The study aims to identify the related substances in fasudil hydrochloride by hyphenated techniques. A WondaSil C18 (250 mm x 4.6 mm, 5 microm) column was used for the separation of the related substances with a mixture of methanol and ammonium acetate buffer solution as the mobile phase by gradient elution. The structures of the related substances were speculated by electrospray positive ionization LC-TOF/MS accurate ion mass and MS/MS determination and elucidation, and verified further through synthesis and spectroscopic analysis. Fasudil hydrochloride and the related substances were separated under the established HPLC condition. Three related substances in fasudil hydrochloride were characterized by hyphenated techniques. The hyphenated LC-MS method is useful for the identification of related substances in fasudil hydrochloride and the results obtained are valuable for its manufacturing process and quality control.

Drug metabolism will change significantly during inflammation, including the reduction of expression and activity of many drug metabolizing enzymes and transporters. Body would release a series of inflammatory cytokines which can regulate drug metabolizing enzymes. Recent studies have revealed that drug transporters are also regulated by the cytokines with obvious species difference. Mechanism studies show that several transcription factors play important roles during the signal pathways of regulation. This review focuses on the progress in the regulation of drug transporters during inflammation.

A sensitive and selective liquid chromatography–tandem mass spectrometric (LC ? MS/MS) method was established to determine 2-oxo-clopidogrel, a crucial intermediate metabolite in human plasma. A chromatographic separation was performed on a Sapphire C18 column following a liquid–liquid extraction sample preparation with methyl t-butyl ether. Detection was carried out on a triple quadrupole mass spectrometer operated in multiple reaction monitoring (MRM) with an electrospray ionization (ESI) mode. The method was validated in terms of specificity, accuracy, precision and limit of quantification. The calibration curves ranged from 0.50 to 50.0 ng/mL with good linearity. The stability was fully validated with addition of 1,4-dithio-DL-threitol (DTT) into the plasma sample prior to and in the preparation procedure. The validated method was proved to be suitable for use in pharmacokinetic study after single oral administration of 75 mg clopidogrel tablets in human subjects, which could make contribution to intensive study of the clinical drug–drug interactions of clopidogrel and individual treatment.

Objective To investigate the application value of three-dimensional (3D) laparoscopic pancreaticoduodenectomy (LPD) and compare the clinical outcomes between 3D-LPD and open pancreaticoduodenectomy (OPD).Methods The retrospective cohort study was adopted.The clinicopathological data of 349 patients who underwent pancreaticoduodenectomy at the Affiliated Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology between July 2014 and March 2016 were collected.Of 349 patients,146 undergoing 3D-LPD were allocated into the 3D group and 203 undergoing OPD were allocated into the OPD group.Observation indicators:(1) surgical situations:operation time,volume of intraoperative blood loss,cases of blood transfusion,number of lymph node dissected,resection margin and vascular resection and reconstruction,(2) postoperative situations:time of gastric tube removal,duration of intensive care unit (ICU) stay,duration of hospital stay,(3) complications:pancreatic fistula,delayed gastric emptying,intra-abdominal infection or abscess,bile leakage,hemorrhage,pulmonary infection or wound infection,(4) follow-up.All the patients were followed up by telephone interview to detect the tumor-free survival rate up to June 2016.Measurement data with normal distribution were presented as (x) ± s and comparison between groups was analyzed using the t test.Count data were analyzed using the chi-square test.Results (1) Surgical situations:all the patients underwent successful pancreaticoduodenectomy.Operation time,volume of intraoperative blood loss,cases of blood transfusion,number of lymph node dissected and positive resection margin were (334 ± 175)minutes,(254 ± 107)mL,29,13 ±8,1 in the 3D group and(320 ±91)minutes,(290 ± 101) mL,35,14 ±9,5 in the OPD group,respectively,with no statistically significant difference between the 2 groups (t =0.975,1.383,x2=0.390,t =12.155,x2=1.589,P ＞ 0.05).Vascular resection and reconstruction were respectively applied to 0 patient in the 3D group and 14 patients in the OPD group,with a statistically significant difference between the 2 groups (x2 =10.490,P ＜ 0.05).(2) Postoperative situations:time of gastric tube removal,duration of ICU stay and duration of hospital stay were (2.9 ± 1.9) days,(6.9 ± 2.1) days,(12.9 ± 7.2) days in the 3D group and (5.1 ± 1.7) days,(7.4 ± 1.2) days,(19.8 ± 7.1) days in the OPD group,respectively,with statistically significant differences between the 2 groups (t =11.350,2.814,8.903,P ＜ 0.05).(3) Complications:of 146 patients in the 3D group,40 had postoperative complications with incidence of complications of 27.40％ (40/146).Twenty-nine patients with pancreatic fistula (20 in grade A,9 in grade B and C) were improved by conservative treatment.Thirteen patients with delayed gastric emptying were cured by gastrointestinal decompression and enhancing gastric motility.Of 5 patients with postoperative hemorrhage,3 were improved by conservative treatment,and 2 were improved by small vein hemostasis behind the head of pancreas.One patient died of systemic inflammatory response syndrome.Partial patients were combined with multiple complications.Of 203 patients in the OPD group,60 had postoperative complications with incidence of complications of 29.56％ (60/203),including 39 patients with pancreatic fistula (31 in grade A,8 in grade B and C),25 with delayed gastric emptying,15 with intra-abdominal infection and 13 with systemic inflammatory response syndrome,and they were improved by conservative treatment.Of 8 patients with postoperative hemorrhage,4 were improved by conservative treatment,and 4 were cured by hemostatic therapy after ineffectual blood transfusion and interventional treatment.Two patients died of cardiopulmonary complication.Partial patients were combined with multiple complications.There was no statistically significant difference in the incidence of postoperative complication between the 2 groups (x2 =10.490,P ＞ 0.05).(4) Follow-up:all the patients were followed up at postoperative month 6.Tumor-free survival rate was 90.41％ (132/146) in the 3D group and 85.22％ (173/203) in the OPD group,with no statistically significant difference between the 2 groups (x2 =2.076,P ＞ 0.05).Conclusion Compared with OPD,3D-LPD can provide the more realistic visual effects and refinement of surgical procedures,with a good short-term outcome.

Objective T o infer the frequency of dosage and m edication history investigate of the victim s in drug facilitated cases by the segm ental analysis of clonazepam in hair. Methods Freezing m illing un-der liquid nitrogen environm ent com bined w ith ultrasonic bath w as used as sam ple pretreatm ent in this study, and liquid chrom atography-tandem m ass spectrom etry w as used for the segm ental analysis of the hair sam ples collected from 6 victim s in different cases. T he concentrations of clonazepam and 7-am in-oclonazepam w ere detected in each hair section. Results C lonazepam and its m etabolite 7-am inoclon-azepam w ere detected in parts of hair sections from the 6 victim s. T he occurrence tim e of drug peak concentration w as consistent w ith the intake tim ing provided by victim s. Conclusion Segm ental analysis of hair can provide the inform ation of frequency of dosage and intake tim ing, w hich show s an unique evidential value in drug facilitated crim es.

Objective:To analyze the correlation between intra-extracranial arterial stenosis and silent cerebral infarction(SCI) in the elder with essential hypertension(EH). Methods:The results of color duplex ultrasonography(Duplex) and digital subtraction angiography(DSA) examination of 86 patients with essential hypertension complicated silent cerebral infarction were analyzed.The incidence of intra-and extracranial arterial stenosis and arthrosclerosis plaque were calculated.The comparative value of Duplex and DSA for evaluating atherosclerosis of extracranial carotid artery was analyzed using statistic methods. Results:The incidence of arthrosclerosis plaque was higher in SCI group than that in normal control group(62.79%,24%,P

Objective To establish a stable and reliable HPLC method and fingerprint reference substance for the measurement of the fingerprint, the practical quality control, and assay of the water-soluble components of Salvia miltiorrhiza. Methods The HPLC was run on C 18 columns with methanol-1.0 % glacial acetic acid solution as mobile phase in gradient elution mode at a flow rate of 1.0 mL/min. The chromatographic system suitability, the gradient elution mode, mobile phase acidity, and the effect of column type on fingerprint repeatability were tested. Results The HPLC fingerprints of the water-soluble extract of reference S. miltiorrhiza were obtained with very good resolution under the established chromatographic system. Fifteen peaks in the chromatograms were selected for the fingerprint identification and quality control of S. miltiorrhiza. The quality of ten batches of S. miltiorrhiza samples from different hibitats were assessed by comparing their chromatographic fingerprints with the reference fingerprints obtained at the same time, and the similarity showed no difference, eventhough the column filler was changed. Conclusion Because the inherent complexity of medicinal material components has been reflected by chromatographic fingerprints, there are many factors affecting the fingerprint repeatability for the changes of column type. The results of the quality assessment of S. miltiorrhiza, using fingerprints from different columns, are not all coincidence. In order to obtain the comparable and repeatable results in different laboratories, it is much practical with both a defined chromatographic system suitability and a fingerprint reference substance.

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

An LC-TOF /MS and LC-MS /MS method was established for the identification the related substances in ambrisentan.HPLC separation was carried out on an XBridge C18 column(4.6 mm ×150 mm,3.5 μm)with linear gradient elution using a mobile phase consists of acetonitrile,water and 0.15% formic acid.The structures of the related substances were identified by electrospray positive ESI high resolution TOF /MS and MS /MS spec-tra,and verified further through reference substances.Ambrisentan and its related substances can be separated under the established HPLC conditions.Ten related substances were detected and identified.The established method is useful for the identification of related substances in ambrisentan.The results obtained are valuable for its manufacturing process optimization and quality control.

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.