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 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.

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.

Pulmonary vein isolation (PVI) is a new ,effective and radical method to cure atrial fibrillation .Within a period after radiofrequency ablation (RFA) ,coagulation system is activated in patients ,then thrombus incident such as cerebral embolism may happen .The present article made a review on its mechanism .

Objective Breast intraductal papillary lesion ( BIPL) has a low incidence but a high rate of malignancy .This study discusses the diagnostic value of conventional ultrasonography ( US) combined with ultrasonic elastography ( UE) for breast papil-lary lesion. Methods We analyzed the preoperative ultrasound data of 48 patients with 63 BIPLs, and classified them according to the characteristics of two-dimensional ultrasound (2DUS) images.Then we compared their color Doppler ultrasound characteristics and UE features with the pathological results . Results Based on the 2DUS findings, the BIPLs were divided into 4 types.The sensitivi-ty, specificity, and accuracy of conventional US +UE in the diagnosis of BIPL were 93.2%, 88.9%, and 90.5%, respectively, markedly higher than those of conventional US (75.6%, 66.7%, and 73.0%), with statistically significant differences in the areas under the curve between the two methods (0.918 vs 0.838, P<0.05). Conclusion Conventional US combined with UE can im-prove the diagnosis of breast intraductal papillary lesion .

Objective To explore the effect of extracellular regulated protein kinases (ERK) signaling pathway on early brain injury and autophagy of nerve cell in hippocampus area in rats with subarachnoid hemorrhage (SAH). Methods Forty-eight adult male Sprague-Daw-ley rats were randomly divided into sham group, SAH group, SAH+dimethyl sulfoxide (DMSO) group and SAH+U0126 group, with 12 rats in each group. The SAH model was established with puncture of internal carotid artery. The SAH+U0126 group was injected with U0126 0.05 mg/kg;the sham group and SAH group were injected with normal saline, and the SAH+DMSO group was injected with DMSO 30 min-utes before modeling. They were sacrificed 24 hours after modeling. The brain water content was measured with wet and dry method. The morphology changes of neural cells in hippocampus CA1 were observed by HE staining. The expression of phosphorylation ERK (p-ERK), Beclin-1 and LC3-Ⅱwere detected with immunohistochemical method and Western blotting. Results Compared with the sham group, the brain water content increased (P<0.05), the number of survival neurons decreased (P<0.05), the expression of p-ERK, Beclin-1 and LC3-Ⅱincreased in SAH group (P<0.05). Compared with SAH group, the brain water content increased, the number of survival neurons decreased (P<0.05), the expression of p-ERK, Beclin-1 and LC3-Ⅱ decreased in SAH+U0126 group (P<0.05); and no significant difference was found in SAH+DMSO group (P>0.05). Conclusion The activation of ERK signaling pathway may alleviate early brain injury after SAH by regulation of autophagy.

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.

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.