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.

Cetuximab has become an important molecular targeted drug for the treatment of metastatic colorectal cancer (mCRC), which increases the curative effect of chemotherapy and prolongs the survival time. However, some patients develop insensitiveness or resistance to cetuximab, while the complicated molecular mechanisms are not quite clear. With the deep research in epidermal growth factor receptor (EGFR) signaling pathway, the genetic alteration of KRAS, BRAF, PTEN and PIK3CA and polymorphism of microRNA (miRNA) have been proved to associated with cetuximab resistance. Wnt signaling pathway with its negative regulator RNF43 is also considered to be related with cetuximab resistance in recent studies. The review of the progress on molecular mechanisms of cetuximab resistance in mCRC can establish theoretical basis for finding out reasonable drugs to overcome the resistance.

The solid wastes of Chinese materia dedica industrialization represented by Salvia miltiorrhiza residues have a strong small-molecule bio-recalcitrance in the process of high-value utilization of biotransformation. Highly tolerant strains were bred to break bio-recalcitrance of Salvia miltiorrhiza residues and produce high-value added cellulose, which has a significant significance for recycling and industrial utilization of solid waste. In this study, a strain of fungus, Penicillium expansum SZ13, was found with small-molecule antibacterial substance tanshinone contained in Salvia miltiorrhiza residues by a biological method. The optimal enzyme production process and peak period of SZ13 were determined. It was found that SZ13 could maintain peak enzyme production for 5 days by degrading residues under the conditions of temperature 35 ℃, rotation speed 180 r·min~(-1), 5% of residues addition, and 5% seed solution addition. Meanwhile, the ability of SZ13 to degrade the enzyme production of multiple types of residues was explored. The results showed a high enzyme activity and stable enzyme production of SZ13 in the process of degrading residues. SZ13 could efficiently utilize various types of Chinese medicine residues, such as Salvia miltiorrhiza residues, to realize the high-value utilization of cellulose in multiple types of residues.
Cellulase/biosynthesis* ; China ; Drug Industry ; Drugs, Chinese Herbal ; Fermentation ; Materia Medica ; Penicillium/metabolism* ; Salvia miltiorrhiza ; Solid Waste

Background: Previously, the authors modified the surgical technique to preserve tibial bone mass for Oxford unicompartmental knee arthroplasty (UKA). The purpose of this study was to determine the clinical outcomes and values of this modified technique. Methods: Clinical data of 34 consecutive patients who underwent the unilateral modified UKA technique (modified group, 34 knees) were retrospectively analyzed. To compare the outcome, a match-paired control group (conventional group, 34 knees) of an equal number of patients using the conventional technique system in the same period were selected and matched with respect to diagnosis, age, pre-operative range of motion (ROM), and radiological grade of knee arthrosis. Clinical outcomes including knee Hospital for Special Surgery (HSS) score, ROM, and complications were compared between the two groups. Post-operative radiographic assessments included hip-knee-ankle angle (HKA), joint line change, implant position, and alignment. Results: The mean follow-up time was 38.2 ± 6.3 months. There was no difference in baseline between the two groups. The amount of proximal tibial bone cut in the modified group was significantly less than that of the conventional group (4.7 ± 1.1 mm vs. 6.7 ± 1.3 mm, t = 6.45, P < 0.001). Joint line was elevated by 2.1 ± 1.0 mm in the modified group compared with -0.5 ± 1.7 mm in the conventional group (t = -7.46, P < 0.001). No significant differences were observed between the two groups after UKA with respect to HSS score, VAS score, ROM, and HKA. Additionally, the accuracy of the post-operative implant position and alignment was similar in both groups. As for implant size, the tibial implant size in the modified group was larger than that in the conventional group (χ² = 4.95, P = 0.035). Conclusions The modified technique for tibial bone sparing was comparable with the conventional technique in terms of clinical outcomes and radiographic assessments. It can preserve tibial bone mass and achieve a larger cement surface on the tibial side.

Objective: To explore experience of wound treatment of extremely severe mass burn patients involved in August 2nd Kunshan factory aluminum dust explosion accident. Methods: On August 2nd, 2014, 98 extremely severe burn mass patients involved in August 2nd Kunshan factory aluminum dust explosion accident were admitted to 20 hospitals in China. The patients with complete medical record were enrolled in the study and divided into microskin graft group with 56 patients and Meek skin graft group with 42 patients. Split-thickness skin in area of residual skin were resected to repair wounds of patients in microskin graft group and Meek skin graft group by microskin grafting and Meek miniature skin grafting, respectively. The residual wound size on 28 days post injury and wound infection after skin grafting of patients in the two groups, and position of donor site of all patients were retrospectively analyzed. Data were processed with t test and chi-square test. Results: The size of residual wound of patients in Meek skin graft group on 28 days post injury was (59±13)% total body surface area (TBSA), which was obviously smaller than that in microskin graft group [(70±14)%TBSA, t=4.379, P<0.05]. Twenty-nine patients in microskin graft group and 11 patients in Meek skin graft group suffered from obvious wound infection after skin grafting. Wounds of patients in two groups were repaired with residual skin around wound in head, trunk, groin, armpit, and uncommon donor sites of scrotum (4 patients), vola (10 patients), and toe or finger web (8 patients). Conclusions Meek skin graft is the first choice for wound repair of extremely severe burn mass patients, with faster wound healing, less wound infection. Uncommon donor sites of scrotum, vola, and toe or finger web can also be used for wound repair in case of lack of skin.

The chemical shift of fluoxetine hydrochloride appears at delta 14.15 in 19F NMR analysis. The delta moved upfield slightly from 14.158 to 14.145 when the concentration of solution became diluted from 2.00 to 0.05 mmol x L(-1). Spiking test was suggested to confirm the existence of the compound for qualitative analysis. 19F NMR detection sensitivity test illustrated that a concentration of 17 mg in 1 L water could be detected while the sample was scanned 500 times with optimum parameters. In quantitative analysis, standard curve of concentration versus fluorine signal intensity was proposed to determine the amount of fluoxetine. Long capillary tube containing trifluoroacetic acid was used as internal standard for the integration measurements and straight line was obtained with good fitting. Direct additions of trifluoroethanol to fluoxetine solutions gave a poorer standard curve.
Fluorine ; chemistry ; Fluoxetine ; analysis ; chemistry ; Magnetic Resonance Spectroscopy ; Molecular Structure ; Trifluoroacetic Acid ; analysis

objective To explore the impact ot ideal health behaviors and health tactors on the detection rate of the carotid plaques.Methods Subjects with previous stroke,TIA,myocardial infarction were excluded from the study.A total of 5852 employees (active and retired employers from Tangshan Kailuan company) aged 40 years and over were included through stratified random sampling.Information was obtained from the unified questionnaire,measurements of blood biochemistry and carotid artery ultrasonography.Results (1) The carotid artery plaque detection rates were 67.0％,52.3％,50.5％,44.3％,37.2％,31.9％,26.1％ and 4.2％ in the groups with0,1,2,3,4,5,6 and 7 components of ideal cardiovascular health behaviors and health factors,respectively.(2) The carotid artery plaques total burden score [TBS:M (Q1,Q3)] were7(7,7),7(5,7),7(5,7),5(3,5),5(3,5),5(3,5),3(3,3),3(3,3) in the groups with 0,1,2,3,4,5,6 and 7 components of ideal cardiovascular health behaviors and health factors,respectively.(3) Multiple logistic regression analysis showed that 3,4,5 and greater than 5 components of ideal cardiovascular health behaviors and health factors were protective factors against carotid plaques compared to less than 2 components of ideal cardiovascular health behaviors and factors (all P ＜ 0.05),the OR (95％ CI) values were 0.78 (0.62-0.98),0.53 (0.62-0.98),0.52 (0.39-0.71) and 0.40 (0.25-0.64),respectively.Conclusion Increasing ideal cardiovascular health behaviors and factors are negatively linked with the detection rate and TBS of the carotid plaques.

OBJECTIVEThis paper is to explore the DNA repair mechanism of immune adaptive response (AR) induced by low dose radiation (LDR), the changes of mRNA levels and protein expressions of p53, ATM, DNA-PK catalytic subunit (DNA-PKcs) and PARP-1 genes in the LDR-induced AR in EL-4 cells.

METHODSThe apoptosis and cell cycle progression of EL-4 cells were detected by flow cytometry in 12 h after the cells received the pre-exposure of 0.075 Gy X-rays (inductive dose, D1) and the succeeding high dose irradiation (challenge dose, D2; 1.0, 1.5, and 2.0 Gy X-rays, respectively) with or without wortmannin (inhibitor of ATM and DNA-PK) and 3-aminobenzamid (inhibitor of PARP-1). And the protein expressions and mRNA levels related to these genes were detected with flow cytometry and reverse transcription-polymerase chain reaction in 12 h after irradiation with D2.

RESULTSThe mRNA and protein expressions of p53 and PARP-1 in EL-4 cells in the D1 + D2 groups were much lower than those in the D2 groups, and those of PARP-1 in the 3-AB + D2 and the 3-AB + D1 + D2 groups were much lower than those in the D2 and the D1 + D2 groups. The percentage of apoptotic EL-4 cells in the 3-AB + D1 + D2 groups was much higher than that in the D1 + D2 groups, that in the G₀/G₁ and the G₂ + M phases was much higher, and that in the S phase were much lower. Although the ATM and DNA-PKcs mRNA and protein expressions in wortmannin + D1 + D2 groups were much lower than those in the D1 + D2 groups, there were no significant changes in the apoptosis and cell cycle progression between the wortmannin + D1 + D2 and the D1 + D2 groups.

CONCLUSIONPARP-1 and p53 might play important roles in AR induced by LDR.

Androstadienes ; Animals ; Apoptosis ; Cell Cycle ; Cell Line, Tumor ; DNA Repair ; Dose-Response Relationship, Radiation ; Gene Expression Regulation ; radiation effects ; Mice ; Poly (ADP-Ribose) Polymerase-1 ; Poly(ADP-ribose) Polymerases ; genetics ; metabolism ; RNA, Messenger ; genetics ; metabolism ; Radiation, Ionizing ; Tumor Suppressor Protein p53 ; metabolism

OBJECTIVETo describe the experience with extracorporeal membrane oxygenation (ECMO) for cardiorespiratory support of 100 patients.

METHODSRetrospective analysis of the medical files of 100 patients submitted to the implant of extracorporeal membrane oxygenation system for cardiorespiratory assistance of acute and refractory cardiogenic shock from December 2004 to September 2008. There were 67 males and 33 females, age ranged from 5 d to 76 years with a mean of (28+/-26) years, body mass ranged from 3.8 to 100.0 kg with a mean of (42+/-30) kg. The inter-surface of the ECMO equipment system was completely coated by heparin-coating technique. All patients were applied veno-artery ECMO and activated clotting time was maintained between 120 and 180 s and heparin usage dose was 5 to 20 Uxkg(-1)xh(-1). Mean blood flow was 40 to 220 mlxkg(-1)min(-1) during ECMO assistant period.

RESULTSThe shortest ECMO time was 12 to 504 h with a mean of (119+/-80) h. Sixty-one patients (61.0%) weaned off successfully from ECMO, 55 of them (90.2%) were discharged and 6 died of post-operative complications. Thirty-nine patients could not weaned off from ECMO. Total survival discharge rate was 55.0%. Mean aortic pressure before ECMO in survived patients was significantly higher than that of dead patients (P=0.038). Lactic acid concentration of artery blood before ECMO in survived patients was significantly lower than that of dead patients (P=0.005).

CONCLUSIONSECMO is an effective mechanical assistant therapy method for cardiac and pulmonary failure after cardiac surgery. Earlier usage of ECMO for heart lung failure patient and avoiding the main organs from un-recovery trauma are key success.

Adolescent ; Adult ; Aged ; Child ; Child, Preschool ; Extracorporeal Membrane Oxygenation ; Female ; Heart Failure ; therapy ; Humans ; Infant ; Infant, Newborn ; Male ; Middle Aged ; Respiratory Insufficiency ; therapy ; Retrospective Studies ; Young Adult