RESUMEN
The generally nonpolar SrTiO3 has attracted more attention recently because of its possibly induced novel polar states and related paraelectric-ferroelectric phase transitions. By using controlled pulsed laser deposition, high-quality, ultrathin, and strained SrTiO3 layers were obtained. Here, transmission electron microscopy and theoretical simulations have unveiled highly polar states in SrTiO3 films even down to one unit cell at room temperature, which were stabilized in the PbTiO3/SrTiO3/PbTiO3 sandwich structures by in-plane tensile strain and interfacial coupling, as evidenced by large tetragonality (â¼1.05), notable polar ion displacement (0.019 nm), and thus ultrahigh spontaneous polarization (up to â¼50 µC/cm2). These values are nearly comparable to those of the strong ferroelectrics as the PbZrxTi1-xO3 family. Our findings provide an effective and practical approach for integrating large strain states into oxide films and inducing polarization in nonpolar materials, which may broaden the functionality of nonpolar oxides and pave the way for the discovery of new electronic materials.
RESUMEN
Antiferroelectrics characterized by voltage-driven reversible transitions between antiparallel and parallel polarity are promising for cutting-edge electronic and electrical power applications. Wide-ranging explorations revealing the macroscopic performances and microstructural characteristics of typical antiferroelectric systems have been conducted. However, the underlying mechanism has not yet been fully unraveled, which depends largely on the atomistic processes. Herein, based on atomic-resolution transmission electron microscopy, the deterministic phase transition pathway along with the underlying lattice-by-lattice details in lead zirconate thin films was elucidated. Specifically, we identified a new type of ferrielectric-like dipole configuration with both angular and amplitude modulations, which plays the role of a precursor for a subsequent antiferroelectric to ferroelectric transformation. With the participation of the ferrielectric-like phase, the phase transition pathways driven by the phase boundary have been revealed. We provide new insights into the consecutive phase transformation in low-dimensional lead zirconate, which thus would promote potential antiferroelectric-based multifunctional devices.
RESUMEN
CerSs (ceramide synthases), a group of enzymes that catalyze the formation of ceramides from sphingoid base and acyl-CoA substrates. As far, six types of CerSs (CerS1-CerS6) have been found in mammals. Each of these enzymes have unique characteristics, but maybe more noteworthy is the ability of individual CerS isoform to produce a ceramide with a characteristic acyl chain distribution. As key regulators of sphingolipid metabolism, CerSs highlight their unique characteristics and have emerging roles in regulating programmed cell death, cancer and many other aspects of biology. However, the role of CerSs in lung cancer has not been fully elucidated. In this study, there was no significant change in the sequence or copy number of CerSs gene, which could explain the stability of malignant tumor development through COSMIC database. In addition, gene expression in lung cancer was examined using the OncomineTM database, and the prognostic value of each gene in non-small cell lung cancer (NSCLC) was analyzed by Kaplan-Meier analysis. The results showed that high mRNA expression levels of CerS2, CerS3, CerS4 and CerS5 in all NSCLC patients were associated with improved prognosis. Among them, CerS2 and CerS5 are also highly expressed in adenocarcinoma (Ade), but not in squamous cell carcinoma (SCC). In contrast, high or low expression of CerS1 and CerS6 no difference was observed in patients with NSCLC, Ade and SCC. Integrated the data of this study suggested that these CerSs may be a potential tumor markers or drug target of new research direction.
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Animales , Apoptosis , Carcinoma de Pulmón de Células no Pequeñas/genética , Ceramidas , Humanos , Neoplasias Pulmonares/genética , PronósticoRESUMEN
BACKGROUND: Circulating cell-free DNA (ccf-DNA) in plasma may contain both specific and non-specific of tumor markers. The concentration and integrity of ccf-DNA may be clinical useful for detecting and predicting cancer progression. METHODS: Plasma samples from 40 healthy controls and 73 patients with gastric cancers (two stage 0, 17 stage I, 11 stage II, 33 stage III, and 10 stage IV according to American Joint Committee on Cancer stage) were assessed respectively. qPCR targeting the Alu repeats was performed using two different sets of primers amplifying the long and short segments. DNA integrity was calculated as a ratio of the long to the short fragments of Alu repeats. RESULTS: Plasma DNA concentration was significantly higher in patients with stage III and IV gastric cancers than in healthy controls (p = 0.028 and 0.029 respectively). The receiver operating characteristic (ROC) curve for discriminating patients with stage III and IV gastric cancers from healthy controls had an area under the curve (AUC) of 0.744 (95% CI, 0.64 to 0.85). Circulating cell-free DNA concentration increased within 21 days following surgery and dropped by 3 months after surgery. CONCLUSIONS: Concentration of ccf-DNA is a promising molecular marker for assessing gastric cancer progression. TRIAL REGISTRATION: Current Controlled Trials ChiCTR-DDT-12002848 , 8 October 2012.
Asunto(s)
ADN/genética , Neoplasias Hepáticas/secundario , Neoplasias Pulmonares/secundario , Neoplasias Peritoneales/secundario , Neoplasias Gástricas/patología , Adulto , Anciano , Estudios de Casos y Controles , ADN/sangre , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Hepáticas/sangre , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/cirugía , Neoplasias Pulmonares/sangre , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/cirugía , Metástasis Linfática , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Estadificación de Neoplasias , Neoplasias Peritoneales/sangre , Neoplasias Peritoneales/genética , Neoplasias Peritoneales/cirugía , Reacción en Cadena de la Polimerasa , Pronóstico , Neoplasias Gástricas/sangre , Neoplasias Gástricas/genética , Neoplasias Gástricas/cirugíaRESUMEN
Chronic Pseudomonas aeruginosa (PA) infection significantly contributes to morbidity and mortality in bronchiectasis patients. Initiating antibiotics early may lead to the eradication of PA. Here we outline the design of a trial (ERASE; NCT06093191) assessing the efficacy and safety of inhaled tobramycin, alone or with oral ciprofloxacin, in bronchiectasis patients with a new isolation of PA. This multicentre, 2×2 factorial randomised, double-blind, placebo-controlled, parallel-group trial includes a 2-week screening period, a 12-week treatment phase (with a combination of ciprofloxacin or a placebo at initial 2â weeks) and a 24-week follow-up. 364 adults with bronchiectasis and a new PA isolation will be randomly assigned to one of four groups: placebo (inhaled saline and ciprofloxacin placebo twice daily), ciprofloxacin alone (750â mg ciprofloxacin and inhaled saline twice daily), inhaled tobramycin alone (inhaled 300â mg tobramycin and ciprofloxacin placebo twice daily) or a combination of both drugs (inhaled 300â mg tobramycin and 750â mg ciprofloxacin twice daily). The primary objective of this study is to assess the proportion of patients successfully eradicating PA in each group by the end of the study. Efficacy will be evaluated based on the eradication rate of PA at other time points (12, 24 and 36â weeks), the occurrence of exacerbations and hospitalisations, time to first pulmonary exacerbations, patient-reported outcomes, symptom measures, pulmonary function tests and the cost of hospitalisations. To date no randomised trial has evaluated the benefit of different PA eradication strategies in bronchiectasis patients. The ERASE trial will therefore generate crucial data to inform future clinical guidelines.
RESUMEN
OBJECTIVE: The goal of the study was to evaluate the quality of life of children after the older corrective arterial switch operation (ASO) by means of the Pediatric Quality of Life Inventory (PedsQL), version 4.0. METHODS: The records of 86 patients who had complete transposition of the great arteries plus a nonrestrictive ventricular septal defect, or a Taussig-Bing anomaly, and severe pulmonary arterial hypertension, and who underwent a corrective ASO at an older age (>6 months) between May 2000 and October 2008 were reviewed retrospectively. Eighty survivors were followed up, and the health-related quality of life of the survivors was evaluated with the PedsQL, version 4.0. RESULTS: There were 6 hospital deaths. The mean (SD) follow-up interval was 3.5 ± 2.3 years, and the mean age at last visit was 7.0 ± 1.2 years. Two late deaths occurred, and 8 patients were lost to follow-up. Patients who underwent a corrective ASO at an older age showed acceptable scores for all scales, and they were all comparable with those of a healthy population. CONCLUSIONS: Our data suggest that the quality of life of children who undergo a corrective ASO at an older age (>6 months) is acceptable, compared with that of healthy children in China.
Asunto(s)
Procedimientos de Cirugía Plástica/mortalidad , Complicaciones Posoperatorias/mortalidad , Calidad de Vida , Transposición de los Grandes Vasos/mortalidad , Transposición de los Grandes Vasos/cirugía , Procedimientos Quirúrgicos Vasculares/mortalidad , Adolescente , Niño , Preescolar , China/epidemiología , Comorbilidad , Humanos , Masculino , Prevalencia , Análisis de Supervivencia , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
BACKGROUND: Acute exacerbation is a primary cause of repeated hospitalization and death in chronic obstructive pulmonary disease (COPD) patients. Therefore, how to control the symptoms of COPD at stable stage and reduce the number of acute exacerbation is a hot spot of medical research. Acupoint application (AA) is a significant part of external treatment of traditional Chinese medicine (TCM), Previous researches have reported that AA can be applied to the treatment of COPD. Nevertheless, its effectiveness is still inconclusive. This systematic review (SR) and meta-analysis is designed to appraise its effectiveness and safety for the treatment of patients with COPD. METHODS: Eight databases will be systematically retrieved from their inceptions to February 2021. Inclusion criteria are randomized control trials of AA combined with routine western medicine interventions in the treatment of COPD at stable stage. The primary outcomes we focus on comprise clinical effective rate, TCM symptom score, quality of life, dyspnea, exercise capacity, lung function, frequency of acute exacerbation, adverse events. The research screening, data extraction, and risk of bias assessment will be conducted by 2 individuals independently, and divergence will be adjudicated by a third senior investigator. The Stata 13.1 software will be used for meta-analysis. The confidence of evidence will be classified adopting grading of recommendations assessment, development and evaluation (GRADE) algorithm and methodological quality of this SR will be assessed using assessment of multiple systematic reviews-2 (AMSTAR-2) tool. RESULTS: This SR will provide evidence-based medical proof for the treatment of COPD at stable stage by AA combined with conventional western medicine interventions. The findings of this SR will be presented at relevant conferences and submitted for peer-review publication. CONCLUSIONS: The findings of this SR will provide up-todated summary proof for evaluating the effectiveness and safety of AA for COPD. REGISTRATION NUMBER: INPLASY 202140080.
Asunto(s)
Puntos de Acupuntura , Medicamentos Herbarios Chinos/administración & dosificación , Enfermedad Pulmonar Obstructiva Crónica/terapia , Administración Tópica , Medicamentos Herbarios Chinos/efectos adversos , Humanos , Metaanálisis como Asunto , Brote de los Síntomas , Revisiones Sistemáticas como Asunto , Resultado del TratamientoRESUMEN
Advanced pulmonary arterial hypertension is characterized by extensive vascular remodeling that is usually resistant to vasodilator therapy. As the major component of the vascular media, decreased apoptosis of pulmonary arterial smooth muscle cell (PASMC) plays key roles during pulmonary vascular remodeling. Recent studies showed that enhancement of apoptosis of PASMC can reverse pulmonary vascular remodeling and severe pulmonary arterial hypertension. Enhancement of apoptosis of PASMC is becoming a novel strategy to reverse severe pulmonary arterial hypertension. This review analyzes some potential strategies to reverse pulmonary vascular remodeling.
Asunto(s)
Apoptosis/efectos de los fármacos , Hipertensión Pulmonar/tratamiento farmacológico , Músculo Liso Vascular/efectos de los fármacos , Arteria Pulmonar/efectos de los fármacos , Animales , Proliferación Celular/efectos de los fármacos , Ácido Dicloroacético/uso terapéutico , Humanos , Hipertensión Pulmonar/fisiopatología , Pulmón/irrigación sanguínea , Pulmón/fisiopatología , Ratones , Músculo Liso Vascular/fisiopatología , Elastasa Pancreática/antagonistas & inhibidores , Canales de Potasio/análisis , Proteínas Proto-Oncogénicas c-bcl-2/análisis , Arteria Pulmonar/fisiopatología , Ratas , Vasodilatadores/farmacología , Quinasas Asociadas a rho/antagonistas & inhibidoresRESUMEN
Congenital heart disease (CHD) is the most common type of birth defect. Despite the many advances in the understanding of cardiac development and the identification of many genes related to cardiac development, the fundamental etiology for the majority of cases of congenital heart disease remains unknown. This review summarizes normal cardiac development, and outlines the recent discoveries of the genetic causes of congenital heart disease and provides possible strategies for exploring genetic causes.
Asunto(s)
Cardiopatías Congénitas/etiología , Cardiopatías Congénitas/genética , Corazón/embriología , Corazón/crecimiento & desarrollo , Organogénesis , Animales , Epigénesis Genética , Corazón/anatomía & histología , Hemodinámica , Humanos , MicroARNs/genética , MicroARNs/metabolismoRESUMEN
BACKGROUND: The therapeutic strategies of idiopathic pulmonary fibrosis (IPF) tend to be comprehensive. Improving the major symptoms and quality of life (QoL) is as important as postponing the process of fibrosis. However, only pirfenidone and nintedanib conditionally recommended by guidelines and no definite proof indicate that they can significantly ameliorate the main symptoms and QoL of IPF sufferers. At present, multiple types of Traditional Chinese Medicine (TCM) interventions alone or in combination with conventional western medicine managements are widespreadly applied in IPF treatment, which seemingly have a promising clinical effect, especially in ameliorating the main symptoms and improving QoL. Subsequently, the number of relevant studies in systematic reviews(SRs) and meta-analyses of randomized controlled trials(RCTs) increased significantly. Hence, we plan to implement an overview to collect, evaluate, and summarize the results of these SRs. METHODS: An all-round literature retrieval will be conducted in 9 electronic databases, including PubMed, EMBASE, CINAHL, Cochrane Library, Epistemonikos, CNKI, CBM, Wanfang, and VIP. We will focus on the systematic review and meta-analysis of RCTs for multiple TCM interventions alone or in combination with routine western medicine measures in IPF treatment. The main outcomes we follow with interest include the improvement of major symptoms (cough, dyspnea) and QoL. Secondary outcomes will consist of minor symptoms improvement, clinical total effective rate, lung function, blood gas analysis, 6-minute walk text, adverse events, acute exacerbation, all-cause mortality, and IPF-related mortality. Two reviewers will independently select the SRs satisfactory with the enrolling criteria, extract key characteristics, and datas on predefined form, evaluate methodological quality by AMSTAR-2, ROBIS and PRISMA tools, and the quality of evidences adopting GRADE method. In case of any divergence will be reached an agreement by discussion or adjudicated by a third senior reviewer. We will perform a narrative synthesis of the proofs from SRs included. RESULTS: The findings of this overvew will be presented at relevant conferences and submitted for peer-review publication. CONCLUSIONS: We expect to obtain comprehensive and reliable evidence of IPF treated by diversified TCM interventions from the potential standard SRs, which may provide suggestions for future RCTs and SRs. REGISTRATION NUMBER: INPLASY 202080110.
Asunto(s)
Fibrosis Pulmonar Idiopática/terapia , Medicina Tradicional China , Humanos , Metaanálisis como Asunto , Revisiones Sistemáticas como AsuntoRESUMEN
INTRODUCTION: The morbidity of idiopathic pulmonary fibrosis (IPF) was found in an increasing trend, progressive worsening of symptoms and deterioration in lung function tend to trigger off a lower quality of life (QoL). Only pirfenidone and nintedanib have been recommended in the guidelines, which can modify the disease process. However, no evidence was verified to significantly alleviate the main clinical manifestations of IPF. At present, Chinese herbal formula (CHF) is widely prescribed as an adjunct to western medicine to treat the disease, and have shown promising benefits on clinical symptoms and QoL. There are mainly 3 Traditional Chinese Medicine (TCM) treatment methods guiding the composition of CHFs, which are devoting to comfort the common symptoms of IPF. Nevertheless, the paucity of direct comparative evidence of them posed a challenge for clinicians to determine the relative merits options. Therefore, we formulate this protocol, which is described for a systematic review to investigate relative advantages among different TCM treatment method and provide more reliable evidence for clinical decision-making. METHODS AND ANALYSIS: A systematic literature search will be employed in 10 electronic databases. Inclusion criteria are randomized control trials of CHFs composed based on the 3 TCM treatment methods, which act as an adjuvant treatment with routine drugs, compared with routine drugs alone. The primary outcomes we focus on include St George's Hospital Respiratory Questionnaire (SGRQ) scores, TCM symptom (dyspnea, cough) scores. The research screening, data extraction, and methodological quality assessment will be conducted by 2 individuals separately, and dispute will be adjudicated by a third senior reviewer. We will employ network meta-analysis (NMA) in a Bayesian framework with vague priors and the surface under the cumulative ranking curve (SUCRA) to obtain the comprehensive rank for the 3 TCM treatment methods. RESULTS: This systematic review will provide an evidence of CHFs composed under the guidance by 3 TCM treatment methods with routine drugs, compared with routine drugs alone for IPF, and will submit to a peer-reviewed journal for publication. CONCLUSION: The conclusion of this systematic review will provide evidence for relative advantages among the 3 TCM treatment methods.
Asunto(s)
Antiinflamatorios no Esteroideos , Medicamentos Herbarios Chinos , Fibrosis Pulmonar Idiopática , Medicina Tradicional China , Proyectos de Investigación , Humanos , Acetilcisteína/uso terapéutico , Antiinflamatorios no Esteroideos/administración & dosificación , Antiinflamatorios no Esteroideos/uso terapéutico , Teorema de Bayes , Quimioterapia Combinada , Medicamentos Herbarios Chinos/administración & dosificación , Medicamentos Herbarios Chinos/uso terapéutico , Fibrosis Pulmonar Idiopática/tratamiento farmacológico , Indoles/uso terapéutico , Medicina Tradicional China/métodos , Metaanálisis en Red , Piridonas/uso terapéutico , Calidad de Vida , Ensayos Clínicos Controlados Aleatorios como Asunto , Pruebas de Función Respiratoria , Índice de Severidad de la Enfermedad , Análisis de Supervivencia , Metaanálisis como Asunto , Revisiones Sistemáticas como AsuntoRESUMEN
The ubiquitin-proteasome pathway is an important protein degradation regulatory system in cells. This pathway is also a reversible process that is strictly regulated, and the regulation of deubiquitinating enzymes (DUBs) represents an important facet of the process. Ovarian tumor-associated proteases domain-containing proteins (OTUDs), as a subfamily within the DUB family, serve an important role in regulatory mechanisms of several biological processes, through the regulation of gene transcription, cell cycle, immune response, inflammation and tumor growth processes, and may be important in the diagnosis of various diseases and constitute novel drug targets. However, the role of OTUDs in non-small-cell lung cancer (NSCLC) has not been fully elucidated. In the present study, the Oncomine database was used to examine gene expression in NSCLC, and the prognostic value of each gene was analyzed by Kaplan-Meier analysis. The results indicated that high mRNA expression levels of OTUD1, OTUD3, OTUD4 and putative bifunctional UDP-N-acetylglucosamine transferase and deubiquitinase ALG13 were associated with improved prognosis in all NSCLC and adenocarcinoma, but not in squamous cell carcinoma. By contrast, high expression levels of OTUD2 mRNA were associated with poorer overall survival in patients with NSCLC. These data suggested that these OTUD isozymes may be a potential drug target for NSCLC.
RESUMEN
BACKGROUND: Although the incidence of tuberculosis (TB) has dropped substantially, it still is a serious threat to human health. And in recent years, the emergence of resistant bacilli and inadequate disease control and prevention has led to a significant rise in the global TB epidemic. It is known that the cause of TB is Mycobacterium tuberculosis infection. But it is not clear why some infected patients are active while others are latent. METHODS: We analyzed the blood gene expression profiles of 69 latent TB patients and 54 active pulmonary TB patients from GEO (Transcript Expression Omnibus) database. RESULTS: By applying minimal redundancy maximal relevance and incremental feature selection, we identified 24 signature genes which can predict the TB activation. The support vector machine predictor based on these 24 genes had a sensitivity of 0.907, specificity of 0.913, and accuracy of 0.911, respectively. Although they need to be validated in a large independent dataset, the biological analysis of these 24 genes showed great promise. CONCLUSION: We found that cytokine production was a key process during TB activation and genes like CYBB, TSPO, CD36, and STAT1 worth further investigation.
RESUMEN
Background: The current standard approach to the treatment of patients with non-small-cell lung cancer (NSCLC) harboring epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI)-sensitizing mutations has been the treatment with a first-generation EGFR-TKIs. While, with resistance developed against first-generation EGFR-TKIs, second/third-generation TKIs have attracted all the attention, and replaced first-generation EGFR- TKIs upon disease progression due to the greater efficacy and more favorable tolerability. In the past few years, this strategy has been challenged by clinical evidence when next-generation EGFR-TKIs are used in patients with advanced NSCLC. Objective: In this study, we performed a meta- analysis to investigate the efficacy of next-generation TKIs comparison with first-generation TKIs in the treatment of NSCLC. Methods: The multiple databases including Pubmed, Embase, Cochrane library databases were adopted to search for the relevant studies, and full-text articles involving to comparison of next-generation TKIs and first-generation TKIs were reviewed. After rigorous reviewing on quality, the data was extracted from eligible randomized controlled trial (RCT). Meta-analysis Revman 5.3 software was used to analyze the combined pooled ORs with the corresponding 95% confidence interval using fixed- or random-effects models according to the heterogeneity. Results: A total of 5 randomized controlled trials were included in this analysis. The group of next-generation TKIs did achieved benefit in progression-free survival (PFS) (OR = 0.58, 95%CI = 0.45-0.75, Pï¼0.0001), overall survival (OS) (OR = 0.76, 95%CI = 0.65-0.90, P = 0.001) as well with the objective response rate (ORR) (OR = 1.27, 95%CI = 1.01-1.61, P = 0.04), respectively. In the results of subgroup analysis of PFS with EGFR mutations, there is also significant differences with exon 19 deletion (OR = 0.56, 95%CI = 0.41-0.77, P = 0.0003) and exon 21 (L858R) mutation (OR = 0.60, 95%CI = 0.49-0.75, Pï¼ï¼0.00001). While, the treatment-related severe adverse event (SAE) between the next-generation TKIs and first-generation TKIs did not have statistical significance (OR = 1.48, 95%CI = 0.62-3.55, P = 0.38). Conclusion: The next-generation TKIs significantly improved efficacy outcomes in the treatment of EGFR mutation-positive advanced NSCLC compared with the first-generation TKIs, with a manageable safety profile. These results are potentially important for clinical decision making for these patients.
Asunto(s)
Antineoplásicos/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Supervivencia sin Enfermedad , Diseño de Fármacos , Receptores ErbB/antagonistas & inhibidores , Receptores ErbB/genética , Exones , Humanos , Neoplasias Pulmonares/mortalidad , Mutación , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del TratamientoRESUMEN
BACKGROUND: Randomized controlled trials (RCTs) of roflumilast effect on chronic obstructive pulmonary disease (COPD) have been reported in the last decade. The current meta-analysis was designed to systematically review and perform meta-analysis of the RCTs of roflumilast treatment in COPD. METHODS: Electronic databases including PubMed, EMBASE, Web of Science, and Cochrane clinical trials database were searched to identify RCTs of roflumilast treatment on COPD. The primary outcomes were effect of roflumilast on pre-bronchodilator FEV1, post-bronchodilator FEV1, and exacerbation rate. Secondary outcomes were effect of roflumilast on airway inflammation and adverse effect. RESULTS: A total of 11 RCTs were enrolled into the current analysis. Roflumilast significantly improved both pre-bronchodilator FEV1 (standardized difference in mean ± SD was 0.621 ± 0.161; 95% CI 0.306~0.936, p < 0.001) and post-bronchodilator FEV1 (standardized difference in mean ± SD was 0.563 ± 0.149, 95% CI 0.270~0.855, p < 0.001) compared with placebo. Roflumilast also significantly reduced exacerbation of COPD (standardized difference in mean ± SD 0.099 ± 0.020, 95% CI 0.061~0.138; p < 0.001) and suppressed airway inflammation (standardized difference in mean ± SD 1.354 ± 0.260, 95% CI 0.845~1.862, p < 0.001) compared with placebo. However, roflumilast significantly increased adverse effect such as diarrhea (rate ratio 2.945, 95% CI 2.453~3.536, p < 0.001) and weight loss (rate ratio 3.814, 95% CI 3.091~4.707, p < 0.001) compared with placebo. CONCLUSION: These findings indicated that roflumilast treatment could improve COPD patients' lung function and reduce exacerbation, and that inhibition of airway inflammation by roflumilast might contribute to the beneficial effect of PDE-4 inhibitors on COPD.
Asunto(s)
Aminopiridinas/uso terapéutico , Benzamidas/uso terapéutico , Inhibidores de Fosfodiesterasa 4/uso terapéutico , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Aminopiridinas/farmacología , Benzamidas/farmacología , Ciclopropanos/farmacología , Ciclopropanos/uso terapéutico , Humanos , Inhibidores de Fosfodiesterasa 4/farmacología , Enfermedad Pulmonar Obstructiva Crónica/patologíaRESUMEN
BACKGROUND: Casitas B-lineage lymphoma proto-oncogene-b (CBLB) influences the threshold of T cell activation and controlling peripheral T cell tolerance. In the present study, we hypothesize that potentially functional single nucleotide polymorphisms (SNPs) in CBLB are associated with clinical outcomes in patients advanced non-small cell lung cancer (NSCLC) treated with the first-line chemotherapy. METHODS: We genotyped three SNPs (rs2305035, rs3772534 and rs9657904) at CBLB in 116 advanced NSCLC patients with progression free survival (PFS) data and 133 advanced NSCLC patients with overall survival (OS) data, and we assessed their associations, 95% confidence interval (CI), with clinical outcomes by using Cox proportional hazards regression analyses. In silico functional analysis was also performed for the SNPs under investigation. RESULTS: We found that associations between the three SNPs and PFS/OS were not significant in the overall NSCLC patients. The rs2305035 AA genotype was associated with a worse PFS in female patients and those of non-smokers or light smokers (95% CI, 1.14-11.81, P=0.030; 95% CI, 1.42-10.24, P=0.008; and 95% CI, 1.39-9.93, P=0.009; respectively), compared with the GG+AA genotypes. We also found that the rs9657904 CC genotype was significantly associated with a worse OS than TT + TC genotypes in male advanced NSCLC patients. Further in silico functional analysis revealed that the rs965704 T allele was significantly associated with lower mRNA expression levels of the CBLB gene. CONCLUSIONS: Our findings identified two CBLB SNPs (rs2305035 and rs9657904) that were significantly associated with PFS and OS in several subgroups of Chinese advanced NSCLC patients after the first-line chemotherapy.
RESUMEN
OBJECTIVES: To compare laparoscopic extraperitoneal colostomy with transperitoneal colostomy for construction of a permanent stoma by measuring the incidence of parastomal hernia, and other postoperative complications related to colostomy. METHODS: The meta-analysis was carried out in the General Surgery Department of the Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, China in 2014. A literature search of Medline, EMBASE, Cochrane database, and the Chinese Biomedical Literature Database (CBM) from the years 1990 to 2014 was performed. The literature searches were carried out using medical subject headings and free-text words: extraperitoneal colostomy, transperitoneal colostomy, laparoscopic extraperitoneal colostomy, rectal cancer, laparoscopic abdominoperineal resection, parastomal hernia, permanent stoma, and colostomy-related complications. Two different reviewers carried out the search and evaluated studies independently. RESULTS: One randomized controlled trial and 6 retrospective studies were included. A total of 378 patients (209 extraperitoneal colostomy and 169 transperitoneal colostomy) were identified. Our analysis showed that there was a significantly lower rate of parastomal hernia (odds ratio 0.10; 95% confidence interval 0.03-0.29, p<0.0001) in the extraperitoneal colostomy group. However, the other stoma-related complications were not significantly different between the 2 groups. CONCLUSION: Colostomy construction via the extraperitoneal route using a laparoscopic approach can largely reduce the incidence of parastomal hernia. Laparoscopic permanent sigmoid stoma creation through the extraperitoneal route should be the first choice after laparoscopic abdominoperineal resection.
Asunto(s)
Colon Sigmoide/cirugía , Laparoscopía/métodos , Peritoneo/cirugía , Estomas Quirúrgicos , Humanos , Laparoscopía/efectos adversosRESUMEN
PURPOSE: Although surgical treatments evolved, the short-term postoperative mortality is still high in children with anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA), and long-term survivors may suffer from restrained functional recovery. Therefore, an optimal means in predicting postoperative reversal is demanded. In this study, we assess the utility of myocardial perfusion/F-18 fluorodeoxyglucose (FDG) imaging in the evaluation of myocardial viability and postsurgery functional recovery in children with ALCAPA. MATERIALS AND METHODS: A retrospective study was performed in 7 children with diagnosed ALCAPA who underwent myocardial perfusion/F-18 FDG imaging preoperatively. Global viability index was used to evaluate myocardial viability and was compared with the preoperative deviations of left ventricular ejection fraction (LVEF) and left ventricular end-diastolic diameter (LVEDD) from age-matched healthy children and with the postoperative durations of intensive care. RESULTS: Children with more viable myocardium had less severe clinical symptoms. The viability index was correlated well with the preoperative deviations of LVEF (r = -0.98, P = 0.001) and LVEDD (r = 0.87, P = 0.02) and postoperative durations of intensive care hospitalization (r = 0.77, P = 0.04) and mechanical ventilation (r = 0.83, P = 0.02). LVEF and LVEDD reached normal range within 5 months in viable children, whereas incomplete reversal was observed in partial- and nonviable children. CONCLUSIONS: In children with ALCAPA, myocardial viability evaluated by perfusion/F-18 FDG imaging is related to the preoperative clinical manifestations and cardiac function. Additionally, it may predict functional recovery after surgical repair.
Asunto(s)
Fístula Arterio-Arterial/diagnóstico por imagen , Anomalías de los Vasos Coronarios/diagnóstico por imagen , Fluorodesoxiglucosa F18 , Imagen de Perfusión Miocárdica/métodos , Aturdimiento Miocárdico/diagnóstico por imagen , Arteria Pulmonar/anomalías , Arteria Pulmonar/diagnóstico por imagen , Niño , Preescolar , Vasos Coronarios/diagnóstico por imagen , Femenino , Humanos , Lactante , Masculino , Radiografía , Radiofármacos , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: Congenital heart disease with near-systemic pulmonary arterial pressures, previously thought to have irreversible pulmonary vascular disease (PVD), has been successfully corrected at our institution recently. Whether the PVD is reversible remains unknown. This study aimed to examine the nature of the pulmonary arterial vessels in these selective patients. METHODS: All patients with congenital heart disease and severe pulmonary hypertension (PH) were selected using Diagnostic-treatment to undergo radical repair (n=49). Lung biopsy specimens were obtained during operation. The nature of PVD was determined by Heath-Edwards classification system. All specimens were quantitatively analyzed by calculating percentage media wall area, percentage media wall thickness and arteriole density. RESULTS: Transcutaneous oxygen saturation of all selected patients increased significantly after Diagnostic-treatment (P<0.001). There were no operative deaths. Mean pulmonary artery pressure and pulmonary vascular resistance regressed significantly postoperatively (P<0.001). The incidence of postoperative PH was 59.2% (29/49). Of 49 selected patients with severe PH, 38 (77.6%) showed grade I change, 5 (10.2%) showed grade II change, 4 (8.2%) showed grade III change and only 2 (4%) showed grade IV change with plexiform lesion. The percentage media wall area, percentage media wall thickness and arteriole density were significantly increased in patients associated with PH than in normal subjects (P<0.001). Follow-up data showed the reversal of PVD in these 2 patients with plexiform lesions. CONCLUSIONS: The PVD in these selective patients with congenital heart disease and severe PH using a Diagnostic-treatment-and-Repair strategy is generally reversible and these patients are operable in current era.
Asunto(s)
Cardiopatías Congénitas/complicaciones , Hipertensión Pulmonar , Pulmón/patología , Procedimientos Quirúrgicos Pulmonares , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Arteriolas/patología , Biopsia , Niño , Elasticidad , Femenino , Estudios de Seguimiento , Humanos , Hipertensión Pulmonar/etiología , Hipertensión Pulmonar/patología , Hipertensión Pulmonar/cirugía , Masculino , Persona de Mediana Edad , Oximetría , Arteria Pulmonar/patología , Índice de Severidad de la Enfermedad , Resistencia Vascular , Adulto JovenRESUMEN
BACKGROUND: We reviewed our experience with congenital ruptured sinus of Valsalva aneurysms (RSVA) to determine risk factors influencing occurrence and postoperative worsening of aortic regurgitation (AR). METHODS: Over an 11-year period, 210 patients (33 ± 9.7 years old) underwent surgical repair of RSVA. Aneurysm originated from the right noncoronary sinus and other sinuses in 171, 35 and 4 patients, respectively; and ruptured into right ventricle outlet tract in 115 patients, right ventricle in 16, right atrium in 75, and other chambers in 4. Aortic regurgitation (111) and ventricular septal defect (108) were common coexisting anomalies. Patch closure of RSVA was performed in 61 patients, direct sutures in 18 patients, patch closure plus direct sutures in 88 patients, and repair simultaneous with aortic valve replacement in 43 patients. RESULTS: All but one patient survived the operation. In early postoperative periods, AR improved in 26 patients and worsened in 23. In 114 late follow-up patients with echocardiographic assessment, 18 showed deteriorated AR. By logistic regression analysis, RSVA ruptured into the right ventricle outlet tract and secondary changes of the aortic valve were risk factors for preoperative AR, and RSVA repaired with direct sutures had a significantly higher incidence of early worsening of AR. By Cox regression analysis, AR at discharge was an independent risk factor for late follow-up AR worsening. CONCLUSIONS: The RSVA can be repaired with a low mortality and excellent long-term result. An early, aggressive treatment should be recommended to prevent postoperative AR, and a direct-suture closure of RSVA should be avoided to prevent early worsening of AR.