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1.
Arch Dis Child ; 106(3): 231-237, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33355158

RESUMO

BACKGROUND: Diagnosis of congenital syphilis (CS) is not straightforward and can be challenging. This study aimed to evaluate the validity of an algorithm using timing of maternal antisyphilis treatment and titres of non-treponemal antibody as predictors of CS. METHODS: Confirmed CS cases and those where CS was excluded were obtained from the Guangzhou Prevention of Mother-to-Child Transmission of syphilis programme between 2011 and 2019. We calculated sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) using receiver operating characteristics (ROC) in two situations: (1) receiving antisyphilis treatment or no-treatment during pregnancy and (2) initiating treatment before 28 gestational weeks (GWs), initiating after 28 GWs or receiving no treatment for syphilis seropositive women. RESULTS: Among 1558 syphilis-exposed children, 39 had confirmed CS. Area under the curve, sensitivity and specificity of maternal non-treponemal titres before treatment and treatment during pregnancy were 0.80, 76.9%, 78.7% and 0.79, 69.2%, 88.7%, respectively, for children with CS. For the algorithm, ROC results showed that PPV and NPV for predicting CS were 37.3% and 96.4% (non-treponemal titres cut-off value 1:8 and no antisyphilis treatment), 9.4% and 100% (non-treponemal titres cut-off value 1:16 and treatment after 28 GWs), 4.2% and 99.5% (non-treponemal titres cut-off value 1:32 and treatment before 28 GWs), respectively. CONCLUSIONS: An algorithm using maternal non-treponemal titres and timing of treatment during pregnancy could be an effective strategy to diagnose or rule out CS, especially when the rate of loss to follow-up is high or there are no straightforward diagnostic tools.


Assuntos
Programas de Rastreamento/métodos , Complicações Infecciosas na Gravidez/imunologia , Sífilis Congênita/diagnóstico , Sífilis Congênita/imunologia , Adulto , Algoritmos , China/epidemiologia , Feminino , Idade Gestacional , Humanos , Incidência , Recém-Nascido , Transmissão Vertical de Doença Infecciosa/prevenção & controle , Valor Preditivo dos Testes , Gravidez , Complicações Infecciosas na Gravidez/epidemiologia , Complicações Infecciosas na Gravidez/prevenção & controle , Estudos Retrospectivos , Fatores de Risco , Sensibilidade e Especificidade , Sorodiagnóstico da Sífilis/métodos , Sífilis Congênita/tratamento farmacológico , Sífilis Congênita/epidemiologia , Treponema pallidum/imunologia
2.
Biomed Res Int ; 2020: 7626274, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32462016

RESUMO

Background: To eliminate mother-to-child transmission of syphilis, the Chinese government recommends a treatment regimen that slightly differs from the World Health Organization- (WHO-) recommended treatment. However, little is known about their difference in efficacy. This study is aimed at comparing the effect of China-recommended and WHO-recommend treatment regimens on adverse pregnancy outcomes (APOs) and at examining associated risk factors of APOs among syphilis-seropositive women. Methods: Using the syphilis registry data, we retrospectively collected data from 4488 syphilis-infected pregnant women in Guangzhou during 2011-2018. Multivariate analyses were used to investigate the association between treatment regimens and APOs (ectopic pregnancy, spontaneous abortion, stillbirth, preterm birth or low birth weight, newborn smaller than gestational age, congenital syphilis, and infant death) and the association between risk factors and APOs. Results: Of 3474 participants, 27.3% had at least one APO. Compared to those receiving WHO-recommended treatment, women who received China-recommended treatment were less likely to have APOs (odds ratio (OR) 0.47, 95% confidence interval (CI) 0.38-0.57), whereas those who received no treatment had 1.6 times higher odds of experiencing APOs. One common risk factor across different APOs was high levels of log2-transformed toluidine red unheated serum test (TRUST) titers before treatment (OR 1.14, 95% CI 1.10-1.19). China-recommended treatment was effective in reducing APOs for those with TRUST ≥ 1 : 8 (OR 0.21, 95% CI 0.14-0.29) and those with TRUST < 1 : 8 (OR 0.62, 95% CI 0.50-0.77). Conclusions: Syphilis-seropositive women receiving China-recommended treatment had lower odds of APOs, especially when TRUST titers before treatment were high. Findings can be used to guide health professionals to reduce APOs among syphilis-infected mothers and promote nationwide use of China-recommended treatment.

3.
Biomed Environ Sci ; 32(10): 719-729, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31843042

RESUMO

OBJECTIVE: This study aimed to evaluate the effects of in-utero exposure to HIV and ART on pregnancy outcome and early growth of children. METHODS: This cohort study enrolled 802 HIV-infected pregnant women between October 2009 and May 2018 in Guangzhou, China. The women were assigned to receive combination ART (cART) or mono/dual ART or no treatment. The primary outcomes were the combined endpoints of any adverse pregnancy outcome [including ectopic pregnancy, spontaneous abortion, stillbirth, preterm birth, small for gestational age (SGA)] and adverse early growth outcome (including infant death, HIV infection of mother-to-child transmission, and underweight, wasting and stunting of infants at 4 weeks of age). RESULTS: Adverse pregnancy outcomes occurred in 202 (35.1%) of all enrolled HIV-infected women, and 121 (31.3%) of all infants exhibited adverse effects on early growth at 4 weeks of age. The rates of adverse pregnancy outcomes, spontaneous abortion, ectopic pregnancy, stillbirth, infant death and perinatal HIV infection were higher among women not receiving ART, compared to those treated with cART or mono/dual ART (P < 0.05). However, women treated with cART had a higher rate of SGA, compared to untreated women (P < 0.05). No differences in early infant growth were observed among the different treatment regimens. CONCLUSION: Our findings underscore the essentiality of prioritizing HIV-positive pregnant women for ART, as even mono/dual ART available in resource-limited countries could improve pregnancy outcomes and infant survival..


Assuntos
Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/transmissão , Transmissão Vertical de Doença Infecciosa , Complicações Infecciosas na Gravidez/epidemiologia , Resultado da Gravidez/epidemiologia , Adulto , China/epidemiologia , Estudos de Coortes , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Gravidez , Complicações Infecciosas na Gravidez/virologia , Estudos Prospectivos , Adulto Jovem
4.
Tumori ; 105(3): 231-242, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30674231

RESUMO

The present study aimed to investigate the role of semaphorin 4D (Sema4D) in bladder cancer cell proliferation and metastasis in vivo and in vitro. Effects of Sema4D modulation on cancer cell viability and clonogenic abilities were assessed by MTT assay and colony formation assay. Cell apoptosis, cell cycle analysis, transwell assays, and wound-healing assays were also assayed. A mouse model of bladder cancer was established to observe the tumorigenesis in vivo. Our data showed that Sema4D was 4-fold upregulated in clinical bladder cancer tissues relative to noncancerous ones and differentially expressed in bladder cancer cell lines. Knockdown of Sema4D in bladder cancer T24 and 5637 cells significantly decreased cell proliferation, clonogenic potential, and motility. On the contrary, overexpression of Sema4D in bladder cancer SV-HUC-1 cells significantly increased cell viability and motility. Concordantly, knockdown of Sema4D impaired while overexpression of Sema4D promoted bladder cancer cell growth rates in xenotransplanted mice. Cell cycle was arrested by modulation of Sema4D. Cell apoptotic rates and the mitochondrial membrane potentials were consistently increased upon knockdown of Sema4D in T24 cells and 5637 cells. Western blotting revealed that epithelial-mesenchymal transition was promoted by Sema4D. The PI3K/AKT pathway was activated upon Sema4D overexpression in SV-HUC-1 cells, while it was inactivated by knockdown of Sema4D in T24 cells. All these data suggest that Sema4D promotes cell proliferation and metastasis in bladder cancer in vivo and in vitro. The oncogenic behavior of Sema4D is achieved by activating the PI3K/AKT pathway.


Assuntos
Antígenos CD/genética , Proliferação de Células/genética , Transição Epitelial-Mesenquimal/genética , Semaforinas/genética , Neoplasias da Bexiga Urinária/genética , Animais , Apoptose/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Sobrevivência Celular/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Camundongos , Metástase Neoplásica , Fosfatidilinositol 3-Quinases/genética , Proteínas Proto-Oncogênicas c-akt/genética , Transdução de Sinais/genética , Neoplasias da Bexiga Urinária/patologia , Ensaios Antitumorais Modelo de Xenoenxerto
5.
Zhen Ci Yan Jiu ; 43(10): 661-5, 2018 Oct 25.
Artigo em Chinês | MEDLINE | ID: mdl-30365263

RESUMO

OBJECTIVE: To compare the therapeutic effect of acupuncture plus moxibustion and simple acupuncture in the treatment of patients with knee osteoarthritis (KOA) of yang-deficiency syndrome. METHODS: Fifty-eight KOA patients with yang-deficiency syndrome were chosen and randomly divided into acupuncture plus moxibustion group (n=30) and acupuncture group (n=28). Neixiyan (EX-LE 4), Dubi (ST 35), Liangqiu (ST 34), Heding (EX-LE 2), Xuehai (SP 10), Yanglingquan (GB 34) on the affected side of the body were punctured with filiform needles or/and stimulated with moxibustion using seed-sized moxa cones. The treatment was conducted once daily for 10 days, followed with another 10 days after 2 days interval. The pain severity was evaluated by using visual analogue scale (VAS), and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores were used to measure the KOA pain, stiffness and function before and after the treatment, and 1 month after the treatment. The therapeutic effect was also evaluated according to the "Standards for Diagnosis and Therapeutic Effect Evaluation of Diseases/Syndromes of Traditional Chinese Medicine" (issued by the State Administration of Traditional Chinese Medicine of China in 1994). RESULTS: Twenty days and 1 month after the treatment, the scores of VAS, and KOA pain, stiffness and motor function of WOMAC were significantly decreased in both groups in comparison with their own pre-treatment (P<0.01), and were obviously lower in the acupuncture plus moxibustion group than in the acupuncture group (P<0.05, P<0.01). Of the 28 and 30 cases in the acupuncture and acupuncture plus moxibustion groups, 7 and 12 experienced marked improvement, 12 and 16 were effective, 9 and 2 ineffective, with the therapeutic effect being 67.86% and 93.33%, respectively. The therapeutic effect of acupuncture plus moxibustion was apparently superior to that of simple acupuncture (P<0.05). CONCLUSION: Acupuncture plus moxibustion is significantly superior to simple acupuncture therapy in relieving symptoms of KOA patients, and also has a better post-effect.


Assuntos
Terapia por Acupuntura , Moxibustão , Osteoartrite do Joelho , China , Humanos , Osteoartrite do Joelho/terapia , Resultado do Tratamento
6.
Oncotarget ; 7(52): 87462-87472, 2016 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-27974680

RESUMO

Midkine, a heparin-binding growth factor, has been identified as a promising cancer biomarker. In non-small cell lung cancer (NSCLC), the serum and urine midkine levels have not been intensively investigated. The aim of the present study was to investigate the diagnostic and prognostic potential of serum and urine midkine levels in patients with NSCLC. The serum midkine levels were measured in 153 patients with NSCLC, 23 patients with benign pulmonary disease and 95 healthy controls using ELISA. Urine midkine levels were examined in 20 controls and 45 patients with NSCLC. Midkine expression in tumor tissues from 72 patients with NSCLC who underwent definitive surgical resection without any pre-operative treatments was examined by immunohistochemistry. Serum levels were significantly higher in patients with NSCLC than in healthy controls (657.36±496.58 pg/ml vs. 194.49±122.57 pg/ml, P<0.001). As shown in the ROC curve analysis, the sensitivity and specificity of the cut-off serum midkine concentration of 400 pg/ml for predicting the presence of NSCLC were 71.2% and 88.1%, respectively. Positive correlations between the serum midkine levels and immunohistochemistry staining scores (r=0.315, P=0.007) and between the serum midkine levels and urine midkine levels (r=0.636, P<0.001) were observed using Spearman's bivariate correlations. The serum midkine concentration was identified as an independent prognostic factor by multivariate analysis, and its overexpression yielded a relative risk of death of 2.072 (0.01.


Assuntos
Biomarcadores Tumorais/análise , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Citocinas/análise , Neoplasias Pulmonares/diagnóstico , Adulto , Idoso , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Citocinas/sangue , Citocinas/urina , Feminino , Humanos , Imuno-Histoquímica , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Midkina , Prognóstico
7.
Growth Factors ; 34(1-2): 19-32, 2016 02.
Artigo em Inglês | MEDLINE | ID: mdl-27144323

RESUMO

Brain-derived neurotrophic factor (BDNF) plays important roles in neural stem cell (NSC) growth. In this study, we investigated whether BDNF exerts its neurotrophic effects through the Wnt/ß-catenin signaling pathway in human embryonic spinal cord NSCs (hESC-NSCs) in vitro. We found an increase in hESC-NSC growth by BDNF overexpression. Furthermore, expression of Wnt1, Frizzled1 and Dsh was upregulated, whereas GSK-3ß expression was downregulated. In contrast, hESC-NSC growth was decreased by BDNF RNA interference. BDNF, Wnt1 and ß-catenin components were all downregulated, whereas GSK-3ß was upregulated. Next, we treated hESC-NSCs with 6-bromoindirubin-3'-oxime (BIO), a small molecule inhibitor of GSK-3ß. BIO reduced the effects of BDNF upregulation/downregulation on the cell number, soma size and differentiation, and suppressed the effect of BDNF modulation on the Wnt signaling pathway. Our findings suggest that BDNF promotes hESC-NSC growth in vitro through crosstalk with the Wnt/ß-catenin signaling pathway, and that this interaction may be mediated by GSK-3ß.


Assuntos
Fator Neurotrófico Derivado do Encéfalo/genética , Proliferação de Células , Células-Tronco Embrionárias/metabolismo , Glicogênio Sintase Quinase 3 beta/metabolismo , Células-Tronco Neurais/metabolismo , Via de Sinalização Wnt , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Células Cultivadas , Células-Tronco Embrionárias/fisiologia , Receptores Frizzled/genética , Receptores Frizzled/metabolismo , Humanos , Células-Tronco Neurais/fisiologia , Regulação para Cima , beta Catenina/metabolismo
8.
Mol Oncol ; 10(4): 610-24, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26774881

RESUMO

Cyclooxygenase-2 (COX-2) is highly expressed in tumor cells and has been regarded as a hallmarker for cancers, but the excise regulatory mechanism of COX-2 in tumorigenesis remains largely unknown. Here, we pulled down and identified a novel COX-2 regulator, heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNPA2/B1), which could specifically bind to COX-2 core promoter and regulate tumor growth in non-small-cell lung cancers (NSCLCs). Knockdown of hnRNPA2/B1 by shRNA or siRNA downregulated COX-2 expression and prostaglandin E2 (PGE2) production, and suppressed tumor cell growth in NSCLC cells in vitro and in vivo. Conversely, overexpression of hnRNPA2/B1 up-regulated the levels of COX-2 and PGE2 and promoted tumor cell growth. We also showed that hnRNPA2/B1 expression was positively correlated with COX-2 expression in NSCLC cell lines and tumor tissues, and the up-regulated expression of hnRNPA2/B1 and COX-2 predicted worse prognosis in NSCLC patients. Furthermore, we demonstrated that the activation of COX-2 expression by hnRNPA2/B1 was mediated through the cooperation with p300, a transcriptional co-activator, in NSCLC cells. The hnRNPA2/B1 could interact with p300 directly and be acetylated by p300. Exogenous overexpression of p300, but not its histone acetyltransferase (HAT) domain deletion mutation, augmented the acetylation of hnRNPA2/B1 and enhanced its binding on COX-2 promoter, thereby promoted COX-2 expression and lung cancer cell growth. Collectively, our results demonstrate that hnRNPA2/B1 promotes tumor cell growth by activating COX-2 signaling in NSCLC cells and imply that the hnRNPA2/B1/COX-2 pathway may be a potential therapeutic target for human lung cancers.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/metabolismo , Ciclo-Oxigenase 2/biossíntese , Regulação Neoplásica da Expressão Gênica , Ribonucleoproteínas Nucleares Heterogêneas Grupo A-B/metabolismo , Neoplasias Pulmonares/metabolismo , Proteínas de Neoplasias/metabolismo , Regulação para Cima , Animais , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Ciclo-Oxigenase 2/genética , Indução Enzimática , Feminino , Ribonucleoproteínas Nucleares Heterogêneas Grupo A-B/genética , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Masculino , Camundongos , Camundongos Nus , Proteínas de Neoplasias/genética , Regiões Promotoras Genéticas , Transdução de Sinais/genética
9.
Oncotarget ; 7(3): 2985-3001, 2016 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-26672764

RESUMO

Melatonin, a molecule produced throughout the animal and plant kingdoms, and berberine, a plant derived agent, both exhibit antitumor and multiple biological and pharmacological effects, but they have never been combined altogether for the inhibition of human lung cancers. In this study, we investigated the role and underlying mechanisms of melatonin in the regulation of antitumor activity of berberine in lung cancer cells. Treatment with melatonin effectively increased the berberine-mediated inhibitions of cell proliferation, colony formation and cell migration, thereby enhancing the sensitivities of lung cancer cells to berberine. Melatonin also markedly increased apoptosis induced by berberine. Further mechanism study showed that melatonin promoted the cleavage of caspse-9 and PARP, enhanced the inhibition of Bcl2, and triggered the releasing of cytochrome C (Cyto C), thereby increasing the berberine-induced apoptosis. Melatonin also enhanced the berberine-mediated inhibition of telomerase reverses transcriptase (hTERT) by down-regulating the expression of AP-2ß and its binding on hTERT promoter. Moreover, melatonin enhanced the berberine-mediated inhibition of cyclooxygenase 2 (COX-2) by inhibiting the nuclear translocation of NF-κB and its binding on COX-2 promoter. Melatonin also increased the berberine-mediated inhibition of the phosphorylated Akt and ERK. Collectively, our results demonstrated that melatonin enhanced the antitumor activity of berberine by activating caspase/Cyto C and inhibiting AP-2ß/hTERT, NF-κB/COX-2 and Akt/ERK signaling pathways. Our findings provide new insights in exploring the potential therapeutic strategies and novel targets for lung cancer treatment.


Assuntos
Antineoplásicos/farmacologia , Berberina/farmacologia , Inibidores de Ciclo-Oxigenase 2/farmacologia , MAP Quinases Reguladas por Sinal Extracelular/antagonistas & inibidores , Neoplasias Pulmonares/tratamento farmacológico , Melatonina/farmacologia , NF-kappa B/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Telomerase/antagonistas & inibidores , Fator de Transcrição AP-2/antagonistas & inibidores , Transporte Ativo do Núcleo Celular , Animais , Protocolos de Quimioterapia Combinada Antineoplásica , Apoptose/efeitos dos fármacos , Caspase 9/metabolismo , Linhagem Celular Tumoral , Ciclo-Oxigenase 2/metabolismo , Citocromos c/metabolismo , Proteínas de Ligação a DNA/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , NF-kappa B/metabolismo , Poli(ADP-Ribose) Polimerases/metabolismo , Regiões Promotoras Genéticas/genética , Proteínas Proto-Oncogênicas c-bcl-2/antagonistas & inibidores , Transdução de Sinais/efeitos dos fármacos , Fator de Transcrição AP-2/biossíntese , Ensaios Antitumorais Modelo de Xenoenxerto
10.
Oncotarget ; 6(32): 33878-92, 2015 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-26418899

RESUMO

BPTF, a subunit of NURF, is well known to be involved in the development of eukaryotic cell, but little is known about its roles in cancers, especially in non-small-cell lung cancer (NSCLC). Here we showed that BPTF was specifically overexpressed in NSCLC cell lines and lung adenocarcinoma tissues. Knockdown of BPTF by siRNA significantly inhibited cell proliferation, induced cell apoptosis and arrested cell cycle progress from G1 to S phase. We also found that BPTF knockdown downregulated the expression of the phosphorylated Erk1/2, PI3K and Akt proteins and induced the cleavage of caspase-8, caspase-7 and PARP proteins, thereby inhibiting the MAPK and PI3K/AKT signaling and activating apoptotic pathway. BPTF knockdown by siRNA also upregulated the cell cycle inhibitors such as p21 and p18 but inhibited the expression of cyclin D, phospho-Rb and phospho-cdc2 in lung cancer cells. Moreover, BPTF knockdown by its specific shRNA inhibited lung cancer growth in vivo in the xenografts of A549 cells accompanied by the suppression of VEGF, p-Erk and p-Akt expression. Immunohistochemical assay for tumor tissue microarrays of lung tumor tissues showed that BPTF overexpression predicted a poor prognosis in the patients with lung adenocarcinomas. Therefore, our data indicate that BPTF plays an essential role in cell growth and survival by targeting multiply signaling pathways in human lung cancers.


Assuntos
Adenocarcinoma/metabolismo , Antígenos Nucleares/metabolismo , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Fatores de Transcrição/metabolismo , Adenocarcinoma de Pulmão , Idoso , Animais , Apoptose , Ciclo Celular , Linhagem Celular Tumoral , Proliferação de Células , Separação Celular , Sobrevivência Celular , Feminino , Fibroblastos/metabolismo , Citometria de Fluxo , Humanos , Imuno-Histoquímica , Sistema de Sinalização das MAP Quinases , Masculino , Camundongos , Camundongos Nus , Pessoa de Meia-Idade , Transplante de Neoplasias , Análise de Sequência com Séries de Oligonucleotídeos , Fosfatidilinositol 3-Quinases/metabolismo , Prognóstico , Modelos de Riscos Proporcionais , RNA Interferente Pequeno/metabolismo , Transdução de Sinais
11.
Asian Pac J Cancer Prev ; 16(11): 4577-81, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26107206

RESUMO

BACKGROUND: To explore the hospitalizations of breast cancer patients undergoing mastectomy, and to provide a basis for management, clinical prevention and treatment. MATERIALS AND METHODS: We conducted an investigation by means of the retrospective survey and the medical records retrieval system, and made out the data of patients suffered from breast cancer in a hospital in Guangzhou from 2004 to 2013, including age, medical payment methods, pathological type, treatment, treatment results, complications, hospitalization days, cost and so on. RESULTS: The average age of the inpatients was 50.14 years old. The main histologic types were infiltrating duct carcinoma (88.06%). The main surgery was modified radical mastectomy (80.41%). The cure rate was 90.80% during the 10 years. The main medical payment method was self-paying (57.28%). The average hospital stay was 13.51 days, and average hospitalization cost was RMB 23,083.66 yuan, proportion of drug fees up to 39.70%. Postoperative complication rate was 0.79%. The self-paying group was with the highest proportion of drug fees (P<0.05), while the free medical service group was with the longest hospitalization days (P<0.05). CONCLUSIONS: The payment methods significantly affected the proportion of drug fees and hospitalization days. The therapeutic effect was satisfactory with less complications and reasonable proportion of drug fees in our hospital.


Assuntos
Adenocarcinoma Mucinoso/cirurgia , Neoplasias da Mama/cirurgia , Carcinoma Ductal de Mama/cirurgia , Carcinoma Lobular/cirurgia , Hospitalização/economia , Mastectomia/economia , Adenocarcinoma Mucinoso/economia , Adenocarcinoma Mucinoso/secundário , Adulto , Neoplasias da Mama/economia , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/economia , Carcinoma Ductal de Mama/secundário , Carcinoma Lobular/economia , Carcinoma Lobular/secundário , China , Feminino , Seguimentos , Custos Hospitalares , Humanos , Pacientes Internados , Tempo de Internação , Metástase Linfática , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Fatores de Tempo
12.
Int J Clin Exp Med ; 8(3): 3227-33, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26064212

RESUMO

OBJECTIVE: To investigate the expression of mir-16 in lung adenocarcinoma cancer line and to observe the effect of mir-16 on the biological behaviors of human lung adenocarcinoma cancer A549 cell. Methods the expression of mir-16 in A549 cells was examined by quantitative real-time (qRT)-PCR. mir-16 minics was chemically synthesized and transfected into A549 cells by Lipofectamine 2000. The cell cycle and apoptosis changes were assayed by flow cytometry, the cell proliferation was measured by MTS assay. The wild-type and mutant wip1 3'-UTR luciferase reporter rectors were constructed. The relative activity of renila luciferase was detected to confirm the binding site of mir-16 on wip1 mRNA. Results, the expression of mir-16 is reduced in A549 cell compared with the normal bronchial epithelial cell. Transfection of mir-16 minics significantly suppressed the luciferase reporter containing wild type not mutant wip1 3'-UTR. Furthermore enforced expression of mir-16 lead to reduced A549 cell proliferation and promote apoptosis. Conclusion Therapeutic strategies to resume miRNA-16 expression may be benefit to patients with NSCLC in the feature.

13.
Proc Natl Acad Sci U S A ; 112(16): 5225-30, 2015 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-25847999

RESUMO

Alzheimer's disease (AD) is one of most devastating diseases affecting elderly people. Amyloid-ß (Aß) accumulation and the downstream pathological events such as oxidative stress play critical roles in pathogenesis of AD. Lessons from failures of current clinical trials suggest that targeting multiple key pathways of the AD pathogenesis is necessary to halt the disease progression. Here we show that Edaravone, a free radical scavenger that is marketed for acute ischemic stroke, has a potent capacity of inhibiting Aß aggregation and attenuating Aß-induced oxidation in vitro. When given before or after the onset of Aß deposition via i.p. injection, Edaravone substantially reduces Aß deposition, alleviates oxidative stress, attenuates the downstream pathologies including Tau hyperphosphorylation, glial activation, neuroinflammation, neuronal loss, synaptic dysfunction, and rescues the behavioral deficits of APPswe/PS1 mice. Oral administration of Edaravone also ameliorates the AD-like pathologies and memory deficits of the mice. These findings suggest that Edaravone holds a promise as a therapeutic agent for AD by targeting multiple key pathways of the disease pathogenesis.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Antipirina/análogos & derivados , Transtornos Cognitivos/tratamento farmacológico , Administração Oral , Doença de Alzheimer/complicações , Doença de Alzheimer/patologia , Amiloide/metabolismo , Peptídeos beta-Amiloides/toxicidade , Animais , Antipirina/administração & dosagem , Antipirina/química , Antipirina/farmacologia , Antipirina/uso terapêutico , Comportamento Animal/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Encéfalo/patologia , Linhagem Celular , Transtornos Cognitivos/complicações , Transtornos Cognitivos/patologia , Dendritos/efeitos dos fármacos , Dendritos/patologia , Edaravone , Humanos , Inflamação/patologia , Camundongos Transgênicos , Neurotoxinas/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Fosforilação/efeitos dos fármacos , Presenilina-1/metabolismo , Agregação Patológica de Proteínas/complicações , Agregação Patológica de Proteínas/tratamento farmacológico , Processamento de Proteína Pós-Traducional/efeitos dos fármacos , Proteínas tau/metabolismo
14.
Anim Sci J ; 86(6): 588-94, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25488605

RESUMO

The present study evaluates the effects of embryonic age and proteolytic enzymes on the isolation and primary culture of chicken enterocyte and to establish an effective technique for chicken intestinal epithelial cell (IEC) cultivation. Fourteen-day-old, 16-day-old and 18-day-old embryos (average weight: 52.23 ± 0.76 g, 50.86 ± 0.99 g, 48.98 ± 1.03 g) were the source for preparation of enterocyte culture, and trypsin-ethylene diamine tetraacetic acid, collagenase, thermolysin and combination of collagenase and thermolysin were used for digestion medium. Optimal culture protocols were determined by qualitative assays of proliferation. Cells isolated by using 14-day-old embryo and collagenase obtain the best attachment and growth in culture, and the production of continuously growing IEC cultures. Thus, we conclude that the use of collagenase as a dissociating enzyme and 14-day-old embryo as a source can be advantageously applied to the isolation of chicken IEC and this method may be useful for various applications and basic studies of the intestinal tract concerning such objects as physiology, immunology and toxicology.


Assuntos
Técnicas de Cultura de Células/métodos , Separação Celular/métodos , Colagenases/metabolismo , Enterócitos/citologia , Mucosa Intestinal/citologia , Mucosa Intestinal/embriologia , Animais , Proliferação de Células , Células Cultivadas , Embrião de Galinha , Galinhas , Meios de Cultura , Ácido Edético/farmacologia , Desenvolvimento Embrionário , Mucosa Intestinal/enzimologia , Termolisina/metabolismo , Tripsina/farmacologia
15.
Zhonghua Nan Ke Xue ; 20(5): 430-4, 2014 May.
Artigo em Chinês | MEDLINE | ID: mdl-24908734

RESUMO

OBJECTIVE: To study the safety, effectiveness and feasibility of suprapubis-assisted umbilical laparoendoscopic mini-dual-site surgery (SAU-LEMDS) in the treatment of varicocele. METHODS: This study included 80 varicocele patients aged 24 - 44 (mean 28.5 +/- 2.6) years, 25 cases of grade I, 45 cases of grade II and 10 cases of grade III, 58 cases in the left side, 6 in the right and 16 in both sides, and all with asthenospermia. The patients were treated by SAU-LEMDS under subarachnoid anesthesia combined with general anesthesia in a supine position with a head-down-feet-up slope of 15 degrees. Two 5 mm trocars were inserted bilaterally at the umbilical edge, one with a 5 mm 30 degrees laparoscope placed in it, and another into the abdominal cavity below the pubic hairline with a 5 mm laparoendoscopic clipper placed in it. The operation procedure was similar to that of standard laparoscopic ligation of spermatic veins, with reservation of the spermatic artery and double-ligation of spermatic veins. And the procedure was repeated for the contralateral lesion in the bilateral cases. Postoperative follow-up was conducted for the incidences of orchiatrophy and testicular hydrocele and changes of seminal parameters. RESULTS: All the operations were successful, with the mean operation time of (10 +/- 5.0) min (range 8 to 25 min) for the unilateral cases and (18 +/- 6.5) min (range 15 to 30 min) for the bilateral cases, the mean blood loss of (1.5 +/- 0.5) ml (range 1 to 2 ml), and the mean postoperative hospital stay of (2 +/- 0.5) d (range 1.5 to 3 d). The patients were followed up for 6 -24 (12 +/- 2.5) months, which showed significant improvement in sperm motility as compared with the baseline ([28.53 +/- 5.21] vs [19.62 +/- 3.56]%, P < 0.05), with 28 cases (35.0%) restored to normal. Recurrence was found in 4 cases (5.0%). Testicular hydrocele occurred in 7 cases (8.75%), but orchiatrophy in none. The scars in the umbilicus and suprapubis were invisible because of the wrinkles and pubic hair. CONCLUSION: SAU-LEMDS is safe, effective and feasible for the treatment of varicocele. It is superior to umbilical laparoendoscopic single-site surgery (U-LESS) for its less invasiveness, simpler operation, and better cosmetic appearance.


Assuntos
Laparoscopia/métodos , Cordão Espermático/irrigação sanguínea , Varicocele/cirurgia , Adulto , Astenozoospermia , Humanos , Laparoscopia/efeitos adversos , Tempo de Internação , Ligadura/métodos , Masculino , Duração da Cirurgia , Período Pós-Operatório , Recidiva , Hidrocele Testicular/etiologia , Resultado do Tratamento , Umbigo , Veias
16.
Zhonghua Wei Chang Wai Ke Za Zhi ; 16(12): 1191-4, 2013 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-24369404

RESUMO

OBJECTIVE: To investigate the expression of vascular endothelial growth factor D (VEGF-D) in human esophageal squamous cell carcinoma (ESCC) and its significance. METHODS: The expression of VEGF-C mRNA in tumor tissues and non-cancer tissues from 39 ESCC patients in our hospital from March 2009 to February 2010 was detected by in situ hybridization (ISH) method. The expression of D2-40 was detected by immunohistochemistry,and microlymphatic vessel density (MLVD) was determined by lymphatic endothelial specific marker D2-40. The associations of VEGF-C mRNA expression with clinical data and MLVD were analyzed. RESULTS: Positive ISH VEGF-D mRNA was observed in tumor tissue samples of 22 cases (56.4%, 22/39) and non-cancer tissue sample of 1 case (2.6%, 1/39), whose difference was statistically significant (P<0.05). The expression of VEGF-D mRNA in ESCC was significantly associated with lymph node metastasis [92.9% (13/14) vs. 36.0% (9/25), P<0.05] and MLVD [(8.20±1.22) vs. (5.31±0.97), P<0.01], but not significantly associated with age, sex, pathological grade and depth of infiltration. CONCLUSION: VEGF-D can promote lymphatic metastasis of ESSC by induction of lymphangiogenesis.


Assuntos
Carcinoma de Células Escamosas/metabolismo , Neoplasias Esofágicas/metabolismo , Fator D de Crescimento do Endotélio Vascular/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas do Esôfago , Feminino , Humanos , Imuno-Histoquímica , Metástase Linfática , Masculino , Pessoa de Meia-Idade
17.
Hum Vaccin Immunother ; 9(7): 1430-7, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23571172

RESUMO

Enterovirus 71 (EV71) is one of the major causative agents for hand, foot and mouth disease (HFMD) in childhood. Nowadays, HFMD or EV71 infections have already become an important public health issue throughout the world. Vaccination may be the most effective measure to control the transmission of the virus. Therefore, to pave EV71 vaccine into human clinical trial, in the present study a comprehensive preclinical safety assessment of inactivated EV71 vaccine including single- and repeat-dose toxicity studies were conducted in rats and cynomolgus monkeys. No abnormal findings were observed in rats following single intramuscular administration with EV71 vaccine (640 U). The results also showed no obvious systemic toxicities from four repetitive intramuscular injections, with a 14-d interval, of two dosages of EV71 vaccine in the two animal species. Antinuclear antibody response was not detected after the repeated administrations. Histopathological examination demonstrated the minimal to severe inflammatory changes in muscle tissues of the injection sites in EV71 vaccine-injected animals and most of findings have been improved over time. Furthermore, test article could induce highly EV71-specfic neutralizing antibody response in both animal species. Taken together, these data suggested a favorable safety profile for inactivated EV71 vaccine and supported this product to enter human phase I clinical trial.


Assuntos
Enterovirus Humano A/imunologia , Doença de Mão, Pé e Boca/imunologia , Doença de Mão, Pé e Boca/prevenção & controle , Vacinas Virais/efeitos adversos , Vacinas Virais/uso terapêutico , Animais , Anticorpos Antinucleares/sangue , Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Feminino , Macaca fascicularis , Masculino , Ratos , Ratos Wistar , Vacinas de Produtos Inativados/efeitos adversos , Vacinas de Produtos Inativados/imunologia , Vacinas de Produtos Inativados/uso terapêutico , Vacinas Virais/imunologia
18.
J Neurochem ; 122(5): 1010-22, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22731248

RESUMO

Amyloid precursor protein (APP) is involved in the pathogenesis of Alzheimer's disease. It is axonally transported, endocytosed and sorted to different cellular compartments where amyloid beta (Aß) is produced. However, the mechanism of APP trafficking remains unclear. We present evidence that huntingtin associated protein 1 (HAP1) may reduce Aß production by regulating APP trafficking to the non-amyloidogenic pathway. HAP1 and APP are highly colocalized in a number of brain regions, with similar distribution patterns in both mouse and human brains. They are associated with each other, the interacting site is the 371-599 of HAP1. APP is more retained in cis-Golgi, trans-Golgi complex, early endosome and ER-Golgi intermediate compartment in HAP1-/- neurons. HAP1 deletion significantly alters APP endocytosis and reduces the re-insertion of APP into the cytoplasmic membrane. Amyloid precursor protein-YFP(APP-YFP) vesicles in HAP1-/- neurons reveal a decreased trafficking rate and an increased number of motionless vesicles. Knock-down of HAP1 protein in cultured cortical neurons of Alzheimer's disease mouse model increases Aß levels. Our data suggest that HAP1 regulates APP subcellular trafficking to the non-amyloidogenic pathway and may negatively regulate Aß production in neurons.


Assuntos
Doença de Alzheimer/patologia , Peptídeos beta-Amiloides/metabolismo , Precursor de Proteína beta-Amiloide/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Neurônios/metabolismo , Doença de Alzheimer/genética , Precursor de Proteína beta-Amiloide/genética , Análise de Variância , Animais , Autoantígenos/metabolismo , Biotinilação , Encéfalo/metabolismo , Células Cultivadas , Córtex Cerebral/patologia , Citoplasma/metabolismo , Modelos Animais de Doenças , Endocitose/genética , Ensaio de Imunoadsorção Enzimática , Transferência Ressonante de Energia de Fluorescência/métodos , Proteínas de Choque Térmico/metabolismo , Humanos , Imunoprecipitação , Integrinas/metabolismo , Proteínas Luminescentes/genética , Proteínas Luminescentes/metabolismo , Proteína 1 de Membrana Associada ao Lisossomo/metabolismo , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Proteínas do Tecido Nervoso/deficiência , Neurônios/ultraestrutura , Fotodegradação , Presenilina-1/genética , Presenilina-1/metabolismo , Transporte Proteico/genética , Interferência de RNA/fisiologia , Transfecção/métodos , Proteínas de Transporte Vesicular/metabolismo , Rede trans-Golgi/genética , Rede trans-Golgi/metabolismo
19.
PLoS One ; 7(4): e35883, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22558255

RESUMO

BACKGROUND: Neurons extend their dendrites and axons to build functional neural circuits, which are regulated by both positive and negative signals during development. Brain-derived neurotrophic factor (BDNF) is a positive regulator for neurite outgrowth and neuronal survival but the functions of its precursor (proBDNF) are less characterized. METHODOLOGY/PRINCIPAL FINDINGS: Here we show that proBDNF collapses neurite outgrowth in murine dorsal root ganglion (DRG) neurons and cortical neurons by activating RhoA via the p75 neurotrophin receptor (p75NTR). We demonstrated that the receptor proteins for proBDNF, p75NTR and sortilin, were highly expressed in cultured DRG or cortical neurons. ProBDNF caused a dramatic neurite collapse in a dose-dependent manner and this effect was about 500 fold more potent than myelin-associated glycoprotein. Neutralization of endogenous proBDNF by using antibodies enhanced neurite outgrowth in vitro and in vivo, but this effect was lost in p75NTR(-/-) mice. The neurite outgrowth of cortical neurons from p75NTR deficient (p75NTR(-/-)) mice was insensitive to proBDNF. There was a time-dependent reduction of length and number of filopodia in response to proBDNF which was accompanied with a polarized RhoA activation in growth cones. Moreover, proBDNF treatment of cortical neurons resulted in a time-dependent activation of RhoA but not Cdc42 and the effect was absent in p75NTR(-/-) neurons. Rho kinase (ROCK) and the collapsin response mediator protein-2 (CRMP-2) were also involved in the proBDNF action. CONCLUSIONS: proBDNF has an opposing role in neurite outgrowth to that of mature BDNF. Our observations suggest that proBDNF collapses neurites outgrowth and filopodial growth cones by activating RhoA through the p75NTR signaling pathway.


Assuntos
Fator Neurotrófico Derivado do Encéfalo/fisiologia , Gânglios Espinais/efeitos dos fármacos , Regulação da Expressão Gênica no Desenvolvimento/fisiologia , Precursores de Proteínas/fisiologia , Proteínas rho de Ligação ao GTP/agonistas , Proteínas Adaptadoras de Transporte Vesicular/genética , Proteínas Adaptadoras de Transporte Vesicular/metabolismo , Animais , Anticorpos/farmacologia , Fator Neurotrófico Derivado do Encéfalo/antagonistas & inibidores , Fator Neurotrófico Derivado do Encéfalo/farmacologia , Células Cultivadas , Gânglios Espinais/citologia , Gânglios Espinais/fisiologia , Camundongos , Camundongos Knockout , Fibras Nervosas/efeitos dos fármacos , Fibras Nervosas/fisiologia , Neuritos/efeitos dos fármacos , Neuritos/fisiologia , Precursores de Proteínas/farmacologia , Pseudópodes/efeitos dos fármacos , Pseudópodes/fisiologia , Receptores de Fator de Crescimento Neural/deficiência , Receptores de Fator de Crescimento Neural/genética , Transdução de Sinais/fisiologia , Imagem com Lapso de Tempo , Proteínas rho de Ligação ao GTP/genética , Proteínas rho de Ligação ao GTP/metabolismo , Proteína rhoA de Ligação ao GTP
20.
Biochem Pharmacol ; 82(10): 1500-9, 2011 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-21762680

RESUMO

Alzheimer's disease (AD), the most common form of dementia, is characterized by the deposition of amyloid plaques, accumulation of fibrillary tangles in neurons, neurite degeneration, loss of neurons, and a progressive loss of cognitive function. The pathogenesis of AD is not fully understood, and no strong disease-modifying therapies are currently available. Recent studies suggest that the pan-neurotrophin receptor, p75NTR, is a critical factor involved in the pathogenesis of AD. In this review, we have discussed the roles of p75NTR in the production of amyloid-beta (Aß), neuronal death, neurite degeneration, tau hyperphosphorylation, cell cycle re-entry and cognition decline in AD, and proposed that p75NTR is a potential target for the development of therapeutic drugs for AD. Finally we provide perspectives in developing various therapeutic strategies targeting different aspects of AD hallmarks which relate to p75NTR functions and breaking the p75NTR-mediated positive feedback loop which promotes the cascades in the pathogenesis of AD.


Assuntos
Doença de Alzheimer/etiologia , Receptor de Fator de Crescimento Neural/metabolismo , Morte Celular , Regulação da Expressão Gênica , Humanos , Neurônios/citologia , Neurônios/metabolismo , Receptor de Fator de Crescimento Neural/genética , Proteína Amiloide A Sérica/metabolismo
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