Objective:To evaluate the efficacy and safety of hypomethylating agents (HMA) in patients with myelodysplastic syndromes (MDS) .Methods:A total of 409 MDS patients from 45 hospitals in Zhejiang province who received at least four consecutive cycles of HMA monotherapy as initial therapy were enrolled to evaluate the efficacy and safety of HMA. Mann-Whitney U or Chi-square tests were used to compare the differences in the clinical data. Logistic regression and Cox regression were used to analyze the factors affecting efficacy and survival. Kaplan-Meier was used for survival analysis. Results:Patients received HMA treatment for a median of 6 cycles (range, 4-25 cycles) . The complete remission (CR) rate was 33.98% and the overall response rate (ORR) was 77.02%. Multivariate analysis revealed that complex karyotype ( P=0.02, OR=0.39, 95% CI 0.18-0.84) was an independent favorable factor for CR rate. TP53 mutation ( P=0.02, OR=0.22, 95% CI 0.06-0.77) was a predictive factor for a higher ORR. The median OS for the HMA-treated patients was 25.67 (95% CI 21.14-30.19) months. HMA response ( P=0.036, HR=0.47, 95% CI 0.23-0.95) was an independent favorable prognostic factor, whereas complex karyotype ( P=0.024, HR=2.14, 95% CI 1.10-4.15) , leukemia transformation ( P<0.001, HR=2.839, 95% CI 1.64-4.92) , and TP53 mutation ( P=0.012, HR=2.19, 95% CI 1.19-4.07) were independent adverse prognostic factors. There was no significant difference in efficacy and survival between the reduced and standard doses of HMA. The CR rate and ORR of MDS patients treated with decitabine and azacitidine were not significantly different. The median OS of patients treated with decitabine was longer compared with that of patients treated with azacitidine (29.53 months vs 20.17 months, P=0.007) . The incidence of bone marrow suppression and pneumonia in the decitabine group was higher compared with that in the azacitidine group. Conclusion:Continuous and regular use of appropriate doses of hypomethylating agents may benefit MDS patients to the greatest extent if it is tolerated.

Glutamate decarboxylase, a unique pyridoxal 5'-phosphate-dependent enzyme, catalyzes α-decarboxylation of L-glutamate to γ-aminobutyrate. However, glutamate decarboxylase from different sources has the common problem of poor thermostability that affects its application in industry. In this study, proline was introduced at 13 different positions in glutamate decarboxylase by using the design strategy of homologous sequence alignment between Thermococcus kodakarensis and Lactobacillus brevis CGMCC No.1306. A mutant enzyme G364P with higher thermostability was obtained. Compared to the wild type, thermostability of the mutant G364P was significantly improved, the half-life time (t1/2) at 55 °C and the semi-inactivation temperature (T₅₀ ¹⁵) of the mutant G364P increased 19.4 min and 5.3 °C, respectively, while kcat/Km of the mutant enzyme remained nearly unchanged. Further analysis of their thermostability by molecular dynamics simulations were performed. The root mean square deviation of G364P and root mean square fluctuation in the loop region including G364 were lower than the wild type at 313 K for 10 ns, and G364P increased one hydrophobic interaction in the loop region. It proves that mutation of flexible 364-Gly to rigid proline endows glutamate decarboxylase with enhanced thermostability.
Glutamate Decarboxylase ; Glutamic Acid ; Lactobacillus brevis ; Molecular Dynamics Simulation ; Proline

OBJECTIVE:To discuss clinical efficacy and safety of alteplase combined with butylphthalide to the patients with acute ischemic stroke. METHODS:98 patients with acute ischemic stroke in our hospital were selected and divided into ob-servation group and control group according to random number table,with 49 patients in each group. Control group was addition-ally given Butylphthalide and sodium chloride injection 100 ml,ivgtt,bid,on the basis of routine treatment as controlling blood glucose,blood pressure,etc.;observation group additionally received Alteplase for injection 5 mg added into NS 10 ml,iv+Al-teplase for injection 45 mg added into NS 100 ml,ivgtt,qd,on the basis of control group. Both groups were treated for 2 weeks. Clinical efficacies of 2 groups were compared as well as cerebral infarction area,NIHSS score,ability score of daily liv-ing,the levels of IL-6,IL-8,IL-10,CRP,24 h urine protein,Scr and creatinine clearance rate before and after treatment. The occurrence of ADR was also recorded. RESULTS:1 patient of observation group and 2 patients of control group withdrew from the study due to severe hemorrhage. Total effective rate of observation group(95.83%)was significantly higher than that of con-trol group(80.85%),with statistical significance(P<0.05). Before treatment,there was no statistical significance in above in-dexes between 2 groups (P>0.05). The cerebral infarction area and NIHSS score were reduced significantly in observation group after treatment,ability score of daily living were increased significantly in observation group after treatment,and the im-provement of observation group was significantly better than control group,with statistical significance (P<0.05). 24 h urine protein and Scr of observation group was significantly lower than those of control group,with statistical significance(P<0.05). the level of IL-6 in observation group 1 week after treatment and the levels of IL-6,IL-8,IL-10 and CRP 2 weeks after treat-ment were significantly lower than in control group,with statistical significance(P<0.05). There was no statistical significance in the incidence of ADR between 2 groups (P>0.05). CONCLUSIONS:Alteplase combined with butylphthalide show signifi-cant therapeutic efficacy,can effectively reduce the level of serum inflammatory factors,control brain tissue ischemia and cere-bral infarction area,and improve neurologic function and pro-tect renal function in patients with acute ischemic stroke.

OBJECTIVETo compare the image quality of isotropic 3-dimensional fast spin echo (3D-FSE), 3D fast field echo (3D-FFE), and 2D fast spin echo (2D-FSE) sequences in magnetic resonance imaging (MRI) of the anatomical structure of the ankle joint.

METHODSThe ankle joints of 10 healthy volunteers were examined with isotropic 3D-FSE, 3D-FFE and 2D-FSE sequences using a 1.5T MR scanner and 3D reconstruction. The signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) of the tissues were measured. Two radiologists evaluated the image quality of the 3 sequences using a 5-point Likert scale in a double-blinded manner.

RESULTSThe 3D-FSE sequences resulted in the highest SNRs for all the tissues and the highest CNRs for differentiation between cartilage and marrow, between muscle and tendon, and between tendon and fluid. In the estimation of image quality for cartilages, 3D-FFE had the highest score followed by 3D-FSE, and the latter had the highest score among the 3 sequences in displaying the tendon.

CONCLUSION3D-FSE sequence has a high performance in displaying the anatomical structures of complex joints especially for cartilage, ligament, and tendon tissues.

PurposeTo investigate the physical characteristics of the lumbar bone marrow fat content by analyzing the correlation of the lumbar bone marrow fat content with age, gender, body mass index (BMI) and waist circumference. It may be helpful to deepen the understanding the occurrence regularity of osteoporosis. Materials and Methods A total of 144 subjects were recruited including both healthy volunteers and the patients with chronic low back pain. The height, weight and waist circumference were measured, and the body mass index was calculated. All the subjects took spectroscopy sequence at the third lumber vertebra with single-voxel point resolved spectroscopy (PRESS) method. Lipid (1.3 ppm) to water (4.67 ppm) ratio (LWR) and lipid fractions (FF%) were measured. LWR and FF% of L3 were compared among the patients with different gender, age, BMI and waist circumference. The correlation of LWR and FF% of L3 and age were analyzed.Results The LWR and FF% of L3 showed no signiifcant difference between the male and female (t=-0.267 and-0.993,P>0.05). There was statistical difference of LWR and FF% among the different age groups (F=3.723 and 5.478,P<0.05). LWR and FF% of female in 61-70 year-old group showed signiifcant higher than that in 20-30, 31-40, 41-50 and 51-60 year-old group (P<0.05). FF% of L3 in 20-30 year-old female group showed signiifcant lower than that in >70 year-old group (P<0.05). LWR of L3 for both male and female in 60-70 year-old group also showed signiifcant higher than that in 20-30, 31-40, 41-50 and 51-60 year-old group (P<0.05). FF% for both male and female in 20-30 year-old group showed signiifcant lower than that in 31-40, 41-50, 51-60, 61-70 and>70 year-old group (P<0.05). FF% of 61-70 year-old group was signiifcant different from that in 31-40, 41-50, 51-60 year-old group (P<0.05). The LWR and FF% of L3 showed no signiifcant difference between the different BMI groups and waist circumference groups (P>0.05). Age was positive correlated with FF% of L3 (r=0.321,P<0.05).Conclusion The lumbar bone marrow fat content is correlated with age, but is not correlated with gender, BMI and waist circumference.

Objective To investigate the relationship between the whole blood detection of 0-13 years old children infected with trace elements of magnesium ,zinc ,copper ,ferrum and calcium ,and infectious diseases .Methods we were measured the whole blood trace elements by the atomic absorption spectrometry in a population of 1 183 cases of infectious diseases ,the infection group were made up of the male 638 cases and female 545 cases ,according to the different infection system was divided into 828 infectious cases of the respiratory system ,251 cases in digestive system infection ,104 cases in other system infection .The control group used earlier to our hospital outpatient department of Pediatrics voluntary to examine for the healthy children in 160 cases ,including male 96 ca‐ses ,female 64 cases .Results Zinc ,ferrum and calcium that infectious diseases group compared with the control group was obvious difference(P<0 .05) .The trace elements that compared with the different age groups or the different infectious diseases were also difference ,In the middle of infectious diseases the lack of zinc ,ferrum ,calcium children aged 0-13 years old accounted for 14 .2% , 10 .3% ,6 .7% .Magnesium and copper′s deficiency is rare .Conclusion Children of infectious diseases aged 0 to 13 years show the lack of zinc ,ferrum ,calcium ,so we could have reasonable supplement according to the specific circumstances .

Objective To compare the image quality of isotropic 3-dimensional fast spin echo (3D-FSE), 3D fast field echo (3D-FFE), and 2D fast spin echo (2D-FSE) sequences in magnetic resonance imaging (MRI) of the anatomical structure of the ankle joint. Methods The ankle joints of 10 healthy volunteers were examined with isotropic 3D-FSE, 3D-FFE and 2D-FSE sequences using a 1.5T MR scanner and 3D reconstruction. The signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) of the tissues were measured. Two radiologists evaluated the image quality of the 3 sequences using a 5-point Likert scale in a double-blinded manner. Results The 3D-FSE sequences resulted in the highest SNRs for all the tissues and the highest CNRs for differentiation between cartilage and marrow, between muscle and tendon, and between tendon and fluid. In the estimation of image quality for cartilages, 3D-FFE had the highest score followed by 3D-FSE, and the latter had the highest score among the 3 sequences in displaying the tendon. Conclusion 3D-FSE sequence has a high performance in displaying the anatomical structures of complex joints especially for cartilage, ligament, and tendon tissues.

Objective To compare the image quality of isotropic 3-dimensional fast spin echo (3D-FSE), 3D fast field echo (3D-FFE), and 2D fast spin echo (2D-FSE) sequences in magnetic resonance imaging (MRI) of the anatomical structure of the ankle joint. Methods The ankle joints of 10 healthy volunteers were examined with isotropic 3D-FSE, 3D-FFE and 2D-FSE sequences using a 1.5T MR scanner and 3D reconstruction. The signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) of the tissues were measured. Two radiologists evaluated the image quality of the 3 sequences using a 5-point Likert scale in a double-blinded manner. Results The 3D-FSE sequences resulted in the highest SNRs for all the tissues and the highest CNRs for differentiation between cartilage and marrow, between muscle and tendon, and between tendon and fluid. In the estimation of image quality for cartilages, 3D-FFE had the highest score followed by 3D-FSE, and the latter had the highest score among the 3 sequences in displaying the tendon. Conclusion 3D-FSE sequence has a high performance in displaying the anatomical structures of complex joints especially for cartilage, ligament, and tendon tissues.

BACKGROUND:Recently, a neuroprotective effect of granulocyte colony-stimulating factor was reported in a model of cerebral infarction and a model of acute spinal cord injury. However, the applied animal model was not established by impact method, different from pathophysiological process of human.
OBJECTIVE:To observe effects of granulocyte colony-stimulating factor on motor function in a rat model of spinal cord injury induced by Al en’s method.
METHODS:Wistar rats were used to establish spinal cord injury at T 10 level using modified Al en’s method. They were randomly assigned to two groups, granulocyte colony-stimulating factor group, treated with granulocyte colony-stimulating factor, and vehicle group, treated with equal volume of PBS. The motor function was evaluated with Basso-Beattie-Bresnahan score and modified Rivlin loxotic plate test monitored at 1, 7, 14, 21, 28 and 35 days, and four-limb muscle strength was assessed using Grid walk test at 7, 14, 21, 28 and 35 days post-operatively.
RESULTS AND CONCLUSION:Hind limbs paralysis occurred in al animals postoperatively. Scores of Basso-Beattie-Bresnahan and modified Rivlin loxotic plate test were greater in granulocyte colony-stimulating factor group compared with vehicle group at 7, 14, 21, 28 and 35 days (P<0.05-0.01);mean Grid walk test errors were less in granulocyte colony-stimulating factor group compared with vehicle group at 14, 21, 28 and 35 days (P<0.05-0.01). Results indicate that motor function and four-limb muscle strength were improved fol owing granulocyte colony-stimulating factor therapy compared with vehicle group, indicating that granulocyte colony-stimulating factor has a positive effect on spinal cord injury.

Objective Establishing a fingerprint method to identify the characteristic chemicals in the roots of Gentiana macrophylla and evaluate their quality.Methods RP-HPLC was developed for fingerprint analysis and determination of four ingredients in G macrophylla roots from different sources.LC-ESI-TOF-MS was employed to identify the chromatographic peaks of the fingerprint.Results Five common peaks were identified by comparing their retention time with reference secoiridoid glucosides.Eight major peaks in chromatographic fingerprint were analyzed by on-line LC-ESI-TOF-MS.Four secoiridoid glucosides were identified based on their MS data.Conclusion The method is specific and could be served for the quality identification and comprehensive evaluation of G macrophylla.