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

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.

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.

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 .

ABSTRACT:Objective To explore role of U0126,the specific inhibitor of ERK signaling pathway,in early brain injury (EBI)and the autophagy of nerve cells in hippocampus area in subarachnoid hemorrhage (SAH). Methods A total of 48 male adult SD rats were randomly divided into control group,SAH group,DMSO+SAH group,and U0126+SAH group,with 12 in each.We established SAH rat model by the puncture of internal carotid artery.The same amount of saline water,DMSO and U0126 solution of 0.5 mL per rat was injected respectively into the rats of different groups 30 min before modeling.The rats were killed at 24 h.To measure brain water content by Wet and dry method after 24 h,the morphological changes of hippocampus CA1 neural cells were observed by microscopy;the expression levels of ERK,Beclin-1 and LC3 were detected by using immunohistochemical method. Results Compared with that in sham group,brain water content increased obviously in SAH model group.The density of surviving neurons in SAH group was significantly lower than that in control group (P<0 .0 5 ).ERK signaling pathway was activated obviously,the expressions of Beclin 1 and LC3-Ⅱ were significantly higher than those in control group (P<0.05).Compared with SAH model group,in U0126 group brain water content increased obviously.Compared with those in SAH group,the density of surviving neurons was significantly lower (P<0.05), ERK signaling pathway was suppressed,the expressions of Beclin-1 and LC3-Ⅱ were significantly lower (P<0.05). Conclusion The U0126,the ERK signaling pathway inhibitor,can inhibit neuron autophagy and increase EBR of SAH.

Objective To detect the mutation frequency of EML4-ALK fusion gene in lung cancer patients, and to inves-tigate the distribution of mutation character for EML4-ALK fusion gene in Ⅰ stage lung cancer patients and clinical features as well as provide a reference for the individual treatment of lung cancer .Methods 256 fresh tumor tissue specimens of lung cancer patients were screened from the specimen bank of our hospital and all the patients had accepted the surgical treatment from February 2013 to December 2014.Total RNA was extracted and then be transcribed into cDNA, the amplification-refrac-tory mutation system(ARMS) was used to detect mutation of EML4-ALK fusion gene.The results according to the positive con-trol, negative control and RNA quality control for EML4-ALK fusion type were analyzed.Results During the 256 patients ofⅠ stage lung cancer, there were 17 patients(6.64%) had mutations in EML4-ALK fusion gene.In lung adenocarcinoma mu-tation rate(16/207, 7.73%) was higher than that of lung squamous cell mutation rate(1/39, 2.56%), lung adeno-squamous mutation rate(0/4, 0) and large cell carcinoma(0/5, 0) of the mutation rate;young lung cancer patients( <63 years) of the mutation rate(14/139, 10.07%) was significantly higher than the high age of lung cancer patients(≥63 years old) mutation rate(3/117, 2.56%), P =0.009.EML4-ALK fusion with tumor invasion and visceral pleura group incidence (9/80, 11. 25%) was significantly higher than that of non-invasive and visceral pleura group incidence rate(8/176, 4.55%), P =0.045.Conclusion The occurence of EML4-ALK fusion correlates with patients’ age as well as whether visceral pleura is in-vaded, type 1 EML4-ALK fusion was detected more in phase I lung cancer patients.

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 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.