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Community-acquired respiratory infection is the commonest cause of sepsis presenting to emergency departments. Yet current experimental animal models simulate peritoneal sepsis with intraperitoneal (I.P.) injection of lipopolysaccharide (LPS) as the predominant route. We aimed to compare the progression of organ injury between I.P. LPS and intranasal (I.N.) LPS in order to establish a better endotoxemia murine model of respiratory sepsis. Eight weeks old male BALB/c mice received LPS-Escherichia coli doses at 0.15, 1, 10, 20, 40 and 100 mg per kg body weight (e.g. LPS-10 is a dose of 10 mg/kg body weight). Disease severity was monitored by a modified Mouse Clinical Assessment Score for Sepsis (M-CASS; range 0–21). A M-CASS score ≥ 10 or a weight reduction of ≥ 20%, was used as a criterion for euthanasia. The primary outcome was the survival rate (either no death or no need for euthanasia). The progression of disease was specified as M-CASS, body weight, blood glucose, histopathological changes to lung, liver, spleen, kidney, brain and heart tissues. Survival rate in I.P. LPS-20 mice was 0% (2/3 died; 1/3 euthanized with M-CASS > 10) at 24 h. Survival rate in all doses of I.N. LPS was 100% (20/20; 3–4 per group) at 96 h. 24 h mean M-CASS post-I.P. LPS-10 was 6.4/21 significantly higher than I.N. LPS-10 of 1.7/21 (Unpaired t test, P < 0.05). Organ injury was present at 96 h in the I.P. LPS-10 group: lung (3/3; 100%), spleen (3/3; 100%) and liver (1/3; 33%). At 24 h in the I.P. LPS-20 group, kidney injury was observed in the euthanized mouse. At 96 h in the post-I.N. LPS-20 group, only lung injury was observed in 2/3 (67%) mice (Kruskal-Wallis test with Dunn’s, P < 0.01). At 24 h in the post-I.N. LPS-100 group all (4/4) mice had evidence of lung injury. Variable doses of I.N. LPS in mice produced lung injury but did not produce sepsis. Higher doses of I.P. LPS induced multi-organ injury but not respiratory sepsis. Lethal models of respiratory virus, e.g., influenza A, might provide alternative avenues that can be explored in future research.
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【Objective】 We combined the concept of traditional medicine with magnetic induction technology, originally brought up the research concept of magnetic hyperthermia to cure KOA, explored the mechanism and constructed a new treatment of KOA with modern medical features. 【Methods】 Through establishing a primary KOA model in rats and constructing ferrimagnetic vortex domain iron oxide nanorings (FVIOs) as a platform for highly efficient magnetic hyperthermia agent, the lesions of KOA were heated accurately under the low-intensity magnetic field. We confirmed the curative effect through the results of pain perception, histopathology, knee joint morphology and microscopic bone structure and the content of serum inflammatory factor, to study the therapeutic mechanism of magnetic hyperthermia for KOA. 【Results】 Compared with the model group, the recovery of mechanical pain threshold after magnetic hyperthermia improved by approximately 48.9%; the degree of hyperemia and edema of joint capsule and synovial tissue and the wear degree of joint cartilage surface, were significantly reduced; the Mankin and OARSI scores decreased by about 33% and 20%, respectively; the MicroCT results indicated that the degree of hardening of the subchondral bone also improved; the expression of inflammatory factors in the serum was reduced. 【Conclusion】 In this study, we utilized the FVIOs as a high-efficiency magnetic hyperthermia platform for the treatment of KOA. The efficacy of magnetic hyperthermia on KOA is clarified, and the mechanism is related to the inhibition of inflammatory factors.
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Heat shock protein 70(HSP70)is a highly conserved polypeptide protein,which plays an im-portant role in protein homeostasis,apoptosis,invasion and cell signaling transduction. Many studies have shown that the expression level of HSP70 is closely related to the development and progression of tumor,which is a low expression in normal tissues and the overexpression in tumor tissue. Hepatocellular carcinoma ( HCC ) is con-cealed,and the related study reported that the expression of HSP70 can be used as a sensitive biological index for the diagnosis and differential diagnosis for early HCC,and also affects the treatment and prognosis of patients with HCC. This article will summary the relationship between the expression of HSP70 and HCC.
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Objective To explore the application of amide proton transfer (APT) imaging in differentiating glioma from treatment effect and to evaluate the diagnostic efficiency of the quantitative APT-related parameters.Methods A total of 23 patients (15 males, 8 females, age: 13-80 years) with 27 lesions who had underwent APT imaging in Tongji Hospital(Wuhan, China) from October 2014 to June 2015 were enrolled in this prospective study.The scan protocols were MRI normal plain scanning, diffusion WI, contrast-enhancement T1WI and APT imaging.Both the magnetization transfer ratio (MTR) and the relative MTR (rMTR) of lesions were manually measured by drawing ROI in the functional post-processing workstation.The results were compared with those of pathologic examinations and radiographic follow-up (≥3 months).Mann-Whitney u test was used to analyze the data.Results Compared with contralateral white matter, the primary gliomas (n=12) and recurrent gliomas (n=8) manifested hyper-intensity, while the treatment induced injuries (n=7) showed iso-or hypo-intensity.The difference of MTR between tumors and treatment effects was significant (102.78(101.93,103.84) vs 100.17(99.94, 100.63);z=-3.76, P<0.01), so was the difference of rMTR between tumors and treatment effects (3.92%(2.69%,4.67%) vs 0.47%(-0.79%,1.11%);z=-3.43, P<0.01).Both those two quantitative parameters exhibited excellent diagnostic performance with the AUC of 0.986 and 0.943.The sensitivity, specificity and accuracy of MTR were 100%(20/20), 6/7 and 96.3%(26/27) in the threshold of 100.68, while those of rMTR were 95.0%(19/20), 6/7 and 92.6%(25/27) in the threshold of 1.66%.Conclusions Combined with the routine MRI images, APT imaging can provide excellent qualitative and quantitative information in differentiating glioma from treatment effect.Both MTR and rMTR are helpful for the differentiation with high sensitivity and specificity and can be used as non-invasive imaging biomarkers in evaluating treatment effect of glioma.
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Objective To develop a kind of gelatin microspheres which is capable of being visualized on radiography,CT and MR examinations.Methods Emulsion chemical cross-linking method was used to prepare gelatin microspheres that carried only solid Fe3O4 nanoparticles.Optical microscope was adopted to observe the morphology,particle diameter and the dispersity of the gelatin microspheres.Using thermogravimetric analysis method,the loading rate of Fe3O4 nanoparticles encapsulated in the gelatin microspheres was calculated.The multimodal visualization ability of the gelatin microspheres was evaluated by radiography,CT and MR examinations.The blood in rabbit heart and human vascular endothelial cells were used to make microsphere hemolysis test and in vitro cytotoxicity test.The elastic characteristics and the swelling characteristics of the gelatin microspheres were determined,and the sterile technique was tested.Results The optimal synthesis condition of microspheres was to use 2:1 of Fe3O4-to-gelatin quality ratio,under this situation,the microspheres showed a roundness appearance with satisfactory dispersion,the spherulization rate was high (up to 77%),the drug loading rate was very high (up to 73.27%),the particle diameter was moderate (199.78±142.90 μm),and the microspheres had multimodal visualization ability for radiography,CT and MR examinations.The optimization CT value of microspheres could be up to (1 028.0± 69.5) Hu (when concentration=25 mg/ml).Hemolysis test and in vitro cytotoxicity test showed that no statistically significant differences in the hemolysis rate and absorption value existed between the study group and the control group (P>0.05).In acid solution,the microspheres exhibited swelling characteristics,while in ethanol the microspheres showed no swelling phenomenon.Conclusion Using solid Fe3O4 nanoparticles as visualization material as well as gelatin as polymer materials,a special gelatin microspheres can be prepared with emulsion chemical cross-linking method.This kind of microspheres carries the following features:high drug loading,regular in shape,smooth surface,not easy to agglomerate,stronger multimodal visualization ability (radiography,CT and MR),high biological safety and convenient disinfection.
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Objective To conduct a single-center retrospective analysis on the distribution characteristics and prevalence of idiopathic membranous nephropathy (IMN) patients diagnosed with pathology for the past 16 years,to investigate diagnostic and differential diagnostic value of serum antiphospholipase A2 receptor antibodies (PLA2R-Ab),and to evaluate the correlation between PLA2R-Ab and clinical disease activity.Methods (1) 6996 biopsy-proven primary glomerular nephropathy (PGN) patients,including 1567 IMN cases,admitted to the First Affiliated Hospital of Xi'an Jiaotong University from January 2000 to December 2015 were involved.Demographics and pathological type were gathered from all patients.(2) 433 cases receiving renal biopsy and testing PLA2R-Ab from June 2015 to December 2015 were involved,with their clinical and laboratorial data being collected.During the period patients' follow-up time,therapeutic schedule and laboratory results were recorded.Results (1) IMN accounted for 22.4% of primary glomerular disease,and patients above 40 years old accounted for more than 60% of the IMN.(2) The sensitivity and specificity of serological PLA2R-Ab were 58.1%(95%CI 47.0%-68.5%) and 98.6%(95%CI 95.6%-99.6%) respectively.PLA2R-Ab positive rate was affected by immunosuppression therapy.(3) The PLA2R-Ab titers wasn't correlated with 24-hour urinary protein (r=-0.017,P=0.887),serum albumin (r=-0.072,P=0.549) and urinary red blood cell count (r=-0.030,P=0.802).There was no difference between PLA2R-Ab positive positive and PLA2R-Ab negative on proportion of IMN pathological stage Ⅰ-Ⅱ (P > 0.05).Thirteen cases of patients with PLA2R-Ab positive were all prescribed glucocorticoid combined with immunosuppressant.After (2.21± 1.09) months,the decrease of PLA2R-Ab titers was in accordance with 24-hour urinary protein quantity descending and serum albumin ascending (P < 0.05).Condusions The incidence of IMN increase year by year,especially in the mid-aged and the elderly.Serum PLA2R-Ab correlates not with IMN pathological stage,but with the development of IMN.Monitoring PLA2R-Ab titers individually may access the efficiency of treatment.
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This paper provides a brief overview of the current research activities which focused on the bio-application of gold magnetic nanocomposite particles. By combining the magnetic characteristics of the iron oxide core with the unique features of nano-gold particles such as targeting by surface modification and optical properties, such composite nanoparticles have a wide range of applications in cancer hyperthermia, CT and MRI imaging, bio-separation, bio sensors, gene diagnosis, drug targeting and many other biomedical fields.
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Humans , Diagnostic Imaging , Drug Delivery Systems , Ferric Compounds , Chemistry , Gold , Chemistry , Magnetics , Nanocomposites , Chemistry , Nanoparticles , Chemistry , NeoplasmsABSTRACT
Brain iron deposition has been proposed to play an important role in the pathophysiology of Alzheimer disease (AD). The aim of this study was to investigate the correlation of brain iron accumulation with the severity of cognitive impairment in patients with AD by using quantitative MR relaxation rate R2' measurements. Fifteen patients with AD, 15 age- and sex-matched healthy controls, and 30 healthy volunteers underwent 1.5T MR multi-echo T2 mapping and T2* mapping for the measurement of transverse relaxation rate R2' (R2'=R2*-R2). We statistically analyzed the R2' and iron concentrations of bilateral hippocampus (HP), parietal cortex (PC), frontal white matter (FWM), putamen (PU), caudate nucleus (CN), thalamus (TH), red nucleus (RN), substantia nigra (SN), and dentate nucleus (DN) of the cerebellum for the correlation with the severity of dementia. Two-tailed t-test, Student-Newman-Keuls test (ANOVA) and linear correlation test were used for statistical analysis. In 30 healthy volunteers, the R2' values of bilateral SN, RN, PU, CN, globus pallidus (GP), TH, and FWM were measured. The correlation with the postmortem iron concentration in normal adults was analyzed in order to establish a formula on the relationship between regional R2' and brain iron concentration. The iron concentration of regions of interest (ROI) in AD patients and controls was calculated by this formula and its correlation with the severity of AD was analyzed. Regional R2' was positively correlated with regional brain iron concentration in normal adults (r=0.977, P<0.01). Iron concentrations in bilateral HP, PC, PU, CN, and DN of patients with AD were significantly higher than those of the controls (P<0.05); Moreover, the brain iron concentrations, especially in parietal cortex and hippocampus at the early stage of AD, were positively correlated with the severity of patients' cognitive impairment (P<0.05). The higher the R2' and iron concentrations were, the more severe the cognitive impairment was. Regional R2' and iron concentration in parietal cortex and hippocampus were positively correlated with the severity of AD patients' cognitive impairment, indicating that it may be used as a biomarker to evaluate the progression of AD.
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Objective To study the effects of alternating magnetic field with different intensities on the proliferation of human squa-mous tongue cancer cells in vitro. Methods Viable cells with the OD value cell and flow cytometry were revealed through MTT assay to evaluate the proliferation and apeptosis and cell cycle respectively after the cells were exposed to electromagnetic fields of different intensity (5mT,8mT,11mT) once per day lasting 1 hour for 3 days. The sham -exposure controls were correspondingly established. Results We compared the electromagnetic field groups with the normal groups by MTT assay after 24,48,72 hours. By analyzing the data in SPSS sta-tistical software , we found that the OD value of electromagnetic field groups was significantly less than that of the control groups (P <0.01) . The rates of apoptosis cells by flow cytometry revealed that EMF groups had no change as compared with control groups. But the cell cycle displayed significant chang at 0.5rot. Conclusion The cells displayed significant changes with obvious Tca8113 cell prolifera-tion inhibition and hold - up cell cycle after being exposed to alternating magnetic field of different intensity. But human squamous tongue cancer ceils could not be induced to apeptosis.
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Objective To investigate the dose-response relationship of the treatment temperatures and heating time on human cervical carcinoma hela cells,aiming at providing experimental evidences for clinical hy-perthermia. Methods Hela cells were heated at 37 ~ 70 ℃ in temperature-controlled water baths, the tempera-ture was divided into nine groups,each time was divided into eight subgroups (1 ~ 30 min). The morphology changes of cells after hyperthermia were detected by inverted microscope. Proliferation rates were measured by MTT colorimetric assay. The apoptesis rates were determined by flow eytometric analyse. The levels of prolifera-ring cell nuclear antigen (PCNA) were measured with immunohistochemistry. Results lnereaseing the heating time at the same temperature, or increaseing heating temperature at the same time, the cell proliferation, survival rates and PCNA expression decreased. There was no significant morphological change about cells ,but have small amount of apoptosis and a direct role of the suppression and destruction at 41 ℃ and 43 ℃ group. A large num-ber of cells shrinked to round and a major role for apoptosis at 46℃ group. Cell necrosis was major role at 50 ℃and 55 ℃ group. More than 55 ℃ for necrotic cells. Conclusion With the increase of heating temperature and heating time, its treatment of Hela cells gradually enhance. So combining dose-effect relationship of hyperthermia temperature and time can reach the best therapeutic effects.
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Although single thermotherapy has certain curative effect for cancer treatment,it normally leads to the recurrence of tumor in clinical application.Multi-thermotherapy could be an effective approach to solve the problem.Multi-thermotherapy not only kills the tumor cells by heating cells above the physiological temperature,but also induces the anti-tumor immunity of the body to further kill the tumor cells.In order to obrain optimal treatment effect,the time interval of thermotherapy is often set once or twice a week for the consideration of thermotolerance.
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Possessing the unique feathers of high targeting and inducing the active immunity of patients,magnetic-mediated hyperthermia(MMH)has been regarded as a very promising cancer-treatment approach.Researches about in-stent MMH for esophagus cancel have been widely carried out with focusing on heating mechanism,feasibility studies and clinical trials.
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[Objective]To investigave the feasibility of commensalism of stem cells and olfactory ensheathing cells and to study the preliminary results of graft of stem cells and olfactory ensheathing cells for the treatment of spinal cord injury.[Method]Under the condition of sterility,the stem cells and olfactory ensheathing cells were collected from the embryon of induced labor for 4 to 6 months and the patients.The stem cells and olfactory ensheathing cells were cultured individually until transduced generation,then were cultured together and transplanted into the place where the spinal cord was injuried in the patient.[Result]Eight patients who had the spinal cord injury were treated with the graft of stem cells and olfactory ensheathing cells and were followed up for 1 to 6 months after the operation.One case with the T_(5~7) spinal cord injury got the recovery of superfical and deep sensation of the lower limbs.The other 7 patients had not obvious recovery.[Conclusion]There was no appearance of inhibition when the stem cells and olfactory ensheathing cells were cultured together.The united graft of the stem cells and olfactory ensheathing cells for the treatment of spinal cord injury is safe with the short-term observation.
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Objective To evaluate the magneto-heating effect and cytotoxicity of the carbonyl iron powder as a feasibility for arterial embolization hyperthermia. Methods Different doses of carbonyl iron powder suspensions were prepared in vitro(10 mg/ml,100%;10 mg/ml,50%;or 64 g/L phenol solutions),and heated for 20 minutes in an alternating magnetic field(49.9,79.9,and 110.2 Oe).The influences of the doses of suspensions and currency of magnetic field on the heating effect were observed.Meanwhile,mouse fibroblast L-929 cells were cultured with the suspensions for 2,4,or 7 days.The morphology and relative growth rate(RGR) of the cells were determined by microscopy and MTT assay.The cytotoxicity of the suspensions was then classified. Results The heating ability of the carbonyl iron powder increased with the suspension concentration and the strength of the magnetic field.A optimal therapeutic temperature was achieved at 110.2 Oe with 60 mg/ml carbonyl iron powder suspension.The L-929 cells showed normal morphology after been treated by the carbonyl iron powder(10 mg/ml 100% solution and 50% solution) for 2,4 and 7 days with the 0-1 degree cytotoxicity.Conclusion The carbonyl iron powder has good heating effect under the alternating magnetic field,and is compatible with the tested cells.