Background Poly(adenosine diphosphate-ribose) polymerase 1 (PARP-1) plays an important role in the pathogenesis of diabetic retinopathy (DR),and Notch1 signal pathway is one of the important signal transduction pathways in the organism which may antagonize retinal vascular diseases.However,if Notch1 signaling pathway is involved in pathogenesis of DR has not been confirmed yet.Objective This study was to investigate the expressions of Notch1,Dll4,PARP-1,Akt,nuclear factor-κB (NF-κB) and caspase-3 in the retina of diabetic mouse model and retinal vascular endothelial cells (RVECs) under the high glucose.Methods The expressions of Notch1,Dll4,PARP-1,Akt,NF-κB and caspase-3 in the retina of diabetic mouse models were investigated using immunochemistry and Western blot method after the diabetic mouse models were established.And these proteins were detected in retinal RVECs under the high glucose by Western blot.Results The expressions of Notch1,Dll4 and phosphorylated Akt (p-Akt) in retinas reduced significantly and simultaneously companied with increases of PARP-1 and caspase-3 in diabetic mice compared with normal mice (all at P＜0.05).However,no obvious change was found in the expression of NF-κB (P＞0.05).Expressions of Notch1 and p-Akt in RVECs increased with the increase of glucose concentration,but expressions of cleaved PARP-1 and caspase-3 decreased,especially in the 30 mmol/L group,showing significant differences in comparison with the normal control group (all at P＜0.05).But no altering of NF-κB expression was seen in the mice with diabetes mellitus.Conclusions The expressions of cleaved-PARP-1 and caspase-3 in the retinas is up-regulated,but the expressions of Notch1 and p-Akt are down-regulated in diabetic mice.

Objective To study the effect of Yuzhenxifeng Decoction on the brain ferritin in PD mouse models .Methods All ex‐perimental animals were devided into 4 groups:the control group ,the model group ,the positive drug group and TCM group .Prepare PD model mice with MPTP ,then use the immunohistochemical staining technique to observe the change of expression of Fn .Results the results showed that compared with the model group ,movement coordination disorder of rats in TCM group were relieved ;the Fn level of the model group on 6th ,13th ,20th were higher than control group(P<0 .05) ,and were 2 .21 times ,1 .15 times and 0 .36 times higher respectively .Compared with model group mice ,expression of Fn were enhanced in the treatment group .Conclusion Yuzhenxifeng Decoction can improve the expression of Fn in the brain ,which provide the basis for further study on mechanism of the treatment of Parkinson′s disease .

Objective To compare the efficacy and safety between Chinese generic imatinib (Xinwei(R),Jiansu Hansoh Pharmaceutical Group Co.,Ltd.) versus branded imatinib (Glivec(R),Novartis) in patients with newly-diagnosed chronic myeloid leukemia in chronic phase (CML-CP).Methods Patients with newly diagnosed CML-CP were enrolled and assigned to receive either Xinwei or Glivec at an initial dose of 400 mg/d according to patients' financial capability.The efficacy and adverse effects were evaluated.Results From January 2014 to September 2015,145 eligible patients were assigned to Xinwei (n =89) or Glivec (n =56) group.All patients were treated and followed up at least 3 months.At 3 months,the complete response rates were 95.5％ (85/89) and 100％ (56/56),major cytogenetic response rates were 74.2％ (66/89) and 80.4％ (45/56),and the proportions of achieving BCR-ALBIS ≤ 10％ were 76.1％ (67/88) and 82.1％ (46/56) in Xinwei and Glivec groups respectively (all P ＞0.05).With a median follow-up of 12 months,2 patients in each group progressed to accelerate or blast phase.Hematologic and non-hematologic side effects were similar between the 2 groups.Conclusions Early hematological,cytogenetic and molecular responses between Xinwei and Glivec are comparable in newly-diagnosed CML-CP patients.The progression rate and side effects are also similar between the 2 groups.

AIM: The cytoplasm Ca 2+, expression of Bcl-2 and Bax and germ cell apoptosis of testes in adult male rats with varicocele were observed to investigate the relationship between apoptosis and infertility. METHODS: Thirty-five healthy male Wistar rats were divided into two groups randomly: varicocele group (VG, n=20) and sham operation group (SOG, n=15). Bilateral testes were removed after ten weeks. One part of it was homogenized, the other part was performed for tissue sectioning. The atomic absorption method was used to detect the cytoplasm Ca 2+. The germ cell apoptosis was detected by the TdT-mediated dUTP-biotin nick end labeling (TUNEL) technique. The expression of Bcl-2/Bax was detected by immunohistochemical method. RESULTS: The cytoplasm Ca 2+ in testes of rats with varicocele was decreased obviously. The apoptosis indexes of germ cells and Bax expression in VG were significantly increased as compared with those in the SOG, while Bcl-2 expression was obviously decreased. CONCLUSION: The results showed that apoptosis was increased in testes of VG rats, suggesting that male infertility with varicocele may be caused by some apoptosis agents such as high temperature, testes toxin and oxygen free radical. The cytoplasm Ca 2+ and change of expression of Bcl-2/Bax may contribute to germ cell apoptosis and cause male infertility.

Cytogenetic Analysis ; standards ; Humans ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; genetics

ObjectiveTo compare the levels of sFas in the sera among Kawasaki disease (KD),incomplete Kawasaki disease (IKD),and normal control groups,and to analyze the relationship of sFas with IKD children.MethodsA total of 32 cases of acute KD and acute IKD children,and 20 cases of the control children were selected,respectively.The levels of serum sFas among three groups were measured using ELISA kits.Each child among the three groups was examined by echocardiography.Results(1)The levels of serum sFas among the three groups were[ (0.54±0.20)ng/L in KD,(0.55±0.16)ng/L in IKD,and (0.24 ± 0.04) ng/L] in control group,respectively.The overall means of sFas in the KD and IKD groups were higher than the control group,and the differences were statistically significant( F=29.276,P＜0.05 ).(2)The levels of serum sFas among echocardiography abnormal and normal groups were[ (0.65±0.19) ng/L and (0.49±0.10)ng/L],respectively; and the difference between two groups were statistically significant ( t=3.139,P ＜ 0.05 ).ConclusionsThe expression levels of sFas in the peripheral serum of IKD children were increased,and there was a close association of overexpression of sFas with the cardiovascular damage in IKD children.

Objective:To explore the hemodynamic changes in aged patients with essential hypertension (EH).
Methods: Our research included 2 groups, EH group, n=180 patients and Control group, n=100 subjects without cardiovascular diseases. The relevant indexes were recorded and compared by BioZ.com noninvasive hemodynamic monitor between 2 groups.
Results: With statistic processing, the cardiac output/index (CO/CI), cardiac index, thoracic lfuid content (TFC), systemic vascular resistance/index (SVR/SVRI) were signiifcantly different between EH group and Control group, all P<0.05.
Conclusion: The hemodynamic changes exist at certain degree indicating the potential injury of cardiac function in aged EH patients, such changes might be helpful for clinical diagnosis and treatment in EH patients.

OBJECTIVETo investigate the mechanism of STI571 inducing apoptosis of K562 cells which express P210(BCR/ABL).

METHODSApoptosis was analyzed by Annexin-V/PI, DioC6 [3] staining, DCFH-DA staining, DNA-PI staining and DNA ladder. Western blot was used to analyse mitochondrial and cytosolic cyto C, Bcl-X(L), caspase-3, actin protein and the level of tyrosine phosphorylation.

RESULTSAfter exposure to STI571, K562 cells were induced to apoptosis. Tyrosine phosphorylation level of P210(BCR/ABL) and Bcl-X(L) was decreased. Caspase-3 was activated and there was an cytosolic accumulation of cyto C.

CONCLUSIONSTI571 could rapidly decrease the tyrosine phosphorylation level of P210(BCR/ABL). The signal pathway mediated by the cytosolic translocation of mitochondrial cyto C was one of the mechanisms that STI571 inducing apoptosis. STI571 was an effective gene targeting therapeutic agent.

Antineoplastic Agents ; pharmacology ; Apoptosis ; Benzamides ; Caspase 3 ; Caspases ; metabolism ; Cytochrome c Group ; metabolism ; Cytoplasm ; metabolism ; Enzyme Precursors ; metabolism ; Fusion Proteins, bcr-abl ; metabolism ; Humans ; Imatinib Mesylate ; K562 Cells ; Membrane Potentials ; drug effects ; Mitochondria ; drug effects ; Piperazines ; pharmacology ; Pyrimidines ; pharmacology ; Reactive Oxygen Species ; metabolism

Objective To evaluate preliminarily the significance of dynamic detection of Wilms'tumor gene(WT1)expression level on monitoring minimal residual disease(MRD)and predicting clinical relapse in patients of malignancy following allogeneic hematopoietic stem cell transplantation(allo-HSCT).Methods WT1 expression level WaS measured with real.time quantitative reverse transcription polymerase chain reaction(RQ-RT-PCR)method on 102 bone marrow specimens from 31 patients following allo.HSCT.WT1 expression level was determined as the ratio of WT1 mRNA to ABL mRNA times 100%.Resuits The levels of WT1 expression showed significant difference between the relapsed group and the non-relapsed group(P＜0.01),with 0.80%and 0.17%as their median expression level respectively.After dynamic measuring WT1 expression level on patients in the relapsed group.the level was found to increase significantly as compared with those during or before the clinical hematological relapse.both being＞1.0%.The level at the time of relapse Was significantly higher than the latest previous one(P＜0.05).Conclusion Dynamic detection of WT1 expression level with RQ-RT-PCR may be of help in monitoring MRD and warning clinical relapse Oil the patients following allo-HSCT.

OBJECTIVETo evaluate the efficiency of dasatinib as the second- or third-line tyrosine kinase inhibitor (TKI)in imatinib-resistant patients with chronic myeloid leukemia (CML)based on BCR-ABL mutation detection.

METHODS122 CML patients received dasatinib treatment, including 83 with imatinib-resistance and 39 with both imatinib- and nilotinib-resistance, 55 in the chronic-phase (CP), 21 in the accelerated- phase (AP)and 46 in the blast- phase (BP). Those harboring dasatinib highly- resistant mutations (T315I/A, F317L/V/C and V299L)were excluded based on BCR-ABL kinase domain mutation screening by Sanger sequencing at baseline. Hematologic, cytogenetic and molecular responses were evaluated regularly, and rates of progression-free-survival (PFS)and overall survival (OS)were analyzed. BCR- ABL mutation detection was performed once the patients failed on dasatinib.

RESULTSIn the CP patients, the rates of complete hematological response (CHR), complete cytogenetic response (CCyR), major molecular response (MMR)and molecular response 4.5 (MR4.5)were 92.7%, 53.7%, 29.6% and 14.8%, respectively. 4-year PFS and OS rates were 84.4% and 89.5%, respectively. In the AP patients, HR and CCyR rates were 81.0% and 35.0%; and 3-year PFS and OS rates were 56.1% and 59.3%, respectively. In the BP patients, HR and CCyR rates were 63.0% and 21.4%; and 1-year PFS and OS rates were 43.6% and 61.8%, respectively. Outcomes were similar when dasatinib was used as the second- line TKI or the third-line TKI. Of the 75 patients who were resistant to dasatinib, 37 (48.7%)developed new mutation(s), and T315I (59.5%)was the most common mutation type. The patients who already harbored mutation(s)before dasatinib therapy achieved similar responses and outcomes to those with no mutation at baseline. However, they had higher likelihood of developing additional mutations associated with resistance to dasatinib (65.7%vs 34.1%,P=0.006).

CONCLUSIONSDasatinib was proved to be effective in the treatment of imatinib- or/and nilotinib-resistant CML patients, especially in both CP and AP cohorts. The significance of BCR-ABL mutation screening and monitoring should be highlighted before and during dasatinib therapy.

Blast Crisis ; Cytogenetics ; Dasatinib ; therapeutic use ; Disease-Free Survival ; Drug Resistance, Neoplasm ; Fusion Proteins, bcr-abl ; metabolism ; Humans ; Imatinib Mesylate ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; drug therapy ; Mutation ; Protein Kinase Inhibitors ; therapeutic use ; Pyrimidines