Abstract: 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.

This study was aimed to find out the correlation between chemical component contents and physical prop-erties of tanshinone extract powders. The contents of cryptotanshinone and tanshinone IIA from 50 batches of tanshi-none extract powders were determined by HPLC. And the physical properties were determined by classical methods. The correlation analysis between component contents and physical properties were also investigated. The results showed that two sets of variables had good intraclass correlation, especially for the contents of cryptotanshinone and tanshinone IIA, among D10, D50, D90, there were relatively strong correlation between the bulk density and tapped density, between the Hausner ratio and compressibility index. The angle of repose had a certain correlation with the uniformity, Hausner ratio and compressibility index, but with no strong correlation. The correlation coefficient be-tween two sets was below 0.400, suggesting there was a not so good inter-group correlation. After the canonical cor-relation analysis, three pairs of canonical variables had significant correlations with correlation coefficients being 0.851, 0.674 and 0.565, respectively. It was concluded that there was a good intraclass correlation for each of physi-cal and/or chemical quality set, but the correlation between the two sets was bad. Canonical variables performed bet-ter inter-group correlation compared with original variables, indicating there was a certain correlation between chem-ical and physical quality attributes of tanshinone extract powders.

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 discuss the clinical value of transabdominal sonography after bowl preparation in diagnosis of ileocecal valve syndrome ( IVS) .Methods The ultrasonic features of IVS in 37 cases were summerized and correlated with the follow-up findings after conservative treatment or the pathologic results after operation .Twenty-eight cases were confirmed by follow-up and 9 cases by operative pathology.Results Among the 37 cases of IVS,28 were idiopathic IVS (75.7%,28/37) and 9 were secondary IVS (24.3%, 9/37%).For the secondary cases, the primary diseases included 5 acute appendicitis,2 Meckel diverticulum,1 terminal ileitis and 1 carcinoma of ascending colon .The diagnostic accuracy rate of ultrasound was 89.2%(33/37).Misdiagnosis rate was 10.8%(4/37),including 1 case of idiopathic and 3 cases of secondary IVS .The IVS ultrasonic images coulde be displayed clearly using 7.0-10.0 MHz probes.In fasting examination,three ultrasonic characteristic signss were found in interminal ileum region at the right lower abdomen .And these features were bagel-shaped sign [91.9%(34/37),average size (1.9 ±1.6) cm ×(0.8 ±0.3) cm],short sleevelet-shaped sign [91.9% (34/37,average size (2.1 ± 0.4)cm ×(1.3 ±0.2) cm],and rose-shaped sign [83.8% (31/37),average size (1.4 ±0.2) cm × (1.0 ±0.2) cm].The shapes of some signs were changeable when the probe compressed .In the case of idiopathic IVS ,several pathologic changes could be seen on sonography after intestinal tract filling of oral 20%mannitol,including slight thickened mucosa and submucosa of erminalileum ,enlarged ieocecal valve and the crocodile-mouth sign.Conclusions Transabdominal ultrasonic examination with high frequency probe after bowl preparation plays an important role in diagnosis of IVS .The method is simple and accurate and should be recommended and applied clinically .

BACKGROUNDTo evaluate treatment effectiveness and safety of bicyclo tablets in children with chronic hepatitis B or C.

METHODSA randomized controlled trial was conducted in 148 children with chronic hepatitis B or C for evaluating safety, tolerability, and efficacy of treatment with bicyclo tablets or Hugan tablets. Children in therapy group were treated with bicyclo tablets and control group treated with Hugan tablets.

RESULTS(1) ALT and AST level decreased more prominently in therapy group than in control group (P<0.01). (2) Bicyclo was more effective than Hugan tablets (P<0.01). (3) Symptoms were ameliorated more prominently in bicyclo group than in control group (P<0.01). (4) Both groups had no significant adverse events.

CONCLUSIONSatisfactory therapeutic effect and safety were obtained with bicyclo tablets in children with chronic hepatitis B or C.

Adolescent ; Biphenyl Compounds ; adverse effects ; therapeutic use ; Child ; Child, Preschool ; Hepatitis B, Chronic ; drug therapy ; Hepatitis C, Chronic ; drug therapy ; Humans ; Tablets ; Treatment Outcome

OBJECTIVETo investigate the clinical manifestations and endoscopic features of abdominal type Henoch purpura in children and improve the diagnostic level.

METHODSRetrospective review was made on the clinical, endoscopic and histopathological features of 57 cases of children with Henoch purpura abdominal type who had been hospitalized from Jan. 2002 to May 2007. Upper gastrointestinal endoscopy was performed in all cases. All the cases had various digestive system symptoms without cutaneous purpura before endoscopy. Mucosal specimens were taken from sinus ventriculi and duodenum for histopathological analysis. Helicobacter pylori (H.pylori) infection was identified by rapid urease test and histology, and diagnosis of H.pylori infection was made when both were positive.

RESULTSThe common gastrointestinal symptoms of Henoch purpura were abdominal pain (46 cases), vomiting (32 cases), hematochezia (11 cases), diarrhea (4 cases) and abdominal distention (1 case). Three cases had arthralgia and joint swelling. The main laboratory findings were increased peripheral white blood cells (33 cases, 57.9%), 1/5 of cases had elevated C reactive protein (CRP), low serum albumin and seroperitoneum. Endoscopy demonstrated the damages to the mucosa, which varied from congestion, edema, petechia and ecchymosis (37 cases, 64.9%) to erosive and multiple ulcers (14 cases, 24.6%), granulation of mucosa in descendent duodenum (4 cases, 7.0%), and diffuse hemorrhage of mucosa (2 cases, 3.5%). The upper gastrointestinal endoscopy showed that the commonest and most serious position involved was the descendent duodenum (55 cases, 96.5%), followed by duodenal bulb (32 cases, 56.1%) and stomach (18 cases, 36.1%), esophagus was less involved (1 case, 1.8%). Histological manifestations showed swollen vascular endothelial cells of capillary vessels and small blood vessels, fibrotic necrosis of small vessels and bleeding, diffuse perivascular lymphocytic and neutrophilic infiltration and nuclear debris in mucosa and submucosa. Three cases (5.3%) were found infected with H. pylori. In 49 cases (86.0%) cutaneous purpura appeared 1 - 7 days after endoscopy. Eight cases had no cutaneous purpura until they left hospital. Two cases were lost to follow up and 6 cases (10.5%) remained free from cutaneous purpura were followed up until now (1 - 5 years).

CONCLUSIONDescending duodenum is the commonest and most serious position of upper gastrointestinal tract involved in Henoch purpura. Upper gastrointestinal endoscopy with the mucosal biopsy are useful for the early diagnosis of Henoch purpura.

Abdominal Pain ; pathology ; physiopathology ; Child ; Duodenum ; pathology ; physiopathology ; Endoscopy ; instrumentation ; Humans ; Purpura, Schoenlein-Henoch ; pathology ; physiopathology

Aim To study the effect of genistein on apoptosis in human breast cancer MDA-MB-231 cells and the underlying mechanisms. Methods MTT as-say was used to observe the inhibitory rate on human breast cancer MDA-MB-231 cells treated with genistein. Colony assay was used to determine the cell colony formation rate on human breast cancer MDA-MB-231 cells treated with genistein. Western blot was used to detect the expression of Bcl-2, Bax, caspase-3,NF-κB, ERK, p-ERK, JNK and p-JNK in human breast cancer MDA-MB-231 cells treated with genistein. Results The results of MTT assay showed that genistein inhibited the viability of breast cancer MDA-MB-231 cells in a time- and concentration-de-pendent manner. Colony assay suggested that genistein had an antiproliferative effect on MDA-MB-231 cells. The expression levels of Bcl-2, NF-κB and p-ERK were significantly down-regulated compared with con-trol(P < 0.01). However, the expression of Bax, caspase-3 and p-JNK was significantly up-regulated(P<0.01). Conclusions Genistein could inhibit the growth of human breast cancer MDA-MB-231 cells and induce apoptosis,and the mechanism may be related to the inhibition of NF-κB, ERK/MAPK signaling path-ways and the activation of JNK/MAPK signaling path-way.

Objective To investigate the efficacy and safety of ademetionine for treatment of cholestatic or mixed-type drug-induced liver disease (DILD) in children.Methods The children with DILD were divided into the treated group and control group.Yinzhihuang Granule was orally administered and Compound Glycyrrhizin Injection intravenously given in patients of both groups.Those patients in the treated group were additionally treated with intravenous infusion of 250-1000 mg ademetionine for 28 d.The incidence of pruritus and adverse effects as well as biochemical parameters in all the patients and compared between the 2 groups.For statistical analysis,X~2 test was used for between-group comparison and t test for processing the data.Results 1) Before treatment,severe pruritus was found in 17 and 16 children in the treated and control group,respectively.Two weeks after the treatment,the symptom was significantly relieved in 14 and 3 patients in the treated and control group,respectively (X~2= 4.52,P＜0.05).2) As for comparisons between the 2 groups,a P value of 0.0014 for AST level was found 4 weeks,0.045 and 0.007 for disappearance and recovery rate of jaundice,0.0014 and 0.0006 for decrease in TBA level and 0.0003 for γGT level 2 and 4 weeks after the treatment.Conclusion Intravenous administration of ademetionine is safe in children with DILD and it can effectively alleviate pruritus,promote the recovery of various biochemical parameters and fasten liver functional recovery in these children.Therefore,ademetionine can be widely used for treatment of intrahepatic cholestasis in children.

Quorum sensing of bacteria and its specific gene expression regulation have a very important role in bacterial biofilm formation. LuxS and agr are the key regulatory genes in quorum sensing of Staphylococcus epidermidis, and RNA Ⅲ is the effector molecule of agr system. In order to evaluate the effects of sodium houttuyfonate in combination with erythromycin on the transcription level of S. epidermidis, serial dilution method was used to determine the MIC of sodium houttuyfonate, erythromycin and vancomycin on S. epidermidis, and fluorescent quantitative PCR method was used to detect the transcription levels of luxS, agr/RNAⅢ in different time periods after treatment on S. epidermidis by sodium houttuyfonate in combination with erythromycin, vancomycin, and erythromycin alone. Our results showed that in treatment by 1/2MIC, 1/4MIC sodium houttuyfonate, 1/2MIC sodium houttuyfonate +1/2MIC erythromycin, 1/4MIC sodium houttuyfonate+1/4MIC erythromycin, and 1/8MIC sodium houttuyfonate+1/8MIC erythromycin for ATCC 35984, they could rapidly up-regulate the expression of luxS of S. epidermidis from the beginning as compared with negative control, with significant differences (P<0.05); furthermore, sodium houttuyfonate can still up-regulate the expression of luxS even after treatment for 6, 12 and 48 h. Sodium houttuyfonate in MIC and 1/2MIC concentration can significantly down-regulate the expression of agr (P<0.05); 1/2MIC sodium houttuyfonate+1/2MIC erythromycin, 1/4MIC sodium houttuyfonate+1/4MIC erythromycin, can also significantly down-regulate the expression of agr in 6 h, 12 h and 24 h(P<0.05). Sodium houttuyfonate in MIC, can significantly down-regulate the expression of RNA Ⅲ (P<0.05), and 1/2MIC sodium houttuyfonate+1/2MIC erythromycin can also significantly down-regulate the expression of RNAⅢ(P<0.05). Therefore, our presented results showed that sodium houttuyfonate in combination with erythromycin can rapidly up-regulate the transcription of luxS of S. epidermidis, and can down-regulate the expression of agr/RNA Ⅲ in certain concentrations, and suggested that sodium houttuyfonate in combination of erythromycin could inhibit mutual aggregation between S. epidermidis and biofilm bacteria, inhibit membrane nutrition and formation of water transport channels, prevent separation of bacterial cells in biofilm, and inhibit the formation of bacterial exotoxin of S. epidermidis.

OBJECTIVETo explore the value of CT perfusion in early diagnosis and management of superacute local cerebral infarction in rhesus monkeys.

METHODAcute local cerebral infarction was induced in the rhesus monkeys during digital subtraction angiography (DSA) by introduction of pale thrombus prepared from autologous blood into the M1 branch of the middle cerebral artery (MCA). Plain CT scan and CT perfusion scanning were performed at different time points before and after DSA operation, and the results were analyzed in conjunction with the pathologic changes.

RESULTSIschemic lesions were displayed on CT perfusion images, which showed local hypoperfusion, reduced cerebral blood flow and volume, and mean transit time delay in the compromised area. Local hypointense infarct area was identified in plain CT scan 24 h after the DSA operation, and the results were in good agreement with pathological examination during autopsy.

CONCLUSIONCT perfusion imaging of the brain can accurately capture the cerebral perfusion deficits in acute ischemic stroke before morphologic changes take place, and therefore provides good means for thrombolytic treatment evaluation of stroke.

Acute Disease ; Animals ; Brain ; diagnostic imaging ; Brain Ischemia ; diagnosis ; Cerebral Infarction ; diagnosis ; Contrast Media ; administration & dosage ; Early Diagnosis ; Macaca mulatta ; Perfusion ; Sensitivity and Specificity ; Tomography, X-Ray Computed ; methods