With the advance of drug development and research techniques, the drug metabolic processes and mechanism can be more deeply achieved. As the drug metabolism and pharmacokinetics process are mediated by drug metabolizing enzymes and transporters, study of drug metabolizing enzymes and transporters has become an important part for drug development. The traditional immunoassays with low sensitivity and poor specificity can not reflect the accurate expression level of drug metabolizing enzymes and transporters. We now give a brief review on the quantitative study of drug metabolizing enzymes and transporters by mass spectrometry-based proteomic approach.

Objective To explore the correlation of B-type natriuretic peptide (BNP) with blood lipids and renal function in elderly patients with coronary heart disease (CHD).Methods According to the four quantiles of BNP level,325 subjects aged 65 years and over were divided into four groups:group A (≤32.4 ng/L),group B (32.5 ng/L),group C (62.4 ng/L),group D (＞ 162.5 ng/L).The left ventricular ejection fraction (LVEF),left ventricular end-diastole dimension (LVEDD),levels of blood lipids and renal function were compared among the groups.Results With the increase of BNP level,the LVEF was gradually decreased [(63.3±8.2) ％,(59.6±7.4) ％,(57.9±9.7)％,(55.2±10.6)％,respectively,F=11.54,P＜0.01] and the LVEDD was gradually increased (F=6.76,P＜0.01),the level of triglyceride (TG) was gradually decreased (F=2.73,P ＜0.05) in group A,B,C and D.Creatinine clearance was gradually decreased [(1.24±0.31) ml ·s-1 · 1.73 m-2,(1.21±0.31) ml· s-1 · 1.73 m-2,(1.24±0.29) ml · s-1 · 1.73 m 2,(1.09± 0.33) ml · s-1 · 1.73 m-2,respectively,F=3.62,P＜0.05],and blood urea nitrogen was gradually increased (F=4.43,P＜0.05) in group A,B,C and D.Multi-linear regression analysis showed that levels of total cholesterol,triglyceride,low density lipoprotein-cholesterol,high density lipoproteincholesterol,very low density lipoprotein-cholesterol,creatinine clearance and blood urea nitrogen were influencing factors for BNP (all P＜0.05).Conclusions BNP level can be used as a sensitive indicator for the diagnosis of heart failure and the assessment of its severity.The levels of blood lipids and renal function are associated with BNP.

OBJECTIVETo compare efficacy of unilateral external fixators and locking compression plates in treating type C fractures of the distal radius.

METHODSFrom January 2009 to June 2010, 76 patients with distal radius fracture were treated with LCP and external fixators, 54 patients were followed up. Among them, 29 cases were male and 25 cases were female with an average age of 45.31 (ranged, 24 to 68) years old. There were 29 patients in LCP group. According to AO classification, 8 cases were type C1, 7 cases were type C2 and 14 cases were type C3. There were 25 cases in external fixators group. According to AO classification, 6 cases were type C1, 8 cases were type C2 and 11 cases were type C3. Radial height, volar tilt and radial inclination were compared, advanced Gartland-Werley scoring were used to assessed wrist joint function after 6 and 12 months' following up.

RESULTSTwo cases were suffered from nail infection in external fixators group. Fifty-four patients were followed up from 12 to 24 months with an average of 21.3 months. Radial height was (9.60 +/- 0.72) mm, volar tilt was (9.55 +/- 0.80) degrees and radial inclination was (21.40 +/- 0.78) degrees in LCP group,while those were (9.40 +/- 0.70) mm, (9.47 +/- 0.71) degrees and (21.20 +/- 0.73) degrees in external fixtors group, and with no statistical significance (P>0.05). Advanced Gartland-Werley score after 6 months' following up was 3.31 +/- 1.17 in LCP group, 5.56 +/- 1.58 in external fixtors group, and with significant difference (t=-5.99,P<0.05); after 12 months' following up, advanced Gartland-Werley score was respectively 2.66 +/- 1.01 and 3.08 +/- 1.00, but with no statistical meaning (t=-1.55, P>0.05).

CONCLUSIONLCP and external fixtors can receive good curative effects in treating type C distal radius fracture, and LCP can obtain obviously short-term efficacy, while there is no significant difference between two groups in long-term results. For serious distal radius comminuted fracture which unable to plate internal fixation, external fixators is a better choice.

Adult ; Aged ; Bone Plates ; External Fixators ; Female ; Fracture Fixation, Internal ; Fractures, Comminuted ; surgery ; Humans ; Male ; Middle Aged ; Radius ; surgery ; Radius Fractures ; surgery ; Treatment Outcome ; Young Adult

This paper is to evaluate the biocompatibility and cytotoxicity of a new Ni-free Zr-based bulk metallic glass (BMG), Zr60.14 Cu22.31 Fe4.85 Al9.7 Ag3, by comparing it with conventional Ti6Al4V alloy. According to ISO 10993-5: 1999 and GB/T 16886.5-1997 standards, Zr60.14 Cu22.31 Fe4.85 Al9.7 Ag3, pure Zr and Ti6Al4V materials were extracted with surface area of sample/volume of medium ratio being 1 cm2/mL and 0.5 cm2/mL, respectively. The viabilities of MG-63 cells (Human osteosarcoma cell line) cultured in the BMG medium extracts for 1, 3 and 5 days were determined by CCK-8 assay. The cellular morphology of MG-63 cells cultured on the surface of samples for 3 days was tested through laser scanning confocal microscopy (LSCM) and scanning electron microscopy (SEM). The relative growth rate (RGR) of MG-63 cells cultured in Zr60.14 Cu22.31 Fe4.85 Al9.7 Ag3 and pure Zr were both more than 85%, indicating that the cytotoxicity of BMG was relatively low and met the national biomedical material eligibility standard. There was insignificant difference in the morphology of MG-63 cells cultured in the BMG medium extracts and the control group through LSCM and SEM, which showed the BMG had excellent biological compatibility. The Zr-based bulk metallic glass Zr60.14 Cu22.31 Fe4.85 Al9.7 Ag3 and the conventional Ti6Al4V alloy both had no obvious cytotoxicity to MG-63 cells. These results provided evidence that the new Zr-based bulk metallic glass could be potential replacement material for the orthopedic surgical implant.
Alloys ; Biocompatible Materials ; Cell Line ; Glass ; Humans ; Microscopy, Electron, Scanning ; Nickel ; Titanium ; Zirconium

Objective To explore the differences of the joint function and the patient's satisfaction between two different methods to reconstruct limb length for unilateral Crowe Ⅳ developmental dysplasia of the hip (DDH).Methods The clinical controlled study were used.21 cases with unilateral DDH Crowe Ⅳ treated with total hip arthroplasty were divided into 2 groups randomly.The patients in the first group were reconstructed the limb with the compensatory length and those in the second group were did with the real length.The patients were followed up 10 years.Two independent sample t-test was used to compare these two operations.Harris scores and SF-36 scores were used in the test.Survival analysis with Kaplan-Meier method was involved in the survival of the prosthesis and then test with Log-rank test.X-ray films of different period were compared to confirm the prosthetic loosening.Results Seventeen patients were followed up 8-10 years.There were no significant differences both in Harris score and most of the SF-36 scores at the median follow-up of 10 years.The item mental healthy of SF-36 expressed significant difference.Five patients required revision.There were 10 cases suffered with polyethylene wear,6 cases with severe osteoporosis in greater trochanter,and 3 cases with osteolytic reaction.Conclusion There are no significant differences between the two surgical method in the survival rate of prosthesis and the joint function in the median follow up.The satisfaction of the control groups is lower than the trial groups both at the early stage after the operation and the median follow up.The revision rate between the two groups is similar but the reason is different.

Objective To investigate the expression difference of vascular endothelial growth factor (VEGF)between lung cancer and lung benign disease,and its relation to clinical characteristics and prognosis of non-small cell lung cancer(NSCLC),and to research the possible role of VEGF in the growth of lung can- cer.Methods The expression of VEGF and microvascular density(MVD)were detected in 60 lung cancer tissues and 30 lung benign disease tissues after operation by immunohistochemical method and put up statisti- cal analysis.Results The positive rate of VEGF expression(63%)and MVD(45.13?10.27)in lung cancer tissues were both higher than those in lung benign disease tissues(27%,33?6.49)(P

In this study, the rapid resolution liquid chromatography-quadrupole time-of-flight mass spectrometry (RRLC-QTOF/MS) was used to profile the metabolites of urine samples from chronic heart failure (CHF) patients and healthy controls to find the differential metabolites which could provide the scientific evidence to explain the pathogenesis of the disease and supply a better therapy plan.Urine samples from 15 CHF patients (age (62.27±3.14) years) and 15 healthy controls (age (65.41±4.63) years) were analyzed by RRLC-QTOF/MS.After processing the data, the multivariate statistical analysis (principal component analysis, PCA) was performed to find the potential biomarkers.Result showed that urine samples of CHF patients were successfully distinguished from those of healthy controls.Two significantly differentially expressed metabolites, uridine and alanyltryptophan, were found and identified as potential biomarkers.The result showed that the LC-MS based metabolomics approach had good performance to identify potential biomarkers, and the disorder of uracil metabolism and Tryptophan metabolism may play an important role in the mechanism of CHF.

With the advance of drug development and research techniques, the drug metabolic processes and mechanism can be more deeply achieved. As the drug metabolism and pharmacokinetics process are mediated by drug metabolizing enzymes and transporters, study of drug metabolizing enzymes and transporters has become an important part for drug development. The traditional immunoassays with low sensitivity and poor specificity can not reflect the accurate expression level of drug metabolizing enzymes and transporters. We now give a brief review on the quantitative study of drug metabolizing enzymes and transporters by mass spectrometry-based proteomic approach.
Enzymes ; chemistry ; Humans ; Inactivation, Metabolic ; Mass Spectrometry ; Membrane Transport Proteins ; chemistry ; Pharmacokinetics ; Proteomics

Xiaoyao pills are a famous traditional Chinese medicine collected in Welfare Pharmacy, which is a classic prescription for treating liver depression and spleen deficiency. However, its composition is complex. In order to better control the quality of Xiaoyao pills, in this study, HPLC-ion-trap time-of-flight mass spectrometry (LC-IT-TOF/MS) was used to identify the main ingredients of Xiaoyao pills, paeoniflorin, albiflorin, glycyrrhizic acid, saikosaponin A and saikosaponin B2. Then a liquid chromatography tandem mass spectrometry (LC-MS/MS) was developed for simultaneous determination and quantification of the main compounds. Fragmentation pathways of five active components were obtained. The method was validated. Five active ingredients in Xiaoyao pills had a good linear relationship, and the values of RSD (%) of repeatability were all less than 5%, the recovery ranges were between 90% and 115%, and the values of RSD (%) of each substance were less than 10% after the sample solution is placed for 24 hours. Three batches of Xiaoyao pills (concentrated pellets) and two batches of Xiaoyao pills (water pellets) were determined, the contents of paeoniflorin in concentrated pills were more than 4.0 mg·g^-1, and those in water pills were more than 2.5 mg·g^-1, which was accordance with Chinese Pharmacopoeia. However, other compounds behave differently. This method has high sensitivity and reliable measurement results, which provides basis for quality control of Xiaoyao pills and material basis for pharmacology research.

OBJECTIVETo explore indication and approaches of neurotomy of tibial nerve for the treatment of the talipes equinovarus and spastic paralysis.

METHODA total of 25 patients including 15 patients with cerebral paralysis and other 10 patients were diagnosed with clear etiology, spastic muscles with supplied nerves were analyzed in detail, neurotomy of the tibial nerve was performed under microscope, during operation, motor nerve was lovated with electronic stimuli and monitored with induced electromyography. The surgical results were analyzed.

RESULTSA total of 36 of 37 (97%) neurotomy of the tibial nerve were improved with dorsum flex of ankle at 10 - 45 degree, and 22 of 24 (85%) talipes equinovarus improved clinically. Of 37 feet with surgery, 24 feet (65%) were in normal position and could touch ground completely, 9 feet (24%) had 10 degree with ground or could contact ground with external one third of the feet, 4 feet (11%) were abnormal. Of 25 patents, 21 (84%) had improvement of motor activity at discretion, 5 patients (20%) improved dramatically. All the 4 patients failed after the operation were cerebral paralysis, and were presumably related to disorders of spinal function, abnormal reflex and the disappearance of inhibitory reflex.

CONCLUSIONNeurotomy is an effective method to treat talipes equinovarus, and can improve the motor activity of low extremity.

Adolescent ; Adult ; Child ; Child, Preschool ; Clubfoot ; surgery ; Equinus Deformity ; surgery ; Female ; Humans ; Male ; Microsurgery ; Middle Aged ; Neurosurgical Procedures ; methods ; Tibial Nerve ; surgery ; Treatment Outcome