This study was aimed to develop a maximum a posteriori Bayesian (MAPB) estimation method to estimate individual pharmacokinetic parameters based on D-optimal sampling strategy. Meanwhile, the performance of MAPB was compared with the multiple linear regression (MLR) method in terms of accuracy and precision. Pharmacokinetic study of pioglitazone was employed as the example case. The population pharmacokinetics was characterized by nonlinear mixed effects model (NONMEM). The sparse sampling strategy (1-4 points) was identified by D-optimal algorithm using WinPOPT software. The simulated data generated by Monte Carlo method were used to access the performance of MAPB and MLR. As the number of samples per subject decreased, the accuracy and precision of MAPB method tended to get worse. The estimation for CL and Vby MAPB using D-optimal two-point design had less bias with low inter-individual variability, and had more bias and imprecision with high residue variability. The estimation of AUC by MAPB using D-optimal 2 points design had similar accuracy and precision to MLR. However, MAPB estimation was better than MLR while adjusting the sampling time to one hour. Overall, the MAPB method had similar predictive performance as MLR, but MAPB could provide more pharmacokinetic information with higher sampling flexibility.

OBJECTIVE: To evaluate the efficacy and safety of standardized subcutaneous immunotherapy for dust mite in patients with allergic rhinitis. METHOD: Using self-control methods, 35 cases with allergic rhinitis were treated with specific immunotherapy for 2 years. Symptom score and visual analogue scale (VAS) score were observed before treatment and 1 years, 2 years after treatment respectively. RESULT: The symptoms, signs and VAS score of the 35 patients who were treated with specific immunotherapy after 1 year were significantly reduced than that before treatment, the differences were statistically significant (P < 0.05). The symptoms, signs and VAS score of the patients who completed 2 years' treatment, compared with that of pretreatment and 1 year treatment were significantly reduced, the differences were statistically significant (P < 0.05). CONCLUSION Standardized immunotherapy for dust mite is a safe, effective method for patients with perennial allergic rhinitis, which can be used as a routine treatment for allergic rhinitis. To further improve the therapeutic effect, immunotherapy should be continued for at least 2 years.
Adolescent ; Adult ; Allergens ; administration & dosage ; Child ; Female ; Humans ; Immunotherapy ; Male ; Middle Aged ; Rhinitis, Allergic ; therapy ; Treatment Outcome ; Young Adult

The purpose of this study is to investigate the effects of multiple-trough sampling design and nonlinear mixed effect modeling (NONMEM) algorithm on the estimation of population and individual pharmacokinetic parameters. Oxcarbazepine and tacrolimus were used as one-compartment and two-compartment model drugs, respectively. Seven sampling designs were investigated using various number of trough concentrations per individual ranging from 1-4. Monte Carlo simulations were performed to produce state-steady trough concentrations. One-compartment model was used to fit simulated data from oxcarbazepine and tacrolimus. The accuracy and precision of the estimated parameters were evaluated using the median prediction error (PE), the median absolute PE and boxplot. The results indicated that trough concentrations could yield reliable estimates of apparent clearance (CL/F). For oxcarbazepine, as the number of trough concentrations per subject increased, the accuracy and precision of CL/F, between-subject variability (BSV) of CL/F and residual variability (RUV) tended to be improved. For tacrolimus, however, although no improvement were observed in the accuracy of CL/F and BSV of CL/F, the PE distribution ranges were significantly narrowed and the RUV estimates were less bias and imprecise. In terms of algorithm, Monte Carlo importance sampling (IMP) and IMP assisted by mode a posteriori estimation (IMPMAP) were consistently better than other methods. Additionally, the sampling design had no significant effects on the individual parameter estimates, which were only depended on the interaction between BSV and RUV in various algorithms. Decreased in BSV and RUV levels can improve the accuracy and precision of the estimation for both population and individual pharmacokinetic parameter estimates.

Objective To evaluate the clinical effects of AO clavicula hook plate in treatment of acromioclavicular dislocation. Methods According to the specific anatomic, physiological and biomechanical conditions of the patients, 43 cases of complete acromioclavicular dislocation were treated either by AO clavicula hook plate (23 cases),or by Kirschner pin and steer wire tension band (20 cases). Results The results were evaluated by radiographic representations and joint function recovery according to Karlsson's criteria. The excellent results of the 2 methods were 95.6% and 65% respectively. There was significant difference. Conclusions The AO clavicula hook plate can meet the clinic requirements and be used with satisfactory results in the treatment of acromioclavicular dislocation.

Objective To investigate the prognosis of the intra-aortic balloon pump (IABP) used for patients with acute myocardial infarction and to the risk factors. Methods 88 patients accepted IABP were analyzed retrospectively. Results In spite of overall survival rate (54.5%), under circumstances of percutaneous coronary intervention (PCI), survival rate could reached to 59.9%, with 31.6% and 72.5% in cardiogenic shock group and high-risk group respectively. The time of IABP application increased in drug group. Multivariate Logistic Regression Analysis demonstrated independent-predictor effects of C-reactive protein (CRP), pulmonary infection, renal dysfunction, and wall motion disorder. Moreover, type of coronary artery disease (CAD), renal function, ejection fraction and pre-IABP mean arterial blood pressure could influence the time of IABP application. Conclusion In view of safety, IABP could be used to provide circulatory support for patients with very high risk as well as with cardiogenic shock. Application of IABP could hardly improve in-hospital mortality, and the time of IABP-using could be influenced by many clinical factors, such as type of CAD, renal dysfunction, etc.

ObjectiveTo observe the clinical effect of Kangxiuke apozem in the treatment of severe bum shock.Methods40 patients of severe burn shock were randomly divided into a treatment group and a control group,with 20 patients in each group.All the patients were treated by the same route of counter-shock therapy,and the treatment group was additionally given Kangxiuke apozem (nasal feeding,qd,150 ml/d).Level of blood lactic acid,heart rate and urinary volume were evaluated by time.Main shock symptoms,including restlessness,hydrodipsia,perspiration and coldness,were observed.ResultsThe treatment group was significantly superior to the control group in the amelioration of blood lactic acid,heart rate and urinary volume ( t =10.485、3.219、7.429,P＜ 0.01 ).The symptomatic extinction of restlessness,hydrodipsia,perspiration and coldness in the extremities in the treatment group were significantly superior to those in the control group (x2=10.16、7.37、5.63、4.29,P＜0.05).ConclusionAt the same time of routine counter-shock therapy,thereby prompt burn patients to smoothly go through shock period and decreas late complications.

BACKGROUND:Extracellular matrix can simulate microenvironment and make the stem cells proliferate maintaining the characteristics of stem cells wel in vitro. OBJECTIVE:To prepare the extracellular matrix from human bone marrow cells and to analyze its microstructure and composition preliminarily. METHODS:Human bone marrow cells of passage 4 were cultured for 14 days, and the induction medium was used during the last 8 days. After decellularization, cells were removed to prepare human bone marrow cells-derived extracellular matrix. The surface morphology of human bone marrow cells-derived extracellular matrix was observed by inverted microscope and scanning electron microscope. Changes of col agen I and biglycan before and after decellularization were observed by immunofluorescence staining. Human periodontal ligament stem cells were seeded onto human bone marrow cells-derived extracellular matrix, fibronectin coated 6-wel plate and normal culture plate to compare the influence of different matrix on cellmorphology and adhesion. RESULTS AND CONCLUSION:We obtained intact human bone marrow cells-derived extracellular matrix by chemical combined with physical decellularization. The structure and amount of col agen I and biglycan had not been compromised dramatical y after decellularization. Human periodontal ligament stem cells growing on the human bone marrow cells-derived extracellular matrix developed in accordance with the orbit of the extracellular matrix, differing from the original cellmorphology. There were more human periodontal ligament stem cells adhering to the extracellular matrix during the same time. These findings indicate that effective decellularization can produce intact the extracellular matrix membrane without destroying its microstructure. Extracellular matrix protein is not compromised due to decellularization. The extracellular matrix affects cellmorphology and promotes celladhesion. We can use the extracellular matrix model to simulate stem cellmicroenvironment and thereafter, acquire a large number of adult stem cells with high quality in vitro.

Objective To investigate the effects of tuina manipulation on creep rate and maximal breaking stress of contractural Achilles tendons of rabbits. Methods Twenty-four rabbits were randomly divided into contrac-tural Achilles tendon model group, free activities group and tuina manipulation group. The opposite legs of model group were used as normal controls. Creep rate and maximal breaking stress of Achilles tendons were compared among the 4 groups. Results The average creep rate in tuina manipulation group approximated to that in normal group and was lower than that in model and free activities groups. The average maximal breaking stress in tuina manipulation group approximated to that in normal group and was higher than that in model and free activities groups. Conclusion Tuina manipulation can promote the creep rate and maximal breaking stress of contractura Achilles tendon approximately to normal level. Tuina manipulation may be useful in rehabilitation.

Objective To investigate low density lipoprotein receptor (LDLR)gene mutation in familial hypercholesterolemia (FH) patients. Methods The proband was given clinical diagnosis of homozygous FH based on marked features and blood lipid tests results. After apoB100R3500Q mutation was excluded, the promoter region and all of the 18 exons of LDLR gene were amplified by touch-downpolymerase chain reaction (PCR). The PCR products were analyzed by single-strand conformationalpolymorphism (SSCP). The PCR products with abnormal single strands were sequenced directly. Thesecondary structures of the mutational and wild type proteins were analyzed and compared byANTHEPROT5.0, and then the tertiary structures of the mutant and wild type LDLR were predicted atSWISS MODEL homepage online. Results A homozygous mutation A606T at exon 13 of the patients wasfound by SSCP and confirmed by DNA sequencing. GOR Ⅰ method in ANTHEPROT5.0 indicates that therandom coils and turns would replace some helixes at the mutation site. The online prediction from theSWISS MODEL homepage indicates the backbone structure of the mutant LDLR has no difference from thewild type one. Conclusion The results suggest the A606T mutation of LDLR gene is the cause of the FH inthis pedigree.

Objective To observe the short-term effect of radial head replacement for the treatment of terrible triad of the elbow.Methods In the period between June 2011 and June 2012,the radial head replacements were carried out in six patients with terrible triad of elbow.There were five acute elbow fracture-dislocation cases and one old fractnre case.All cases underwent open reduction and fixation coronoid fracture with screws or nonabsorbable sutures,radial head replacement,repair of lateral ligament complex and repair or reconstruction of annular ligament.All patients initiated the rehabilitation program under supervision within 5-7 days after surgery.The X-ray and Computed tomography of elbow was used to evaluate the posi tion of radial head prosthesis.Functional outcome of elbow was assessed by Mayo Elbow Performance Score (MEPS) and complications.Results All patients were participated in follow-up for 10-24 months and the mean duration of follow-up was 16.8 months.The MEPS was from 85 to 95 points and the mean MEPS was 91.7 points.The outcome of MEPS was excellent in 5 cases,good in 1 case.The range motion of elbow flexion was from 82 to 95 degrees and the average of elbow flexion was 87 degrees; the range motion of extension was from 15 to 32 degrees and the average of elbow extension was 21 degrees.The range motion of fore-ann pronation was from 82 to 90 degrees with 86 degrees in average.The motion range of supination was from 45 to 80 degrees with 56 degrees in average.All cases got persistent stability in elbow with painless movement.None of patient suffered traumatic arthritis and infection.The motion range of elbow was restricted due to the unfit relative position of radial head prosthesis and capi tellum in one case,characterized by decreasing radiocapitellar joint space.Two cases developed into heterotopic ossification in elbow without hampering the motion range of elbow.Conclusion The outcome of the radial head replacement on the treatment of radial head fracture in the elbow terrible triad was satisfactory.However,the longer duration of observation was essential to verify the favorable effect of radial head replacement on dealing with terrible triad in elbow.