the plasma and liver of Acetaminophen -induced liver injured mice. METHODS: A time course study was carried out using C57BL/6 mice after intraperitoneal administration of 300 mg/kg Acetaminophen 1 h, 3 h, 6 h, 12 h and 24 h. A high-throughput liquid chromatography mass spectrometry (LC-MS) lipidomic method was utilized to detect phosphatidylcholine and phosphatidylethanolamine species in the plasma and liver. The expressions of phosphatidylcholine and phosphatidylethanolamine metabolism related genes in liver were detected by quantitative Reverse transcription polymerase chain reaction (qRT-PCR) and Western-blot. RESULTS: Following Acetaminophen treatment, the content of many PC and PE species in plasma increased from 1 h time point, peaked at 3 h or 6 h, and tended to return to baseline at 24 h time point. The relative contents of almost all PC species in liver decreased from 1 h, appeared to be lowest at 6 h, and then return to normality at 24 h, which might be partly explained by the suppression of phospholipases mRNA expressions and the induction of choline kinase (Chka) expression. Inconsistent with PC profile, the relative contents of many PE species in liver increased upon Acetaminophen treatment, which might be caused by the down-regulation of phosphatidylethanolamine N-methyltransferase (Pemt). CONCLUSIONS: Acetaminophen overdose induced dramatic change of many PC and PE species in plasma and liver, which might be caused by damaging hepatocytes and interfering the phospholipid metabolism in Acetaminophen -injured liver.


Assuntos
Acetaminofen/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Fígado/efeitos dos fármacos , Fosfatidilcolinas/metabolismo , Fosfatidiletanolaminas/metabolismo , Animais , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/patologia , Colina Quinase/genética , Colina Quinase/metabolismo , Cromatografia Líquida , Regulação da Expressão Gênica , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Hepatócitos/patologia , Injeções Intraperitoneais , Fígado/metabolismo , Fígado/patologia , Masculino , Espectrometria de Massas , Camundongos , Camundongos Endogâmicos C57BL , Fosfatidiletanolamina N-Metiltransferase/genética , Fosfatidiletanolamina N-Metiltransferase/metabolismo , Fosfolipases/genética , Fosfolipases/metabolismo
10.
PLoS One ; 12(5): e0177504, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28542283

RESUMO

BACKGROUND: Cancers from lung and esophagus are the leading causes of cancer-related deaths in China and share many similarities in terms of histological type, risk factors and genetic variants. Recent genome-wide association studies (GWAS) in Chinese esophageal cancer patients have demonstrated six high-risk candidate single nucleotide polymorphisms (SNPs). Thus, the present study aimed to determine the risk of these SNPs predisposing to lung cancer in Chinese population. METHODS: A total of 1170 lung cancer patients and 1530 normal subjects were enrolled in this study from high-incidence areas for esophageal cancer in Henan, northern China. Five milliliters of blood were collected from all subjects for genotyping. Genotyping of 20 high-risk SNP loci identified from genome-wide association studies (GWAS) on esophageal, lung and gastric cancers was performed using TaqMan allelic discrimination assays. Polymorphisms were examined for deviation from Hardy-Weinberg equilibrium (HWE) using Х2 test. Bonferroni correction was performed to correct the statistical significance of 20 SNPs with the risk of lung cancer. The Pearson's Х2 test was used to compare the distributions of gender, TNM stage, histopathological type, smoking and family history by lung susceptibility genotypes. Kaplan-Meier and Cox regression analyses were carried out to evaluate the associations between genetic variants and overall survival. RESULTS: Four of the 20 SNPs identified as high-risk SNPs in Chinese esophageal cancer showed increased risk for Chinese lung cancer, which included rs3769823 (OR = 1.26; 95% CI = 1.107-1.509; P = 0.02), rs10931936 (OR = 1.283; 95% CI = 1.100-1.495; P = 0.04), rs2244438 (OR = 1.294; 95% CI = 1.098-1.525; P = 0.04) and rs13016963 (OR = 1.268; 95% CI = 1.089-1.447; P = 0.04). All these SNPs were located at 2q33 region harboringgenes of CASP8, ALS2CR12 and TRAK2. However, none of these susceptibility SNPs was observed to be significantly associated with gender, TNM stage, histopathological type, smoking, family history and overall survival. CONCLUSIONS: The present study identified four high-risk SNPs at 2q33 locus for Chinese lung cancer and demonstrated the shared susceptibility loci at 2q33 region for Chinese lung and esophageal cancers.


Assuntos
Neoplasias Esofágicas/epidemiologia , Neoplasias Esofágicas/genética , Loci Gênicos/genética , Predisposição Genética para Doença/genética , Neoplasias Pulmonares/genética , Estudos de Casos e Controles , China/epidemiologia , Neoplasias Esofágicas/diagnóstico , Feminino , Estudo de Associação Genômica Ampla , Humanos , Incidência , Neoplasias Pulmonares/diagnóstico , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Prognóstico , Análise de Sobrevida
11.
Hepatol Int ; 11(3): 221-241, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28405790

RESUMO

Drug-induced liver injury (DILI) is an important clinical problem, which has received more attention in recent decades. It can be induced by small chemical molecules, biological agents, traditional Chinese medicines (TCM), natural medicines (NM), health products (HP), and dietary supplements (DS). Idiosyncratic DILI is far more common than intrinsic DILI clinically and can be classified into hepatocellular injury, cholestatic injury, hepatocellular-cholestatic mixed injury, and vascular injury based on the types of injured target cells. The CSH guidelines summarized the epidemiology, pathogenesis, pathology, and clinical manifestation and gives 16 evidence-based recommendations on diagnosis, differential diagnosis, treatment, and prevention of DILI.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/epidemiologia , Colestase/induzido quimicamente , Suplementos Nutricionais/efeitos adversos , Hepatopatias/epidemiologia , Antibacterianos/efeitos adversos , Antibacterianos/toxicidade , Anti-Infecciosos/efeitos adversos , Anti-Infecciosos/toxicidade , Doença Hepática Induzida por Substâncias e Drogas/patologia , Doença Hepática Induzida por Substâncias e Drogas/fisiopatologia , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , China/epidemiologia , Colestase/complicações , Colestase/patologia , Diagnóstico Diferencial , Suplementos Nutricionais/toxicidade , Medicamentos de Ervas Chinesas/efeitos adversos , Feminino , Guias como Assunto , Humanos , Incidência , Hepatopatias/patologia , Hepatopatias/fisiopatologia , Hepatopatias/terapia , Masculino , Prognóstico , Fatores de Risco , Índice de Gravidade de Doença
12.
Exp Mol Med ; 49(1): e283, 2017 01 13.
Artigo em Inglês | MEDLINE | ID: mdl-28082742

RESUMO

We sought to identify common key regulators and build a gene-metabolite network in different nonalcoholic fatty liver disease (NAFLD) phenotypes. We used a high-fat diet (HFD), a methionine-choline-deficient diet (MCDD) and streptozocin (STZ) to establish nonalcoholic fatty liver (NAFL), nonalcoholic steatohepatitis (NASH) and NAFL+type 2 diabetes mellitus (T2DM) in rat models, respectively. Transcriptomics and metabolomics analyses were performed in rat livers and serum. A functional network-based regulation model was constructed using Cytoscape with information derived from transcriptomics and metabolomics. The results revealed that 96 genes, 17 liver metabolites and 4 serum metabolites consistently changed in different NAFLD phenotypes (>2-fold, P<0.05). Gene-metabolite network analysis identified ccl2 and jun as hubs with the largest connections to other genes, which were mainly involved in tumor necrosis factor, P53, nuclear factor-kappa B, chemokine, peroxisome proliferator activated receptor and Toll-like receptor signaling pathways. The specifically regulated genes and metabolites in different NAFLD phenotypes constructed their own networks, which were mainly involved in the lipid and fatty acid metabolism in HFD models, the inflammatory and immune response in MCDD models, and the AMPK signaling pathway and response to insulin in HFD+STZ models. Our study identified networks showing the general and specific characteristics in different NAFLD phenotypes, complementing the genetic and metabolic features in NAFLD with hepatic and extra-hepatic manifestations.


Assuntos
Regulação da Expressão Gênica , Redes Reguladoras de Genes , Redes e Vias Metabólicas , Hepatopatia Gordurosa não Alcoólica/genética , Hepatopatia Gordurosa não Alcoólica/metabolismo , Fenótipo , Animais , Biomarcadores , Diabetes Mellitus Tipo 2 , Modelos Animais de Doenças , Perfilação da Expressão Gênica , Fígado/metabolismo , Fígado/patologia , Masculino , Metaboloma , Metabolômica/métodos , Hepatopatia Gordurosa não Alcoólica/sangue , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Ratos , Reprodutibilidade dos Testes , Transdução de Sinais , Transcriptoma
13.
Gut ; 65(10): 1611-8, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-26129866

RESUMO

OBJECTIVE: Genome-wide association studies (GWAS) of gastric cancer have reported differences in single-nucleotide polymorphism (SNP) associations for tumour subtypes, particularly when divided by location into the gastric cardia versus the non-cardia. DESIGN: Here we present results for a GWAS using 2350 East Asian gastric cancer cases divided as 1189 gastric cardia and 1027 gastric non-cardia cases and 2708 controls. We also included up to 3042 cardia cases, 4359 non-cardia cases and 7548 controls for replication from two Chinese studies and one Korean study. From the GWAS, we selected 12 top SNPs for each gastric cancer subtype, 4 top SNPs for total gastric cancer and 1 SNP in MUC1 for replication testing. RESULTS: We observed genome-wide significant associations for rs10074991 in PRKAA1 at 5p13.1 for cardia (p=7.36×10(-12)) and non-cardia cancers (p=2.42×10(-23)) with per allele OR (95% CI) for the combined endpoint of 0.80 (0.77 to 0.83). At 6p21.1, rs2294693 near UNC5CL was significantly associated with gastric non-cardia cancer risk (p=2.50×10(-8)), with OR (95% CI) of 1.18 (1.12 to 1.26), but there was only a nominal association for cardia cancer (p=1.47×10(-2)). We also confirmed a previously reported association for rs4072037 in MUC1 with p=6.59×10(-8) for total gastric cancer and similar estimates for cardia and non-cardia cancers. Three SNPs in PSCA previously reported to be associated with gastric non-cardia cancer showed no apparent association for cardia cancer. CONCLUSIONS: Our results suggest that associations for SNPs with gastric cancer show some different results by tumour location in the stomach.


Assuntos
Proteínas Quinases Ativadas por AMP/genética , Adenocarcinoma , Cárdia , Peptídeos e Proteínas de Sinalização Intracelular/genética , Mucina-1/genética , Neoplasias Gástricas , Adenocarcinoma/epidemiologia , Adenocarcinoma/genética , Adenocarcinoma/patologia , Grupo com Ancestrais do Continente Asiático , Estudos de Casos e Controles , China/epidemiologia , Feminino , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Humanos , Masculino , Polimorfismo de Nucleotídeo Único , República da Coreia/epidemiologia , Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia
14.
Int J Clin Exp Med ; 8(1): 1051-8, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25785092

RESUMO

Lung cancer is one of the most common cancers in the world, especially in China. It is believed that genetic polymorphisms played a role in cancer susceptibility. Here we investigated the association of interleukin-6 (IL-6) and interleukin-10 (IL-10) gene polymorphisms with the susceptibility of lung cancer in never-smoking Chinese Han population. In this study, we performed a case-control study including 330 cases of never-smoking lung cancer patients and 336 cancer-free never-smoking controls in Chinese Han population. We used polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method to identify gene polymorphisms, and then verified by sequencing method. The results indicated that the four single nucleotide polymorphisms (IL-6 -1363T/G and -572G/C, IL-10 -819T/C and -592A/C) were genotyped by PCR-RFLP and confirmed by sequencing, and we found that the allelic frequencies of G in IL-6 -1363T/G, C in IL-10 -819T/C and C in IL-10 -592A/C were significantly increased in lung cancer patients, by comparing with the control group. However, there was no significant difference in the distribution of the IL-6 572G/C polymorphisms between patients and controls. In conclusion, the IL-6 -1363T/G, IL-10 -819T/C and IL-10 -592A/C polymorphisms are closely related to genetic susceptibility to lung cancer in never-smoking Chinese Han population, and these genetic variants might be used as molecular markers for detecting lung cancer susceptibility.

15.
Lung ; 192(4): 625-7, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24728306

RESUMO

INTRODUCTION: Heterozygous germline mutations of the bone morphogenetic protein type II receptor (BMPR2) gene BMPR2 are the most important predisposing factors for heritable pulmonary arterial hypertension. BMPR2 mutation was occasionally reported in pulmonary veno-occlusive disease, appetite suppressant-related pulmonary arterial hypertension (PAH), and PAH with congenital heart disease. MATERIALS AND METHODS: In this study we identified a missense mutation (c.2296A > G) located in BMPR2 exon 12 in a patient with chronic thromboembolic pulmonary hypertension (CTEPH). CONCLUSION: It is the first report of a BMPR2 mutation in CTEPH. Our study provides innovative insight into etiology of CTEPH. The genetic predisposing factor is an important component in the process of this CTEPH patient.


Assuntos
Receptores de Proteínas Morfogenéticas Ósseas Tipo II/genética , Mutação em Linhagem Germinativa , Hipertensão Pulmonar/genética , Mutação de Sentido Incorreto , Embolia Pulmonar/genética , Adulto , Anticoagulantes/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Doença Crônica , Análise Mutacional de DNA , Evolução Fatal , Feminino , Predisposição Genética para Doença , Humanos , Hipertensão Pulmonar/diagnóstico , Hipertensão Pulmonar/fisiopatologia , Hipertensão Pulmonar/terapia , Fenótipo , Embolia Pulmonar/diagnóstico , Embolia Pulmonar/fisiopatologia , Embolia Pulmonar/terapia , Fatores de Tempo , Resultado do Tratamento
16.
Circ Cardiovasc Genet ; 5(5): 511-8, 2012 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-22923421

RESUMO

BACKGROUND: BMPR2 mutations predispose to idiopathic and heritable pulmonary arterial hypertension (IPAH and HPAH). The influence of BMPR2 mutations on clinical outcome is not concordant in different ethnic groups. Although the BMPR2 mutation spectrum and mutation rate in Chinese PAH patients has been reported previously, the influence of genotype on phenotype and whether this influence is associated with sex have not been investigated. METHODS AND RESULTS: We analyzed data from 305 PAH patients considered as either idiopathic or heritable who underwent genetic counseling in Shanghai Pulmonary Hospital. The clinical, functional, and hemodynamic characteristics of BMPR2 mutation carriers and noncarriers were compared. The more severe hemodynamic compromise at diagnosis in BMPR2 mutation carriers versus noncarriers is concordant with other ethnic groups. In the Chinese PAH cohort, BMPR2 mutations were associated with a higher risk of mortality after adjustment for age and sex (hazard ratio, 1.971; 95% confidence interval, 1.121-3.466; P=0.018). The overall survival difference between mutation carriers and noncarriers was more obvious in male patients, which was reflected by a higher mortality risk of male mutation carriers than that of male noncarriers after adjustment for age at diagnosis (hazard ratio, 3.702; 95% confidence interval, 1.416-9.679; P=0.008). In females, this trend did not reach statistical significance. CONCLUSIONS: BMPR2 mutations influence phenotype more obviously in male PAH patients. The pathogenesis of female PAH patients is more complicated, and the influence of BMPR2 mutations may be modified by other unknown factors, making disparities in the prognosis between female mutation carriers and noncarriers less evident.


Assuntos
Receptores de Proteínas Morfogenéticas Ósseas Tipo II/genética , Hipertensão Pulmonar/metabolismo , Adulto , Fatores Etários , Receptores de Proteínas Morfogenéticas Ósseas Tipo II/metabolismo , Estudos de Coortes , Hipertensão Pulmonar Primária Familiar , Feminino , Aconselhamento Genético , Hemodinâmica , Humanos , Hipertensão Pulmonar/mortalidade , Hipertensão Pulmonar/patologia , Masculino , Pessoa de Meia-Idade , Mutação , Fenótipo , Fatores Sexuais , Análise de Sobrevida
17.
Zhonghua Jie He He Hu Xi Za Zhi ; 35(4): 259-63, 2012 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-22781197

RESUMO

OBJECTIVE: To evaluate the prevalence of pulmonary embolism(PE) in patients with chronic obstructive pulmonary disease (COPD) exacerbations of unknown origin and to explore the risk factors associated with PE. METHODS: A total of 208 consecutive patients with COPD were referred to this hospital for severe exacerbations of unknown origin. Their age was 50 - 82 years, with a mean of (62 ± 12) years. All patients were examined within 48 h of admission by CT pulmonary angiography (CTPA) and lower extremity ultrasonography. The patients were classified as PE positive (positive results on CTPA) or PE negative (negative results on CTPA). Arterial blood gas, the levels of D-dimer and ET-1 were measured in all the patients. Differences between groups were analyzed using a two-tailed unpaired t test for normally distributed variables and a Mann-Whitney u test for non-normally distributed variables. Qualitative data were assessed using chi-square test, and risk factors were analyzed using logistic regression analysis. RESULTS: The frequency of PE was 33% in this series of 208 consecutive patients with COPD referred for exacerbations of unknown origin. There were differences between PE positive and PE negative groups in the following factors (χ(2) = 4.32 - 6.79, mean P < 0.05): immobilization ≥ 7 days 21.7% (15/208) vs 13.7% (19/208); difference in circumference of lower limbs ≥ 1 cm 34.8% (24/208) vs 15.1% (21/208); deep venous thrombosis (DVT) 37.7% (26/208) vs 12.2% (17/208); syncope 11.6% (8/208) vs 0.06% (9/208); S(I)Q(III)T(III) syndrome 11.6% (8/208) vs 0.04% (5/208); decrease in PaCO2 ≥ 5 mm Hg (1 mm Hg = 0.133 kPa) 27.5% (19/208) vs 9.3% (13/208). Plasma D-dimer and ET-1 levels were significantly higher in patients with PE as compared to patients without PE. D-dimer levels were (760 ± 152) µg/L and (253 ± 56) µg/L (Z = -2.946, P < 0.01); ET-1 levels were 5.4 ng/L (1.6 - 6.9 ng/L) and 1.8 ng/L (1.3 - 4.8 ng/L), Z = -2.532, P < 0.01. Risk factors identified by logistic regression analysis included immobilization ≥ 7 days (P < 0.05, OR = 3.24, 95%CI = 1.56 - 4.98), difference in circumference of lower limbs ≥ 1 cm (P < 0.05, OR = 2.56, 95%CI = 1.48 - 3.93), and deep venous thrombosis (DVT) (P < 0.05, OR = 2.31, 95%CI = 1.23 - 3.58). CONCLUSIONS: This study showed a 33% prevalence of PE in patients with COPD who were hospitalized for severe exacerbations of unknown origin. Immobilization ≥ 7 days, difference in circumference of lower limbs ≥ 1 cm, and DVT were risk factors for PE in this group of patients.


Assuntos
Doença Pulmonar Obstrutiva Crônica/complicações , Embolia Pulmonar/complicações , Idoso , Idoso de 80 Anos ou mais , Progressão da Doença , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Trombose Venosa
19.
Zhonghua Gan Zang Bing Za Zhi ; 19(5): 362-6, 2011 May.
Artigo em Chinês | MEDLINE | ID: mdl-21645445

RESUMO

OBJECTIVE: To assess the characteristics and daily treatment compliance of non-alcoholic fatty liver disease (NAFLD) patients in China. METHODS: NAFLD adult patients from 21 clinics of 12 cities in China were enrolled in this registry. Physical examination such as demographic characteristics (height, weight, waist circumference measurement), blood pressure and clinical laboratory and ultrasonographic examination of liver were undertaken. Daily practice including life style and medication were recorded and assessed in accordance with 2006 Chinese NAFLD treatment guidelines. RESULTS: A total of 1656 patients were enrolled (1146 male and 510 female), mean of 45.8 ± 12.6 years old, mean duration of NAFLD history was (47.2 ± 47.7) months. 44.9% of NAFLD were suffering from metabolic syndromes. Patients with central obesity have higher incidence of hypertension and lower level of high-density lipoprotein cholesterol (HDL-C) than those without central obesity, P < 0.05. Body mass index (BMI), waist circumference, triglyceride (TG) and low-density lipoprotein cholesterol (LDL-C) in ALT abnormal group were higher than those in ALT normal group (P < 0.05), HDL-C was lower in ALT abnormal group (P < 0.05). Significant differences existed between the BMI, female waist circumference, TG, fast insulin, HOMA index, ALT, AST and HDL-C among subgroups with mild, moderate and severe steatosis. Majority of the patients did not follow recommendations of NAFLD treatment guidelines. Among targeted population only 15.3% of patients used insulin sensitizers and 23.8% took lipid lowering medicine according to the guideline. CONCLUSION: Data indicated that nearly half of NAFLD patients co-morbid with metabolic disorders. Therapy compliance was unsatisfactory and the gap between current practice and Chinese NAFLD treatment guidelines was not optimal.


Assuntos
Fígado Gorduroso/diagnóstico , Fígado Gorduroso/epidemiologia , Adulto , Grupo com Ancestrais do Continente Asiático , China/epidemiologia , Fígado Gorduroso/terapia , Feminino , Humanos , Masculino , Síndrome Metabólica/epidemiologia , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica , Fatores de Risco , Circunferência da Cintura
20.
Zhonghua Gan Zang Bing Za Zhi ; 19(10): 782-4, 2011 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-22409854

RESUMO

OBJECTIVE: To validate transient elastography (Fibroscan) in assessment of hepatic fibrosis in autoimmune hepatitis (AIH). METHODS: Liver stiffness was assessed using Fibroscan in totally 30 patients with AIH. We compared the results of Fibroscan with the Scheuer fibrosis stage in liver biopsy in each patient. RESULTS: 4 patients were shown as liver fibrosis stage S0, 6 as S1, 5 as S2, 11 as S3 and 4 as S4. Failure of the Fibroscan measurement occurred in 1 case (3.3%) because of her increased body mass index (BMI). The stiffness of Fibroscan was significantly correlated with the liver biopsy fibrosis stage (r = 0.801, P less than 0.001). The liver stiffnesses between mild and moderate fibrosis (S0-2) and advanced fibrosis (S3-4) were significantly different (t = -3.937, P = 0.001). CONCLUSION: Transient elastography (Fibroscan) is a promising non-invasive method for detection of fibrosis in patients with autoimmune hepatitis. Its use for the follow up and management of these patients and should be evaluated further.


Assuntos
Técnicas de Imagem por Elasticidade/métodos , Hepatite Autoimune/diagnóstico por imagem , Cirrose Hepática/diagnóstico por imagem , Fígado/diagnóstico por imagem , Humanos
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