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1.
J Med Genet ; 2021 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-34544842

RESUMO

BACKGROUND: A large number of new causative and risk genes for amyotrophic lateral sclerosis (ALS) have been identified mostly in patients of European ancestry. In contrast, we know relatively little regarding the genetics of ALS in other ethnic populations. This study aims to provide a comprehensive analysis of the genetics of ALS in an unprecedented large cohort of Chinese mainland population and correlate with the clinical features of rare variants carriers. METHODS: A total of 1587 patients, including 64 familial ALS (FALS) and 1523 sporadic ALS (SALS), and 1866 in-house controls were analysed by whole-exome sequencing and/or testing for G4C2 repeats in C9orf72. Forty-one ALS-associated genes were analysed. FINDINGS: 155 patients, including 26 (40.6%) FALS and 129 (8.5%) SALS, carrying rare pathogenic/likely pathogenic (P/LP) variants of ALS causative genes were identified. SOD1 was the most common mutated gene, followed by C9orf72, FUS, NEK1, TARDBP and TBK1. By burden analysis, rare variants in SOD1, FUS and TARDBP contributed to the collective risk for ALS (p<2.5e-6) at the gene level, but at the allelic level TARDBP p.Gly294Val and FUS p.Arg521Cys and p.Arg521His were the most important single variants causing ALS. Clinically, P/LP variants in TARDBP and C9orf72 were associated with poor prognosis, in FUS linked with younger age of onset, and C9orf72 repeats tended to affect cognition. CONCLUSIONS: Our data provide essential information for understanding the genetic and clinical features of ALS in China and for optimal design of genetic testing and evaluation of disease prognosis.

2.
Int J Gen Med ; 14: 4155-4159, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34385835

RESUMO

Objective: This study aimed to determine the incidence of iron-deficiency anemia (IDA) complicated by splenomegaly in our hospital over the past 6 years and to analyze the possible causes of this result. Methods: This is a retrospective study. In total, 668 patients with IDA who were hospitalized in the hematology department of our hospital from 2013 to 2019 were selected as the research subjects and included in the IDA group, and 3201 patients who underwent outpatient physical examinations in our hospital during the same period were included in the control group. The incidences of splenomegaly in the IDA and control groups were calculated, and the difference was analyzed by means of statistical methods. Results: Among the 668 IDA patients, 46 (6.9%) had splenomegaly, and among the 3201 patients in the control group, 21 had splenomegaly (0.7%). The incidence of splenomegaly was significantly higher in the IDA group than in the control group, and the severity of anemia in the IDA group was associated with the occurrence of splenomegaly. Specifically, the incidence of splenomegaly was 12.4% among patients with severe anemia and as high as 50% among patients with extremely severe anemia. Conclusion: IDA is correlated with the incidence of splenomegaly, and the incidence of splenomegaly significantly increases as the severity of IDA increases. This is considered to be caused by extramedullary hematopoiesis.

3.
Medicine (Baltimore) ; 100(4): e24300, 2021 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-33530219

RESUMO

RATIONALE: Lung cancer is a leading cause of cancer-related mortality worldwide. Currently, targeted therapy has proved highly efficient in the treatment of advanced non-small cell lung cancer (NSCLC). Mesenchymal-epithelial transition factor (MET) is considered a validated molecular target in NSCLC. Given the low incidence of MET exon 14 skipping mutation, the planning of precision treatment for patients is a clinical problem that needs to be solved. In this report, we present a MET-positive case that benefited from crizotinib and cabozantinib treatment. PATIENT CONCERNS: A 77-year-old patient was diagnosed with lung adenocarcinoma in our hospital. Positron emission tomography-computed tomography (PET-CT) showed a right upper lobe mass (58 × 56 mm, SUVmax 15.6), right hilar enlarged lymph nodes, and multiple bone and left adrenal metastases (c-T3N1M1c). DIAGNOSES: MET exon 14 mutation (exon14, c.2888-1G>C) was examined using the lung puncture sample by next generation sequencing. Therefore, the patient was diagnosed with late-stage lung adenocarcinoma with MET exon14 skipping gene mutation. INTERVENTIONS: Crizotinib was given as the first-line treatment from August 2019. Considering the resistance of crizotinib, cabozantinib was given for second-line treatment. OUTCOMES: Crizotinib was administered (250 mg bid) for 8 months, and her disease achieved partial regression (PR) and progression-free survival (PFS), which lasted for 8 months. The patient also reached PR after the second-line treatment with cabozantinib, and is currently under follow-up, with an overall survival (OS) of >12 months. LESSONS: As MET exon 14 skipping mutation is rare in clinical practices, MET-TKIs (tyrosine kinase inhibitors) treatment can boost curative effects and improve prognosis of patients with advanced lung adenocarcinoma. This case report supports a rationale for the treatment of lung adenocarcinoma patients with a MET exon 14 skipping mutation and provides alternative treatment options for these types of NSCLC patients.


Assuntos
Adenocarcinoma de Pulmão/tratamento farmacológico , Anilidas/administração & dosagem , Antineoplásicos/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Crizotinibe/administração & dosagem , Neoplasias Pulmonares/tratamento farmacológico , Proteínas Proto-Oncogênicas c-met/genética , Piridinas/administração & dosagem , Adenocarcinoma de Pulmão/genética , Idoso , Quimioterapia Combinada , Transição Epitelial-Mesenquimal/genética , Éxons , Feminino , Humanos , Neoplasias Pulmonares/genética , Mutação , Resultado do Tratamento
4.
Med Sci Monit ; 26: e922673, 2020 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-32555132

RESUMO

BACKGROUND Cell cycle arrest and autophagy have been demonstrated to be involved in various transforming growth factor (TGF)-ß-mediated phenotype alterations of tubular epithelial cells (TECs) and tubulointerstitial fibrosis. But the relationship between cell cycle arrest and the autophagy induced by TGF-ß has not been explored well. MATERIAL AND METHODS The effects of autophagy inhibition on TGF-ß-induced cell cycle arrest in TECs were explored in vitro. Human kidney-2 (HK-2) cells were stimulated by TGF-ß with or without a combined treatment of autophagy inhibitor chloroquine (CQ) or bafilomycin A1 (Baf). RESULTS Autophagy inhibition by CQ or Baf promotes the suppression of growth in TGF-ß-treated HK-2 cells, as detected by the Cell Counting Kit-8 (CCK-8) method. In addition, CQ or Baf stimulation enhances G1 arrest in TGF-ß treated HK-2 cells, as investigated using propidium iodide (PI) staining and flow cytometry, which was further confirmed by a decrease in the expression of phosphorylated retinoblastoma protein (p-RB) and cyclin-dependent kinase 4 (CDK4). The upregulation of p21 induced by CQ or Baf may mediate an enhanced G1 arrest in TGF-ß treated HK-2 cells. Western blot analysis showed that TGF-ß-induced expression of extracellular matrix fibronectin was notably upregulated in the presence of autophagy inhibitors. CONCLUSIONS Inhibition of autophagy sensitizes the TECs to G1 arrest and proliferation suppression induced by TGF-ß that contributes to the induction of tubulointerstitial fibrosis.


Assuntos
Autofagia/efeitos dos fármacos , Cloroquina/farmacologia , Inibidores Enzimáticos/farmacologia , Células Epiteliais/efeitos dos fármacos , Pontos de Checagem da Fase G1 do Ciclo Celular/efeitos dos fármacos , Macrolídeos/farmacologia , Insuficiência Renal Crônica/patologia , Fator de Crescimento Transformador beta/farmacologia , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Quinase 4 Dependente de Ciclina/efeitos dos fármacos , Quinase 4 Dependente de Ciclina/metabolismo , Inibidor de Quinase Dependente de Ciclina p21/efeitos dos fármacos , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Fibronectinas/efeitos dos fármacos , Fibronectinas/metabolismo , Fibrose , Humanos , Técnicas In Vitro , Túbulos Renais/citologia , Insuficiência Renal Crônica/metabolismo , Proteína do Retinoblastoma/efeitos dos fármacos , Proteína do Retinoblastoma/metabolismo
5.
BMC Genet ; 21(1): 63, 2020 06 18.
Artigo em Inglês | MEDLINE | ID: mdl-32552710

RESUMO

BACKGROUND: The disease gene of fragile X syndrome, FMR1 gene, encodes fragile X mental retardation protein (FMRP). The alternative splicing (AS) of FMR1 can affect the structure and function of FMRP. However, the biological functions of alternatively spliced isoforms remain elusive. In a previous study, we identified a new 140bp exon from the intron 9 of human FMR1 gene. In this study, we further examined the biological functions of this new exon and its underlying signaling pathways. RESULTS: qRT-PCR results showed that this novel exon is commonly expressed in the peripheral blood of normal individuals. Comparative genomics showed that sequences paralogous to the 140 bp sequence only exist in the genomes of primates. To explore the biological functions of the new transcript, we constructed recombinant eukaryotic expression vectors and lentiviral overexpression vectors. Results showed that the spliced transcript encoded a truncated protein which was expressed mainly in the cell nucleus. Additionally, several genes, including the BEX1 gene involved in mGluR-LTP or mGluR-LTD signaling pathways were significantly influenced when the truncated FMRP was overexpressed. CONCLUSIONS: our work identified a new exon from amid intron 9 of human FMR1 gene with wide expression in normal healthy individuals, which emphasizes the notion that the AS of FMR1 gene is complex and may in a large part account for the multiple functions of FMRP.


Assuntos
Processamento Alternativo , Éxons , Proteína do X Frágil de Retardo Mental/genética , Células HEK293 , Humanos , Íntrons
6.
J Assist Reprod Genet ; 37(8): 1931-1938, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32519010

RESUMO

PURPOSE: Higher serum estradiol levels occur in women undergoing assisted reproductive technology (ART) owing to ovarian stimulation. Here, we investigated the association between maternal serum estradiol levels and the intellectual development of offspring conceived with ART. METHODS: A total of 204 singletons born after fresh embryo transfer were recruited for this cohort study. Among them, 102 children were born from mothers with high serum estradiol levels (> 12,000 pmol/L) on the day that human chorionic gonadotropin was administered. Another 102 children, matched by gestational age and age of the children, were recruited as controls from mothers with low serum estradiol (≤ 12,000 pmol/L). The Wechsler Preschool and Primary Scale of Intelligence was used to evaluate the intellectual development of the children. RESULTS: Children from mothers with higher serum estradiol levels scored lower in the verbal intelligence quotient (IQ) tests and verbal comprehension than children whose mothers had lower estradiol levels. The main difference between the two groups was in verbal subtests including information, vocabulary, and sorting. Partial correlation analysis revealed that the logarithm of maternal serum estradiol level negatively correlated with verbal IQ, performance IQ, and full scale IQ. CONCLUSION: Our data demonstrate that a high maternal serum estradiol level may negatively associate the verbal ability of children conceived via ART.


Assuntos
Estradiol/sangue , Deficiência Intelectual/sangue , Inteligência/fisiologia , Técnicas de Reprodução Assistida/efeitos adversos , Adulto , Criança , Pré-Escolar , Gonadotropina Coriônica/administração & dosagem , Estudos de Coortes , Transferência Embrionária/efeitos adversos , Feminino , Fertilização In Vitro/efeitos adversos , Humanos , Deficiência Intelectual/etiologia , Deficiência Intelectual/fisiopatologia , Testes de Inteligência , Masculino , Injeções de Esperma Intracitoplásmicas/efeitos adversos
7.
Infect Dis Poverty ; 9(1): 50, 2020 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-32381098

RESUMO

BACKGROUND: China is the second highest pulmonary tuberculosis (PTB) burden country worldwide. However, retreatment of PTB has often developed resistance to at least one of the four first-line anti-TB drugs. The cure rate (approximately 50.0-73.3%) and management of retreatment of PTB in China needs to be improved. Qinbudan decoction has been widely used to treat PTB in China since the 1960s. Previously clinical studies have shown that the Qinbudan tablet (QBDT) promoted sputum-culture negative conversion and lesion absorption. However, powerful evidence from a randomized controlled clinical trial is lacking. Therefore, the aim of this study was to compare the efficacy and safety of QBDT as an adjunct therapy for retreatment of PTB. METHODS: We conducted a multicenter, randomized, double-blind, placebo-controlled clinical trial in China. People diagnosed with PTB were enrolled who received previous anti-TB treatment from April 2011 to March 2013. The treatment group received an anti-TB regimen and QBDT, and the control group was administered an anti-TB regimen plus placebo. Anti-TB treatment options included isoniazid, rifampicin, pyrazinamide, ethambutol, streptomycin for 2 months (2HRZES), followed by isoniazid, rifampicin, ethambutol for 6 months (6HRE), daily for 8 months. Primary outcome was sputum-culture conversion using the MGIT 960 liquid medium method. Secondary outcomes included lung lesion absorption and cavity closure. Adverse events and reactions were observed after treatment. A structured questionnaire was used to record demographic information and clinical symptoms of all subjects. Data analysis was performed by SPSS 25.0 software in the full analysis set (FAS) population. RESULTS: One hundred eighty-one cases of retreatment PTB were randomly divided into two groups: the placebo group (88 cases) and the QBDT group (93 cases). A total of 166 patients completed the trial and 15 patients lost to follow-up. The culture conversion rate of the QBDT group and placebo group did not show a noticeable improvement by using the covariate sites to correct the rate differences (79.6% vs 69.3%; rate difference = 0.10, 95% confidence interval (CI): - 0.02-0.23; F = 2.48, P = 0.12) after treatment. A significant 16.6% increase in lesion absorption was observed in the QBDT group when compared with the placebo group (67.7% vs 51.1%; rate difference = 0.17, 95% CI: 0.02-0.31; χ2 = 5.56, P = 0.02). The intervention and placebo group did not differ in terms of cavity closure (25.5% vs 21.1%; rate difference = 0.04, 95% CI: - 0.21-0.12; χ2 = 0.27, P = 0.60). Two patients who received chemotherapy and combined QBDT reported pruritus/nausea and vomiting. CONCLUSIONS: No significant improvement in culture conversion was observed for retreatment PTB with traditional Chinese medicine plus standard anti-TB regimen. However, QBDT as an adjunct therapy significantly promoted lesion absorption, thereby reducing lung injury due to Mycobacterium tuberculosis infection. TRIAL REGISTRATION: This trial is registered at ClinicalTrials.gov, NCT02313610.


Assuntos
Antituberculosos/uso terapêutico , Medicina Tradicional Chinesa/estatística & dados numéricos , Tuberculose Pulmonar/tratamento farmacológico , Adulto , Antituberculosos/efeitos adversos , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Retratamento/estatística & dados numéricos , Comprimidos , Tuberculose Pulmonar/patologia , Adulto Jovem
8.
J Dig Dis ; 21(3): 147-159, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32040250

RESUMO

Gut microbiota constitute the largest reservoir of the human microbiome and are an abundant and stable ecosystem-based on its diversity, complexity, redundancy, and host interactions This ecosystem is indispensable for human development and health. The integrity of the intestinal mucosal barrier depends on its interactions with gut microbiota. The commensal bacterial community is implicated in the pathogenesis of inflammatory bowel disease (IBD), including ulcerative colitis (UC). The dysbiosis of microbes is characterized by reduced biodiversity, abnormal composition of gut microbiota, altered spatial distribution, as well as interactions among microbiota, between different strains of microbiota, and with the host. The defects in microecology, with the related metabolic pathways and molecular mechanisms, play a critical role in the innate immunity of the intestinal mucosa in UC. Fecal microbiota transplantation (FMT) has been used to treat many diseases related to gut microbiota, with the most promising outcome reported in antibiotic-associated diarrhea, followed by IBD. This review evaluated the results of various reports of FMT in UC. The efficacy of FMT remains highly controversial, and needs to be regularized by integrated management, standardization of procedures, and individualization of treatment.


Assuntos
Colite Ulcerativa/terapia , Disbiose/terapia , Transplante de Microbiota Fecal/métodos , Microbioma Gastrointestinal/imunologia , Mucosa Intestinal/microbiologia , Colite Ulcerativa/imunologia , Colite Ulcerativa/microbiologia , Disbiose/imunologia , Disbiose/microbiologia , Humanos , Imunidade Inata , Mucosa Intestinal/imunologia , Resultado do Tratamento
9.
Gene ; 731: 144359, 2020 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-31935509

RESUMO

FMRP is an RNA-binding protein, loss of which causes fragile X syndrome (FXS). FMRP has several isoforms resulted from alternative splicing (AS) of fragile X mental retardation 1 (FMR1) gene, but their biological functions are still poorly understood. In the analysis of alternatively spliced FMR1 transcripts in the blood cells from a patient with FXS-like phenotypes (normal CGG repeats and no mutation in coding sequence of FMR1), we identified three novel FMR1 transcripts that include a previously unidentified microexon (46 bp), terming the exon 9a. This microexon exists widely in unaffected individuals, inclusion of which introduces an in-frame termination codon. To address whether these exon 9a-containing transcripts could produce protein by evading nonsense-mediated decay (NMD), Western blot was used to analysis blood cell lysate from unaffected individuals and a 34 kDa protein that consistent in size with the molecular weight of the predicted truncated protein produced from mRNA with this microexon was found. Meanwhile, treatment of peripheral blood mononuclear cells with an inhibitor of NMD (Cycloheximide) did not result in significant increase in exon 9a-containing transcripts. Using confocal immunofluorescence, we found the truncated protein displayed both nuclear and cytoplasmic localization in HEK293T and HeLa cells due to lacking C-terminal domains including KH2, NES, and RGG, while the full-length FMRP protein mainly localized in the cytoplasm. Therefore, we hypothesize that the inclusion of this microexon to generate exon 9a-containing transcripts may regulate the normal functionality of FMRP, and the dysregulation of normal FMRP due to increased exon 9a-containing alternatively spliced transcripts in that patient may be associated with the manifestation of FXS phenotype.


Assuntos
Proteína do X Frágil de Retardo Mental/genética , Proteína do X Frágil de Retardo Mental/metabolismo , Splicing de RNA/fisiologia , Adulto , Processamento Alternativo/fisiologia , Estudos de Casos e Controles , Núcleo Celular/metabolismo , Citoplasma/metabolismo , Éxons/genética , Síndrome do Cromossomo X Frágil/genética , Síndrome do Cromossomo X Frágil/metabolismo , Síndrome do Cromossomo X Frágil/patologia , Células HEK293 , Células HeLa , Humanos , Masculino , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Distribuição Tecidual
10.
Adv Healthc Mater ; 9(1): e1901229, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31750997

RESUMO

The emergence of drug-resistant bacteria is becoming the focus of global public health. Early-stage pathogen bioimaging will offer a unique perspective to obtain infection information in patients. A photoacoustic (PA) contrast agent based on functional peptide modified gold nanoparticles (AuNPs@P1) is developed. These nanoparticles can be specifically tailored surface peptides by bacterial overexpressed enzyme inducing in situ aggregation of the gold nanoparticles. In the meantime, the close aggregation based on the hydrogen bonding, π-π stacking, and hydrophobic interaction of the peptide residues on the surface of gold nanoparticles exhibits a typical redshifted and broadened plasmon band. In addition, this active targeting and following in situ stimuli-induced aggregation contribute to increased nanoparticle accumulation in the infected site. Finally, the dynamic aggregation of AuNPs@P1 results in dramatically enhanced photoacoustic signals for bioimaging bacterial infection in vivo with high sensitivity and specificity. It is envisioned that this PA contrast agent may provide a new approach for early detection of bacterial infection in vivo.


Assuntos
Infecções Bacterianas/diagnóstico por imagem , Ouro/química , Nanopartículas Metálicas/química , Técnicas Fotoacústicas/métodos , Animais , Infecções Bacterianas/microbiologia , Colagenases/metabolismo , Meios de Contraste/química , Feminino , Ligação de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Camundongos , Camundongos Endogâmicos BALB C , Peptídeos/síntese química , Peptídeos/química , Staphylococcus aureus/patogenicidade , Ressonância de Plasmônio de Superfície
11.
Angew Chem Int Ed Engl ; 58(40): 14197-14201, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31385423

RESUMO

Bimetal-S-O composites have been rarely researched in electrochemical reduction of CO2 . Now, an amorphous Ag-Bi-S-O decorated Bi0 catalyst derived from Ag0.95 BiS0.75 O3.1 nanorods by electrochemical pre-treatment was used for catalyzing eCO2 RR, which exhibited a formate FE of 94.3 % with a formate partial current density of 12.52 mA cm-2 at an overpotential of only 450 mV. This superior performance was attributed to the attached amorphous Ag-Bi-S-O substance. S could be retained in the amorphous region after electrochemical pre-treatment only in samples derived from metal-S-O composites, and it would greatly enhance the formate selectivity by accelerating the dissociation of H2 O. The existence of Ag would increase the current density, resulting in a higher local pH, which made the role of S in activating H2 O more significantly and suppressed H2 evolution more effectively, thus endowing the catalyst with a higher formate FE at low overpotentials.

12.
Artigo em Inglês | MEDLINE | ID: mdl-31998705

RESUMO

L-ornithine, a valuable non-protein amino acid, has a wide range of applications in the pharmaceutical and food industries. Currently, microbial fermentation is a promising, sustainable, and environment-friendly method to produce L-ornithine. However, the industrial production capacity of L-ornithine by microbial fermentation is low and rarely meets the market demands. Various strategies have been employed to improve the L-ornithine production titers in the model strain, Corynebacterium glutamicum, which serves as a major indicator for improving the cost-effectiveness of L-ornithine production by microbial fermentation. This review focuses on the development of high L-ornithine-producing strains by metabolic engineering and reviews the recent advances in breeding strategies, such as reducing by-product formation, improving the supplementation of precursor glutamate, releasing negative regulation and negative feedback inhibition, increasing the supply of intracellular cofactors, modulating the central metabolic pathway, enhancing the transport system, and adaptive evolution for improving L-ornithine production.

13.
World J Clin Cases ; 7(24): 4366-4376, 2019 Dec 26.
Artigo em Inglês | MEDLINE | ID: mdl-31911920

RESUMO

BACKGROUND: Inflammatory myofibroblastic tumor (IMT) is a rare mesenchymal tumor that is characterized by spindle cells differentiated from muscle fibroblasts and infiltration of various types of inflammatory cells. IMT can occur at any age and at any anatomic site. The most common location of IMT is the bladder in the genitourinary tract. Only scarce cases of kidney IMT have been reported in the literature. CASE SUMMARY: A 77-year-old woman, with a history of bilateral renal calculus for 15 years, was admitted to the Department of Urology of our hospital complaining of recurrent painless gross hematuria for one month. The treatment with cephalosporin was ineffective. Computed tomography imaging showed a mixed density and slightly heterogeneously enhanced lesion in the middle pole of the left kidney and ipsilateral adrenal enlargement. The patient underwent surgical treatment by retroperitoneoscopic left radical nephrectomy plus adrenalectomy. A large number of typical spindle cells surrounded by plasma cells and lymphocytes were observed microscopically. Immunohistochemical analyses indicated that these spindle cells were positive for vimentin, cytokeratin (CK), Ki-67, CK7, CD34, and CD31 and were focally positive for CD10 and anaplastic lymphoma kinase (ALK-1). Thus, a diagnosis of IMT was made definitively. The patient recovered well after operation, and no recurrence or metastasis was noted during the 22-mo follow-up. CONCLUSION: Since kidney IMT is very rare and lacks characteristic clinical manifestation, it is easily misdiagnosed as a malignant tumor before operation. Surgery remains the best choice for diagnosis and treatment, and such cases must be followed carefully because of the uncertain biological behavior of this tumor. This report suggests that renal calculus may be one of the causes of IMT, but further investigation is necessary to prove it.

14.
Arch Gynecol Obstet ; 298(5): 861-871, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30220024

RESUMO

OBJECTIVE: The aim of this meta-analysis is to explore the beneficial role of granulocyte colony-stimulating factor (G-CSF) on infertile women under artificial reproduction technology treatment. METHOD: Medline, Embase and ISI Web of Science databases were searched to identify relevant randomized control trials. Studies before July, 2017 were included for primary screening. Meta-analysis of the total and subgroup patients was conducted, and relative risks (RRs) and their 95% confidence intervals (95% CI) were calculated by a fixed-effect model if no heterogeneity (evaluated as I2 statistic) existed. Otherwise, a random-effects model was adopted. Subgroup analysis was performed by administrating route or clinical indication. Egger test and influence analysis were conducted to evaluate the publication bias and study power, respectively. RESULTS: The final selection enrolled 10 RCTs, involving 1016 IVF-ET cycles (521 distributed to the G-CSF group and 495 to the control). Compared with control group, G-CSF administration could significantly improve clinical pregnancy rate (CPR, RR 1.89, 95% CI 1.53-2.33), while it had no beneficial effect on embryo implantation rate (IR, RR 1.84, 95% CI 0.84-4.03). The subgroup analysis by administration route showed that both uterine infusion and subcutaneous injection can produce a substantial increase in CPR, with the pooled RRs (95% CI) 1.46 (1.04-2.05) and 2.23 (1.68-2.95), respectively. Nevertheless, most of included RCTs dealt with the RIF subjects, and the pooled analysis of this data showed a higher PR and IR in G-CSF group as compared to that in the control, with the RRs (95% CI) 2.07 (1.64-2.61) and 1.52 (1.08-2.14), respectively. Egger regression test did not demonstrate any significance for the publication bias. CONCLUSION: G-CSF administration has a beneficial role on the clinical outcome after embryo transfer by both routes of local infusion and systematic administration, especially for the cases with RIF. Further RCTs are needed to investigate the role of G-CSF in thin endometrium patients.


Assuntos
Transferência Embrionária/métodos , Fertilização In Vitro/métodos , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Infertilidade Feminina/tratamento farmacológico , Adulto , Feminino , Fator Estimulador de Colônias de Granulócitos/farmacologia , Humanos , Infertilidade Feminina/patologia , Gravidez
15.
Biomed Environ Sci ; 31(5): 399-402, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29866223

RESUMO

Infrasound widely exists in nature, our living condition, productive and traffic environment. Gastrointestinal tract is relatively sensitive to infrasound. However, the effect of infrasound on gastrointestinal function is unclear. Therefore, the purpose of our study was to observe the effects of infrasound on gastric motility and gastric morphology and to assess the expression of nitric oxide synthase (NOS) in gastric antrum after exposure to infrasound of 8 Hz - 130 dB for 2 hours per day for 14 consecutive days. Gastric motility was assessed by gastric fluid-emptying rate. Gastric morphology was evaluated by HE. The expression of NOS was measured by tissue microarray technology. The results would contribute to understand the role of infrasound in gastroenterology, and help to explain the mechanism of infrasound on gastroenterology.


Assuntos
Motilidade Gastrointestinal , Óxido Nítrico Sintase/metabolismo , Som/efeitos adversos , Estômago , Animais , Regulação Enzimológica da Expressão Gênica , Masculino , Ratos
16.
Nan Fang Yi Ke Da Xue Xue Bao ; 38(2): 234-238, 2018 Feb 20.
Artigo em Chinês | MEDLINE | ID: mdl-29502066

RESUMO

OBJECTIVE: To compare the expression of pinopodes, the marker of endometrial receptivity, during the implantation window in Kunming mice stimulated with two different doses of raloxifene (RAL). METHODS: Forty-eight 8-week-old female Kunming mice were randomly divided into 4 groups (n=12), namely saline group, clomiphene citrate (CC, 18 mg/kg) group, RAL (33 mg/kg) group and RAL (44 mg/kg group). In each group, the mice received intragastric administration of 1 mL of normal saline containing CC or RAL at the specified doses or saline only as indicated for ovulation induction, once daily for 2 days. The mice received then injection with 5 IU human chorionic gonadotropin (HCG) and mated and on day 4.5 of gestation, the pregnant mice were sacrificed for examination of the uterus with scanning electron microscopy. RESULTS: Abundant and well developed pinopodes were observed in the endometrium of the mice in the 2 RAL groups and in the saline control group. The mice in CC group showed obviously reduced endometrial pinopodes with poor development. CONCLUSIONS: RAL at two different doses does not obviously affect the expression of pinopodes in the uterine epithelium of mice, suggesting the safety of RAL at these two doses for ovulation induction without causing adverse effects on endometrial receptivity.


Assuntos
Implantação do Embrião , Endométrio/fisiologia , Indução da Ovulação , Cloridrato de Raloxifeno/administração & dosagem , Animais , Gonadotropina Coriônica/administração & dosagem , Feminino , Humanos , Camundongos , Gravidez , Cloridrato de Raloxifeno/farmacologia , Distribuição Aleatória
17.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 26(1): 132-135, 2018 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-29397831

RESUMO

OBJECTIVE: To compare the diagnostic values of CD64 infection index, C-reactive protein (CRP), procalcitonin (PCT) and the percentage of neutrophils (NEU%) in leukemia patients complicated with bacterial infection. METHODS: Sixty cases of leukemia complicated with bacterial infection (combination with infection group), 60 cases of leukemia without bacterial infection (non-combination with infection group) and 60 cases of healthy persons (control group) were selected in our hospital. CD64 infection index, CRP, PCT and NEU% were detected in the 3 group. RESULTS: CD64 infection index, CRP, PCT and NEU% in combination with infection group were significantly higher than those in the non-combination with infection group and also significantly higher than those in the control group (all P<0.05). The CD64 infection index, CRP, PCT and NEU% in the non-combination with infection group were significantly higher than those in the control group (all P<0.05). The sensitivities of CD64, CRP, PCT and NEU% in the diagnosis of the leukemia with bacterial infection were 71.06%, 84.86%, 66.93% and 59.25% respectively, and the specificities of CD64, CRP, PCT and NEU% were 91.46%, 75.94%, 88.79% and 85.36% respectively. CONCLUSION: Compared with CRP, PCT and NEU%, CD64 infection index for diagnosis of leukemia complicated with bacterial infection has higher specificity, which is helpful for the early diagnosis of the disease.


Assuntos
Leucemia , Infecções Bacterianas , Biomarcadores , Proteína C-Reativa , Calcitonina , Peptídeo Relacionado com Gene de Calcitonina , Humanos , Receptores de IgG
18.
Mol Med Rep ; 16(4): 4603-4612, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28849186

RESUMO

The development of targeted tyrosine kinase inhibitors (TKIs) has succeeded in altering the course of chronic myeloid leukemia (CML). However, a number of patients have failed to respond or experienced disease relapse following TKI treatment. Proviral integration site for moloney murine leukemia virus­1 (PIM­1) is a serine/threonine kinase that participates in regulating apoptosis, cell cycle, signal transduction and transcriptional pathways, which are associated with tumor progression, and poor prognosis. SMI­4a is a selective PIM­1 kinase inhibitor that inhibits PIM­1 kinase activity in vivo and in vitro. The present study aimed to explore the mechanism underlying the antitumor effect of SMI­4a in K562 and imatinib­resistant K562 (K562/G) cell lines. It was demonstrated that SMI­4a inhibited the proliferation of K562 and K562/G cells using a WST­8 assay. The Annexin V­propidium iodide assay demonstrated that SMI­4a induced apoptosis of K562 and K562/G cells in a dose­, and time­dependent manner. Furthermore, Hoechst 33342 staining was used to verify the apoptosis rate. The clone formation assay revealed that SMI­4a significantly inhibited the colony formation capacity of K562 and K562/G cells. Western blot analysis demonstrated that SMI­4a decreased phosphorylated (p)­Ser9­glycogen synthase kinase (GSK) 3ß/pGSK3ß and inhibited the translocation of ß­catenin. In addition, the downstream gene expression of apoptosis regulator Bax and poly(ADP­ribose) polymerase­1 was upregulated, and apoptosis regulator Bcl­2 and Myc proto­oncogene protein expression levels were downregulated. Immunofluorescence results demonstrated changes in the expression level of ß­catenin in the plasma and nucleus. The results of the present study suggest that SMI­4a is an effective drug to use in combination with current chemotherapeutics for the treatment of imatinib-resistant CML.


Assuntos
Antineoplásicos/farmacologia , Compostos de Benzilideno/farmacologia , Glicogênio Sintase Quinase 3 beta/metabolismo , Proteínas Proto-Oncogênicas c-pim-1/antagonistas & inibidores , Tiazolidinedionas/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/metabolismo , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Inibidores de Proteínas Quinases/farmacologia , Transporte Proteico , beta Catenina/metabolismo
19.
Clin Chim Acta ; 471: 243-247, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28624500

RESUMO

BACKGROUND: Polycystic ovary syndrome (PCOS) is commonly characterized by obesity, insulin resistance (IR), hyperandrogenemia and hirsutism. Following the reported relationship between phoenixin-14 and gonadotropin production in rat hypothalamic-pituitary-gonadal axis, the present study was designed to investigate the circulating concentrations of phoenixin-14 and their associations with the concentrations of sex hormones including luteinizing hormone (LH), follicular stimulating hormone (FSH), estradiol (E2), progesterone (P4) and total testosterone (TT) in PCOS patients. METHODS: A total of 41 women with diagnosed PCOS using Rotterdam criteria and 37 healthy individuals were enrolled in the study. RESULTS: Serum phoenixin-14 concentration in PCOS patients (n=41) was 0.515±0.044ng/ml, significantly higher than that in healthy controls (0.289±0.046ng/ml, n=37). PCOS patients had higher serum LH, dehydroepiandrosterone and fasting blood glucose concentrations, and higher index of homeostasis model of assessment-IR than those in healthy women. Correlation analysis showed significantly positive correlations of phoenixin-14 with LH, FSH, TT, P4, BMI and nesfatin-1 concentrations, and significantly negative correlations with E2 and serum insulin (FSI) concentrations, respectively. CONCLUSIONS: Compared to control women, PCOS patients had significantly increased serum phoenixin-14, LH and androgen concentrations. The positive correlations of phoenixin-14 concentrations with LH and TT concentrations suggest a possible role of phoenixin-14 in the development of PCOS.


Assuntos
Proteínas de Ligação ao Cálcio/sangue , Proteínas de Ligação a DNA/sangue , Hormônio Luteinizante/sangue , Proteínas do Tecido Nervoso/sangue , Neuropeptídeos/sangue , Síndrome do Ovário Policístico/sangue , Adulto , Feminino , Humanos , Nucleobindinas , Adulto Jovem
20.
Hepatol Int ; 11(3): 221-241, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28405790

RESUMO

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


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/epidemiologia , Colestase/induzido quimicamente , Suplementos Nutricionais/efeitos adversos , Hepatopatias/epidemiologia , Antibacterianos/efeitos adversos , Antibacterianos/toxicidade , Anti-Infecciosos/efeitos adversos , Anti-Infecciosos/toxicidade , Doença Hepática Induzida por Substâncias e Drogas/patologia , Doença Hepática Induzida por Substâncias e Drogas/fisiopatologia , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , China/epidemiologia , Colestase/complicações , Colestase/patologia , Diagnóstico Diferencial , Suplementos Nutricionais/toxicidade , Medicamentos de Ervas Chinesas/efeitos adversos , Feminino , Guias como Assunto , Humanos , Incidência , Hepatopatias/patologia , Hepatopatias/fisiopatologia , Hepatopatias/terapia , Masculino , Prognóstico , Fatores de Risco , Índice de Gravidade de Doença
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