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1.
J Mol Neurosci ; 70(1): 71-83, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31478134

RESUMO

The disruption of the blood-brain barrier (BBB) and the consequent brain edema are major contributors to the pathogenesis of cerebral ischemia/reperfusion injury. RhoA is generally thought to play a crucial role in the process of BBB disruption and participate in the signaling pathways emanating from TLR4. However, it remains unverified the regulatory role of TLR4 in the RhoA/ROCK pathway in cerebral I/R injury and its effects on the BBB as well. The present study probes into the protective effect of ANF on the BBB after cerebral I/R injury and the possible mechanisms. Focal cerebral ischemia was induced by 120 min of transient middle cerebral artery occlusion (MCAO). ANF (1, 2, 4 µg/kg) was achieved by intravenous injection after 120 min of MCAO followed by 1, 24, 48, and 72 h reperfusion. Evans blue extravasation, brain water content, RhoA activity, and the expressions of TLR4, ROCK1/2, p-MLC2, MMP-2/9, ZO-1, occludin, and claudin-5 protein in rat brain were evaluated 72 h after reperfusion. ANF could significantly reduce the Evans blue extravasation and water content in the ipsilateral hemisphere and obviously increase the occludin, claudin-5, and ZO-1 expression after cerebral I/R injury. Furthermore, cerebral I/R injury induced apparently increased expression of TLR4, RhoA-GTP, ROCK1/2, p-MLC2, and MMMP-2/9, which, however, could be remarkably alleviated by ANF intervention. Taken together, the TLR4/RhoA/ROCK signaling pathway is implicated in BBB breakdown after cerebral I/R injury, and ANF preserves BBB integrity, probably via inhibiting the TLR4/RhoA/ROCK signaling pathway.

2.
World J Surg Oncol ; 17(1): 3, 2019 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-30606195

RESUMO

BACKGROUND: Although pathological evaluation has been considered an effective evaluation method, some problems still exist in practice. Therefore, we explored whether there are more reasonable and practical pathological evaluation criteria for neoadjuvant chemotherapy in patients with advanced gastric cancer. Here, we aim to determine pathological judgment criteria for neoadjuvant chemotherapy in patients with advanced gastric cancer. METHODS: Eighty-seven patients with cT2-4 or cN+ were enrolled in this study. Pathological factors for overall survival (OS) were investigated using univariate and multivariate analyses, and the pathological criteria for neoadjuvant chemotherapy were then determined. RESULTS: A total of 87 patients underwent 3-4 cycles of neoadjuvant chemotherapy, with 67 (77.0%), 15 (17.2%), and 5 (5.8%) receiving Folfox6, Xelox, and SOX regimens, respectively. All patients showed different levels of graded histological regression (GHR) of the primary tumor, with a ≥ 50% regression rate of 50.6%. The univariate analysis showed that GHR ≥ 50% (p = 0.022), 66.7% (p = 0.013), and 90% (p = 0.028) were significantly correlated with OS. The multivariate analysis demonstrated that ypTNM (II/III) stage was significantly associated with OS compared with ypTNM (0+I) stage [HR = 3.553, 95% CI 1.886-6.617; HR = 3.576, 95% CI 1.908-6.703, respectively] and that the Lauren classification of diffuse type was also an independent risk factor for OS compared with the intestinal type (HR = 3.843, 95% CI 1.443-10.237). CONCLUSIONS: The Lauren classification and ypTNM stage after neoadjuvant chemotherapy are independent prognostic factors in advanced gastric cancer. A GHR ≥ 50%/< 50% can be used as the primary criterion for advanced gastric cancer after neoadjuvant chemotherapy to determine postoperative adjuvant chemotherapy regimens.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Terapia Neoadjuvante/métodos , Seleção de Pacientes , Neoplasias Gástricas/terapia , Estômago/patologia , Feminino , Seguimentos , Gastrectomia , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Estômago/cirurgia , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Análise de Sobrevida , Resultado do Tratamento
3.
Sensors (Basel) ; 18(12)2018 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-30501037

RESUMO

Feature-based matching can provide high robust correspondences and it is usually invariant to image scale and rotation. Nevertheless, in remote sensing, the robust feature-matching algorithms often require costly computations for matching dense features extracted from high-resolution satellite images due to that the computational complexity of conventional feature-matching model is O ( N 2 ) . For replacing the conventional feature-matching model, a fast dense (FD) feature-matching model is proposed in this paper. The FD model reduces the computational complexity to linear by splitting the global one-to-one matching into a set of local matchings based on a classic frame-based rectification method. To investigate the possibility of applying the classic frame-based method on cross-track pushbroom images, a feasibility study is given by testing the frame-based method on 2.1 million independent experiments provided by a pushbroom based feature-correspondences simulation platform. Moreover, to improve the stability of the frame-based method, a correspondence-direction-constraint algorithm is proposed for providing the most favourable seed-matches/control-points. The performances of the FD and the conventional models are evaluated on both an automatic feature-matching evaluation platform and real satellite images. The evaluation results show that, for the feature-matching algorithms which have high computational complexity, their running time for matching dense features reduces from hours level to minutes level when they are operated on the FD model. Meanwhile, based the FD method, feature-matching algorithms can achieve comparable matching results as they achieved based on the conventional model.

4.
Medicine (Baltimore) ; 97(34): e11977, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30142829

RESUMO

Burn infections pose a serious obstacle to recovery. To investigate and analyze the antimicrobial resistance and distribution of pathogenic bacteria among hospitalized burn patients. A 3-year retrospective study was conducted in the southeast of China.The electronic medical records system was used to collect all clinical data on 1449 hospitalized patients from Fujian Medical University Union Hospital, the 180th Hospital of Chinese People's Liberation Army (PLA), the 92nd Hospital of PLA, and the First Hospital of Longyan City.A total of 1891 strains of pathogenic bacteria were detected from 3835 clinical specimens, and the total detection rate was 49.3% (1891/3835). The main pathogens were gram-negative bacteria (1089 strains; 57.6%), followed by gram-positive bacteria (689 strains; 36.4%), and fungi (113 strains; 6.0%). The predominant five bacteria were Staphylococcus aureus (19.0%), Acinetobacter baumannii (17.6%), Pseudomonas aeruginosa (16.7%), Klebsiella pneumoniae (7.4%), and Enterococcus faecalis (4.5%). Methicillin-resistant Staphylococcus aureus (MRSA) accounted for 74.1% (265/359) of S aureus isolates. Staphylococcus epidermidis accounted for 40.6% (69/170) of coagulase-negative staphylococcal isolates, 72.5% (50/69) of which were methicillin-resistant Staphylococcus epidermidis (MRSE). Both MRSA and MRSE were 100% resistant to penicillin and ampicillin. A baumannii was the most commonly isolated strain of gram-negative bacteria with 100% resistance to ampicillin, amoxicillin, amoxicillin/clavulanic acid, and aztreonam. More than 80% of K pneumoniae isolates were resistant to ampicillin, amoxicillin and cefazolin. More than 80% of Escherichia coli isolates were resistant to ampicillin, piperacillin, cefazolin, amoxicillin, tetracycline, and sulfamethoxazole trimethoprim. The detection rates of extended-spectrum ß-lactamases (ESBL) among K pneumoniae and E coli isolates were 44.6% (62/139) and 67.2% (41/61), respectively. Low-resistance antibiotics included teicoplanin, tigecycline, vancomycin, and linezolid.The pathogens presented high resistance to antimicrobial agents, especially MRSA and A baumannii. Monitoring of bacterial population dynamics should be established to inhibit the progression of bacterial resistance.


Assuntos
Antibacterianos/farmacologia , Infecções Bacterianas/microbiologia , Queimaduras/microbiologia , Infecção Hospitalar/microbiologia , Farmacorresistência Bacteriana , Adolescente , Adulto , Infecções Bacterianas/tratamento farmacológico , Criança , Pré-Escolar , China , Feminino , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Negativas/isolamento & purificação , Bactérias Gram-Positivas/efeitos dos fármacos , Bactérias Gram-Positivas/isolamento & purificação , Hospitalização , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Micoses/tratamento farmacológico , Micoses/microbiologia , Estudos Retrospectivos , Adulto Jovem
5.
Surg Oncol ; 27(2): 172-176, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29937168

RESUMO

OBJECTIVE: To study the correlations between the sonographic features of papillary thyroid microcarcinoma (PTMC) and the presence of high-volume lymph node metastasis. METHOD: Medical records of 2363 PTMC patients were reviewed form October 2013 to December 2015. All the patients with lymph node metastasis identified by histopathology were included. Preoperative sonographic features, such as multifocality, tumour size, echogenicity, calcification, vascularity of papillary microcarcinoma, and capsule invasion, were recorded. Univariate and multivariate analyses were performed to investigate the relationships between sonographic features and high-volume lymph node metastasis (number of metastatic lymph nodes >5). RESULTS: In total, 152 patients had high-volume central lymph node metastasis (6.4%, 152/2363). Multiple logistic regression analysis showed that the preoperative ultrasonic features of microcalcifications (OR = 3.33, p = 0.022), larger tumour size (>7 mm) (OR = 2.802, p < 0.001), and capsule invasion (OR = 2.141, p = 0.006) were independent risk factors for high-volume lymph node metastasis in the central compartment of PTMC. CONCLUSION: The sonographic features of primary papillary microcarcinoma of the thyroid are correlated with high-volume central lymph node metastasis.


Assuntos
Carcinoma Papilar/diagnóstico por imagem , Carcinoma Papilar/patologia , Linfonodos/diagnóstico por imagem , Linfonodos/patologia , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/patologia , Ultrassonografia/métodos , Carcinoma Papilar/cirurgia , Feminino , Seguimentos , Humanos , Linfonodos/cirurgia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Neoplasias da Glândula Tireoide/cirurgia , Tireoidectomia
6.
Mol Nutr Food Res ; 62(12): e1700757, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29710380

RESUMO

SCOPE: To investigate the effects of postoperative parenteral nutrition (PN) with multivitamins supplementation on oxidative stress and metabolism. METHODS AND RESULTS: The participants are randomly assigned in a 1:1 ratio to groups: total nutrient admixture (TNA) + multivitamin (n = 14, Group A) and TNA + normal saline (n = 16, Group B). The levels of blood vitamins, ILs, and MDA are assessed and the dysregulation of metabolism is analyzed using nontargeted metabolite profiling. The degree of postoperative stress in Group A is significantly lower than that in Group B by analyzing changes in the levels of IL-8 and MDA. A set of 43 features are qualified to have a variable importance parameter score of >1.5 of a partial least-squares discriminate analysis model and fold change of >1.5 at p-value <0.05 between Groups A and B. The principal metabolic alternations in Group A include increased tricarboxylic acid cycle and ketogenesis with reduced plasma-free amino acids. Backing the results of clinical biomarkers, increased levels of antioxidative molecules, together with decreased levels of inflammatory related polyunsaturated fatty acids, are observed. CONCLUSION: Postoperative PN enhanced by multivitamins can alleviate traumatic stress and improve metabolic transition from catabolism to anabolism in gastric cancer patients.


Assuntos
Nutrição Parenteral/métodos , Neoplasias Gástricas/cirurgia , Vitaminas/farmacologia , Idoso , Biomarcadores/sangue , Feminino , Humanos , Interleucinas/sangue , Masculino , Malondialdeído/sangue , Metaboloma/efeitos dos fármacos , Pessoa de Meia-Idade , Estresse Oxidativo/efeitos dos fármacos , Cuidados Pós-Operatórios , Espectrometria de Massas em Tandem , Resultado do Tratamento , Vitaminas/sangue
7.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 39(5): 675-681, 2017 10 30.
Artigo em Inglês | MEDLINE | ID: mdl-29125111

RESUMO

Objective To explore the ultrasound features and levels of cervical lymph node metastases in primary and recurrent/persistent papillary thyroid cancer (PTC).Methods We retrospectively analyzed the clinical data of 2181 patients who underwent cervical lymph nodes dissection for PTC from January 1st 2015 to January 1st 2016.Totally 418 PTC patients (with 622 lymph nodes) who met the inclusion criteria entered the final analysis.Patients who had not received any prior thyroid treatment (surgery with or without radioactive iodine) were categorized as the primary group (352 patients with 527 metastatic lymph nodes),and patients who had received prior treatment (thyroidectomy with or without radioactive iodine) for PTC were categorized as recurrent/persistent group (66 patients with 95 metastatic lymph nodes).Pathological results from lymph node dissections were used as the gold standards by means of level-to-level analysis.Results The mean of the minimum axis diameter of the lymph nodes in the primary group was (6.7±3.6)mm,and that of the recurrent/persistent group was (6.6±3.1)mm (U=0.180,P=0.857).The proportion of metastasis in the central area of primary group was 40.0%,which was significantly higher than that in the recurrent/persistent group (12.6%);the proportion of metastasis in the lateral area was 60.6% in the primary group,which was significantly lower than that in the recurrent/persistent group (87.4%)(χ2=26.288,P<0.001).In lateral metastatic lymph nodes,Ⅲ level was the most common place in both groups.Level Ⅴ metastatic lymph was rare in both primary group and recurrent/persistent group.Calcifications (63.1% vs. 48.2%;χ2=7.207,P=0.007) and peripheral vascularity (81.1% vs. 59.4%;χ2= 16.147, P<0.001) were more common in the recurrent/persistent group.The round shape,absence of an echogenic hilum,hyperechogenicity,and cystic aspects were not significantly different between these two groups (all P>0.05).Conclusions Primary metastatic lymph nodes often occur in the central area of lymph nodes,while lateral metastatic lymph nodes are more common in recurrent/persistent PTC.For metastatic lymph nodes,calcifications and peripheral vascularity are more common in recurrent/persistent PTC.


Assuntos
Carcinoma Papilar/diagnóstico por imagem , Linfonodos/diagnóstico por imagem , Câncer Papilífero da Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Humanos , Metástase Linfática/diagnóstico por imagem , Recidiva Local de Neoplasia/diagnóstico por imagem , Estudos Retrospectivos , Tireoidectomia
8.
Oncotarget ; 8(37): 61731-61741, 2017 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-28977900

RESUMO

miR-145 has been implicated in the progression of breast cancer. Here, we report that its expression is decreased in breast cancer specimens and cell lines and that this low level of expression is associated with DNA methylation of its gene, MIR145. Methylation of MIR145 has previously been correlated with cell migration and invasion, both in vivo and in vitro. We found that demethylation of MIR145 reactivates miR-145 and contributes to the anti-cancer properties of 5-aza-2'-deoxyazacytidine (5-AzaC). Therefore, miR-145 is a potentially valuable biomarker for breast cancer.

9.
Chemistry ; 23(33): 7990-7996, 2017 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-28326629

RESUMO

An unprecedented reversible dynamic transformation is reported in a metal-organic framework involving bond formation, which is accompanied by two important structural changes; achiral to chiral and two- to three-dimensions. Using two bent organic ligands (diimpym=4,6-di(1H-imidazol-1-yl)pyrimidine; H2 npta=5-nitroisophthalic acid) and CoII (NO3 )2 ⋅6 H2 O the coordination polymer Co(diimpym)(npta)⋅CH3 OH, (1⋅CH3 OH), was obtained solvothermally. Its structure consists of knitted pairs of square layers (44 -sql net) of five-coordinated Co and disordered methanol, and it crystallized in the achiral Pbca space group at room temperature. It undergoes a single crystal to single crystal (SC-SC) transformation to a 3D interpenetrated framework (α-polonium-type net, pcu) of six-coordinated Co and ordered methanol in the chiral P21 21 21 space group below 220 K. Most unusual is the dynamic temperature-dependent shortening of a Co⋅⋅⋅O connection from a non-bonded 2.640 Š(298 K) to a bonded 2.347 Šdistance (100 K) transforming the square pyramidal cobalt polyhedron to a distorted octahedron. The desolvated crystals (1) obtained at 480 K retain the full crystallinity and crystallize in the achiral Pbca space group between 100 and 298 K but the dynamic shortening of the Co⋅⋅⋅O distance connecting the layers into the 3D pcu framework structure is observed. Following post-synthetic insertion of ethanol (1⋅CH3 CH2 OH) it does not exhibit the transformation and retains the knitted 2D achiral Pbca structure for all temperatures (100-298 K) and the ethanol is always disordered. The structural analyses thus conclude that the ordering of the methanol induces the chirality while the available space controls the dynamic motion of the knitted 2D networks into the 3D interpenetrated framework. Consequently, 1 selectively adsorbs CO2 to N2 and exhibits Type-III isotherms indicating dynamic motion of the 2D networks to accommodate the CO2 at 273 and 298 K in contrast to the rigidity of the 3D framework at 77 K preventing N2 from penetrating the solid. The magnetic properties are also reported.

10.
Sheng Li Xue Bao ; 69(1): 33-40, 2017 Feb 25.
Artigo em Chinês | MEDLINE | ID: mdl-28217805

RESUMO

Senescence-associated secretory phenotype (SASP) is often a concomitant result of cell senescence, embodied by the enhanced function of secretion. The SASP factors secreted by senescent cells include cytokines, proteases and chemokines, etc, which can exert great influence on local as well as systemic environment and participate in the process of cell senescence, immunoregulation, angiogenesis, cell proliferation and tumor invasion, etc. Relative to the abundance of SASP models in human cells, the in vitro SASP model derived from mouse cells is scarce at present. Therefore, the study aimed to establish a mouse SASP model to facilitate the research in the field. With this objective, we treated the INK4a-deficient mouse NIH-3T3 cells and the wildtype mouse embryonic fibroblasts (MEF) respectively with mitomycin C (MMC), an anticarcinoma drug which could induce DNA damage. The occurring of cell senescence was evaluated by cell morphology, ß-gal staining, integration ratio of EdU and Western blot. Quantitative RT-PCR and ELISA were used to detect the expression and secretion of SASP factors, respectively. The results showed that, 8 days after the treatment of NIH-3T3 cells with MMC (1 µg/mL) for 12 h or 24 h, the cells became enlarged and the ratios of ß-gal-positive (blue-stained) cells significantly increased, up to 77.4% and 90.4%, respectively. Meanwhile, the expression of P21 protein increased and the integration ratios of EdU significantly decreased (P < 0.01). Quantitative RT-PCR detection showed that the mRNA levels of several SASP genes, including IL-6, TNF-α, IL-1α and IL-1ß increased evidently. ELISA detection further observed an enhanced secretion of IL-6 (P < 0.01). On the contrary, although wildtype MEF could also be induced into senescence by MMC treatment for 12 h or 24 h, embodied by the enlarged cell volume, increased ratios of ß-gal-positive cells (up to 71.7% and 80.2%, respectively) and enhanced expression of P21 protein, the secretion of IL-6 displayed no significant change. Our study indicated that, although MMC could induce senescence in both mouse NIH-3T3 cells and wildtype MEF, only senescent NIH-3T3 cells displayed the canonical SASP phenomena. Current study suggested that senescent NIH-3T3 cells might be an appropriate in vitro SASP model of mouse cells.


Assuntos
Senescência Celular/efeitos dos fármacos , Fibroblastos/efeitos dos fármacos , Mitomicina/farmacologia , Animais , Proliferação de Células , Inibidor de Quinase Dependente de Ciclina p21/genética , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Citocinas/genética , Citocinas/metabolismo , Dano ao DNA , Interleucina-6/metabolismo , Camundongos , Células NIH 3T3 , Fenótipo
11.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 38(5): 554-558, 2016 10 10.
Artigo em Inglês | MEDLINE | ID: mdl-27825413

RESUMO

Objective To summarize the characteristics of lymph node metastasis in patients with papillary thyroid carcinoma accompanied with Graves disease,and to provide evidence for clinical treatment. Methods Totally 98 patients with papillary thyroid carcinoma and Graves disease who had been treated in Peking Union Medical College Hospital from January 2004 to December 2013 were divided into the lymph node metastasis positive group (n=34) and lymph node metastasis negative group (n=64). The general information,blood biochemical results,pathological results,and prognoses were compared between these two groups. Results These two groups showed no significant differences in gender (χ2=0.2113,P=0.6458),age (t=1.7000,P=0.0922),tumor diameter (t=1.2559,P=0.2122),and multifocal tumors (χ2=1.9170,P=0.1661). The median level of thyrotropin receptor antibody (TR-Ab) value in the lymph node metastasis positive group was 4.84 U/L,which was significantly higher than that in the negative group which was 2.99 U/L (t=2.0169,P=0.0465). There were no significant differences in serum thyroid stimulating hormone (t=0.0257,P=0.9800),free triiodothyronine (t=1.3610,P=0.1770),free thyroxine (t=0.0082,P=0.9930),thyroid peroxidase antibody (t=0.0177,P=0.9860),and thyroglobulin antibody levels (t=1.1450,P=0.2550) between two groups. The postoperative pathological results showed that tumor capsular invasion rate (26.5% vs. 9.38%;χ2=5.006,P=0.0253) and lymph node recurrence rate (14.7% vs. 1.56%;χ2=4.583,P=0.0323) were significantly higher in the positive group than in the negative group. The distal metastasis rate in the positive group and negative group were 5.88% and 0,respectively. Conclusions There is no definite association between lymph node metastasis and tumor size in patients with thyroid papillary carcinoma associated with Graves disease. The risk factors for lymph node metastasis include TR-Ab and tumor capsular invasion,with a higher incidence of lymph nodes recurrence.


Assuntos
Carcinoma/patologia , Doença de Graves/patologia , Neoplasias da Glândula Tireoide/patologia , Carcinoma/complicações , Carcinoma Papilar , Doença de Graves/complicações , Humanos , Linfonodos/patologia , Metástase Linfática , Recidiva Local de Neoplasia , Prognóstico , Fatores de Risco , Tireoglobulina/sangue , Câncer Papilífero da Tireoide , Neoplasias da Glândula Tireoide/complicações , Tireotropina/sangue
12.
Dalton Trans ; 44(24): 11013-20, 2015 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-25994514

RESUMO

It has been a challenge to decipher the in situ ligand reaction mechanism in assembly processes, involving metals and ligands. The present study shows two crystalline mixed-ligand Cu(II) coordination polymers isolated by controlled in situ ligand reactions under the same hydrothermal conditions. Two closely related examples provide a precious chance to access the in-depth mechanistic issues surrounding in situ reactions. The solid structure of 1 demonstrated that maleic acid was completely transformed to malic acid, whereas when fumaric acid was used in the same reaction conditions, an incomplete transformation from fumaric acid to malic acid was observed in the solid structure of 2. Compound 1 exhibits a 3D 6-connected sni network based on a binuclear copper(ii) secondary building unit, whereas the 3D network of 2 is classified to a (6,8)-connected topology network. The difference in steric hindrance between maleic acid and fumaric acid dictates the degree of the in situ nucleophilic addition reaction. The comparison of synthesis and final solid structures indicates that the one-step nucleophilic addition mechanism for in situ generated malic acid under the current reaction conditions of 1 is plausible. The magnetic sensitivity measurements of 1 demonstrated that overall antiferromagnetic coupling exists between Cu1 and Cu2 ions and between Cu3 and Cu4 ions. Furthermore, the obtained 1 can be an active catalyst for the solvent-free silylcyanation of aromatic aldehydes under mild conditions.

13.
Chin Med J (Engl) ; 128(8): 1037-41, 2015 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-25881596

RESUMO

BACKGROUND: Familial nonmedullary thyroid carcinoma (FNMTC) is a variant of nonmedullary thyroid carcinoma(NMTC) with particular clinicopathologic features. In recent years, a number of studies have shown that FNMTC is more invasive than sporadic NMTC(SNMTC). The purpose of this study was to explore the differences in clinicopathologic features of FNMTC between different types of families and to determine in which of these families more invasive FNMTC occurred. METHODS: We retrospectively reviewed all patients with thyroid carcinoma admitted to Peking Union Medical College Hospital from January 2009 to July 2013 in the database. Of all 2000 cases, 55 met the inclusive criteria for FNMTC and were studied. There are two different grouping methods. The first is that all samples were allocated to families with three or more first-degree relatives affected (FNMTC-3 group) and families with only two affected first-degree relatives (FNMTC-2 group). The second is that all patients were divided into families with three or more affected first-degree relatives over two generations (FNMTC-3-2 group) and the other families. We compared the clinicopathologic features such as sex, age, tumor size, multifocality, location, complications by thyroiditis, complications by benign thyroid nodules, surgical procedure, capsule invasion, histological type, lymph node metastases, tumor node metastasis stage, and BRAF mutation between FNMTC-2 group and FNMTC-3 group. We also made the same comparison between FNMTC-3-2 group and other families. RESULTS: No pronounced differences in clinicopathological features were present between FNMTC-2 group and FNMTC-3 group. The proportion of FNMTC-3-2 group aged <45 years was significantly higher than that in the other families (58.8% vs. 26.3%, P = 0.021). A similar difference was found in the proportion of lymph node metastasis (64.7% vs. 34.2%, P = 0.035). CONCLUSIONS: FNMTC-3-2 is more invasive than the other families. Early screening and positive treatment for members of these families are recommended.


Assuntos
Carcinoma/diagnóstico , Neoplasias da Glândula Tireoide/diagnóstico , Adulto , Carcinoma Papilar , Feminino , Predisposição Genética para Doença/genética , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Proteínas Proto-Oncogênicas B-raf/genética , Estudos Retrospectivos , Câncer Papilífero da Tireoide
14.
Br J Pharmacol ; 172(15): 3904-16, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25917571

RESUMO

BACKGROUND AND PURPOSE: Ischaemic stroke is a serious disease with limited therapy options. Glycoprotein (GP)Ib binding to von Willebrand factor (vWF) exposed at vascular injury initiates platelet adhesion and contributes to platelet aggregation. GPIb has been suggested as an effective target for antithrombotic therapy in stroke. Anfibatide is a GPIb antagonist derived from snake venom and we investigated its protective effect on experimental brain ischaemia in mice. EXPERIMENTAL APPROACH: Focal cerebral ischaemia was induced by 90 min of transient middle cerebral artery occlusion (MCAO). These mice were then treated with anfibatide (4, 2, 1 µg·kg(-1) ), injected i.v., after 90 min of MCAO, followed by 1 h of reperfusion. Tirofiban, a GPIIb/IIIα antagonist, was used as a positive control. KEY RESULTS: Twenty-four hours after MCAO, anfibatide-treated mice showed significantly improved ischaemic lesions in a dose-dependent manner. The mice had smaller infarct volumes, less severe neurological deficits and histopathology of cerebrum tissues compared with the untreated MCAO mice. Moreover, anfibatide decreased the amount of GPIbα, vWF and accumulation of fibrin(ogen) in the vasculature of the ischaemic hemisphere. Tirofiban had similar effects on infarct size and fibrin(ogen) deposition compared with the MCAO group. Importantly, the anfibatide-treated mice showed a lower incidence of intracerebral haemorrhage and shorter tail bleeding time compared with the tirofiban-treated mice. CONCLUSIONS AND IMPLICATIONS: Our data indicate anfibatide is a safe GPIb antagonist that exerts a protective effect on cerebral ischaemia and reperfusion injury. Anfibatide is a promising candidate that could be beneficial for the treatment of ischaemic stroke.


Assuntos
Isquemia Encefálica/prevenção & controle , Venenos de Crotalídeos/farmacologia , Complexo Glicoproteico GPIb-IX de Plaquetas/antagonistas & inibidores , Substâncias Protetoras/farmacologia , Traumatismo por Reperfusão/prevenção & controle , Acidente Vascular Cerebral/prevenção & controle , Animais , Tempo de Sangramento , Plaquetas/efeitos dos fármacos , Isquemia Encefálica/metabolismo , Isquemia Encefálica/patologia , Contagem de Células , Hemorragia Cerebral/prevenção & controle , Relação Dose-Resposta a Droga , Fibrina/metabolismo , Infarto da Artéria Cerebral Média , Lectinas Tipo C , Masculino , Camundongos , Complexo Glicoproteico GPIb-IX de Plaquetas/metabolismo , Acidente Vascular Cerebral/patologia , Tirofibana , Tirosina/análogos & derivados , Tirosina/farmacologia , Fator de von Willebrand/metabolismo
15.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 36(1): 42-6, 2014 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-24581127

RESUMO

OBJECTIVE: To investigate the relationship between the immunity and invasiveness in differentiated thyroid cancer (DTC). METHODS: Totally 74 DTC who were treated in Peking Union Medical College Hospital from September 2012 to December 2012 were enrolled in this study. These 74 patients were divided into membrane invasion group (n=36) and without membrane invasion group (n=38); also, they were divided into distant metastasis group (n=18) and without distant metastasis group (n=56). Natural killer (NK) cells and T-cell subsets were chosen as indicators for cellular immunity to investigate the correlation between cellular immunity and invasiveness in DTC. RESULTS: Univariate analysis showed that the membrane invasion (Χ(2)=12.175, P=0.000) and distant metastasis (Χ(2)=8.139, P=0.006) correlated with cell immunity, whereas distant metastasis correlated with lymphocytic thyroiditis (Χ(2)=7.094, P=0.008). Further investigation shows that distant metastasis was associated with the percentage of CD8+T cell subgroup (Χ(2)=5.429, P=0.020), and membrane invasion was significantly associated with NK cells (Χ(2)=2.445, P=0.018) and CD4/CD8 disorder subgroup (Χ(2)=8.079, P=0.002). Multivariate analysis showed that cell immunity disorder was a risk factor for membrane invasion [OR=5.701,95%CI(2.075~15.666), P=0.001] and distant metastasis [OR=5.063,95%CI (1.571~16.320), P=0.008]. Further analysis showed that CD8+T cell was a risk factor for metastasis [OR=2.236,95%CI( 1.084~4.613), P=0.029], and CD4/CD8 disorders were the risk factors for membrane invasion [OR=2.802,95%CI(1.257~6.244), P=0.012]. CONCLUSION: Cell immunity in thyroid cancer has close relationship with membrane invasion and distant metastasis, especially when the percentage of CD8+T cells decreases and when the NK cells and CD4/CD8 are abnormal, which may lead to membrane invasion and distant metastasis.


Assuntos
Adenocarcinoma/imunologia , Adenocarcinoma/patologia , Células Matadoras Naturais/imunologia , Subpopulações de Linfócitos T/imunologia , Neoplasias da Glândula Tireoide/imunologia , Neoplasias da Glândula Tireoide/patologia , Adolescente , Adulto , Criança , Feminino , Humanos , Imunidade Celular , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Adulto Jovem
16.
Asia Pac J Clin Oncol ; 10(2): e28-32, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23279745

RESUMO

AIM: To evaluate the role of endoscopic ultrasound (EUS) in restaging and predicting response after neoadjuvant chemotherapy in patients with advanced gastric cancer. METHODS: In all, 48 advanced gastric cancer patients were recruited from June 2007 to December 2010 after providing their written, informed consent. All patients underwent an EUS before and after three cycles of neoadjuvant chemotherapy (FOLFOX 6), and then a radical resection was performed 3-4 weeks after chemotherapy. The results of EUS were compared to the pathological results of the resected specimens. RESULTS: After chemotherapy, the overall sensitivity of EUS for T classification was 63 percent (T2: 44%, T3: 68%, T4: 90%), and overstaging (31%) was more frequent than understaging (6%). The sensitivity and specificity of EUS for N classification were 56 and 50 percent, respectively (N0: without lymph node metastasis, N1: with lymph node metastasis), with 15 percent overstaged and 32% understaged. EUS revealed that T and/or N downstaging occurred in 46 percent (22/48) of patients after chemotherapy, most of whom had a favorable pathological response to the chemotherapy compared with other patients without T and/or N downstaging. No T or N upstaging was observed after neoadjuvant chemotherapy. CONCLUSIONS: The accuracy of restaging by EUS for T and N classification was not as good as pathological data for locally advanced gastric cancer patients after neoadjuvant chemotherapy. However, T and/or N downstaging confirmed by EUS correlated well with the degree of pathological response to chemotherapy.


Assuntos
Neoplasias Gástricas/diagnóstico por imagem , Neoplasias Gástricas/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Estudos de Coortes , Endossonografia/métodos , Feminino , Fluoruracila/administração & dosagem , Humanos , Leucovorina/administração & dosagem , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Estadiamento de Neoplasias , Compostos Organoplatínicos/administração & dosagem , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia
17.
Zhonghua Shao Shang Za Zhi ; 29(3): 239-44, 2013 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-24059947

RESUMO

OBJECTIVE: To observe the effects of up- or down-regulation of haemoxygenase 1 (HO-1) gene expression on intestinal mucosa injury induced by intra-abdominal hypertension (IAH). METHODS: (1) Reproduction of rat model of up- or down-regulation of HO-1 gene expression. Twenty-four healthy adult Wistar rats were divided into Co-PP (HO-1 specific revulsive) 2.5 mg, Co-PP 5.0 mg, Sn-PP (HO-1 specific inhibitor) 2.5 mg, and control groups according to the random number table, with six rats in each group. Rats in groups Co-PP 2.5 mg and Sn-PP 2.5 mg were respectively given Co-PP 2.5 mg/kg and Sn-PP 2.5 mg/kg by intraperitoneal injection, once every 12 hours for 3 days. The rats in group Co-PP 5.0 mg were intraperitoneally injected with Co-PP 5.0 mg/kg, once a day for 3 days. The rats in control group were treated with equal volume of normal saline by intraperitoneal injection. All rats were sacrificed on post injection day (PID) 4, and intestinal mucosa tissues were collected for determination of HO-1 mRNA expression. Optimal dose of Co-PP was chosen for the following experiment. (2) The influence of up- or down-regulation of HO-1 gene expression on intestinal mucosa injury under IAH condition. Another 24 healthy adult Wistar rats were divided into control, IAH, Co-PP+IAH, and Sn-PP+IAH groups according to the random number table, with six rats in each group. The rats in groups Co-PP+IAH and Sn-PP+IAH were intraperitoneally injected with 2.5 mg/kg Co-PP and 2.5 mg/kg Sn-PP, once every 12 hours for 3 days. Equal volume of normal saline was intraperitoneally injected into the rats in control group, once every 12 hours for 3 days. Then, nitrogen gas pneumoperitoneum was used to establish the model of IAH in rats of the latter three groups on PID 4, with IAP at 20 mm Hg (1 mm Hg = 0.133 kPa) , and it was maintained for 2 hours. Puncture and intubation were performed in rats of control group without inflating nitrogen gas. Jejunal segment in the length of 10-15 cm was harvested for collecting intestinal mucosa tissues to determine the HO-1 mRNA expression and diamine oxidase (DAO) content. Serum obtained from portal vein blood was collected to determine the D-lactate, TNF-α, and IL-6 contents. Another jejunal segment in the length of 1-2 cm was harvested for histopathological examination. Data were processed with one-way analysis of variance and t test. RESULTS: (1) The HO-1 mRNA expression in group Co-PP 2.5 mg was significantly higher than that in control and Co-PP 5.0 mg groups (with t values respectively 4.756, 3.175, P < 0.05 or P < 0.01). The HO-1 mRNA expression in group Sn-PP 2.5 mg was significantly lower than that in control group (t = 4.880, P < 0.01). The optimal dose of Co-PP for the following experiment was 2.5 mg/kg. (2) HO-1 mRNA expression in group Co-PP+IAH was 60 ± 5, and it was obviously higher than that of group IAH (49 ± 5, t = 3.811, P < 0.01) and control group (39 ± 4, t = 8.034, P < .001) . HO-1 mRNA expression was higher in group IAH than in control group (t = 3.826, P < 0.01). HO-1 mRNA expression in group Sn-PP+IAH was 29 ± 4, which was obviously lower than that of control group (t = 4.330, P < 0.01). The contents of DAO and D-lactate in group Co-PP+IAH were (0.52 ± 0.05) U/mL and (1.9 ± 0.6) mg/L, which were significantly lower than those in group IAH [(0.88 ± 0.06) U/mL and (4.3 ± 0.7) mg/L, with t values respectively 11.291, 6.376, P values all below 0.01], but still higher than those in control group [(0.34 ± 0.04) U/mL, (1.2 ± 0.5) mg/L, with t values respectively 6.886, 2.295, P < 0.05 or P < 0.01]. The contents of TNF-α and IL-6 were much lower in group Co-PP+IAH than in group IAH, but still higher than in control group (with t values from 3.781 to 18.557, P values all below 0.01). The contents of DAO, D-lactate, TNF-α, and IL-6 in group Sn-PP+IAH were all higher than those in the other 3 groups (with t values from 4.181 to 32.938, P values all below 0.01). Structure of epithelial cells from intestinal mucosa was intact and regularly arranged in rats of control group. Intestinal mucosal tissue was edematous, and the top of villi was anabrotic and necrotic in rats of group IAH. Compared with that of group IAH, the degree of intestinal mucosa injury was alleviated in rats of group Co-PP+IAH, while the pathology was aggravated in rats of group Sn-PP+IAH. CONCLUSIONS: Up-regulation of HO-1 gene expression can ameliorate intestinal mucosa injury caused by IAH, thus protecting intestinal mucosa tissues.


Assuntos
Heme Oxigenase (Desciclizante)/metabolismo , Mucosa Intestinal/patologia , Hipertensão Intra-Abdominal/enzimologia , Animais , Modelos Animais de Doenças , Regulação da Expressão Gênica , Mucosa Intestinal/enzimologia , Hipertensão Intra-Abdominal/patologia , Ratos , Ratos Wistar , Regulação para Cima
18.
Chin Med J (Engl) ; 126(16): 3013-8, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23981603

RESUMO

BACKGROUND: BRAF(V600E) mutation is correlated with local aggressive clinicopathological features in papillary thyroid carcinoma; yet the relationship between this genetic variation and distant papillary thyroid carcinoma metastasis was unclear. This study aimed to investigate whether BRAF(V600E) is predictive for distant metastasis in the Chinese population. METHODS: One hundred and seven patients with papillary thyroid carcinoma were enrolled in this study, including 43 patients with distant metastasis and 64 patients without. Quantitative real-time polymerase chain reaction was used to detect BRAF(V600E) mutation, while immunohistochemistry was performed to detect vascular endothelial growth factor (VEGF) expression. The associations between distant metastasis and BRAF(V600E) mutation, and VEGF expression as well as local clinicopathological factors were determined. RESULTS: A total of 28.6% of the patients in the distant metastasis group harbored BRAF(V600E) mutation, which was significantly lower than in the without distant metastasis group (68.8%, P < 0.001). BRAF(V600E) mutation was negatively correlated with positive VEGF expression (P = 0.001). Furthermore, 52.2% of the patients with distant metastasis exhibited VEGF expression, compared with 25.0% of those without. Higher levels of VEGF expression were also observed in the distant metastasis group. Tumor size, extra-thyroid invasion, and BRAF(V600E) mutation were independent predictors for distant metastasis according to multivariate analysis (odds ratios were 2.8, 12.4, and 0.3; 95% CI 1.483-5.334, and 2.950-52.407, 0.100-0.890; P = 0.002, 0.001, and 0.030, respectively). BRAF(V600E) mutation was negatively correlated with distant metastasis in adult subgroup analysis (P = 0.005) but was not an independent parameter. CONCLUSIONS: BRAF(V600E) mutation is predictive for distant metastasis in papillary thyroid carcinoma but not positively. VEGF may be involved in the pathogenesis of distant metastasis.


Assuntos
Carcinoma/genética , Mutação , Proteínas Proto-Oncogênicas B-raf/genética , Neoplasias da Glândula Tireoide/genética , Adulto , Carcinoma/química , Carcinoma/patologia , Carcinoma Papilar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Câncer Papilífero da Tireoide , Neoplasias da Glândula Tireoide/química , Neoplasias da Glândula Tireoide/patologia , Fator A de Crescimento do Endotélio Vascular/análise
19.
PLoS One ; 8(2): e56004, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23457491

RESUMO

In this study, we examined anti-fungal and anti-inflammatory effects of the synthetic melanocortin peptide (Ac-Cys-Lys-Pro-Val-NH2)2 or (CKPV)2 against Candida albicans vaginitis. Our in vitro results showed that (CKPV)2 dose-dependently inhibited Candida albicans colonies formation. In a rat Candida albicans vaginitis model, (CKPV)2 significantly inhibited vaginal Candida albicans survival and macrophages sub-epithelial mucosa infiltration. For mechanisms study, we observed that (CKPV)2 inhibited macrophages phagocytosis of Candida albicans. Meanwhile, (CKPV)2 administration inhibited macrophage pro-inflammatory cytokines (TNF-α, IL-1ß and IL-6) release, while increasing the arginase activity and anti-inflammatory cytokine IL-10 production, suggesting macrophages M1 to M2 polarization. Cyclic AMP (cAMP) production was also induced by (CKPV)2 administration in macrophages. These above effects on macrophages by (CKPV)2 were almost reversed by melanocortin receptor-1(MC1R) siRNA knockdown, indicating the requirement of MC1R in the process. Altogether, our results suggest that (CKPV)2 exerted anti-fungal and anti-inflammatory activities against Candida albicans vaginitis probably through inducing macrophages M1 to M2 polarization and MC1R activation.


Assuntos
Anti-Inflamatórios/farmacologia , Antifúngicos/farmacologia , Candida albicans/efeitos dos fármacos , Candidíase Vulvovaginal/tratamento farmacológico , Macrófagos/efeitos dos fármacos , Melanocortinas/farmacologia , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/uso terapêutico , Antifúngicos/química , Antifúngicos/uso terapêutico , Células COS , Candidíase Vulvovaginal/imunologia , Candidíase Vulvovaginal/microbiologia , Células Cultivadas , Citocinas/imunologia , Feminino , Humanos , Macrófagos/citologia , Macrófagos/imunologia , Macrófagos/microbiologia , Melanocortinas/química , Melanocortinas/uso terapêutico , Camundongos , Fagocitose/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Receptor Tipo 1 de Melanocortina/imunologia , Vagina/efeitos dos fármacos , Vagina/imunologia , Vagina/microbiologia
20.
J Ultrasound Med ; 31(11): 1767-75, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23091247

RESUMO

OBJECTIVES: To assess the efficacy of sonography for discriminating nodular Hashimoto thyroiditis from papillary thyroid carcinoma in patients with sonographically evident diffuse Hashimoto thyroiditis. METHODS: This study included 20 patients with 24 surgically confirmed Hashimoto thyroiditis nodules and 40 patients with 40 papillary thyroid carcinoma nodules; all had sonographically evident diffuse Hashimoto thyroiditis. A retrospective review of the sonograms was performed, and significant benign and malignant sonographic features were selected by univariate and multivariate analyses. The combined likelihood ratio was calculated as the product of each feature's likelihood ratio for papillary thyroid carcinoma. We compared the abilities of the original sonographic features and combined likelihood ratios in diagnosing nodular Hashimoto thyroiditis and papillary thyroid carcinoma by their sensitivity, specificity, and Youden index. RESULTS: The diagnostic capabilities of the sonographic features varied greatly, with Youden indices ranging from 0.175 to 0.700. Compared with single features, combinations of features were unable to improve the Youden indices effectively because the sensitivity and specificity usually changed in opposite directions. For combined likelihood ratios, however, the sensitivity improved greatly without an obvious reduction in specificity, which resulted in the maximum Youden index (0.825). With a combined likelihood ratio greater than 7.00 as the diagnostic criterion for papillary thyroid carcinoma, sensitivity reached 82.5%, whereas specificity remained at 100.0%. With a combined likelihood ratio less than 1.00 for nodular Hashimoto thyroiditis, sensitivity and specificity were 90.0% and 92.5%, respectively. CONCLUSIONS: Several sonographic features of nodular Hashimoto thyroiditis and papillary thyroid carcinoma in a background of diffuse Hashimoto thyroiditis were significantly different. The combined likelihood ratio may be superior to original sonographic features for discrimination of nodular Hashimoto thyroiditis from papillary thyroid carcinoma; therefore, it is a promising risk index for thyroid nodules and warrants further investigation.


Assuntos
Algoritmos , Carcinoma/diagnóstico por imagem , Doença de Hashimoto/diagnóstico por imagem , Interpretação de Imagem Assistida por Computador/métodos , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Adulto , Carcinoma Papilar , Interpretação Estatística de Dados , Diagnóstico Diferencial , Feminino , Humanos , Aumento da Imagem/métodos , Funções Verossimilhança , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Câncer Papilífero da Tireoide , Ultrassonografia
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