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1.
BMC Pregnancy Childbirth ; 24(1): 375, 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38760653

RESUMO

BACKGROUND: Limited evidence exists regarding the association between gestational diabetes mellitus (GDM) and elevated levels of thyroid-stimulating hormone (TSH) in newborns. Therefore, this study aimed to investigate the potential risk of elevated TSH levels in infants exposed to maternal GDM, considering the type and number of abnormal values obtained from the 75-gram oral glucose tolerance test (OGTT). METHODS: A population-based, prospective birth cohort study was conducted in Wuhan, China. The study included women who underwent GDM screening using a 75-g OGTT. Neonatal TSH levels were measured via a time-resolved immunofluorescence assay. We estimated and stratified the overall risk (adjusted Risk Ratio [RR]) of elevated TSH levels (defined as TSH > 10 mIU/L or > 20 mIU/L) in offspring based on the type and number of abnormal OGTT values. RESULTS: Out of 15,236 eligible mother-offspring pairs, 11.5% (1,753) of mothers were diagnosed with GDM. Offspring born to women diagnosed with GDM demonstrated a statistically significant elevation in TSH levels when compared to offspring of non-GDM mothers, with a mean difference of 0.20 [95% CI: 0.04-0.36]. The incidence of elevated TSH levels (TSH > 10 mIU/L) in offspring of non-GDM women was 6.3 per 1,000 live births. Newborns exposed to mothers with three abnormal OGTT values displayed an almost five-fold increased risk of elevated TSH levels (adjusted RR 4.77 [95% CI 1.64-13.96]). Maternal fasting blood glucose was independently and positively correlated with neonatal TSH levels and elevated TSH status (TSH > 20 mIU/L). CONCLUSIONS: For newborns of women with GDM, personalized risk assessment for elevated TSH levels can be predicated on the type and number of abnormal OGTT values. Furthermore, fasting blood glucose emerges as a critical predictive marker for elevated neonatal TSH status.


Assuntos
Diabetes Gestacional , Teste de Tolerância a Glucose , Tireotropina , Humanos , Feminino , Tireotropina/sangue , Gravidez , Diabetes Gestacional/sangue , Recém-Nascido , Adulto , China/epidemiologia , Estudos Prospectivos , Coorte de Nascimento , Masculino , Estudos de Coortes
2.
Ecotoxicol Environ Saf ; 249: 114378, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36525950

RESUMO

BACKGROUND: Environmental inorganic arsenic (iAs) exposure is potentially related to abnormal blood pressure (BP) changes and abnormal platelet activation. However, limited epidemiological studies have explored the impacts of iAs exposure on platelet change mediated by BP, especially for pregnant women. OBJECTIVES: Our purpose was to investigate the associations of arsenic exposure with blood pressure and platelet indices among pregnant women. METHODS: The present study population included 765 pregnant women drawn from a prospective birth cohort study in Wuhan, China, recruited between October 2013 and April 2016. Urine sampled in the second trimester were used to assess arsenic species concentrations. The relative distribution of urinary arsenic species was used to measure human methylation capacity. BP parameters and platelet indices originated from the medical record. We applied multivariable linear regression models to explore the cross-sectional relationships between urinary arsenic metabolites, BP parameters, and platelet indices. We utilized mediation analysis to investigate the impacts of arsenic exposure on platelet indices through BP as mediator variables. RESULTS: We observed significant positive correlations between iAs and systolic BP (SBP), diastolic BP (DBP), and mean arterial pressure (MAP). Pregnant women with higher methylation capacity to metabolize iAs characterized by higher secondary methylation index (SMI) and total methylation index (TMI) had a more significant reduction in SBP, DBP, and MAP. Pregnant women with higher DBP and MAP had higher platelet counts (PLC). A decreased PLC was found in subjects wither higher SMI. Additionally, SMI was negatively linked to PLC mediated through MAP. CONCLUSIONS: Obtained results suggested that higher methylation capacity to metabolize iAs might contribute to decreased PLC among pregnant women, and MAP might mediate the influence of SMI on PLC.


Assuntos
Arsênio , Arsenicais , Humanos , Feminino , Gravidez , Arsênio/análise , Estudos Transversais , Gestantes , Pressão Sanguínea , Estudos de Coortes , Estudos Prospectivos , Arsenicais/análise , Exposição Ambiental/análise , China
3.
Int J Environ Health Res ; 32(8): 1647-1685, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33849343

RESUMO

We used a transparent systematic review framework based on best practices for evaluating study quality and integrating evidence to conduct a review of the available epidemiology studies evaluating associations between long-term exposure to ambient concentrations of PM2.5 and mortality (all-cause and non-accidental) conducted in North America. We found that while there is some consistency across studies for reporting positive associations, these associations are weak and several important methodological issues have led to uncertainties with regard to the evidence from these studies, including potential confounding by measured and unmeasured factors, exposue measurement error, and model misspecification. These uncertainties provide a plausible, alternative explanation to causality for the weakly positive findings across studies. Using a causality framework that incorporates best practices for making causal determinations, we concluded that the evidence for a causal relationship between long-term exposure to ambient PM2.5 concentrations and mortality from these studies is inadequate.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Poluentes Atmosféricos/análise , Poluentes Atmosféricos/toxicidade , Poluição do Ar/efeitos adversos , Poluição do Ar/análise , Exposição Ambiental/efeitos adversos , Mortalidade , Material Particulado/análise , Material Particulado/toxicidade
4.
BMC Med ; 18(1): 330, 2020 10 19.
Artigo em Inglês | MEDLINE | ID: mdl-33070775

RESUMO

BACKGROUND: The coronavirus disease 2019 (COVID-19) outbreak is evolving rapidly worldwide. However, little is known about the association between pregnant women with COVID-19 and the risk of adverse birth outcomes. METHOD: We conducted a retrospective cohort study based on the Maternal and Child Health Information System (MCHIMS) of Wuhan, China. All pregnant women with singleton live birth recorded by the system between January 13 and March 18, 2020, were included. The adverse birth outcomes were preterm birth, low birth weight, neonatal asphyxia, premature rupture of membrane (PROM), and cesarean section delivery. Multivariate logistic regression was used to evaluate the associations between maternal COVID-19 diagnosis and adverse birth outcomes. RESULTS: Out of 11,078 pregnant women, 65 were confirmed with coronavirus disease 2019 (COVID-19). No deaths occurred from these confirmed cases or their newborns. Compared to pregnant women without COVID-19, pregnant women with a confirmed COVID-19 diagnosis had an increased risk of preterm birth (OR 3.34, 95% CI 1.60-7.00) and cesarean section (OR 3.63, 95% CI 1.95-6.76). There was no statistical difference in low birth weight, neonatal asphyxia, and PROM between the mothers with and without COVID-19. Among these newborns that were born to mothers with confirmed COVID-19, none was tested severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive or had abnormal CT results. Only one had diarrhea and three had a fever. CONCLUSIONS: This population-based cohort study suggests that COVID-19 during the later pregnancy is associated with an increased risk of adverse birth outcomes, including iatrogenic preterm birth and cesarean section delivery. Our data provide little evidence for maternal-fetal vertical transmission of SARS-CoV-2. It is important to monitor the long-term health effects of SARS-CoV-2 infection on pregnant women and their children.


Assuntos
Infecções por Coronavirus/transmissão , Pneumonia Viral/transmissão , Complicações Infecciosas na Gravidez , Adulto , Betacoronavirus , COVID-19 , Cesárea , China , Estudos de Coortes , Feminino , Humanos , Lactente , Recém-Nascido de Baixo Peso , Recém-Nascido , Doenças do Recém-Nascido/etiologia , Modelos Logísticos , Masculino , Pandemias , Gravidez , Complicações na Gravidez/epidemiologia , Resultado da Gravidez , Nascimento Prematuro/epidemiologia , Nascimento Prematuro/etiologia , Estudos Retrospectivos , SARS-CoV-2
5.
Pediatr Res ; 88(4): 668-675, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32018276

RESUMO

BACKGROUND: Maternal hypertensive disorders of pregnancy (HDP) are the major causes of maternal mortality. However, the association between HDP and offspring's neurodevelopment remains unclear. METHOD: Participants were 4031 singleton live births from a prospective cohort study in Wuhan, China, during October 2013 to October 2014. Neurodevelopment of infant was evaluated by using Chinese version of Gesell Developmental Schedules at 0.5 year of age. Maternal HDP and potential confounders were ascertained by healthcare records at baseline. RESULTS: Generalized linear model analysis indicated that maternal chronic hypertension were significantly associated with development quotient on fine motor (ß = -3.32, 95% CI: -6.33 to -0.31), adaptability (ß = -2.87, 95% CI: -5.31 to -0.43), language (ß = -1.23, 95% CI: -2.12 to -0.34) and social behavior (ß = -2.53, 95% CI: -4.69 to -0.37), and gestational hypertension was significantly associated with development quotient on social behavior (ß = -1.42, 95% CI: -2.03 to -0.81), even after adjustment of major confounders. Multivariable logistic regression analysis showed that maternal chronic hypertension also increased the risk of diagnosis of "neurodevelopmental delay" on fine motor (OR = 1.85, 95% CI: 1.19-2.89), adaptability (OR = 2.32, 95% CI: 1.42-3.78), language (OR = 2.86, 95% CI: 1.74-4.70), and social behavior (OR = 2.13, 95% CI: 1.73-2.59). CONCLUSION: This study suggests that exposure to HDP is associated with an increased risk of neurodevelopment impairment in the offspring at the age of 0.5 year.


Assuntos
Hipertensão Induzida pela Gravidez/diagnóstico , Hipertensão Induzida pela Gravidez/fisiopatologia , Efeitos Tardios da Exposição Pré-Natal , Adulto , Pressão Sanguínea , Índice de Massa Corporal , China/epidemiologia , Feminino , Humanos , Lactente , Recém-Nascido , Modelos Lineares , Estudos Longitudinais , Masculino , Idade Materna , Transtornos do Neurodesenvolvimento/etiologia , Gravidez , Estudos Prospectivos , Fatores de Tempo
6.
J Cell Biochem ; 118(11): 4020-4032, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28422315

RESUMO

Positive transcription elongation factor-b (P-TEFb) is required for the release of RNA polymerase II (RNAPII) from its pause near the gene promoters and thus for efficient proceeding to the transcription elongation. It consists of two core subunits-CDK9 and one of T-typed or K-typed cyclin, of which, cyclin T1/CDK9 is the major and most studied combination. We have previously identified a novel splice variant of cyclin T1, cyclin T1b, which negatively regulates the transcription elongation of HIV-1 genes as well as several host genes. In this study, we revealed the serine-arginine-rich protein, ASF/SF2, as a regulatory factor of the alternative splicing of cyclin T1 gene. ASF/SF2 promotes the production of cyclin T1b versus cyclin T1a and regulates the expression of cyclin T1-depedent genes at the transcription level. We further found that a cis-element on exon 8 is responsible for the skipping of exon 7 mediated by ASF/SF2. Collectively, ASF/SF2 is identified as a splicing regulator of cyclin T1, which contributes to the control of the subsequent transcription events. J. Cell. Biochem. 118: 4020-4032, 2017. © 2017 Wiley Periodicals, Inc.


Assuntos
Processamento Alternativo/fisiologia , Ciclina T/biossíntese , Fatores de Processamento de Serina-Arginina/metabolismo , Linhagem Celular , Ciclina T/genética , Humanos , Isoformas de Proteínas/biossíntese , Isoformas de Proteínas/genética , Fatores de Processamento de Serina-Arginina/genética
7.
Clin Gastroenterol Hepatol ; 14(9): 1266-1273.e1, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27211503

RESUMO

BACKGROUND & AIMS: Diseases of the stomach, including gastric cancer and peptic ulcer, are the most common digestive diseases. It is impossible to visualize the entire stomach with the passive capsule currently used in practice because of the large size of the gastric cavity. A magnetically controlled capsule endoscopy (MCE) system has been designed to explore the stomach. We performed a prospective study to compare the accuracy of detection of gastric focal lesions by MCE vs conventional gastroscopy (the standard method). METHODS: We performed a multicenter blinded study comparing MCE with conventional gastroscopy in 350 patients (mean age, 46.6 y), with upper abdominal complaints scheduled to undergo gastroscopy at a tertiary center in China from August 2014 through December 2014. All patients underwent MCE, followed by conventional gastroscopy 2 hours later, without sedation. We calculated the sensitivity, specificity, positive predictive value, and negative predictive value of detection of gastric focal lesions by MCE, using gastroscopy as the standard. RESULTS: MCE detected gastric focal lesions in the whole stomach with 90.4% sensitivity (95% confidence interval [CI], 84.7%-96.1%), 94.7% specificity (95% CI, 91.9%-97.5%), a positive predictive value of 87.9% (95% CI, 81.7%-94.0%), a negative predictive value of 95.9% (95% CI, 93.4%-98.4%), and 93.4% accuracy (95% CI, 90.83%-96.02%). MCE detected focal lesions in the upper stomach (cardia, fundus, and body) with 90.2% sensitivity (95% CI, 82.0%-98.4%) and 96.7% specificity (95% CI, 94.4%-98.9%). MCE detected focal lesions in the lower stomach (angulus, antrum, and pylorus) with 90.6% sensitivity (95% CI, 82.7%-98.4%) and 97.9% specificity (95% CI, 96.1%-99.7%). MCE detected 1 advanced gastric carcinoma, 2 malignant lymphomas, and 1 early stage gastric tumor. MCE did not miss any lesions of significance (including tumors or large ulcers). Among the 350 patients, 5 reported 9 adverse events (1.4%) and 335 preferred MCE over gastroscopy (95.7%). CONCLUSIONS: MCE detects focal lesions in the upper and lower stomach with comparable accuracy with conventional gastroscopy. MCE is preferred by almost all patients, compared with gastroscopy, and can be used to screen gastric diseases without sedation. Clinicaltrials.gov number: NCT02219529.


Assuntos
Endoscopia por Cápsula/métodos , Gastroscopia/métodos , Gastropatias/diagnóstico , Adolescente , Adulto , Idoso , Animais , China , Feminino , Humanos , Magnetismo , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Sensibilidade e Especificidade , Centros de Atenção Terciária , Adulto Jovem
8.
Scand J Gastroenterol ; 51(4): 494-500, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26212517

RESUMO

OBJECTIVE: Peroral endoscopic myotomy (POEM) has been developed to treat achalasia as a novel less invasive modality. We aimed to compare the efficacy and safety of conventional knife versus Hybrid knife (HK) during POEM procedure. MATERIALS AND METHODS: Between June 2012 and July 2014, 31 patients underwent POEM using HK in our department (HK group), and 36 patients underwent POEM using conventional method (injection needle and triangular tip [TT] knife, TT group). Procedure-related parameters, symptom relief, adverse events were compared between two groups. RESULTS: There were no significant differences in the age, sex and other baseline characteristics between the two groups. The mean procedural time was significantly shorter in HK group than TT group (53.0 ± 17.2 vs. 67.6 ± 28.4 min, p = 0.015). The mean frequency of devices exchange was 4.7 ± 1.7 in HK group and 10.9 ± 1.8 in TT group (p = 0.000). No serious adverse events occurred postoperatively in both groups. At one-year follow-up, a total of 94% treatment success was achieved in all patients (93.5% in HK group and 94.4% in TT group, p = 0.877). CONCLUSION: HK in POEM can shorten the procedural time, and achieve similar treatment success compared to conventional TT knife.


Assuntos
Acalasia Esofágica/cirurgia , Esofagoscopia , Cirurgia Endoscópica por Orifício Natural , Adolescente , Adulto , Idoso , Estudos de Casos e Controles , Esofagectomia/instrumentação , Esofagectomia/métodos , Esofagoscopia/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
9.
Surg Endosc ; 30(9): 3774-82, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-26659228

RESUMO

BACKGROUND: Peroral endoscopic myotomy (POEM) has been described as a novel treatment for esophageal achalasia. Owing to its technical difficulty, POEM is not widely performed. This study was aimed to prospectively assess the factor predicting technical difficulty of POEM in a single center with large volume cases. METHODS: A total of 105 cases of achalasia treated by POEM from April 2011 to September 2014 were analyzed. Difficult cases of POEM were defined as procedure time ≥90 min and occurrence of adverse events, including mucosal perforation, pneumothorax, and major bleeding. Univariate and multivariate logistic regression analyses were performed to assess the predictive factors of difficult POEM. RESULTS: POEM was successfully completed in all the patients, and no one was converted to laparoscopy. The number of cases with procedure time ≥90 min was 17. Mucosal perforations occurred in six (5.7 %) patients during submucosal tunnel creation, major bleeding occurred in seven (6.7 %) patients, and pneumothorax occurred in six (5.7 %) patients immediately after procedure. All the complications were managed conservatively. No other intraoperative and immediate postoperative complications, including infections and pneumoperitoneum, occurred. Multivariate analysis showed that early period (odds ratio [OR] 4.173, 95 % confidence interval [95 % CI] 1.36-6.829, P = 0.023) and triangular tip knife ([OR] 6.712, [95 % CI] 1.479-30.460, P = 0.014) were independent factors associated with technical difficulty regarding longer procedure time (procedure time ≥90 min). CONCLUSION: POEM is safe for the treatment of esophageal achalasia. Triangular tip knife and early period were independent risk factors for longer procedural time.


Assuntos
Endoscopia Gastrointestinal/métodos , Acalasia Esofágica/cirurgia , Adolescente , Adulto , Esfíncter Esofágico Inferior/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Cirurgia Endoscópica por Orifício Natural/métodos , Razão de Chances , Complicações Pós-Operatórias/etiologia , Estudos Prospectivos , Adulto Jovem
10.
Pediatr Surg Int ; 31(7): 633-8, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25957132

RESUMO

INTRODUCTION: Achalasia is a rare esophageal motility disorder in the pediatric population. Peroral endoscopic myotomy (POEM) has been demonstrated to be effective and safe for the treatment of achalasia as a novel endoscopic technique, but data involving its utility in pediatric patients are limited. We aimed to assess the safety and efficacy of POEM for pediatric patients with achalasia. MATERIALS AND METHODS: Between July 2012 and August 2014, five consecutive pediatric patients (2 female and 3 male, with a median age of 15 years) with achalasia underwent POEM in our center. Diagnosis was based on symptoms, manometry, radiology and endoscopy. Preoperative and postoperative symptoms scores, and manometry outcomes were recorded and analyzed. RESULTS: Procedure was performed successfully in all patients, and the median time required for the procedure was 50 min (range 40-90 min). There were no mortalities and no serious intraoperative and postoperative complications. The median length of myotomy was 8 cm (range 6-11 cm). During a median follow-up period of 18 months, treatment success (Eckardt score ≤3) was achieved in all patients. There was a significant improvement of symptoms relief, dysphagia score and lower esophageal sphincter pressure decrease after POEM. No patient developed gastroesophageal reflux disease. CONCLUSION: Our study suggests that POEM is a safe and effective technique for treating pediatric achalasia. Further studies with long-term follow-up in large-volume pediatric patients are warranted to clearly define the durability of the procedure.


Assuntos
Acalasia Esofágica/cirurgia , Cirurgia Endoscópica por Orifício Natural/métodos , Adolescente , Esofagoscopia/métodos , Feminino , Humanos , Masculino , Complicações Pós-Operatórias , Resultado do Tratamento
11.
Int J Mol Sci ; 16(1): 1928-48, 2015 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-25603177

RESUMO

Post-translational modifications have been identified to be of great importance in cancers and lysine acetylation, which can attract the multifunctional transcription factor BRD4, has been identified as a potential therapeutic target. In this paper, we identify that BRD4 has an important role in colorectal cancer; and that its inhibition substantially wipes out tumor cells. Treatment with inhibitor MS417 potently affects cancer cells, although such effects were not always outright necrosis or apoptosis. We report that BRD4 inhibition also limits distal metastasis by regulating several key proteins in the progression of epithelial-to-mesenchymal transition (EMT). This effect of BRD4 inhibitor is demonstrated via liver metastasis in animal model as well as migration and invasion experiments in vitro. Together, our results demonstrate a new application of BRD4 inhibitor that may be of clinical use by virtue of its ability to limit metastasis while also being tumorcidal.


Assuntos
Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Dibenzazepinas/farmacologia , Neoplasias Hepáticas/secundário , Metástase Neoplásica/tratamento farmacológico , Proteínas Nucleares/antagonistas & inibidores , Fatores de Transcrição/antagonistas & inibidores , Adulto , Idoso , Animais , Proteínas de Ciclo Celular , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Neoplasias Colorretais/genética , Transição Epitelial-Mesenquimal/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Camundongos Nus , Pessoa de Meia-Idade , Proteínas Nucleares/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Fatores de Transcrição/metabolismo , Adulto Jovem
12.
J Biol Chem ; 288(20): 14297-14309, 2013 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-23569210

RESUMO

A variety of cellular factors participates in the HIV-1 life cycle. Among them is the well characterized cyclin T1 (CYCT1). CycT1 binds to cyclin-dependent kinase 9 (CDK9) and forms the positive transcription elongation factor-b (P-TEFb). P-TEFb is then recruited by HIV-1 TAT to the HIV-1 long terminal repeat (LTR) promoter and subsequently leads to phosphorylation of the C-terminal domain of RNA polymerase II (pol II), enhanced processivity of pol II, and transcription of a full-length HIV-1 RNA. In this study, we report the identification of a new CYCT1 splice variant, designated as CYCT1b, and accordingly we renamed CYCT1 as CYCT1a. CYCT1b was detected in several cell lines, including primary human CD4 T cells, and its expression was subject to cell cycle regulation. Similar to CYCT1a, CYCT1b was primarily localized in the nucleus. CYCT1b expression was found to be inversely correlated with HIV-1 gene expression and replication. This inverse correlation appeared to involve TAT transactivation, CDK9 binding, and subsequent recruitment of P-TEFb to the HIV-1 LTR promoter and pol II C-terminal domain phosphorylation. In agreement with these findings, CYCT1b expression led to direct inhibition of TAT-transactivated transcription of the HIV-1 LTR promoter. Taken together, these results show that the newly identified CYCT1b splice variant inhibits HIV-1 transcription and may provide new clues for the development of anti-HIV strategies.


Assuntos
Ciclina T/genética , Regulação Viral da Expressão Gênica , HIV-1/metabolismo , Transcrição Gênica , Produtos do Gene tat do Vírus da Imunodeficiência Humana/metabolismo , Processamento Alternativo , Sequência de Aminoácidos , Sequência de Bases , Ciclina T/metabolismo , Perfilação da Expressão Gênica , Células HEK293 , Células HeLa , Humanos , Células Jurkat , Dados de Sequência Molecular , Fases de Leitura Aberta , Fosforilação , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , RNA Mensageiro/metabolismo , Ativação Transcricional , Técnicas do Sistema de Duplo-Híbrido
13.
Discov Med ; 36(186): 1477-1485, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39054718

RESUMO

BACKGROUND: Metastatic colorectal cancer (mCRC) is increasingly characterized by myriad genomic alterations beyond the well-known factors such as RAS, BRAF, and microsatellite instability (MSI). Novel genomic changes, including ERBB2 amplifications, mutations, and gene fusions, are now recognized as potential targets for precision therapy. This study aims to explore the genomic landscape of a Chinese cohort with mCRC to identify potentially targetable genetic alterations for personalized treatment strategies. METHODS: A total of 500 mCRC patients in China were enrolled, based on which genomic profiling was performed using capture-based targeted sequencing across a panel of 520 genes on tumor tissues to identify prevalent genomic alterations. The mutations were analyzed by optimized proprietary algorithms. MSI and mismatch repair deficiency status were analyzed using the read-count-distribution approach. Besides, the overall survival (OS) related to these molecular changes was estimated. RESULTS: The cohort's genomic profiling revealed TP53 mutations in 78%, APC in 60%, and KRAS in 47% of the patients. MSI-High status was confirmed in 5.8% of cases via a next-generation sequencing (NGS)-based algorithm. ERBB2/HER2 amplifications were found in 12% (60/500) of patients, with potential therapeutic implications for those without concurrent KRAS mutations. A subset of patients (1.2%; 6/500) showed fusions and DNA damage response (DDR) gene mutations (except TP53) that could be targeted therapeutically. The KRAS (G12C) variant was detected in 14 patients (2.8%), and 61 (12.2%) had a BRAF V600E mutation. Notably, survival analysis showed no significant differences in OS between KRAS mutant loci and NRAS mutations (p = 0.436). However, BRAF V600E mutations were associated with a poorer prognosis than BRAF wild-type and non-V600E mutations (16.3 months vs. 29.5 and 31.1 months, respectively; p < 0.001). CONCLUSIONS: This study validates the feasibility of using NGS to detect prognostic and therapeutically actionable genetic variants in Chinese mCRC patients, contributing to understanding the genomic variation within this population and highlighting the potential for personalized medicine in managing mCRC.


Assuntos
Neoplasias Colorretais , Mutação , Metástase Neoplásica , Humanos , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Adulto , China/epidemiologia , Povo Asiático/genética , Instabilidade de Microssatélites , Genômica/métodos , Sequenciamento de Nucleotídeos em Larga Escala , Idoso de 80 Anos ou mais , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo , Proteínas Proto-Oncogênicas p21(ras)/genética , População do Leste Asiático
14.
Int J Hyg Environ Health ; 256: 114324, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38271819

RESUMO

BACKGROUND: Women with multiple pregnancies are vulnerable to experience postpartum depression (PPD). Emerging evidence indicates an association between poly- and perfluoroalkyl substances (PFAS) exposure and PPD in women delivering singletons. The health risks of PFAS may also be present in women delivering twins. OBJECTIVE: To estimate the impacts of prenatal PFAS exposure on the risk of PPD in women with twin pregnancies. METHODS: Our study included 150 mothers who gave birth to twins and were enrolled in the Wuhan Twin Birth Cohort. The concentrations of maternal plasma PFAS were measured in each trimester and averaged. Eight individual PFAS were included in analyses. We used Edinburgh Postnatal Depression Scale to evaluate maternal depression at early pregnancy and 1 and 6 months after childbirth. The outcome was dichotomized using a cutoff value of ≥10 for main analyses. Associations were examined using multiple informant models and modified Poisson regressions. PFAS mixture effects were estimated using quantile g-computation. RESULTS: Using quantile g-computation models, a quartile increase in the PFAS mixture during the first, second, third, and average pregnancy was significantly associated with a relative risk (RR) of 1.73 (95% CI: 1.42, 2.12), 1.54 (95% CI: 1.27, 1.84), 1.75 (95% CI: 1.49, 2.08), and 1.63 (95% CI: 1.35, 1.97) for PPD at 6 months after childbirth, respectively. The results of the single-PFAS models also indicated significant positive associations between individual PFAS and PPD at both 1 and 6 months. CONCLUSIONS: The first study of women with twin pregnancies suggests that prenatal exposure to PFAS increases PPD risk up to 6 months postpartum. Twin pregnant women should receive long-term follow-up after delivery and extensive social support.


Assuntos
Ácidos Alcanossulfônicos , Depressão Pós-Parto , Poluentes Ambientais , Fluorocarbonos , Efeitos Tardios da Exposição Pré-Natal , Humanos , Gravidez , Feminino , Gravidez de Gêmeos , Depressão Pós-Parto/epidemiologia
15.
Int J Occup Saf Ergon ; 29(1): 181-191, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35037824

RESUMO

Objectives. The putty polishing procedure usually produces a large number of micron-sized particles, which can lead to serious respiratory diseases as well as skin conditions. The diagonal ventilation system is widely used to decrease the particle concentration in different environments. However, it becomes less effective for a large empty factory workshop, such as the polishing workshop for high-speed rail carriages, in which the diagonal ventilation mode usually results in turbulence in the airflow. In this article we report that the situation can be improved by optimizing the number and locations of the air inlets and outlets in the carriage-polishing workshop. Three modified ventilation modes are proposed, whose efficiencies are evaluated by numerical simulations and compared to the diagonal mode. Results. The results show that the mode with two inlets close to the ceiling and two outlets close to the floor yields the best performance. Besides, the optimum airflow rate under this mode is further determined by both simulations and in-situ measurements. The results reported can serve as a reference for the design of the ventilation systems in the polishing workshops of similar sizes.


Assuntos
Poluição do Ar em Ambientes Fechados , Humanos , Ventilação/métodos , Pisos e Cobertura de Pisos , Tamanho da Partícula
16.
Food Funct ; 14(8): 3815-3823, 2023 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-37010155

RESUMO

Objective: Protein powder has attracted attention due to its possible adverse effects. We aimed to investigate the association of protein powder supplementation in early pregnancy with gestational diabetes mellitus (GDM) risk. Methods: We included 6897 participants with singleton pregnancies from a prospective birth cohort. Protein powder supplementation and GDM relationships were examined by unadjusted and multivariable analysis, 1 : 2 propensity score matching, and inverse probability weighting (IPW). A multinomial logistic regression model was used to further explore the effects of protein powder supplementation on the risk of GDM subtypes. Results: Overall, 14.6% of pregnant women (1010) were diagnosed with GDM. In the crude and multivariable analysis before propensity score matching, participants who had received protein powder supplements were more likely to have GDM than women who did not (OR, 1.39 [95% CI: 1.07-1.79]; OR, 1.32 [95% CI: 1.01-1.72]). Protein powder supplementation was significantly associated with a higher GDM risk on IPW analysis (OR, 1.41 [95% CI, 1.08-1.83]), propensity score matching analysis (OR, 1.40 [95% CI, 1.01-1.93]) and multivariable analysis adjusted for propensity score (OR, 1.53 [95% CI, 1.10-2.12]). In the multinomial logistic regression model, protein powder supplementation was only positively associated with the risk of GDM with isolated fasting hyperglycaemia (IFH) in the crude and multivariable models (OR, 1.87 [95% CI: 1.29-2.73]; OR, 1.82 [95% CI: 1.23-2.68]). Conclusions: Protein powder supplementation in early pregnancy is significantly associated with a greater risk of GDM, especially for GDM-IFH. Additional comparative studies are needed to validate these findings.


Assuntos
Diabetes Gestacional , Hiperglicemia , Gravidez , Humanos , Feminino , Diabetes Gestacional/metabolismo , Estudos Prospectivos , Pós , Suplementos Nutricionais/efeitos adversos , Fatores de Risco
17.
Environ Sci Pollut Res Int ; 29(14): 20289-20295, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34734336

RESUMO

As an advanced oxidation process, vacuum ultraviolet/ultraviolet (VUV/UV) has been intensively studied for drinking water treatment, but assessment of its feasibility for wastewater treatment has rarely been conducted. This study investigated the treatment of fluorine-containing pharmaceutical wastewater by VUV/UV process and examined the defluorination and therefore the improvement of biodegradability of the wastewater after the process. The results indicated that the degradation of a model fluorine-containing organic compound (namely, 4-fluorophenol) was mainly achieved via the attack of the fluorine atom linking directly to the aromatic ring by the HO• generated from VUV photolysis of water. As the solution pH increased from 4.0 to 10.0, the COD removal efficiency of the real pharmaceutical wastewater decreased slightly from 18.1 to 15.9%, while the release ratio of F- increased from 50.8 to 75.5%. As the dissolved oxygen increased from 0.15 to 12 mg L-1, the removal efficiency of COD and the release ratio of F- increased from 9.2 to 17.1% and from 48.2 to 75.5%, respectively. The biodegradability index (BOD/COD) increased significantly from 0.24 to 0.47 after the VUV/UV irradiation, which confirmed the feasibility of applying the VUV/UV process for improving biodegradability of the pharmaceutical wastewater.


Assuntos
Preparações Farmacêuticas , Poluentes Químicos da Água , Purificação da Água , Flúor , Oxirredução , Raios Ultravioleta , Vácuo , Águas Residuárias/química , Poluentes Químicos da Água/análise
18.
Ultrason Sonochem ; 82: 105891, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34954630

RESUMO

Pesticide residue in vegetables has been considered as a serious food safety problem across the whole world. This study investigates a novel advanced oxidation process (AOP), namely the coupled free chlorine/ultrasound (FC/US) process for the removal of three typical pesticides from lettuce. The removal efficiencies of dimethoate (DMT), trichlorfon (TCF) and carbofuran (CBF) from lettuce reached 86.7%, 79.8% and 71.3%, respectively by the FC/US process. There existed a synergistic effect in the coupled FC/US process for pesticide removal and the synergistic factors reached 22.3%, 19.0% and 36.4% for DMT, TCF and CBF, respectively. Based on the analysis of mass balance of pesticides, the synergistic effect was probably attributed to the efficient oxidation of pesticides both in vegetables and in water by the generated free radicals and FC. The surface area and surface structure of vegetables strongly affected the removal of pesticides by FC/US. The removal efficiency of DMT increased from 80.9% to 88.1% as solution pH increased from 5.0 to 8.0, and then decreased to 84.1% when solution pH further increased to 9.0. When the ultrasonic frequency changed from 20 to 40 kHz, a remarkable improvement in pesticide removal by FC/US was observed. As the FC concentration increased from 0 to 15 mg L-l, the removal efficiencies of pesticides increased firstly, and then became stagnant when the FC concentration further increased to 25 mg L-l. The pesticide degradation pathways based on the identified intermediates were proposed. The total chlorophyll content was reduced by less than 5% after the FC/US process, indicating a negligible damage to the quality of vegetables. It suggests that the FC/US process is a promising AOP for pesticides removal from vegetables.


Assuntos
Verduras , Cloro , Dimetoato/análise , Resíduos de Praguicidas
19.
Sci Total Environ ; 838(Pt 2): 156047, 2022 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-35598668

RESUMO

Dimethyl phthalate (DMP), a low-molecular-weight phthalate ester, exists in ectoparasiticides, plastics, and insect repellants, and has been linked to neurotoxic, reproductive, and endocrine disruptive responses. However, its blood immunotoxic effects and mechanism are still poorly understood. In this study, rats were exposed to gradient concentrations of DMP through intragastric administration to assess the blood immunotoxic effects in the combined assay of biomarker, cytometry, and transcriptomics. DMP treatment altered the redox status of rats, thus causing oxidative damage. Significantly decreased blood cell counts and disordered antibody and cytokine secretion were observed in treated rats, suggesting the suppressed immune defense and destructed inflammatory regulation. Flow cytometry showed that in lymphocytes, especially CD3+CD4+ T cells, the occurrence of apoptosis/necrosis was positively related to DMP exposure level. Transcriptomics revealed an oxidative stress-related mechanism. The overexpression of the Bcl-2 family genes and the activation of the Fas/FasL pathway triggered downstream caspase cascade and caused reactive oxygen species signaling-mediated apoptosis/necrosis. To the best of our knowledge, it was the first report that the exposure to low-molecular-weight phthalate esters potentially triggered blood immunotoxicity. The result and underlying mechanisms can provide an essential basis for understanding phthalate ester toxicity and usage regulation.


Assuntos
Ácidos Ftálicos , Animais , Apoptose , Ésteres , Necrose , Estresse Oxidativo , Ácidos Ftálicos/toxicidade , Ratos
20.
Curr Med Sci ; 42(1): 210-216, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34985609

RESUMO

OBJECTIVE: Childhood obesity is a major health concern worldwide. Previous studies have explored the relationship between obesity and gut microbiota. However, the results from such studies remain contradictory. METHODS: In the present nested case-control study, based on a twin birth cohort study, the relationship between gut microbiota diversity and overweight/obesity in 1- and 6-month-old infants was explored. Twins were enrolled when one child had normal weight and the other child was overweight/obese at six months old. For both infants, stool samples were collected at 1 and 6 months of age. Finally, 12 twins were enrolled in the study. The gut microbiota was identified by 16S rRNA gene sequencing in the V3-V4 area. Six of the twins were monozygotic. RESULTS: The results revealed that the microbiota communities of monozygotic twins were similar to those of dizygotic twins. The relative abundance (RA) of microbiota of 1-month-old twins was significantly higher than that of 6-month-old twins. However, the microbiota diversity of 1-month-old twins was significantly lower than that of 6-month-old twins. In addition, 6-month-old twins had significantly higher RA levels of Bifidobacterium and Lachnospiracea incertae sedis than 1-month-old twins. The 6-month-old group had significantly lower RA levels of Veillonella, Klebsiella, Akkermansia, Streptococcus, or Staphylococcus than the 1-month-old group. At six months, the RA level of Clostridium sensu stricto was higher in the overweight/obesity group than the normal-weight group. CONCLUSION: These findings imply that changes in gut microbiota diversity during infancy may contribute to the development of obesity in early infancy.


Assuntos
Microbioma Gastrointestinal , Sobrepeso/microbiologia , Obesidade Infantil/microbiologia , Coorte de Nascimento , Estudos de Casos e Controles , Feminino , Humanos , Lactente , Masculino , RNA Ribossômico 16S
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