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OBJECTIVE To prepare the nanoporous flower-shaped lactose （FL）-loaded curcumin （Cur） solid lipid nanoparticles （SLN） inhalation powder （Cur-SLN-FL）， and to investigate its inhibition effect on LPS-induced apoptosis of BEAS- 2B cells. METHODS Using different kinds （lactose， sucrose， mannitol， trehalose） and different amounts （2%， 3%， 5%） of freeze-dried protectants as objects， the suspension of Cur-SLN was micronized by freeze-drying technology into lyophilized powder， which was then mixed with FL and sieved by a 200-mesh sieve to obtain Cur-SLN-FL. The physicochemical properties of Cur-SLN-FL was characterized by scanning electron microscopy and laser particle size analyzer. Using BEAS-2B cells cultured in vitro as objects， LPS-induced apoptosis and the changes of mitochondrial membrane potential after treatment of Cur-SLN-FL were detected by Annexin Ⅴ/PI double staining method and JC-1 kit. RESULTS With 3% trehalose as Cur-SLN freeze-dried protective agent， the freeze-dried powder obtained was compact and full in shape， did not shrink and collapse， and was uniform in color and light-yellow powder， which could be completely dissolved in 30 s. When FL and Cur-SLN freeze-dried powder were mixed at a ratio of 1∶2， it had a higher deposition rate of secondary distribution （[ 40.92±0.02）%]. SEM results showed that Cur-SLN-FL had a flower-shaped appearance with an average particle size of （4.95±0.57） μm and an aerodynamic particle size of （4.03±0.40） μm. The critical relative humidity of Cur-SLN-FL was about 54%， and the evacuation rate was （90.34 ± 1.21）%； the quantity of fine particles that could be inhaled by Cur-SLN-FL in the 2-7 receiving discs was （47.5±0.7）%， and the measured aerodynamic particle size was （4.33±0.08） μm. The LD50 of Cur-SLN-FL to BEAS-2B cells was 5.809 mg/mL. The apoptosis rate of model cells was significantly reduced after treatment of Cur-SLN-FL， and the mitochondrial membrane potential was significantly increased （P＜0.05）. CONCLUSIONS The preparation process of Cur-SLN-FL is simple and feasible. Cur-SLN-FL can improve LPS-induced apoptosis of BEAS-2B cells， and this effect is related to the regulation of mitochondrial membrane potential.
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OBJECTIVE To investigate the effects and mechanism of curcumin （Cur） solid lipid nanoparticles （SLN） loaded with flower-shaped lactose （Cur-SLN-FL） for lung inhalation on lung inflammation in chronic obstructive pulmonary disease （COPD） model mice. METHODS Firstly， the irritation of Cur-SLN-FL to lung tissue was investigated， and the local safety of inhalation materials was determined. Then， 10 mice were randomly selected and injected with normal saline through the trachea， and the other 50 mice were all injected with porcine trypsin solution （concentration of 33.3 mg/mL， dosage of 1.0 mL/kg） to induce the COPD model. After normal feeding for 28 days， the mice were divided into sham operation group， model group， budesonide group （20 mg/kg）， Cur-SLN-FL high-dose and low-dose groups （100， 50 mg/kg）， with 10 mice in each group. The corresponding drugs were given to each group， once a day， for 14 consecutive days. Twenty-four hours after the last administration， the bronchoalveolar lavage fluid （BALF） of mice in each group was collected and the differential count of white blood cells was determined. Hematoxylin-eosin （HE） staining was used to observe the histopathology of the trachea and lung tissue in each group. Masson staining was used to detect collagen deposition in the lung tissue of mice in each group. Immunohistochemical method was used to detect the positive expressions of nucleotide-binding oligomerization domains-like receptor protein-3 （NLRP3）， caspase-1 and interleukin-1β （IL-1β） in lung tissue of mice. Western blot assay was used to detect the protein expressions of NLRP3， caspase-1 and nuclear factor of kappa B（NF-κB） in lung tissue. RESULTS Cur-SLN-FL had no obvious pulmonary irritation. Compared with the sham operation group， the total number of white blood cells， neutrophils and eosinophils in BALF of the model group increased significantly， while the number of lymphocytes decreased significantly （P＜0.05）； ciliated columnar epithelium proliferated， thickened and exfoliated in the trachea， mucus accumulated in the cavity and interstitial inflammatory cells infiltrated in the lung tissue；the deposition of collagen fibers in lung tissue increased significantly， the positive expressions of NLRP3， caspase-1 and IL-1β in lung tissue increased significantly， and the expressions of NLRP3， caspase-1 and NF-κB protein in lung tissue all increased significantly （P＜0.05）. After giving Cur-SLN-FL， the above indexes were all improved to certain extent. CONCLUSIONS Cur-SLN-FL can improve the pulmonary inflammatory reaction in COPD model mice，and its mechanism may be through regulating the NLRP3 signaling pathway， inhibiting the expressions of caspase-1， NF-κB and IL-1β， thus alleviating the process of pulmonary fibrosis in COPD model mice.
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AIM: To investigate the role and possible mechanism of gastrodin combined with dexamethasone in myocardial cell injury induced by oxygen-glucose deprivation. METHODS: Oxygen-glucose deprivation (OGD) model was established. The cells were divided into 5 groups: normal control group, OGD group, DEX group, GAS group and DEX+GAS group. The activity of myocardial cells was detected by CCK-8 test in each group. The activity of LDH was detected by colorimetry in each group. The apoptosis of myocardial cells was detected by TUNEL method in each group. The ELISA assay was used to detect the inflammatory factors in culture medium of myocardial cells in each group. Western blot was used to detect the expression of Notch1, Bax, Bcl-2 and Beclin1 in myocardial cells in each group.RESULTS: The results showed that GAS combined with DEX could significantly increase the activity of myocardial cells and decrease the apoptosis, reduce production of TNF-α, IL-6, IL-1β and promote production of IL-10, decrease the release of LDH significantly of myocardial cells induced by OGD. The results of Western blot showed that GAS combined with DEX increased the expression of Notch1, Bcl-2 and autophagy-related gene Beclin1, but decreased the expression of Bax of myocardial cells induced by OGD. CONCLUSION: The combination of GAS and DEX may promote autophagy and increase cell activity, inhibit apoptosis and inflammatory reaction by activating Notch signaling pathway, thereby reducing OGD-induced myocardial cells damage.
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OBJECTIVE：To preparea novel Curcumin （Cur）dry powder inhalation （DPI）loaded by nanoporous flower-shaped lactose（FL），and to provide a safe and effective intrapulmonary drug delivery method for the therapy of chronic obstructive pulmonary disease with insoluble drugs. METHODS ：FL-loaded Cur （Cur-FL） compound powder was prepared by solution adsorption method. Using drug-loading amount and adsorption rate as indicators ，single-factor experiment was used to optimize Cur concentration，Cur-FL ratio （m/m）and adsorption time so as to determine the optimal preparation technology for Cur-FL compound powder. Fourier transform infrared spectroscopy ，scanning electron microscope and differential scanning calorimetry were used to characterize the physical and chemical properties of Cur-FL compound powder prepared with optimal technology. The water content and aerodynamic properties were determined ；in vitro drug release behavior was investigated by simulating the environment of artificial lung fluid. RESULTS ：The optimal preparation technology of Cur-FL compound powder was Cur concentration of 5 mg/mL，Cur-FL ratio of 1 ∶ 4，adsorption time of 1 h. The drug-loading amount of compound powder was （23.37±0.43）％，the encapsulation rate was （91.64±0.44）％，and the adsorption rate was （30.50±0.72）％. Cur-FL particles were flower shaped ；Cur was physically adsorbed in the pores of FL without chemical changes. The bulk density of Cur-FL compound was （0.21±0.02） g/cm3，tap density was （0.33±0.01）g/cm3，angle of repose was（24.07±0.31）°，average particle size was （3.96±0.80） μm，aerodynamic particle size was （3.33±0.99）μm，water content was （5.63 ±0.24）％，emptying rate was （92.53± 0.87）％，and deposition rate of effective parts in vitro was son- （45.93 ± 1.77）％ . Its 24 h solubility in artificial lung gwen.tan@csu.edu.cn fluid [（358.93±1.67）μg/mL] were 3.28 times of Cur ，48 h cumulative release ratesin in vitro （90.21％）were 1.63 times of Cur ，but Cur+FL physical mixture could not improve the solubility and release of Cur in artificial lung fluid. CONCLUSIONS ：Cur-FL compound powder has good in vitro release property ，and its powder properties ，solubility，water content ，fluidity and aerodynamic properties meet the requirements of DPI in Chinese Pharmacopoeia.
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Objective:To analyze the brain functional fluctuation of benign epilepsy in children with central-temporal spikes(BECTS) by using ReHo algorithm based on the resting-state brain functional imaging, and to explore the connection of the brain function and changes of the connection pattern, so as to find the damage of the cognitive function of BECTS children in the early stage.Method:s Perspectiveness and simple random selection of 20 BECTS children and 20 healthy control children admitted to Shenzhen Children′s Hospital from January 2015 to December 2017 were conducted for basic information collection and functional magnetic resonance imaging (fMRI) testing in a resting-state.Result:s Significantly lower ReHo value appeared in the default mode network (DMN) area, and the precuneus (voxel=422, t=-5.085 6), cuneus (voxel=85, t=-4.240 3), angular gyrus (voxel=191, t=-4.681 2), cingulate cortex (voxel=313, t=-5.238 2), anterior central gyrus (voxel=12, t=-3.482 7), and supplementary motor area (voxel=1 356, t-6.596 2). The significantly increased ReHo was found in the bilateral cerebellum (voxel=71, t=5.658 2), right superior temporal gyrus (voxel=24, t= 5.184 0), operculum insulae (voxel=337, t=6.814 9), left parietal lobe (voxel=12, t=4.378 7), and inferior parietal lobule (voxel=11, t=3.433 7). Conclusions:Significant impairment of DMN, Wernicke and angular gyrus functions in BECTS children may be one of the mechanisms of cognitive dysfunction.Enhanced sensorimotor area and cortical brain functions near the operculum insulae and central sulcus lead to seizures with typical clinical symptoms.fMRI has a high specificity and sensitivity for evaluating the brain function of children with BECTS, and it can detect the impairment of cognitive function in children with this type of epilepsy at an early stage.
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Currently, enhanced recovery after surgery (ERAS) has been widely accepted by surgery and anesthesiology all over the world, and applied in colorectal surgery, gynecology, liver surgery, breast surgery, urology and spinal surgery. But ERAS are rarely used in the field of interventional bronchoscopy. In recent years, more and more researchers have begun to explore the application of ERAS in bronchoscopic interventional therapy. This article discussed that preoperative preparation, anesthesia, intraoperative operation, postoperative observation and other aspects can influence interventional bronchoscopy. .
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Humans , Anesthesia , Methods , Bronchoscopy , Methods , Length of Stay , Outcome Assessment, Health Care , Perioperative Care , Methods , Recovery of Function , Tracheal Neoplasms , General Surgery , Tracheotomy , MethodsABSTRACT
ObjectiveTo investigate the expression of D-bifunctional protein (DBP) in hepatocellular carcinoma (HCC) tissue and its correlation with serum tumor markers alpha-fetoprotein (AFP) and carbohydrate antigen 19-9 (CA19-9), as well as the clinical value of DBP in early diagnosis and prognostic evaluation of HCC. MethodsA total of 20 patients who underwent hepatectomy for liver cancer in Tangshan Maternal and Child Health Hospital and Tangshan People’s Hospital from June 2015 to May 2017 were enrolled as experimental group, and 20 healthy subjects who underwent physical examination in these two hospital during the same period of time were enrolled as control group. Chemiluminescence was used to measure the expression of AFP and CA19-9, and immunohistochemistry was used to measure the expression of DBP, which was expressed as integrated optical density (IOD), in HCC tissue and adjacent tissue. The t-test was used for comparison of continuous data between groups, and the Pearson correlation analysis was used to investigate correlation between indices. ResultsThe IOD value of DBP in HCC tissue was significantly higher than that in adjacent tissues (220.52±101.30 vs 40.49±1932, t=-7.00, P＜0.01). The expression of DBP was positively correlated with that of AFP (r2=0.868, P＜0.01) and CA19-9 (r2=0.814, P＜0.01). ConclusionThe expression of DBP increases in HCC patients, which is closely associated with the development and progression of HCC. Therefore, it provides a new target for the diagnosis of HCC.
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To explore the feasibility and efficacy of artificial neural network for differentiating high-grade glioma and low-grade glioma using image information. Methods: A total of 130 glioma patients with confirmed pathological diagnosis were selected retrospectively from 2012 to 2017. Forty one imaging features were extracted from each subjects based on 2-dimension magnetic resonance T1 weighted imaging with contrast-enhancement. An artificial neural network model was created and optimized according to the performance of feature selection. The training dataset was randomly selected half of the whole dataset, and the other half dataset was used to verify the performance of the neural network for glioma grading. The training-verification process was repeated for 100 times and the performance was averaged. Results: A total of 5 imaging features were selected as the ultimate input features for the neural network. The mean accuracy of the neural network for glioma grading was 90.32%, with a mean sensitivity at 87.86% and a mean specificity at 92.49%. The area under the curve of receiver operating characteristic curve was 0.9486. Conclusion: As a technique of artificial intelligence, neural network can reach a relatively high accuracy for the grading of glioma and provide a non-invasive and promising computer-aided diagnostic process for the pre-operative grading of glioma.
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Humans , Brain Neoplasms , Diagnostic Imaging , Pathology , Glioma , Diagnostic Imaging , Pathology , Magnetic Resonance Imaging , Neoplasm Grading , Neural Networks, Computer , ROC Curve , Retrospective Studies , Sensitivity and SpecificityABSTRACT
Angelman syndrome is also called happy puppet syndrome.It is firstly reported by British sci-entist in 1965.It is a chromosome disorder disease,mainly of chromosome 15q11-13 regional anomaly.The An-gelman syndrome patients are often accompanied by mental retardation and special features,90% with epilepsy and the specific electroencephalogram patterns,and the prognosis is unfavorable.The diagnosis of Angelman syn-drome depends mainly on genetic testing,but some patients with genetic testing may show no abnormalities, these patients need referring the clinical diagnosis and the distinctive electroencephalogram.Before the distinctive clinical manifestation and genetic testing,the abnormal electroencephalogram can help diagnose Angelman syn-drome in advance,thereby improving the early detection rate of the disease.This review is mainly to summarize the electroencephalogram patterns in Angelman syndrome in recent years.
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Objective To investigate the role of glycogen synthase kinase -3beta(GSK3β)on invasion and metastasis of human osteosarcoma cells .Methods Expression and phosphorylation of GSK 3βwere examined in osteosarcoma cell lines and tumor tissue from osteosarcoma patients by Western blot .The effects of small mole-cule GSK3βinhibitors on cell metastasis were detected by cell invasion assay and cell migration assay .Results Osteosarcoma cell lines showed increased GSK 3βexpression and abnormal activity regulation .In tumor tissue of patients with osteosarcoma metastasis and non -metastasis,GSK3βwere detected expression and abnormal activi-ty,especially in tumor tissue of the patients with osteosarcoma metastasis .Inhibition of GSK3βactivity resulted in inhibiting cells invasion and migration in osteosarcoma cell line .Conclusion In this research,we demonstrated that GSK3βencouraged osteosarcoma cells metastasis .The result will open up a potential target for clinical treat-ment of osteosarcoma .
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OBJECTIVE:To establish a method of determining the plasma concentration of capecitabine/polyethylene glycol 1000/montmorillonite (CAP/PEG1000/MMT) in rats’plasma for the study on pharmacokinetics of CAP compound in rats in vivo. METHODS:HPLC was adopted. The determination was performed on Kromasil C18 with mobile phase consisted of 0.1% glacial acetic acid-acetonitrile(73∶27),at the flow rate of 1.0 ml/min. The detection wavelength was 250 nm and column temperature was 40 ℃. The sample size was 10 μl. 18 Wistar rats were randomly divided into CAP group,CAP/MMT group(MMT as carrier)and CAP/PEG1000/MMT group(PEG1000/MMT as carrier)and ig given corresponding drugs,that equal to 200 mg/kg of CAP. Blood sample was respectively taken 15,30,60,90,120,180,240,300 and 360 min after the administration of drugs,and plasma was isolated and added with internal standard ferulic acid. The concentration of the drug in the plasma was determined by HPLC fol-lowing protein precipitation with methanol,based on which the pharmacokinetic parameters were calculated by 3p97 software. RE-SULTS:The linear range of CAP was 0.054 9-4.390 0 μg/ml (r=0.998 2) with the method recovery of 98.2%-102.1%(RSD=1.50%-3.29%, n=5) and absolute recovery of 76.2%-78.9%(RSD=2.29%-2.99%, n=5). In the above-mentioned three groups,t1/2 were(1.11±0.32),(1.57±0.32)and(1.62±0.10)h;cmax were(2.91±0.36),(0.91±0.23)and(0.91±0.14)μg/ml;AUC0-6 h were (8.70 ± 1.79),(3.76 ± 0.27) and (3.73 ± 0.25)μg·h/ml;and tmax were (0.97 ± 0.20),(1.55 ± 0.47) and (1.50 ± 0.07) h,respectively. There was no significant difference in the pharmacokinetic parameters between the CAP/MMT group and CAP/PEG1000/MMT group(P>0.05). CONCLUSIONS:The method is reliable and simple,and can be used for pharmacokinetic study of CAP/PEG1000/MMT in rats. MMT and PEG1000/MMT compound can prolong CAP acting time in the body.
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Objective To observe the effect of Galectin -3 gene knock out to the mouse skin tumor growth and discuss the mechanism of inhibition of the mouse cutaneous tumor induced by 12 -o -tetrade-canoylphorbol-13-acetate which caused by Galectin -3 knock out.Methods The DMBA +TPA multi-step induced skin tumor in mice model were used to establish the skin cancer model .The control group was the same age wild type mice .We observed the inhibition of the mouse tumor growth by Galectin -3 knock out .In situ tumor cells were collected and cultured on soft agar for colony formation assay .The side population of the situ cancer cells was analyzed quantitatively by flow cytometry .Results 1.Compared with wild type mice group(group A), Galectin-3 knock out mice group ( group B) displayed a significant delay of the appearance of tumor .The tumor incidence and the average number of tumor per mice between group A and group B had obvious difference ( P<0.01).2.In vitro,data of soft agar colony formation assay showed that colony formation rate in group A are signif -icantly higher than group B(P<0.01).3.The collection and separation of A and B group in situ tumor cells ,u-sing flow cytometry instrument for in situ tumor cell side population quantitative analysis ,group A compared with group B had obvious difference(P<0.01).Conclusion The knock out of the Galectin -3 gene reduces the skin cancer stem cells ,inhibits tumor cell proliferation ,depresses chemical carcinogenesis of mice skin .Galectin-3 gene may become the new target for skin cancer chemotherapy .
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Objective To investigate the clinical efficacy,curative effects and cosmetic results of nipple-sparing modified radical mastectomy (NSM) in the treatment of breast cancer.Methods Ninety-six patients who received initial therapy in Linyi Cancer Hospital from January 1,2007 to January 1,2010 were selected.Among them,35 patients undergoing NSM were chosen as NSM group,61 patients undergoing modified radical mastectomy (MRM) were chosen as MRM group.The postoperative complications,aesthetic assessment,local recurrence and distant metastasis of the two groups were compared.Results In postoperative complications,the difference of the two groups had no statistical significance (x2 =3.140,P =0.061).NSM group was better than MRM group in aesthetic evaluation (x2 =82.786,P =0.000).Follow-up was obtained in all patients with range of 48 to 84 months and 63 months in average.Neither of them had local recurrence.Two patients(5.7％) in NSM group and three patients(4.9％) in MRM group developed distant metastasis.The incidents of distant metastasis had no statistically significant difference (x2 =0.029,P =0.866).Conclusion NSM can obtain the same therapeutic effect as MRM,and is easily accepted by patients before operation and has the better aesthetic assessment after operation.NSM is worth spreading widely.
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Objective To study the effect of the toothpaste containing FE enzyme on oral care to for critically ill patients with stroke. Methods Sixty cases of critically ill stroke patients were randomly divided into the experiment group and the control group with 30 cases in each group.The toothpaste containing FE enzyme was used in experiment group for oral care,and the routine oral care was used in the control group.The two groups were compared in terms of the oral cleaning effect,dental plaque and costs for the oral care.Results The incidences of bad breath,oral uncleanness and oral infection were significantly lower than those of the control group(P<0.01 or P<0.05). The dental plaque index after oral care was significantly lower in the experiment group than that in the control group(P<0.001).The cost in the experiment group was significantly lower than that in the control group(P<0.01).Conclusion Oral care using toothpaste containing FE enzymecan not only achieve an effective oral cleaning purpose,but also reduce the cost of oral care.