TA method for the content determination of methionine sulfoxide and methionine sulfone in compound amino acid injection (18AA-II) was established in order to investigate their level in 155 batches of this product, and to explore the reason for the generation of these two impurities.The determination was performed on an Agilent Poroshell 120 EC-C18 column with mobile phases of sodium acetate/tetrahydrofuran solution (A) and sodium acetate solution -acetonitrile-methanol (B, 200∶400∶400) (gradient elution) at the flow rate of 0.5 mL/min.The excitation wavelength and the emission wavelength of the fluorescence detector were 233 nm and 441 nm, respectively.The column temperature was 40 °C, and the injection volume was 8 μL.The contents of methionine sulfoxide and methionine sulfone from 155 batches of compound amino acid injection (18AA-II) was determined using this method, and the residual oxygen content was detected by headspace gas analyzer.The results showed that the linear range of methionine sulfoxide and methionine sulfone were 0.128 1-10.250 0 μg/mL (r = 0.999 9) and 0.261 0-10.440 0 μg/mL (r = 0.999 8), respectively.The limits of quantitation were 0.13 μg/mL and 0.26 μg/mL, respectively; the limits of detection were 0.04 μg/mL and 0.09 μg/mL, respectively.RSDs of precision, stability and repetitive test were all lower than 1.3%.The recoveries ranged 98.00%-100.79% (RSD = 1.15%, n = 9) and 98.19%-102.31% (RSD = 1.33%, n = 9).The content level of oxidized related substances from different manufacturers showed significant difference, showing relevance with the residual oxygen content to some extent, yet no significant correlation with the added amount of antioxygen (sodium pyrosulfite).The method is validated to be useful for the content control of methionine sulfoxide and methionine sulfone in compound amino acid injection (18AA-II).It is quite necessary to include the determination of oxidized related substance into the quality specification.Manufacturers should strengthen the control of remaining oxygen in their products.

Background and purpose: Cetuximab-containing regimen has been increasingly applied in the treatment of patients with metastatic colorectal cancer. Simultaneously, the predictive factors of outcome for cetuximab have been thoroughly researched. The aim of this study was to evaluate the relationship between K-ras status and efficacy of cetuximab containing regimen in the treatment of patients with metastatic eolorectal cancer. Methods: Between March 2006 and June 2008, twenty-seven patients with metastatic colorectal cancer were treated with cetuximab in combination with chemotherapy. The K-ras mutation status [wild-type (wt) or mutation (nat)] was examined by polymerase chain reaction (PCR) and direct sequencing. The influence of K-ras mutation status on efficacy of cetuximab-containing regimen was analyzed. Results: For 27 patiants in this cohort, K-ras wt was detected in 55.6% (15/27) cases and K-ras mt in 44.4% (12/27) cases. Statistically significant differences were found between the patients with K-ras wt and K-ras mt in terms of overall response rate (ORR) (66.7% vs 25.0%,P=0.035) and progression-free survival (PFS) (8 months vs 4 months, P=0.0028). However, there was no significant difference in overall survival (OS) (19 months vs 12 months, P>0.05). The most common treatment-related adverse effect was skin reaction, with incidence rate of 80.0% and 66.7% (P>0.05), respectively. No treatment related death was observed. Conclusion: K-ras mutation status is a predictive factor of good efficacy of cetuximab-containing regimen in the treatment of patients with metastatic colorectal cancer. Patients with K-ras wt could benefit from cetuximab in combination with chemotherapy.

Conditional forebrain-specific presenilin-1 and presenilin-2 double knockout mice (dKO mice) exhibit several neurodegenerative phenotypes of Alzheimer's disease (AD) pathology, such as tau hyperphosphorylation, neuron loss, forebrain cortical shrinkage and memory impairment. By using capillary electrophoresis assay, monoamine neurotransmitters in forebrain cortex, hippocampus and other forebrain region of dKO mice aged at 6, 9 and 12 months were measured to illustrate the relationship among presenilins function deficiency, neurodegenerative phenotypes and monoamine neurotransmitters. Data showed that levels of monoamine neurotransmitters in forebrain cortex of dKO mice were significantly decreased at 6 months when compared to controls, while as mice getting older, levels of monoamine neurotransmitters increased to that of controls, or even higher. In hippocampus, 5-hydroxytryptamin and epinephrine in dKO mice had a significant increase at 6 months, followed with a significant increase of each monoamine neurotransmitter at 12 months age. In other forebrain region, 5-hydroxytryptamin and dopamine had a similar level between control and dKO mice at 6 and 9 months but a significant decrease at 12 months; however, level of norepinephrine and epinephrine were significantly decreased at 6 and 12 months except epinephrine of 6 months. These results demonstrated that knockout of presenilins genes could lead to the variation of monoamine neurotransmitters, and the variation profiles were different among forebrain cortex, hippocampus and other forebrain region. However, whether presenilins deficiency caused the variation of monoamine neurotransmitter directly or not, and how about the effects of variation of monoamine neurotransmitters on AD-like pathology need to be further analyzed.

Background and purpose: Uridine diphosphoglucu-ronosyl transferase 1A1 (UGT1A1) is an important enzyme for metabolism of irinotecan. The activity of UGT1A1 enzyme was significantly affected by the gene polymorphism. This study aimed to investigate the correlation of UGT1A1*28 and *6 gene polymorphisms with irinotecan-based chemotherapy in colorectal cancer(CRC). Methods: Analysis of UGT1A1*28 and *6 gene polymorphisms was performed in 160 gastrointestinal cancer patients admitted to Zhongshan Hospital Fudan University from Apr. 2013 to Dec. 2013 by amplifying the gene fragments using PCR, STR and Sanger sequencing. Eighty-two cases with CRC treated with irinotecan were chosen to observe the adverse events during chemotherapy. The incidence of different genotypes was compared. Results:The distribution of the genotypes in 160 gastrointestinal cancer patients was as followed:UGT1A1*28 wild-type genotype TA6/6 (124, 77.5%), heterozygous genotype TA6/7 (33, 20.5%), and homozygous genotype TA7/7 (3, 2.0%);UGT1A1*6 wild-type genotype GG (105, 65.6%), heterozygous genotype GA (48, 30.0%), and homozygous genotype AA (7, 4.4%). In the 82 CRC cases, the incidences of grade 3 and 4 neutropenia in the patients carrying UGT1A1*28 (TA6/7+TA7/7 ) were higher than those in the WT genotype (TA6/6) (58.3%vs 0.0, P<0.001), and increased the total incidence of adverse events (76.0%vs 45.6%, P<0.001). There was no signiifcant relevance between UGT1A1*6 genotype, age, gender chemotherapy and adverse events. Conclusion:In the CRC cases with irinotecan-based chemotherapy, the UGT1A1*28 (TA6/7+TA7/7) genotype signiifcantly increased the risk of grade 3 and 4 neutropenia. Detecting UGT1A1 gene polymorphisms may guide individualized treatment and predict adverse events.

As the most common organ-specific autoimmune disease,autoimmune thyroiditis (AIT) is characterized by intrathyroidal lymphocyte infiltration and specificthyroid autoantibodies.Modern medicine is short of effective etiological treatment at present,and has no specific medicine foreuthyroidism of AIT patients,who have been followed-up passively.Chinese medicine treatmenthas the characteristics of multiple-targets,multiple-links and multiple-pathways,which plays a special superiorityrole in the prevention and treatment of AIT.The purpose of this article was to sort out and set forthmore Chinese medicine pharmacology on AIT recently,which provided evidence for further clinical apply.

Objective To investigate the effect of microcolumn gel reagent card,micro-column glass bead reagent card and classical test tube on the antibody titer of O-type pregnant women with ABO blood group.Determination of antibody potency of pregnant women with rabbit by reagent card.Methods Using microcolumn gel reagent card,micro-column glass beads reagent card,and classical test tube parallel detection to detect the IgG blood group antibody titer of O blood type pregnant women.Results There was no significant difference in the positive detection rate between the microcolumn gel reagent card and the microcolumn glass beads reagent card at 1:128 and the test tube method at 1:64 (P＞0.05).Conclusion The clinical reference value of microcolumn gel reagent card and microcolumn glass beads reagent kit for detecting antibody titer of IgG blood group in O-type pregnant women should be set to ≥ 1:128.

The current study was designed to determine the safety, tolerability and pharmacokinetic parameters of recombinant human parathyroid hormone [rhPTH (1-84)] used for the treatment of osteoporosis. In the single-dose format pharmacokinetic study, thirty-six healthy male volunteers received three dose levels of rhPTH (1-84) subcutaneously: 1, 2, and 4 mug/kg. The blood was timing drawn and the serum concentration of rhPTH (1-84) was determined by enzyme linked immunosorbent assay (ELISA). Serum concentration-time curves of PTH (1-84) exhibited a double-peak pattern, the first peak appearing about 10 to 30 min after administration and the second peak occurring about 1.5 to2 h after administration. Serum terminal half-time of PTH (1-84) was approximately 2 h. The parameters indicated the serum levels were directly proportional to the administered dose, with the mean C(max) and AUC(0-24) ranging from approximately 543.47 to 1845 pg/mL and 2358.6 to 9232.12 pg.h.mL(-1) over the dose range. The drug was well tolerated, the clinical symptoms were generally mild and of short duration.

Objective To observe the effect of aerobics exercise on myocardial fibrosis after acute myocardial infarction (AMI) in rat.Methods Twenty-four AMI Sprague Dawley (SD) rats were randomly assigned to sham-operated group (Sham),AMI group and aerobics exercise treatment group (ET).Except Sham,other groups of rats were underwent anterior wall myocardial infarction.After ten weeks,the myocardial mRNA level of connective tissue growth factor (CTGF),collagen Ⅰ (COL1 a1),collagen Ⅲ (COL3a1) detected by real time-quantitative polymerase chain reaction (PCR) analysis and myocardial collagen volume fraction (CVF) was determined on Masson stained sections.Results Campared to Sham-operated group,AMI group the level of CTGF,COL1a1,COL3a1,and CVF were increased (P ＜0.05,P ＜ 0.01).Campared to AMI and ET groups,the levels of CTGF,COL1a1,COL3a1,and CVF were decreased (P ＜ 0.05,P ＜ 0.01).Conclusions Aerobics exercise can reduced the myocardial fibrosis after AMI in rat.

Objective To explore the relationship between plasma interleukin-11(sIL-11) level and platelet count post-chemotherapy with hematological malignancy patients and analyse a sIL-11 level which may maintain a safe platelet count so as to guide the treatment. Methods Blood samples were collected from the patients with hematological malignancy at certain time point of pre-and post-chemotherapy, and serum level of sIL-11 and platelet count were determined separately. Different statistical methods were applied to test the relationship between sIL-11 level and platelet changes. Results 99 cases finished this study. The findings are: the sIL-11 level went up and reached the peak on day 6 post-chemotherapy, while the platelet count kept dropping to the lowest on day 10, the sIL-11 peak occurred before the lowest platelet count, patients with faster sIL-11 increase may maintain a comparatively higher plateled count. 99 eases were grouped according to the lowest platelet count and compared: the group with higher platelet count tend to have higher peak sIL-11, more cases with higher peak sIL-11, with faster daily average sIL-11 increase, the lowest platelet count occurred later. Logistic regression analysis showed the factors contributed to lower platelet includes slower daily average sIL-11 increase and sIL-11 level less than 2000 pg/ml on Day4 post-chemotherapy. Conclusion There were correlation between the serum sIL-11 level and platelet counts, the platelet count change may be predicted by determining the plasma sIL-11 level post-chemotherapy. Patients with sIL-11 level less than 2000 pg/ml on Day4 post-chemotherapy may be endangered with severe thrombocytopenia, rhIL-11 or platelet transfusion treatment should be considered.

Objective To analyze the current situation and influencing factors of job satisfaction of advanced practice nurses ( APN ) in military hospital after training, and provide scientific basis for further research on the rational use of APN. Methods Self-designed general information questionnaire and Spector′s job satisfaction questionnaire were used to survey the job satisfaction and influencing factors of 338 cardiovascular APN in military hospital ( cluster sampling method ) . Results The total score of job satisfaction of 338 cardiovascular disease nurses was (130. 79 ± 22. 06), which was lower than that of the American norm(t= -2. 300,P<0. 05). Multiple linear regression analysis showed that the time of certification, category of personnel and work position affected the nurses′job satisfaction. Conclusions The job satisfaction of APN in the military cardiovascular disease should be strengthened. Hospital managers should be according to the influencing factors, change the management mode to realize the transition from identity management to postmanagement, and provide APN better work environment, so as to exert the positive role of clinical nurse specialist.