Objective To investigate the preventive effect of complete Freund's adjuvant induced thymocyte apoptosis on NOD mice with type 1 diabetes.Methods Forty-two female NOD mice of 3 weeks old were randomly divided into complete Freund's adjuvant group(CFA)and phosphate buffer saline group(PBS)(21 each).Animals of CFA group received injection of 50?l CFA at hind foot-pad,and those in PBS group received 50?l PBS at the same location.Five mice of each group were sacrificed at the 6th and 12th week,respectively,and the remainders of each group were sacrificed at the 30th week for the examination of insular ? cell apoptosis,thymocytes apoptosis,insulitis severity and diabetes incidence.Results Both the insulitis severity score and the ? cell apoptosis declined(P

Abstract Ten compounds were isolated from the stems of Viburnum plicatum Thunb.vat.tomentosum Miq.and were identified as 3,4,5-trimethoxyphenyl-l-O-β-D-glucopyranoside (1),isotachioside (2),tachioside (3),koaburaside (4),glucosyringic acid (5),lupeol (6),ursolic acid (7),chlorogenic acid (8),5-O-caffeoyl quinic acid butyl ester (9),and tricin-7-O-β-D-glucoside (10),respectively.Compounds 1-10 were isolated from this plant for the first time.

Objective To randomly compare the therapeutic effect and safety between Levetiracetam (LEV) and Phenobarbital (PB) in the treatment of neonatal seizures.Methods A total of 61 infants with acute convulsion were randomly divided into 2 groups:LEV group (n =30) and PB group (n =31) during January 2013 to December 2014 in Urumqi Children's Hospital.All neonates received routine management including etiology treatment and adverse drug reaction monitoring.In the LEV group,subjects received oral formulation of LEV with initial loading dose 30 mg/kg,followed by 15 mg/kg twice a day.If the seizures were not controlled completely,PB treatment was added until seizures were completed controlled.If seizures were controlled quickly,the dose of PB was gradually reduced and LEV was used as monotherapy.The subjects in PB group received intramuscular or intravenous injection of PB with 10 mg/kg as the first dose,then 5 mg/(kg · d) oral PB was administered,if seizures were not controlled,LEV treatment was added,then dose of PB was gradually reduced until seizures were controlled completely,and then patients were switched to LEV monotherapy gradually.The drug adverse reactions were observed.Results (1) After LEV or PB monotherapy,66.7％ (20/30 cases) and 54.8％ (17/31 cases) of the subjects obtained sustainable seizure free respectively.Although,there was a higher control ratio in LEV group,but no significant difference was observed between the 2 groups (P ＞0.05).(2) LEV group (16/30 cases,53.33％) had higher rapid seizure control ratio with seizure controlled within 24 h after first dosage administration than that of PB group (8/31 cases,25.80％),and there was significant difference (x2 =4.841,P =0.028).Further more,if adding the cases who had to change to use another comparative one (LEV or PB) due to their seizures failure control with the first one treated,LEV group (21/44 cases,47.72％) still had higher rapid seizure control ratio in total patients than that of PB group(10/41 cases,24.39％),and there was significant difference (x2 =4.988,P =0.026).(3) Eight cases who changed to LEV after PB as the first treatment drug failed obtained sustainable seizure free.(4) One case in PB group with transient urinary retention was observed but the symptom disappeared 36 h after PB withdrawal,and no significant drug adverse reaction was observed in LEV group.Conclusion LEV is more rapid and safe for seizure control of neonates than PB.

Objective To investigate the subtype distribution and changing trend of human immunodeficiency virus (HIV)-1 strains among men who have sex with men (MSM) during 2005-2011 in Beijing.Methods Five serial cross-sectional surveys of MSM were conducted in the year of 2005-2006,2007,2008,2009,and 2010-2011 in Chaoyang district of Beijing.Whole blood samples were collected and then RNA was extracted.HIV-1 gag gene was characterized by reverse transcriptase and nested polymerase chain reaction (RT-PCR) amplification,DNA sequencing,and phylogenetic analysis of viral sequences to determine the HIV-1 subtypes.Results Phylogenetic analysis of the sequences revealed that the predominant subtypes of HIV-1 gag gene included subtype B,CRF01_AE and CRF07_BC.And CRF15_01B was detected from the year of 2008.In addition,significant changes of the distributions of subtypes and CRFs occurred from 2005 to 2011 in HIV+ MSM.Subtype B showed a significant decreased trend,while the proportions of CRF01 _AE and CRF07_BC significantly increased in the 7-year period,particularly that of CRF01_AE.Conclusions The substantial changes are observed in the diversity of HIV-1 strains circulating among MSM in Beijing during a 7-year period.

This study was designed to determine the impact of chrysoeriol on proliferation and cell cycle progression in the human multiple myeloma cell lines RPMI 8226 and KM3, and its related molecular mechanisms. Chryseoriol was identified by using the phosphorylated AKT-specific cytoblot high throughput assay. CCK-8 assay was employed to examine the growth inhibition rate and IC(50) (48 h) in peripheral blood mononuclear cells (PBMNCs), RPMI 8226 and KM3 cells treated with chrysoeriol at various concentrations. Cells were labeled with 5-6-carboxyfluorescein diacetate succinimidyl ester (CFSE), and the proliferation dynamics was detected by flow cytometry and analyzed with ModFit software. The cell cycles of RPMI 8226 and KM3 cells were measured by flow cytometry when the IC(50) concentration of chrysoeriol was adopted. The alterations in cell-cycle related proteins (Cyclin B1, Cyclin D1, p21) and proteins in PI3K-AKT-mTOR pathway were determined by Western blot analysis. The results showed the proliferation of multiple myeloma cells was significantly inhibited by chrysoeriol, resulting in cell cycle arrest in G(2)/M phase. Chrysoeriol could significantly reduce the expression of p-AKT (s473) and p-4eBP1 (t37/46) protein, meanwhile enhanced Cyclin B1 and p21 protein expression. Similar effects were not observed in PBMNCs from normal donors. It was concluded that chrysoeriol was a selective PI3K-AKT-mTOR pathway inhibitor. It restrained the proliferation of human multiple myeloma cells, but didn't affect proliferation of PBMNCs from normal donors. It might exhibit the cell cycle regulatory effect via the inhibition of PI3K-AKT-mTOR signal pathway.

Herein we reported a case of follicular lymphoma with 50.26% clonal malignant lymphocytes and 50% tumor cells positive for the immunoglobulin heavy chain gene and B-cell lymphoma 2 gene (IGH-BCL2). To determine whether endothelial cells (ECs) within the tumor share the feature of advanced malignancy, we isolated and purified the ECs from the tumor by using the immunomagnetic beads conjugated with a monoclonal antibody against CD34, a surface marker of ECs. Thereafter, we identified ECs according to their morphology and found that ECs presented consistently flat and elongated appearance with a lot of Weibel-Palade bodies in the cytoplasm. Results of flow cytometry confirmed that ECs isolated from the follicular lymphoma expressed high level of both vWF and CD34 and the purity of the ECs fraction was more than 90%. Additionally, we used FISH to check chromosomal aberration in the purified ECs and found that some of the ECs had only one fusion signal for the green IGH probe and the red BCL2 probe in contrast to typical t(14;18)(q32;q21) translocation with two fusion signals. This phenomenon was also observed in the tumor cells. It might be a different breakpoint of IGH in this case, which induced the loss of the fusion signal, indicating t(14;18)(q32;q21) translocation. The positive cells accounted for 18% of the isolated ECs from the tumor, indicating that a proportion of ECs from follicular lymphoma had the same chromosome aberration as the neoplastic cells.

Objective To investigate the efficacy and safety of Levertiracetam (LEV) in treating the neonates with intractable seizure, those who had under gone failed Phenobarbital (PB) treatment previously switched to or added LEV treatment currently.Methods Totally 14 neonates,designed as intractable seizure by clinical data and video electroencephalography(VEEG) and failed to PB treatment were enrolled in the study, and all neonates were switched to LEV or LEV + PB treatment.The initial loading dose of LEV was 30 mg/kg, followed by 15 mg/kg twice a day if symptoms were controlled 8-12 h,if not, followed by 30 mg/kg once.All neonates were switched to LEV monotherapy after the symptoms were controlled 48-72 h,if the symptoms could not be controlled by combined therapy of PB and LEV after 72 h, other therapies were administered.Electrocardiogram breath synchronous monitoring was performed during the first 72 h treatment.VEEG was performed during 1-3 months follow-up.Results (1) The symptoms of 8 (57.14％) out of 14 cases were completely controlled,2 neonates(14.29％) reduced seizure more than 50％ ,4 neonates(28.57％) failed to LEV or LEV + PB treatment,as a result,all of those neonates were switched to other treatments.(2) No drug adverse effect was observed.(3) One neonate died of hypoxic-ischemic encephalopathy combined with multiple organ failure during follow-up period, 7 cases were seizure-free with normal VEEG, 5 cases were switched to or added other antiepileptic drugs because of uncontrolled symptoms, and one neonate discontinued the follow-ups.Conclusions The high efficiency and safety of LEV for the treatment of the newborn seizures were proved by small samples of patients.And currently there is no evidence to prove PB might increase neuronal excessive apoptosis of the brain and the cognitive impairment, and more clinical researches are needed to promote LEV as a gleam of rescue medications of neonatal seizure as soon as possible.

The aim of this study was to evaluate the safety and efficiency of a novel, oncolytic adenovirus mutant M1 administered in conjunction with immunosuppressive agents. Animal models were established by administering purified M1 either intravenously or retroperitoneally. At different time points, blood samples were taken from the mice for testing of liver and renal function. Microscopic examination of the liver was performed to observe pathological changes. Immunohistochemical analyses were used to evaluate the expression of the adenovirus in the liver. Lymphocyte recruitment to the liver and the activation of adenovirus specific T cells were also analyzed. No signs of general toxicity were observed, but transient increases in ALT and Scr were observed following the administration of M1. Microscopic examination revealed a mild inflammatory response in the liver. Compared to intravenous injection, higher expression levels of adenoviral proteins were observed after retroperitoneal injection. Combined treatment with cyclosporine A resolved the liver and kidney dysfunction and increased the concentration of the adenovirus in the liver. The use of the novel oncolytic adenovirus mutant M1 in vivo is safe, and the combined administration of M1 with immunosuppressive agents was able to enhance the effectiveness and safety profile of M1.

The aim of this study was to evaluate the safety and efficiency of a novel, oncolytic adenovirus mutant M1 administered in conjunction with immunosuppressive agents. Animal models were established by administering purified M1 either intravenously or retroperitoneally. At different time points, blood samples were taken from the mice for testing of liver and renal function. Microscopic examination of the liver was performed to observe pathological changes. Immunohistochemical analyses were used to evaluate the expression of the adenovirus in the liver. Lymphocyte recruitment to the liver and the activation of adenovirus specific T cells were also analyzed. No signs of general toxicity were observed, but transient increases in ALT and Scr were observed following the administration of M1. Microscopic examination revealed a mild inflammatory response in the liver. Compared to intravenous injection, higher expression levels of adenoviral proteins were observed after retroperitoneal injection. Combined treatment with cyclosporine A resolved the liver and kidney dysfunction and increased the concentration of the adenovirus in the liver. The use of the novel oncolytic adenovirus mutant M1 in vivo is safe, and the combined administration of M1 with immunosuppressive agents was able to enhance the effectiveness and safety profile of M1.
Adenoviridae ; genetics ; immunology ; Animals ; Female ; Kidney ; immunology ; virology ; Liver ; immunology ; virology ; Mice ; Mice, Inbred BALB C ; Mutation ; genetics

Herein we reported a case of follicular lymphoma with 50.26% clonal malignant lymphocytes and 50% tumor cells positive for the immunoglobulin heavy chain gene and B-cell lymphoma 2 gene (IGH-BCL2). To determine whether endothelial cells (ECs) within the tumor share the feature of advanced malignancy, we isolated and purified the ECs from the tumor by using the immunomagnetic beads conjugated with a monoclonal antibody against CD34, a surface marker of ECs. Thereafter, we identified ECs according to their morphology and found that ECs presented consistently flat and elongated appearance with a lot of Weibel-Palade bodies in the cytoplasm. Results of flow cytometry confirmed that ECs isolated from the follicular lymphoma expressed high level of both vWF and CD34 and the purity of the ECs fraction was more than 90%. Additionally, we used FISH to check chromosomal aberration in the purified ECs and found that some of the ECs had only one fusion signal for the green IGH probe and the red BCL2 probe in contrast to typical t(14;18)(q32;q21) translocation with two fusion signals. This phenomenon was also observed in the tumor cells. It might be a different breakpoint of IGH in this case, which induced the loss of the fusion signal, indicating t(14;18)(q32;q21) translocation. The positive cells accounted for 18% of the isolated ECs from the tumor, indicating that a proportion of ECs from follicular lymphoma had the same chromosome aberration as the neoplastic cells.
Adult ; Cells, Cultured ; Chromosomes, Human, Pair 14 ; genetics ; Chromosomes, Human, Pair 18 ; genetics ; Endothelial Cells ; Female ; Humans ; Lymph Nodes ; physiopathology ; Lymphoma, B-Cell ; genetics ; Recombinant Fusion Proteins ; genetics ; Translocation, Genetic ; genetics