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1.
EBioMedicine ; 41: 276-285, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30824384

RESUMO

BACKGROUND: The prognostic roles of three common lymph node staging schemes, number of positive lymph nodes (pN), lymph node ratio (LNR) and log odds of positive lymph nodes (LODDS) in small bowel adenocarcinoma (SBA) are unclear. We assessed their prognostic ability in SBA. METHODS: A total of 2128 patients diagnosed with SBA between 1988 and 2010 from the Surveillance, Epidemiology, and End Results (SEER) database and 186 patients from 15 hospitals in France and China were identified. We evaluated the prognostic ability of the schemes in both continuous and stratified patterns using R2, Harrell's C, and time-dependent receiver operating characteristic curve analyses. FINDINGS: For continuous pattern, the LODDS had a better capacity of discrimination and higher accuracy of prognosis than pN and LNR. Similarly, the stratified LODDS classification had a better performance of discrimination and higher accuracy of prognosis than the pN and LNR classification. The multivariable model using the LODDS classification also showed superiorly predictive accuracy and discriminatory capacity to those of the 7th and, 8th TNM node and LNR classification. These results were fully validated in an independent international multicentre cohort. INTERPRETATION: The LODDS scheme showed a better prognostic performance than the LNR or pN schemes in patients with SBA regardless of continuous or stratified pattern. The LODDS scheme could serve as an auxiliary to lymph node staging systems in future revisions of the American Joint Committee on Cancer (AJCC) manual. FUND: This work was funded by the Zhejiang Province Natural Science Fund of China.


Assuntos
Adenocarcinoma/patologia , Neoplasias Intestinais/patologia , Linfonodos/patologia , Adenocarcinoma/classificação , Adenocarcinoma/mortalidade , Área Sob a Curva , Estudos de Coortes , Bases de Dados Factuais , Feminino , Humanos , Neoplasias Intestinais/classificação , Neoplasias Intestinais/mortalidade , Estimativa de Kaplan-Meier , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estadiamento de Neoplasias , Prognóstico , Curva ROC
2.
J Neuroinflammation ; 16(1): 52, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30823934

RESUMO

BACKGROUND: Amlexanox (ALX), a TBK1 inhibitor, can modulate immune responses and has anti-inflammatory properties. To investigate its role in regulating the progression of experimental autoimmune encephalomyelitis (EAE), we studied the effect of ALX on the maturation of dendritic cells (DCs) and the responses of effector and regulatory T cells (Tregs). METHODS: In vitro, bone marrow-derived DCs (BMDCs) were cultured and treated with ALX. Their proliferation, maturation, and their stimulatory function to induce T cells responses were detected. In vivo, the development of EAE from different groups was recorded. At the peak stage of disease, HE, LFB, and electronic microscope (EM) were used to evaluate inflammation and demyelination. Maturation of splenic DC and Th1/Th17/Treg response in the CNS and peripheral were also detected. To further explore the mechanism underlying the action of ALX in DC maturation, the activation of TBK1, IRF3, and AKT was analyzed. RESULTS: Our data indicated that ALX significantly inhibited the proliferation and maturation of BMDCs, characterized by the reduced MHCII, a co-stimulatory molecule, IL12, and IL-23 expression, along with morphological alterations. Co-culture of ALX-treated BMDCs inhibited allogeneic T cell proliferation and MOG-specific T cell response. In EAE mice, ALX significantly attenuated the EAE development by decreasing inflammatory infiltration and demyelination in the spinal cords, accompanied by reduced frequency of splenic pathogenic Th1 and Th17 cells and increased Tregs. Moreover, ALX treatment decreased Th1 and Th17 cytokines, but increased Treg cytokines in the CNS and spleen. Notably, ALX treatment reduced the frequency and expression of CD80 and CD86 on splenic DCs and lowered IL-12 and IL-23 secretion, further supporting an impaired maturation of splenic DCs. In addition, ALX potently reduced the phosphorylation of IRF3 and AKT in BMDC and splenic DCs, both of which are substrates of TBK1 and associated with DC maturation. CONCLUSIONS: ALX, a TBK1 inhibitor, mitigated EAE development by inhibiting DC maturation and subsequent pathogenic Th1 and Th17 responses while increasing Treg responses through attenuating the TBK1/AKT and TBK1/IRF3 signaling.


Assuntos
Aminopiridinas/farmacologia , Células Dendríticas/efeitos dos fármacos , Encefalomielite Autoimune Experimental/imunologia , Linfócitos T/efeitos dos fármacos , Animais , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/imunologia , Fator Regulador 3 de Interferon/efeitos dos fármacos , Fator Regulador 3 de Interferon/metabolismo , Ativação Linfocitária/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Proteínas Serina-Treonina Quinases/efeitos dos fármacos , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Linfócitos T/imunologia , Linfócitos T Reguladores/efeitos dos fármacos , Linfócitos T Reguladores/imunologia , Células Th1/efeitos dos fármacos , Células Th1/imunologia , Células Th17/efeitos dos fármacos , Células Th17/imunologia
3.
Ying Yong Sheng Tai Xue Bao ; 29(12): 3995-4003, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30584726

RESUMO

Geographic Object-Based Image Analysis (GEOBIA) was a product under the background of increasing high-resolution remote sensing data. How to improve the accuracy and efficiency of classification of high-resolution images is one of the important topics in image processing. After objects segmented multiscale by QuickBird image was classified, the efficiency of C5.0, C4.5, and CART decision trees in object-oriented classification of forest areas was analyzed. The accuracy of those three methods were compared with kNN method. The eCognition software was used to multiscale segmentation of remote sensing images, with the result showing that 90 and 40 were the optimal scales. After separating vegetation and non-vegetation at 90 scale, 21 features such as spectrum, texture and shape of different vegetation types were extracted at 40 scale, knowledge mining was carried out by using C5.0, C4.5 and CART decision tree algorithms respectively, and classification rules were automatically established. The vegetation area was classified based on the classification rules and the classification accuracy of different methods was compared. The results showed that the classification accuracy based on decision-tree was higher than that of the traditional kNN method. The accuracy of C5.0 method was the best, with the overall accuracy and Kappa coefficient reaching 90.0% and 0.87, respectively. The decision tree algorithm could effectively improve the accuracy in classification of forest species. The Boosting algorithm of the C5.0 decision tree had the most significant improvement on the classification.


Assuntos
Monitoramento Ambiental/métodos , Florestas , Tecnologia de Sensoriamento Remoto , Algoritmos , Árvores de Decisões , Processamento de Imagem Assistida por Computador
4.
Molecules ; 23(11)2018 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-30423818

RESUMO

Glioma is the common highly malignant primary brain tumor. However, the molecular pathways that result in the pathogenesis of glioma remain elusive. In this study, we found that microRNA-103 (miR-103), microRNA-195 (miR-195), or microRNA-15b (miR-15b), which all have the same 5' "seed" miRNA portion and share common binding sites in the SALL4 3'-untranslated region (UTR), were downregulated in glioma tissues and cell lines. These miRNAs suppressed glioma cell proliferation, migration, and invasion, induced cell apoptosis, and decreased the level of the SALL4 protein, but not that of SALL4 mRNA, which was identified as a direct target of all three miRNAs. The caspase-3/7 activity expression in U251 cells overexpressing these miRNAs was rescued during SALL4 upregulation. An obvious inverse correlation was observed between SALL4 and miR-103 or miR-195 expression levels in clinical glioma samples. Moreover, enforced expression of SALL4 stimulated cell proliferation, migration, and invasion. In conclusion, these data suggest that miR-103, miR-195, and miR-15b post-transcriptionally downregulated the expression of SALL4 and suppressed glioma cell growth, migration, and invasion, and increased cell apoptosis. These results provide a potential therapeutic target that may downregulate SALL4 in glioma.

5.
Zootaxa ; 4497(1): 99-110, 2018 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-30313667

RESUMO

Grasshoppers (Orthoptera: Acridoidea) are the main pests in agriculture, animal husbandry and forestry, and some species of grasshoppers can cause serious disaster. Taxonomy is the basis of pest control. Traditional morphological identification is time-consuming and laborious. It may be due to the existence of cryptic species or the limited number of morphologists, making the identification extremely unstable. In recent years, with the development of molecular systematics, DNA barcoding technology has been applied to environment, ecology, quarantine and so on. This study focuses on testing the feasibility of DNA barcoding in the species identification for superfamily Acridoidea. Sequences of the cox1 gene were obtained from 245 individuals of 43 species of Acridoidea and one species of Tetrigoidea as outgroup from Hebei Province. Phylogenetic, genetic distance and sequence difference threshold analyses using the Maximum Likelihood (ML), Automatic Barcode Gap Discovery (ABGD) and Molecular Defined Operational Taxonomic Units (MOTU) methods, respectively, were performed for obtained sequences and the 139 additional sequences of 21 species downloaded from GenBank. The results have shown that 40, 33, and 35 species among the 48 species are consistent with the traditional morphological classification based on the phylogenetic tree, ABGD and MOTU results, respectively and the DNA barcoding technology is very efficient and helpful for identifying the species of the superfamily Acridoidea; however, the morphological approach is still playing a key role in the species identifications. It also indicates that the cox1 gene is suitable for the phylogeny of genera and species level, but it is not suitable for the phylogenetic relationship of the advanced taxa such as families.

6.
Curr Med Sci ; 38(4): 640-647, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30128873

RESUMO

This study aimed to assess the relationship of OAS2 rs739901 5,-flanking C/A polymorphisms with the susceptibility to Enterovirus-71 (EV71) infection. We investigated 294 hand-foot-mouth disease (HFMD) Chinese children with EV71 infection (165 mild cases and 129 encephalitis cases). The improved multiplex ligation detection reaction (iMLDR) technique was used to test the genotypes. In EV71-infected patients, the CA genotype distribution (P=0.007), A allele frequency (OR 1.32,95% CI 1.0-1.7, P=0.034) and CA+AA carriage frequency (P=0.003) of OAS2 rs739901 5'-flanking were obviously elevated as compared with controls, but there were no statistically significant differences between mild cases and encephalitis cases. In EV71-infected patients, the counts of white blood cells (P=0.034) and blood glucose concentrations (P=0.042) were raised in A carriers (CA+AA). Among different genotypes of encephalitis cases, the contents of cerebrospinal fluid (CSF) showed no significant differences. IFN-γ levels in EV71-infected patients were higher than those in controls (mild group vs. control group, P<0.01; encephalitis group vs. control group, P<0.01;). In encephalitis cases, IFN-γ levels were reduced (P<0.05) in A carriers compared to CC genotype, however, there were no significant differences between genotypes CA and AA (P=0.226). These findings suggest that OAS2 rs739901 5'-flanking C/A genetic polymorphisms involve the susceptibility to EV71 infection, and A allele might be a risk factor of the susceptibility to EV-71 infection.


Assuntos
2',5'-Oligoadenilato Sintetase/genética , Doença de Mão, Pé e Boca/genética , Polimorfismo de Nucleotídeo Único , Glicemia/metabolismo , Estudos de Casos e Controles , Criança , Pré-Escolar , China , Feminino , Frequência do Gene , Doença de Mão, Pé e Boca/sangue , Heterozigoto , Humanos , Interferon gama/sangue , Masculino
7.
J Cell Biochem ; 119(10): 8249-8259, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29968931

RESUMO

Currently, the combination of ultrasonography and fine-needle aspiration biopsy (FNAB) can not discriminate between benign and malignant tumor of thyroid in some cases. The main issue in assessing the patients with thyroid nodules is to distinguish thyroid cancer from benign nodules, and reduce diagnostic surgery. To identify potential molecular biomarkers for patients with indeterminate FNAB, we explored the differentially expressed genes (DEGs) and differentially expressed long non-coding RNAs (DElncRNAs) in TCGA database between 318 papillary thyroid carcinoma (PTC) tissues and 35 normal thyroid gland tissues by DESeq R. Furthermore, DEGs were verified by gene expression profile GSE33630. Ten top DEGs and DElncRNAs were identified as candidate biomarkers for diagnosis and Lasso (Least Absolute Shrinkage and Selection Operator) logistic regression analysis were performed to improve the diagnostic accuracy of them. Besides, partial molecular biomarkers of top DEGs and DElncRNAs were closely related to the tumor stage (T), lymph node metastasis (N), metastasis (M) and pathological stage of PTC, which could reflect behavior of tumor progression. According to multivariate Cox analysis, the combination of two DEGs (METTL7B and KCTD16) and two DElncRNAs (LINC02454 and LINC02471) could predict the outcome in a more exact way. In conclusion, top DEGs and DElncRNAs could raise diagnosis of PTC in indeterminate FNAB specimens, and some could function as molecule biomarkers for tumor progression and prognosis.

8.
Medicine (Baltimore) ; 97(29): e11599, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30024565

RESUMO

There is little information regarding the predictive ability of albumin-bilirubin grades (ALBI) plus platelet-to-lymphocyte ratio (PLR) in patients with hepatocellular carcinoma (HCC) following liver resection. In this study, we aimed to evaluate the prognostic power of the ALBI-PLR score in patients with hepatitis B virus-related (HBV-related) HCC within Barcelona Clinic Liver Cancer (BCLC) stage A after liver resection.Around 475 patients were included in this study. Patients with preoperative ALBI grades 1, 2, or 3 were allocated a score of 0, 1, or 2, respectively. Patients with preoperative PLR >150 or ≤150 were allocated a score of 0 or 1, respectively. The ALBI-PLR score was the summary of the ALBI and PLR scores.During the follow-up period, 256 patients experienced recurrence, and 150 patients died. Multivariate analysis revealed tumor size, multiple tumors, positive HBV-DNA load, cirrhosis, and ALBI-PLR score as being independently associated with postoperative recurrence, whereas tumor size, high preoperative α-fetoprotein level, and ALBI-PLR score were independent risk factors for postoperative mortality. HCC patients with high ALBI-PLR score had poor recurrence-free and overall survival.The preoperative ALBI-PLR score is a surrogate marker for predicting HBV-related HCC patient's prognosis after liver resection. A high ALBI-PLR score is associated with a high incidence of postoperative recurrence and mortality.


Assuntos
Bilirrubina/sangue , Carcinoma Hepatocelular/sangue , Neoplasias Hepáticas/sangue , Contagem de Linfócitos/métodos , Contagem de Plaquetas/métodos , Albumina Sérica/análise , Adulto , Idoso , Biomarcadores Tumorais/análise , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/cirurgia , Feminino , Seguimentos , Hepatectomia , Hepatite B/complicações , Humanos , Estimativa de Kaplan-Meier , Fígado/patologia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Prognóstico , Estudos Retrospectivos , Medição de Risco , Fatores de Risco
9.
Onco Targets Ther ; 11: 3119-3127, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29872323

RESUMO

Background: Despite wide usage, peripherally inserted central catheter (PICC)-related venous thromboembolism (VTE) is common in nasopharyngeal carcinoma (NPC) patients. Patients and methods: This was a retrospective cohort study of NPC patients with PICC insertions from February 2, 2007 to December 25, 2014 in Sun Yat-Sen University Cancer Centre. Univariable and multivariable logistic regression analyses were used to estimate odds ratios (ORs) with 95% confidence intervals (CIs) for the correlations between risk factors and symptomatic PICC-VTE. Results: Of the 1,363 NPC patients, 76 developed symptomatic VTE. In univariable analysis, body mass index (BMI), Eastern Cooperative Oncology Group (ECOG) score, metastasis stage (M stage), and VTE history were associated with symptomatic PICC-VTE. Following multivariable adjustments, BMI (OR 0.900, p=0.007), ECOG score (OR 4.162, p=0.011), M stage (OR 2.717, p=0.019), and VTE history (OR 109.772, p<0.001) were still statistically significant. Conclusion: PICC-VTE is a common complication in NPC patients, with an incidence of 5.6% in our analysis. Those with VTE history and lower BMI and worse ECOG performance score metastatic NPC patients are more susceptible to symptomatic PICC-related thrombosis and thus may require prophylactic anticoagulation.

10.
Int J Immunogenet ; 45(4): 225-229, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29799674

RESUMO

The human leucocyte antigen (HLA) is the most polymorphic region of the human genome. Compared with Sanger-sequencing-based typing (SBT) methods, next-generation sequencing (NGS) has significantly higher throughput and depth sequencing characteristics, having dramatic impacts on HLA typing in clinical settings. Here, we performed NGS technology with Ion Torrent S5 platform to evaluate the potential four novel HLA alleles detected in five donors from Chinese Marrow Donor Program (CMDP, Shaanxi Province) during routine Sanger SBT testing. We also predicted the highest estimated relative frequency novel allele-bearing haplotypes according to their phenotypes and HaploStats database. NGS assays, as it provided the phase-defined and complete sequencing information, undoubtedly increase novel allele identification which will greatly enrich HLA database and provide more information for donor selection.


Assuntos
Alelos , Antígenos HLA/genética , Sequenciamento de Nucleotídeos em Larga Escala , Doadores de Tecidos , Grupo com Ancestrais do Continente Asiático , China , Feminino , Humanos , Masculino
11.
Clin Exp Med ; 18(3): 433-443, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29696462

RESUMO

The correlation between improvement in longitudinal liver stiffness and fibrosis regression has not been properly evaluated during long-term antiviral therapy in chronic hepatitis B (CHB) patients. In this study, liver stiffness was serially performed by FibroScan® every 26 weeks in a prospective cohort of CHB patients receiving entecavir. Results were compared with liver biopsies at baseline and week 78. A total of 120 treatment-naïve CHB patients were analyzed, in which 54 (45%) patients had fibrosis regression at 78 weeks of antiviral therapy. Liver stiffness measurement presented as a rapid-to-slow decline pattern and decreased more significantly in patients with fibrosis regression than those without improvement in fibrosis at week 78 (- 46.4 vs. - 28.6%, P < 0.001). Multivariate analysis revealed that percentage decline of 52-week and 78-week liver stiffness from baseline was independent predictive factors for fibrosis regression (OR = 46.6, P < 0.001; OR = 17.8, P = 0.002, respectively). Moreover, percentage decline of 78-week liver stiffness was moderately predictive of fibrosis regression (AUROC = 0.694, P < 0.001), while the optimal cutoff values were different between non-cirrhosis and cirrhosis patients (38 vs. 45%). Fibrosis regression could be predicted with a high positive predictive value (96%) in non-cirrhosis patients and could be excluded with a high negative predictive value (94%) in cirrhosis patients. In conclusion, serial liver stiffness measurement could be applied for longitudinal monitoring of fibrosis status in CHB patients. Continuous decline of liver stiffness after effective antiviral treatment could partially reflect fibrosis regression at an optimal cutoff value.


Assuntos
Antivirais/uso terapêutico , Guanina/análogos & derivados , Hepatite B Crônica/diagnóstico por imagem , Cirrose Hepática/diagnóstico por imagem , Fígado/diagnóstico por imagem , Monitorização Fisiológica/métodos , Adulto , Biópsia , Técnicas de Imagem por Elasticidade , Feminino , Guanina/uso terapêutico , Hepacivirus/efeitos dos fármacos , Hepacivirus/crescimento & desenvolvimento , Hepacivirus/patogenicidade , Hepatite B Crônica/tratamento farmacológico , Hepatite B Crônica/patologia , Hepatite B Crônica/virologia , Humanos , Fígado/efeitos dos fármacos , Fígado/patologia , Fígado/virologia , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/patologia , Cirrose Hepática/virologia , Masculino , Pessoa de Meia-Idade , Monitorização Fisiológica/instrumentação , Análise Multivariada , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Indução de Remissão
12.
Medicine (Baltimore) ; 97(12): e0226, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29561452

RESUMO

Minimal information is available concerning platelet-albumin-bilirubin (PALBI) grades in patients with hepatocellular carcinoma (HCC) following liver resection. This study aimed to investigate the predictive ability of PALBI grades in patients with a Child-Pugh class A score and hepatitis B virus-related (HBV-related) HCC after liver resection.The data of patients with HBV-related HCC who underwent liver resection from 2010 to 2017 at our center were reviewed (n = 785). Cox regression was used to determine factors independently associated with postoperative recurrence and mortality. The area under the receiver operating characteristic curve (AUC) was used to estimate the predictive accuracy of different tools.During the follow-up period, 505 (64.3%) patients experienced recurrence, and 374 (47.6%) patients died. Multivariate analysis revealed that the tumor-node-metastasis (TNM) stage (HR = 1.591, 95%CI = 1.414-1.789, P < .001), PALBI grade (HR = 1.326, 95%CI = 1.139-1.544, P < .001), a high AFP level (HR = 1.382, 95%CI = 1.158-1.649, P < .001) and transfusion (HR = 1.364, 95%CI = 1.087-1.712, P = 0.007) were independently associated with recurrence. Additionally, microvascular invasion (HR = 1.674, 95%CI = 1.292-2.169, P < .001), beyond the Milan criteria (HR = 0.477, 95%CI = 0.346-0.657, P < .001), PALBI grade (HR = 1.356, 95%CI = 1.151-1.598, P < .001), a high AFP level (HR = 1.542, 95%CI = 1.252-1.900, P < .001), and transfusion (HR = 1.548, 95%CI = 1.199-1.999, P = 0.001) adversely impacted the overall survival. The AUCs of the PALBI grades for postoperative recurrence and mortality were significantly higher than the albumin-bilirubin grade and Child-Pugh score. The prognostic significance of the PALBI grade for postoperative recurrence and mortality was maintained when stratified by the TNM stage.The preoperative PALBI grade is a surrogate marker for the postoperative prognosis in patients with HBV-related HCC after liver resection.


Assuntos
Bilirrubina/sangue , Carcinoma Hepatocelular/sangue , Hepatite B/complicações , Neoplasias Hepáticas/sangue , Fígado/cirurgia , Albumina Sérica/metabolismo , Biomarcadores Tumorais/sangue , Carcinoma Hepatocelular/complicações , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/cirurgia , Feminino , Seguimentos , Hepatite B/sangue , Hepatite B/mortalidade , Vírus da Hepatite B , Humanos , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Prognóstico , Estudos Retrospectivos , Índice de Gravidade de Doença , Resultado do Tratamento
13.
Int J Ophthalmol ; 11(2): 208-215, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29487808

RESUMO

AIM: To explore the effect of the Notch signaling pathway on retinal ganglion cells (RGCs) and optic nerve in rats with acute ocular hypertension (OH). METHODS: Totally 48 Sprague-Dawley (SD) rats were included, among which 36 rats were selected to establish acute OH models. OH rats received a single intravitreal injection of 2 µL phosphate buffered solution (PBS) and another group of OH rats received a single intravitreal injection of 10 µmol/L γ-secretase inhibitor (DAPT). Quantitative real-time polymerase chain reaction (qPCR) and Western blot assay were adopted to determine the mRNA level of Notch and the protein levels of Notch, Bcl-2, Bax, caspase-3, and growth-associated protein 43 (GAP-43). The RGC apoptosis conditions were assessed by TUNEL staining. RESULTS: The OH rats and PBS-injected rats had increased expression levels of Notch1, Bax, caspase-3, and GAP-43, decreased expression levels of Bcl-2, and increased RGC apoptosis, with severer macular edema and RGCs more loosely aligned, when compared with the normal rats. The DAPT-treated rats displayed increased expression levels of Notch1, Bax, caspase-3, and GAP-43, decreased expression levels of Bcl-2, and increased RGC apoptosis, in comparison with the OH rats and PBS-injected rats. RGCs were hardly observed and macular edema became severe in the DAPT-treated rat. CONCLUSION: The Notch signaling pathway may suppress the apoptosis of retinal ganglion cells and enhances the regeneration of the damaged optic nerves in rats with acute OH.

14.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 26(1): 32-41, 2018 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-29397815

RESUMO

OBJECTIVE: To investigate the potential relationship between the high-resolution HLA-A,-B,-DRB1 alleles and haplotype polymorphism with actute myeloid leukemia (AML) and chronic myeloid leukemia (CML) of Han people in North China. METHODS: A total of 1241 healthy unrelated Han people's bone marrow donors in North China were used as a control group, 259 patients with myeloid leukemia were genotyped at high-resolution level by means of PCR-SBT, -SSO and -SSP typing methods for HLA-A,-B,-DRB1 loci. The frequencies of HLA allele and haplotype were calculated by software Arleguin 3.5.2. The different distribution of genes and haplotypes was analyzed by case control study, and the odd ratio (OR) of leukemia was also calculated. The structural difference of HLA alleles was analyzed 111by HLA three-dimensional structure modeling and software Swiss-PdbViewer v4.1. RESULTS: χ2 test and correction showed that an increased frequency of A*02:07 (8.47% vs 5.28%, P' =0.013), A*29:01 (1.85% vs 0.68%, P=0.044), B*07:02 (5.29% vs 3.10%, P=0.029), B*07:05:01G (1.85% vs 0.68%, P=0.044) and B*35:02 (1.06% vs 0.20%, P=0.023) were found in AML patients (n=189) as compared with controls, respectively; whereas A*02:03 was less frequent in AML as compared with controls (0.79% vs 3.10%, P=0.011). The frequency of B*46:01 was lower in CML patients (n=70) as compared with controls (2.86% vs 7.82%, P=0.031). However, the above-mentioned discrepancies were not statistically significant by Bonferroni correction. Through Fisher exact test and Bonferroni correction, the frequency of DRB1*11:28 and its haplotype A*24:02-B*15:01-DRB1*11:28 in CML group were very significantly higher than in controls (1.43% vs 0.00%, Pc=0.015; 1.43% vs 0.00%, P=0.003). Three-dimensional structure modeling of DRB1*11:28 and DRB1*11:01 presented significant structure differentiation (RMSD=0.09 nm) in peptide binding region of the backbone calculated by Swiss-PdbViewer v4.1. The haplotype A*03:01-B*50:01-DRB1*07:01 in AML and A*11:01-B*40:06-DRB1*09:01 in CML patients were significantly higher than that in controls (1.06% vs 0.00%, Pc=0.000; 2.86% vs 0.07%, Pc=0.000), and positively correlated with leukemia (OR=59.66, 95% CI=3.21-1110.39; OR=42.91, 95% CI=7.07-260.32). CONCLUSION: The relationship of HLA-A,-B,-DRB1 alleles and haplotype polymorphism with leukemia at high-resolution level were obtained and unique in north Chinese Han population. AML and CML patients in Northern Han people carry particular susceptible haplotypes. DRB1*11:28, which might not actively present bcr-abl peptide to CD4+ T cells, and is a susceptibile gene for CML patients of Northern Han people, especially in Shaanxi Province (OR=89.62, 95% CI=4.28-1875.87), as well as correlated with its particular haplotype.


Assuntos
Leucemia Mieloide , Alelos , Grupo com Ancestrais do Continente Asiático , Estudos de Casos e Controles , China , Frequência do Gene , Antígenos HLA-A , Antígenos HLA-B , Cadeias HLA-DRB1 , Haplótipos , Humanos
15.
Fitoterapia ; 125: 117-122, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29307850

RESUMO

Five rare sesquiterpene lactone dimers, vlasouliolides E-I, were isolated from Vladimiria souliei. Their chemical structures were elucidated by spectroscopic analysis. Furthermore, 2 and 4 were unambiguously confirmed by Cu-Kα X-ray crystallographic analysis. Compounds 1, 2, 4 and 5 exhibited significant anti-inflammatory activity against LPS-induced NO production in RAW 264.7 cells with IC50 values of 1.88, 4.89, 7.24 and 2.46µM, respectively. Additionally, compounds 1 and 2 were revealed with potent inhibitory activity of the phosphorylation progress of NF-κB P65.


Assuntos
Anti-Inflamatórios/isolamento & purificação , Asteraceae/química , Lactonas/isolamento & purificação , Sesquiterpenos/isolamento & purificação , Animais , Anti-Inflamatórios/farmacologia , Lactonas/farmacologia , Camundongos , Estrutura Molecular , Óxido Nítrico/metabolismo , Raízes de Plantas/química , Células RAW 264.7 , Sesquiterpenos/farmacologia , Fator de Transcrição RelA/metabolismo
16.
Asian J Androl ; 20(4): 342-348, 2018 Jul-Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29319007

RESUMO

Calpain activation contributes to hyperglycemia-induced endothelial dysfunction and apoptosis. This study was designed to investigate the role of calpain inhibition in improving diabetic erectile dysfunction (ED) in mice. Thirty-eight-week-old male C57BL/6J mice were divided into three groups: (1) nondiabetic control group, (2) diabetic mice + vehicle group, and (3) diabetic mice + MDL28170 (an inhibitor of calpain) group. Type 1 diabetes was induced by intraperitoneal injection of streptozotocin at 60 mg kg-1 body weight for 5 consecutive days. Thirteen weeks later, diabetic mice were treated with MDL28170 or vehicle for 4 weeks. The erectile function was assessed by electrical stimulation of the cavernous nerve. Penile tissues were collected for measurement of calpain activity and the endothelial nitric oxide synthase (eNOS)-nitric oxide (NO)-cyclic guanosine monophosphate (cGMP) pathway. Terminal deoxynucleotidyl transferase 2'-deoxyuridine 5'-triphosphate nick end labeling (TUNEL) staining was used to evaluate apoptosis. Caspase-3 expression and activity were also measured to determine apoptosis. Our results showed that erectile function was enhanced by MDL28170 treatment in diabetic mice compared with the vehicle diabetic group. No differences in calpain-1 and calpain-2 expressions were observed among the three groups. However, calpain activity was increased in the diabetic group and reduced by MDL28170. The eNOS-NO-cGMP pathway was upregulated by MDL28170 treatment in diabetic mice. Additionally, MDL28170 could attenuate apoptosis and increase the endothelium and smooth muscle levels in corpus cavernosum. Inhibition of calpain could improve erectile function, probably by upregulating the eNOS-NO-cGMP pathway and reducing apoptosis.

17.
Asian J Androl ; 20(1): 30-36, 2018 Jan-Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28361811

RESUMO

We performed this meta-analysis to evaluate the predictive value of different parameters in the sperm retrieval rate (SRR) of microdissection testicular sperm extraction (TESE) in patients with nonobstructive azoospermia (NOA). All relevant studies were searched in PubMed, Web of Science, EMBASE, Cochrane Library, and EBSCO. We chose three parameters to perform the meta-analysis: follicle-stimulating hormone (FSH), testicular volume, and testicular histopathological findings which included three patterns: hypospermatogenesis (HS), maturation arrest (MA), and Sertoli-cell-only syndrome (SCOS). If there was a threshold effect, only the area under the summary receiver operating characteristic curve (AUSROC) was calculated. Otherwise, the pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and the diagnostic odds ratio (DOR) were also calculated. Twenty-one articles were included in our study finally. There was a threshold effect among studies investigating FSH and SCOS. The AUSROCs of FSH, testicular volume, HS, MA, and SCOS were 0.6119, 0.6389, 0.6758, 0.5535, and 0.2763, respectively. The DORs of testicular volume, HS, and MA were 1.98, 16.49, and 1.26, respectively. The sensitivities of them were 0.80, 0.30, and 0.27, while the specificities of them were 0.35, 0.98, and 0.76, respectively. The PLRs of them were 1.49, 10.63, and 1.15, respectively. And NLRs were 0.73, 0.72, and 0.95, respectively. All the investigated factors in our study had limited predictive value. However, the histopathological findings were helpful to some extent. Most patients with HS could get sperm by microdissection TESE.

18.
Zhongguo Zhong Yao Za Zhi ; 42(8): 1609-1616, 2017 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-29071870

RESUMO

To explore the medication rules of famous veteran traditional Chinese medicine (TCM) doctors in treatment of chronic bronchitis, a structured medical record database for famous veteran TCM doctors in modern clinical books was established. First, Lantern 3.1.2(Kongmin light) implicit structure analysis software was used to build an implicit structure model and make an implicit interpretation. Then, SAS 9.1 was adopted to mine herb-herb, herb-symptom and herb-syndrome association rules. Through the mining, 1 274 commonly used herbs for chronic bronchitis were found, including liquorice, bitter almond, pinellia, dried tangerine or orange peel, poria cocos. The medicine types included antiasthmatic medicine, qi-tonifying medicine, and heat-phlegm removing medicine. The medicine tastes included sweet, pungent and bitter. The meridian distributions included lung, spleen and stomach channels. The famous commonly used prescriptions included Xiaoqinglong decoction, Maxing Shigan decoction and Erchen decoction. The 147-herb implicit structure model for the first diagnosis was built to get 44 hidden variables, 88 hidden classes, 7 comprehensive clustering models, 9 dual herb associations, 50 triple herb associations and 89 quadruple associations. Totally 297 medical records for the second diagnosis were compared to obtain 24 herb-symptom associations, which reduced ephedra, bitter almond, pinellia and added poria cocos, atractylodes, dangshen, 20 dual herb associations and 8 triple herb associations. A model for the top 83 symptoms and top 96 herbs in the first diagnosis was built to get 50 hidden variables and 101 hidden classes. The commonly used herbs of famous veteran TCM doctors included bitter almond, pinellia, dried tangerine or orange peel, poria cocos, which feature mild property and sweet favor and enter lung, spleen, kidney meridians; the commonly herbal pairs included atractylodes and poria cocos, asarum, fructus schisandrae and pinellia, as well as poria cocos, dangshen, pinellia and dried tangerine or orange peel. The herb-syndrome associations involved ephedra, bitter almond, cassia twig and scanty sputum, pinellia and external cold and internal fluid syndrome, turbid phlegm obstructing lung syndrome and spleen deficiency syndrome, bitter almond and turbid phlegm obstructing lung syndrome, phlegm-heat accumulated in the lung and wind-cold invading the lung. The implicit structure model can be used to quantify tacit knowledge of TCM, extend to the herb and syndrome level for the first time, and quantify the major, minor and compatible statues of different variables in the same data. This study concluded that the medication rules of famous veteran TCM doctors in treatment of chronic bronchitis have certain reference value for the clinical diagnosis and treatment. The data sources, analysis methods and mining results were relatively reliable and objective, and can provide a reference for rules of other disease treatment based on syndrome differentiation.


Assuntos
Bronquite Crônica/terapia , Medicamentos de Ervas Chinesas/uso terapêutico , Medicina Tradicional Chinesa , Humanos , Meridianos
19.
Biomed Res Int ; 2017: 8617076, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28758124

RESUMO

This study aimed to investigate the etiology and risk factors of neonatal sepsis. A retrospective analysis was conducted on 192 patients with sepsis from August 2013 to March 2015. One hundred and six healthy neonates were used as the control group. Logistic regression was used to analyze the risk factors and ROC curve analysis performed in laboratory which indicated a significant correlation. The results of univariate analysis showed that postnatal age, body weight, and parity were significantly related to neonatal sepsis (P < 0.5). Logistic regression analysis demonstrated that postnatal age and parity are independent risk factors for neonatal sepsis (OR were 1.176 and 0.692, resp., P < 0.001). The maximum area underneath the curve (ROCAUC) of soluble CD14 (sCD14-ST), which was the most indicative biomarker of sepsis diagnostically, was 0.953 with sensitivity and specificity of 93.8% and 84.9%, respectively. Escherichia coli, Staphylococcus aureus, and Streptococcus agalactiae were the main bacterial strains causing neonatal sepsis, while postnatal age was an independent risk factor for the onset of disease. sCD14-ST could be a potential useful diagnostic marker for pediatric sepsis.


Assuntos
Doenças do Recém-Nascido/sangue , Doenças do Recém-Nascido/epidemiologia , Sepse/sangue , Sepse/epidemiologia , Fatores Etários , Biomarcadores/sangue , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Fatores de Risco
20.
Sci Rep ; 7(1): 4005, 2017 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-28638088

RESUMO

We previously demonstrated that the chemokine receptor CXCR4 plays an important role in cancer-induced bone pain by activating spinal neurons and glial cells. However, the specific neuronal mechanism of CXCR4 signaling is not clear. We further report that CXCR4 contributes to the activation of the neuronal CaMKII/CREB pathway in cancer-induced bone pain. We used a tumor cell implantation (TCI) model and observed that CXCR4, p-CaMKII and p-CREB were persistently up-regulated in spinal neurons. CXCR4 also co-expressed with p-CaMKII and p-CREB, and mediated p-CaMKII and p-CREB expression after TCI. Intrathecal delivery of CXCR4 siRNA or CaMKII inhibitor AIP2 abrogated TCI-induced pain hypersensitivity and TCI-induced increase in p-CaMKII and p-CREB expression. Intrathecal injection of the principal ligand for CXCR4, SDF-1, promoted p-CaMKII and p-CREB expression in naive rats, which was prevented by post-administration of CXCR4 inhibitor Plerixafor or PLC inhibitor U73122. Plerixafor, U73122, or AIP2 also alleviated SDF-1-elicited pain behaviors. Intrathecal injection of CXCR4 siRNA significantly suppressed TCI-induced up-regulation of NMDAR1 mRNA and protein, which is a known gene target of CREB. Collectively, these results suggest that the CaMKII/CREB pathway in spinal neurons mediates CXCR4-facilitated pain hypersensitivity in cancer rats.

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