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Objective: To establish a method for the determination of sulfur dioxide (SO2) in the air of workplace, which including the process of collection by absorption in triethanolamine aqueous solution and the process of analysis and detection by iron chromatography directly without derivatization. Methods: SO2 in the air of workplace was collected at a flow rate of 0.5 L/min for 15 min through 10 ml of 3% triethanolamine aqueous solution filled in a porous glass plate absorption tube. The absorption solution passed through IonPacAS14A analytical column (4 mm×250 mm) and IonPacAG14 protective column (4 mm×50 mm) at a column temperature of 30 â, using Na2CO3 (3.0 mmol/L) -NaHCO3 (1.0 mmol/L) as mobile phase with the flow rate of 1.2 ml/min, and was detected by conductivity detector. Results: It showed that SO2 in triethanolamine solution could be stored for at least 7 d at room temperature (25 â) and 37 â. There was a linear relationship within the determination range of 0-8.00 µg/ml, the linear correlation coefficient was 0.9999. The sampling absorption efficiency was 98.1%-100.0%, the detection limit of the method was 0.018 µg/ml, the minimum detection concentration was 0.024 mg/m3 (based on V0=7.5 L) . The recovery rate was 99.22%-101.69%, the intra batch precision was 0.41%-1.34%, and the inter batch precision was 0.73%-1.77%. Conclusion: The method has the advantages of simple operation, high sensitivity and good accuracy. It can prevent SO2 from being oxidized and realize the direct detection of SO2 in the air of workplace without derivation.
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Poluentes Ocupacionais do Ar , Local de Trabalho , Poluentes Ocupacionais do Ar/análise , Cromatografia , Dióxido de EnxofreRESUMO
Objective: To investigate the value of contrast-enhanced ultrasound (CEUS) in the diagnosis of benign and malignant lateral cervical lymph nodes. Methods: One hundred and fifteen cases of suspected lymph nodes disease, 60 males, 55 females, between November 2018 and June 2019 from clinic and inpatient in Fujian Cancer Hospital were collected. Routine ultrasound and CEUS were performed in 115 cases of lateral cervical lymph nodes. All cases underwent ultrasound-guided biopsy, and were divided into two groups of benign and malignant lymph nodes according to pathological results. The differences between the two groups were analyzed and statistically analyzed. The rate and frequency were used to qualitatively describe the ultrasound performance and observed lymph node morphology between the two groups of routine ultrasound and CEUS. The sensitivity, specificity, accuracy, negative predictive value and positive predictive value were used to evaluate the efficacy of routine ultrasound and CEUS. Results: There were 37 cases of benign lymph nodes and 78 cases of malignant lymph nodes. In benign lymph nodes, 51.4% (19/37) showed uniform high enhancement, and 48.6% (18/37) showed uneven or circular enhancement with clear boundaries and no focal enhancement area. In malignant lymph nodes, 94.9% (74/78) showed uneven enhancement, and only 5.1% (4/78) showed uniform enhancement. The difference of ultrasonic contrast medium uniformities in differentiating benign from malignant was statistically significant (P<0.001). The sensitivity, accuracy, negative predictive value and positive predictive value of routine ultrasound to differentiate benign and malignant lymph nodes were 64.1%, 65.2%, 47.2%, and 66.7%, respectively, while the corresponding values of CEUS were 93.6%, 75.7%, 73.7% and 83.9%. Conclusion: CEUS may provide a valuable basis for the differential diagnosis of benign and malignant lateral cervical lymph nodes.
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Linfonodos , Pescoço , Meios de Contraste , Diagnóstico Diferencial , Feminino , Humanos , Metástase Linfática , Masculino , Sensibilidade e Especificidade , UltrassonografiaRESUMO
Objective: To evaluate the accuracy and influencing factors of T-stage restaging of rectal cancer following neoadjuvant therapy with endorectal ultrasonography (ERUS). Methods: In a retrospective study, endorectal ultrasound was performed in 86 patients with rectal cancer following neoadjuvant therapy. The imaging results were compared with postoperative pathological T-stage. Results: The accuracy of overall T-stage restaging with ERUS was 67.4% (58/86). Additionally, the accuracy of restaging in middle and high rectal cancer was higher, with an accuracy of 76.1%(35/46)and 100%(4/4) respectively. Univariate analysis showed that the location of tumors was an independent factor affecting the accuracy of ERUS(P=0.033). Conclusion: ERUS is an effective method to restage T-stage of rectal cancer following neoadjuvant therapy.
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Terapia Neoadjuvante , Neoplasias Retais , Endossonografia , Humanos , Estadiamento de Neoplasias , Neoplasias Retais/diagnóstico por imagem , Neoplasias Retais/terapia , Estudos Retrospectivos , UltrassonografiaRESUMO
Objective: To explore the value of dual contrast-enhanced ultrasound in preoperative T staging of rectal carcinoma. Methods: Dual contrast-enhanced ultrasound examinations were performed on 72 patients with rectal carcinoma via transrectal infusion and intravenous injection. The accordance of preoperative dual contrast-enhanced ultrasound results and postoperative pathologic results was evaluated retrospectively. Results: The overall accordance rate of preoperative T staging was 73.6% (53/72). And accordance rate was 100.0% (3/3), 100.0% (5/5), 68.4% (13/19), 71.4% (25/35)and 70.0% (7/10) for Tis , T1, T2, T3 and T4, respectively. The consistency was good (κ=0.607, χ(2) =8.363, P<0.01). The accordance rate of middle/lower vs high rectal carcinoma was 68.7% and 85.7%. Conclusion: Dual contrast-enhanced ultrasound can provide reference for preoperative T staging for patients with rectal carcinoma.
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Estadiamento de Neoplasias , Neoplasias Retais , Meios de Contraste , Humanos , Estudos RetrospectivosRESUMO
Objective: To discuss the etiology, clinical features and treatment principles of the orbital and periorbital abscess. Methods: A retrospective case series of 17 cases with orbital and periorbital abscess between July 2010 and November 2015 were conducted. All patients(,) clinical data including medical history, etiology, abscess location, paranasal sinus involvement, eye involvement, microbiological test results, imaging features, treatment and prognosis were summarized and analyzed. Results: In all 17 patients, there were 10 males and 7 females with age from 3.0 to 71.0 years (the average age was 33.9 years).Eight patients(,) bacterial cultures of the pus and secretion were positive in all 17 patients. Orbital and periorbital abscess patients could manifest decreased vision, redness and swelling of eyelid, conjunctival congestion and edema, ocular motility disorders, displacement of eyeball, increased orbital pressure, abscess rupture etc. CT showed us the soft tissue mass, accompanied with sinusitis or paranasal sinus mass. MR performed with the long T(1) and T(2) signals. The signals of the abscess cavity were not uniform. For the etiology,11 cases were secondary to sinusitis, including 1 case of diabetes; 2 cases with orbital fractures.One case was secondary to orbital fracture repairment surgery. One case was secondary to the remnant of sequestrum and foreign bodys in the wound after repairment surgery. One case was injured by the hard object. One case was secondary to paranasal sinuses large B-cell lymphoma. One case had diabetic history and the blood sugar was controlled unstablly. For the treatment, 7 cases were treated by the drainage surgery which was performed via the sinus with endoscopic and abscess resection performed via the skin.Two cases were treatment by the abscess resection only.One case was treated by the drainage surgery performed via the sinus with endoscopic only. Six cases were treated by the drainage surgery performed via the skin. One case was only administered intravenous antibiotic. Sixteen cases acquired well prognosis without serious complications except 1 case which occurred central retinal artery and vein occlusion. Conclusions: The orbital and periorbital abscess is mainly a complication of paranasal sinus infection, or secondary to trauma, surgery, tumor, etc; Orbital and periorbital abscess always manifest inflammatory neoplastic clinical features, the key of the diagnosis is to make sure the etiology; Incision and drainage of the abscess is the main treatment method when necessary. We can do the surgery with other departments to avoid the occurrence of serious complications.(Chin J Ophthalmol, 2017, 53: 588-593).
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Abscesso , Doenças Orbitárias , Sinusite , Abscesso/etiologia , Abscesso/terapia , Adulto , Antibacterianos , Drenagem , Feminino , Humanos , Masculino , Doenças Orbitárias/etiologia , Doenças Orbitárias/terapia , Seios Paranasais , Estudos Retrospectivos , Sinusite/etiologia , Sinusite/terapiaRESUMO
AIM: The study assessed whether the addition of monoclonal antibodies (MoAbs) to first-line chemotherapy for advanced colorectal cancer (CRC) increases the complete response (CR) compared with controls. METHOD: PubMed was reviewed for randomized clinical trials (RCTs) with approved MoAbs (bevacizumab, cetuximab and panitumumab) vs non-MoAbs as first-line therapy for patients with advanced CRC. The incidence and ratio of CR events were calculated in patients assigned to MoAbs compared with controls. RESULTS: A total of 3790 patients from nine RCTs were included for analysis. The overall incidence of CR in patients treated with MoAbs was 2.4% (95% CI: 1.7-3.3%) compared with 1.3% (95% CI: 0.8-2.2%) in controls. Comparison of the different types of MoAbs showed that the incidence of CR was higher for bevacizumab (3.1%, 95% CI: 2.1-4.3%) than for cetuximab (0.8%, 95% CI: 0.4-1.8%). The addition of MoAbs to chemotherapy significantly increased the OR of obtaining a CR compared with controls (OR = 1.96; 95% CI: 1.12-3.46; P = 0.02). No significant differences in the OR were observed in any of the subgroups. CONCLUSION: The CR is a rare event in advanced CRC; however, the addition of MoAbs to first-line chemotherapy significantly increases the curative rate of metastatic disease compared with controls.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais Humanizados/administração & dosagem , Antineoplásicos/administração & dosagem , Bevacizumab , Cetuximab , Humanos , Modelos Estatísticos , Panitumumabe , Resultado do TratamentoRESUMO
BACKGROUND: We aimed at determining the overall incidence and risk of hemorrhagic events associated with vascular endothelial growth factor receptor-tyrosine-kinase inhibitors (VEGFR-TKIs). METHODS: We searched PubMed, EMBASE and Cochrane library databases for relevant prospective, randomized controlled trials (RCTs). Statistical analyses were conducted to calculate the summary incidence, relative risks (RRs) and 95% confidence intervals (CIs) by using either random-effects or fixed-effects models according to the heterogeneity of included studies. RESULTS: The overall incidence of all-grade and high-grade hemorrhagic events was 9.1% (95% CI: 6.8-12.1%) and 1.3% (95% CI 0.8% to 2.1%), respectively. And the use of VEGFR-TKIs was associated with an increased risk of hemorrhagic events, with a relative risk (RR) of 1.67 (95% CI 1.19-2.33, P = 0.003), but not for high-grade hemorrhagic events (RR 1.23, 95% CI 0.86-1.77, P = 0.25). The risk of developing all-grade hemorrhagic events varied significantly with tumor types (P < 0.001) and different VEGFR-TKIs (P < 0.001). Additionally, the most common causes of all-grade hemorrhagic events were hemoptysis (48.6%) and epistaxis (20.7%), while hemoptysis (41.8%) and CNS hemorrhage (13.4%) was the most common cause of high-grade hemorrhagic events. CONCLUSIONS: While the use of VEGFR-TKIs is associated with a significantly increased risk of developing hemorrhagic events in cancer patients, this is primarily for lower grade events.
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Antineoplásicos/efeitos adversos , Hemorragia/induzido quimicamente , Inibidores de Proteínas Quinases/efeitos adversos , Antineoplásicos/uso terapêutico , Hemorragia/epidemiologia , Humanos , Incidência , Neoplasias/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Receptores de Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidores , Fatores de RiscoRESUMO
Recent studies have shown that insulin-like growth factor (IGF) signaling components have been involved in the pathogenesis and progression of different types of sarcomas. There has been some evidence to indicate the differential expression of IGF2 and insulin-like growth factor 1 receptor (IGF1R) in human sarcomas. The present study utilized immunohistochemistry (IHC) and in situ hybridization (ISH) to determine the expression of IGF2 and IGF1R in eighty-two cases of human sarcoma specimens and eight cases of non-tumor tissue (NTT). IGF2/IGF1R signaling was blocked by recombinant adenovirus-mediated IGF1R small hairpin RNA (shIGF1R), which was used to transfect into human osteosarcoma (OS) MG-63 cells. The expression of IGF2, IGF1R, matrix metallopeptidase-2 (MMP-2) and MMP-9 was detected by Real-time PCR. Cell migration was evaluated by wound healing assay. As a consequence, the expression of IGF1R and IGF2 was found in human OS with higher strong reactivity rate compared with the NTT (85.0 percent vs 50.0 percent, P=0.022; 95.0 percent vs 100.0 percent, P=0.042), elevating with the ascending order of tumor malignancy. Also, IGF1R had differential expression in different types of sarcomas (P=0.002), while IGF2 had no significant difference (P=0.105). Targeted blockade of IGF2/IGF1R signaling decreased the expression of IGF2, IGF1R, and MMP-2/-9, and diminished the migration capabilities of MG-63 cells. In conclusion, IGF1R is differentially-expressed in different types of human sarcomas, and targeted blockade of IGF1R pathway may inhibit human OS migration through down-regulation of MMP-2/-9 expression. IGF1R pathway may represent a significant therapeutic modality for the treatment of sarcomas.
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Neoplasias Ósseas/metabolismo , Fator de Crescimento Insulin-Like II/metabolismo , Receptor IGF Tipo 1/metabolismo , Sarcoma/metabolismo , Linhagem Celular Tumoral , Ensaios de Migração Celular , Humanos , Fator de Crescimento Insulin-Like II/genética , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 9 da Matriz/genética , RNA Mensageiro/metabolismo , Receptor IGF Tipo 1/genéticaRESUMO
BACKGROUND: Smoking is an important modifiable risk factor of morbidities and mortality. Although healthcare professionals play an important role in smoking cessation, their adoption of such practices is relatively low because of inadequate training. To address this issue, we incorporated a service-learning model to operate the Youth Quitline. Undergraduate nursing students were trained and received supervision while delivering smoking cessation counseling through the Youth Quitline as their clinical placement. OBJECTIVES: We evaluated the effectiveness of the placement by assessing students' knowledge, attitudes and practices regarding smoking cessation and tobacco control. DESIGN: One-group pretest-posttest design. SETTING: Youth Quitline. PARTICIPANTS: A total of 61 third-year students in a mental health nursing program. METHODS: Students were required to complete 80 h at the Youth Quitline. The 80 h were divided into 20 sessions; students used four sessions to approach and recruit youth smokers in the community, then provided them with telephone counseling for the rest of the time. Prior to the placement, students attended a 2-day workshop. The outcomes were changes in students' knowledge, attitudes and practices regarding smoking cessation and tobacco control 3 months after the placement compared with baseline. RESULTS: From January-June 2021, students conducted 105 outreach activities to identify 3142 smokers in the community, and provided telephone counseling for 336 smokers via Youth Quitline. Compared with baseline, significant improvements were observed in students' knowledge, attitudes and practices regarding smoking cessation and tobacco control at 3-month follow-up. CONCLUSIONS: The clinical placement improved students' knowledge, attitudes and practices regarding smoking cessation and tobacco control, enhancing their competency in providing support to assist smokers to quit in their future practice. Incorporating the service-learning model in existing community-based services can provide additional venues for nursing students to practice. This is particularly important because many venues have restricted access during the COVID-19 pandemic.
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COVID-19 , Bacharelado em Enfermagem , Abandono do Hábito de Fumar , Estudantes de Enfermagem , Adolescente , Aconselhamento , Atenção à Saúde , Humanos , Pandemias , Abandono do Hábito de Fumar/psicologiaRESUMO
Objective: To explore the role of the enhanced milieu teaching (EMT) model in early intervention of children with language developmental delay (LDD) in outpatient child healthcare clinic. Methods: Case-control study design was adopted. Twenty-eight children aged 2.5 to 4.0 years who were diagnosed with LDD from June 2019 to June 2020 at the Division of Child Healthcare, Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology were recruited as the intervention group, and participated in one-on-one EMT model language rehabilitation sessions for 3 months (12 sessions). Another 27 children with LDD who attended the Division of Child Healthcare around the same period of time were recruited as control group, all of whom did not attend any types of language intervention in the subsequent three months. Both groups were followed up three months later. Gesell developmental scale (GDS) and diagnostic receptive and expressive assessment of Mandarin-comprehensive (DREAM-C) standardized language test were used to evaluate and compare children's development level at the first and follow-up visit, with the treatment effect of the EMT model being evaluated with independent sample t-test. Results: The language development quotient of GDS of the intervention group (22 boys and 6 girls) at the follow-up visit was significantly higher than that of at the first visit (64±21 vs. 52±17,t=4.960, P<0.01). The Dream-C test scores of total language (89±16 vs. 77±14, t=5.061, P<0.01), receptive language (90±16 vs. 77±15, t=5.301, P<0.01), semantics (93±20 vs. 79±19, t=5.06, P<0.01), and syntax after training (84±14 vs. 76±11, t=3.209, P<0.01) were significantly higher than those at the first visit. In the control group (19 boys and 8 girls), the only improvement was found in the Dream-C semantics score (82±26 vs. 71±18, t=2.330, P<0.05). There was no significant difference in any domains in GDS at the first and follow-up visit (all P>0.05). Conclusions: Early language rehabilitation training based on the EMT model has a significant effect on all domains of language development for children with LDD. Therefore, EMT model is a language intervention model compatible in the child healthcare outpatient clinic settings.
Assuntos
Transtornos do Desenvolvimento da Linguagem , Pacientes Ambulatoriais , Instituições de Assistência Ambulatorial , Estudos de Casos e Controles , Criança , Atenção à Saúde , Feminino , Humanos , Transtornos do Desenvolvimento da Linguagem/terapia , MasculinoRESUMO
OBJECTIVE: To explore the effects and mechanism of action of micro ribonucleic acid (miR)-21 on the proliferation and migration of vascular smooth muscle (VSM) in atherosclerosis (AS). MATERIALS AND METHODS: The rats were fed with a high-fat diet, and the oil red staining was adopted to compare AS between Sprague Dawley (SD) rats and miR-21 knockdown rats. At the in-vitro level, primary rat VSM cells (VSMCs) were selected and divided into miR-NC blank control group [miR-normal control (NC) group] and miR-21 overexpression group (miR-21 group) for relevant experimental detection. Wound healing assay and transwell assay were used to detect the effects of miR-21 on the proliferation and migration of VSMCs. Westernn blotting was applied to examine the changes in the levels of Cyclin D, a cell cycle-related protein, and the key factors of the Akt/ERK signaling pathway, such as phosphorylated-Akt (p-AKT), AKT, p-ERK1/2, and ERK1/2. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cell activity assay kit was applied to determine the effects of miR-21 on the proliferation of VSMCs through regulating the Akt/ERK signaling pathway after the ERK signaling pathway inhibitor PD98059 and AKT inhibitor MK-2206 were given. RESULTS: Compared with that in miR-NC group, the level of AS in miR-21 knockdown rats were decreased significantly (p < 0.05). In the cell-level experiment, the overexpression of miR-21 promoted abnormal proliferation of VSMCs and activated the Akt/ERK signaling pathway (p < 0.05). MTT assay results revealed that inhibiting the Akt/ERK pathway could reverse the effects of miR-21 promoting proliferation and migration. CONCLUSIONS: MiR-21 promotes the proliferation and migration of VSMCs by activating the Akt/ERK pathway and aggravates AS. Knocking down miR-21 or inhibiting the Akt/ERK pathway can suppress the activation of VSMCs.
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Aterosclerose/genética , Dieta Hiperlipídica/efeitos adversos , MicroRNAs/genética , Músculo Liso Vascular/citologia , Animais , Aterosclerose/induzido quimicamente , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Modelos Animais de Doenças , Flavonoides/farmacologia , Regulação da Expressão Gênica , Técnicas de Silenciamento de Genes , Compostos Heterocíclicos com 3 Anéis/farmacologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Masculino , Músculo Liso Vascular/efeitos dos fármacos , Músculo Liso Vascular/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Fosforilação , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Ratos Sprague-DawleyRESUMO
Objective: To investigate the efficacy and safety of rapamycin in children with tuberous sclerosis complex (TSC) associated renal disease. Methods: A prospective self-control study was conducted. The clinical data of 92 children diagnosed with tuberous sclerosis complex associated kidney disease at the People's Liberation Army General Hospital from January 2011 to January 2019 were collected. The long-term rapamycin treatment for all patients initiated at 1 mg/(m(2)·d), which was gradually adjusted to reach a blood concentration of 5-10 µg/L. The changes of the maximum diameter of renal lesions in children after rapamycin treatment were observed and analyzed with Wilcoxon test. Results: Ninety-two children, including 52 males and 40 females, who met the criteria were analyzed. Sixty patients had only renal angiomyolipoma(RAML), while 24 patients had only multiple renal cysts(MRC), and 8 patients had both lesions. The age of TSC diagnosis was 16.0 (7.0, 42.0) months, and the age of initial treatment with rapamycin was 63.5 (21.0, 103.0) months. The follow-up lasted for 12.0 (4.0, 23.0) months. Sequencing of TSC1 and TSC2 genes was performed in 54 children with TSC, including 3 patients (6%) with mutations in TSC1 gene and 51 patients (94%) with mutations in TSC2 gene. The maximum RAML diameter before treatment was 7.0 (4.0, 9.0) mm. The best effect reached at 3 months of treatment, with the diameter of 4.0 (0,7.0) mm. The maximum diameters at 6 months, 1 year and 1-2 years were 5.0 (0,9.8) mm, 5.0 (1.5, 8.5) mm, 5.5 (3.0, 9.0) mm, respectively, and were significantly different from the baseline (Z=-2.404,-2.350,-2.750,P=0.016,0.019,0.006, respectively). The maximum diameter after 2-3 years, and ≥3 years were 5.0 (3.9,7.0) mm and 6.0 (1.0, 11.0) mm, without significant difference from the baseline (Z=-0.856,-0.102,P=0.393,0.919, respectively).The maximum diameters of MRC after 3 months, 6 months, 1 year,1-2 years, 2-3 years, and ≥3 years were 11.0 (5.0, 14.0) mm,3.0 (0.0,11.0) mm,5.0 (0,21.0) mm,0 (0,14.0) mm,0 (0,10.0) mm, and 0 (0,18.3) mm, respectively, but were not significantly different rom the baseline (7.0 (5.0, 15.7) mm)(Z=-0.944,-1.214,-1.035,-1.896,-1.603,-1.214,P=0.345,0.225,0.301,0.058,0.109,0.225, respectively).Twenty-nine patients (32%) had oral ulcers during the entire treatment period, and no serious adverse reactions were observed. Conclusions: Rapamycin could decrease the diameter of TSC-related RAML, but could not inhibit the growth of cysts. It is well tolerated in the treatment of renal diseases associated with tuberous sclerosis complex.
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Angiomiolipoma/tratamento farmacológico , Antineoplásicos/uso terapêutico , Neoplasias Renais/tratamento farmacológico , Sirolimo/uso terapêutico , Esclerose Tuberosa/complicações , Angiomiolipoma/etiologia , Criança , China , Feminino , Humanos , Recém-Nascido , Neoplasias Renais/etiologia , Masculino , Estudos Prospectivos , Sirolimo/administração & dosagemRESUMO
BACKGROUND AND PURPOSE: N(6)-(3-methoxyl-4-hydroxybenzyl) adenine riboside (B2) is an analog of N(6)-(4-hydroxybenzyl) adenine riboside (NHBA), which was originally isolated from Gastrodia elata Blume. Our laboratory has previously demonstrated that B2 can produce strong sedative and hypnotic effects, but the mechanism remains to be determined. There is evidence that gamma-aminobutyric acid (GABA) acts as an inhibitory neurotransmitter in the brain, plays a major role in sleep regulation, and participates in the sedative and hypnotic effects of B2. Therefore, we studied the interactions between B2 and several GABAergic neurochemical parameters based on the sedative and hypnotic effects of B2. EXPERIMENTAL APPROACH: The GABA and glutamic acid (Glu) in the mouse brain were derivatized with o-phthalaldehyde (OPA) and measured by high performance liquid chromatography-electrochemical detection (HPLC-ECD). The GAD and GABA-T enzyme activities were determined by measuring GABA and NADH production, respectively. The sleep structure analyses were performed by EEG studies in mice. KEY RESULTS: B2 increased the GABA levels and GAD enzyme activity in the mouse hypothalamus and cortex. The EEG results confirmed that B2 significantly shortened the sleep latency and increased the amount of NREM sleep. The GAD enzyme inhibitor semicarbazide (SCZ) blocked the sedative and hypnotic effects of B2. CONCLUSIONS AND IMPLICATIONS: These findings suggest that the GAD enzyme plays a significant role in the sedative and hypnotic effects of B2. Therefore B2 may be a promising candidate for further clinical studies and the appropriate use of GAD agonist may be a promising approach for sleep disorders.
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Adenosina/análogos & derivados , Glutamato Descarboxilase/metabolismo , Hipnóticos e Sedativos/farmacologia , 4-Aminobutirato Transaminase/metabolismo , Adenosina/antagonistas & inibidores , Adenosina/farmacologia , Animais , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/enzimologia , Córtex Cerebral/metabolismo , Eletroencefalografia , Ativação Enzimática/efeitos dos fármacos , Ácido Glutâmico/metabolismo , Hipnóticos e Sedativos/antagonistas & inibidores , Hipotálamo/efeitos dos fármacos , Hipotálamo/enzimologia , Hipotálamo/metabolismo , Masculino , Camundongos , Semicarbazidas/farmacologia , Fases do Sono/efeitos dos fármacos , Ácido gama-Aminobutírico/metabolismoRESUMO
Breast cancer metastasis to bone represents a devastating complication of advanced breast cancer, frequently resulting in significant increases in morbidity and mortality. An understanding of the mechanisms that govern breast cancer metastasis at the molecular level should lead to more effective therapies. Recently, the kringle 1 domain of human hepatocyte growth factor (HGFK1) was identified as a candidate metastasis suppressor gene. Here, we investigated whether HGFK1 is a key regulator of breast cancer bone metastasis. Of the 193 human breast carcinoma tissue samples examined, HGFK1 expression was relative higher in 82 (42.4%) by western blot and in 84 (43.5%) by quantitative real-time PCR. The higher expression of HGFK1 was significantly associated with a better prognostic value (P<0.001) and inversely correlated with bone metastasis (P=0.003). The efficacy of adeno-associated virus carrying HGFK1 (AAV-HGFK1) in osteolytic bone metastasis was then evaluated using an in vivo bone metastasis model. AAV-HGFK1 significantly inhibited osteolytic bone metastasis and prolonged the survival of mice in this model (P<0.01). In vitro, HGFK1 expression resulted in significant anti-invasion effects, enhanced the phosphorylation of TAK1 (transforming growth factor-ß-activated kinase 1), p38 MAPK (mitogen-activated protein kinase) and MAPKAPK2 (MAPK-activated protein kinase 2) and decreased the expression of receptor activator of nuclear factor-κB (RANK), which was abrogated by the p38 MAPK inhibitor SB203580. This study shows for the first time that HGFK1 significantly inhibits the metastasis of breast cancer to bone by activating the TAK1/p38 MAPK signaling pathway and inhibiting RANK expression. Thus, AAV-HGFK1 treatment represents a potential therapy for bone metastasis in breast cancer.