To study the related substances in nicergoline, electrospray positive ionization high resolution TOF/MS was used for the determination of the accurate mass and elemental composition of the related substances. Triple quadrupoles tandem MS/MS was employed for the determination of the fragmentations of the parent ions. 16 related substances were detected and identified to be eight synthetic by-products and eight degradation products, by using impurity references matching, product mass spectra fragmentations elucidation, and verified further according to synthetic processes and stress testing results. The results obtained are valuable for nicergoline manufacturing process control and quality assurance.
Chromatography, High Pressure Liquid ; Nicergoline ; chemical synthesis ; chemistry ; Quality Control ; Tandem Mass Spectrometry

Objective To assess the feasibility and safety of transradial puncture route for digital subtraction angiography (DSA)in young patients with ischemic cerebrovascular disease. Methods One hundred young patients with cerebrovascular disease who underwent whole brain angiography at the Department of Neurology,the 81 st Hospital of PLA were enrolled. They were divided into either a radial group (n =50)or a femoral group (n = 50)using a computer random number method. The time of puncture,success rate of puncture,success rate of selective angiography,exposure time,and incidence of complications were compared and analyzed. Results (1)The puncture time of the radial group was significantly longer than that of the femoral group,they were 3. 00 ± 0. 50 min and 1. 50 ± 0. 25 min respectively. There was significant difference (t = 18. 97,P < 0. 05). There were no significant differences in the success rate of puncture (98% vs. 100%),success rate of selective angiography (100% vs. 100%),and exposure time (5. 3 ± 2. 2 vs. 4. 8 ± 1. 7 min)between the two groups (all P > 0. 05). (2)The incidence of complications of the radial group (4%,n = 2)was significantly 1ower than that of the femoral group (18%,n = 9 ). There was significant difference between the two groups (χ2 = 5. 01,P < 0. 05 ). Conclusion Transradial route puncture for whole brain DSA in young patients with cerebrovascular disease is safely and feasible.

To study the related substances in nicergoline, electrospray positive ionization high resolution TOF/MS was used for the determination of the accurate mass and elemental composition of the related substances. Triple quadrupoles tandem MS/MS was employed for the determination of the fragmentations of the parent ions. 16 related substances were detected and identified to be eight synthetic by-products and eight degradation products, by using impurity references matching, product mass spectra fragmentations elucidation, and verified further according to synthetic processes and stress testing results. The results obtained are valuable for nicergoline manufacturing process control and quality assurance.

Objective To study the early clinical outcome of patients undergone minimally invasive direct coronary bypass(MIDCAB) surgery,and the mid-term patency of left internal mammary artery(LIMA)-left anterior descending(LAD) anastomosis.Methods From Jannuary 2007 to May 2014,47 cases underwent MIDCAB surgery in our department,with 35 males and 12 females,aged 48-76 years,with the average of (62.9 ± 8.1) years old.Types of LAD lesions were as followed:1 case was ostial total obstruction,28 severe stenosis at proximal segment,10 long and severe stenosis,3 calcified lesion with severe stenosis,5 myocardial bridge.All patients had symptomatic angina,typical myocardial ischemia could be detected by electrocardiogram for all patients with myocardial bridge.Comorbidities included:hypertension 38 cases,27 diabetes mellitus,3 COPD and 3 chronic kidney disease.Results All surgery went well without transfer to mid-sternotomy.LIMA harvest time was 38-53 minutes,mean LIMA flow rate was(22 ± 6) ml/min after anastomosis.Surgery duration was 117-143 minutes,blood loss was less than 100 ml for each operation.No blood transfusion was required.Tracheal intubation time was 4-16 hours,ICU stay time was 22-45 hours,hospital stay time was 6-10 days.There was no peri-operative death,either no myocardial infarction or cerebral vessel accident.During follow-up,all LIMA-LAD appeared to be patent by coronary CT angiography.Conclusion High patency rate of LIMA-LAD anastomosis could also be obtained during MIDCAB surgery.It was reserved as a safe and effective surgery for well-selected patients.

Objective To analyze the cause of puncturing failure in ultrasonography guided minimal-invasive percutaneous nephrolithotomy (MPCNL). Methods A retrospective analysis involved total 612 patients with upper urinary tract lithialisis treated with MPCNL from May 2005 to May 2010.382 cases were acupunctured by traditional G18 puncturing instrument (group A),and the other 230 cases were performed by the improved ARROW Raulerson blue syringe (group B).The average renal pelvis range was 24 mm vs.21 mm before operation,and largest diameter of renal calculi was 3.7 cm vs.3.8 cm (P ＞ 0.05).Success rate and time cost as well as therapeutic effect were compared between the 2 groups. Results There were 29 cases of puncturing failure in group A (totally 382 cases) while only 2 in group B (totally 230 cases).The successful rate of establishment of working channel was significantly higher in group B (P ＜ 0.05).Average time of puncture procedure was 5.1 min and 4.8 min respectively (P ＞ 0.05).There was no puncturing-related severe complication in any group.The unsuccessful cases in the group A and related causes were:5 cases for obesity,13 cases for puncture needle slipping,9 cases for channel dropout,and 2 cases for needle route dropout.However,only 2 cases failed in group B,the accurate position of calculi was at upper and lower calyx.One case was over-weighted,another was because of pathway-loss during the calculi elimination processs.And the one-off puncture successful rate of A and B group was 92.4％ vs.99.1％,and the one-off puncture successful rate was significantly higher in group B. Conclusions Overobesity of patients is an important cause of puncturing failure for sonographically MPCNL.The establishment of working-channel with ARROW Raulerson blue syringe could be feasible and the success rate was significantly higher.

0bjective To investigate the pattern of disease relapse and prognostic risk factor of patients with cervical carcinoma and pelvic lymph node metastasis.Methotis A total of 124 cases of International Federation of Gynecology and Obstetricfi(FIG0)I bl-Ⅱ a cervical carcinoma with pelvic node metastasis who were treated at the Cancer Center of Sun Yat-sen University during January 1994 to December 2001 were selected for this study.Prognosis and recurrence were retrospectively analyzed using the clinico.pathological data.Results The overall 5 year flun,ival and 5 year disease-free survival were 63.3% and 61.4%.respectively.Overall recurrence rate was 39.5%(49/124),among which intra-pelvic relapse (61.0%,25/41)was significantly more common than extra-pelvic relapse(31.7%,13/41;P=0.008).Multivariate analysis identified involvement of common iliac node as an independent prognostic factor(P=O.035).According to this factor,node-positive patients could be divided into low risk group(without common iliac node involvement,104 cases)and hiSh risk group(with common iliac node involvement,20 cases).The 5 year disease-free survival were 69.4%and 24.5%respectively,with a significant difference(P=0.003).Intra.pelvic relapse was observed in 22.1%(23/104)of low risk and 25.0% (5/20)of high risk group respectively,with no significant difference(P>0.05).However extra-pelvicrelapse wag seen in 7.7%(8/104)of low risk and 40.0%(8/20)of hish risk group,with a significant difference(P<0.01).Conclusions Common iliac node involvement is a significant factor influencing the prognosis of patients with cervical carcinoma and pelvic lymph node metastasis.Patients with positive common iliae nodes have significantly decreased 5 year disease.free survival and hishcr extra-pelvic disease recurrence rates compared with those whose common iliac nodes are negative.These findings provide impo.rtant data for design of individualized treatment mode.

To investigate the relationships among plasma secreted frizzled-related protein ( sfrp) 5 level and body fat parameters, glucolipid metabolism, insulin resistance index, and inflammation. 89 subjects with normal glucose tolerance(NGT) and 87 patients with type 2 diabetes mellitus (T2DM) were enrolled and each group was divided into no-obese and obese subgroups. Obesity was defined as body mass index ( BMI)≥25 kg/m2 according to the World Health Organization -Western Pacific Region diagnostic criteria ( 2000 ) . Body fat parameters were measured and BMI, waist-hip ratio were evaluated, meanwhile, the levels of blood glucose-lipid parameters and fasting insulin were also determined. Insulin resistance index ( IR) was assessed by homeostasis model assessment ( HOMA) . The concentrations of plasma sfrp5 and interleukin 6 were detected by enzyme-linked immunosorbent assay. Plasma sfrp5 level in T2DM group was significantly lower than that in NGT group [(8. 35±3. 38 vs 11. 35±3. 69)ng/ml, P<0. 01]. The levels of plasma sfrp5 in subjects with obesity were also lower than those in subjects with no-obesity in both NGT and T2DM groups [(9. 46±2. 70 vs 13. 12±3. 62)ng/ml and(6. 70±2. 34 vs 10. 12±3. 45) ng/ml, both P<0. 01]. Plasma concentrations of sfrp5 in T2DM-obese group were significantly lower than that in NGT-obese group(P<0. 01). Correlation analysis showed that plasma sfrp5 levels were negatively correlated with waist-hip ratio, HbA1C, fasting insulin, triglycerides, waist circumference, fasting plasma glucose, interleukin 6, natural logarithm of HOMA-IR [ln(HOMA-IR)], and BMI(P<0. 01 or P<0. 05). Multiple linear regression showed that ln(HOMA-IR), BMI, triglycerides were independent related factors in influencing the levels of plasma sfrp5 (r2=0. 216, 0. 177, 0. 113, all P<0. 05). Plasma sfrp5 levels were decreased in obesity and T2DM subjects and were correlated with body fat disposition, glucose-lipid metabolism, insulin resistance and inflammation. Lack of sfrp5 may contribute to the pathophysiology of obesity and T2DM.

This study aims to investigate the function of two SNPs (rs8904C > T and rs696G >A) in 3' untranslated region (3'UTR) of NFKBIA gene by constructing luciferase reporter gene. A patient's genomic DNA with rs8904 CC and rs696 GA genotype was used as the PCR template. Full-length 3'UTR of NFKBIA gene was amplified by different primers. After sequencing validation, these fragments were inserted to the luciferase reporter vector, pGL3-promoter to construct recombinant plasmids containing four kinds of haplotypes, pGL3-rs8904C/rs696G, pGL3-rs8904C/rs696A, pGL3-rs8904T/rs696G and pGL3-rs8904T/rs696A. Then these plasmids were transfected into LS174T cells and the luciferase activity was detected. Compared with pGL3-vector transfected cells (negative control), the luciferase activity of the four kinds of recombinant plasmids was significantly decreased (P < 0.001). For rs696G > A, the luciferase activity of the recombinant plasmids containing A allele (pGL3-rs8904C/rs696A and pGL3-rs8904T/rs696A) was about 45.1% (P < 0.05) and 56.1% (P < 0.001) lower than those containing G allele (pGL3-rs8904C/rs696G and pGL3-rs8904T/rs696G), respectively. For rs8904C > T, there were no significant differences in the luciferase activity between the recombinant plasmids containing T allele and those with C allele. Together, the luciferase reporter gene vectors containing SNPs in NFKBIA gene 3'UTR were constructed successfully and rs696G > A could decrease the luciferase activity while rs8904C >T didn't have much effect on the luciferase activity.

Objective:To investigate the effects of ursolic acid (UA) on the proliferation and differentiation of osteoclasts (OC), and to explore its role in orthodontic force-induced root resorption and its relationship with OC.Methods:The mononuclear / macrophage cells RAW264.7 were induced to the OC.Tacrolimus acid phosphatase (TRAP) staining and bone resorption lacunae observation were used to identify the induction.CCK-8 method was used to select the appropriate concentration of UA for RAW264.7 cell-free biotoxicity and to observe its effect on the proliferation and differentiation of RAW264.7.In experimental groups, UA with gradient concentrations (1.0,2.5,5.0,10.0,20.0and 40.0 μmol·L-1)were added.UA was not added in control group.Results:The TRAP staining and bone resorption lacunae observation showed that after the RAW264.7 cells were induced for 5 d, the TRAP staining positive cells were found;the resorption lacunae were rounded,and oval, etc,the bottom wall was coarser,and the boundary was clear,which indicated that the RAW264.7 cells were successfully differentiated into the osteoclasts.The CCK-8 detection results showed that high concentration of UA (> 10.0 μmol·L-1) significantly inhibited the proliferation of OC;the appropriate concentration of UA (5.0 μmol·L-1) was in the biological safety concentration range and could inhibit the OC proliferation;low concentration of UA (<2.5 μmol·L-1) had no effect.Conclusion:RANKL can induce the differentiation and maturation of RAW264.7 cells.UA is correlated with the proliferation and differentiation of OC;UA has inhibitory effect on OC at the appropriate concentration (5.0 μmol·L-1) in a time-dependent manner.