Effect of carrier size and surface morphology on the aerosolization of formulation in a capsule-based dry powder inhaler / 药学学报

The size and surface morphology of carrier lactose had influence on the aerosolization performance of dry powder inhalers. In this article, chlorpheniramine maleate was blended with two types of commercial carrier lactose, which were Lactohale 100® and Respitose SV003® (SV003), as formulation model. In vitro experiments were conducted using fast screening impactor at 30 L·min-1 and 60 L·min-1 respectively. Meanwhile, computational fluid dynamics (CFD) coupling with discrete element modelling (DEM) was applied to discuss the movements of those two carrier particles in Handihaler® at the flow rate mentioned above. The dispersion characteristics of two formulations and the dispersion mechanism of Handihaler® were analyzed by establishing the relationship between in vitro experiments and numerical simulation. The results of in vitro experiments and CFD-DEM demonstrated that the aerosolization performance of formulation with SV003 was better. The linear correlation (R2 = 0.940 1) between fine particle dose and total energy loss by carrier collision within the wall of device was found by comparing the in vitro experimental results with CFD-DEM results. It revealed that particle-wall collision in Handihaler® had direct impact on the dispersion results of formulation.

Cloning and characterization of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR) gene from Paris fargesii Franch.

3-Hydroxy-3-methylglutaryl-coenzyme A reductase (HMGR) plays an important role in catalyzing the first committed step of isoprenoids biosynthesis in mevalonic acid (MVA) pathway. Here, we cloned a full-length transcript of Paris fargesii Franch. The full-length cDNA of P. fargesii HMGR (Pf-HMGR, GenBank accession no. JX508638) was 1,973 bp and contained a 1,728 bp ORF encoding 576 amino acids. Sequence analysis revealed that the deduced Pf-HMGR had high similarity with HMGRs from other plants, including Ricinus communis (77%), Litchi chinensis (76%), Michelia chapensis (75%) and Panax quinquefolius (72%). It had a calculated molecular mass of about 62.13 kDa and an isoelectric point (pI) of 8.47. It contained two transmembrane domains, two putative HMGR binding sites and two NADP(H)-binding sites. The predicted 3-D structure revealed that Pf-HMGR had a similar spatial structure with other plant HMGRs. Three catalytic regions, including L-domain, N-domain and S-domain were detected by structural modeling of HMGR. Tissue expression analysis revealed that Pf-HMGR was strongly expressed in roots and stems than in leaves. Taken together, our data laid a foundation for further investigation of HMGR's functions and regulatory mechanisms in plants.

Efficacy of lamivudine on acute-on-chronic liver failure in patients with chronic hepatitis B / 中华肝脏病杂志

To observe the therapeutic effects of lamivudine treatment in patients with early- to mid-stage hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF). Clinical data of 73 hospitalized patients with HBV-ACLF were retrospectively analyzed. Prothrombin time (PT, active coagulation), HBV DNA, and model for end-stage liver disease (MELD) score data from treatment weeks 4, 8, 24, and 48 were collected and analyzed using the statistical t-test. During the treatment duration, the complete virologic response rates were 57.5% (42/73) at 4 weeks, 71.0% (44/62) at 8 weeks, 83.1% (49/59) at 24 weeks, and 86.5% (45/52) at 48 weeks. The partial virologic response rates were 30.1% (22/73) at 4 weeks, 25.8% (16/62) at 8 weeks, 17.0% (10/59) at 24 weeks, and 13.5% (7/52) at 48 weeks. At week 48, the survival rate was 71.2% (52/73) and the probability of survival was higher in the complete virological response rate (VRR) group than in the partial VRR group [45/73 (61.6%) vs. 7/73 (30.1%), respectively; P = 0.000]. In addition, there were significant improvements in the serum normalization rate of HBV DNA, alanine aminotransferase, aspartate aminotransferase, albumin, total bilirubin, PT and MELD score in surviving patients compared to baseline (P less than 0.05) and in the complete VRR group compared to the partial VRR group (P less than 0.05). Antiviral therapy using lamivudine may be an effective therapeutic option for patients with HBV-ACLF.

Construction and identification of siRNA eukaryotic expression vectors targeting on TGFβ1, TIMP-1 and TIMP-2 genes in vitro / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To construct the siRNA eukaryotic expression vectors targeting on TGFβ1, TIMP-1 and TIMP-2 and to investigate the inhibitory efficiency of target genes expression on rat hepatic stellate cell in vitro.</p><p><b>METHODS</b>The siRNA cDNA sequences of TGFβ1, TIMP-1 and TIMP-2 were designed, synthesized and inserted into plasmid pGenesil-1 respectively to generate eukaryotic expression plasmids. The plasmids were transfected into HSC T6 cells in vitro and the inhibitory efficiency of target genes expression was observed with real-time PCR and Western blot.</p><p><b>RESULTS</b>The eukaryotic expression vectors were constructed successfully. The expressions of TGFβ1 mRNA, TIMP-1 mRNA and TIMP-2mRNA in siRNA-transfected groups were decreased by 63.4% ± 8.0%, 64.5% ± 9.0% and 55.0% ± 17.0% respectively and the expressions of TGFβ1 protein, TIMP-1 protein and TIMP-2 protein were decreased by 57.8% ± 3.0%, 55.1% ± 5.0%, 49.3% ± 1.0% respectively as compared to the control groups.</p><p><b>CONCLUSIONS</b>The siRNA eukaryotic expression vectors constructed targeting on TGFβ1, TIMP-1 and TIMP-2 could reduce the expressions of target genes and they might be able to used for the exploration of new anti-fibrosis drugs genetically.</p>

Development and application of the physical hypoxic models of C. elegans / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To develop a suitable hypoxic injury model, which is important for revealing pathological molecular mechanism of hypoxia.</p><p><b>METHODS</b>We focused on C. elegans by treatment with different hypoxic times and systematically observed mortality, movement, Cellular morphology and the related-protein expression of the animals.</p><p><b>RESULTS</b>We demonstrated that hypoxia (0.2% partial pressure of oxygen) induced morphological cell defects, and then leading to death of C. elegans. The mortality of C. elegans increased along with hypoxic time, while hypoxia-inducible factor (HIF-1) was significantly up-regulated. In addition, by using neuron-specific transgenic wonns with green fluorescent protein--we observed the neuron-specffic injury caused by hypoxic stress.</p><p><b>CONCLUSION</b>We successfully established an effective, convenient physical hypoxic model of C. elegans, which will facilitate the studies of hypoxic pathology and molecular mechanisms of hypoxic response in the future.</p>

Clinical Characteristics of Paroxysmal Kinesigenic Choreoathetosis:Diagnosis,Treatment and Prognosis / 华中科技大学学报（医学）（英德文版）

The clinical characters,diagnosis and differential diagnosis of paroxysmal kinesigenic choreoathetosis (PKC),and efficacy of the anti-epileptic drugs (AEDs) were investigated.Thirty-one patients with PKC were collected,and the clinical characters and change of EEG were analyzed.The average age of the first attack was 16.8 years old and the pinnacle was 10 to 20 years old.There were definite causes for every attack and the sudden movement was the most common one (92%).Time for the whole attack was always less than 1 rain.The attack presented with muscle tension disturbance (83.9%),movement like dancing (16.1%),abnormal movement of mouth and face and other symp-toms (16.2%).The attack tended to be very frequent and 71% patients were beyond once per day.The EEG examination and image scan of primary PKC were normal in most patients.Low dosage of AEDs could control the attack of 50%-77.3% patients.It was concluded that PKC was a common disease of movement disorder.The therapy by AEDs was very effective.PKC should be differentiated from epilepsy and the relationship between PKC and epilepsy needs further research.

An approach to adaptive stereo brain image's segmentation / 中国医疗器械杂志

This paper presents a new method for automatically segmenting brain parenchyma and cerebrospinal fluid in routine single-echo MR images. This method is based on the coupled Markov models. They can model intensity measurement at each voxel site to implement piecewise smoothness constraint, and at the same time, model discontinuities to control the interaction between each pair of the neighboring voxel. The method is to derive the maximum a posteriori estimate of the regions and the boundaries by using Bayesian inference and neighborhood constraints based on Markov random fields (MRFs) models. This method has the following desirable properties: (1) the brain image can be well classified into white matter, grey matter and cerebrospinal fluid (CSF), and (2) it has a better robustness to noise and intensity inhomogeneity.

Multi-target extraction algorithm based on edge restriction and attraction field regularization / 中国医疗器械杂志

The topologically-adaptable model is an effective method for the contour detection of multiple objects on an image. However, it meets many problems when we apply it to MR brain images, such as poor convergence to boundary concavities, resulting from the broken boundary, and miserable anti-noise ability. In this paper, we proposes a new algorithm, named multi-target extraction algorithm based on edge restriction and attraction field regularization, to overcome these shortcomings. This new algorithm uses prior knowledge about target to perform edge restriction to get the only edge of the object of interest and to regularize attraction field to enlarge attraction field. Results show that the new algorithm can extract the target contour quickly and accurately when we apply it in MR brain images.

Segmenting lung fields in serial chest radiographs using both population and patient-specific shape statistics / 中国医疗器械杂志

This paper presents a new deformable model using both population-based and patient-specific shape statistics to segment lung fields from serial chest radiographs. First, a modified scale-invariant feature transform (SIFT) local descriptor is used to characterize the image features in the vicinity of each pixel, so that the deformable model deforms in a way that seeks for the region with similar SIFT local descriptors; second, the deformable model is constrained by both population-based and patient-specific shape statistics. At first, population-based shape statistics plays an leading role when the number of serial images is small, and gradually, patient-specific shape statistics plays a more and more important role after a sufficient number of segmentation results on the same patient have been obtained. The proposed deformable model can adapt to the shape variability of different patients, and obtain more robust and accurate segmentation results.

Non-linear registration of MR brain images integrated with machine learning / 中国医疗器械杂志

This paper presents a machine learning method to select best geometric features for deformable brain registration for each brain location. By incorporating those learned best attribute vector into the framework of HAMMER registration algorithm, The accuracy has increased by about 10% in estimating the simulated deformation fields. At the same time, on real MR brain images, we have found a great deal of improvement of registration in cortical regions.