Objective To investigate technique methods of dense emolization of intracranial aneurysms, factors resulting incomplete embolization. Methods 58 patients with intracranial aneurysms, using different embolization technique treated narrow and wide aneurysms with GDC. Dense emolization rate of aneurysms was elevated. Results dense emolization 50 aneurysms (86.2%), 95% in 3 aneurysms (5.2%), 90% in 3 aneurysms (5.2%), 80% in 2 aneurysms (3.4%). All embolizated aneurysms showed no enlarging recurrence or rebleeding.Conclusions Dense embolization of intracranial aneurysms should try to obtain.

Objective To study adrenomedullin (AM) mRNA and protein expression level in myocardium of autoimmune myocarditis animal models induced by immunization of mice with lactobacillus casei cell wall element(LCWE). Methods Forty-five Balb/c male mice were randomly divided into experimental group (n = 30) and control group (n = 15), which were intraperitoneally injected with LCWE and phosphate buffered solution(PBS) at day 0,3,5 and 10,respectively. Sera and myocardium samples were gained 14,21 and 28 days after the first immunization. AM expression levels were determined by semiquantitative reverse transcriptase-polymerase chain reaction(RT- PCR) and immunchistochemistry,and mycardial histopathological lesions were observed. The anti- myosin antibodies in different stages were examined by an ELISA. Results There were myocardial necrosis or inflammatory infiltration in the experimental group, but myocardial lesions were not found in the control group. Anti - myosin antibodies were detected in sera of experimental mice,but not in control group. Immunchistochemistry findings demonstrated that AM expression level was higher in the experimental group than in the control group( P

To investigate the cardioprotective effect of formononetin (FMN) on no-reflow (NR) after myocardial ischemia-reperfusion and its molecular mechanism based on integrated pharmacology and experimental verification, firstly, human breast cancer MCF-7 cells and myocardial NR rats were used to confirm the estrogenic activity and the effect of alleviating NR of FMN, respectively. Male SD rats were divided into Sham, NR, FMN (20 mg·kg^-1) and sodium nitroprusside (SNP, 5.0 mg·kg^-1) groups, which were administered once a day for one week, the experiment was approved by the Ethics Committee of Tianjin University of Traditional Chinese Medicine (TCM-LAEC2019095). The pharmacological analysis and in vivo study of NR rats were integrated to reveal the mechanism of FMN improving NR. The results showed that FMN had estrogenic effect and reduced NR by improving cardiac structure and function, reducing NR, ischemic myocardial area and pathological injury of cardiomyocytes. Integrated pharmacology predicts that the mechanism of FMN improving NR is mainly related to phosphatidyinositol-3-kinase-protein kinase B (PI3K-Akt) signal pathway. Phytoestrogens play a role in cardiovascular protection mainly by activating G protein-coupled estrogen receptor (GPER). GPER is also an important regulator in the upstream of PI3K-Akt signaling pathway. This study found that FMN can significantly activate GPER, p-PI3K, p-Akt and phospho-endothelial nitric oxide synthase (p-eNOS). It has good binding ability with GPER and eNOS protein. In this study, through the integration of pharmacology and experimental evaluation, it is revealed that FMN activates PI3K/Akt/eNOS signal pathway by activating GPER, thus significantly improving NR.

To explore the influence of matrix materials in complicate ingredients on traditional Chinese medicine and investigate the excipients selection model based on balanced release characteristics of multicomponents, the influence of HPMC (K4M, K15M, K100M) and Carbomer (934P, 971P, 974P) was illustrated by testing in vitro release of ginsenoside-Rg1, ginsenoside-Rb1 and notoginsenoside-R1 in Panax notoginseng saponins (model drug, PNS). According to in vitro release results of PNS matrix tablets in water and artificial intestinal juice, the release curves were analyzed with Peppas equation and simulating factor (f). Significant differences in k value and n value among ginsenoside-Rg1, ginsenoside-Rb1 and notoginsenoside-R1 existed in various formulations. The release behaviors from various excipients could be described with Non-Fickian transport or super Case II transport pattern. The f2 values for ginsenoside-Rg1, ginsenoside-Rb1 and notoginsenoside-R1 in 971P matrix tablet containing 30% Carbomer 971P were 74.91, 53.45, 57.89 in water and 79.35, 55.51, 51.89 in artificial intestinal juice, respectively. The release profiles fit for the regulation of FDA. The result revealed that the balanced release rates of Rg1, Rb1 and R1 in 971P matrix tablet were obtained.
Acrylates ; chemistry ; Acrylic Resins ; chemistry ; Delayed-Action Preparations ; Excipients ; chemistry ; Ginsenosides ; isolation & purification ; pharmacokinetics ; Lactose ; analogs & derivatives ; chemistry ; Methylcellulose ; analogs & derivatives ; chemistry ; Panax notoginseng ; chemistry ; Plants, Medicinal ; chemistry ; Saponins ; administration & dosage ; isolation & purification ; pharmacokinetics ; Tablets

Objective: To investigate the clinical features of adult B-cell acute lymphoblastic leukemia (B-ALL) with E2A-PBX1 fusion gene positive. Methods: The clinical data of 91 Philadelphia chromosome negative B-ALL patients who received chemotherapy regularly in Nanfang Hospital of Southern Medical University from March 2015 to December 2017 were collected. According to the fusion gene detection results, the patients were divided into E2A-PBX1 fusion gene positive group and E2A-PBX1 fusion gene negative group. The clinical features and prognosis of both groups were retrospectively analyzed. And then E2A-PBX1 fusion gene negative group was further divided into MLL-AF4 fusion gene positive group and the other ALL groups,which were compared with E2A-PBX1 fusion gene positive group in the prognosis. Results: There were 11 ALL patients with E2A-PBX1 fusion gene positive, and 80 ALL patients with E2A-PBX1 fusion gene negative. The level of lactic dehydrogenase (LDH) in E2A-PBX1 fusion gene positive group was higher than that in E2A-PBX1 fusion gene negative group [4 063 U/L (1 070- 9 554 U/L) vs. 454 U/L (103- 18 651 U/L), U=-4.700, P < 0.01], and there were no statistically significant differences in age, gender, white blood cell count and extramedullary invasion (all P > 0.05). The immunophenotypes of ALL patients with E2A-PBX1 fusion gene positive were all common B-cell phenotype. Out 4 of 7 ALL patients showed the different expression of Philadelphia-like ALL phenotype CRLF2 or phosphorylated CRKL or phosphorylated STAT5 by using flow cytometry. The complete remission (CR), minimal residual disease (MRD)-negative and the recurrence for 11 cases of E2A-PBX1 fusion gene positive group included 9, 7, 8 cases, respectively after first course of induction chemotherapy. The CR, MRD-negative and the recurrence for 80 cases of E2A-PBX1 fusion gene negative group included 71, 53, 26 cases, respectively after the first course of induction chemotherapy. There were no statistically significant differences in the CR and MRD-negative between the two groups after the first course of induction chemotherapy (P= 0.721, P= 0.487), but there was a statistical difference in the recurrence (χ²= 7.751, P= 0.012). The median follow-up time was 17 months (1-44 months), and the 1-year overall survival (OS) rate and 1-year event-free survival (EFS) rate of E2A-PBX1 fusion gene positive ALL group were lower than those of the negative group (OS: 43.6% vs. 70.0%, P= 0.020; EFS: 13.6% vs. 60.0%, P= 0.002). Subgroup analysis showed that there were no statistical differences between E2A-PBX1 fusion gene positive group and MLL-AF4 fusion gene positive group in 1-year OS rate and 1-year EFS rate (P= 0.617, P= 0.984). Conclusions E2A-PBX1 fusion gene positive rate is low in adult B-ALL patients with a good response to traditional chemotherapy in the early stage, but its cumulative recurrence rate is high. It is a high-risk cytogenetic abnormality which is similar to MLL gene rearrangement and needs to explore novel therapy strategies.

OBJECTIVETo analyze the effect of sorafenib as salvage therapy used before and/or after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in refractory relapsed FLT3-positive acute myeloid leukemia (AML).

METHODSA total of 16 patients with refractory relapsed FLT3-positive AML, including 10 refractory relapsed pre-transplantation and 6 relapsed after allo-HSCT, were enrolled in this retrospective study. Sorafenib treatment protocols included sorafenib in combination with chemotherapy inducing remission, and sorafenib monotherapy as mauntenance treatment after complete remission (CR).

RESULTSThirteen of the 16 patients achieved CR after one or two courses of induction therapy, including 7 refractory relapsed pre-transplantation and 6 relapsed after allo-HSCT. With a median follow up of 472 (range, 59-1569) days post-transplantation, 12 patients survived and 4 died. Causes of death included leukemia relapse (n=3) and acute graft-versus-host disease (n=1). The 2-year overall and disease-free survival post-transplantation of the 16 patients were (75.0±10.8) % and (50.5±13.7) % respectively. The main side effect of sorafenib was the skin rash. The incidence of rash was lower in the patients used sorafenib pre-transplantation than those post-transplantation (30.0% vs 75.0%, P=0.043).

CONCLUSIONSorafenib used as salvage therapy befor and/or after transplantation for refractory relapsed FLT3-positive AML could reduce the relapse rate and improve the survival.

Antineoplastic Agents ; therapeutic use ; Disease-Free Survival ; Graft vs Host Disease ; Hematopoietic Stem Cell Transplantation ; Humans ; Induction Chemotherapy ; Leukemia, Myeloid, Acute ; genetics ; therapy ; Mutation ; Niacinamide ; analogs & derivatives ; therapeutic use ; Phenylurea Compounds ; therapeutic use ; Recurrence ; Remission Induction ; Retrospective Studies ; Salvage Therapy ; Treatment Outcome ; fms-Like Tyrosine Kinase 3 ; genetics

To confirm the mechanism of exosomes as tumor vaccines inducing immunity response, dendritic cells (DCs) were induced from human peripheral blood mononuclear cells, while exosomes were isolated from DC loaded tumor antigen. The effect of exosomes on priming T cell proliferation was analysed under conditions with or without DCs, or DCs at different mature stages. The function of exosomes in immunity was detected through block test after blocking some molecules (CD11a, CD11b, CD11c, CD54, MFG-E8 and CD83). The effect of DCs on embedded exosomes was observed by confocal microscopy, the effect of blocking surface molecules on exosomes on DC-embedding exosomes was assayed by flow cytometry. The results indicated that both exosomes derived from imDC (imDex) and exosomes derived from mDC (mDex) could not prime T cells without DC or with imDC. The exosomes derived from mDC induced with different cytokines (LPS, TNF-alpha, CpG, CD40L) were no significant difference in concentrations but were different in effect. The immunity function of exosomes depended on CD11a, CD11b, CD11c, CD54, MFG-E8 and CD83 molecules, the effect of priming T cells is reduced when these molecules were blocked. Confocal microscopy and FACS assay showed that blocking CD11a and CD54 could inhibit exosome-targeted DC and DC-embedded exosomes. It is concluded that the exosomes target DCs through their surface molecules, therefore results in immune response of T cells.
Antigens, Neoplasm ; immunology ; Cells, Cultured ; Dendritic Cells ; cytology ; immunology ; secretion ; Exosomes ; immunology ; Humans ; K562 Cells ; Lymphocyte Activation ; drug effects ; T-Lymphocytes ; cytology ; immunology

AIM:To observe the influence of erythropoietin (EPO) on eryptosis and production of reactive oxygen species (ROS) in erythrocytes under stimulation of hydrogen peroxide (H2O2),.and to explore its related mecha-nism. METHODS:The erythrocyte suspension (1%) was cultured in vitro and divided into 3 groups:control group (C group,the culture medium was PBS),H2O2group (H group,the culture medium was PBS containing H2O2at final con-centration of 100 μmol/L) and EPO group (E group,the culture medium was PBS containing H2O2at final concentration of 100 μmol/L and EPO at final concentration of 2×104U/L). The erythrocytes were collected at 24 h and 60 h. The eryptosis was detected by flow cytometry with Annexin V staining. The production of ROS and intracellular calcium ion con-centration (Ca2+]i) were also analyzed by flow cytometry. RESULTS:The eryptosis in C group was increased as the in-cubating time extended. The eryptosis in H group was higher than that in C group (P<0.01),while that in E group was lower than that in H group(P<0.01). Meanwhile,ROS production andCa2+]iwere higher in H group than those in C group (P<0.01), but those were lower in E group than those in H group (P<0.05 or P<0.01). CONCLUSION:EPO inhibits eryptosis induced by H2O2and its mechanism may be related to antioxidant effect and change of Ca2+]i.

XueBiJing is an intravenous five-herb injection used to treat sepsis in China.The study aimed to develop a liquid chromatography-tandem mass spectrometry(LC-MS/MS)-or liquid chromatography-ultraviolet(LC-UV)-based assay for quality evaluation of XueBiJing.Assay development involved identifying marker constituents to make the assay therapeutically relevant and building a reliable one-point cali-brator for monitoring the various analytes in parallel.Nine marker constituents from the five herbs were selected based on XueBiJing's chemical composition,pharmacokinetics,and pharmacodynamics.A selectivity test(for"similarity of response")was developed to identify and minimize interference by non-target constituents.Then,an intercept test was developed to fulfill"linearity through zero"for each analyte(absolute ratio of intercept to C response,＜2％).Using the newly developed assays,we analyzed samples from 33 batches of XueBiJing,manufactured over three years,and found small batch-to-batch variability in contents of the marker constituents(4.1％-14.8％),except for senkyunolide I(26.5％).

OBJECTIVESTo explore relationship between rat brain tissues hurts of gas explosion and the expression of Protein Kinase C alpha mRNA.

METHODSBuild up rat hurt model of gas explosion. In Situ Hybridization (IDH) technique was used to test Protein Kinase C alpha mRNA. Immunohistochemical Assays (IHA) was used to determine c-fos gene protein.

RESULTSOnly a little a mount expression of PKC alpha mRNA and c-fos of the control group was detected. The expression of the cerebral cortex and hippocampus of PKC alpha mRNA 24 h, 48 h and the 48 h increased obviously, and the 48 h reached the peak of expression; (t = 4.12 P < 0.01). The expression of c-fos protein of the cerebral cortex and hippocampus started to increase obviously at 0.5 h and the 4 h reached the peak, then the strength lowered gradually and the expression level came back normal level on fifth day.

CONCLUSIONThe anoxia of brain tissues due to the gas explosion may promote the expression of PKCamRNA, and PKCamRNA could regulate the expression of the gene of c-fos. Both PKCamRNA and the gene of c-fos are involved in harmful processes to the nerve cells.

Animals ; Brain ; metabolism ; Brain Injuries ; metabolism ; Disease Models, Animal ; Explosions ; Hypoxia ; metabolism ; Protein Kinase C-alpha ; metabolism ; Proto-Oncogene Proteins c-fos ; metabolism ; RNA, Messenger ; genetics ; Rats ; Rats, Sprague-Dawley ; Tear Gases