Aim To investigate the effects of 1 7-me-thoxyl-7-hydroxyl-benzofuran chalcone(YLSC)on my-ocardial ischemia /reperfusion injury(MI /RI)by mod-ulating PI3K/Akt signaling pathway and the possible mechanisms.Methods Male SD rats were randomly
divided into sham group,model group,YLSC group, wortmannin(WM)group and YLSC +WM group(n =8).The rat model of MI /RI was established by ligation of the left anterior descending artery for 30 min fol-lowed by loosening the ligature for 2 h.After reperfu-
sion,blood samples were obtained to determine serum contents of CK-MB,LDH,NO and TNF-α.The pro-tein levels of total (t)-Akt,phosphorylated (p)-Akt and LC3-Ⅱ were detected by Western blot.Caspase-3,Beclin1 and eNOS mRNA expression was evaluated by FQ-PCR.Results YLSC pretreatment greatly re-duced serum levels of CK-MB,LDH and TNF-α,and elevated NO content.It also inhibited the expression of
caspase-3,Beclin1 and LC3-Ⅱ,while enhanced p-Akt and eNOS expression.Conclusion YLSC protects the heart against MI /RI via inhibition of apoptosis and excessive autophagy,in which protective effect is regu-lated by activation of the PI3K/Akt pathway.

Objective To investigate the efficacy and safety of secondary anti-fungal prophylaxis (SAP) in haematopoietic stem cell recipients who had a history of antecedent invasive fungal infection(IFI). Methods The patients with hematological diseases,who were scheduled to undergo haernatopoietic stem cell transplantation (HSCT) in our unit from April 2005 to July 2008, received our routine conditioning regimen. Patients,who had a history of antecedent IFI,were given SAP from the start of conditioning chemotherapy until the end of the at-risk period. We chose the effective antifungal drug that was used for antecedent IFI as the secondary prophylaxis drug. Results There were 26 patients at entry. Six patients had probably adverse events (AEs) related to the secondary prophylaxis drug during the prophylactic process and the secondary prophylaxis terminated in two patients because of AEs. The remaining patients received SAP for a medium of 75 days (range 10-212 days). Relapsing IFI occurred in four patients during SAP and in one after SAP. The rate of reLapsing IFI was 19. 2% (5/26). The median time of re]apsing IFI was day 42(range,1-146). The mortality rate among relapsed patients was 60. 0% (3/5). No risk factors that might be associated with IFI was identified by logistic regression model. Conclusion Prior IFI is not an absolute contraindication for HSCT. Secondary antifungal prophylaxis can reduce the risk of recurrent infection in patients with prior IFI, but its schedule and time of therapy need further study.

Aryl hydrocarbon receptor ( AhR) is a ligand-depend-ent transcription factor that mediates the toxicity of xenobiotic ligands like 2,3,7,8-tetrachlorodibenzo-p-dioxins(TCDDs). AhR influences tumor growth, survival, migration and invasion by regulating proliferation, apoptosis and immune metabolism of tumor cells. AhR has two ways to regulate tumor development, and ligands like polycyclic aromatic hydrocarbons( PAHs) , hal-ogenated aromatic hydrocarbons( HAHs) can induce tumorigene-sis. However, some compounds such as benzothiazole and amin-oflavone can activate AhR, which suppresses the tumor progres-sion and suggests that AhR may be a novel drug target for anti-tumor therapy. The paper discussed the role of AhR in tumori-genesis, the mechanism of the drugs targetting AhR and the sta-tus of studying AhR as a potential target in anticancer therapy.

Objective To investigate the feasibility of labeling mice spleen lymphocytes with superparamagnetic iron oxide(SPIO)and in vitro MR imaging of the labeled cells.Methods Spleen lymphocytes of 5 mice were isolated and then labeled with SPIO of 100,50,25,15,10,5 μg/ml,which was previously prepared with PLL.Prussian blue staining was performed to show the intracellular iron.Cell viability was compared among fresh,labeled and unlabeled cells.Different concentrations of mice spleen lymphocytes were screened using 3.0 T MR on T2WI,T2 * WI and SWI sequences in vitro.Cell viability was compared using independent-sample t test between groups.The MRI values among different groups were compared using one-way ANOVA.Results SPIO prepared with PLL could successfully label mice spleen lymphocytes,the optimum concentration of SPIO was 5 μg/ml.The Prussian blue staining showed intracellular blue spots and a labeling efficiency of(93.6 ± 2.1)％.Three groups of fresh,labeled and unlabeled cells showed a Trypan blue staining result of(94.8 ± 3.1)％,(88.7 ± 2.7)％,and(88.9 ±3.2)％,respectively; no statistically significant difference was found in cell viability between labeled and unlabeled lymphocytes(t =0.281,P ＞ 0.05); however,the cell viability of fresh cells were statistically significant higher than the labeled and unlabeled lymphocytes(t =8.125 and 7.253 respectively,P ＜0.05for all).Among the T2 WI,T2 * WI and SWI sequences under the same concentrations of cells,the SWI sequence was the most sensitive.Conclusions The mice spleen lymphocytes can be effectively labeled with SPIO with no impact on cell viability,and MR can be used to track these labeled cells in vitro.The SWI sequence is the most sensitive.

AIM:To observe and analyze the effect of cardiopulmonary bypass ( CPB) for 30 min on surface ultra-structure and mechanical properties of the erythrocyte membrane by atomic force microscopy (AFM).METHODS:Ten cases of elective patients in cardiac surgery were selected in the study and divided into control ( CON) group and CPB group.The central venous blood (2 mL) before surgery and 30 min after CPB was collected with heparin anticoagulation . The non-circular red blood cells were counted under a stand fluorescence microscope .AFM was used to examine the ultra-structure of the membrane surface and measure the force curve of the erythrocytes .RESULTS:The percentage of non-cir-cular red blood cells in CPB group showed no statistically significant differences as compared with CON group .AFM images showed that the significant differences of membrane surface concave and convex , evenness , particle distribution , the sur-face average roughness (Ra), the surface root mean square roughness (Rq) and cell membrane adhesion between CPB group and CON group were observed .However, the membrane deformation resilience and curve slope had no significant difference between the 2 groups.CONCLUSION:Cardiopulmonary bypass for 30 min changes the morphology and ultra-structure of the erythrocyte membrane surface , and increases the adhesion between cells .

Objective To investigate the clinical effect and safety of surgical treatment for severe, refractory hemorrhagic cystitis (HC) after allogeneic hematopoietic stem cell transplantation (allo-HSCT).Methods Patients with severe HC, who were admitted to Peking University Institute of Hematology from January 2010 to December 2015, were enrolled in this study.All patients were refractory to medical managements and received bladder surgery including mucous electrocoagulation and/or selective transcatheter arterial embolization.Results A total of 17 patients with severe HC (grade Ⅲ, n=5;grade Ⅳ, n=12) received surgical treatment, including 11 embolization and 18 mucous electrocoagulation.The median time from allo-HSCT to surgery was 107 d (46-179 d) and 75 d after HC.Eight patients only received embolization.Four patients only received mucous electrocoagulation.Five patients were given combined embolization and electrocoagulation.HC was cured in 11 patients, improved in 1 patient, which corresponded to a response rate of 70.6% and complete remission rate of 64.7%.Five patients didn′t respond to these methods.In patients with response, macroscopic hematuria disappeared 3 to 10 days after treatments whereas microscopic hematuria vanished after 25 to 32 days.Both procedures were well tolerated and no severe adverse effects were observed.Conclusion Surgery of bladder mucous electrocoagulation and/or selective arterial embolization are safe and effective for severe HC.

OBJECTIVETo explore the subcellular localization of ataxin-3 and the effect of polyglutamine (polyQ) expansion mutation on the morphology of mitochondrion, golgi apparatus and endoplasmic reticulum.

METHODSTransient transfection was employed to build cell models expressing wild-type or mutant ataxin-3 proteins. Indirect immunofluorescence was applied to identify markers of organelle membrane. The results were observed under a laser scanning confocal microscope.

RESULTSNo co-localization was observed for ataxin-3 protein and mitochondrial marker TOM20, but the percentage of cells with mitochondrial fragmentation has increased in cells expressing mutant ataxin-3 (P<0.05). No co-localization was observed for ataxin-3 protein and golgi marker GM130, and mutant ataxin-3 did not cause golgi fragmentation. Wide type and polyQ-expanded ataxin-3 both showed partial co-localization with ER marker calnexin. The latter showed more overlap with calnexin, and the overlapping signals were mostly located in the places where aggregates were situated.

CONCLUSIONPolyQ-expanded ataxin-3 protein may indirectly affect the integrity of mitochondria, but may cause no effect on the structure and functions of golgi apparatus. Endoplasmic reticulum may be another place where extended ataxin-3 protein can induce cytotoxicity in addition to the nucleus.

Ataxin-3 ; Cytoplasm ; genetics ; metabolism ; Endoplasmic Reticulum ; genetics ; metabolism ; HeLa Cells ; Humans ; Machado-Joseph Disease ; genetics ; metabolism ; Mitochondria ; genetics ; metabolism ; Nerve Tissue Proteins ; genetics ; metabolism ; Nuclear Proteins ; genetics ; metabolism ; Protein Transport ; Repressor Proteins ; genetics ; metabolism

In order to remove the endotoxin from the blood of endotoxemia patients, we prepared a new adsorbent with heparin space arm and polymyxin B (PMB) ligand. The carrier of chloromethyl polystyrene resin was activated and heparin space arm was grafted, and then PMB ligand was immobilized onto adsorbent with glutaraldehyde. We employed in vitro FITC-lipopolysaccharide (FITC-LPS) static adsorption to characterize the adsorption properties on the adsorbent, and conducted in vitro lipopolysaccharide (LPS) static adsorption to measure quantitavely the adsorption capacity and rate, and then evaluated the blood compatibility. The in vitro static adsorption indicated that the adsorbent had the removal rate of LPS above 70% with the adsorption equilibrium time for 2 hours. Blood compatibility experiment showed that the adsorbent had little negative effects on blood cells and plasma protein, and their adsorption rates were less than 10% for hemocytes and 20% for plasma protein respectively. This adsorbent exhibited high selectivity, high adsorption capacity and good biocompatibility, and presented a promising clinical application in the treatment of endotoxemia.
Adsorption ; Endotoxemia ; therapy ; Endotoxins ; isolation & purification ; Hemofiltration ; instrumentation ; methods ; Heparin ; chemistry ; Humans ; Ion Exchange Resins ; chemistry ; Ligands ; Polymyxin B ; chemistry ; Sorption Detoxification ; methods

Methyl (S)-4-(6-amino-9H-purin-9-yl)-2-hydroxybutanoate (DZ2002) is a potent reversible inhibitor of S-adenosyl-L-homocysteine hydrolase (SAHH). Due to its ester structure, DZ2002 is rapidly hydrolyzed in rat blood to 4-(6-amino-9H-purin-9-yl)-2-hydroxybutyric acid (DZA) during and after blood sampling from rats; this hampers accurate determination of the circulating DZ2002 and its acid metabolite DZA in rats. To this end, a method for determining the blood concentrations of DZ2002 and DZA in rats was developed by using methanol to immediately deactivate blood carboxylesterases during sampling. The newly developed bioanalytical assay possessed favorable accuracy and precision with lower limit of quantification of 31 nM for DZ2002 and DZA. This validated assay was applied to a rat pharmacokinetic study of DZ2002. After oral administration, DZ2002 was found to be extensively converted into DZA. The level of systemic exposure to DZ2002 was significantly lower than that of DZA. The apparent oral bioavailability of DZ2002 was 90％–159％. The mean terminal half-lives of DZ2002 and DZA were 0.3–0.9 and 1.3–5.1 h, respectively. The sample preparation method illustrated here may be adopted for de-termination of other circulating ester drugs and their acid metabolites in rodents.

Objective: To understand emotional and behavioral problems of children aged 3-6 years, and to explore the role of parenting style in the development of those problems. Methods: A total of 2 278 children from 11 public kindergartens in Tongling City from April to June 2018 were selected by cluster sampling method. The questionnaire was made up by parents. The questionnaire mainly included: children, basic information of parents and children, children’s psychology and behavior, and parents’ education style, etc. Results: Among 2 278 children, 192(8.43%) had abnormal emotional symptoms, 214 (9.39%) had conduct problems, 376(16.50%) had hyperactivity problems, 537(23.57%) had peer problems, 233(10.2%) had abnormal total difficulty scores and 254(11.15%) had prosocial behaviors. Gender, age, health status of the child, second-hand smoke exposure of the baby, parents’ education level, family economic conditions, and parents’ education mode are all the influencing factors of children’s emotion and behavior(P<0.05). Logistic analysis showed that father’s support participation(OR=0.96, 95%CI=0.95-0.98), mother’s support participation (OR=0.94, 95%CI=0.92-0.95), mother’s hostility compulsion (OR=1.08, 95%CI=1.06-1.10) and 3-6-year-old children’s abnormal mood and behavior were correlated(P<0.01). Conclusion Parental support and maternal hostile are related to emotional and behavioral problems of 3-6-year-old children.