Notch signaling can control T cell development and differentiation and lead to acute T cell lymphoma/leukemia (T-ALL). Most Notch1mutations in human T-ALL are the HD domain and the PEST domain. Aberrant Notch1activation can induce T-ALL by PI3K/Akt, mTOR or/and NF-κB pathways. Some recent reports suggested that Notch signaling could not only control T cell development,but also has a role in acute myeloid leukemia (AML) and Graft-versus-host Disease (GVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT).Moreover,Notch signaling can regulate the expansion of HSC as well as generate increased numbers of progenitor cells which are capable of rapid repopulation to improve HSC homeostasis and hematopoietic recovery after allo-HSCT.

Objective To explore the effect of erythropoietin(EPO) on Bcl-xl expression in hippocampal CA1 subregion and cognizing function in rats with cerebral ischemia-reperfusion(IR).Methods Male SD rats were randomly separated into sham-operated group,IR group and EPO group,and the IR models were made.At 3 h before IR models made,rHu-EPO and saline were injected into rat lateral ventricles in EPO group and IR group,respectively,with help of stereotaxic coordinates.Bcl-xl protein expression of Hippocampal CA1 subregion was detected by immunohistochemistry at 24 h after operation.The learning and memory abilities were examined by electricity maze at 4 weeks after operation.Results Compared to sham-operated group,Bcl-xl protein expression in EPO group and IR group were obviously decreased,but EPO group was significantly increased than IR group(all P

Objective: To study the protective roll of neuregulin-1 (NRG-1) on high glucose caused myocardial cell injury in rat’s embryo H9c2 myocardial cells with its mechanism. Methods: Cultured rat’s embryo H9c2 myocardial cells were divided into 5 groups:①Control group,②High glucose (HG) group, containing glucose 33 mmol/L,③HG+NRG-1 10 nmol/L (N1) group,④HG+NRG-1 50 nmol/L (N2) group and⑤HG+NRG-1 250 nmol/L (N3) group. All cells were treated for 24 hours. Myocardial cell survival rate was measured by CCK-8 method, intracellular reactive oxygen species (ROS) level and the apoptosis rate were detected by lfow cytometry, enzymes activities of CK, LDH, SOD and MDA content were examined, proteins expressions of NRG-1 receptor as ErbB2 and ErbB4 were assessed by Western blot analysis. NRG-1 treated myocardial cell apoptosis in type II diabetic cardiomyopathy rats was observed by Tunel staining. Results: Compared with HG group, from N1 group to N3 group, myocardial cell survival rates were increased from (63.33±3.56) %to (85.88±4.55) %, ROS levels decrease form (33.75±4.23) % to (15.88±4.55) %, apoptosis rates reduced from (36.44±4.86) % to (14.77±4.21) %, receptor expressions of ErbB2 was elevated from (0.26±0.04) to (0.84±0.03) and ErbB4 was elevated from (0.39±0.03) to (0.72±0.04), allP<0.05; enzymes activities of CK, LDH and MDA content were gradually decreased and SOD activity was gradually increased, allP<0.05. NRG-1 treated myocardial cell apoptosis in type II diabetic cardiomyopathy rats was also obviously reduced. Conclusion: NRG-1 could increase the survival rate and reduce the oxidative stress injury and apoptosis of cultured rat’s embryo H9c2 myocardial cells in HG condition which might be related to NRG-1 binding to ErbB2/ErbB4 molecules in the cells.

Objective To explore the relapse,therapeutic effect,risk and prognostic factors of the pulmonary invasive fungal disease(IFD)in patients with a history of pulmonary IFD following allogeneic hematopoietic stem cell transplantation(allo-HSCT).Methods Fourteen patients with a history of pulmonary IFD received allo-HSCT between March 2005 and October 2006.Before transplantation,10 patients obtained complete remission(CR)and 4 partial remission(PR)after antifungal therapy.Antifungal prophylaxis was initiated on the first day of the conditioning therapy.Logistic regression models were used for multivariable analyses.Results The relapse rate of pulmonary IFD after allo-HSCT was 71.43%(10/14).Of 10 patients in CR,6 relapsed and all four patients in PR relapsed.Seven patients relapsed less than 3 months and 3 relapsed between four and six months after transplantation.Among the 10 patients with a history of IFD who relapsed after transplantation,9 patients received antifungal therapy,4 obtained CR,2 PR again and the other 3 didn't obtain remission.The effective rate of anti-fungal therapy was 66.67% and the pulmonary IFD-related mortality was 35.71%(5/14).There was no significant difference between amphotericin B,itraconazde and voriconazole for antifungal prophylaxis in patients with a history of pulmonary IFD(P=0.122).No risk and prognostic factors of the pulmonary IFD was identified by multivariable analyses.Conclusion Pulmonary was not an absolute contraindication for allo-HSCT,and patients with a history of pulmonary IFD had a higher relapse rate and transplant-related mortality after receiving allo-HSCT.

Objective To investigate the trend in incidence, causative drugs, clinical types and treatment of drug eruption. Methods Clinical data were collected from 922 inpatients with drug eruption in Huashan Hospital, Fudan University from January 2009 to December 2013, and analyzed retrospectively. Results From 2009 to 2013, the percentage of inpatients with drug eruption among all inpatients in the Department of Dermatology in a given year varied from 9.45% to 10.01%, and the percentage of inpatients with severe drug eruption among inpatients with drug eruption from 17.45% to 28.24%. Of the 922 cases, 371 (40.2%)were caused by single drugs, and 551 (59.8%)by multiple drugs. Among the 371 cases of drug eruption caused by single drugs, the top five causative drugs were traditional Chinese medicine(72 cases), cephalosporins(38 cases), amoxicillin(27 cases), antipyretic analgesics(26 cases)and tetanus antitoxin (24 cases)in 278 cases of non-severe drug eruption, antiepileptic agents (33 cases), allopurinol (28 cases), antipyretic analgesics (7 cases), cephalosporins (6 cases)and traditional Chinese medicine (6 cases)in 93 cases of severe drug eruption. Of the 922 patients, 422 (45.8%)presented with maculopapular eruption, 259 (28.1%)with urticaria, 135(14.6%)with Stevens-Johnson syndrome, 49(5.3%)with toxic epidermal necrolysis, 33(3.6%)with drug reaction with eosinophilia and systemic symptoms (DRESS), and 7 (0.8%)with acute generalized exanthematous pustulosis (AGEP). A total of 791 (85.8%)patients with drug eruption received glucocorticoid treatment. The dose of glucocorticoids was(47.61 ± 12.07)mg prednisone equivalent per day in 550 patients with non-severe drug eruption, and (73.10 ± 18.23)mg prednisone equivalent per day in 221 patients with severe drug eruption. Totally, 110 (11.0%) patients with drug eruption were treated with combined intravenous immunoglobulin (IVIG)because of poor response to glucocorticoids alone. Of 224 patients with severe drug eruption, only 2 (0.9%)died. Conclusions Carbamazepine and allopurinol are the main causative drugs for severe drug eruption, while traditional Chinese medicine is the first causative drug for non-severe drug eruption. From 2009 to 2013, the annual mortality of severe drug eruption decreased considerably.

Objective To observe the influence of acupuncture treatment on parturition process.Methods 545 pregnant women delivered in our hospital were selected,excluding those with cesarean section indication.On voluntary principle and randomized principle,primipara aged from 22 to 30 who agreed with natural labor were divided into two groups:observation group and control group.Pregnant women in observation group were received acupuncture treatment during latent phase.The following indexes of the two groups were recorded and compared:labor time of the first stage and the second stage,the case for inertia of uterus,cesarean sections,postpartum hemorrhage amount and Apgar score of new-born.Results The labor time of the first stage and the second stage of the control group were (178.55 ± 56.87) min and (130.70 ± 77.22) min,and which of the observation group were (53.87 ±22.33) min and (33.25 ± 15.55) min,there was significant differenec between the two groups(t =3.97,4.11,all P ＜0.05).The differences in the pilot failed to cesarean section rate(14.2％ and 13.6％),postpartum hemorrhage and the perinatal outcome were not significant between the two groups.Conclusion Acupuncture and moxibustion can accelerate labor.

Objective: To explore the effect of salvianolate combined with the conventional therapy on acute ischemic stroke and observe the influence on serum inflammatory cytokines of interleukin-6(IL-6).Methods: According to the random number table, 70 patients were randomly divided into the observation group (n =35) and the control group (n =35), and both were given the conventional therapy for acute ischemic stroke.The observation group was given intravenous injection of 200mg salvianolate in 250ml normal saline once a day additionally.The treatment course was 2 weeks.Another 30 persons with physical examination were in the healthy control group.The neurologic damage deficiency score (NIHSS score) was evaluated after the 3-, 7-,10-and 14-day treatment in the groups, the serum IL-6 in 24 h after onset, and after the 3-, 7-,10-and 14-day treatment was detected and compared with that in the healthy control group.Results: After the 7-day treatment, NIHSS score in the observation group decreased significantly when compared with that on admission (P＜0.05), and remained the decreasing trend.After the 10-day treatment, NIHSS score in the control group decreased significantly when compared with that on admission (P＜0.05).After the 7-day treatment, NIHSS score in the observation group was lower than that in the control group (P＜0.05).Compared with that in the healthy control group, the serum level of IL-6 in the observation group and the control group was higher in 24 h of admission (P＜0.05).The serum level of IL-6 in the observation group decreased after the 7-day treatment, and was similar to that in the healthy control group after the 14-day treatment (P＞0.05).The serum level of IL-6 in the control group decreased after the 10-day treatment, while was higher than that in the healthy control group during the whole study period (P＜0.05).The serum level of IL-6 in the observation group was lower than that in the control group after the 7-day treatment (P＜0.05), and the peak value in the observation group was notably lower than that in the control group (P＜0.05).Conclusion: Salvianolate combined with the conventional therapy can effectively decrease the NIHSS score and the content of IL-6 in the patients with acute ischemic stroke, which shows better effect than the conventional therapy alone.

Objective To explore the possible effects of methyl methanesulfonate sensitive 2(MMS2)in the process of angiotensin Ⅱ inducing differentiation of neural stem cells (NSCs) into dopaminegic phenotype neurons. Methods NSCs were isolated from the brain of newborn rats and were cultured in the serum-free medium.Identification of neural precursor cells was done by Nestin immunocyt ochemical staining. Then the second generation of NSCs was divided into the following six groups: A, control; B, AⅡ; C, AT1 antagonist ZD7155; D, ZD7155+AⅡ; E, AT2 antagonist PD123319; F, PD123319+AⅡ. The detection of expression of MMS2 and TH mRNA level was done by real-time PCR. The silence of the expression of MMS2 in NSCs was brought about via the transfection of MMS2-siRNA, and then the NSCs were induced to differentiate into dopaminegic neurons. The expression of TH mRNA level in the cells of the groups after transfection was detected by real-time PCR. Results Nestin-positive cells were observed in suspended growth in the medium.Real-Time PCR revealed that the MMS2 and TH mRNA expression of group B and D were significantly higher than that of the control group(P<0.05), There was no significant difference in MMS2 and TH mRNA expression between group C, E, F and the control, respectively. Conclusion AⅡ increased the expression of MMS2 mRNA in NSCs and induced the differentiation of NSCs into DA neurons via AT2 recepter. MMS2 may play important roles in the process of angiotensin Ⅱ inducing NSCs to differentiate into dopaminergic neurons.

Objective To investigate the morbidity,clinical manifestations,and imageology characteristics,and the influencing factors of severe cyclosporine A(CsA)-related neurotoxicity(SNCT)in the patients after allogenic hematopoietic stem cell transplantation(allo-HSCT).Methods Finding of SNCT was carried out in 164 allo-HSCT recipients from January 2003 to June 2006.Clinical characteristics were analysed,including precursory symptoms and clinical manifestations.Associations between the onset of SNCT with blood CsA levels,age,transplant types,human leucocyte antigen(HIJA)matching,conditioning regimens,antihuman thymocyte globulin(ATG)used in the prevention and treatment for graft-versus-host disease(GVHD)and intravenous corticosteroid used for acute GVHD were analyzed.Statistical analysis was performed with Binary Logistic Regression using SPSS/PC version 11.0.Results Thirteen patients(7.93%)were identified to have SNCT,including seizures(n=8,4.88%),paralysis(n=6,3.66%),coma(n:2,1.22%),cerebllar ataxia(n=3,1.83%)and chondrioid encephalomyopathy (n=1,0.61%).All the patients had precursory symptoms prior SNCT including headache(n=8),agitation(n=4)and hypertension(n=6).Magnetic resonance imaging(MRI)performed in twelve patients after SNCT showed that eleven patients had signal abnormalities in cerebral cortex and cerebral white matter.Six patients examined with computerized tomography(CT)had no abnormal findings.After extenuation or withdrawal of CsA.ten patients had complete recovery.two had partial recovery and one died of SNCT.Simple effect analysis of Binary Logistic Regression showed that the associations between the onset of SNCT with blood CsA levels.transplanta types.HLA matching.ATG used in the prevention and treatment for GVHD and intravenous corticosteroid used for acute GVHD were of statistical significance.The multiple effect analysis of Binary Logistic Regression showed that the associations of the onset of SNCT with blood CsA levels and ATG used had statistical significance and the odds ratio(OR)was 1.007(P=0.006) and 6.727(P=0.030),respectively.Conclusions 91.67%of the allo-HSCT recipients with SNCT have MRI abnormalities.High blood CsA levels and the use of ATG Call elevate the risk of the occurrence of SNCT.

Objective To investigate the impact of auto and allogenic mesenchymal stem cells (MSC) transplantation on hematopoietic reconstitution. Methods MSC from auto, donor bone marrow or embryonic tissue were cultured and expanded in vitro in the serum culture system. Five patients received hematopoietic stem cell transplantation (HSCT) were investigated. Case 1 of systemic lupus erythematosus and Case 2 of non-hodgkin' s lymphoma (NHL) received auto MSC transplant before auto-HSCT. Case 3 of paroxysmal nocturnal hemoglobinuria received HLA-identical allogenic MSC transplant before HLA-identical allo-HSCT.Case 4 of chronic myelocytic leukemia and Case 5 of NHL had delayed hematopoietic reconstitution (129th and 78th day, respectively) after allo- and auto-HSCT, respectively, and received MSC from embryonic tissue.Results Case 1, 2 and 3 had no manifested side effects after MSC transplantation combined with HSCT.Neutrophil count of case 1, 2, and 3 were over 0.5 ×109/L at 1st, 10th and 10th day, respectively, platelet count were over 20 ×109/L at 1st, 8th and 33th day, respectively, and agranulocytosis at Ost, 7th and 12th day, respectively. The treatment of embryonic tissue MSC transplant was confirmed to fail for Case 4 and 5.Conclusion The time of MSC transplant has a great impact on hematopoietic reconstitution. MSC transplantation and HSCT performed simultaneously can improve hematopoietic reconstitution. However, the impact of MSC on patients with delayed hematopoietic reconstitution after HSCT needs further study.