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1.
BMC Pregnancy Childbirth ; 23(1): 791, 2023 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-37964244

RESUMO

BACKGROUND: Although the traditional contingent screening strategy is effective, there are still undetected low-risk trisomy 21. This study aims to define appropriate cut-off values of serum biochemical markers at low-risk and develop a strategy for sequential prenatal testing associated with first-trimester screening to increase the detection rate of trisomy 21. METHODS: This was a 9-year retrospective analysis of singleton pregnant women who underwent serum biochemical screening or combined first-trimester screening (CFTS) in the first trimester. For the low-risk group, the cut-off values of the serum biochemical markers were adjusted to determine the appropriate detection efficiency. Gravidas with abnormal serum biochemical markers at low-risk were advised to undergo further non-invasive prenatal screening (NIPS), whereas others continued with routine prenatal care. RESULTS: When cut-off values of free beta subunit of human chorionic gonadotropin (free ß-hCG) multiples of the median (MoM) or pregnancy-associated plasma protein A (PAPP-A) MoM were defined with ≥ 2.75 or ≤ 0.5, 7.72% (2,194/28,405) in the serum biochemical screening group and 12.36% (4,005/32,403) in CFTS group could be detected as abnormal results for further NIPS. Finally, 55.56% (5/9) and 85.71% (6/7) of trisomy 21 cases with false-negative results were detected, and the overall detection rate for trisomy 21 was improved by 10.64% (5/47) and 12.77% (6/47), respectively. CONCLUSIONS: The new contingent screening strategy can increase the detection rate of trisomy 21 compared with the traditional contingent screening strategy.


Assuntos
Síndrome de Down , Gravidez , Humanos , Feminino , Síndrome de Down/diagnóstico , Primeiro Trimestre da Gravidez , Gonadotropina Coriônica Humana Subunidade beta , Diagnóstico Pré-Natal/métodos , Estudos Retrospectivos , Medição da Translucência Nucal , Biomarcadores , Proteína Plasmática A Associada à Gravidez/análise , Trissomia
2.
J Pediatr ; 233: 150-155.e4, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33631166

RESUMO

OBJECTIVES: To investigate the efficacy and safety of sirolimus in the treatment of cardiac rhabdomyomas associated with tuberous sclerosis complex and the specific benefits in different subgroups. STUDY DESIGN: The study was a prospective cohort and self-controlled case series study. Based on the prevalence of cardiac rhabdomyoma at different ages, we estimated the natural tumor disappearance rate. The subgroup analysis was done by Cox regression. Self-controlled case series method was used to assess the magnitude and duration of the drug effect. Adverse events were described. RESULTS: A total of 217 patients were included in the cohort study. Tumor disappearance rate was higher in younger age groups (hazard ratio = 0.99, P = .027) and female patients (hazard ratio = 2.08, P = .015). The age-adjusted incidence ratio showed that the disappearance of rhabdomyomas between 3 and 6 months was more related to sirolimus. Adverse events were observed 60 times in 42 of 217 children, mainly stomatitis. CONCLUSIONS: Sirolimus can increase the disappearance rate of cardiac rhabdomyoma in the tuberous sclerosis complex population. Efficacy varies by sex and age: female and younger patients have higher tumor disappearance rate. Sirolimus is well-tolerated.


Assuntos
Antibióticos Antineoplásicos/uso terapêutico , Neoplasias Cardíacas/tratamento farmacológico , Rabdomioma/tratamento farmacológico , Sirolimo/uso terapêutico , Esclerose Tuberosa/complicações , Fatores Etários , Pré-Escolar , Estudos de Coortes , Feminino , Neoplasias Cardíacas/etiologia , Humanos , Lactente , Masculino , Rabdomioma/etiologia , Fatores Sexuais
3.
BMC Cardiovasc Disord ; 21(1): 215, 2021 04 27.
Artigo em Inglês | MEDLINE | ID: mdl-33906602

RESUMO

BACKGROUND: Myocardial ischemia-reperfusion injury (MIRI) is the main pathological manifestation of cardiovascular diseases such as myocardial infarction. The potential therapeutic effects of bone marrow-derived mesenchymal stem cells (BM-MSCs) and the participation of regulatory T cells (Tregs) in MIRI remains to be defined. METHODS: We used the experimental acute MIRI that was induced in mice by left ascending coronary ischemia, which were subsequently randomized to receive immunoglobulin G (IgG) or anti-CD25 antibody PC61 with or without intravenously injected BM-MSCs. The splenectomized mice underwent prior to experimental MIRI followed by intravenous administration of BM-MSCs. At 72 h post-MIRI, the hearts and spleens were harvested and subjected to cytometric and histologic analyses. RESULTS: CD25+Foxp3+ regulatory T cells were significantly elevated after MIRI in the hearts and spleens of mice receiving IgG + BM-MSCs and PC61 + BM-MSCs compared to the respective control mice (all p < 0.01). This was accompanied by upregulation of interleukin 10 and transforming growth factor ß1 and downregulation of creatinine kinase and lactate dehydrogenase in the serum. The post-MIRI mice receiving BM-MSCs showed attenuated inflammation and cellular apoptosis in the heart. Meanwhile, splenectomy compromised all therapeutic effects of BM-MSCs. CONCLUSION: Administration of BM-MSCs effectively alleviates MIRI in mice through inducing Treg activation, particularly in the spleen.


Assuntos
Transplante de Células-Tronco Mesenquimais , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Miocárdio/imunologia , Baço/imunologia , Linfócitos T Reguladores/imunologia , Animais , Anticorpos Monoclonais/farmacologia , Apoptose , Creatina Quinase/sangue , Modelos Animais de Doenças , Imunoglobulina G/farmacologia , Interleucina-10/sangue , L-Lactato Desidrogenase/sangue , Masculino , Camundongos Endogâmicos C57BL , Traumatismo por Reperfusão Miocárdica/imunologia , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/patologia , Miocárdio/metabolismo , Miocárdio/patologia , Necrose , Fenótipo , Baço/efeitos dos fármacos , Baço/metabolismo , Esplenectomia , Linfócitos T Reguladores/efeitos dos fármacos , Linfócitos T Reguladores/metabolismo , Fator de Crescimento Transformador beta1/sangue
4.
Dysphagia ; 36(3): 339-350, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-32458145

RESUMO

OBJECTIVE: To determine the prevalence of dysphagia among an older population and patients with stroke, head and neck cancers (HNCs) or neurodegenerative diseases (NDDs) in China, to identify the factors associated with this condition, and to explore the relationship between dysphagia and nutritional status. METHODS: This study included participants 65 years and older living in the community or in nursing homes and patients who had sustained a stroke, HNC, or NDD also recruited in hospitals from 14 provinces of China. The presence of dysphagia was determined by use of a questionnaire, water swallowing test, and/or a videofluoroscopic swallowing study. Logistic regression analysis was used to assess the possible associated risk factors. Body mass index was assessed as an indicator of malnutrition. RESULTS: A total of 5943 persons met the inclusion criteria and 2341 (39.4%) were identified with dysphagia, including the following: 51.14% of patients with stroke, 34.4% in HNCs, 48.3% in NDDs, and 19.2% of otherwise healthy older adults. The elderly with comorbidity (OR = 2.90, p < 0.01) and stroke patients (OR = 2.27, p < 0.01) were significantly more likely to exhibit signs of dysphagia. Dysphagic participants were at significantly greater risk of malnutrition (OR = 1.91, p < 0.01) compared to those without dysphagia. CONCLUSION: Dysphagia is prevalent in China among older individuals and people who have suffered a stroke, HNCs, or NDDs. The prevalence of dysphagia increases steadily with increasing age and presence of comorbid disease. People with dysphagia are more likely to suffer from malnutrition.


Assuntos
Transtornos de Deglutição , Idoso , China/epidemiologia , Estudos Transversais , Transtornos de Deglutição/epidemiologia , Humanos , Prevalência , Inquéritos e Questionários
5.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 51(1): 49-53, 2020 Jan.
Artigo em Zh | MEDLINE | ID: mdl-31950789

RESUMO

OBJECTIVE: To compare the effect of different first-trimester screening programmes for Down syndrome in Sichuan Province. METHODS: We retrospectively collected the data of singleton pregnancies that were screened by serum biochemistry markers combined with nuchal translucency screening tests in the first trimester in Prenatal Diagnosis Center of West China Second University Hospital of Sichuan University from January 2011 to December 2017. The fetal chromosome results were obtained by amniocentesis or by telephone follow-up. The screening effect of maternal age, nuchal translucency thickness, maternal serum biochemistry markers and combined screening in the first trimester were analyzed. RESULTS: Among the 21 723 singleton pregnancies, 33 cases were diagnosed as Down syndrome, and 19 cases were diagnosed as trisomy 18 sex chromosome abnormalities were found in 4 cases, and other chromosome abnormalities were found in 8 cases. For the combined screening, the detection rate of Down syndrome was 72.73%, and the false positive rate was 2.49%; the detection rate of trisomy 18 syndrome was 73.68% with the false positive rate of 0.39%. With a 5% false positive rate, maternal age, nuchal translucency thickness, serum biochemistry markers and combined screening would respectively detect 15.15%, 57.58%, 60.61% and 87.88% of Down syndrome fetuses. CONCLUSION: Compared with the other three screening programmes, the combined screening can effectively screen fetuses with Down syndrome and other chromosomal abnormalities.


Assuntos
Síndrome de Down , Diagnóstico Pré-Natal , Ultrassonografia Pré-Natal , Amniocentese , Biomarcadores/análise , Biomarcadores/sangue , China , Aberrações Cromossômicas , Síndrome de Down/sangue , Síndrome de Down/diagnóstico por imagem , Feminino , Humanos , Gravidez , Primeiro Trimestre da Gravidez , Estudos Retrospectivos
6.
Arch Psychiatr Nurs ; 33(6): 160-166, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31753223

RESUMO

PURPOSE: To evaluate the associations between BADL/IADL disability and depressive symptoms from the perspective of gender among older adults in China. METHODS: This cross-sectional study used the data from the second wave of the China Health and Retirement Longitudinal Study (CHARLS). The sample included 3463 older adults aged 60 years and older across China. Multivariable logistic regression models were conducted. RESULTS: Among 3463 older adults, 1240 (35.8%) were classified as depressed, the prevalence of BADL and IADL disabilities were 756 (21.8%) and 1194 (34.5%), respectively. After controlling for covariates, BADL/IADL disability was significantly associated with an increased risk of depression prevalence both in men and women among older adults. Compared with IADL independent, IADL disability was about two times more likely to develop depressive symptoms in men (OR = 2.165, 95% CI = 1.661-2.822), which was much higher than that in women (OR = 1.748, 95% CI = 1.415-2.160). In contrast, the odds of being depressed for women with BADL disability (OR = 1.824, 95% CI = 1.447-2.299) were much higher than the odds for men with BADL disability (OR = 1.791, 95% CI = 1.348-2.379). CONCLUSIONS: Older adults with BADL/IADL disability were more likely to have depressive symptoms both for men and women. However, the associations between depressive symptoms and BADL/IADL disability were different in gender. Our results suggest that differential institutional care service and appropriate strategies for improvement in mental health are required.


Assuntos
Atividades Cotidianas , Depressão/epidemiologia , Idoso , Idoso de 80 Anos ou mais , China/epidemiologia , Estudos Transversais , Depressão/etiologia , Pessoas com Deficiência/psicologia , Pessoas com Deficiência/estatística & dados numéricos , Feminino , Humanos , Modelos Logísticos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Escalas de Graduação Psiquiátrica , Fatores de Risco , Fatores Sexuais , Inquéritos e Questionários
7.
BMC Neurol ; 17(1): 164, 2017 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-28841844

RESUMO

BACKGROUND: Acute autonomic neuropathy (AAN) is rare disorder with anecdotal report, especially for childhood onset patients. Misdiagnosis or delays in treatment can always be found in clinical practice. We conducted this study to give a description of the manifestations and treatment of AAN in children and therefore help clinicians to make the accurate diagnosis early so that the prognosis of the patients can be improved. METHODS: A systematic record from 3 clinical centers was used to identify 11 subject, 3 males and 8 females, with clinical diagnosed AAN. RESULT: The age ranged from 2 years and 4 months to 14 years and 6 months (mean, 9 ± 3.6 years old) and the course from onset to diagnosis ranged from 7 days to 8 months. All children shared prominent initial symptoms, 7 with frequent vomiting and 4 with motor dysfunctions. The condition of 9 patients improved after treatment of IVIg and intravenous glucocorticoid. CONCLUSION: The clinical manifestations of AAN are diverse, generalized, and non-specific. Gastrointestinal disorders were the most common initial symptoms. Symptoms of gastrointestinal system and abnormal secretion of glands were severe and more common than other symptoms. The mechanism of AAN remains unknown. Although IVIg and intravenous glucocorticoid can be used in clinical practice, there is still no treatment recommendation and further study is needed.


Assuntos
Doenças do Sistema Nervoso Autônomo , Gastroenteropatias , Criança , Pré-Escolar , Feminino , Humanos , Masculino
8.
Exp Lung Res ; 43(8): 283-292, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-29140133

RESUMO

AIM: Pulmonary arterial hypertension (PAH), a deadly disorder is associated with excessive growth of human pulmonary artery endothelial (HPAECs) and smooth muscle (HPASMCs) cells. Current therapies primarily aim at promoting vasodilation, which only ameliorates clinical symptoms without a cure. 2-(1'H-indole-3'-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE) is an endogenous aryl hydrocarbon receptor (AhR) ligand, and mediates many cellular function including cell growth. However, the roles of ITE in human lung endothelial cells remain elusive. Herein, we tested a hypothesis that ITE inhibits growth of human pulmonary artery endothelial cells via AhR. MATERIALS AND METHODS: Immunohistochemistry was performed to localize AhR expression in human lung tissues. The crystal violet method and MTT assay were used to determine ITE's effects on growth of HPAECs. The AhR activation in HPAECs was confirmed using Western blotting and RT-qPCR. The role of AhR in ITE-affected proliferation of HPAECs was assessed using siRNA knockdown method followed by the crystal violet method. RESULTS: Immunohistochemistry revealed that AhR was present in human lung tissues, primarily in endothelial and smooth muscle cells of pulmonary veins and arteries, as well as in bronchial and alveolar sac epithelia. We also found that ITE dose- and time-dependently inhibited proliferation of HPAECs with a maximum inhibition of 83% at 20 µM after 6 days of treatment. ITE rapidly decreased AhR protein levels, while it increased mRNA levels of cytochrome P450 (CYP), family 1, member A1 (CYP1A1) and B1 (CYP1B1), indicating activation of the AhR/CYP1A1 and AhR/CYP1B1 pathways in HPAECs. The AhR siRNA significantly suppressed AhR protein expression, whereas it did not significantly alter ITE-inhibited growth of HPAECs. CONCLUSIONS: ITE suppresses growth of HPAECs independent of AhR, suggesting that ITE may play an important role in preventing excessive growth of lung endothelial cells.


Assuntos
Proliferação de Células/efeitos dos fármacos , Células Endoteliais/efeitos dos fármacos , Indóis/farmacologia , Artéria Pulmonar/citologia , Tiazóis/farmacologia , Células Cultivadas , Citocromo P-450 CYP1A1/genética , Citocromo P-450 CYP1A1/metabolismo , Citocromo P-450 CYP1B1/genética , Citocromo P-450 CYP1B1/metabolismo , Células Endoteliais/citologia , Humanos , Receptores de Hidrocarboneto Arílico/análise , Receptores de Hidrocarboneto Arílico/efeitos dos fármacos , Receptores de Hidrocarboneto Arílico/metabolismo , Fatores de Tempo
9.
Epilepsy Behav ; 77: 13-18, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-29073472

RESUMO

Mental retardation (MR) is one of the most common cognitive comorbidities in children with tuberous sclerosis, and there are enormous studies about its risk factors. The genetic difference and the severity of epilepsy are the two main factors, but their weight in the occurrence of MR is still unclear. Two hundred twenty-three patients with tuberous sclerosis who received intelligence assessment, genetic mutation analysis, and the epilepsy severity assessment were included in our study. Genotype-neurocognitive phenotype correlations and epilepsy-neurocognitive phenotype correlations were analyzed by binary logistic regression analysis. No statistical significant result was found on genotype-neurocognitive phenotype correlations, which contrasted the previous report. The prevalence of MR was 50.0% for the patients with tuberous sclerosis complex-1 (TSC1) mutation, 54.5% for TSC2 (p=0.561), 54.7% for patients with protein-truncating (PT) and 50.0% for patients with nontruncating (NT) (p=0.791), and 54.3% for patients with family history and 53.7% for patients without family history (p=0.748). Statistical significant results were found on epilepsy-neurocognitive phenotype correlations, both on E-chess score (p=0.01) and the occurrence of infantile spasms (p=0.014), which was consistent to the previous study. For children with tuberous sclerosis, instead of genetic factors, epilepsy may play the main role for the presence of mental retardation. Patients with mental retardation tend to have earlier seizure attack, take more AEDs, have more seizure types, and have higher seizure frequency. Among the four cognitive functions in Denver II, social ability and language ability are more vulnerable to be influenced than fine and gross motor ability.


Assuntos
Epilepsia/complicações , Deficiência Intelectual/etiologia , Inteligência/fisiologia , Convulsões/complicações , Esclerose Tuberosa/complicações , Pré-Escolar , Cognição/fisiologia , Análise Mutacional de DNA , Epilepsia/genética , Epilepsia/psicologia , Feminino , Estudos de Associação Genética , Humanos , Deficiência Intelectual/genética , Deficiência Intelectual/psicologia , Masculino , Mutação , Testes Neuropsicológicos , Fenótipo , Estudos Retrospectivos , Fatores de Risco , Convulsões/genética , Convulsões/psicologia , Habilidades Sociais , Esclerose Tuberosa/genética , Esclerose Tuberosa/psicologia
10.
J Phys Ther Sci ; 29(2): 209-211, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28265140

RESUMO

[Purpose] This study examined the measurement of the thickness of the transverse abdominal muscle in different tasks. [Subjects and Methods] The subjects were eleven healthy adult females. Thicknesses of transverse abdominal muscle were measured in seven tasks in the supine position. The tasks were: 1) Resting state, 2) Maximal contraction of transverse abdominal muscle, 3) Maximal contraction of levator ani muscle, 4) Maximal simultaneous contraction of both transverse abdominal muscle and levator ani muscle, 5) Maximal simultaneous contraction of both transverse abdominal muscle and levator ani muscle with front side resistance added to both knee, 6) Maximal simultaneous contraction of both transverse abdominal muscle and levator ani muscle with diagonal resistance added to both knees, and 7) Maximal simultaneous contraction of both transverse abdominal muscle and levator ani muscle with lateral resistance added to both knees. [Results] The thicknesses of transverse abdominal muscle during maximal simultaneous contraction and maximal simultaneous contraction with resistance were greater than during the resting state. [Conclusion] The muscle output during simultaneous contraction and resistance movement were larger than that of each individual muscle.

11.
Am J Ther ; 23(2): e624-7, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26938751

RESUMO

Diurnal frequent urination is a common condition in elementary school children who are especially at risk for associated somatic and behavioral problems. Levetiracetam (LEV) is a broad-spectrum antiepileptic drug that has been used in both partial and generalized seizures and less commonly adverse effects including psychiatric and behavioral problems. Diurnal frequent urination is not a well-known adverse effect of LEV. Here, we reported 2 pediatric cases with epilepsy that developed diurnal frequent urination after LEV administration. Case 1 was a 6-year-old male patient who presented urinary frequency and urgency in the daytime since the third day after LEV was given as adjunctive therapy. Symptoms increased accompanied by the raised dosage of LEV. Laboratory tests and auxiliary examinations did not found evidence of organic disease. Diurnal frequent urination due to LEV was suspected, and then the drug was discontinued. As expected, his frequency of urination returned to normal levels. Another 13-year-old female patient got similar clinical manifestations after oral LEV monotherapy and the symptoms became aggravated while in stress state. Since the most common causes of frequent micturition had been ruled out, the patient was considered to be diagnosed with LEV-associated psychogenic frequent urination. The dosage of LEV was reduced to one-third, and the frequency of urination was reduced by 60%. Both patients got the Naranjo score of 6, which indicated that LEV was a "probable" cause of diurnal frequent urination. Although a definite causal link between LEV and diurnal urinary frequency in the 2 cases remains to be established, we argue that diurnal frequent urination associated with LEV deserves clinician's attention.


Assuntos
Anticonvulsivantes/efeitos adversos , Ritmo Circadiano/fisiologia , Piracetam/análogos & derivados , Micção/efeitos dos fármacos , Adolescente , Criança , Feminino , Humanos , Levetiracetam , Masculino , Piracetam/efeitos adversos
12.
Int J Mol Sci ; 17(5)2016 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-27136543

RESUMO

Immune checkpoint inhibitors, which unleash a patient's own T cells to kill tumors, are revolutionizing cancer treatment. Several independent studies suggest that higher non-synonymous mutational burden assessed by whole exome sequencing (WES) in tumors is associated with improved objective response, durable clinical benefit, and progression-free survival in immune checkpoint inhibitors treatment. Next-generation sequencing (NGS) is a promising technology being used in the clinic to direct patient treatment. Cancer genome WES poses a unique challenge due to tumor heterogeneity and sequencing artifacts introduced by formalin-fixed, paraffin-embedded (FFPE) tissue. In order to evaluate the data interoperability of WES data from different sources to survey tumor mutational landscape, we compared WES data of several tumor/normal matched samples from five commercial vendors. A large data discrepancy was observed from vendors' self-reported data. Independent data analysis from vendors' raw NGS data shows that whole exome sequencing data from qualified vendors can be combined and analyzed uniformly to derive comparable quantitative estimates of tumor mutational burden.


Assuntos
Sequenciamento de Nucleotídeos em Larga Escala , Neoplasias/genética , Linhagem Celular Tumoral , Intervalo Livre de Doença , Humanos , Laboratórios , Mutação , Neoplasias/mortalidade , Neoplasias/patologia , Inclusão em Parafina , Análise de Sequência de DNA
13.
Int J Mol Sci ; 17(9)2016 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-27657050

RESUMO

In cancer drug discovery, it is important to investigate the genetic determinants of response or resistance to cancer therapy as well as factors that contribute to adverse events in the course of clinical trials. Despite the emergence of new technologies and the ability to measure more diverse analytes (e.g., circulating tumor cell (CTC), circulating tumor DNA (ctDNA), etc.), tumor tissue is still the most common and reliable source for biomarker investigation. Because of its worldwide use and ability to preserve samples for many decades at ambient temperature, formalin-fixed, paraffin-embedded tumor tissue (FFPE) is likely to be the preferred choice for tissue preservation in clinical practice for the foreseeable future. Multiple analyses are routinely performed on the same FFPE samples (such as Immunohistochemistry (IHC), in situ hybridization, RNAseq, DNAseq, TILseq, Methyl-Seq, etc.). Thus, specimen prioritization and optimization of the isolation of analytes is critical to ensure successful completion of each assay. FFPE is notorious for producing suboptimal DNA quality and low DNA yield. However, commercial vendors tend to request higher DNA sample mass than what is actually required for downstream assays, which restricts the breadth of biomarker work that can be performed. We evaluated multiple genomics service laboratories to assess the current state of NGS pre-analytical processing of FFPE. Significant differences in pre-analytical capabilities were observed. Key aspects are highlighted and recommendations are made to improve the current practice in translational research.

14.
Mol Genet Genomics ; 290(5): 1659-71, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25773316

RESUMO

Brown adipose tissue (BAT) functions to dissipate energy in response to cold exposure or overfeeding. Counteracting obesity has been extensively considered as a promising target. Long noncoding RNAs (lncRNAs) are an important class of pervasive genes involved in a variety of biological functions. However, the potential biological functions of lncRNAs during mouse brown fat cell differentiation have not been fully understood. Here, we performed lncRNA and mRNA expression profile analysis using microarray technology and identified 1064 lncRNAs with differential expression (fold change| ≥4, p ≤ 0.01) on day 0 and day 8 during differentiation. Furthermore, candidate lncRNAs were characterized by comprehensive examination of their genomic context, gene ontology (GO) enrichment of their associated protein-coding genes and pathway analysis. We identified three lncRNAs (Gm15051, Tmem189 and Cebpd) associated with their flanking coding genes (Hoxa1, C/EBPß and C/EBPδ), which participated in adipose commitment. Collectively, our findings indicated lncRNAs are involved in mouse BAT development and provide potential targets for obesity therapy.


Assuntos
Adipócitos/citologia , Tecido Adiposo Marrom/citologia , Diferenciação Celular/genética , RNA Longo não Codificante/fisiologia , Transcriptoma , Animais , Perfilação da Expressão Gênica , Camundongos , Camundongos Endogâmicos C57BL , RNA Longo não Codificante/genética , Reação em Cadeia da Polimerase em Tempo Real , Fatores de Transcrição/genética
15.
Mol Biol Rep ; 42(5): 927-35, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25421647

RESUMO

MicroRNAs (miRNAs) are small non-coding RNAs involved in the regulation of gene expression. MiR-1908 is a recently identified miRNA that is highly expressed in human adipocytes. However, it is not known what role of miR-1908 is involved in the regulation of human adipocytes. In this study, we demonstrate that the level of miR-1908 increases during the adipogenesis of human multipotent adipose-derived stem (hMADS) cells and human preadipocytes-visceral. Overexpression of miR-1908 in hMADS cells inhibited adipogenic differentiation and increased cell proliferation, suggesting that miR-1908 is involved in the regulation of adipocyte cell differentiation and metabolism, and, thus, may have an effect on human obesity.


Assuntos
Adipócitos/fisiologia , Adipogenia/fisiologia , MicroRNAs/fisiologia , Adipogenia/genética , Diferenciação Celular/genética , Proliferação de Células/genética , Regulação da Expressão Gênica , Humanos , MicroRNAs/genética
16.
Orphanet J Rare Dis ; 19(1): 299, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-39148107

RESUMO

BACKGROUND: Sirolimus is increasingly utilized in treating diseases associated with mTOR pathway overactivation. Despite its potential, the lack of evidence regarding its long-term safety across all age groups, particularly in pediatric patients, has limited its further application. This study aims to assess the long-term safety of sirolimus, with a specific focus on its impact on growth patterns in pediatric patients. METHODS: This pooled analysis inlcudes two prospective cohort studies spanning 10 years, including 1,738 participants (aged 5 days to 69 years) diagnosed with tuberous sclerosis and/or lymphangioleiomyomatosis. All participants were mTOR inhibitor-naive and received 1 mg/m²/day of sirolimus, with dose adjustments during a two-week titration period to maintain trough blood concentrations between 5 and 10 ng/ml (maximum dose 2 mg). Indicators of physical growth, hematopoietic, liver, renal function, and blood lipid levels were all primary outcomes and were analyzed. The adverse events and related management were also recorded. RESULTS: Sirolimus administration did not lead to deviations from normal growth ranges, but higher doses exhibited a positive association with Z-scores exceeding 2 SD in height, weight, and BMI. Transient elevations in red blood cell and white blood cell counts, along with hyperlipidemia, were primarily observed within the first year of treatment. Other measured parameters remained largely unchanged, displaying only weak correlations with drug use. Stomatitis is the most common adverse event (920/1738, 52.9%). In adult females, menstrual disorders were observed in 48.5% (112/217). CONCLUSIONS: Sirolimus's long-term administration is not associated with adverse effects on children's physical growth pattern, nor significant alterations in hematopoietic, liver, renal function, or lipid levels. A potential dose-dependent influence on growth merits further exploration. TRIAL REGISTRATION: Pediatric patients: Chinese clinical trial registry, No. ChiCTR-OOB-15,006,535. Adult patients: ClinicalTrials, No. NCT03193892.


Assuntos
Sirolimo , Humanos , Sirolimo/efeitos adversos , Sirolimo/uso terapêutico , Criança , Feminino , Adolescente , Pré-Escolar , Adulto , Masculino , Lactente , Adulto Jovem , Pessoa de Meia-Idade , Recém-Nascido , Idoso , Esclerose Tuberosa/tratamento farmacológico , Linfangioleiomiomatose/tratamento farmacológico , Estudos Prospectivos
17.
Future Oncol ; 9(6): 909-13, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23718311

RESUMO

Pancreatic neuroendocrine tumors (PNETs) are rare, accounting for approximately 2% of primary malignant tumors of the pancreas. Compared with common pancreatic ductal adenocarcinomas, they grow more slowly, are less invasive and have a better prognosis. At present, surgery is the preferred method of treatment of PNETs, and offers the only chance of a cure. However, owing to the occult onset of PNETs, once diagnosed they are often inoperable when the diagnosis is established, and the optimal treatment of patients with inoperable liver metastases remains uncertain. In recent years, targeted drug therapies have emerged and have proved effective in prolonging progression-free survival in patients with advanced well-differentiated PNETs, but hardly any progress has been made in the treatment of poorly differentiated PNETs. In the patient described in this report, who had a poorly differentiated PNET with multiple hepatic metastases and had refused cytotoxic chemotherapy, oral sunitinib malate treatment for 22 months with regular follow-ups proved tolerable and effective in significantly reducing the size of the intrahepatic masses.


Assuntos
Indóis/administração & dosagem , Tumores Neuroendócrinos/tratamento farmacológico , Neoplasias Pancreáticas/tratamento farmacológico , Pirróis/administração & dosagem , Intervalo Livre de Doença , Feminino , Humanos , Indóis/efeitos adversos , Pessoa de Meia-Idade , Tumores Neuroendócrinos/patologia , Neoplasias Pancreáticas/patologia , Prognóstico , Pirróis/efeitos adversos , Sunitinibe
18.
Clin Nephrol ; 79(1): 50-6, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22948117

RESUMO

AIM: Chronic kidney disease (CKD) is increasingly recognized as a predictor of end-stage renal and cardiovascular disease. There is no data on CKD prevalence in numerous minority communities of China such as the Guangxi Jing community. We determined CKD prevalence and related risk factors in Jing adults. METHODS: A stratified cluster random sampling method was used in this study comprising 757 Jing adults. Questionnaires, physical examinations and laboratory tests including measurements of urinary albumin and hematuria, were performed. Estimated glomerular filtration rate (eGFR) was calculated using the improved Chinese population MDRD formula. CKD-related risk factors were also examined. RESULTS: After standardization for age and gender, the prevalence of albuminuria, haematuria and eGFR < 60 ml/min per 1.73 m2 was 12.5%, 3.8% and 0.4%, respectively Overall CKD prevalence was 15.3%, while the awareness rate was only 11.6%. Females had a significantly higher (p < 0.05) prevalence of albuminuria, hematuria and eGFR < 60 ml/min compared to males. CKD prevalence tended to increase significantly (< 0.05) with increase in age. Using the standardized age and gender ratios, the prevalence of hypertension, diabetes, hyperlipidemia and hyperuricemia was 14.8%, 5.2%, 38% and 16.2%, respectively, with awareness of 41.0%, 41.2%, 6.6% and 0.9%. Prevalence of overweight or obesity status and metabolic syndrome was 12.1% and 3.0%. Females showed a significantly higher prevalence of hyperuricemia and obesity or overweight status. CKD prevalence was also significantly higher in people with risk diseases. Regression analysis showed that age, gender, hypertension, high cholesterol and diabetes were CKD-related risk factors, while culture (higher education level) was a protective factor. CONCLUSION: Jing adults showed a high CKD prevalence of 15.3%, with a low awareness rate of 11.6%. Older subjects and females were more susceptible with a high prevalence of hypertension, diabetes, hyperlipidemia, metabolic syndrome etc. being associated closely with CKD.


Assuntos
Hiperuricemia/complicações , Síndrome Metabólica/complicações , Obesidade/complicações , Insuficiência Renal Crônica/epidemiologia , População Rural , Adolescente , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , China/epidemiologia , Feminino , Taxa de Filtração Glomerular , Humanos , Hiperuricemia/epidemiologia , Masculino , Síndrome Metabólica/epidemiologia , Pessoa de Meia-Idade , Obesidade/epidemiologia , Prevalência , Prognóstico , Insuficiência Renal Crônica/etiologia , Insuficiência Renal Crônica/fisiopatologia , Fatores de Risco , Distribuição por Sexo , Adulto Jovem
19.
Infect Drug Resist ; 16: 5405-5411, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37614681

RESUMO

Voriconazole is the therapy of choice for aspergillosis. However, hepatotoxicity is the most common reason for the discontinuation of voriconazole. In contrast, posaconazole is well tolerated, with a low incidence of hepatotoxicity. In most cases, hepatotoxicity is associated with high voriconazole trough concentration influenced mainly by cytochrome P450 (CYP) 2C19 gene polymorphism. Compared with normal metabolizers, intermediate and poor metabolizers generally have higher voriconazole trough concentrations with an increased risk of hepatotoxicity. Here, we describe changes in hepatotoxicity throughout azole therapy in a patient with pulmonary aspergillosis (PA). Nevertheless, the patient with the normal metabolism genotype of CYP2C19 developed severe hepatotoxicity caused by voriconazole but tolerated posaconazole well, with a lack of direct cross-hepatotoxicity between the both. Interestingly, the patient had a high risk of hepatotoxicity at a low voriconazole trough concentration. Fortunately, elevated liver enzymes declined to the baselines with posaconazole treatment.

20.
Front Immunol ; 13: 972302, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36072586

RESUMO

We report here a patient with advanced hepatocellular carcinoma (HCC) and psoriasis treated with immune checkpoint inhibitor (ICI) therapy who experienced tumor partial response and psoriatic exacerbation. Meanwhile, the patient contracted mycobacterium neoaurum during the treatment period, while it was an opportunistic infection and mainly happened in immunosuppressed patients. We discussed the possibility that this infection was an ICI-associated infection independent of immunosuppression due to dysregulated immunity, which was the result of the effects of immunotherapy and autoimmune disease (AID), and the characteristics and treatment of M. neoaurum, which was rarely reported in China. This case highlights the fact that some infections can be precipitated by ICIs in the absence of immunosuppressive treatment, especially the patients with AID.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Infecções por Mycobacterium , Psoríase , Carcinoma Hepatocelular/complicações , Carcinoma Hepatocelular/tratamento farmacológico , Humanos , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/tratamento farmacológico , Mycobacteriaceae , Infecções por Mycobacterium/complicações , Infecções por Mycobacterium/diagnóstico , Infecções por Mycobacterium/tratamento farmacológico , Psoríase/complicações , Psoríase/tratamento farmacológico
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