Safety of butylphthalide and edaravone in patients with ischemic stroke:a multicenter real-world study

BACKGROUND Butylphthalide(NBP)and edaravone(EDV)injection are common acute ischemic stroke medications in China,but there is a lack of large real-world safety studies on them.This study aimed to determine the incidence of adverse events,detect relevant safety signals,and assess the risk factors associated with these medications in real-world populations.METHODS In this study,data of acute ischemic stroke patients were extracted from the electronic medical record database of six tertiary hospitals between January 2019 and August 2021.Baseline confounders were eliminated using propensity score matching.The drugs’safety was estimated by comparing the results of 24 laboratory tests standards on liver function,kidney function,lipid level,and coagulation function.The drugs’relative risk was estimated by logistic regression.A third group with patients who did not receive NBP or EDV was constructed as a reference.Prescription sequence symmetry analysis was used to evaluate the associations between adverse events and NBP and EDV,respectively.RESULTS 81,292 patients were included in this study.After propensity score matching,the NBP,EDV,and third groups with 727patients in each group.Among the 15 test items,the incidence of adverse events was lower in the NBP group than in the EDV group,and the differences were statistically significant.The multivariate logistic regression equation revealed that NBP injection was not a promoting factor for abnormal laboratory test results,whereas EDV had statistically significant effects on aspartate transaminase,low-density lipoprotein cholesterol and total cholesterol.Prescription sequence symmetry analysis showed that NBP had a weak correlation with abnormal platelet count.EDV had a positive signal associated with abnormal results in gamma-glutamyl transferase,alanine aminotransferase,aspartate aminotransferase,prothrombin time,and platelet count.CONCLUSIONS In a large real-world population,NBP has a lower incidence of adverse events and a better safety profile than EDV or other usual medications.

Effects of sputtering power and annealing temperature on surface roughness of gold films for high-reflectivity synchrotron radiation mirrors

Gold films deposited by direct current magnetron sputtering are used for synchrotron radiation optics. In this study, the microstructure and surface roughness of gold films were investigated for the purpose of developing high-reflectivity mirrors. The deposition process was first optimized. Films were fabricated at different sputtering powers (15, 40, 80, and 120 W) and characterized using grazing incidence X-ray reflectometry, X-ray diffraction, and atomic force microscopy. The results showed that all the films were highly textured, having a dominant Au (111) orientation, and the film deposited at 80 W had the lowest surface roughness. Subsequently, post-deposition annealing from 100 to 200℃ in a vacuum was performed on the films deposited at 80 W to investigate the effect of annealing on the microstructure and surface roughness of the films. The grain size, surface roughness, and their relationship were investigated as a function of annealing temperature. AFM and XRD results revealed that at annealing temperatures of 175 ℃ and below, microstructural change of the films was mainly manifested by the elimination of voids. At annealing temperatures higher than 175℃, grain coalescence occurred in addition to the void elimination, causing the surface roughness to increase.

Metal-organic framework IRMOFs coated with a temperaturesensitive gel delivering norcantharidin to treat liver cancer

BACKGROUND Norcantharidin(NCTD)is suitable for the treatment of primary liver cancer,especially early and middle primary liver cancer.This compound can reduce tumors and improve immune function.However,the side effects of NCTD have limited its application.There is a marked need to reduce the side effects and increase the efficacy of NCTD.AIM To develop a nanomaterial carrier,NCTD-loaded metal-organic framework IRMOF-3 coated with a temperature-sensitive gel(NCTD-IRMOF-3-Gel),aiming to improve the anticancer activity of NCTD and reduce the drug dose.METHODS NCTD-IRMOF-3-Gel was obtained by a coordination reaction.The apparent characteristics and in vitro release of NCTD-IRMOF-3-Gel were investigated.Cell cytotoxicity assays,flow cytometry,and apoptosis experiments in mouse hepatoma(Hepa1-6)cells were used to determine the anti-liver cancer activity of NCTD-IRMOF-3-Gel in in vitro models.RESULTS The particle size of NCTD-IRMOF-3-Gel was 50-100 nm,and the particle size distribution was uniform.The release curve showed that NCTD-IRMOF-3-Gel had an obvious sustained-release effect.The cytotoxicity assays showed that the free drug NCTD and NCTD-IRMOF-3-Gel treatments markedly inhibited Hepa1-6 cell proliferation,and the inhibition rate increased with increasing drug concentration.By flow cytometry,NCTD-IRMOF-3-Gel was observed to block the Hepa1-6 cell cycle in the S and G2/M phases,and the thermosensitive gel nanoparticles may inhibit cell proliferation by inducing cell cycle arrest.Apoptosis experiments showed that NCTD-IRMOF-3-Gel induced the apoptosis of Hepa1-6 cells.CONCLUSION Our results indicated that the NCTD-IRMOF-3-Gel may be beneficial for liver cancer disease treatment.

Stress, Roughness and Reflectivity Properties of Sputter-Deposited B4C Coatings for X-Ray Mirrors

Boron carbide(B4C)coatings have high reflectivity and are widely used as mirrors for free-electron lasers in the x-ray range.However,B4C coatings fabricated by direct-current magnetron sputtering show a strong compressive stress of about-3 GPa.By changing the argon gas pressure and nitrogen-argon gas mixing ratio,we are able to reduce the intrinsic stress to less than-1 GPa for a 50-nm-thick B4C coating.It is found that the stress in a coating deposited at 10 m Torr is-0.69 GPa,the rms roughness of the coating surface is 0.53 nm,and the coating reflectivity is 88%,which is lower than those of coatings produced at lower working pressures.When the working gas contains 8%nitrogen and 92%argon,the B4 C coating shows not only-1.19 GPa stress but also a low rms roughness of 0.16 nm,and the measured reflectivity is 93%at the wavelength of 0.154 nm.

Structural characterization of calcium glycinate,magnesium glycinate and zinc glycinate

Metal glycinate chelates are formed by glycine and metal compounds through chemical reactions.Calcium glycinate,magnesium glycinate and zinc glycinate are kinds of new-type and ideal nutrient supplements,which have satisfactory physico-chemical properties and bioactivities.They are important for prophylaxis and treat metal deficiency.The structural characterization shows that the metal ion is bonded to the amino and carboxyl group to form two five-membered rings.This paper mainly studies the structure characterization of the metal chelated glycinates by their solubility,infrared spectrum,thermal analysis,mass spectrometry,polycrystal difrac-tion,the metal contents and glycine contents of calcium glycinate,magnesium glycinate and zinc glycinate.

Experimental study of qishen yiqi drop pill combined with bone marrow mesenchymal stem cell transplantation on angiogenesis and cardiac function in mice with myocardial infarction

Objective:To investigate the effects ofQishengyiqi drop pill combined with bone marrow mesenchymal stem cell transplantation on angiogenesis and cardiac function in mice after myocardial infarction through in vitro cell molecular biology experiments.Methods:The animals used in this experiment were male mice with eGFP+/-.Sixty mice were randomly divided into three groups(n=20):myocardial infarction group(MI+PBS),myocardial infarction+mesenchyme plasma stem cell transplantation group(MI+MSCs)and myocardial infarction+Qishenyiqi drip pill combined with mesenchymal stem cell transplantation group(MI+MSCs+QSYQ).Qishenyiqi dripping pills were prepared into a medicinal solution with a concentration of 3.9 mg/mL with distilled water.The MI+MSCs+QSYQ group was orally administered with 0.1 mL/kg/day,and the other two groups were orally administered with an equal amount of normal saline.Mice in each group were adaptively fed continuously for 2 weeks,and the myocardial infarction model was established by ligation of the anterior descending coronary artery by thoracic ligation.Twenty-four hours after the model was established,bone marrow mesenchymal stem cells were isolated from the tibia of the mice and injected intracardiacly Bone marrow-derived mesenchymal stem cells were transplanted,and multiple injections were made around the myocardial infarction area of mice.The control group was injected with the same amount of PBS.0h,3 days,7 days,and 14 days after cell transplantation,observe the stem cell morphology under a microscope;on day 7 of cell transplantation,track the expression of eGFP-positive cells with a fluorescence microscope;before modeling,14 and 21 days after cell transplantation,use Cardiac function was measured by echocardiography.After 21 days of modeling,the mice were sacrificed,and heart samples were taken.The angiogenesis of the mice was observed by immunohistochemical staining and microvascular density determination.Results:The morphological growth of transplanted stem cells was proportional to the time of cell transplantation.Compared with MI+PBS group,CD90.2 and y6A were highly expressed on the surface of bone marrow mesenchymal stem cells in MI+MSCs group and MI+MSCs+QSYQ group,while CD31 and CD117 were almost not expressed.On the 21st day after stem cell transplantation,the values of LVDd and LVSD in MI+MSCs+QSYQ group were significantly lower than those in MI+PBS group and MI+MSCs group.At the same time,LVEF and LVFS increased significantly.The results of quantitative immunohistochemical analysis showed that the angiogenesis density in the MI+MSCs+QSYQ group increased significantly,and the difference between the groups was statistically significant(P<0.05).Conclusion:Qishen Yiqi dripping pills combined with bone marrow mesenchymal stem cell transplantation can not only promote angiogenesis in mice with myocardial infarction,but also play a positive role in improving cardiac function.

A theoretical study of miRNA155-DNA methylation mediated mitokATP regulating mitochondrial autophagy in the improvement of myocardial ischemia-reperfusion injury by Qishen Yiqi Dropping Pills

In the state of acute myocardial ischemia,miRNA expression can regulate related genes and proteins,reduce myocardial cell damage,and thus play a protective role in the myocardium.However,the specific mechanism still needs to be further explored.Recent studies have found that the opening of the mitoKATP channel can regulate mitochondrial autophagy,and the initiation of miRNA-DNA methylation plays a regulatory role in inducing cell autophagy.The applicant research team previously found that Qishen Yiqi Dropping Pills could significantly improve myocardial ischemia by mediating MitokATP channels to regulate mitochondrial autophagy.,and animal experiments have confirmed that miR-155 plays a significant role in the aspect of autophagy regulates,inflammatory reaction and Vascular smooth muscle cell migration.Therefore,the applicant innovatively proposed that Qishen Yiqi Dropping Pills can regulate miRNA155-DNA methylation to mediate the opening of mitoKATP,thereby regulating mitochondrial autophagy and improving myocardial ischemia.In this paper,the association between mitochondrial autophagy and oxidative stress injury after myocardial ischemia was described,and the possible mechanism of Qisen Yiqi dropping pills regulating mitochondrial autophagy by regulating miRNA155-DNA methylation to mediate MitokATP to improve myocardial ischemia reperfusion injury was discussed,so as to provide theoretical ideas for related research.

Effects of Qishen Yiqi dripping pills-containing serum on KATP channel opening and PI3K/AKT signaling pathway in hypoxic/reoxygenated H9C2 cardiocytes

Objective:To investigate the effects of Qishen Yiqi dropping pills serum on KATP channel opening and PI3K/AKT signaling pathway of hypoxic/reoxygenated H9C2 cardiocytes.Methods:H9C2 cardiocytes cultured in vitro were randomly divided into five groups,A:H9C2 cell group B:H9C2 cells+H2O2 model group C:H9C2 cells+H2O2 model+Qishen Yiqi group D:H9C2 cells+H2O2 model+Qishen Yiqi+wort group E:H9C2 cells+H2O2 model+Qishenyiqi+5-HD group,the drug intervention is according to the corresponding conditions.CCK-8 method was used to detect the cell activity of each group;Western blot was used to detect the expression of AKT and P-Akt proteins in myocardial cells in each group.The current was recorded by the standard patch clamp whole cell recording method,and the current was collected and analyzed by Pclamp6.0 software.Results:CCK-8 test results showed that compared with group A,the activity of myocardial cells in group B was significantly decreased,and the difference was statistically significant(P<0.01);compared with group B,the difference in group C was statistically significant(P<0.01);compared with C,cardiomyocyte activity in D and E group were significantly decreased,and the difference was statistically significant(P<0.05);WB results showed that compared with A,p-Akt protein expression in B,C,D and E groups were significantly decreased,and the difference was statistically significant(P<0.01);compared with group B,p-Akt protein expression in C,D and E group were significantly increased,and the difference was statistically significant(P<0.01),but there was no significant difference in AKT expression among groups(P>0.05);The results of whole cell patch clamp experiment showed that the outward current of B was significantly increased compared with that of A,and the difference between groups was statistically significant(P<0.01);compared with group B,cardiomyocytes in group C further increased the outward current,and the difference between groups was statistically significant(P<0.01);compared with C,the current of D and E group were significantly decreased,with statistical significance between groups(P<0.01).Conclusion:QishenYiqi dropping pills can protect cardiomyocytes by activating p-Akt protein expression and KATP channel opening in H9C2 cardiomyocytes.

Update on establishment of TCM animal model of myocardial ischemia and Chinese medicine treatment

The prevention and treatment of myocardial ischemia is a hot and difficult point in clinical research and animal experimental research in the cardiovascular field.The combined disease and syndrome animal model with the disease characteristics of Western medicine and guided by the theory of Chinese medicineto replicate the"syndrome"of Chinese medicine on the model animals by using experimental methods is an effective tool for the research of Chinese medicine.This article summarized the methoding methods and evaluation index of the animal model combined disease of coronary heart disease myocardial ischemia with cold blood stasis,phlegm and blood stasis,qi deficiency and blood stasis syndrome,kidney deficiency and blood stasis,and concluded the treatment of Traditional Chinese medicine.At the same time,it analyzed the main deficiencies of myocardial ischemia syndrome combined with animal models to provide reference for the establishment and research of related animal models.

Clinical study on the correlation between plasma lipopolysaccharide and the structural characteristics of coronary intravascular ultrasound plaques

Objective:To study the correlation between plasma lipopolysaccharide and coronary atherosclerotic heart disease risk factors and plaque stability.Methods:136 patients with unstable angina pectoris who underwent coronary angiography and intravascular ultrasound were selected from the First Affiliated Hospital of Guangxi University of Traditional Chinese Medicine.According to the results of IVUS,they were divided into stable plaques(stable plaques,SP)group of 72 patients With 64 cases in the Unstable plaques(UP)group,venous blood was drawn from the two groups of patients for blood lipid and lipopolysaccharide index detection,and the general baseline data of the two groups were recorded;the structural characteristics of the intravascular ultrasound plaques in the two groups were analyzed.To study the influencing factors of unstable plaques,the correlation between lipopolysaccharide and plaque structural characteristics,and the diagnostic efficacy of unstable plaques.Results:The expression levels of cholesterol,low-density lipoprotein,and LPS in the UP group were higher than those in the SP group(P<0.05),and the high-density lipoprotein expression levels were lower than those in the SP group(P=0.035);and the intravascular ultrasound structure of the plaque was UP The lipid pool area,the ratio of lipid pool to plaque area,the plaque eccentricity index,and the maximum plaque thickness of the group were higher than those of the SP group(P<0.05),and the minimum plaque thickness was smaller than that of the SP group and the difference was statistically significant(P<0.05);LPS was positively correlated with cholesterol,low-density lipoprotein,lipid pool area,ratio of lipid pool to plaque area,plaque eccentricity index,and maximum plaque thickness by Pearson correlation test(P<0.05),Is negatively correlated with high-density lipoprotein(P=0.021);LPS is a risk factor for coronary plaque stability,and HDL is a protective factor for coronary plaque stability by binary logistic regression test.The difference is statistically significant Scientific significance(P=0.049,P=0.002);LPS diagnosis of coronary atherosclerotic plaque stability ROC area under the curve(AUC)is 0.889,95%CI is(0.805,0.974),the best diagnosis point is 57.485 mg/L,the sensitivity is 80.60%,and the specificity is 73.70%.Conclusion:Plasma lipopolysaccharide is a risk factor of unstable plaque,which has certain diagnostic value for coronary artery plaque,and can be used as a quantitative diagnostic index of plaque vulnerability.

Effect of programmed cell death factor 4 on the severity of coronary heart disease and coronary artery disease with blood stasis and toxin

Objective:To explore the diagnostic value of PDCD4 on the degree of arterial stenosis in"blood stasis"coronary heart disease.Methods:Select 80 patients with coronary heart disease in the Second Cardiovascular Zone of the First Affiliated Hospital of Guangxi University of Traditional Chinese Medicine in April 2020,and divide them into the"phlegm toxin"group(n=40)and the"phlegm stasis"group(n=40)based on the dialectics of traditional Chinese medicine.).Record the gender,age,smoking,and alcohol consumption of the subjects between the two groups,and detect their white blood cell count,neutrophil count,platelet count,platelet volume,platelet distribution width,blood creatinine,uric acid,cystatin,and fibrin The expression levels of original,high-sensitivity C-reactive protein,D-dimer,total cholesterol,triglycerides,high-density lipoprotein,low-density lipoprotein,apolipoprotein a,apolipoprotein b,and PDCD4.Multivariate logistic regression analysis was used to screen out the risk factors that affect coronary plaque formation,and the receiver operating characteristic(ROC)curve of each index was established to evaluate the severity of coronary stenosis in patients with stasis coronary heart disease by each index and combined index Diagnostic efficiency.Results:The two groups of patients were tested in terms of gender,age,smoking,drinking,triglycerides,cholesterol,high-density lipoprotein,low-density lipoprotein,apolipoprotein-a,apolipoprotein-b,white blood cell count,neutrophil The cell count,platelet count,platelet volume width and platelet distribution width were not statistically significant(P>0.05);the expression levels of hypersensitivity-C-reactive protein,serum creatinine,cystatin,uric acid and PDCD4 were statistically significant between the two groups Difference(P<0.05),and the corresponding hypersensitivity-C-reactive protein,creatinine,cystatin,uric acid and PDCD4 expression levels in the blood stasis group were higher than those in the phlegm blood stasis group.After multivariate logistic regression analysis,the level of PDCD4 in peripheral blood[OR=31.088,95%CI(2.498,3.869)]was an independent influencing factor of the"stagnation"type of coronary heart disease,and PDCD4 was diagnosed as the"stagnation"type of coronary heart disease The area under the ROC curve(AUC)is 88.6%,95%CI(1.894,2.532)(P=0.29);the level of PDCD4 in peripheral blood is positively correlated with the number and severity of coronary artery disease,the number of coronary artery disease and stenosis The greater the degree,the higher the detection value of PDCD4,(P<0.05).Conclusion:The expression level of PDCD4 in peripheral blood is closely related to the subtype of"stasis toxin"and the severity of coronary vascular stenosis.It can be used as a quantitative diagnostic index for the diagnosis of"stasis toxin"coronary heart disease and the severity of coronary vascular stenosis.

Anaphylaxis effect and substance basis of honeysuckle extract

Objective:To explore the anaphylaxis effect and anaphylaxis substances of honeysuckle.Methods:Rat peritoneal mast cells(PMC)were separated and purified,the cells were incubated with compound 48/80(0.02 g/L),physiological saline and honeysuckle extract(120 g/L)at 37°C for 0,15,30,45 and 60 min.Degranulation were observed by optical microscope and transmission electron microscope.Annexin V positive cell rate was detected by flow cytometry to reflect the degranulation rate of PMC.SD rats were supplied with honeysuckle extract by intravenous injection at a dose of 2.25 g/L.After administration,different parameters were analyzed,including the symptoms,histamine(HIS)and tryptase(MCT)levels,which were determined to explore the effect of anaphylaxis.Regression analysis was used to calculate the relationships between the peaks and the pharmacological effects to explore potentially anaphylactoid components.Results:The percentage of Annxin V positive cells and the degranulation ratio were markedly elevated in PMC treated with honeysuckle extract for more than 15 min(P<0.05).HIS and MCT level were significantly elevated after injection of honeysuckle extract for more than 15 min.Morphology of PMC and systemic symptoms were also changed compared with the controlled group(P<0.05).Regression analysis was used to calculate the relationship between peaks and pharmacological effects,and to determine peaks 7,10 and 13 as possible anaphylactoid ingredients.Conclusion:This study established a prospective method to clarify the anaphylactoid components of honeysuckle extract,which would provide guidance for screening anaphylactoid components in traditional Chinese medicine injections containing honeysuckle in the prescription.

Investigation of natural contamination layer growth on optical substrates

The surface contamination layer on mirrors can cause significant degradation of the optical performance, which is widely observed in applications, particularly in the fabrication of X-ray focusing telescopes. In this paper, we study the natural contamination layer arising from adsorption precipitation of hydrocarbons or other organic and water molecules in the absence of any external factor. Temporal evolution of the layer formed on super-smooth fused silica, borosilicate glass, and silicon substrates is studied by X-ray reflectometry, atomic force microscopy, and transmission electron microscopy for a one-year period after surface cleaning. The general characteristics of adhesion layer growth are established and discussed. The reconstructed dielectric constant profiles demonstrate that an increase in the adhesion layer thickness, deposited mass and density over time obeys power laws with extremely small exponents. Therefore, the adhesion layer growth is rapid immediately after surface cleaning, with a - 1 nm thick layer formed within the first day on all three substrates studied, while the layer density is low （- 1 g/cm^3）. The layer growth on the fused silica and silicon substrates became very slow in the succeeding days, with only a 1.4-1.5 nm thick layer and 1.2-1.3 g/cm^3 density after one year of storage in air. At the same time, the adhesion layer growth on the glass substrate showed unexpected acceleration about two months after cleaning, so that the layer thickness reached - 2.2 nm after one year of storage. The reason for this effect, which is connected with leaching of the glass, is discussed briefly.

A guinea pig model of Ciwujia Injection-induced anaphylaxis for allergic substance screening

Objective: Though especially efficient for cardiovascular and cerebrovascular diseases treatment, many serious anaphylactic diseases could be induced by Ciwujia Injection(CWJI). However, study of the mechanism and detection of allergies have been investigated by the unknown sources of allergenic substances.In this study, a guinea pig model which could mimic the symptoms of anaphylactic reactions induced by Ciwujia Injection(CWJI) was modeled and used to screen the allergenic substance of CWJI.Methods: Guinea pigs were sensitized three times every other day with CWJI and excitated 14 d after the last sensitization administration. Then, the histamine, trypsin, IL-4 and IFN-γ levels, and the Annexin V positive rate of peritoneal mast cells(PMC) were detected, the numbers of B lymphocyte and the pathological changes were also analyzed to verify the guinea pig allergy model, PCA test and Ig E antibody levels were determined to study the mechanism.Results: The levels of total IgE, histamine, and trypsin were significantly increased after CWJI sensitization, IL-4 level was elevated, Annexin V positive of PMC cell rate, local skin reactions, and declined IFN-γwere observed after excitation. Histological examination showed that mild pathological changes in lungs were found.Conclusion: This guinea pig model may provide a powerful tool to study the mechanism in CWJI induced anaphylaxis and screen the allergic source of CWJI.