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1.
Ann Hematol ; 102(7): 1713-1721, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37199788

RESUMO

Realgar-Indigo naturalis formula (RIF), with A4S4 as a major ingredient, is an oral arsenic used in China to treat pediatric acute promyelocytic leukemia (APL). The efficacy of RIF is similar to that of arsenic trioxide (ATO). However, the effects of these two arsenicals on differentiation syndrome (DS) and coagulation disorders, the two main life-threatening events in children with APL, remain unclear. We retrospectively analyzed 68 consecutive children with APL from South China Children Leukemia Group-APL (SCCLG-APL) study. Patients received all-trans retinoic acid (ATRA) on day 1 of induction therapy. ATO 0.16 mg/kg day or RIF 135 mg/kg·day was administrated on day 5, while mitoxantrone was administered on day 3 (non-high-risk) or days 2-4 (high-risk). The incidences of DS were 3.0% and 5.7% in ATO (n = 33) and RIF (n = 35) arms (p = 0.590), and 10.3% and 0% in patients with and without differentiation-related hyperleukocytosis (p = 0.04), respectively. Moreover, in patients with differentiation-related hyperleukocytosis, the incidence of DS was not significantly different between ATO and RIF arms. The dynamic changes of leukocyte count between arms were not statistically different. However, patients with leukocyte count > 2.61 × 109/L or percentage of promyelocytes in peripheral blood > 26.5% tended to develop hyperleukocytosis. The improvement of coagulation indexes in ATO and RIF arms was similar, with fibrinogen and prothrombin time having the quickest recovery rate. This study showed that the incidence of DS and recovery of coagulopathy are similar when treating pediatric APL with RIF or ATO.


Assuntos
Arsênio , Arsenicais , Transtornos da Coagulação Sanguínea , Leucemia Promielocítica Aguda , Criança , Humanos , Leucemia Promielocítica Aguda/tratamento farmacológico , Arsênio/uso terapêutico , Estudos Retrospectivos , Trióxido de Arsênio , Tretinoína , Protocolos de Quimioterapia Combinada Antineoplásica , Óxidos , Resultado do Tratamento
2.
BMC Infect Dis ; 23(1): 192, 2023 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-36997914

RESUMO

BACKGROUND: Streptococcus dysgalactiae subsp. dysgalactiae has been identified as an animal pathogen that is thought to occur only in animal populations. Between 2009 and 2022, humans infected with SDSD were reported rarely. There is a lack of details on the natural history, clinical features, and management of disease caused by this pathogen. This case outlines a human SDSD with muscle aches and progressive loss of muscle strength leading to immobility and multi-organ dysfunction syndrome. CASE PRESENTATION: She presented with muscle pain and weakness, and later developed a sore throat, headache and fever with a maximum temperature of 40.5 °C. The muscle strength of the extremities gradually decreased to grade 1 and the patient was unable to move on his own. Next-generation blood sequencing and multi-culture confirmed the presence of Streptococcus dysgalactiae and Streptococcus dysgalactiae subsp. Dysgalactiae, respectively. A Sequential Organ Failure Assessment score of 6 indicated septicemia, and therapeutic antibiotics were prescribed empirically. After 19 days of inpatient treatment, the patient's condition greatly improved and completely recovered within a month. CONCLUSION: Symptoms of Streptococcus dysgalactiae subsp. dysgalactiae presenting with progressive limb weakness resemble polymyositis, so a precise differential diagnosis is essential. Multidisciplinary consultation is helpful when polymyositis cannot be ruled out and facilitates the choice of an optimal treatment protocol. In the context of this case, penicillin is an effective antibiotic for Streptococcus dysgalactiae subsp. dysgalactiae infection.


Assuntos
Infecções Estreptocócicas , Animais , Feminino , Humanos , Infecções Estreptocócicas/diagnóstico , Infecções Estreptocócicas/tratamento farmacológico , Insuficiência de Múltiplos Órgãos , Extremidades
3.
Zhongguo Dang Dai Er Ke Za Zhi ; 25(3): 315-320, 2023 Mar 15.
Artigo em Zh | MEDLINE | ID: mdl-36946169

RESUMO

Acute lymphoblastic leukemia (ALL) is the most common malignant neoplastic disease in children. With the continuous improvement in diagnosis and treatment, there has been an increasing number of ALL children who achieve long-term survival after complete remission; however, a considerable proportion of these children have cognitive impairment, which has a serious adverse impact on their learning, employment, and social life. This article reviews the latest research on cognitive impairment in children with ALL from the aspects of the influencing factors, detection techniques, and prevention/treatment methods for cognitive impairment.


Assuntos
Disfunção Cognitiva , Leucemia-Linfoma Linfoblástico de Células Precursoras , Criança , Humanos , Disfunção Cognitiva/epidemiologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/epidemiologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia
4.
Zhongguo Dang Dai Er Ke Za Zhi ; 25(12): 1282-1286, 2023 Dec 15.
Artigo em Zh | MEDLINE | ID: mdl-38112148

RESUMO

This article reports two cases of children with B-cell acute lymphoblastic leukemia (B-ALL) complicated by invasive fungal disease (IFD) who received bridging treatment using blinatumomab. Case 1 was a 4-month-old female infant who experienced recurrent high fever and limb weakness during chemotherapy. Blood culture was negative, and next-generation sequencing (NGS) of peripheral blood, bronchoalveolar lavage fluid, and cerebrospinal fluid were all negative. Chest CT and cranial MRI revealed obvious infection foci. Case 2 was a 2-year-old male patient who experienced recurrent high fever with multiple inflammatory masses during chemotherapy. Candida tropicalis was detected in peripheral blood and abscess fluid using NGS, while blood culture and imaging examinations showed no obvious abnormalities. After antifungal and blinatumomab therapy, both cases showed significant improvement in symptoms, signs, and imaging, and B-ALL remained in continuous remission. The report indicates that bridging treatment with blinatumomab in children with B-ALL complicated by IFD can rebuild the immune system and control the underlying disease in the presence of immunosuppression and severe fungal infection.


Assuntos
Anticorpos Biespecíficos , Infecções Fúngicas Invasivas , Leucemia-Linfoma Linfoblástico de Células Precursoras B , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Anticorpos Biespecíficos/uso terapêutico , Infecções Fúngicas Invasivas/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras B/complicações , Leucemia-Linfoma Linfoblástico de Células Precursoras B/tratamento farmacológico , Indução de Remissão
5.
BMC Med ; 20(1): 208, 2022 06 20.
Artigo em Inglês | MEDLINE | ID: mdl-35718771

RESUMO

BACKGROUND: Recent guidelines recommended a systolic blood pressure (SBP) target of < 130 mmHg for patients with or without diabetes but without providing a lower bound. Our study aimed to explore whether additional clinical benefits remain at achieved blood pressure (BP) levels below the recommended target. METHODS: We performed a secondary analysis of the Systolic Blood Pressure Intervention Trial (SPRINT) among the non-diabetic population and the Action to Control Cardiovascular Risk in Diabetes BP (ACCORD-BP) trial among diabetic subjects. We used the propensity score method to match patients from the intensive BP group to those from the standard group in each trial. Individuals with different achieved BP levels from the intensive BP group were used as "reference." For each stratum, the trial-specific primary outcome (i.e., composite outcome of myocardial infarction (MI), acute coronary syndrome not resulting in MI, stroke, acute decompensated heart failure (HF), or cardiovascular death for SPRINT; non-fatal MI, non-fatal stroke, or cardiovascular death for ACCORD-BP) was compared by Cox regression. RESULTS: A non-linear association was observed between the mean achieved BP and incidence of composite cardiovascular events, regardless of treatment allocation. The significant treatment benefit for primary outcome remained at SBP 110-120 mmHg (hazard ratio, 0.59 [95% CI, 0.46, 0.76] for SPRINT; 0.67 [0.52, 0.88] for ACCORD-BP) and SBP 120-130 mmHg for SPRINT (0.47 [0.34, 0.63]) but not for ACCORD-BP (0.93 [0.70, 1.23]). The results were similar for the secondary outcomes including all-cause mortality, cardiovascular mortality, MI, stroke, and HF. Intensive BP treatment benefits existed among patients maintaining a diastolic BP of 60-70 mmHg but were less distinct. CONCLUSIONS: The treatment benefit persists at as low as SBP 110-120 mmHg irrespective of diabetes status. Achieved very low BP levels appeared to increase cardiovascular events and all-cause mortality.


Assuntos
Doenças Cardiovasculares , Diabetes Mellitus , Insuficiência Cardíaca , Hipertensão , Infarto do Miocárdio , Acidente Vascular Cerebral , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/fisiologia , Diabetes Mellitus/tratamento farmacológico , Diabetes Mellitus/epidemiologia , Insuficiência Cardíaca/epidemiologia , Humanos , Hipertensão/complicações , Hipertensão/tratamento farmacológico , Pontuação de Propensão , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco , Acidente Vascular Cerebral/complicações
6.
BMC Womens Health ; 22(1): 166, 2022 05 13.
Artigo em Inglês | MEDLINE | ID: mdl-35562706

RESUMO

BACKGROUND: To determine the incidence, clinical and MRI features of sacral insufficiency fracture (SIF) after radiotherapy (RT) in patients with cervical cancer. METHODS: Our study included 167 patients with cervical cancer after radiotherapy that underwent pelvic MRI for follow-up. MRIs included pre-enhanced T1-weighted, coronal fat-Suppressed T2-weighted (FS-T2W) and enhanced T1-weighted imaging. The clinical and MRI dates were reviewed. The gold standard of SIF was based on radiologic findings, clinical data and follow-up at least 12 months. RESULTS: 28 patients (10.8%) with 47 sites were diagnosed with SIFs, including 9 patients with unilateral SIF and 19 patients with bilateral SIFs. The median age was 60 years (range 41-72 years), and 89.3% (25/28) of patients were postmenopausal. 64.3% (18/28) of patients were symptomatic, and 53.6% of patients (15/28) had concomitant pelvic fractures. The median interval time from RT to SIFs was 10 months (range 3-34 months). For the lesion-wise analysis based on all MR images, all lesions were detected by visualizing bone marrow edema patterns, and fracture lines were detected in 64.6% (31/47) of SIFs. No soft-tissue tumors were founded. For each MRI sequence analysis, coronal FS-T2WI detected the most bone marrow edema pattern and fracture line than T1WI or enhanced T1WI. CONCLUSION: SIF is a common complication in cervical cancer after radiotherapy, which has some certain clinical and MRI features. Coronal FS-T2WI may be more useful to detect and characterize these fractures than other imaging sequences.


Assuntos
Fraturas de Estresse , Fraturas da Coluna Vertebral , Neoplasias do Colo do Útero , Adulto , Idoso , Feminino , Fraturas de Estresse/diagnóstico por imagem , Fraturas de Estresse/etiologia , Humanos , Imageamento por Ressonância Magnética/métodos , Pessoa de Meia-Idade , Estudos Retrospectivos , Sacro/diagnóstico por imagem , Fraturas da Coluna Vertebral/complicações , Fraturas da Coluna Vertebral/etiologia , Neoplasias do Colo do Útero/complicações , Neoplasias do Colo do Útero/diagnóstico por imagem , Neoplasias do Colo do Útero/radioterapia
7.
Zhongguo Dang Dai Er Ke Za Zhi ; 24(5): 550-560, 2022 May 15.
Artigo em Zh | MEDLINE | ID: mdl-35644196

RESUMO

OBJECTIVES: To examine the changes of intestinal flora in children newly diagnosed with acute lymphoblastic leukemia (ALL) and the influence of chemotherapy on intestinal flora. METHODS: Fecal samples were collected from 40 children newly diagnosed with ALL before chemotherapy and at 2 weeks, 1 month, and 2 months after chemotherapy. Ten healthy children served as the control group. 16S rDNA sequencing and analysis were performed to compare the differences in intestinal flora between the ALL and control groups and children with ALL before and after chemotherapy. RESULTS: The ALL group had a significant reduction in the abundance of intestinal flora at 1 and 2 months after chemotherapy, with a significant reduction compared with the control group (P<0.05). Compared with the control group, the ALL group had a significant reduction in the diversity of intestinal flora before and after chemotherapy (P<0.05). At the phylum level, compared with the control group, the ALL group had a significant reduction in the relative abundance of Actinobacteria at 2 weeks, 1 month, and 2 months after chemotherapy (P<0.05) and a significant increase in the relative abundance of Proteobacteria at 1 and 2 months after chemotherapy (P<0.05). At the genus level, compared with the control group, the ALL group had a significant reduction in the relative abundance of Bifidobacterium at 2 weeks, 1 month, and 2 months after chemotherapy (P<0.05); the relative abundance of Klebsiella in the ALL group was significantly higher than that in the control group at 1 and 2 months after chemotherapy and showed a significant increase at 1 month after chemotherapy (P<0.05); the relative abundance of Faecalibacterium in the ALL group was significantly lower than that in the control group before and after chemotherapy and showed a significant reduction at 2 weeks and 1 month after chemotherapy (P<0.05). The relative abundance of Enterococcus increased significantly at 1 and 2 months after chemotherapy in the ALL group (P<0.05), and was significantly higher than that in the control group (P<0.05). CONCLUSIONS: The diversity of intestinal flora in children with ALL is significantly lower than that in healthy children. Chemotherapy significantly reduces the abundance of intestinal flora and can reduce the abundance of some probiotic bacteria (Bifidobacterium and Faecalibacterium) and increase the abundance of pathogenic bacteria (Klebsiella and Enterococcus) in children with ALL.


Assuntos
Microbioma Gastrointestinal , Leucemia-Linfoma Linfoblástico de Células Precursoras , Bactérias/genética , Bifidobacterium , Criança , Fezes/microbiologia , Humanos , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico
8.
BMC Pregnancy Childbirth ; 21(1): 669, 2021 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-34602066

RESUMO

BACKGROUND: The neuroimaging manifestations of eclampsia and preeclampsia often overlap, mainly presenting as posterior reversible encephalopathy syndrome (PRES). The purpose of this retrospective study was to compare the extent and nature of brain edema in eclampsia and preeclampsia patients with PRES based on MRI characteristics. METHODS: One hundred fifty women diagnosed with preeclampsia-eclampsia and undergoing cranial MRI were enrolled; 24 of these were diagnosed as having eclampsia. According to clinicoradiologic diagnosis of PRES, eligible patients were classified as having eclampsia with PRES (group E-PRES) and preeclampsia with PRES (group P-PRES). A scale on T2W FLAIR-SPIR images was established to evaluate the extent of brain edema, and the score of brain edema (SBE) of both groups was compared. In patients of the two groups who also underwent DWI sequence, the presence or absence of hyperintensity on DWI and hypointensity on ADC maps were determined to compare the nature of brain edema. Furthermore, clinical and biochemical data of the two groups were compared. RESULTS: The incidence of PRES in eclampsia patients was significantly higher than that in preeclampsia patients (87.50% vs. 46.03%, P<0.001). The SBE of all regions and typical regions in group E-PRES patients were significantly higher than those in group P-PRES patients (15.88±8.72 vs. 10.90±10.21, P=0.021; 8.52±3.87 vs. 5.01±4.19, P=0.002; respectively). The presence of hyperintensity on DWI was determined more frequently in group E-PRES patients than group P-PRES patients (71.43% vs. 32.00%, P=0.024). Age, systolic blood pressure, white blood cell count, neutrophil count and percentage of neutrophils were significantly different between the two groups (P<0.05). CONCLUSIONS: Certain MRI characteristics that reflect the extent and nature of brain edema were different between eclampsia and preeclampsia patients with PRES. Additional prospective studies are still required to explore whether these MRI characteristics of brain edema may further become a potential predictor for eclamptic seizures in preeclampsia patients with PRES.


Assuntos
Edema Encefálico/diagnóstico por imagem , Eclampsia/diagnóstico por imagem , Imageamento por Ressonância Magnética , Neuroimagem , Síndrome da Leucoencefalopatia Posterior/diagnóstico por imagem , Pré-Eclâmpsia/diagnóstico por imagem , Complicações na Gravidez/diagnóstico por imagem , Adulto , Eclampsia/epidemiologia , Feminino , Humanos , Síndrome da Leucoencefalopatia Posterior/complicações , Síndrome da Leucoencefalopatia Posterior/epidemiologia , Pré-Eclâmpsia/epidemiologia , Gravidez , Complicações na Gravidez/epidemiologia , Estudos Retrospectivos
9.
BMC Med Imaging ; 21(1): 48, 2021 03 12.
Artigo em Inglês | MEDLINE | ID: mdl-33706695

RESUMO

BACKGROUND: Non-mass enhancement (NME) is a diagnostic dilemma and highly reliant on the experience of the radiologists. Texture analysis (TA) could serve as an objective method to quantify lesion characteristics. However, it remains unclear what role TA plays in a predictive model based on routine MRI characteristics. The purpose of this study was to explore the value of TA in distinguishing between benign and malignant NME in premenopausal women. METHODS: Women in whom NME was histologically proven (n = 147) were enrolled (benign: 58; malignant: 89) was retrospective. Then, 102 and 45 patients were classified as the training and validation groups, respectively. Scanning sequences included Fat-suppressed T2-weighted and fat-suppressed contrast-enhanced T1-weighted which were acquired on a 1.5T MRI system. Clinical and routine MR characteristics (CRMC) were evaluated by two radiologists according to the Breast Imaging and Reporting and Data system (2013). Texture features were extracted from all post-contrast sequences in the training group. The combination model was built and then assessed in the validation group. Pearson's chi-square test and Mann-Whitney U test were used to compare categorical variables and continuous variables, respectively. Logistic regression analysis and receiver operating characteristic curve were employed to assess the diagnostic performance of CRMC, TA, and their combination model in NME diagnosis. RESULTS: The combination model showed superior diagnostic performance in differentiating between benign and malignant NME compared to that of CRMC or TA alone (AUC, 0.887 vs 0.832 vs 0.74). Moreover, compared to CRMC, the model showed high specificity (72.5% vs 80%). The results obtained in the validation group confirmed the model was promising. CONCLUSIONS: With the combined use of TA and CRMC could afford an improved diagnostic performance in differentiating between benign and malignant NME.


Assuntos
Doenças Mamárias/diagnóstico por imagem , Mama/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Pré-Menopausa , Adulto , Mama/patologia , Doenças Mamárias/patologia , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Meios de Contraste , Diagnóstico Diferencial , Feminino , Humanos , Pessoa de Meia-Idade , Curva ROC , Análise de Regressão , Estudos Retrospectivos , Sensibilidade e Especificidade , Estatísticas não Paramétricas , Adulto Jovem
10.
Eur Radiol ; 30(4): 1885-1895, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31822977

RESUMO

OBJECTIVES: We sought to determine the added value of diffusion-weighted magnetic resonance imaging (DWI) in the differentiation of pelvic insufficiency fracture (PIF) from bone metastasis after radiotherapy in cervical cancer patients. METHODS: In the present study, 42 cervical cancer patients after radiotherapy with 61 bone lesions (n = 40, PIFs; n = 21, bone metastasis) were included. Conventional MRI and DWI were performed in all patients. For qualitative imaging diagnosis, two sets of images were reviewed independently by three observers, including a conventional MRI set (unenhanced T1-weighted, T2-weighted, and enhanced T1-weighted images) and a DWI set (conventional MRIs, DW images, and ADC maps). The mean ADC value of each lesson was measured on ADC maps. The diagnostic performance was assessed by using the area under the receiver operating characteristic curve (Az), and sensitivity and specificity were determined. RESULTS: For all observers, the Az value and sensitivity of the DWI set showed improvement compared with the conventional MRI set. The observer who had the least experience (3 years) demonstrated significant improvement in diagnostic performance with the addition of DWI; Az value increased from 0.804 to 0.915 (p = 0.042) and sensitivity increased from 75.0 to 92.5% (p = 0.035). The mean ADCs of the PIFs were significantly higher than the bone metastases (p < 0.001); ADC values > 0.97 × 10-3 mm2/s yielded an Az of 0.887, a sensitivity of 92.5%, and a specificity of 76.2%. CONCLUSIONS: The addition of DWI to conventional MRI improved the differentiation of PIF from bone metastasis after RT in patients with cervical cancer. KEY POINTS: • DWI showed additive value to conventional MRI in the differentiation of PIF from bone metastasis after RT. • For qualitative diagnosis, the addition of DWI can improve diagnostic performance compared with conventional MRI alone and can particularly improve the sensitivity. • Quantitative ADC assessment showed potential value for identifying PIF from bone metastasis.


Assuntos
Neoplasias Ósseas/diagnóstico por imagem , Diagnóstico Diferencial , Fraturas de Estresse/diagnóstico por imagem , Ossos Pélvicos/diagnóstico por imagem , Neoplasias do Colo do Útero/patologia , Idoso , Neoplasias Ósseas/secundário , Imagem de Difusão por Ressonância Magnética/métodos , Feminino , Humanos , Aumento da Imagem/métodos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Curva ROC , Sensibilidade e Especificidade , Neoplasias do Colo do Útero/radioterapia
11.
J Cell Physiol ; 234(7): 10411-10420, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30511419

RESUMO

G protein-coupled receptor kinase 5 (GRK5) is a serine/threonine kinase whose dysfunction results in cognitive impairment and Alzheimer-like pathology, including tau hyperphosphorylation. However, the mechanisms whereby GRK5 influences tau phosphorylation remain incompletely understood. In the current study, we showed that GRK5 influenced the phosphorylation of tau via glycogen synthase kinase 3ß (GSK3ß). The activity of both tau and GSK3ß in the hippocampus was increased in aged GRK5-knockout mice, which is consistent with what occurs in APP/PS1 transgenic mice. Furthermore, GRK5 regulated the activity of GSK3ß and phosphorylated tau in vitro. Regardless of changes of GRK5 protein levels, tau hyperphosphorylation remained reduced after GSK3ß activity was inhibited, suggesting that GRK5 may specifically influence tau hyperphosphorylation by modulating GSK3ß activity. Taken together, our findings suggest that GRK5 deficiency contributes to the pathogenesis of Alzheimer's disease by influencing the hyperphosphorylation of tau through the activation of GSK3ß.


Assuntos
Doença de Alzheimer/metabolismo , Quinase 5 de Receptor Acoplado a Proteína G/metabolismo , Glicogênio Sintase Quinase 3 beta/metabolismo , Fosforilação/fisiologia , Proteínas tau/metabolismo , Peptídeos beta-Amiloides/metabolismo , Precursor de Proteína beta-Amiloide/metabolismo , Animais , Disfunção Cognitiva/metabolismo , Células HEK293 , Hipocampo/metabolismo , Humanos , Aprendizagem em Labirinto/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , Transdução de Sinais/fisiologia
12.
J Cell Biochem ; 120(1): 658-670, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30203578

RESUMO

Emerging evidence indicated that changes in DNA methylation early in breast cancer (BC) development might be clinically relevant for therapeutic decisions. Through analysis of whole-genome gene expression microarray and DNA methylation microarray, we explored genes with abnormal DNA methylation in BC for early detection. Firstly, human BC tissues and adjacent non-cancerous tissues were collected from nine BC patients. Gene expression microarray sequencing was conducted for identifying differentially expressed genes and DNA methylation microarray sequencing for differentially methylated genes in BC. Differentially expressed genes and methylated genes in BC were further explored using the Cancer Genome Atlas database. The correlation between DNA methylation and gene expression was illustrated by multiple comparisons. In other 60 clinical samples, methylation specific polymerase chain reaction (PCR) and reverse transcription quantitative PCR were applied for the methylation of HOXA4 and IGF1 genes in BC and adjacent non-cancerous tissues. In total, 1680 upregulated genes and 1249 downregulated genes were determined in BC. Chromosome 16 and 17 showed more differentially methylated genes, and DNA methylation level was increased in BC tissues in each gene region. Chromosome 19 showed more differentially methylated genes, and DNA methylation level was increased in BC tissues in the exoniensis 1, untranslated region-5 and transcriptional start site 200 gene regions. In other 60 clinical samples, HOXA4 and IGF1 in BC tissues presented increased DNA methylation and decreased gene expression in BC. MCF7 cells treated with RG108 showed decreased HOXA4 and IGF1 expressions. It was estimated that HOXA4 and IGF1 were identified with increased DNA methylation and decreased gene expression in BC, which may serve as biomarkers in early BC detection.


Assuntos
Neoplasias da Mama/genética , Metilação de DNA/genética , Detecção Precoce de Câncer , Genoma Humano/genética , Proteínas de Homeodomínio/genética , Fator de Crescimento Insulin-Like I/genética , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Fatores de Transcrição/genética , Adulto , Idoso , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , DNA (Citosina-5-)-Metiltransferases/antagonistas & inibidores , Metilação de DNA/efeitos dos fármacos , Bases de Dados de Ácidos Nucleicos , Feminino , Regulação Neoplásica da Expressão Gênica , Proteínas de Homeodomínio/metabolismo , Humanos , Fator de Crescimento Insulin-Like I/metabolismo , Células MCF-7 , Pessoa de Meia-Idade , Ftalimidas/farmacologia , Transdução de Sinais/efeitos dos fármacos , Fatores de Transcrição/metabolismo , Transcriptoma/genética , Triptofano/análogos & derivados , Triptofano/farmacologia , Regulação para Cima/genética
13.
J Cell Mol Med ; 22(3): 1883-1893, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29363864

RESUMO

D-serine is a predominant N-methyl-D-aspartate receptor co-agonist with glutamate, and excessive activation of the receptor plays a substantial role in epileptic seizures. Serine racemase (SRR) is responsible for transforming L-serine to D-serine. In this study, we aimed to investigate the genetic roles of SRR and a neighbouring gene, nonsense-mediated mRNA decay factor (SMG6), in temporal lobe epilepsy (TLE). Here, a total of 496 TLE patients and 528 healthy individuals were successfully genotyped for three SRR tag single nucleotide polymorphisms. The frequencies of the GG genotype at rs4523957 T > G were reduced in the TLE cases in the initial cohort (cohort 1) and were confirmed in the independent cohort (cohort 2). An analysis of all TLE cases in cohort 1 + 2 revealed that the seizure frequency and drug-resistant incidence were significantly decreased in carriers of the GG genotype at rs4523957. Intriguingly, the activity of the SMG6 promoter with the mutant allele at rs4523957 decreased by 22% in the dual-luciferase assay, and up-regulated expression of SMG6 was observed in an epilepsy rat model. This study provides the first demonstration that the GG genotype is a protective marker against TLE. In particular, variation at rs4523957 likely inhibits SMG6 transcription and plays a key role against susceptibility to and severity of TLE. The significance of SMG6 hyperfunction in epileptic seizures deserves to be investigated in future studies.


Assuntos
Epilepsia do Lobo Temporal/genética , Polimorfismo de Nucleotídeo Único , Racemases e Epimerases/genética , Receptores de N-Metil-D-Aspartato/genética , Telomerase/genética , Animais , Estudos de Casos e Controles , Estudos de Coortes , Biologia Computacional , Modelos Animais de Doenças , Epilepsia do Lobo Temporal/metabolismo , Epilepsia do Lobo Temporal/patologia , Feminino , Regulação da Expressão Gênica , Genes Reporter , Genótipo , Ácido Glutâmico/metabolismo , Hipocampo/metabolismo , Hipocampo/patologia , Humanos , Íntrons , Luciferases/genética , Luciferases/metabolismo , Masculino , Regiões Promotoras Genéticas , Racemases e Epimerases/metabolismo , Ratos , Receptores de N-Metil-D-Aspartato/metabolismo , Serina/metabolismo , Transdução de Sinais , Telomerase/metabolismo
14.
Cell Physiol Biochem ; 51(6): 2732-2745, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30562735

RESUMO

BACKGROUND/AIMS: Increasing evidence suggests the important role of sirtuin 2 (SIRT2) in the pathology of Parkinson's disease (PD). However, the association between potential functional polymorphisms in the SIRT2 gene and PD still needs to be identified. Exploring the molecular mechanism underlying this potential association could also provide novel insights into the pathogenesis of this disorder. METHODS: Bioinformatics analysis and screening were first performed to find potential microRNAs (miRNAs) that could target the SIRT2 gene, and molecular biology experiments were carried out to further identify the regulation between miRNA and SIRT2 and characterize the pivotal role of miRNA in PD models. Moreover, a clinical case-control study was performed with 304 PD patients and 312 healthy controls from the Chinese Han population to identify the possible association of single nucleotide polymorphisms (SNPs) within the miRNA binding sites of SIRT2 with the risk of PD. RESULTS: Here, we demonstrate that miR-486-3p binds to the 3' UTR of SIRT2 and influences the translation of SIRT2. MiR-486-3p mimics can decrease the level of SIRT2 and reduce a-synuclein (α-syn)-induced aggregation and toxicity, which may contribute to the progression of PD. Interestingly, we find that a SNP, rs2241703, may disrupt miR-486-3p binding sites in the 3' UTR of SIRT2, subsequently influencing the translation of SIRT2. Through the clinical case-control study, we further verify that rs2241703 is associated with PD risk in the Chinese Han population. CONCLUSION: The present study confirms that the rs2241703 polymorphism in the SIRT2 gene is associated with PD in the Chinese Han population, provides the potential mechanism of the susceptibility locus in determining PD risk and reveals a potential target of miRNA for the treatment and prevention of PD.


Assuntos
MicroRNAs/genética , Doença de Parkinson/genética , Polimorfismo de Nucleotídeo Único , Sirtuína 2/genética , alfa-Sinucleína/metabolismo , Regiões 3' não Traduzidas , Idoso , Povo Asiático/genética , Estudos de Casos e Controles , Linhagem Celular , Feminino , Regulação da Expressão Gênica , Predisposição Genética para Doença , Humanos , Masculino , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Doença de Parkinson/metabolismo , Agregação Patológica de Proteínas/genética , Agregação Patológica de Proteínas/metabolismo , Biossíntese de Proteínas , Sirtuína 2/metabolismo
15.
Am J Hematol ; 93(12): 1467-1473, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30160789

RESUMO

Intravenous arsenic trioxide (ATO) has been adopted as the first-line treatment for acute promyelocytic leukemia (APL). Another arsenic compound named the Realgar-Indigo naturalis formula (RIF), an oral traditional Chinese medicine containing As4 S4 , has been shown to be highly effective in treating adult APL. In the treatment of pediatric APL, the safety and efficacy of RIF remains to be confirmed. This randomized, multicenter, and noninferiority trial was conducted to determine whether intravenous ATO can be substituted by oral RIF in the treatment of pediatric APL. From September 2011 to January 2017, among 92 patients who were 16 years old or younger with newly diagnosed PML-RARa positive APL, 82 met eligible criteria and were randomly assigned to ATO (n = 42) or RIF (n = 40) group. The remaining 10 patients did not fulfilled eligible criteria because five did not accept randomization, four died and one had hemiplegia prior to arsenic randomization due to intracranial hemorrhage or cerebral thrombosis. Induction and consolidation treatment contained ATO or RIF, all-trans-retinoic acid and low intensity chemotherapy. End points included event-free survival (EFS), adverse events and hospital days. After a median 3-year follow-up, the estimated 5-year EFS was 100% in both groups, and adverse events were mild. However, patients in the RIF group had significantly less hospital stay than those in the ATO group. This interim analysis shows that oral RIF is as effective and safe as intravenous ATO for the treatment of pediatric APL, with the advantage of reducing hospital stay. Final trial analysis will reveal mature outcome data.


Assuntos
Trióxido de Arsênio/uso terapêutico , Medicamentos de Ervas Chinesas/uso terapêutico , Leucemia Promielocítica Aguda/tratamento farmacológico , Adolescente , Trióxido de Arsênio/administração & dosagem , Trióxido de Arsênio/efeitos adversos , Criança , Pré-Escolar , Intervalo Livre de Doença , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/efeitos adversos , Humanos , Lactente , Tempo de Internação , Masculino , Resultado do Tratamento , Tretinoína/uso terapêutico
16.
Zhongguo Dang Dai Er Ke Za Zhi ; 20(1): 12-16, 2018 Jan.
Artigo em Zh | MEDLINE | ID: mdl-29335075

RESUMO

OBJECTIVE: Ververck index (VI) reflects thoracic development, body type, and nutritional status. This study aimed to investigate the VI of singleton neonates with a gestational age (GA) of 27-42 weeks at birth, and to establish percentile curves of VI of the neonates. METHODS: Cross-sectional cluster sampling was performed between April 2013 and September 2015. Body weight, body length, and chest circumference were measured for 16 865 singleton neonates with a GA of 27-42 weeks in two hospitals in Shenzhen, China. VI was calculated and the percentile curves of VI were plotted for the neonates. RESULTS: Mean VIs were obtained for singleton neonates with a gestational age of 27-42 weeks (in three groups of male, female, and both sexes), and related 3rd-97th percentile curves were plotted. As for the 50th percentile curve, the singleton neonates with a GA of 27 weeks had the lowest 50th percentile value of VI, which gradually increased with the increase in GA. The singleton neonates with a GA of 42 weeks had the highest 50th percentile value of VI. Girls had a slightly higher 50th percentile value of VI than boys in all GA groups. CONCLUSIONS: VI of neonates increases with the increase in GA. Female neonates may have a slightly better thoracic development, body type, and nutritional status than male neonates at birth. The percentile curves of VI plotted for singleton neonates with a GA of 27-42 weeks (in three groups of male, female, and both sexes) can provide a basis for evaluating thoracic development, body type, and nutritional status of neonates at birth in Shenzhen, China.


Assuntos
Estado Nutricional , Somatotipos , Tórax/crescimento & desenvolvimento , Estudos Transversais , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Masculino , Caracteres Sexuais
17.
Zhongguo Dang Dai Er Ke Za Zhi ; 20(4): 267-273, 2018 Apr.
Artigo em Zh | MEDLINE | ID: mdl-29658449

RESUMO

OBJECTIVE: To establish the intrauterine growth curve of twin neonates, and to investigate the intrauterine growth status of twin neonates. METHODS: Cross-sectional cluster sampling was performed for an on-the-spot investigation of 1 296 live twin neonates who were born in two hospitals in Shenzhen between April 2013 and September 2015. The Lambda-Mu-Sigma method was used for the curve fitting of body weight, body length, head circumference, chest circumference, and crown-rump length. RESULTS: The means and 3rd-97th percentile intrauterine growth curves for body weight, body length, head circumference, chest circumference, and crown-rump length were obtained for the 1 296 twin neonates with a gestational age of 27-40 weeks. The curve values of the 1 296 twin neonates for body weight, body length, head circumference, chest circumference, and crown-rump length were all lower than those of singleton neonates in Shenzhen that had been reported, and the difference increased with increasing gestational age. CONCLUSIONS: The intrauterine growth curves for body weight, body length, head circumference, chest circumference, and crown-rump length of twin neonates with a gestational age of 27-40 weeks in Shenzhen obtained in this study can provide a reference for evaluating the intrauterine growth status of twin neonates among the current population in Shenzhen.


Assuntos
Desenvolvimento Fetal , Gêmeos , Estatura , Peso Corporal , Estudos Transversais , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Masculino , Gravidez
18.
Zhongguo Dang Dai Er Ke Za Zhi ; 20(5): 358-362, 2018 May.
Artigo em Zh | MEDLINE | ID: mdl-29764570

RESUMO

OBJECTIVE: To study the Kaup index (KI), an index used to evaluate body burliness and nutritional status, of neonates with a gestational age (GA) of 27-42 weeks at birth, and to establish the percentile curves of KI. METHODS: Cross-sectional cluster sampling was performed from April 2013 to September 2015 to select 16 887 singleton neonates with a GA of 27-42 weeks in two hospitals in Shenzhen, China. Body weight and body length were measured to calculate KI. The percentile curves of KI were plotted in these neonates. RESULTS: Mean KIs and corresponding standard deviations were obtained for singleton neonates with a gestational age of 27-42 weeks (in male, female, and mixed groups), and the 3rd-97th percentile curves of KI were plotted. The singleton neonates with a GA of 27 weeks had the lowest 50th percentile value of KI, and KI gradually increased with GA. Boys had a higher 50th percentile value of KI than girls in each GA group. In all groups except the 33-week GA group, boys had a higher mean KI than girls, and there was a significant difference in the mean KI between boys and girls in the GA groups of 34 and 36-40 weeks (P<0.05). CONCLUSIONS: KI of neonates at birth increases with GA, suggesting that body density and body burliness increase with GA. Boys have better body burliness than girls at birth. The percentile curves of KI plotted for singleton neonates with a GA of 27-42 weeks (in male, female, and mixed groups) can provide a reference for evaluating the body burliness and nutritional status of neonates at birth in Shenzhen.


Assuntos
Idade Gestacional , Estado Nutricional , Estudos Transversais , Feminino , Humanos , Recém-Nascido , Masculino
19.
Zhongguo Dang Dai Er Ke Za Zhi ; 20(3): 184-188, 2018 Mar.
Artigo em Zh | MEDLINE | ID: mdl-29530116

RESUMO

OBJECTIVE: To establish the intrauterine growth percentile curves of full-term neonates with different gestational ages (GAs) born to primiparous or multiparous women, and to investigate the influence of parity on intrauterine growth potential. METHODS: Cross-sectional cluster sampling was performed from April 2013 to September 2015 to measure physical growth in full-term singleton infants with a GA of 37-41 weeks in two hospitals in Shenzhen, China. The Lambda-Mu-Sigma method was used for curve fitting. RESULTS: The mean values of birth weight, body length, head circumference, chest circumference, and crown-rump length were obtained in 14 529 full-term infants. The 10th, 25th, 50th, 75th, and 90th percentile curves of the five indices were established. The full-term infants born to multiparous women had similar patterns and growth trends of the five percentile curves of the above five indices to those born to primiparous women, while the full-term infants with a GA of 37-41 weeks born to multiparous women had higher mean values and percentile curve values of the above five indices than those born to primiparous women. In the group with a GA of 41 weeks, there was no significant difference in the crown-rump length between the infants born to primiparous women and those born to multiparous women, but there were significant differences in the means of the above five indices in all the other GA groups between the two group infants (P<0.05). CONCLUSIONS: Full-term infants with a GA of 37-41 weeks born to multiparous women have higher intrauterine growth levels of birth weight, body length, head circumference, chest circumference, and crown-rump length than those born to primiparous women, suggesting that parity is an important influencing factor for intrauterine growth potential.


Assuntos
Desenvolvimento Fetal , Paridade , Peso ao Nascer , Estatura , Estudos Transversais , Feminino , Idade Gestacional , Humanos , Recém-Nascido , Masculino , Gravidez
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