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There remains a significant gap in our quantitative understanding of crosstalk between apoptosis and necroptosis pathways. By employing the SWATH-MS technique, we quantified absolute amounts of up to thousands of proteins in dynamic assembling/de-assembling of TNF signaling complexes. Combining SWATH-MS-based network modeling and experimental validation, we found that when RIP1 level is below ~1000 molecules/cell (mpc), the cell solely undergoes TRADD-dependent apoptosis. When RIP1 is above ~1000 mpc, pro-caspase-8 and RIP3 are recruited to necrosome respectively with linear and nonlinear dependence on RIP1 amount, which well explains the co-occurrence of apoptosis and necroptosis and the paradoxical observations that RIP1 is required for necroptosis but its increase down-regulates necroptosis. Higher amount of RIP1 (>~46,000 mpc) suppresses apoptosis, leading to necroptosis alone. The relation between RIP1 level and occurrence of necroptosis or total cell death is biphasic. Our study provides a resource for encoding the complexity of TNF signaling and a quantitative picture how distinct dynamic interplay among proteins function as basis sets in signaling complexes, enabling RIP1 to play diverse roles in governing cell fate decisions.
Subject(s)
Animals , Humans , Mice , Apoptosis , Caspase 8/metabolism , GTPase-Activating Proteins/metabolism , HEK293 Cells , Mice, Knockout , Necroptosis , Receptor-Interacting Protein Serine-Threonine Kinases/metabolismABSTRACT
Objective To investigate the imaging findings of combined hepatocellular carcinoma and cholangiocarcinoma(cHCC-CC) with dynamic MRI and spiral CT.Methods Twenty-three patients of cHCC-CC were evaluated.All patients had surgery and diagnoses were confirmed by histopathology.Eighteen patients had pre- and post-contrast scans with spiral CT.Five patients had MR with dynamic multi-phase contrast scanning.Imaging findings in all patients were retrospectively reviewed.Results CT of eighteen patients showed low-density masses with ill-defined margin (n =15 ),lymphadenopathy( n =5 ),invasion of blood vessels ( n =7 ),satellite lesions ( n =5 ),enhancing pseudocapsule ( n =9 ),and dilatation of intrahepatic ducts (n =1 ).MRI of five patients showed lesions with low signal on T1 WI and high signal on T2WI,lymphadenopathy(n =1 ),invasion of blood vessels (n =1 ),enhancing pseudocapsule (n =4).Dynamic CT or MRI enhanced scanning showed areas of heterogeneous enhancement in the interior or periphery of the tumor on the arterial phase,areas of inhomogeneous high signal ( corresponding regions of low signal on the arterial phase) on the portal venous phase,areas of mixed signal intensity due to retention of contrast agents on the delayed phase.Conclusions Combined hepatocellular carcinoma and cholangiocarcinom demonstrate imaging features on conventional and dynamic MRI and spiral CT,which can be helpful to improve the diagnostic accuracy of this disease.
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Objective To study the clinical value of operation in advanced endometrial carcinoma.Methods A retrospective study was carried out in 78 patients with advanced endometrial carcinoma received operation in our hospital from Jan.1,1997 to Dec.31,2007.The basic operation procedures were included total hysterectomy,adnexectomy,omentectomy,appendectomy and resection of metastatic lesions located in abdomino-pelvic cavity.The criteria of satisfied operation Was considered that the sizes of residual leision was smaller than or equal to 2 cm,which Was used to evaluate the effect of operation.The prognostic factors were also analyzed.Results Among the 78 cases,the rate of ideal cytoreductive surgery was 83%(65/78),included 23 cases of no residual leisions,42 cases of residual leisions size smaller than or equal to 2 cm,while 13 cases of residual leisions size larger than 2 cm.The Survival rate of 1-year,3-year and 5-year were 91%(61/67),55%(28/51)and 28%(10/36),respectively.The results by single factor analysis shown that the survival rate were correlated with prognostic factors included extent of disease,ascites,size of residual lesions,circles of chemotherapy.Conclusion It is important value for advanced endometrial carcinoma to ideal cytoredutive surgery followed by combined chemotherapy,while radiotherapy no further therapeutic effects.
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Objective To identify the typical imaging features of steatocystoma multiplex on mammography.Methods Mammographic findings in 9 patients with clinical and pathological diagnosis of steatocystoma multiplex were analyzed along with a review of the current literature.Results Four of the nine patients with steatocystoma multiplex had a positive family history.Nine patients showed multiple,round,thin-walled fatty,radiolucent nodules with well-defined margin.These nodules are located in the superficial layer of the axilla bilaterally.They are also seen on the skin of breast(7 cases),the anterior chest wall (4 cases) and the upper arm (3 cases).Conclusion Recognition of the characteristic mammographic features of Steatocystoma multiplex is important in the management of these patients.
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OBJECTIVE To explore how to establish the hospital infection control process by using evidence-based medicine.METHODS In order to establish the hospital infection control process for every department the data related to hospital infection were collected through searching related literature from MEDLINE,Chinese biomedicine literature database authorized by Institute of Medical Information.Chinese Academy of Medical Sciences and evidence-based medicine network then estimated thoroughly.RESULTS The incidence of hospital infection patients,environment sanitation inspection,medical staff hand-washing compliance,and occupational exposure all were up to scratch(P
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OBJECTIVE:To establish a HPLC method for the simultaneous determination of quercitrin and isoquercetin in hypericum japonicum thunb.injection.METHODS:Merck Lichrospher RP 18 was used as chromatographic column and the mo-bile phase consisted of acetonitrile-(pH=3.0)buffer phosphate(18∶82)with flow rate at1ml/min,column temperature at25℃and detection wavelength at350nm.RESULTS:The linear range for quercitrin and isoquercetin were0.278?g～4.440?g(r=0.9991)and0.315?g～2.520?g(r=0.9991),respectively.The average recovery were98.60%(RSD=2.23%)and97.79%(RSD=1.74%),respectively.CONCLUSION:This method is accurate,reliable and applicable,and suitable for the quality control of hypericum japonicum thunb.injection.
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OBJECTIVE To explore the infection control process in neonatal care unit by using evidence-based medicine(EBM).METHODS Under the guidance of EBM and process management theory,investigating and collecting relevant materials on hospital infection,searching the related literatures from the EBM websites(MEDLINE database,etc) and undertaking comprehensive evaluation,to establish the infection control process in neonatal care unit,in connection with practice,then using it in internal medicine and surgery wards.RESULTS After using infection control process,neonatal infection rate was reduced to 1.87%.Hygienic monitoring index of incubator,ventilator tube,pipe atomization,hand,air and handwashing compliance of medical staff were effectived changed(P
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Two models, mouse hot plate and vocalization indused by electrical stimulation of rat's tail were used to demonstrate the antinocice-ptive action of the neurotoxin ( NT ) from cobra venom.The paw-lick latencies of mice of both NT groups in different dose (0.023 mg/kg, 0.03 mg/kg, im ) were significantly prolonged than that of the control group. In the rats, the vocalization threshold of NT group was significantly higher than that of the control group too. This action of NT showed in these models was in good dose-resp-onse relationship. The onset of antinociceptive action of NT was 2 h and reached highe level 3h after intramuscular injection. This effect could be maintained for more than 24 h 3 groups of mice were continuously given normal saline, NT and morphine respectively for 9 days, and no tolerance showed in NT group of mice, but the acute tolerance to morphine occured in morphine group of mice. These result suggested that the analgesic mechanism of NT may be quite different from that fo morphine.