The design space of the high shear wet granulation process was established and validated within the framework of quality by design (QbD). The system of microcrystalline cellulose-de-ioned water was used in this study. The median granule size and bulk density of granules were identified as critical quality attributes. Plackeet-Burmann experimental design was used to screen these factors as follows: dry mixing time, the impeller and chopper speed of dry mixing, water amount, water addition time, wet massing time, the impeller and chopper speed of wet massing and drying time. And the optimization was implemented with the central composite experimental design based on screened critical process parameters. The design space of the high shear wet granulation process was established based on the quadratic polynomial regression model. Since the P-values of both models were less than 0.05 and values of lack of fit were more than 0.1, the relationship between critical quality attributes and critical process parameters could be well described by the two models. The reliability of design space, illustrated by overlay plot, was improved with the addition of 95% confidence interval. For those granules whose process parameters were in the design space, the granule size could be controlled within 250 to 355 μm, and the bulk density could be controlled within a range of 0.4 to 0.6 g x cm(-3). The robustness and flexibility of the high shear wet granulation process have been enhanced via the establishment of the design space based on the QbD concept.
Cellulose ; chemistry ; Reproducibility of Results ; Technology, Pharmaceutical ; methods ; Water

BACKGROUND:There are various therapies for children limb fractures involving the epiphysis or the metaphysis. According to the different methods, studies on the growth of the epiphyseal plate are a lot, most of which focus on the effects of Kirschner wires with different diameters or holow screw internal fixation on the development of epiphyseal plate. However, there are rare studies on the influence of cross-epiphyseal plate internal fixation on the growth of epiphyseal plate as wel as the influence level. OBJECTIVE:To prepare a peri-epiphyseal fracture model in young rabbits and to observe the effects of cross-epiphyseal plate implantation and removal on the growth of epiphyseal plate. METHODS: Traverse fracture models were made 5 mm above the right femoral distal epiphyseal plate of 60 young rabbits, and then fixed with suitable “L” steel plate and four screws across the epiphyseal plate and peri-epiphyseal fracture line. The left side served as control. Eight rabbits were kiled and observed at 2, 4, 8, 12 weeks after modeling, respectively, to take out the femoral specimens for measurement of femoral length, thickness of the epiphyseal plate, and number of mastocytes per unit column. Histopathology observation was done and changes in mastocytes and thickness of the epiphyseal plate were detected. Another seven rabbits were selected to remove the metal plate, continued to feed for 2 weeks and finaly executed to observe the above-mentioned indexes. RESULTS AND CONCLUSION: (1) There were significant differences in the above indexes between the plate and control groups at 4, 8, 12 weeks after modeling (P < 0.05 orP< 0.001) but not at 2 weeks after modeling (P> 0.05). These findings indicate that within 2 weeks after cross-epiphyseal plate internal fixation, proper pressue has no remarkable influence on the growth of epiphyseal plate; but after persistent internal fixation (> 4 weeks), the growth of epiphyseal plate can be partialy or completed retarded. (2) At 2 and 4 weeks after modeling, the plate was removed, and 2 weeks later, the femoral length, thickness of the epiphyseal plate and mastocyte counting per unit column were improved to different extents, and there were no differences between the plate and control group (P > 0.05). At 8 and 12 weeks after modeling, the plate was removed, and 2 weeks later, the femoral length and thickness of the epiphyseal plate were shortened, and the number of mastocytes per unit column was decreased obviously, which significantly differed from the control group (P < 0.001). These findings indicate that the chondrocytes in the proliferative and hypertrophy layers lose the differentiation and proliferation abilities, and the femoral length and epiphyseal plate thickness are difficult to recover.

OBJECTIVE: To explore the clinical treatment effects of sea buckthorn oil for in different size traumatic perforation of tympanic membrane in different size. METHOD: Prospective, randomized study of 199 outpatients with traumatic perforation of tympanic membrane who were enrolled between December 2012 and December 2014 after informed consent. The patients were divided into treatment group (101 cases) and control group (98 cases). According to the size of the perforations, patients in each group were divided into large perforation group, middle perforation groups and small perforation group. The cases in large perforation group, middle perforation groups and small perforation group were 36, 34, 31 in treatment group and 35, 33, 30 in control group. The patients in treatment group were treated with sea buckthorn oil once a week, while the patient in control group were self-healing and checked once a week. All the patients were followed-up in two months. The healing rate of two groups was applied for the evaluation indicator of clinical effect. We compared the healing rate, average healing time and phological change of tympanic membrane of patients at the first and second month. RESULT: The total healing ratio of patients in treatment group is 62.4% and 79.2% compared with 29.6% and 57.1% in control group at the first and second month (P < 0.05). There is statistical significance between the healing ratios of middle, large perforation groups in treatment group and control group (P < 0.05). There is no statistical significance between the healing ratios of small perforation group in treatment group and control group (P > 0.05). The average healing time of large, middle and small perforation group at the second month are significantly shorter than the control group. CONCLUSION It is better to apply observation method and let it self-healed for small traumatic tympanic membrane perforation according to its higher healing ratio. While, it is better to apply sea buckthorn oil method for middle and large traumatic tympanic membrane perforation according to its lower healing ratios. Sea buckthorn oil treatment is benefitial for increasing the ratio of perforation healing, shorten the healing time, resumpting of the middle ear function earlier, helping most of the patients to avoid operation and the reduce medical expense. Therefore, it is valuable to promote the method in clinical treatment.
Drugs, Chinese Herbal ; therapeutic use ; Hippophae ; Humans ; Plant Oils ; therapeutic use ; Prospective Studies ; Tympanic Membrane ; injuries ; Tympanic Membrane Perforation ; drug therapy ; Wound Healing ; drug effects

OBJECTIVETo study the effect of Jinlida on changes in expression of skeletal muscle lipid transport enzymes in fat-induced insulin resistance ApoE -/- mice.

METHODEight male C57BL/6J mice were selected in the normal group (NF), 40 male ApoE -/- mice were fed for 16 weeks, divided into the model group (HF), the rosiglitazone group ( LGLT), the Jinlida low-dose group (JLDL), the Jinlida medium-dose group (JLDM), the Jinlida high-dose group (JLDH) and then orally given drugs for 8 weeks. The organization free fatty acids, BCA protein concentration determination methods were used to determine the skeletal muscle FFA content. The Real-time fluorescent quantitative reverse transcription PCR ( RT-PCR) and Western blot method were adopted to determine mRNA and protein expressions of mice fatty acids transposition enzyme (FAT/CD36), carnitine palm acyltransferase 1 (CPT1), peroxide proliferators-activated receptor α( PPAR α).

RESULTJinlida could decrease fasting blood glucose (FBG), cholesterol (TC), triglyceride (TG), free fatty acid (FFA) and fasting insulin (FIns) and raise insulin sensitive index (ISI) in mice to varying degrees. It could also up-regulate mRNA and protein expressions of CPT1 and PPARα, and down-regulate mRNA and protein levels of FAT/CD36.

CONCLUSIONJinlida can improve fat-induced insulin resistance ApoE -/- in mice by adjusting the changes in expression of skeletal muscle lipid transport enzymes.

Animals ; Apolipoproteins E ; deficiency ; genetics ; Blood Glucose ; metabolism ; CD36 Antigens ; genetics ; metabolism ; Carnitine O-Palmitoyltransferase ; genetics ; metabolism ; Dietary Fats ; adverse effects ; metabolism ; Drugs, Chinese Herbal ; administration & dosage ; Humans ; Hypoglycemic Agents ; administration & dosage ; Insulin ; metabolism ; Insulin Resistance ; Lipid Metabolism ; drug effects ; Male ; Metabolic Diseases ; drug therapy ; enzymology ; genetics ; metabolism ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Muscle, Skeletal ; drug effects ; metabolism

OBJECTIVETo establish whether Coblation is a suitable modality for removal of early glottic carcinoma.

METHODSFourteen patients with early glottic carcinoma (Tis-T2) without lymph node metastasis underwent resection of laryngeal cancer lesions using transoral endoscopic coblation (TEC), without pre- or post-operative radiotherapy and chemotherapy.

RESULTSNo severe complication such as bleeding and dyspnea occurred in the cases. Only mild postoperative pain happened to the patients. All patients could eat and pronounce on the surgery day. With following-up of 25 - 37 months, no recurrence was observed in 13 cases. One case, with poorly differentiated squamous cell lesion in the anterior commissure invading subglottic, recurred 3 months postoperatively. The patient received the re-resection of laryngeal lesion by coblation, but another recurrence happened to the patient 6 months postoperatively, and then was cured by partial laryngectomy, with recurrence-free survival 21 months postoperatively.

CONCLUSIONThe observation suggests that transoral endoscopic coblation is a reliable and safe modality for the resection of early glottic carcinoma.

Adult ; Aged ; Carcinoma, Squamous Cell ; pathology ; surgery ; Catheter Ablation ; methods ; Glottis ; pathology ; Humans ; Laryngeal Neoplasms ; pathology ; surgery ; Laryngectomy ; Male ; Neoplasm Staging

A cobalt nanoparticles modified ITO electrode (NpCo/ITO) was prepared by casting cobalt nanoparticles onto ITO electrode and the cobalt nanoparticles were synthesized by NaHB4 reduction. The electrochemical behaviors of adriamycin (ADM) on NpCo/ITO were studied. The modified ITO electrode was characterized by cyclic voltammetry (CV), scanning electron microscopy (SEM) and energy dispersive spectroscopy (EDS). In a 0.01 mol L(-1) PBS (pH 8.0) buffer solution, a sensitive reduction peak of ADM was obtained. A linear relationship is held between the peak current and ADM concentration in the range of 1.0 x 10(-8) - 2.0 x 10(-6) mol L(-1) with detection of 5.0 x 10(-9) mol L(-1)- by cyclic voltammetry (CV) response. The reduction process was irreversible with adsorption at the NpCo/ITO electrode. The modified electrode showed an excellent electrocatalytic activity for the ADM electrochemical reduction.
Antineoplastic Agents ; chemistry ; pharmacology ; Clinical Laboratory Techniques ; Cobalt ; chemistry ; Doxorubicin ; chemistry ; pharmacology ; Electrochemistry ; Electrodes ; trends ; Nanoparticles ; chemistry

Animals ; Global Health ; History, 20th Century ; Humans ; Influenza A virus ; genetics ; isolation & purification ; Influenza, Human ; epidemiology ; history ; mortality ; virology ; Orthomyxoviridae Infections ; epidemiology ; veterinary ; virology ; Swine ; Swine Diseases ; epidemiology ; virology

OBJECTIVETo investigate the biochemical characteristic of the neurons associated Zusanli (ST 36) in the rat by using Alexa Fluor 594 conjugated cholera toxin subunit B (AF594-CTB) neural tracing and calcitonin gene-related peptide (CGRP) fluorescent immunohistochemical techniques.

METHODSFour male Sprague Dawley rats were injected with AF594-CTB into the corresponding area of the Zusanli in the human body. After 3 surviving days, the rat's spinal cord and dorsal root ganglia (DRGs) at lumbar segments were dissected following perfusion with 4% paraformaldehyde, cut into sections, and then stained with CGRPfluorescent immunohistochemical method.

RESULTSAF594-CTB labeled sensory neurons were detected in the L3-L6 DRGs with high concentration in L4 DRG, and the labeled motor neurons located in the dorsolateral and intermediate regions of lamina IX from L3-L5 segments with high concentration at L4. Meanwhile, CGRPpositive neural labeling distributed symmetrically on both sides of DRGs, anterior and dorsal horns of spinal cord. In the AF594-CTB labeled neurons, 37% sensory neurons and 100% motor neurons expressed CGRPpositive.

CONCLUSIONThese findings present the morphological evidence to demonstrate that the sensory and motor neurons associated Zusanli in the rat distributed with segmental and regional patterns, and contained CGRP-expression.

Acupuncture Points ; Animals ; Calcitonin Gene-Related Peptide ; metabolism ; Male ; Neurons ; metabolism ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo investigate the clinical value of 64-slice computed tomographic angiography (CTA)-based virtual colonoscopy in the diagnosis of colonic tumors.

METHODSPhilips/Brilliance 64 CT volumetric scanning was performed in 8 patients with colonic cancer and 2 with colonic polypi identified by postoperative pathological examination. Mimics software was used for surface rendering of the intestine with the Marching Cubes algorithm for 3-dimensional (3D) virtual endoscope (VE) reconstruction and CTA-based 3D reconstruction of the large intestine and the surrounding structures. The location, volume and appearance of the lesions displayed by the virtual techniques were compared with the pathological results.

RESULTSThe 3D reconstruction was successfully completed in all the 10 cases, and the imaging diagnoses showed a total match with the pathological diagnoses. No significant differences were found between virtual endoscopy and CT virtual endoscopy. Virtual colonoscopy combined with digital model reconstruction provided valuable information for accurate identification of the position of the lesions and the complex adjacent anatomical structures.

CONCLUSIONVirtual colonoscopy based on 64-slice CTA, when combined with 3D reconstruction technique, allows accurate display of the colonic lesions and potential metastasis, which can be crucial for clinical staging and surgical planning of colonic cancer.

Adult ; Angiography ; methods ; Colorectal Neoplasms ; diagnostic imaging ; therapy ; Female ; Humans ; Image Processing, Computer-Assisted ; methods ; Imaging, Three-Dimensional ; Male ; Middle Aged ; Tomography, Spiral Computed

Objective To improve the system of specialized training by exploring the role of multimodal navigation in the teaching of neurosurgery.Methods The questionnaire was conducted by the experts to obtain the detailed information of 20 residents.They were randomly divided into two groups:the traditional teaching group (n=10) and the multimodal navigation group (n=10).The details were evaluated from the reaction layer,the learning layer,the behavior layer and the result layer by the Kirkpatriek's model.The data were analyzed by SPSS 17.0.The quantitative data were described by mean ± standard deviation and the qualitative data was described by rate or percentage.Two independent-samples t test was used to compare the results of two groups.Results The results of the reaction layer showed that the scores of the multimodal navigation group were significantly higher than those of the traditional teaching group,which were statistically significant (P＜0.05) in the training content,training methods,training facilities and experience after training.The learning results showed that the multimodal navigation group had higher scores in the theoretical examinations,surgical skills and overall scores (P＜0.05).The behavioral results showed that the clinical ability of the multimodal navigation group was more prominent (P＜0.05).The result layer showed that under the guidance of professors,the percentage of residents who can complete the whole surgical operation is higher in multimodal navigation group (50％ vs.20％).Conclusion The application of multimodal navigation technology has a positive effect on the teaching of neurosurgery and specialized training of residents.