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Magnetic resonance-guided radiotherapy (MRgRT) not only offers real time magnetic resonance (MR) imags with high-resolution and good soft tissue contrast to guide the delineation of the target volume during simulation and daily radiotherapy, but also reveals the position and shape changes of the target volumes and organs at risk (OAR) during treatment dynamically, which provides the evidence for the individual-adptive planning revision. Thus, MRgRT has the potential to dramatically impact cancer research and treatment. And this treatment mode is theoretically more suitable for the disease with obvious tissue deformation, such as breast. In this review, application of MR scanner with a linear accelerator (MR-linac) in radiotherapy workflows for breast cancer patients was summarized, and its implications and opportunities on breast cancer irradiation were highlighted.
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Quantitative evaluation of analgesic efficacy improves understanding of the antinociceptive mechanisms of new analgesics and provides important guidance for their development. Lappaconitine (LA), a potent analgesic drug extracted from the root of natural Aconitum species, has been clinically used for years because of its effective analgesic and non-addictive properties. However, being limited to ethological experiments, previous studies have mainly investigated the analgesic effect of LA at the behavioral level, and the associated antinociceptive mechanisms are still unclear. In this study, electrocorticogram (ECoG) technology was used to investigate the analgesic effects of two homologous derivatives of LA, Lappaconitine hydrobromide (LAH) and Lappaconitine trifluoroacetate (LAF), on Sprague-Dawley rats subjected to nociceptive laser stimuli, and to further explore their antinociceptive mechanisms. We found that both LAH and LAF were effective in reducing pain, as manifested in the remarkable reduction of nocifensive behaviors and laser-evoked potentials (LEPs) amplitudes (N2 and P2 waves, and gamma-band oscillations), and significantly prolonged latencies of the LEP-N2/P2. These changes in LEPs reflect the similar antinociceptive mechanism of LAF and LAH, i.e., inhibition of the fast signaling pathways. In addition, there were no changes in the auditory-evoked potential (AEP-N1 component) before and after LAF or LAH treatment, suggesting that neither drug had a central anesthetic effect. Importantly, compared with LAH, LAF was superior in its effects on the magnitudes of gamma-band oscillations and the resting-state spectra, which may be associated with their differences in the octanol/water partition coefficient, degree of dissociation, toxicity, and glycine receptor regulation. Altogether, jointly applying nociceptive laser stimuli and ECoG recordings in rats, we provide solid neural evidence for the analgesic efficacy and antinociceptive mechanisms of derivatives of LA.
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Animals , Rats , Aconitine/pharmacology , Analgesics/pharmacology , Pharmaceutical Preparations , Rats, Sprague-DawleyABSTRACT
Quantitative evaluation of analgesic efficacy improves understanding of the antinociceptive mechanisms of new analgesics and provides important guidance for their development. Lappaconitine (LA), a potent analgesic drug extracted from the root of natural Aconitum species, has been clinically used for years because of its effective analgesic and non-addictive properties. However, being limited to ethological experiments, previous studies have mainly investigated the analgesic effect of LA at the behavioral level, and the associated antinociceptive mechanisms are still unclear. In this study, electrocorticogram (ECoG) technology was used to investigate the analgesic effects of two homologous derivatives of LA, Lappaconitine hydrobromide (LAH) and Lappaconitine trifluoroacetate (LAF), on Sprague-Dawley rats subjected to nociceptive laser stimuli, and to further explore their antinociceptive mechanisms. We found that both LAH and LAF were effective in reducing pain, as manifested in the remarkable reduction of nocifensive behaviors and laser-evoked potentials (LEPs) amplitudes (N2 and P2 waves, and gamma-band oscillations), and significantly prolonged latencies of the LEP-N2/P2. These changes in LEPs reflect the similar antinociceptive mechanism of LAF and LAH, i.e., inhibition of the fast signaling pathways. In addition, there were no changes in the auditory-evoked potential (AEP-N1 component) before and after LAF or LAH treatment, suggesting that neither drug had a central anesthetic effect. Importantly, compared with LAH, LAF was superior in its effects on the magnitudes of gamma-band oscillations and the resting-state spectra, which may be associated with their differences in the octanol/water partition coefficient, degree of dissociation, toxicity, and glycine receptor regulation. Altogether, jointly applying nociceptive laser stimuli and ECoG recordings in rats, we provide solid neural evidence for the analgesic efficacy and antinociceptive mechanisms of derivatives of LA.
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Objective:To observe the feasibility of magnetic resonance (MR)-guided stereotactic body radiotherapy (SBRT) for non-small cell lung cancer, and analyze the dosimetric differences in the presence or absence of magnetic field.Methods:Three patients with non-small cell lung cancer were prospectively treated with MR-guided linac (MR linac) for SBRT, and the dose was calculated with or without magnetic field models. The differences of dose distribution with or without magnetic field models were compared. At the same time, the target coverage, plan pass rate and treatment time were described, and the complexity of the conventional accelerator backup plan and the magnetic field model were compared.Results:The treatment time of 3 patients was (36.67±6.11) min, and the average time of online adaptive planning was (14.4±1.7) min, which was basically tolerated by patients. The treatment plan pass rate (3%/3 mm) was 98.9%, the Gamma pass rate (3%/3 mm) of the online plan during treatment was 98.5% and the target coverage was 99.1%, which met the clinical needs. The dose in the low dose area of the lung was slightly lower than that in the case without magnetic field, whereas the dose in ribs and skin was slightly higher than that in the plan without magnetic field. The number of machine unit (MU) for online adaptive plan was slightly higher than that of the reference plan, and the number of MU for the conventional accelerator standby treatment plan was significantly lower than that of the MR linac plan under the same target coverage. The follow-up results showed that there was no adverse reaction, and the short-term efficacy was partially relieved.Conclusions:In the case of considering the influence of magnetic field, the treatment plan meeting the clinical needs can be obtained. It is proven that SBRT radiotherapy for lung cancer guided by magnetic resonance accelerator is feasible, whereas the treatment time and process are complex.
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Objective@#To establish radiomics models based on different CT scaning phases to distinguish mediastinal metastatic lymph nodes in NSCLC and to explore the diagnostic efficacy of these models.@*Methods@#The CT images of 86 preoperative patients with NSCLC who were performed both plain and enhanced CT scans were analyzed retrospectively. The 231 mediastinal lymph nodes were enrolled in this study which were divided into two independent cohorts: 163 lymph nodes enrolled from January 2015 to June 2017 constituted the training cohort, and 68 lymph nodes enrolled from July 2017 to June 2018 constituted the validation cohort. The regions of interest (ROIs) were delineated on plain scan phase, arterial phase and venous phase CT images respectively, and 841 features were extracted from each ROI. LASSO-logistic regression analysis was used to select features and develop models. The area under the ROC curve (AUC value), sensitivity, specificity, accuracy, positive predictive value and negative predictive value of different models for distinguishing metastatic lymph nodes were compared.@*Results@#A total of 6 models were established, and the AUC values were all greater than 0.800. The plain CT model yielded the highest AUC, specificity, accuracy and positive predictive value with 0.926, 0.860, 0.871, 0.906 in the training cohort and 0.925, 0.769, 0.882, 0.870 in the validation cohort. When plain and venous phase CT images were combined with arterial phase CT images, the sensitivity and negative predictive value of the models increased from 0.879, 0.821 and 0.919, 0.789 to 0.949, 0.878 and 0.979, 0.900 respectively.@*Conclusions@#The CT radiomics model could be used to assist the clinical diagnosis of lymph nodes. The AUC value of the model based on plain scanning was the highest, while the sensitivity and negative predictive value of the model could be improved by combining the arterial phase CT images.
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Objective To establish radiomics models based on different CT scaning phases to distinguish mediastinal metastatic lymph nodes in NSCLC and to explore the diagnostic efficacy of these models.Methods The CT images of 86 preoperative patients with NSCLC who were performed both plain and enhanced CT scans were analyzed retrospectively.The 231 mediastinal lymph nodes were enrolled in this study which were divided into two independent cohorts:163 lymph nodes enrolled from January 2015 to June 2017 constituted the training cohort,and 68 lymph nodes enrolled from July 2017 to June 2018 constituted the validation cohort.The regions of interest (ROIs) were delineated on plain scan phase,arterial phase and venous phase CT images respectively,and 841 features were extracted from each ROI.LASSO-logistic regression analysis was used to select features and develop models.The area under the ROC curve (AUC value),sensitivity,specificity,accuracy,positive predictive value and negative predictive value of different models for distinguishing metastatic lymph nodes were compared.Results A total of 6 models were established,and the AUC values were all greater than 0.800.The plain CT model yielded the highest AUC,specificity,accuracy and positive predictive value with 0.926,0.860,0.871,0.906 in the training cohort and 0.925,0.769,0.882,0.870 in the validation cohort.When plain and venous phase CT images were combined with arterial phase CT images,the sensitivity and negative predictive value of the models increased from 0.879,0.821 and 0.919,0.789 to 0.949,0.878 and 0.979,0.900 respectively.Conclusions The CT radiomics model could be used to assist the clinical diagnosis of lymph nodes.The AUC value of the model based on plain scanning was the highest,while the sensitivity and negative predictive value of the model could be improved by combining the arterial phase CT images.
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Objective To compare the dosimetric and delivery efficiency between intensity-modulated radiation therapy (IMRT) plans based on Halcyon and Trilogy accelerator.Methods Clinical data of 12 patients with cervical cancer receiving Trilogy platform-based IMRT were retrospectively analyzed.The target area and organ at risk were introduced into the Eclipse version 15.1 TPS.The Halcyon-based IMRT was re-designed.The dose coverage of target area and organs at risk,monitor unit (MU) efficiency,delivery time and segment area and the differences between the proximal and distal segment area were statistically compared between two IMRT plans.Results The Halcyon treatment platform could meet the clinical objectives.Dose distribution of the target area was similar to that of the Trilogy plan (P＞O.05).The volumes in the bladder and rectum receiving 30 Gy and the volumes in the left femoral head receiving 20 Gy of Halcyon plan and the mean dose (D) of bladder,rectum and left femoral head were significantly lower compared with those of the Trilogy plan (P=0.001-0.043).The MUs of the Halcyon plan was 2 316.7± 209.7,significantly higher than 1 692.5± 259.5 of the Trilogy plan (P=0.000).The delivery time significantly differed between the Halcyon [(3.01±0.28) min] and Trilogy [(12.38± 1.49) min] (P=0.000).The average segment area of Halcyon plan for proximal and distal MLC was (43.7±32.5) cm2 and (28.8±25.4) cm2,the average segment area of Trilogy plan was (25.7±16.8) cm2,the ratio of the proximal and distal segment area was 1.73±0.43,ranging from 0.71 to 6.28.Conclusions Halcyon treatment platform can meet the clinical requirements and reduce the dosage coverage of normal tissues with better delivery efficiency.The ratio of proximal and distal segment areas should be considered during the plan design.
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Objective@#To explore the ability of computed-tomography (CT) radiomic features to predict the Epidermal growth factor receptor (EGFR) mutation status and the therapeutic response of advanced lung adenocarcinoma to EGFR- Tyrosine kinase inhibitors (TKIs) treatment.@*Methods@#A retrospective analysis was performed on 253 patients diagnosed as advanced lung adenocarcinoma, who underwent EGFR mutation detection, and those with EGFR sensitive mutation were treated with TKIs. Using the Lasso regression model and the 10 fold cross-validation method, the radiomic features of predicted EGFR mutation status and the screening of TKIs for sensitive populations were obtained. 715 radiomic features were extracted from unenhanced, arterial phase and venous phase, respectively.@*Results@#The area under curve (AUC) values of the multi-phases including unenhanced, arterial phase and venous phase of the EGFR mutation status validation group were 0.763, 0.807 and 0.808, respectively. The number of radiomic features extracted from the multi-phases were 5, 18 and 23, respectively, which could distinguish the EGFR mutation status. The AUC values of the multi-phases of the EGFR-TKIs sensitive validation group were 0.730, 0.833 and 0.895, respectively. The number of radiomic features extracted from the multi-phases were 3, 7 and 22, respectively, which can be used to screen the superior population for TKIs treatment. The efficiency of radiomic features extracted from venous phase in predicting EGFR mutant status and EGFR-TKIs sensitivity was significantly superior than those of unenhanced and arterial phase.@*Conclusions@#The radiomic features of CT scanning can be used as the radiomics biomarker to predict the EGFR mutation status of lung adenocarcinoma and to further screen the dominant population in TKIs therapy, which provides the basis for targeted therapy.
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Objective To investigate the relationship between texture features based on CT and radiochemotherapy sensitivity in patients with esophageal squamous cell carcinoma (ESCC).Methods A total of 92 ESCC patients treated at Shandong Cancer Hospital Affiliated to Shandong University between January 2014 and December 2017 were retrospectively collected.All patients were divided into responders (complete response + partial response) and nonresponders (stable disease + progression disease) according to therapeutic sensitivity.The texture features were extracted from CT images for positioning.And the patients were divided into training set (46 patients) and test set (46 patients) using train-test-split,training set for establishing predictive model and test set for model validation.Results There were 31 responders and 15 nonresponders in the training set,and the portion of responders was 67.4％.Univariate analyses showed that the histogram matrix (HISTO)-sknewess was significantly different between the two groups (Z =2.097,P =0.036) and the area under the curve (AUC) was 0.692 with 95％ CI of 0.539-0.820.Sknewess ≤-2.58 intended to be responders.Binary logistic regression of sknewess (Z =2.097,P =0.036) in HISTO,high gray level zone emphasis (HGZE) (Z =1.722,P =0.085) and small zone high gray level emphasis (SZHGE) (Z =1.640,P =0.101) in gray level zone-length matrix (GLZLM) showed that sknewess was the independent influence factor of sensitivity (OR =0.558,95 ％ CI:0.338-0.923,P =0.023),and the AUC of logistic regression model was 0.718 with 95％ CI of 0.550-0.886,which indicted that the model had the ability to predict treatment response of ESCC patients.The model was validated by using test set and the AUC was 0.706,and the sensitivity of the model was 70.6％ while the specificity was 69.0％.It showed that the model had certain ability in predicting treatment response.Conclusion CT texture analysis can predict the radio-chemotherapy sensitivity in patients with ESCC to some extent.
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OBJECTIVE:To study transfer rate of asperosaponinⅥ in standard decoction of Dipsacus asper decoction pieces. METHODS:The content of asperosaponin Ⅵ in Dipsacus asper decoction pieces and its standard decoction was determined by HPLC. The determination was performed on SinoChrom ODS-AP with mobile phase consisted of acetonitrile-water(30∶70,V/V)at the flow rate of 1.0 mL/min. The detection wavelength was set at 212 nm,and column temperature was 30℃. The sample size was 10 μL. By the ingredients content obtained,the transfer rate of asperosaponin Ⅵ was calculated during decoction piece to standard decoction. RESULTS:The linear range of asperosaponin Ⅵ was 0.484-4.84 μ g(r＝0.999 9). RSDs of precision,stability and reproducibility tests were all lower than 2%. The limits of quantification and detection were 0.3 and 0.1 μ g,respectively. The average recoveries in D. asper decoction pieces and standard decoction were 95.13% -100.22%(RSD＝1.78%,n＝6), 97.07%-100.08%(RSD＝0.98%,n＝6). RSD of durability test was lower than 1%.The transfer rate of asperosaponin Ⅵ in standard decoction of D. asper decoction pieces ranged 26.3%-49.5%. CONCLUSIONS:The method is simple,accurate,precise, stable,reproducible and durable,and can be used for transfer rate of asperosaponin Ⅵ in standard decoction of D. asper decoction pieces.
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Radiomics is an emerging tumor diagnosis and auxiliary detection technique that has undergone rapid development in the past few decades.The availability of new imaging equipment and reagents, as well as the use of standardized imaging protocol, has made quantitative and standardized imaging analysis possible.Radiomics is a field of study that involves the extraction of a large number of quantitative features from areas of interest in medical images using data-characterization algorithms, and transformation of these data into first-order or high-order data.The accuracy of clinical diagnosis and prognostic value of radiomics can be further improved by analyzing the relationship between data layers.Although radiomics has many advantages and has made great progress, its standardization, reliability, and application in large data and multicenter studies will need to be further optimized.
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BACKGROUND:Chitosan biological materials can induce bone marrow mesenchymal stem cells to differentiate toward neurons. As a derivative of chitosan, carboxymethyl chitosan has a series of excelent properties. However, whether carboxymethyl chitosan can induce the neuronal differentiation of bone marrow mesenchymal stem cells remains unclear.OBJECTIVE:To investigate the effect of carboxymethyl chitosan thermosensitive hydrogel on the differentiation of bone marrow mesenchymal stem cells into neurons and the possible mechanism.METHODS:Passage 3 bone marrow mesenchymal stem cells from rats were selected and cultured in carboxymethyl chitosan thermosensitive hydrogel extracts in different concentrations (0, 50, 100, 150, 200, 500 g/L). Control cells were cultured in culture medium with no addition of carboxymethyl chitosan thermosensitive hydrogel extracts. MTT assay was performed to investigate the effects of different concentrations of carboxymethyl chitosan thermosensitive hydrogel extracts on bone marrow mesenchymal stem cell proliferation. Western blot assay was used to explore the effect of 150 g/L carboxymethyl chitosan thermosensitive hydrogel extracts on the expression of neuron-specific enolase, Nestin, Vimentin, NF-M, microtubule associated protein 2, glial fibrillary acidic protein, β3-tubulin, Notch1 and Jag1 protein.RESULTS AND CONCLUSION:MTT assay showed that carboxymethyl chitosan thermosensitive hydrogel promoted the cell proliferation, and the proliferation rate reached the peak at the concentration of 150 g/L. Western blot assay showed that the cells induced by 150 g/L carboxymethyl chitosan thermosensitive hydrogel extract had significant increases in neuron-specific enolase, Nestin, Vimentin, NF-M, microtubule associated protein 2, glial fibrillary acidic protein, and β3-tubulin protein expression, and obvious decreases in Notch1 and Jag1 protein expression in comparison with the control group. These results indicate that the carboxymethyl chitosan thermosensitive hydrogel induces rat bone marrow mesenchymal stem cells to differentiate toward neurons, and suppresses the activity of Notch signal pathway in the process of differentiation.
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ObjectiveTo establish an HPLC analytic method for amygdalin inKuxingrenFormula Granules and HPLC characteristic chromatogram.MethodsRP-HPLC method was adopted. The determination was performed on Dionex C18 column (4.6 mm×250 mm, 5μm) with acetonitrile-0.1% phosphoric acid solution (8:92) at the flow rate of 0.6 mL/min. The detection wavelength was set at 207 nm and sample size was 10μL. The column temperature was 30℃. The peak of amygdalin was set as refernce, and 10 batches of samples were analyzed. TCM Chromatogram Fingerprint Similarity Evaluation System (2004 A) was adopted to evaluate similatity.Results The linear equation of amygdalin wasY=6.176×10-7X?3.058×10-3, with a good linear relationship in the range of 0.122 5–1.225μg (r= 0.999 8). The average recovery rate was 98.75% (RSD=1.30%). There were 6 common peaks in the characteristic chromatogram ofKuxingrenFormula Granules, and the similarity of 10 batches of samples was higher than 0.981. ConclusionThe HPLC method is simple, accurate and reproducible, which can be used for the quality control of Kuxingren Granules.
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OBJECTIVE:To investigate the application of fuzzy comprehensive evaluation in formulation screening. METH-ODS:Taking Compound paracetamol and chlorphenamine maleate granules as model drug,based on single factor experiment,L9(34) orthogonal test was used to screen the formulation with the amount of aspartame,hawthorn powder essence,milk powder essence and saccharose as factors,using dissolution rate of caffeine as index. The granules prepared by 9 kinds of formulation in orthogonal test were evaluated with fuzzy comprehensive evaluation in terms of taste,aroma,color and dissolubility. The optimized formula-tion was validated and compared with original formulation. RESULTS:The formulation 5 was the optimal choice in both orthogo-nal test and fuzzy comprehensive evaluation,and obtained same results. Compared with sensory comprehensive score (63.12) and dissolution rate of caffeine (91.3%) in original formulation,two indicators of optimized formulation in 3 tests were 84.00 and 99.07% in average (RSD<2.0%,n=3). CONCLUSIONS:Fuzzy comprehensive evaluation can be used for the formulation screening of sensory evaluation index. It is scientific and accurate.
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OBJECTIVE:To establish the quality standard of Fructus arctii concentrated granules. METHODS:TLC was con-ducted for the qualitative identification and HPLC was used for the content determination of arctiin in F. arctii concentrated gran-ules. The determination was performed on Dionex C18 column with mobile phase consisted of methanol-water(40∶60,V/V) at the flow rate of 1.0 ml/min. The detection wavelength was set at 280 nm,and the column temperature was 30 ℃. The samples size was 10 μl. RESULTS:TLC spectrum showed that the spots of F. arctii concentrated granules and arctiin reference medicinal material had the same color;the linear range of arctiin was 0.5-12.5 μg(r=0.999 8)with the average recovery of 98.41%(RSD=0.81%, n=9). The RSDs of precision,stability,repeatability tests were no more than 1.0%. CONCLUSIONS:The method is feasible and reproducible,and can effectively control the quality of F. arctii concentrated granules.
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The traditional treatment of abdominal aortic aneurysm was open surgery.In the 1990s,endovascular abdominal aortic aneurysm repair (EVAR) began to emerge.In the early stage,this kind of minimally invasive method was applied in highly selected patient cohort due to the limitation of anatomic conditions of patients,age of patients and shortage of available endovascular devices.The indications for open surgery which were used in this new kind of therapeutic modality also influenced the outcomes.As the technique became mature and the properties of endogarft were developed,endovascular treatment can be used to treat more complex pathologies and the results were improved.However,several challenges were rising,including dealing with complex proximal aneurismal neck,intra-and post-operative endoleak,abdominal aortic aneurysm compromising branched arteries and ruptured abdominal aortic aneurysm.To solve these problems,chimney technique,fenestrated stent,branched stent and the sandwich technique had been invented and developed.It is believed that endovascular treatment for abdominal aortic aneurysm could be applied more widely under vascular surgeons' efforts.
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With the increasing application of endovascular stent-graft in the treatment of aortic dissection, there are still some problems and controversies in the selection of the stent-graft oversizing. This review summarized the latest research in the study of the baseline and measurement in stent-graft oversizing selection, the relationship between stent-graft oversizing and prognosis and the selection of stent-graft oversizing in different patients with different conditions, providing a reference for the endovascular stent-graft oversizing selection in the treatment of aortic dissection.
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Humans , Aortic Dissection , Aortic Aneurysm , Aortography , Blood Vessel Prosthesis , Blood Vessel Prosthesis Implantation , Prognosis , StentsABSTRACT
Objective The purpose of this study was to investigate the anti-inflammatory effects on acute and chronic inflammation ofHuamoyan Granules(HMYG).Methods KM mice and SD rats were randomly divided into model group, ibuprofen group and HMYG high, middle and low three dosages groups. The Ibuprofen group was administrated drug by gavage, mice 0.13 g/kg and rats 0.093 g/kg. The HMYG groups were administrated orally, mice 12, 6 and 3g/kg, rats 4, 4.2 and 2.1 g/kg. The model group was given the same volume distilled water, once a day, 3 or 10 continuous days. The increased permeability of mice abdominal capillary was induced by acetic acid, edema of rat hind paw was induced by albumen and carrageenin, which both were adopted to observe the acute anti-inflammatory effects; and cotton pellet granuloma was to observe the chronic anti- inflammation effects of HMYG.Results Compared with the model group, the ibuprofen group, the HMYG high and middle group showed anti-inflammatory actions of mice induced by acetic acid (0.185 ± 0.046, 0.177 ± 0.055, 0.190 ± 0.052vs. 0.246 ± 0.050,P<0.05 orP<0.01); after 0.5, 1, 2, 4 and 6 hrs inflammation, HMYG high dosage group had significant inhibition for the edema of rats hind paw induced byalbumen model, the inhibitory rate was 22.46%, 19.20% and 24.32%, 33.75%, 24.19%; 4 and 6 hrs after inflammation, HMYG high dosage group could reduce rats paw edema induced by carrageenin, the inhibitory rate was 32.05%, 30.56% and 19.23%, 20.83%.Conclusion HMYG has evident anti-inflammatory effects on acute inflammation.
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Objective To evaluate the clinical value of endovascular therapy based on Angiosome concept in critical limb ischemia (CLI) patients.Methods A retrospective study was undertaken in 62 patients (62 limbs) diagnosed as critical limb ischemia (Rutherford class 5/6) and received percutaneous transluminal angioplasty from July 2011 to October 2013.Patients were divided into direct (35 patients) and indirect (27 patients) groups depending on whether feeding artery flow to the site of ulcer was successfully achieved or not based on the angiosome concept,and the between-group clinic outcomes including preoperative and postoperative ankle-brachial index (ABI),ulcer healing,and the rates of freedom from amputation were compared and analyzed.Results There were no significant difference between two groups for ABI pre-operatively (0.16 ±0.26 vs.0.15 ±0.28; P =0.885) and post-operatively (0.82 ± 0.26 vs.0.81 ±0.24; P =0.877).During follow-up,the healing rate of ischemia ulcer in patients without amputation at 1 year (91％ vs.74％ ; P =0.027) were significantly higher in the direct group than in the indirect group.There was no difference between two groups for healing time (162 ±49) d vs.(160 ±46) d; P =0.950).The rates of freedom from amputation at 1 year (84％ ±3％ vs.76％ ±4％ ; P =0.025) and 2 years (79％ ±4％ vs.72％ ±4％ ; P =0.031) were significantly higher in the direct group than in the indirect group.Conclusions Endovascular therapy based on Angiosome concept in CLI patient is an effective procedure with satisfactory clinic outcomes,contributing to healing of ischemia ulcer and increase amputation-free rate.
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<p><b>BACKGROUND</b>MMPs and TIMPs play important roles in tumor angiogenesis and invasion. Studies have shown that TIMP-2 has two roles in tumor invasion. However, its role in leukemic infiltration has not been well investigated. This study explored the roles of TIMP-2 in extramedullary infiltration of acute monocytic leukemic SHI-1 cells both in vitro and in vitro.</p><p><b>METHODS</b>A retroviral vector carrying the human TIMP-2 cDNA was constructed and transfected into the monocytic leukemic cell line SHI-1. The expression of TIMP-2 in the positive clones was determined. The proliferation of SHI-1 cells was examined by MTT assay. Trans-Matrigel invasion assays were used to investigate the infiltration ability in vitro. SHI-1 cells were intravenously injected into pre-treated nu/nu mice to investigate the infiltration ability feature in vitro.</p><p><b>RESULTS</b>The expression of TIMP-2 on the cell membrane was significantly elevated in SHI-1/TIMP-2 cells. Over-expression of TIMP-2 promoted the cells proliferation and the invasions in vitro. The SHI-1/TIMP-2 cells demonstrated higher infiltration ability when intravenously injected into nu/nu mice.</p><p><b>CONCLUSION</b>Over-expression of TIMP-2, especially on the cell membrane, may play important roles in promoting the proliferation and infiltration of SHI-1 leukemic cells.</p>