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Background: Long term hypertension seriously promotes target organ damage in the brain and heart, and has increasingly become serious public health problem worldwide. The anti-hypertensive effects of capsaicin has been reported, however, the role and mechanism of capsaicin within the brain on salt-induced hypertension have yet to be elucidated. This study aimed to verify the hypothesis that capsaicin attenuates salt-induced hypertension via the AMPK/Akt/Nrf2 pathway in hypothalamic paraventricular nucleus (PVN). Methods: Dahl salt-sensitive (Dahl S) rats were used as animal model for the present study. Rats were randomly divided into four groups based on their dietary regimen (0.3% normal salt diet and 8% high salt diet) and treatment methods (infusion of vehicle or capsaicin in the PVN). Capsaicin was chronically administered in the PVN throughout the animal experiment phase of the study that lasted 6 weeks. Results: Our results demonstrated that PVN pretreatment with capsaicin can slow down raise of the blood pressure elevation and heart rate (HR) of Dahl S hypertensive rats given high salt diet. Interestingly, the cardiac hypertrophy was significantly improved. Furthermore, PVN pretreatment with capsaicin induced decrease in the expression of mRNA expression of NADPH oxidase-2 (NOX2), inducible nitric oxide synthase (iNOS), NOX4, p-IKKß and proinflammatory cytokines and increase in number of positive cell level for Nrf2 and HO-1 in the PVN of Dahl S hypertensive rats. Additionally, the protein expressions of phosphatidylinositol 3-kinase (p-PI3K) and phosphorylated protein kinase-B (p-AKT) were decreased, phosphorylated adenosine monophosphate-activated protein kinase (p-AMPK) were increased after the PVN pretreatment with capsaicin. Conclusion: Capsaicin pretreatment attenuates salt-sensitive hypertension by alleviating AMPK/Akt/iNOS pathway in the PVN.
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Abscesso , Neoplasias Testiculares , Humanos , Neoplasias Testiculares/diagnóstico , Neoplasias Testiculares/patologia , Neoplasias Testiculares/cirurgia , Masculino , Abscesso/diagnóstico , Abscesso/cirurgia , Adulto , Orquiectomia/métodos , Neoplasias Embrionárias de Células Germinativas/diagnóstico , Neoplasias Embrionárias de Células Germinativas/cirurgia , Neoplasias Embrionárias de Células Germinativas/patologiaRESUMO
Background: Tobacco cessation is proven to be the most effective and cost-effective strategy for smokers to reduce their risk of smoking-related disease and premature death. Providing effective, efficient, safe, and patient-centred tobacco cessation treatment to reach those who need them is a significant challenge. To date, only a few nationwide studies in China have assessed the overall clinical care practice and treatment outcome of tobacco cessation. Methods: This a prospective, nationwide, multicenter, cohort study covering all Eastern China, Northwest China, Central China, North China, Southwest China, Northeast China, and South China. Participants who were current smokers aged 18-85 years attending clinic for smoking cessation were included. All the participants were treated with 3-month cessation treatment and followed up for 3 months. Data were collected prospectively using online system. The primary outcome was 7-day point abstinence rate at 24 weeks, validated biochemically by an expired carbon monoxide level of less than 10 ppm. The participants lost to follow-up or not providing validation were included as non-abstainers. Findings: A representative sample of 3557 participants were recruited and 2943 participants were included into this analysis. These participants had mean age of 53.05 years, and 94.8% were males, with 75.8% showing symptoms of tobacco dependence. A total of 965 (32.8%) participants were treated with Bupropion + behavioural counselling, followed by 935 (31.8%) with behavioural counselling, 778 (26.4%) with Varenicline + behavioural counselling, 135 (4.6%) with alternative treatments + behavioural counselling, and 130 (4.4%) with nicotine replacement therapy (NRT) + behavioural counselling. After 3-month treatment and 3-month follow-up, 21.74% of the participants quit smoking at 24 weeks. In the multivariable-adjusted analyses, quitting smoking was significantly associated with female, higher socioeconomic status, poor health condition, different treatment received, and less smoking intensity. The tobacco cessation treatment varied widely across different areas of China. In particular, the areas with higher usage of cessation medication were associated with better cessation treatment outcome. Interpretation: The CNTCCS is the first large-scale nationwide cohort study of smoking cessation in China. Rich data collected from this prospective cohort study provided the opportunity to evaluate the clinical practice of tobacco cessation treatment in China. Funding: Chinese Academy of Medical Sciences (CAMS) Initiative for Innovative Medicine (CAMS 2021-I2M-1-010), Heilongjiang Provincial Science and Technology Key Program (2022ZXJ03C02), and National Key R&D Program of China (grant no. 2017YFC1309400).
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Thalictrum aquilegiifolium var. sibiricum, is an annual herb that grows on slopes or in mountain gullies in areas of damp forest. In this study, we report for the first time the complete plastome sequence of T. aquilegiifolium var. sibiricum. The plastome sequence is 156,244 bp in length and comprises a large single-copy region (85,447 bp), a small single-copy region (17,599 bp), and a pair of inverted repeat regions (26,480 bp). The genome encodes 112 unique genes, including 78 protein-coding genes, 30 tRNAs, and four rRNAs, and has total GC content of 38.4%. Phylogenomic analysis based on the plastome sequences of 20 species in the family Ranunculaceae indicated that T. aquilegiifolium var. sibiricum is clustered with Thalictrum minus.
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OBJECTIVES: To evaluate the clinically-significant prostate cancer (csCaP) detection rate of systematic (SBx) vs. targeted biopsy (TBx), after accounting for the overlapping systematic cores within the MRI regions of interest. MATERIALS AND METHODS: We identified 398 consecutive men who underwent both transperineal systematic and targeted biopsy between January 2015 to January 2019. We reclassified overlapping systematic cores in the MRI regions of interest as target cores. The detection rates of SBx and TBx were compared using McNemar's test. RESULTS: Detection rate of csCaP (grade group ≥2) was 42% (168/398). Median number of systematic and targeted cores were 23 (IQR 19-29) and 9 (IQR 6-12) respectively. A median of 3 (IQR 2-4) overlapping systematic cores were reclassified as targeted cores. After accounting for overlap, csPC detection rate on SBx decreased from 37% and 21% while the csCaP detection rate of TBx increased from 34% to 39% (both P < 0.001), with TBx having a better detection rate (39% vs. 21%, P < 0.001). A previous negative biopsy was associated with a lower risk of having csCaP on non-targeted SBx (OR 0.27, 95% CI: 0.12 - 0.58, Pâ¯=â¯0.001). Only 5% (13/243) of those who had no cancer detected on TBx had csCaP on non-targeted SBx compared to 45% (70/155) of those who had csCaP on TBx (P< 0.001). CONCLUSIONS: The utility of SBx in detecting csCaP decreases after accounting for overlap into the MRI region of interest, especially in men with a prior negative biopsy. Overlapping systematic cores improve the csCaP detection rate on TBx.
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Biópsia Guiada por Imagem/métodos , Imageamento por Ressonância Magnética/métodos , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/cirurgia , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
Eleusine coracana is a hardy crop that can grow in diverse environments. In this study, the complete plastome of E. coracana was determined. The plastome was 135,144 bp in size. It consists of a large single-copy region (80,666 bp), a small single-copy region (12,640 bp), and two inverted repeat regions (20,919 bp). The overall guanine-cytosine (GC) content was 38.2%. A total of 111 unique genes were annotated, including 77 protein-coding genes (PCGs), 30 tRNAs, and 4 rRNAs. Phylogenetic analysis showed that Eleusine was sister to Dactyloctenium.
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PURPOSE: Several multiparametric magnetic resonance imaging (mpMRI)-based models have been developed with significant improvements in diagnostic accuracy for clinically significant prostate cancer (csCaP), but lack proper external validation. We therefore sought to externally validate and compare all published mpMRI-based csCaP risk prediction models in an independent Asian population. PATIENTS AND METHODS: A total of 449 men undergoing combined transperineal fusion-targeted/systematic prostate biopsy at our specialist center between 2015 to 2019 were retrospectively analyzed. csCaP was defined as lesions with ISUP (International Society of Urological Pathology) grade group ≥2. The performance of 6 mpMRI-based risk models (MRI-ERSPC-3/4, Distler, Radtke, Mehralivand, van Leeuwen and He) were evaluated in terms of discrimination, calibration and clinical utility, using area under the receiver operating characteristic curve (AUC), calibration curves and decision curve analyses. RESULTS: A total of 202 (45%) subjects were diagnosed with csCaP. All models demonstrated excellent accuracy with AUCs ranging from 0.75 to 0.86, and most significantly outperformed mpMRI PIRADSv2.0 (Prostate Imaging Reporting and Data System version 2.0) alone. The models by Mehralivand and He showed good calibration to our validation population, with respective intercepts of -0.08 and -0.84. All models were nevertheless recalibrated to the csCaP prevalence in our population for analysis. Decision curve analysis showed that above a threshold probability of 10%, all mpMRI-based models demonstrated superior net benefit compared to mpMRI PIRADSv2.0 or a biopsy-all-men strategy. The van Leeuwen model had the greatest net benefit, avoiding 39% of unnecessary biopsies while missing only 4% of csCaP, at a threshold probability of 15%. CONCLUSIONS: The mpMRI-based risk models demonstrate excellent discrimination and clinical utility and are easy to apply in practice, suggesting that individualized risk-based approaches can be considered over mpMRI alone to avoid unnecessary biopsies.
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Imageamento por Ressonância Magnética Multiparamétrica/métodos , Neoplasias da Próstata/diagnóstico por imagem , Medição de Risco/métodos , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
OBJECTIVE: To compare the detection rates of prostate cancer between systematic biopsy and targeted biopsy using a stereotactic robot-assisted transperineal prostate platform. MATERIALS AND METHODS: We identified consecutive patients with suspicious lesion(s) on multiparametric magnetic resonance imaging (mpMRI), who underwent both systematic and MRI-transrectal ultrasonography (US) fusion targeted biopsy using our proprietary transperineal robot-assisted prostate biopsy platform between January 2015 and January 2019 at our institution, for retrospective analysis. Comparative analysis was performed between systematic and targeted biopsy using McNemar's test, and the cohort was further stratified by prior biopsy status and Prostate Imaging Reporting and Data System (PI-RADS) v2.0 score. International Society of Urological Pathology (ISUP) grade group (GG) ≥2 cancers (previously known as Gleason grade ≥7) were considered to be clinically significant. RESULTS: A total of 500 patients were included in our final analysis, of whom 67 (13%) were patients with low-risk cancer on active surveillance. Of the 433 patients without prior diagnosis of cancer, 288 (67%) were biopsy-naïve. A total of 248 (57%) were diagnosed with prostate cancer, with 199 (46%) having clinically significant prostate cancer (ISUP GG ≥2). There were no statistically significant differences in the overall prostate cancer and clinically significant prostate cancer detection rate between systematic and targeted biopsy (51% vs 49% and 40% vs 38% respectively; P = 0.306 and P = 0.609). Of the 248 prostate cancers detected, 75% (187/248) were detected on both systematic and targeted biopsy, 14% (35/248) were detected on systematic biopsy alone and 11% (26/248) were detected on targeted biopsy alone. Of the 199 clinically significant cancers detected, 69% (138/199) were detected on both systematic and targeted biopsy, 17% (33/199) on systematic biopsy alone and 14% (28/199) on targeted biopsy alone. There were no statistically significant differences in the detection rate between systematic and targeted biopsy for both overall and clinically significant prostate cancer, even when the cohort was stratified by prior biopsy status and PI-RADS score. Targeted biopsy has greater sampling efficiency compared to systematic biopsy for both overall and clinically significant prostate cancer (23.2% vs 9.8%, P < 0.001 and 14.8% vs 5.6%, P < 0.001). CONCLUSIONS: Using our robot-assisted transperineal prostate platform, combined MRI-US targeted biopsy with concurrent systematic prostate systematic biopsy probably represents the optimal method for the detection of clinically significant prostate cancer.
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Biópsia Guiada por Imagem/métodos , Imageamento por Ressonância Magnética Multiparamétrica/métodos , Próstata , Procedimentos Cirúrgicos Robóticos/métodos , Ultrassonografia de Intervenção/métodos , Idoso , Humanos , Interpretação de Imagem Assistida por Computador , Masculino , Pessoa de Meia-Idade , Próstata/diagnóstico por imagem , Próstata/patologia , Próstata/cirurgia , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgia , Estudos RetrospectivosRESUMO
This publisher's note contains corrections to Opt. Lett.40, 5224 (2015).OPLEDP0146-959210.1364/OL.40.005224.
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The self-absorption effect is one of the main bottlenecks for the laser-induced breakdown spectroscopy (LIBS) technique. In this Letter, LIBS assisted by laser-stimulated absorption (LSA-LIBS) is proposed to solve this problem. The process of LSA in self-absorption reduction is discussed and confirmed. The serious self-absorption phenomena of spectral lines (K, Mn, and Al) were not observed in LSA-LIBS. The full width at half-maximum (FWHM) of K, Mn, and Al was reduced by about 58%, 25%, and 52%, respectively. The results demonstrate the capability of this approach to self-absorption reduction in the LIBS technique.
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Copper-mediated selective mono- or diaryloxylation of benzamides has been achieved by using 2-aminopyridine 1-oxide as a new and removable N,O-bidentate directing group. The reaction system shows a broad substrate scope and provides a straightforward way for the synthesis of mono- and diaryloxylated benzoic acids.
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OBJECTIVE: In previous studies cellular prion protein (PrPc) is confirmed to be involved in multidrug resistance (MDR) of gastric cancer. Although octarepeat peptides are important functional domains of PrPc and are closely related to the transport of Cu2+/Zn2+ and antioxidative function, the significance in MDR remains unknown. We aimed to investigate the role of octarepeat peptides in gastric cancer MDR. METHODS: Small interfering RNA (siRNA) against PrPc were transfected into adriamycin-resistant gastric cancer cell lines to inhibit the expression of wild type PrPc, and then constructs encoding PrPc without octarepeat peptides and PrPc without the fifth repeat peptide were transfected, respectively, to establish the cell models. In vitro drug sensitivity, cell apoptosis, measurement of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and glutathione (GSH), as well as changes in glutathione S-transferase (GST) were detected. RESULTS: In vitro drug sensitivity test showed that octarepeat peptides could modulate the drug resistance of gastric cancer cells, but the deletion of the fifth repeat peptide had no effect. Specifically, the anti-apoptotic capacity of gastric cancer cells decreased significantly when the octarepeat peptides of PrPc was absent. Moreover, the activities of total SOD, Cu2+/Zn2+-SOD, GSH-Px, GSH, and GST detected in different stressing periods revealed that cells lacking octarepeat peptides of PrPc exhibited weakened responses to stress. However, absence of the fifth repeat peptide did not exert any effect on stress response. CONCLUSION: The octarepeat peptides of prion is responsible for MDR in gastric cancer cells while the fifth repeat peptide is not.
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Adenocarcinoma/enzimologia , Antibióticos Antineoplásicos/farmacologia , Doxorrubicina/farmacologia , Resistencia a Medicamentos Antineoplásicos/genética , Proteínas PrPC/metabolismo , Príons/metabolismo , Neoplasias Gástricas/enzimologia , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/genética , Antibióticos Antineoplásicos/farmacocinética , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Cisplatino/farmacologia , Doxorrubicina/farmacocinética , Resistência a Múltiplos Medicamentos , Etoposídeo/farmacologia , Fluoruracila/farmacologia , Glutationa/efeitos dos fármacos , Glutationa/metabolismo , Glutationa Peroxidase/efeitos dos fármacos , Glutationa Peroxidase/metabolismo , Glutationa Transferase/efeitos dos fármacos , Glutationa Transferase/metabolismo , Humanos , Concentração Inibidora 50 , Proteínas PrPC/genética , Príons/genética , RNA Interferente Pequeno , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/genética , Superóxido Dismutase/efeitos dos fármacos , Superóxido Dismutase/metabolismo , Transfecção , Células Tumorais CultivadasRESUMO
OBJECTIVE: To explore the clinical characteristics of pulmonary embolism (PE) in different age-groups and to analyze prognostic factors of PE. METHODS: Data of 209 PE patients diagnosed in our hospital from 2004 to 2009 were reviewed retrospectively. RESULTS: Of the 209 patients with PE, 95 subjects (45.5%) were over the age of 65, and 114 were ≤ 65 years. The third leading comorbidity were activity limitation that were banding in bed, chronic obstructive pulmonary disease, neoplasm and hypertension, accounting for 42.1%, 24.4% and 21.5%, respectively. The typical clinical presentations included dyspnea(83.7%), cough (74.2%), chest pain (29.2%), haemoptysis (15.3%) and syncope (3.8%). In 186(92.1%) patients, D-dimer was above the normal level, 37.8% (79) and 54.0% (81/150) subjects were found having got a venous thrombosis in lower extremity and pulmonary hypertension, respectively by using ultrasonic visualization. 16.7% (35) and 80.9% (169) had received thrombolytic and anticoagulant therapy, respectively. The death rate of PE was 6.7%. A difference in clinical characteristics was observed between younger and older patients. The later had more comorbidity such as COPD, neoplasm and hypertension, the older patients had fewer complaints of chest pain, haemoptysis, fever, hypotension and typical electrocardiogram (ECG), but had more cough with sputum, pulmonary rales and lower extremity edema, in comparison to the younger patients. The older PE patients were less likely to suffer from large thrombosis and pulmonary infarction, and to received thrombolytic therapy. Multivariate logistic regression showed that PaO(2) < 60 mm Hg (1 mm Hg = 0.133 kPa), having pulmonary rales, having abnormal neutrophilic granulocyte counts, not receiving thrombolysis and anticoagulant therapy, suffering from emergency rescue, having comorbidities with tumor and pneumonia were important prognostic factors. CONCLUSION: The clinical features of PE were various and non-specific. More attention should be paid to PE patients, in particular to older patients who usually had more comorbidities and non-specific clinical manifestations.
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Embolia Pulmonar/diagnóstico , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Embolia Pulmonar/fisiopatologia , Estudos Retrospectivos , Adulto JovemRESUMO
OBJECTIVE: To describe a case of lymphoma presenting with multi-organ involvement, and to review similar cases reported in the English and Chinese literatures since 1994. METHODS: The clinical and pathological features of a patient admitted to our hospital on September 6, 2007 with lymphoma presenting with some unusual clinical symptoms including subcutaneous nodules, pleural effusion and orbital tumor were analyzed and related literatures were reviewed. RESULTS: The patient was a 60-year-old male. The primary manifestations were subcutaneous nodules. The reason for his hospitalization was pleural effusion. Orbital tumor was present. Computed tomography of the chest and the abdomen reveal systemic lymphadenopathy. Lymphoma was proved by pathological study. CONCLUSIONS: Complicated clinical manifestations of lymphoma may have multi-system involvement. Lymphoma with extranodal presentations as the first sign may lead to misdiagnosis.
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Linfoma não Hodgkin/complicações , Linfoma não Hodgkin/diagnóstico , Neoplasias Orbitárias/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Derrame Pleural/diagnóstico , Derrame Pleural/etiologia , Tela Subcutânea/patologiaRESUMO
AIM: To analyze the expression profiles of a human gastric-cancer-related gene, GCRG123, in human gastric signet-ring cell carcinoma tissues, and to perform bioinformatics analysis on GCRG123. METHODS: In situ hybridization was used to explore the GCRG123 expression pattern in paraffin-embedded gastric tissues, including 15 cases of signet-ring cell carcinoma, 15 of intestinal-type adenocarcinoma, and 15 of normal gastric mucosa. Northern blotting was used to analyze the differences in GCRG123 expression between stomach signet-ring cell carcinoma and intestinal-type adenocarcinoma tissues. Online software, including BLAST, Multalin and BLAT, were applied for bioinformatics analysis. National Center for Biotechnology Information (NCBI) and the University of California Santa Cruz (UCSC) databases were used for the analyses. RESULTS: The in situ hybridization signal appeared as blue precipitates restricted to the cytoplasm. Ten out of 15 cases of gastric signet ring cell carcinoma, normal gastric mucosal epithelium and pyloric glands showed high GCRG123 expression. Low GCRG123 expression was observed in gastric intestinal-type adenocarcinoma and normal gastric glands. Northern blotting revealed that GCRG123 was up-regulated in signet-ring cell carcinoma tissue but down-regulated in intestinal-type adenocarcinoma tissue. BLAST and Multalin analyses revealed that the GCRG123 sequence had 92% similarity with the ORF2 sequence of human long interspersed nuclear element retrotransposons (LINE-1, L1). BLAT analysis indicated that GCRG123 mapped to all chromosomes. GCRG123 was found to integrate in the intron-17 and -23 of Rb, 5' flanking region of IL-2 and clotting factor IX genes. CONCLUSION: GCRG123, an active member of the L1 family, was up-regulated in human gastric signet-ring cell carcinoma.
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Carcinoma de Células em Anel de Sinete/genética , Regulação Neoplásica da Expressão Gênica , Laminas/genética , Neoplasias Gástricas/genética , Humanos , Elementos Nucleotídeos Longos e Dispersos , Dados de Sequência Molecular , Regulação para Cima/genéticaRESUMO
OBJECTIVE: To investigate the role of severe acute respiratory syndrome coronavirus (SARS-CoV) in the induction of acute lung injury by promoting the synthesis of chemokine/cytokines in human endothelial cells. METHODS: Twenty-three SARS patients were enrolled in this study, comprising 15 male and 8 female, aged 27 - 55 years, mean (36 +/- 6) years. They were treated at Guangzhou Institute of Respiratory Disease from February to May in 2003. Chemokines/cytokines in the blood of patients with SARS were dynamically screened by liquid chip system. The lung was studied histopathologically using immunohistochemical technique. Spike glycoprotein of SARS-CoV was recombined by using insect-baculovirus expression system and Nickel affinity Magnet Beads, and then used to stimulate cultured human umbilical vein endothelial cells (HUVEC). Morphological changes of HUVEC were observed by microscope. Levels of chemokines/cytokines involved in immunoreaction in response to virus infection were detected in the supernatants of those cells cultured with the Spike glycoprotein by liquid chip system. RESULTS: Interferon-gamma inducible protein 10 (IP-10) was markedly elevated in the blood during the early stage of SARS [(7,600 +/- 2,400) ng/L, P < 0.01], and remained at a high level in the progressive stage [(8,100 +/- 2,300) ng/L, P < 0.01] and the end stage [(8,000 +/- 2,800) ng/L, P < 0.01] until convalescence [(1,250 +/- 450) ng/L, P > 0.05]. Moreover, IP-10 was highly expressed in the lung. Vacuoles appeared in part of HUVEC after Spike glycoprotein stimulation. As time going on, the HUVEC turned to be round in shape and even disrupted. Under normal condition, no detectable IP-10 was found in HUVEC. A high level of IP-10 [(179 +/- 34), (889 +/- 212), (1,676 +/- 199) ng/L, all P < 0.05] was detected in the HUVEC 12 h after Spike glycoprotein (5, 20, 40 mg/L) stimulation respectively, and presented with a significant dose-dependent response. CONCLUSIONS: (1) A significant increase of IP-10 activity in the blood was found in patients with SARS-CoV infection, and remained at a high level until the stage of convalescence. A strong IP-10 protein expression was also found in SARS-CoV infected lung in autopsy. (2) The Spike glycoprotein of SARS-CoV induced a high level of IP-10 in endothelial cells, which in turn damaged endothelial cells. (3) The Spike glycoprotein of SARS-CoV induced IP-10 production by a way independent of IFN-gamma.
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Quimiocina CXCL10/metabolismo , Lesão Pulmonar/etiologia , Glicoproteínas de Membrana/metabolismo , Síndrome Respiratória Aguda Grave/virologia , Coronavírus Relacionado à Síndrome Respiratória Aguda Grave , Proteínas do Envelope Viral/metabolismo , Adulto , Células Cultivadas , Células Endoteliais/metabolismo , Feminino , Humanos , Interferon gama/farmacologia , Masculino , Pessoa de Meia-Idade , Síndrome Respiratória Aguda Grave/metabolismo , Glicoproteína da Espícula de CoronavírusRESUMO
OBJECTIVE: To investigate the validity and safety of different doses of non-steroidal anti-inflammatory drugs (NSAID) in attempting to maintain the regression of colorectal adenomas in patients with familial adenomatous polyposis (FAP) and hereditary nonpolyposis colorectal cancer (HNPCC). METHODS: Twenty-two FAP patients who were willing to receive celecoxib were randomly divided into 2 groups 400 mg/d group (n = 8, taking celecoxib 400 mg/d) and 200 mg/d group (n = 10, taking celecoxib 200 mg/d). Four FAP patients who refused celecoxib and selected aspirin 80 mg/d instead. Six HNPCC patients were given celecoxib 400 mg daily. The treatment lasted for 24 months in all groups. The efficacy was evaluated respectively by the number and grade of polyps by coloscopy every 3 months in the first year and every 6 months in the second year. RESULTS: Either dose of celecoxib could reduce polyps in the FAP patients, with a polyps reduction rate of 86.6% (280/323) in the 400 mg group, significantly higher than that in the 200 mg group [51.81% (129/249) of the aspirin group]. In 5 of the 6 HNPCC patients the polyps completely vanished after 9 months of treatment. Side effects, such as arrhythmia, angina pectoris, and nervous headache, were observed in the celecoxib 400 mg/d group. The side effects could be reversed by decreasing the dose of celecoxib or using aspirin instead. Only one patient in the celecoxib 200 mg/d group showed side effects. CONCLUSION: Celecoxib 400 mg daily is more effective but has more side effects. At first the patients should be treated with celecoxib 200 mg daily for a long time, or 400 mg/d in the first 6 months and then with a daily dose of 200 mg/d to maintain the treatment effects. Soluble aspirin has similar effects.
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Polipose Adenomatosa do Colo/tratamento farmacológico , Neoplasias Colorretais/tratamento farmacológico , Polipose Adenomatosa do Colo/patologia , Adolescente , Adulto , Idoso , Angina Pectoris/induzido quimicamente , Anti-Inflamatórios não Esteroides/efeitos adversos , Anti-Inflamatórios não Esteroides/uso terapêutico , Arritmias Cardíacas/induzido quimicamente , Aspirina/efeitos adversos , Aspirina/uso terapêutico , Celecoxib , Neoplasias Colorretais/patologia , Neoplasias Colorretais Hereditárias sem Polipose/patologia , Relação Dose-Resposta a Droga , Feminino , Cefaleia/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade , Pirazóis/efeitos adversos , Pirazóis/uso terapêutico , Sulfonamidas/efeitos adversos , Sulfonamidas/uso terapêutico , Resultado do TratamentoRESUMO
AIM: To identify the gene that may predispose to human gastric cancer and to analyze its expression in gastric cancer and non-tumorous gastric mucosa. METHODS: Cancer, para-tumor, and non-tumor gastric tissues were studied for gene expression profile using fluorescent differential display reverse transcription polymerase chain reaction (DDRT-PCR). The differentially expressed bands of interest were analyzed by cloning, Northern blotting, and sequencing. The sequencing results were compared with the GenBank database for homology and conserved domain analysis. In situ hybridization with DIG-labeled cRNA probes was used to detect the expression of gene in paraffin embedded gastric adenocarcinoma and non-cancerous tissues. RESULTS: A gene expressed higher in tumor and para-tumor tissues than in their non-tumor counterparts of all 7 tested gastric adenocarcinoma patients was identified by means of DDRT-PCR analysis. It was named GCRG213 (gastric cancer related gene 213). Northern blot confirmed the differential expression. GCRG213 (GenBank No. AY053451) consisted of 1094 base pairs with an open reading frame (ORF) which encoded 142 amino acids. The deduced amino acid sequence contained a putative conserved domain, apurinic/apyrimidinic endonuclease (APE). In situ hybridization analysis showed that GCRG213 was expressed higher in gastric cancer tissues than in their corresponding non-tumor ones. Precancerous leisions of gastric adenocarcinoma showed a high GCRG213 expression, too. No difference of the expression patterns was found between the early and advanced gastric cancer. CONCLUSION: A gene named GCRG213 was identified in human gastric adenocarcinoma. It encoded an APE-like protein which was probably a new member of the APE family. GCRG213 was over-expressed not only in gastric cancer, but also in its precancerous leisions. The role of GCRG213 expression in carcinogenesis needs further study.
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Endonucleases/genética , Neoplasias Gástricas/genética , Regulação para Cima , Adulto , Idoso , Sequência de Aminoácidos/genética , Sequência de Bases/genética , DNA Complementar/genética , Feminino , Humanos , Hibridização In Situ , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Hormônios Peptídicos , RNA Mensageiro/metabolismo , Neoplasias Gástricas/metabolismoRESUMO
OBJECTIVE: To analyze the expression of human anti-apoptotic gene survivin (SVV) in normal human gastric tissues and gastric cancer. METHODS: SVV cDNA clone was obtained from human gastric cancer tissues by virtue of RT-PCR, using Dig-marked cRNA probe in situ hybridization to analyze its expression in normal human gastric tissues and gastric cancer. RESULTS: Two SVV cDNA clones, SVV-S4A and SVV-S1B were obtained. The sequence of the former is identical to that of the well-known SVV cDNA; however, in the sequence of the latter, the third exon was missed, i.e., there are only two exons in SVV-S1B. In situ hybridization showed that SVV-S4A is mainly expressed in gastric cancer tissues whereas SVV-S1B is mostly expressed in normal gastric tissues. CONCLUSION: There is difference between SVV-S4A and SVV-S1B in respect to their characteristics of expression in gastric cancer and normal gastric tissues.
Assuntos
Processamento Alternativo/genética , Proteínas Associadas aos Microtúbulos/genética , Neoplasias Gástricas/genética , Sequência de Bases , Clonagem Molecular , DNA Complementar/química , DNA Complementar/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Proteínas Inibidoras de Apoptose , Dados de Sequência Molecular , Proteínas de Neoplasias , Análise de Sequência de DNA , SurvivinaRESUMO
AIM: To clone genes that may predispose us to human gastric cancer and to analyze it's expression in gastric tissues. METHODS: Specimens of paired tumor, paratumor and normal gastric mucosa tissues collected from fifteen patients who suffered from stomach antrum adenocarcinoma were used for analysis. Seven out of the fifteen cases were first studied by fluorescent differential display reverse transcription polymerase chain reaction (DDTR-PCR) analysis. The differentially expressed bands of interest were cloned, analyzed by Northern blot, sequencing and RT-PCR. Through BLAST, the sequencing results were compared with GenBank database for homology analysis. In situ hybridization with DIG-labeled cRNA probes was used to analyze the expression of interesting cDNA bands in paraffin embedded paired normal gastric mucosa and cancer tissues isolated from 30 gastric adenocarcinoma patients. RESULTS: DDRT-PCR showed that one of the interesting cDNA bands, which was named W2, expressed much higher in all seven tested tumor and paratumor samples than in their normal counterparts, it was sub-cloned into a pGEM-T Easy vector. Two subclones were subsequently obtained. One of the subclone, GCRG224, was studied further. The sequencing result showed that GCRG224 consisted of 1 159 base pairs and had one open reading frame (ORF). It located at human chromosome 11q14. No homologue was found in GenBank database with GCRG224-ORF. This nucleotide sequence data were submitted to GenBank with accession No. AF438406. RT-PCR showed that GCRG224 expressed higher in 11/15 gastric cancer tissues than in non-tumor tissues. However, the result of Northern blot analysis showed a higher GCRG224 expression in the non-tumor tissue than in the tumor one. Human multiple tissue Northern blot analysis revealed that GCRG224 also expressed in human normal colon tissue, and peripheral blood leukocyte. In situ hybridization analysis showed that only 5/30 adenocarcinoma, 3/18 dysplasia and 6/18 intestinal metaplasia showed higher GCRG224 expression level than the normal gastric glands. However, GCRG224 was over-expressed predominantly in 26/30 cases of normal mucosal epithelium. CONCLUSION: A novel gene named GCRG224 was identified from human gastric mucosal tissue. It overexpressed in almost all gastric mucosal epithelium but only a small portion of cancer and precancerous leisions. The role of GCRG224 expression in gastric epithelium needs further study.