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

Objective To investigate the location and the pathogens of systemic lupus erythematosus (SLE) patients who died from infection.Methods Dead cases of hospitalized SLE patients in Peking Union Medical Hospital from January 1986 to May 2011were retrospectively analyzed.Results Severe infection was an important cause of mortality in patients with SLE.There were 252 dead cases of SLE in total from 1986 to 2011,in which 97 cases died from severe infection.The proportion of patients died from infection was gradually increased during the past 26 years,which was 25.7％,24.1％,31.6％,34.9％ and 60.3％ in 1986-1990,1991-1995,1996-2000,2001-2005 and 2006-2011respectively.Lung was the most common site of infec-t ion,accounting for 65％ of all dead cases.Among the 31cases with identified microorganism,14 patients had single microorganism infection and 17 patients had mixed infections.In the single microorganism infection patients,fungal infection contributed to the cause of death in 9 out of 14 (64％) patients,of which 4,2,1,1,and 1 cases were infected with Pneumocystis carinii, Aspergillus fumigates,Fusarium,Candida tropicalis and Cryptococcus respectively.There were 3 cases of bacteria infection,including 2 cases with Methicillinresistant staphylococcus,aureus and 1case with Klebsiella pneumoniae infection.Two patients died from pulmonary tuberculosis.In 17 patients with mixed infection cases, 14 deaths were caused by bacteria infection,including Acinetobacter baumannii, Eschefichia coli, Enterococcus, Klebsiella pneumoniae,Pseudomonas aeruginosa and Enterobacter cloacae.Eleven patients died from mixed fungus infection,including 6 cases of Aspergillus fumigates,3 cases of Candida tropicalis,3 cases of Pneumocystis carinii,2 cases of Aspergillus flavus,1 case of Soil Aspergillus,2 cases of Candida albicans,1 case of Candida glabrata and Candida Krusei.In addition to bacteria and fungi infection,cytomegalovirus infection occurred frequently in SLE death cases.Conclusions Severe infection has been the most frequent cause of death in SLE patients,in which lung infection is the leading cause.Pneumocystis carinii,Aspergillus fumigates,Acinetobacter baumannii and cytomegalovirus are the major pathogens that cause death in SLE patients.

Objective To explore a better method for treatment atrophic rhinitis.Methods 56 patients with atrophic rhinitis(96 lateral)were treated by nasal submucou pediculated bone-suberiosteal muscle flap extracted from anterior wall of sinus maxillaries.Results All patients were followed 2 to 10 years,total effective rate was 100 %, with 49 cases(87.5 %)showing prominent effect.Conclusion The grafted flap cannot be assimilated,felled off and necrosis,because the flap has rich blood supply.This methods has obvious short-term effective and stable long-term effective.No complications were found.

Objective To evallhte factors affecting blood loss during mini-percutaneous nephrolithotomy using ureteroscope and pneumatic intracorporeal lithotripsy(MPCNL). Methods 1156MPCNL procedures in 885 patients from July 2002 to October 2006 were reviewed. Various patientrelated and intraoperative factors were assessed for association with total blood loss using multivariate regression analysis. ResuIts The average hemoglobin drop was(14.2+8.3)g/L.The overall blood transfusion rate was 1.5%. Approximately 0.6%of patients required angiography embolization to control intractable bleeding. Multivariate regression analysis showed that the occurrence ot operative complications(6=0.496,P＜0.001),size of the tract(b=0.405,P＜0.001),mature nephrostomy tract(6=0.377,P＜0.001),multiple tracts(6=0.326,P=0.005),size of stone(b=0.210,P=0.015),operative time(6=0.139,P=0.027),renal parenehymal thickness(b=0.128,P=0.035),prior stone intervention(b=-0.121,P=0.038),diabetes(b=0.110,P=0.051),and bacteriuria(b=-0.095,P=0.058)were significant predictors of blood loss.Factors such as age,sex,side,obesity,hypertension,renal function,operating surgeon,anaesthesia,calix of puncture,number of attempts to successful puncture,urine from puncture needle may not affect the blood loss. Concluslons Maneuvers that may reduce blood loss include reducing the operative time,decreasing the occurrence of intraoperative complications, reducing the tract size and tract number, and staging the procedure.Staging the procedure of MPCNL is a judicious decision in case of a large stone burden,intraoperative complications,multiple-tract,lager tract or diabetes.

OBJECTIVEThis study aimed to compare the prevalence of mental disorders and services for people with mental health problems in Shaoxing city between 1991 and 2001 in order to provide scientific bases for prevention and treatment.

METHODSA population size of 339 651 were investigated in the urban and rural areas with "Psychosis Index Investigate Schedule" plus visit to their homes.

RESULTSThe overall prevalence rates of mental disorders were 10.17 per thousand and 13.85 per thousand and the point prevalence rates of mental disorder were 9.15 per thousand and 12.77 per thousand, respectively in 1991 and 2001. The point prevalence rates in the population aged 15 years and above were 11.70 per thousand and 14.60 per thousand. Prevalence rates of neurosis and alcohol dependence and drug dependence increased significantly from 1991 and 2001. The anterior three mental disorders were neurosis, schizophrenia and dementia in all mental disorders. Situation was better in the city than in the rural areas in terms of receiving care for mental disorder, their work ability, economy condition and gardianship.

CONCLUSIONThere was an increase of prevalence on mental disorder in Shaoxing city during the ten-year period. The increase in the prevalence of mental disorder was related to local economy, socialization and culture.

Adolescent ; Adult ; Aged ; China ; epidemiology ; Dementia ; epidemiology ; Female ; Humans ; Male ; Mental Disorders ; epidemiology ; Mental Health Services ; organization & administration ; Middle Aged ; Prevalence ; Schizophrenia ; epidemiology ; Substance-Related Disorders ; epidemiology

This study plans to prepare lipid bilayer-coated mesoporous silica nanoparticles (LMSNs) which are pH sensitive with core-shell structure to improve the tumor cell lethality of antitumor drug. The lipid coated mesoporous silica nanoparticles loaded with irinotecan (CPT-11) (CPT-11-LMSNs) were prepared by hot water-film hydration method, and the characterized its morphology, particle size and release in vitro. Meanwhile, the intracellular uptake and cell toxicity of CPT-11-LMSNs and intracellular accumulation of CPT-11 were evaluated on human breast carcinoma cell line (MCF-7). The results indicated that the mean diameter of the spherical LMSNs was (120.27 +/- 5.91) nm. The slow release in simulated normal physiological conditions and a rapid release under simulated intracellular condition demonstrated the pH sensitivity of CPT-11-MSNs in vitro. Moreover, the CPT-11-LMSN could improve the intracellular CPT-11 cumulant 2.1 times and reduce half maximal inhibitory concentration (IC50) values of CPT-11 1.4 times compared with CPT-11-MSNs, demonstrating a stronger cell lethality.
Antineoplastic Agents, Phytogenic ; administration & dosage ; pharmacology ; Camptothecin ; administration & dosage ; analogs & derivatives ; pharmacology ; Cell Proliferation ; drug effects ; Drug Carriers ; Humans ; Hydrogen-Ion Concentration ; Lipid Bilayers ; administration & dosage ; chemistry ; MCF-7 Cells ; Nanoparticles ; Particle Size ; Porosity ; Silicon Dioxide ; administration & dosage ; chemistry

In this work, we developed PEO-PPO-PEO micelles loaded with irinotecan hydrochloride (CPT-11) using breast cancer resistance protein (BCRP) inhibitory material PEO20-PPO70-PEO20, and studied its mechanism of decreasing CPT-11 induced delayed diarrhea and intestinal toxicity. BCRP-overexpressing MDCKII (MDCKII/BCRP) cells were used to evaluate the effect of PEO20-PPO70-PEO20 and PEO-PPO-PEO micelles on transmembrane transport of CPT-11 in vitro. The biliary excretion, delayed diarrhea and intestinal damage of CPT-11 loaded PEO-PPO-PEO micelles of rats were investigated. The results showed that the obtained micelles could decrease the biliary excretion of CPT-11, ameliorate delayed diarrhea and intestinal toxicity of rats through inhibiting BCRP-mediated CPT-11 efflux. PEO-PPO-PEO micelles were promising carriers to reduce intestinal toxicity of CPTs.
ATP Binding Cassette Transporter, Sub-Family G, Member 2 ; ATP-Binding Cassette Transporters ; metabolism ; Animals ; Antineoplastic Agents, Phytogenic ; administration & dosage ; adverse effects ; pharmacokinetics ; Bile ; secretion ; Biological Transport ; Camptothecin ; administration & dosage ; adverse effects ; analogs & derivatives ; pharmacokinetics ; Cells, Cultured ; Diarrhea ; chemically induced ; drug therapy ; Dogs ; Drug Carriers ; Intestines ; drug effects ; Madin Darby Canine Kidney Cells ; Male ; Micelles ; Neoplasm Proteins ; metabolism ; Polyethylene Glycols ; administration & dosage ; chemistry ; Propylene Glycols ; administration & dosage ; chemistry ; Rats ; Rats, Sprague-Dawley

Objective: To explore the effect of herb-partitioned moxibustion (HPM) on tight junctions (TJs) of intestinal epithelial cells in Crohn disease (CD) mediated by tumor necrosis factor-α (TNF-α)-nuclear factor kappa B (NF-κB)-myosin-light- chain kinase (MLCK) pathway. Methods: Forty-eight male Sprague-Dawley rats were randomly divided into a normal control (NC) group, a model control (MC) group, an HPM group and a mesalazine (MESA) group, with 12 rats in each group. Trinitrobenzene sulfonic acid (TNBS) was administered to establish CD models. When the model was confirmed a success, the HPM group rats were treated with HPM at Tianshu (ST 25) and Qihai (CV 6), while the MESA group rats were given MESA solution by lavage. When the intervention finished, the colonic epithelial tissues were separated, purified and cultured in each group to establish the intestinal epithelial barrier model in vitro, and TNF-α was added (100 ng/mL) in the culture medium and maintained for 24 h to establish an increased epithelial permeability model. Transepithelial electrical resistance (TEER) was used to examine the permeability of the barrier; Western blot was used to observe the expressions of the proteins related to TJs of intestinal epithelial cells mediated by TNF-α-NF-κB-MLCK pathway; immunofluorescence staining was used to observe the expressions and distributions of tight junction proteins in the intestinal epithelium. Results: After TNF-α induction, compared with the MC+TNF-α group, the TEER value increased significantly in the HPM+TNF-α and MESA+TNF-α groups (both P<0.001); the expressions of nuclear factor kappa B (NF-κB) p65, MLCK, myosin light chain (MLC), tumor necrosis factor receptor-associated factor 6 (TRAF6) and receptor interaction protein-1 (RIP1) decreased significantly (P<0.01 or P<0.05), and the expression of zinc finger protein A20 (A20) increased significantly (P<0.01); the expressions of occludin, claudin-1, zonula occludens protein 1 (ZO-1) and F-actin also increased significantly (all P<0.01). Compared with the MESA+TNF-α group, the expressions of MLC, occludin, claudin-1, ZO-1 and F-actin increased significantly in the HPM+TNF-α group (P<0.01 or P<0.05). Conclusion: HPM can protect or repair the damage of intestinal epithelial barrier in CD rats, which may be achieved through modulating the abnormal TJs in intestinal epithelium mediated by TNF-α-NF-κB-MLCK pathway.

Objective To evaluate the dosimetric difference between fixed-field static intensity-modulated radiotherapy (IMRT), fixed-field dynamic multileaf collimator (DMLC), and volumetric modulated arc therapy (VMAT), all of which involve supraclavicular and infraclavicular regions, in breast cancer patients after breast-conserving surgery.Methods This study included 14 female patients with breast cancer who received radiotherapy after breast-conserving surgery in our hospital from October 2012 to April 2016.The radiation field included the chest wall and supraclavicular and infraclavicular regions.IMRT, DMLC, and VMAT plans were generated for each patient while using identical optimization conditions.The doses to planning target volume (PTV) and organs at risk (OARs) were compared based on dose-volume histogram (DVH);one-way analysis of variance or nonparametric Wilcoxon rank test was used for comparison.Results For the dose distribution of PTV, VMAT achieved the best V95, V98, CI, and HI (P<0.009).Concerning the doses to OARs, VMAT achieved the best V5, V20, and Dmean of the ipsilateral lung and the best V5 and Dmean of the contralateral lung (P<0.022).Dmean of the spinal cord was significantly lower in VMAT than in IMRT and DMLC (P=0.004).Conclusions VMAT is preferred for the patients with breast cancer to be treated with radiotherapy involving supraclavicular and infraclavicular regions after breast-conserving surgery.It can improve the dose distribution of target and reduce the doses to organs at risk and radiotherapy toxicities.

Three Newcastle disease virus (NDV) strains recovered from ND outbreaks in chickens and duck flocks in north china during 2009 to 2011 were completely sequenced and biologically characterized. All the strains were velogenic and had the velogenic motif 112R-R-Q-K-R-F117 which was consistent with the results of biological tests. Analysis of the variable region (nucleotide 47 to 420) of the F gene indicated that the three isolates belonged to genotype VII d. Cross hemagglutination inhibition test indicated that the antigen homology between three isolates and LaSota were 82.5%-89.4%, the homology between the two isolates from chicken was 90%. A cross-protection experiment in which specific-pathogen-free chickens vaccinated with LaSota were challenged by SDLY01 isolate showed that LaSota vaccine could provide complete protection against SDLY01, however virus discharge could be detected on fifth day. Challenge experiment in which Cherry Valley duck of 30 day old challenged with SD03 strain indicated that cherry valley duck had no disease in experiment period, but virus discharge could be detected from Larynx and cloaca until fifth day. Genome length of three NDV isolates was 15192bp and belonged to genotype VII d. Sequence analysis clarified that the whole genomic sequence of these three isolates shared high homology with NDV virus strains isolated from goose and duck over the same period, which elucidated that NDV isolated from goose, duck or chicken had close genetics and epidemiological relationship.
Amino Acid Sequence ; Animals ; Bird Diseases ; virology ; Chickens ; Columbidae ; Ducks ; Geese ; Genome, Viral ; Molecular Sequence Data ; Newcastle Disease ; virology ; Newcastle disease virus ; chemistry ; classification ; genetics ; isolation & purification ; Phylogeny ; Sequence Alignment ; Viral Proteins ; chemistry ; genetics