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Objective: To analyze the survival benefits and treatment related toxic effects of simultaneous integrated boost intensity-modulated radiotherapy (SIB-RT) for non-operative esophageal squamous cell carcinoma patients. Methods: The data of 2 132 ESCC patients who were not suitable for surgery or rejected operation, and underwent radical radiotherapy from 2002 to 2016 in 10 hospitals of Jing-Jin-Ji Esophageal and Esophagogastric Cancer Radiotherapy Oncology Group (3JECROG) were analyzed. Among them, 518 (24.3%) cases underwent SIB (SIB group) and 1 614 (75.7%) cases did not receive SIB (No-SIB group). The two groups were matched with 1â¶2 according to propensity score matching (PSM) method (caliper value=0.02). After PSM, 515 patients in SIB group and 977 patients in No-SIB group were enrolled. Prognosis and treatment related adverse effects of these two groups were compared and the independent prognostic factor were analyzed. Results: The median follow-up time was 61.7 months. Prior to PSM, the 1-, 3-, and 5-years overall survival (OS) rates of SIB group were 72.2%, 42.8%, 35.5%, while of No-SIB group were 74.3%, 41.4%, 31.9%, respectively (P=0.549). After PSM, the 1-, 3-, and 5-years OS rates of the two groups were 72.5%, 43.4%, 36.4% and 75.3%, 41.7%, 31.6%, respectively (P=0.690). The univariate survival analysis of samples after PSM showed that the lesion location, length, T stage, N stage, TNM stage, simultaneous chemoradiotherapy, gross tumor volume (GTV) and underwent SIB-RT or not were significantly associated with the prognosis of advanced esophageal carcinoma patients who underwent radical radiotherapy (P<0.05). Cox model multivariate regression analysis showed lesion location, TNM stage, GTV and simultaneous chemoradiotherapy were independent prognostic factors of advanced esophageal carcinoma patients who underwent radical radiotherapy (P<0.05). Stratified analysis showed that, in the patients whose GTV volume≤50 cm(3), the median survival time of SIB and No-SIB group was 34.7 and 30.3 months (P=0.155), respectively. In the patients whose GTV volume>50 cm(3), the median survival time of SIB and No-SIB group was 16.1 and 20.1 months (P=0.218). The incidence of radiation esophagitis and radiation pneumonitis above Grade 3 in SIB group were 4.3% and 2.5%, significantly lower than 13.1% and 11% of No-SIB group (P<0.001). Conclusions: The survival benefit of SIB-RT in patients with locally advanced esophageal carcinoma is not inferior to non-SIB-RT, but without more adverse reactions, and shortens the treatment time. SIB-RT can be used as one option of the radical radiotherapy for locally advanced esophageal cancer.
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Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Neoplasias de Cabeza y Cuello , Radioterapia de Intensidad Modulada , Neoplasias Gástricas , Quimioradioterapia , Análisis de Datos , Neoplasias Esofágicas/tratamiento farmacológico , Neoplasias Esofágicas/radioterapia , Carcinoma de Células Escamosas de Esófago/tratamiento farmacológico , Humanos , Estudios RetrospectivosRESUMEN
Objective: To evaluate the prognostic factors of T1-2N0M0 esophageal squamous cell carcinoma (ESCC) treated with definitive radiotherapy. Methods: The clinical data of 196 patients with T1-2N0M0 ESCC who were treated with definitive radiotherapy in 10 hospitals were retrospectively analyzed. All sites were members of Jing-Jin-Ji Esophageal and Esophagogastric Cancer Radiotherapy Oncology Group (3JECROG). Radiochemotherapy were applied to 78 patients, while the other 118 patients received radiotherapy only. 96 patients were treated with three-dimensional conformal radiotherapy (3DCRT) and 100 treated with intensity-modulated radiotherapy (IMRT). The median dose of plan target volume(PTV) and gross target volume(GTV) were both 60 Gy. The median follow-up time was 59.2 months. Log rank test and Cox regression analysis were used for univariat and multivariate analysis, respectively. Results: The percentage of normal lung receiving at least 20 Gy (V(20)) was (18.65±7.20)%, with average dose of (10.81±42.05) Gy. The percentage of normal heart receiving at least 30 Gy (V(30)) was (14.21±12.28)%. The maximum dose of exposure in spinal cord was (39.65±8.13) Gy. The incidence of radiation pneumonia and radiation esophagitis were 14.80%(29/196) and 65.82%(129/196), respectively. The adverse events were mostly grade 1-2, without grade 4 toxicity. Median overall survival (OS) and progression-free survival (PFS) were 70.1 months and 62.3 months, respectively. The 1-, 3- and 5-year OS rates of all patients were 75.1%ã57.4% and 53.2%, respectively. The 1-, 3- and 5-year PFS rates were 75.1%ã57.4% and 53.2%, respectively. Multivariate analysis demonstrated that patients'age (HR=1.023, P=0.038) and tumor diameter (HR=1.243, P=0.028)were the independent prognostic factors for OS, while tumor volume were the independent prognostic factor for PFS. Conclusions: Definitive radiotherapy is a promising therapeutic method in patients with T1-2N0M0 ESCC. Patients' age, tumor diameter and tumor volume may impact patients' prognosis.
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Neoplasias Esofágicas/radioterapia , Carcinoma de Células Escamosas de Esófago/radioterapia , Antineoplásicos/uso terapéutico , Quimioradioterapia , Relación Dosis-Respuesta en la Radiación , Neoplasias Esofágicas/tratamiento farmacológico , Neoplasias Esofágicas/mortalidad , Neoplasias Esofágicas/patología , Carcinoma de Células Escamosas de Esófago/tratamiento farmacológico , Carcinoma de Células Escamosas de Esófago/mortalidad , Carcinoma de Células Escamosas de Esófago/patología , Humanos , Pronóstico , Dosificación Radioterapéutica , Radioterapia Conformacional , Radioterapia de Intensidad Modulada , Estudios RetrospectivosRESUMEN
Objective: To evaluate the survival and prognostic factors of radiotherapy in patient with â £ stage esophageal squamous carcinoma treated with radiation or chemoradiation. Methods: The medical records of 608 patients with stage â £ esophageal squamous cell carcinoma who met the inclusion criteria in 10 medical centers in China from 2002 to 2016 were retrospectively analyzed. The overall survival and prognostic factors of all patients at 1, 3 and 5 years were analyzed. Results: The 1-, 3-, 5- year overall survival (OS) rates was 66.7%, 29.5% and 24.3% in stage â £A patients, and 58.8%, 29.0% and 23.5% in stage â £B patients. There was no statistical difference between the two groups (P=0.255). Univariate analysis demonstrated that the length of lesion, treatment plan, planned tumor target volume (PGTV) dose, subsequent chemotherapy, and degrees of anemia, radiation esophagitis, radiation pneumonia were related to the prognoses of patients with â £ stage esophageal carcinomas after radiotherapy and chemotherapy (P<0.05). Multivariate analysis demonstrated that PGTV dose (OR=0.693, P=0.004), radiation esophagitis (OR=0.867, P=0.038), and radiation pneumonia (OR=1.181, P=0.004) were independent prognostic factors for OS. Conclusions: For patients with stage â £ esophageal squamous cell carcinoma, chemoradiotherapy followed by sequential chemotherapy is recommended, which can extend the total survival and improve the prognosis of the patients. PGTV dose more than 60 Gy has better efficacy.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Quimioradioterapia/métodos , Neoplasias Esofágicas/tratamiento farmacológico , Neoplasias Esofágicas/radioterapia , Carcinoma de Células Escamosas de Esófago/tratamiento farmacológico , Carcinoma de Células Escamosas de Esófago/radioterapia , China/epidemiología , Neoplasias Esofágicas/mortalidad , Neoplasias Esofágicas/patología , Carcinoma de Células Escamosas de Esófago/mortalidad , Carcinoma de Células Escamosas de Esófago/patología , Humanos , Estadificación de Neoplasias , Radioterapia de Intensidad Modulada/métodos , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
ABSTRACT: Objective To investigate the sequential changes of the number of neutrophils and myofibroblasts during diabetic wound healing, and discuss its application value in wound age estimation. Methods Diabetic DB mice and mice of the same age in the normal control group were selected, a wound healing model was established, wound samples were taken at different time points, while the number of neutrophils and myofibroblasts during diabetic wound healing were determined by immunohistochemical staining technique. Results The number of infiltrated neutrophils in the wounds of control and diabetic groups reached the peak respectively at 12 h and 5 d after injury. Compared with the control group, the number of neutrophils in the diabetic group decreased significantly from 6 h to 1 d after injury, but increased markedly from 5 d to 14 d. From 5 d to 10 d after injury, the average number of neutrophils at high magnification in wounds of the diabetic group was over 30, while that of neutrophils in wounds of the control group was less than 20. Myofibroblasts appeared in wounds from 3 d to 14 d after injury in the control group and from 5 d to 14 d after injury in the diabetic group. The difference in the number of myofibroblasts in wounds between control group and diabetic group from 3 to 7 d after injury had statistical significance. Conclusion In comparison with normal wound healing, the number of neutrophils and myofibroblasts during diabetic wound healing shows different sequential changes. The results of this study can provide reference for wound age estimation of patients with severe diabetes.
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Diabetes Mellitus Experimental/patología , Miofibroblastos , Neutrófilos , Cicatrización de Heridas/fisiología , Animales , Diabetes Mellitus Experimental/complicaciones , RatonesRESUMEN
Objective: To investigate the application of extracorporeal membrane oxygenation (ECMO) in pediatrics in China as well as the outcomes. Methods: Data was conducted by questionnaire to investigate the use of ECMO in children under the age of 18 in China by June 30, 2017. All patients were divided into two age groups: pediatric patients (29 d-18 y) and neonates (1-28 d); Also by the causes of ECMO treating including cardiac, respiratory and extracorporeal cardiopulmonary resuscitation (ECPR). The form included the numbers of ECMO cases, weaned and discharged cases, according to the different ages and causes. In addition, the departments that routinely participate in ECMO management were acquired. Results: Totally 43 tertiary hospitals were enrolled, of which 30 have implemented ECMO for the children patients (comprising pediatrics and neonates), including 14 general hospitals, 5 cardiothoracic specialty hospitals and 11 children's or women and children's hospitals. ECMO for pediatrics and neonates was firstly carried out at mainland China in 2004. To the deadline of investigation, 800 patients were supported with ECMO, among which 658 were pediatrics, much more than 142 of neonates. As to pediatrics, 453 were supported with ECMO for cardiac indications with 287 (63.4%) weaned off and 215 (47.5%) survived to discharge; for respiratory causes, 79 cases were registered with 47 (59.5%) weaned off and 36 (45.6%) discharged; for ECPR, 126 were enrolled with 62 (49.2%) successfully weaned off and 48 (38.1%) discharged. In contrast, neonatal patients undergoing cardiac ECMO contained 79 cases, with 39 (49.4%) weaned off and 26 (32.9%) discharged; due to respiratory causes, 40 neonates were included, with 26 (65.0%) weaned off and 21 (52.5%) discharged; 23 neonatal patients consisted of ECPR cause and 10 (43.5%) of them successfully weaned off, but only 6 (26.1%) finally survived. Among the 30 hospitals conducted ECMO for pediatrics and neonates, the average number of departments for ECMO management is 4.03±1.87. Conclusions: Although ECMO used for children in mainland China is relatively late, a certain number of cases have been accumulated, and there is still a gap compared with the international standard. Meanwhile, each hospital has preliminarily built up its own ECMO team.
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Oxigenación por Membrana Extracorpórea , Reanimación Cardiopulmonar , Niño , China , Humanos , Lactante , Recién Nacido , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: Serum lipids, including total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-c), increase during pregnancy. Serum Proprotein Convertase Subtilisin Kexin 9 (PCSK9) is a vital regulator in lipoprotein metabolism. Circulating PCSK9 downregulates the LDL receptor on the surface of liver cells inhibiting clearance of LDL-c. OBJECTIVE: To determine the influence of weeks of pregnancy and obesity on circulating levels of essential lipid lipoproteins and PCSK9 in women with normal, uncomplicated pregnancies and deliveries. METHODS: We performed a comprehensive lipid and lipoprotein profile during each trimester of pregnancy in 70 mostly Caucasian women with uncomplicated normal pregnancies and deliveries. Based on their first trimester BMI, we placed them into one of three categories: (<25 kg/m2 n=23, 25-30 kg/m2 n=25, or >30 n=22) kg/m2. Cholesterol, triglycerides, LDL cholesterol (LDL-c), non-HDL particles, and lipoprotein(a) were measured by spectrophotometry, ion mobility, and immunoturbidimetric assays. Elisa assay determined PCSK9 (active and total). Homeostatic Model Assessment (HOMA-IR) assessed insulin resistance in the second and third trimesters of pregnancy. RESULTS: Total and active PCSK9, LDL-c, and nonHDL particle concentrations were higher than reported for non-pregnant normal values, increased after the first trimester of pregnancy, and were highest from mid-gestation to the last trimester of pregnancy in the overweight and the obese. CONCLUSION: PCSK9 levels rise as normal pregnancy progresses. Levels are higher in persons who are obese, even after adjustment for insulin resistance. Defining normal PCSK9 levels during pregnancy must adjust for gestational age and BMI.
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Resistencia a la Insulina , Proproteína Convertasas , Índice de Masa Corporal , Colesterol , LDL-Colesterol , Femenino , Humanos , Lipoproteínas , Obesidad , Embarazo , Proproteína Convertasa 9 , Subtilisinas , TriglicéridosRESUMEN
This article reports the surgical resection of clinically benign tumours in the maxillomandibular deep lobe of the parotid gland via sternocleidomastoid muscle-parotid space (SPS) approach. The use of maxillary-mandibular planes to subdivide the deep lobe of the parotid gland in order to establish the tumour location and accessibility is introduced. This approach, which does not raise a skin flap, may preserve the superficial lobe. Ten patients with clinically benign tumours in the maxillomandibular deep lobe of the parotid gland were treated via the SPS approach. The patients were followed up for 3-5 years and the surgical outcomes were analysed. All tumours were completely enucleated via the SPS approach with an optimal aesthetic outcome. No permanent facial weakness or tumour recurrence was identified during the 3-5 years of follow-up. The SPS approach to surgical resection is an ideal option for clinically benign tumours in the maxillomandibular deep lobe of the parotid gland and demonstrates good results.
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Glándula Parótida , Neoplasias de la Parótida , Estética Dental , Humanos , Músculos del Cuello/diagnóstico por imagen , Músculos del Cuello/cirugía , Recurrencia Local de Neoplasia , Neoplasias de la Parótida/diagnóstico por imagen , Neoplasias de la Parótida/cirugía , Complicaciones Posoperatorias , Estudios RetrospectivosRESUMEN
OBJECTIVE: The specific mechanism of cytokine storm in COVID-19 infected patients is not clear. This study aims to identify the key genes that cause cytokine storm in COVID-19 infected patients. MATERIALS AND METHODS: We conducted a difference analysis on the GSE147507 data set. The analysis results are combined with immune genes to obtain immune-related genes among the differential genes. Finally, GO enrichment analysis, PPI analysis, core gene identification, and ssGSEA enrichment analysis were performed on the new gene set. RESULTS: A total of 232 differential genes were screened out. After merging with immune genes, a total of 29 immune-related genes were obtained. Further analysis revealed that the genes were enriched in 16 pathways, and the protein interaction network had a total of 29 nodes and 139 edges. After screening, the core gene was CXCL10. The ssGSEA results of CXCL10 showed that CD4 and CD8 immune-related signature were significantly enriched in high CXCL10 expression, and the samples with low CXCL10 expression were significantly enriched with monocytes and DC immune-related signature. CONCLUSIONS: CXCL10 may be a key gene related to the cytokine storm of COVID-19 infection, and it is expected to become the therapeutic target.
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Quimiocina CXCL10/genética , Infecciones por Coronavirus/genética , Neumonía Viral/genética , Betacoronavirus/inmunología , Betacoronavirus/aislamiento & purificación , COVID-19 , Quimiocina CXCL10/inmunología , Infecciones por Coronavirus/inmunología , Humanos , Pandemias , Neumonía Viral/inmunología , Mapas de Interacción de Proteínas/genética , Mapas de Interacción de Proteínas/inmunología , SARS-CoV-2RESUMEN
UNLABELLED: The effects of pet exposure and parental atopy on respiratory symptoms were investigated in 12,910 children residing in twelve districts of northeast China. Responses to a self-administered questionnaire completed by parents of children were used to ascertain children with persistent cough, persistent phlegm, doctor-diagnosed asthma, current asthma and current wheeze. Exposure to animals during pregnancy was positively associated with doctor-diagnosed asthma [adjusted odds ratio (ORs), 1.86; 95% confidence interval (CI) 1.35-2.57], current asthma (adjusted OR, 3.06; 95% CI, 1.95-4.81) and asthma-related symptoms. Pet exposure in the first year of life and currently having animals in household were also related to a significantly higher prevalence of doctor-diagnosed asthma and asthma-related symptoms in these children. Associations with respiratory symptoms strengthened with higher levels of animal exposure. Parental atopy increased the risk of asthma diagnosis (OR, 3.49; 95%CI, 2.84-4.30), current asthma (OR, 3.94; 95%CI, 2.81-5.54) and asthma-related symptoms. There was an interaction between parental atopy and pet exposure in persistent phlegm, but not in doctor-diagnosed asthma. We conclude that pet keeping and parental atopy increased the risk of respiratory symptoms in children. Parental atopy did modify the effect of pet exposure on persistent phlegm but not on doctor-diagnosed asthma. PRACTICAL IMPLICATIONS: The relationship between exposure to animals and allergic respiratory diseases in childhood is controversial. Inconsistent with other cross-sectional studies mostly conducted in industrialized countries, our study indicates that exposure to animals may increase the occurrence of respiratory symptoms and diseases in children, and the associations with respiratory symptoms strengthened with higher levels of animal exposure parental atopy did modify the effect of pet exposure on persistent phlegm but not on doctor-diagnosed asthma. These findings support the view that measures should be taken to reduce animal exposure for children in China.
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Animales Domésticos/inmunología , Asma/epidemiología , Adolescente , Contaminación del Aire Interior/efectos adversos , Alérgenos/efectos adversos , Alérgenos/inmunología , Animales , Asma/genética , Asma/inmunología , Niño , China/epidemiología , Femenino , Predisposición Genética a la Enfermedad , Humanos , Masculino , Padres , Factores de RiesgoRESUMEN
A set of resonant inelastic X-ray scattering (RIXS) studies focusing on the 2p64f(n)-->2p54f(n)5d1(2p54f(n+1)5d0)-->2p63d94f(n)5d1(2p63d94f(n+1)5d0) channel of dysprosium in Dy metal, Dy2O3, DyNi3 and Dy25Fe18 compounds have been carried out. Data showed with high statistics and resolution, the different delocalization degree of the 5d band of dysprosium in these compounds, e.g., decreasing from Dy metal to DyNi3, Dy25Fe18 and to dysprosium oxide, in agreement with the high-resolution XANES (HRXANES) spectra. Band structure calculations performed on Dy metal and Dy2O3 confirm both RIXS and HRXANES results in the increasing delocalization of the dysprosium 5d band in Dy metal with respect to Dy2O3. The 5d orbital occupancies of DyNi3 and Dy25Fe18 alloys have been also studied by comparison of the HRXANES white line (WL) area with the behavior of the final states energy position in RIXS spectra and we show that DyNi3 has a higher 5d orbital occupancy than Dy25Fe18.
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Disprosio/química , Rayos X , Aleaciones/química , Análisis EspectralRESUMEN
BACKGROUND: The prognosis of children with juvenile dermatomyositis (JDM) has improved remarkably since the 1960's with the use of corticosteroid and immunosuppressive therapy. Yet there remain a minority of children who have refractory disease. Since 2003 the sporadic use of biologics (genetically-engineered proteins that usually are derived from human genes) for inflammatory myositis has been reported. In 2011-2016 we investigated our collective experience of biologics in JDM through the Childhood Arthritis and Rheumatology Research Alliance (CARRA). METHODS: The JDM biologic study group developed a survey on the CARRA member experience using biologics for Juvenile DM utilizing Delphi consensus methods in 2011-2012. The survey was completed online by the CARRA members interested in JDM in 2012. A second survey was similarly developed that provided more opportunity to describe their experiences with biologics in JDM in detail and was completed by CARRA members in Feb 2013. During three CARRA meetings in 2013-2015, nominal group techniques were used for achieving consensus on the current choices of biologic drugs. A final survey was performed at the 2016 CARRA meeting. RESULTS: One hundred and five of a potential 231 pediatric rheumatologists (42%) responded to the first survey in 2012. Thirty-five of 90 had never used a biologic for Juvenile DM at that time. Fifty-five of 91 (denominators vary) had used biologics for JDM in their practice with 32%, 5%, and 4% using rituximab, etanercept, and infliximab, respectively, and 17% having used more than one of the three drugs. Ten percent used a biologic as monotherapy, 19% a biologic in combination with methotrexate (mtx), 52% a biologic in combination with mtx and corticosteroids, 42% a combination of a biologic, mtx, corticosteroids (steroids), and an immunosuppressive drug, and 43% a combination of a biologic, IVIG and mtx. The results of the second survey supported these findings in considerably more detail with multiple combinations of drugs used with biologics and supported the use of rituximab, abatacept, anti-TNFα drugs, and tocilizumab in that order. One hundred percent recommended that CARRA continue studying biologics for JDM. The CARRA meeting survey in 2016 again supported the study and use of these four biologic drug groups. CONCLUSIONS: Our CARRA JDM biologic work group developed and performed three surveys demonstrating that pediatric rheumatologists in North America have been using multiple biologics for refractory JDM in numerous scenarios from 2011 to 2016. These survey results and our consensus meetings determined our choice of four biologic therapies (rituximab, abatacept, tocilizumab and anti-TNFα drugs) to consider for refractory JDM treatment when indicated and to evaluate for comparative effectiveness and safety in the future. Significance and Innovations This is the first report that provides a substantial clinical experience of a large group of pediatric rheumatologists with biologics for refractory JDM over five years. This experience with biologic therapies for refractory JDM may aid pediatric rheumatologists in the current treatment of these children and form a basis for further clinical research into the comparative effectiveness and safety of biologics for refractory JDM.
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Dermatomiositis , Quimioterapia Combinada , Etanercept/uso terapéutico , Glucocorticoides/uso terapéutico , Infliximab/uso terapéutico , Administración del Tratamiento Farmacológico/tendencias , Metotrexato/uso terapéutico , Rituximab/uso terapéutico , Antirreumáticos/uso terapéutico , Terapia Biológica/métodos , Niño , Dermatomiositis/epidemiología , Dermatomiositis/terapia , Resistencia a la Enfermedad , Quimioterapia Combinada/clasificación , Quimioterapia Combinada/métodos , Quimioterapia Combinada/tendencias , Femenino , Humanos , Masculino , Pediatría/métodos , Pediatría/tendencias , Pautas de la Práctica en Medicina/estadística & datos numéricos , Encuestas y Cuestionarios , Estados Unidos/epidemiologíaRESUMEN
BACKGROUND: Endothelium-derived nitric oxide (NO) is produced by an oxidative reaction catalyzed by endothelial NO synthase (eNOS). NO plays a crucial role in controlling cell growth and apoptosis, as well as having well-characterized vasodilator and antithrombotic actions. More recently, endothelium-derived NO was shown to be involved in postdevelopmental vascular remodeling and angiogenesis, as well as in the formation of limb vasculature during embryogenesis. Therefore, we investigated the role of endothelium-derived NO during cardiovascular development using mice deficient in eNOS. METHODS AND RESULTS: We examined the hearts of 12 mature eNOS-deficient and 26 mature wild-type mice. Five of the mature eNOS-deficient mice had a bicuspid aortic valve; none of the 26 wild-type animals exhibited identifiable valvular or cardiac abnormalities. Immunohistochemical analysis revealed prominent eNOS expression localized to the endothelium lining the valve cusps of the aorta in mature wild-type mice; expression was localized to the myocardium and endothelial cell monolayer lining the valve leaflets in the developing embryo. CONCLUSIONS: These results show a strong association between eNOS deficiency and the presence of a bicuspid aortic valve; they provide the first molecular insight into one of the most common types of congenital cardiac abnormality.
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Válvula Aórtica/anomalías , Óxido Nítrico Sintasa/deficiencia , Animales , Válvula Aórtica/enzimología , Válvula Aórtica/patología , Embrión de Mamíferos/metabolismo , Endotelio Vascular/embriología , Endotelio Vascular/patología , Corazón/embriología , Cardiopatías Congénitas/genética , Inmunohistoquímica , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados/genética , Óxido Nítrico Sintasa/genética , Óxido Nítrico Sintasa/metabolismo , Óxido Nítrico Sintasa de Tipo II , Óxido Nítrico Sintasa de Tipo III , Valores de Referencia , Distribución TisularRESUMEN
OBJECTIVE: As the contamination of implant surface seriously affects the early osseointegration of implants and reduces the survival rate of implants, it has attracted wide attention of researchers. The most oral titanium implants used in current clinical applications are stored in sealed packages. During the process of packaging, storage and usage, the implants inevitably contact air, which results in the surface contamination. As an inert gas, the argon has very inactive chemical properties and is routinely used as a protective gas to cut air pollution. In this study, we investigated whether argon protection can cut air pollution and maintain lasting surface biological activity of titanium implants. MATERIALS AND METHODS: We prepared sandblasting etched titanium samples under air protection or under argon protection. The samples prepared under air protection were used as the control. With the scanning electron microscopy, the contact angle measurements and the X-ray photoelectron spectroscopy, we examined surface morphology, hydrophilicity, chemical structures and components of the implants prepared under two gas protections. By using beagles as the animal model, we assessed the bone guide of the implants prepared under argon protection and morphological changes of surrounding tissues. RESULTS: While compared with those implants prepared under air protection, the surface morphology of implants prepared under argon protection did not change, which had preferable hydrophilicity, and there were differences in percentage of surface chemical elements and chemical structure. After 4 weeks, the bone-implant contact (BIC) in argon protection group was twice of the control group and the difference was statistically significant (p < 0.01). The Implant Niuchu experiments also proved that under argon protection, the implants would have good integration with the surrounding bone tissues. CONCLUSIONS: This study revealed the implants prepared under argon can cut air pollution and have high bone guide property and biological activity.
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Argón/química , Interfase Hueso-Implante , Prótesis e Implantes , Titanio/química , Contaminantes Atmosféricos/análisis , Animales , Materiales Biocompatibles/química , Perros , Masculino , Microscopía Electrónica de Rastreo , Oseointegración , Propiedades de Superficie , TibiaRESUMEN
The CXCR4 chemokine receptor has an important role in cancer cell metastasis. The CXCR4 antagonist, AMD3100, has limited efficacy in controlling metastasis. HuR, an RNA-binding protein, regulates CXCR4 in cancer cells. We therefore investigated whether targeting HuR using a siRNA-based nanoparticle plus AMD3100 would suppress CXCR4 and inhibit lung cancer metastasis. We treated human H1299 lung cancer cells with HuR-specific siRNA contained in a folate-targeted lipid nanoparticle (HuR-FNP) plus AMD3100, and compared this with AMD3100 alone, HuR-FNP alone and no treatment. HuR-FNP plus AMD3100 treatment produced a G1 phase cell cycle arrest and reduced cell viability above and beyond the effects of AMD3100 alone. HuR and CXCR4 mRNA and protein expression levels were markedly reduced in all treatment groups. Phosphorylated (p) AKT(S473) protein was also reduced. P27 protein expression increased with HuR-FNP and combination treatment. Promoter-based reporter studies showed that the combination inhibited CXCR4 promoter activity more than did either treatment alone. Cell migration and invasion was significantly reduced with all treatments; the combination provided the most inhibition. Reduced matrix metalloprotease (MMP)-2 and -9 expression was associated with reduced invasion in all treatment groups. Thus, we found that combined HuR and CXCR4 targeting effectively controlled lung cancer metastasis.
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Antineoplásicos/uso terapéutico , Proteína 1 Similar a ELAV/antagonistas & inhibidores , Compuestos Heterocíclicos/uso terapéutico , Neoplasias Pulmonares/terapia , Nanopartículas/uso terapéutico , Receptores CXCR4/antagonistas & inhibidores , Bencilaminas , Movimiento Celular , Proliferación Celular , Terapia Combinada , Ciclamas , Regulación hacia Abajo , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/fisiopatología , Nanopartículas/metabolismo , Invasividad Neoplásica , ARN Interferente Pequeño , Receptores CXCR4/genéticaRESUMEN
Autoradiographic techniques and 125I-labeled endothelin-1 were used to study the distribution of endothelin-1 binding sites in porcine skin. Specific endothelin-1 binding sites were localized to blood vessels (capillaries, deep cutaneous vascular plexus, arteries, and arterioles), the deep dermal and connective tissue sheath of hair follicles, sebaceous and sweat glands, and arrector pili muscle. Specific binding was inhibited by endothelin-2 and endothelin-3 as well as endothelin-1. Non-specific binding was found in the epidermis and the medulla of hair follicles. No binding was found in connective tissue or fat. These vascular binding sites may represent endothelin receptors, in keeping with the known cutaneous vasoconstrictor actions of the peptide. If all binding sites are receptors, the results suggest that endothelin could also regulate the function of sweat glands and may have trophic effects in the skin.
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Endotelinas/metabolismo , Receptores de Superficie Celular/metabolismo , Piel/metabolismo , Animales , Autorradiografía , Técnicas In Vitro , Radioisótopos de Yodo , Receptores de Endotelina , Piel/citología , PorcinosRESUMEN
Yi-Cheng Zhao was trained in neurosurgery at the Montreal Neurological Institute by Wilder Penfield in 1938. This article presents Zhao's great contributions to the development of neurosurgery in China. He set up the first independent neurosurgical departments in Tianjin (1952) and in Beijing (1954). A basic research unit for neurosurgery, Beijing Neurosurgical Institute, was also established in 1960 under Zhao's insistent efforts. To raise the clinical level, he emphasized subspecialization of neurosurgery and divided the service into tumor, trauma, pediatrics, and miscellaneous groups. He was also enthusiastic about training neurosurgeons. More than 200 students have been trained by him, and most of them have set up centers in different cities in China. At present, the Beijing Neurosurgical Institute is the largest neurosurgical research unit. It plays an important role in the development of Chinese neurosurgery. Zhao devoted nearly 40 years to neurosurgery and died in 1974. The chinese Neurosurgical Association has honored Zhao as "a founder of neurosurgery in China."
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Neurocirugia/historia , China , Historia del Siglo XXRESUMEN
The covalent immobilization of DNA onto self-assembled monolayer (SAM) modified gold electrodes (SAM/Au) was studied by X-ray photoelectron spectrometry and electrochemical method so as to optimize its covalent immobilization on SAMs. Three types of SAMs with hydroxyl, amino, and carboxyl terminal groups, respectively, were examined. Results obtained by both X-ray photoelectron spectrometry and cyclic voltammetry show that the largest covalent immobilization amount of dsDNA could be gained on hydroxyl-terminated SAM/Au. The ratio of amount of dsDNA immobilized on hydroxyl-terminated SAMs to that on carboxyl-terminated SAMs and to that on amino-terminated SAMs is (3-3.5): (1-1.5): 1. The dsDNA immobilized covalently on hydroxyl-terminated SAMs accounts for 82.8-87.6% of its total surface amount (including small amount of dsDNA adsorbed). So the hydroxyl-terminated SAM is a good substrate for the covalent immobilization of dsDNA on gold surfaces.
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The characterization and localization of binding sites for endothelin-1 (ET-1) labeled with iodine 125I were investigated in homogenized tissues and sections of Harder's glands of normal rabbits. The membrane of Harder's glands was harvested and incubated with 125I-ET-1 (0.25-1 nmol/L) in 20 +/- 4 mg of protein per 0.25 mL at 37 degrees C for 90 min in the presence of protease inhibitors. Specific labeling was assessed by coincubating unlabeled ET-1, ET-2, ET-3 and other unrelated cytokines. The tissue labeled with 125I-ET-1 was collected by filtration and counted in a gamma counter. For an in vitro autoradiography study, 15 microns cryostat sections were incubated with 125I-ET-1 (0.1 nmol/L). They were fixed, dipped in liquid emulsion and kept for 6 days before development. Membrane counting showed that the binding of 125I-ET-1 to Harder's gland was saturable. Scatchard data analysis revealed one class of binding with a dissociation constant (Kd) of 0.33 nmol/L and a maximal density of binding (Bmax) of 794 attomole/mg of protein. The binding was inhibited most by ET-1, followed by ET-2 and then ET-3 but not by unrelated peptides. Emulsion-dipped slides with sections showed specific high-density labeling mainly over structures identified from serial sections stained by hematoxylin-eosin as the walls of capillaries, arterioles, arteries, and veins of the glands. Less dense binding was found in both white and pink lobes of the gland. No binding was found in fat and connective tissues. The distribution of endothelin action sites in the glandular blood vessels and Harder's gland suggests that the peptide may have a role in the regulation of blood circulation and glandular secretion in the normal rabbit.
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Endotelinas/metabolismo , Glándula de Harder/metabolismo , Animales , Autorradiografía , Sitios de Unión , Membrana Celular/metabolismo , Femenino , Masculino , Conejos , Ensayo de Unión RadioliganteRESUMEN
OBJECTIVE: To screen Hemolytic Uremic Syndrome (HUS) related differentially expressed genes using the microarray data of neonatal microvascular endothelial cells from human skin treated with or without Shiga toxin, and study the the mechanism of HUS from multiple angles. MATERIALS AND METHODS: The microarray dataset GSE32710 was download from gene expression database GEO (Gene Expression Omnibus), which included a total of 12 samples, 6 samples were treated with Shiga toxin while the others were normal without any treatments. Then the raw chip data were preprocessed by R package, and T-test was utilized for differentially expressed genes screening. The selected differentially expressed genes were subjected to GO functional and KEGG pathway analysis. Following that, human protein interaction network, synergetic effects among the differentially expressed genes and regulation of post-transcriptional miRNA were integrated so as to construct a molecular interaction network associated with HUS and excavate the sub-function modules. RESULTS: Trough differential expression screening, 195 of HUS related marker genes were obtained, and 294 of gene pairs with significant co-expression were achieved. Molecular interaction network associated with HUS excavated 302 miRNAs and 117 differentially expressed genes, among which miRNA-30c and miRNA-30d may play important roles during the development of HUS. CONCLUSIONS: In this study, we used a method that explained the biological mechanism of HUS systematically from gene transcription level and different levels of biological information such as protein interaction, post-transcriptional regulation of gene expression as well as synergy effects of gene expression, which may provide new therapeutic targets for HUS.
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Bases de Datos Genéticas , Redes Reguladoras de Genes/fisiología , Síndrome Hemolítico-Urémico/genética , Síndrome Hemolítico-Urémico/metabolismo , Transducción de Señal/fisiología , Muerte Celular/fisiología , Humanos , MicroARNs/biosíntesis , MicroARNs/genética , Mapas de Interacción de Proteínas/fisiologíaRESUMEN
A physiologically based pharmacokinetics model was developed to predict tulathromycin concentrations in edible swine tissues. Physiological parameters included volumes of and plasma flows through different tissues which were obtained from the literatures. The tissue/plasma partition coefficient was calculated according to the area method, and the model was validated through a comparison of predicted and observed concentrations. Withdrawal times in different tissues were predicted. The physiologically based pharmacokinetics model presented here provided accurate predictions of the observed concentrations in all tissues. The results showed that the injection site had the longest withdrawal time (21 days), followed by skin together with fat (19 days) and then kidney (10 days), lung (6 days), liver (4 days) and muscle (1 day). A withdrawal time of 21 days was finally predicted for tulathromycin in swine after a single intramuscular injection at 2.5 mg/kg body weight.