Objective: To investigate the chemical constituents from the whole plants of Gynura procumbens. Methods: The chemical constituents were isolated and purified by repeated silica gel column chromatography, Sephadex LH-20 gel column chromatography, medium pressure column chromatography, and semi-preparative HPLC, and their structures were elucidated by chemical properties and spectroscopic analyses. Results: Sixteen compounds were identified to be quercetin (1), apigenin (2), luteolin (3), kaempferol (4), astragaline (5), kaempferol-5-O-(6″-O-acetyl)-β-D-glucopyranoside (6), negletein (7), 4-methoxycinnamic acid (8), benzyl-O-β-D-glucopyranoside (9), 2-phenylethyl-O-β-D-glucopyranoside (10), 3,5-dicaffeoylquinic acid methyl ester (11), 3,5-dicaffeoylquinic acid ethyl ester (12), 3,4-dicaffeoylquinic acid methyl ester (13), 4,5-dicaffeoylquinic acid methyl ester (14), protocatechuic acid (15), and eugenol glucoside (16). Conclusion: Compounds 7, 8, 12, 14, and 16 are obtained from the plants in Gynura Cass. for the first time, and compounds 3, 6, 9-11 and 13 are obtained from this plant for the first time.

OBJECTIVETo investigate the chemical constituents from the branch of Fraxinus sieboldiana, and evaluate their antioxidative activity.

METHODThe chemical constituents were isolated and purified by chromatographic techniques over silica gel, macroporous adsorbent resin, Sephadex LH-20, and preparative HPLC. Structures of the compounds were identified by spectroscopic methods. The antioxidant activity was evaluated by Fe(+2)-cystine induced rat liver microsomal lipid peroxidation.

RESULTEight coumarins were obtained and their structures were elucidated as esculin (1) , esculetin (2), fraxin (3), fraxetin (4), 6, 7-di-O-beta-D-glucopyranosylesculetin (5), scopoletin (6), cleomiscosin D (7) and cleomiscosin B (8). At a concentration of 10(-6) mol x L(-1), compound 4 showed antioxidative activity inhibiting Fe(+2)-cystine induced rat liver microsomal lipid peroxidation with inhibitory rate of 60%.

CONCLUSIONCompounds 5, 7 and 8 were obtained from the genus Fraxinus for the first time. Compound 4 showed remarkable antioxidative activity, which was higher than that of VE (35%).

Animals ; Antioxidants ; chemistry ; pharmacology ; Coumarins ; chemistry ; pharmacology ; Fraxinus ; chemistry ; Lipid Peroxidation ; drug effects ; Magnetic Resonance Spectroscopy ; Microsomes, Liver ; drug effects ; metabolism ; Rats ; Scopoletin ; chemistry ; pharmacology ; Spectrometry, Mass, Electrospray Ionization ; Umbelliferones ; chemistry ; pharmacology

Objective To investigate the effect of prior statin use on outcome after intravenous thrombolysis in patients with acute ischemic stroke. Methods Consecutive patients with acute ischemic stroke treated with intravenous thrombolysis at the Department of Neurology, the Third People's Hospital of Chengdu from July 2014 to August 2017 were enrolled, and divided into the statin use group and nonstatin use group according to prior statin use. Symptomatic intracranial hemorrhage and the outcome at 90 days after onset (good outcome and poor outcome were defined as the modified Rankin Scale score 0-2 and > 2, respectively) in the two groups were compared, and multivariate logistic regression analysis was used to identify the effect of prior statin use on the outcome. Results A total of 327 patients were enrolled, including 68 (20. 80％ ) in the statin use group, and 59 (79. 20％ ) in the nonstatin use group. There were no significant differences in the incidence symptomatic intracranial hemorrhage (7. 35％ vs. 10. 04％; χ2 = 0. 453, P = 0. 501), good outcome rate at 90 days (69. 12％ vs. 66. 02％; χ2 = 0. 232, P = 0. 630), and mortality rate (7. 35％ vs. 7. 34％; P = 1. 000) between the statin use group and the nonstatin use group. Multivariable logistic regression analysis showed that prior statin use were not an independent risk factor for symptomatic intracranial hemorrhage (odds ratio 0. 658, 95％ confidence interval 0. 233-1. 857; P = 0. 429) and poor outcome at 90 dafter onset (odds ratio 0. 848, 95％ confidence interval 0. 424-1. 696; P = 0. 641) in patients treated with intravenous thrombolysis. Conclusion Prior statin use is not associated with symptomatic intracranial hemorrhage and outcome after intravenous thrombolysis in patients with acute ischemic stroke.

ObjectiveTo observe the therapeutic effect and antioxidant mechanism of Xiaochuanning granule on psychological stress-related asthma in rats. MethodThe 6-week-old male SD rats were randomly divided into the normal group， asthma group， stress group， stress-related asthma group， western medicine group （atomization of budesonide suspension） and traditional Chinese medicine （TCM） group （Xiaochuanning granule 2.48 g·kg^-1）. The asthma model was established during 28 days by intraperitoneal injection of 10% ovalbumin（OVA）on the 1^st and 8^th days and inhaling of vapourized 1% OVA started at the 15^th day. Stress group， stress-related asthma group， western medicine group and TCM group were given restraint stimulation during the 28 days to establish the psychological stress-related asthma model. Rats in each group were administered with corresponding drug for 14 days from the 15^th day. The sucrose preference test and open field test were performed at the 15^th and 28^th days. At the end of experiment， the body weight， serum interleukin-4 （IL-4）， interleukin-5 （IL-5） and interleukin-13 （IL-13） levels， as well as the levels of malondialdehyde （MDA）， superoxide dismutase （SOD） and glutathione （GSH） in lung tissues were detected by assay kits. Hematoxylin-eosin（HE） staining was conducted to observe the pathological changes in lung tissues. Meanwhile， Western blot was used to detect the protein expression of nuclear factor erythroid 2-related factor 2 （Nrf2） and hemeoxygenase-1 （HO-1） in lung tissues. ResultCompared with the stress-related asthma group， the body weight， sugar water consumption rate and open field distance in the TCM group were significantly increased （P<0.05）， and the serum IL-4， IL-5， IL-13 levels were significantly decreased （P<0.05）， the levels of SOD and GSH in lung tissues increased significantly （P<0.05）， while the level of MDA decreased significantly （P<0.05）. HE staining showed that the bronchial mucosal injury， inflammatory cell infiltration， gland hyperplasia， epithelial degeneration and necrosis were significantly ameliorated in the TCM group than in the stress-related asthma group. The expression of Nrf2 and HO-1 protein in lung tissues also increased significantly （P<0.05）. ConclusionXiaochuanning Granule can regulate the psychological stress state of stress-related asthmatic rats， alleviate airway inflammatory reaction， and suppress oxidation， which is related to its up-regulation of the Nrf2/HO-1 protein expression.

OBJECTIVE: To evaluate the efficacy and safety of tacrolimus in the treatment of children with myasthenia gravis (MG). METHODS: A total of 28 children with MG were treated with tacrolimus. MG-Activities of Daily Living (MG-ADL) scale was used to assess clinical outcome and safety after 1, 3, 6, 9, and 12 months of treatment. RESULTS: After tacrolimus treatment, the MG-ADL score at 1, 3, 6, 9 and 12 months was lower than that at baseline (P<0.05), and the MG-ADL score showed a gradually decreasing trend. The response rates to tacrolimus treatment at 1, 3, 6, 9, and 12 months were 59%, 81%, 84%, 88%, and 88% respectively. At 6, 9, 12, and 18 months of treatment, 4, 13, 14, and 15 children respectively were withdrawn from prednisone. No recurrence was observed during treatment. Major adverse reactions/events were asymptomatic reduction in blood magnesium in 5 children and positive urine occult blood in 1 child, which turned negative without special treatment, and tacrolimus was not stopped due to such adverse reactions/events. One child was withdrawn from tacrolimus due to recurrent vomiting. According to CYP3A5 genotypes, all of the patients were divided into two groups: slow metabolic type (n=19) and non-slow metabolic type (fast metabolic type + intermediate type; n=9). The non-slow metabolism group received a higher dose of tacrolimus, but had a lower trough concentration of tacrolimus than the slow metabolism group (P<0.05). The slow metabolism group had a higher response rates to tacrolimus treatment than the non-slow metabolism group (P<0.05). CONCLUSIONS Tacrolimus appears to be effective and safe in the treatment of children with MG and is thus an option for immunosuppressive therapy. CYP3A5 genotyping has a certain guiding significance for determining the dosage of tacrolimus.
Activities of Daily Living ; Child ; Humans ; Immunosuppressive Agents ; Myasthenia Gravis ; drug therapy ; Neoplasm Recurrence, Local ; Tacrolimus ; therapeutic use

Objective To investigate the influences of atrial fibrillation (AF) on clinical outcome and hemorrhagic transformation (HT) after intravenous thrombolysis for acute ischemic stroke.Methods The patients with acute ischemic stroke treated with intravenous recombinant tissue plasminogen activator thrombolysis were enrolled retrospectively.The modified Rankin Scale score 0-2 at 90 d was defined as a good outcome.Multivariate logistic regression analysis was used to determine the correlation between AF and clinical outcomes after intravenous thrombolvsis.Results A total of 160 patients with acute ischemic stroke treated with intravenous recombinant tissue plasminogen activator thrombolysis were enrolled,including 67 (41.88％) with AF.Compared with the non-AF group,the age was older (median [interquartile range] 77 [71-83] years vs.69 [59-78] years;Z=4.142,P＜ 0.001),baseline National Institutes of Health Stroke Scale (NHISS) score was higher (11.0[6.0-17.0] vs.7.0[4.0-14.0];Z=2.623,P=0.009)in the AF group.There were no significant differences in the NIHSS score reduction and the proportion of patients with good outcomes at 24 h (3.0 [1.0-4.5] vs.2.0 [0-6.0];Z=-0.312,P=0.775) and7d(4.0 [2.0-5.0] vs.5.0[2.0-8.0];Z=l.574,P=0.115) after thrombolysis and the proportion of patients with good outcome at 90 d (38.81％ vs.25.82％;x2 =3.063,P =0.080) between the AF group and the non-AF group,however,the proportions of HT within 24 h (14.93％ vs.5.38％;x2 =4.179,P =0.041) and death within 90 days (16.42％ vs.6.45％;x2 =4.073,P =0.044) in the AF group were significantly higher than those in the non-AF group.Multivariate logistic regression analysis showed that AF was not independent correlation with the clinical outcomes at 90 d (odds ratio [OR] 0.950,95％ confidence interval [CI]0.381-2.366;P =0.912),HT within 24 h (OR 1.992,95％ CI0.580-6.369;P =0.285),and death within 90 d (OR 2.483,95％ CI 0.727-8.586;P=0.146).Conclusion AF is not the independent risk factor that influences on clinical outcome at 90 d and-HT within 24 h after intravenous thrombolysis in patients with acute ischemic stroke.

ObjectiveTo explore the underlying molecular mechanism of Xiaochuanning granules in the treatment of bronchial asthma based on the network pharmacology and experimental verification through the phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt） signaling pathway on ovalbumin （OVA） sensitization-induced bronchial asthma model in rats. MethodThe main active ingredients and targets of Xiaochuanning Granules were screened out from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP） and Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine （BATMAN-TCM）. The targets related to bronchial asthma were obtained from five disease databases such as GeneCards and Online Mendelian Inheritance in Man （OMIM）. The common targets were screened out through the Venn diagram. STRING was used to construct the protein-protein interaction （PPI） network of "compound-disease"， and Cytoscape 3.8.0 was used to establish a network of key active ingredients of Xiaochuanning granules and core target genes （"ingredient-gene" network）. Gene Ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analyses were performed through DAVID. The bronchial asthma model was induced by OVA stimulation in rats. Bronchial and lung tissue inflammation was observed by hematoxylin-eosin （HE） staining， and the enrichment analysis results of the network pharmacology were verified by Western blot. ResultIn this experiment， 232 active ingredients and 4 687 related targets of Xiaochuanning granules were screened out， and 233 common targets of Xiaochuanning granules and bronchial asthma were collected， including eosinophil-derived neurotoxin 1 （EDN1）， cyclic AMP response element-binding protein 1 （CREB1）， cyclin-dependent kinase inhibitor 1A （CDKN1A）， epidermal growth factor receptor （EGFR）， mitogen-activated protein kinase 14 （MAPK14）， and Akt1. KEGG pathway analysis revealed 186 related signaling pathways， indicating that the PI3K/Akt signaling pathway presumedly played a key role in the treatment of bronchial asthma by Xiaochuanning granules. The animal experiment showed that Xiaochuanning granules relieved the airway inflammation and smooth muscle hyperplasia in rats and down-regulated the gene expression of PI3K and Akt as compared with the conditions in the model group （P<0.05）. ConclusionXiaochuanning granules have the characteristics of multi-component， multi-target， and multi-pathway synergistic effect in the treatment of asthma. Xiaochuanning granules may exert anti-inflammatory effects by regulating the expression of genes related to the PI3K/Akt signaling pathway. The present study is expected to provide a theoretical basis for follow-up in-depth research on the complex mechanism of Xiaochuanning granules in the treatment of bronchial asthma.

ObjectiveTo explore the intervention effect of Baofeikang granule （BFK） on the rat model of pulmonary fibrosis through the Wnt/β-catenin signaling pathway. MethodAfter adaptive feeding for one week， 50 healthy rats were randomly divided into a blank group （n=8） and an experimental group （n=42）. After anesthesia， the rats in the experimental group were injected with bleomycin sulfate solution （5 mg·kg^-1） into the trachea for the induction of the pulmonary fibrosis model. Those in the blank group were injected with the same amount of normal saline under the same manipulation. On the 7^th day after modeling， one of the remaining 33 rats alive was randomly removed， and the other 32 model rats were assigned into a model group （n=8）， a prednisone acetate （1.17 mg·kg^-1） group （n=8）， a low-dose BFK （13.59 g·kg^-1） group （n=8）， and a high-dose BFK （27.18 g·kg^-1） group （n=8）. The rats in the groups with drug intervention were treated correspondingly by gavage once per day for 21 days， and those in the blank group and the model group received the same amount of normal saline. The pulmonary compliance and ventilatory function， the scores of pathological changes and fibrosis， the levels of type Ⅰ collagen （Col Ⅰ） in lung tissues and hydroxyproline （HYP） in the serum， and the relative expression of Wnt3a and β-catenin protein in lung tissues were compared. ResultCompared with the blank group， the model group showed reduced pulmonary function indexes， such as forced vital capacity （FVC）， peak expiratory flow （PEF）， the resistance of lung （RL）， and dynamic compliance （Cdyn） （P<0.05， P<0.01）， severely damaged lung tissue morphology， massive formed continuous fibrous foci， increased fibrosis score （P<0.01）， elevated levels of Col Ⅰ in lung tissues and HYP in the serum （P<0.01）， and up-regulated expression of Wnt3a and β-catenin （P<0.01）. FVC， PEF， and Cdyn levels in the prednisone acetate group and the BFK groups were higher than those in the model group （P<0.05， P<0.01）. Pathological changes were improved in the groups with drug intervention， and fibrosis scores were decreased as compared with the model group （P<0.05， P<0.01）. The scores in the BFK groups were lower than that in the prednisone acetate group （P<0.01）. The levels of Col Ⅰ and HYP in the groups with drug intervention were lower than those in the model group （P<0.05， P<0.01）. The level of Col Ⅰ in the prednisone acetate group was higher than that in the high-dose BFK group （P<0.01）. The levels of serum HYP in the BFK groups was lower than that in the prednisone acetate group （P<0.01）. The protein expression of Wnt3a in lung tissues of the high-dose BFK group was lower than that of the model group （P<0.05）. The protein expression of β-catenin in the prednisone acetate group and the BFK groups was lower than that in the model group （P<0.05， P<0.01）， and the expression level in the high-dose BFK group was lower than that in the prednisone acetate group （P<0.01）. ConclusionBFK can relieve bleomycin sulfate-induced pulmonary fibrosis， reduce collagen deposition， improve pulmonary compliance， and enhance pulmonary ventilatory function in rats. One of its mechanisms is presumedly the inhibition of the Wnt/β-catenin signaling pathway.

Objective: To investigate the clinical characteristics, cytogenetics, molecular biology, treatment, and prognosis of patients with therapy-related myelodysplastic syndrome and acute myeloid leukemia (t-MDS/AML) secondary to malignancies. Methods: The clinical data of 86 patients with t-MDS/AML in West China Hospital of Sichuan University between January 2010 and April 2023 were retrospectively analyzed. The clinical characteristics, primary tumor types, and tumor-related therapies were analyzed. Results: The study enrolled a total of 86 patients with t-MDS/AML, including 67 patients with t-AML, including 1 patient with M(0), 6 with M(1), 27 with M(2), 9 with M(3), 12 with M(4), 10 with M(5), 1 with M(6), and 1 with M(7). Sixty-two patients could be genetically stratified, with a median overall survival (OS) of 36 (95% CI 22-52) months for 20 (29.9%) patients in the low-risk group and 6 (95% CI 3-9) months for 10 (14.9%) in the intermediate-risk group. The median OS time was 8 (95% CI 1-15) months in 32 (47.8%) patients in the high-risk group. For patients with non-acute promyelocytic leukemia (APL) and AML, the median OS of the low-risk group was 27 (95% CI 18-36) months, which was significantly longer than that of the non-low-risk group (χ(2)=5.534, P=0.019). All 9 APL cases were treated according to the initial treatment, and the median OS was not reached, and the 1-, 2-, and 3-year OS rates were 100.0%, (75.0±6.2) %, and (75.0±6.2) % respectively. Of the 58 patients with non-APL t-AML (89.7%), 52 received chemotherapy, and 16 achieved complete remission (30.8%) after the first induction chemotherapy. The 1-, 2-, and 3-year OS rates of the non-APL t-AML group were (42.0 ± 6.6) %, (22.9±5.7) %, and (13.4±4.7) %, respectively. The median OS of patients who achieved remission was 24 (95% CI 18-30) months, and the median OS of those who did not achieve remission was 6 (95% CI 3-9) months (χ(2)=10.170, P=0.001). Bone marrow CR was achieved in 7 (53.8%) of 13 patients treated with vineclar-containing chemotherapy, with a median OS of 12 (95% CI 9-15) months, which was not significantly different from that of vineclar-containing chemotherapy (χ(2)=0.600, P=0.437). In 19 patients with t-MDS, the 1-, 2-, and 3-year OS rates were (46.8±11.6) %, (17.5±9.1) %, and (11.7±9.1) % with a median OS of 12 (95% CI 7-17) months, which was not significantly different from that in t-AML (χ(2)=0.232, P=0.630) . Conclusions: Breast cancer, bowel cancer, and other primary tumors are common in patients with t-MDS/AML, which have a higher risk of adverse genetics. Patients with APL had a high induction remission rate and a good long-term prognosis, whereas patients without APL had a low remission rate and a poor long-term prognosis.
Humans ; Retrospective Studies ; Leukemia, Myeloid, Acute/drug therapy* ; Leukemia, Promyelocytic, Acute/therapy* ; Prognosis ; Myelodysplastic Syndromes/drug therapy* ; Neoplasms, Second Primary/drug therapy* ; Remission Induction ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use*