Objective To study the effects of isoflurane anesthesia on the medium- and longterm cognitive function in mice at different months of age. Methods Male C57BL/6J mice at ages of 4 month (n =45)and 20 month (n 45) were randomly assigned to control group,short- term anesthesia and long term anesthesia groups,respectively (n=15 per group).Inhalation anesthesia was applied with 3％ isoflurane for induction and 1.2 ％ isoflurane for maintain in 30 ％ oxygen,and control group received 30％ oxygen only for 60 min.Short- and long- term anesthesia group anesthesia was maintained for 30 min and 60 min,respectively.Cognitive function was determined by alternative behavior and water maze.Alternative behavior was assessed at 1 d before ancsthesia and 7,14 and 28 d after anesthesia,and water maze was assessed from 7 d to 8 d,9 d,10 d,11 d and 28 d after anesthesia. Results The correct rate of alternative behavior at age of 4 month in long-term anesthesia group [(58=6)％] was lower than relative control [(69±9)％] (t=4.26,P＜0.01) at 28 d.The number of arm entries at age of 20 month in short- term anesthesia group (31 ± 6) was increased than control(24±6) and long-term anesthesia group (24±8)(F=5.34,P＜0.01) at 14 d after anesthesia,while the number in long-term anesthesia group (24± 6) was decreased than control (29±7) and short term anesthesia group(30±6)(F=3.29,P＜0.05) with no significant difference in correct rate at 28 d after anesthesia.There was no difference in latent time of water maze between groups at age of 4 month.The ratios of spent time in the target quadrant to the whole time at age of 4 month at 11 d and 28 d after anesthesia in short-term anesthesia group[( 36.6 ± 14.4)％,(34.7 ±9.5)％] and long term anesthesia group [( 36.8 ± 16.4)％ ,(31.8± 12.0)％] were reduced as compared with control [(49.5±8.8) ％,(42.8±12.2) ％] (F=3.31,3.30,all P＜0.05).The latent time of mice at age of 20 month at 11 d after anesthesia in short-term anesthesia[(31±6)s] and longterm anesthesia group [(30±7)s ] were longer than control [(23±6)s](F =3.34,P＜0.05).There were no differences in the ratios of spent time in the target quadrant to the whole time and the number of cross -platform among the groups. Conclusions Isoflurane anesthesia may impact the mediumand long- term cognitive funclion in mice at ages of 4 month and 20 month.

BACKGROUND: In recent years, there are many studies designed to explain the protective effect of lidocaine on brain, but few about the therapeutic effect on traumatic cerebral edema. The content of aquaporin-4(AQP-4) in brain tissue is the highest and it has been proved that AQP-4participants in the formation of cerebral edema induced by cerebral trauma, cerebral infarction, eerebrai tumor and other reasons.OBJECTIVE: To observe the effect of lidocaine on the expression of AQP-4 of experimental rats following brain injury and analyze the therapeutic effect of lidocaine on brain edema.DESIGN: A randomized and control animal experiment.SETTING: Department of Anesthesiology, Affiliated Hospital of Medical College of Qingdao University.MATERIALS: The experiment was carried out in the Institute of Brain Disease, the Medical School Hospital of Qingdao University between January and July 2004. Totally 65 three-month-old healthy male Wistar rats,were enrolled in the experiment and randomly divided into 3 groups: normal control group (n=5), model group (n=30) and treatment group (n=30). Thirty rats in the model group and treatment group were respectively assigned into 6 subgroups according to 6 different time points: 1,4,6,12,24 and 48 hours following brain injury, with 5 rats at each time point.METHODS: Animal models of brain injury at right parietal lobe were created according to the method from Feeney et al. As for the rats of normal control group, they only underwent operation to be injured at the corresponding part. Rats recovered the access to food and water 2 to 8 hours after operation. For the rats in the treatment group, they were intraperitoneally injected of lidocaine at the 1st, 4th,6th, 12th, 24th, and 48th hours following injury, 5 rats at each time point. The initial dosage was 30 mg/kg, then 15 mg/kg was maintained . Administration was conducted every 6 hours in 3 days; For the rats in the model group, they were intraperitoneally injected of 30 mg/kg normal saline and rats in the normal control group were given no special treatments. Water content of brain was calculated 5 days following brain injury with dry and wet weight method:water content of brain=[brain mass (wet)-brain mass (dry)]/brain mass(wet)×100%. Expression of AQP-4 of brain tissue of rats was detected with immunohistochemical method and cytomorphological change of brain tissue was observed under optical microscope.MAIN OUTCOME MEASURES: ① Water content of brain of rats in each group. ② Expression of AQP-4 of brain tissue of rats in each group.③ Pathological results of brain tissue of rats in each group.RESULTS: No rats died accidentally or for other factors in the process of experiment, finally, all the 65 rats entered the stage of result analysis. ①Compared with model group, administration of lidocaine within 6 hours following brain injury could significantly decrease the water content of brain tissue [1 hour after brain injury: (81.09±0.29)%, (83.04±0.25)% ,P ＜ 0.05];[4 hours after brain injury: (81.34±0.35)%, (83.31±0.48)%,P ＜ 0.05] ;[6 hours after brain injury: (82.01±0.21)%, (83.25±0.37)% ,P ＜ 0.05]. Compared with model group, administration of lidocaine could significantly decrease the expression of AQP-4 [1 hour after brain injury:(0.19±0.02), (0.24±0.03),P ＜ 0.05]; [4 hours after brain injury: (0.21±0.05 ), (0.25±0.05) ,P ＜ 0.05]; [6 hours after brain injury: (0.21±0.03 ),(0.24±0.02) ,P ＜ 0.05]. There were no significant differences of AQP-4expression and water content of brain tissue when administration was conducted at the 12th, 24th and 48th hours following brain injury (P ＞ 0.05). ②Under the microscope, AQP-4 positive cells presented vacuolus, they mainly lay in the edema area of peripheral part of trauma, cortex of traumatic side and around the blood vessel as well as astrocyte of white substance, choroid plexus and ependymal layer. ③ Necrosis was found in most cells in the central area of trauma and apoptosis in most cells in the peripheral area. Compared with model group, necrotic and apoptotic cells were significantly less within 6 hours following trauma, but not at the 12th,24th and 48th hours following trauma in the treatment group.CONCLUSION: High dosage of lidocaine can decrease the expression of AQP-4 and lighten cerebral edema following brain injury, but administration should be given as early as possible.

OBJECTIVEThe present study is concerning qualitative and quantitative detection of Poria cocos quality based on FT-near infrared (FT-NIR) spectroscopy combined with chemometrics.

METHODThe Poria cocos polysaccharides contents were determined by UV. Transmission mode was used in the collection of NIR spectral samples. The pretreatment method was first derivation and vector normalization. Then principal component analysis (PCA) was used to build classification model and partial least square (PLS) to build the calibration model.

RESULTThe results showed that conventional criteria such as the R, root mean square error of calibration (RMSEC), and the root mean square error of prediction (RMSEP) are 0.944 0, 0.072 1 and 0.076 2, respectively. The misclassified sample is 0 using the qualitative model built by PCA.

CONCLUSIONThe prediction models based on NIR have a better performance with high precision, good stability and adaptability and can be used to predict the polysaccharose content of Poria cocos rapidly, which can provide a fast approach to discriminate the different parts of Poria cocos.

Fungal Polysaccharides ; analysis ; Least-Squares Analysis ; Poria ; chemistry ; Principal Component Analysis ; Spectroscopy, Near-Infrared ; methods

Objective To examine the possibility that a candidate causal species of the skin and lung tumor promotion induced by exposure to dimethylarsinic acid(DMAv)and dimethylarsinous acid(DMAⅢ),caused by the induction of oxidative stress in mice.Methods Two stages lung tumotigensis animal model induced by lung tumor initiator(4-nitroquinoline 1-oxide,4NQO)and promoter(DMAv)in ddY mice,was used to examine the effect of(-)epigallocatechin gallate(EGCG)on DMAv promoting lung tumorigenesis.Two stages skin tumorigenesis animal model induced by skin tumor initiator[dimethylbenz(α)anthracene,DMBA]and promoter(DMAⅢ)in hairless mice.was used to examine the effects of DMAⅢ in skin tumorigenesis and histopathology.The goxo-2'-deoxyguanosine (8-oxodG)in lung and epidermis were analyzed by HPLC.Results The incidence of lung tumors and 8-oxodG level of lung tissue decreased significantly in 4NQO+DMAv+EGCG group.compared with 4NQO+DMAv group (0.89±0.30 vs 4.00±0.82,1.21±0.09 vs 1.53±0.32,P＜0.01).The incidence of severe keratosis in DMBA+ DMIⅢ group was more than that in DMBA group(25 vs 10,P＜0.05).An significant elevation of 8-oxodG in epidermis was observed in 0.5 h[(1.67±0.17)/105 dG],1.0 h[(1.62±012)/105 dG],2.0 h[(1.66±023)/105dG], 3.0 h[(1.60±0.15)/105 dG],compared with 0 h[(1.25±0.11)/105 dG],being significant(P＜0.05).Conclusion tumor promotion due to DMAv administration is mediated by DMAⅢ through the induction of oxidative stress.

Plants in Ainsliaea genus, belongs to Compositae family, are traditional Chinese medicine and widely used in folk. These plants contain various types of chemical components, and main components are sesquiterpene lactone and its glycosides. In addition, there are triterpenoids, flavonoids, steroids, phenolic acid, long chain fatty acid and volatile oils. Recently, much attention has been payed to varlous research of A. fragrans. This paper reviewed and summarized the chemical components to provide the theoretical basis for the use of Ainsliaea.
Asteraceae ; chemistry ; Drugs, Chinese Herbal ; chemistry ; pharmacology ; Molecular Structure

Animals ; Apoptosis ; drug effects ; Brain ; drug effects ; Caspase 3 ; metabolism ; Curcumin ; pharmacology ; Hypoxia-Ischemia, Brain ; metabolism ; pathology ; Male ; Rats ; Rats, Sprague-Dawley

In this study, we investigated the effect of Cigu Xiaozhi formula on HSC-T6 activity in hypoxic microenvironment based on network pharmacology and computer-aided drug design, and predicted and verified its possible targets and related signaling pathways. The potential active components and targets of Cigu Xiaozhi formula were screened by searching Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), Encyclopaedia of Traditional Chinese Medicine (ETCM) and Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine (BATMAN-TCM) databases, and the liver fibrosis related targets retrieved from Gene Cards and Pharm GK database were integrated to obtain the potential targets of Cigu Xiaozhi formula in the treatment of liver fibrosis. GO enrichment analysis and KEGG signaling pathway enrichment analysis were performed on Omic Share platform, and Cytoscape software was used to construct the "potential active ingredient-key target-pathway" network. The active components and target proteins were subjected to molecular docking analysis by Auto Dock software. According to the results of molecular dynamics simulation and binding free energy calculation, the top 5 active components with degree were scored. The active components stigmasterol and β-sitosterol were subjected to molecular docking. CoCl₂ was used to induce HSC-T6 cells to construct hypoxia model in vitro. The cell viability was detected by CCK-8 assay, and the optimal time and concentration of hypoxia model of HSC-T6 cells was determined to be 100 µmol·L^-1 CoCl₂ for 24 h. Under hypoxia condition, HSC-T6 cells were activated, the wound healing rate was significantly increased, and the fluorescence signal of activation marker protein α-smooth muscle actin (α-SMA) was significantly enhanced. However, 6% drug-containing serum could inhibit the activation of HSC-T6 cells, and the wound healing rate was significantly decreased, and the fluorescence signal of α-SMA was significantly weakened. Further studies showed that the expressions of hypoxia-inducible factor-1α (HIF-1α), α-SMA and key proteins of Hedgehog (Hh) signaling pathway in HSC-T6 cells were up-regulated under hypoxia, while the expressions of HIF-1α, α-SMA, Patched-1 (Ptch-1) and glioma related oncogene homology-1 (Gli-1) were down-regulated in 6% drug-containing serum group, the YC-1 group and the cyclopamine group. These results indicated that HIF-1α and Hh signaling pathways were involved in the activation of HSC-T6 cells, and the traditional Chinese medicine Cigu Xiaozhi formula could inhibit the activation of HSC-T6 cells, and the mechanism may be related to the inhibition of HIF-1α expression and the blocking of Hh signaling pathway. In conclusion, Cigu Xiaozhi formula can inhibit the activation of HSC-T6 cells by directly acting on HIF-1α and Hh signaling pathway, and exert an anti-hepatic fibrosis effect. The animal experimental protocol has been reviewed and approved by Laboratory Animal Ethics Committee of Gansu University of Chinese Medicine, in compliance with the Institutional Animal Care Guidelines.

OBJECTIVETo evaluate the efficacy and safety of etanercept plus Tripterygium wilfordii polyglycoside (TWP) in elderly patients with active rheumatoid arthritis (RA).

METHODSTotally 46 elderly patients with active RA were randomly assigned to the treatment group (22 cases) and the control group (24 cases). All patients received subcutaneous injection of etanercept, 25 mg each time, twice per week. The dosage was reduced to once per week 3 months later. Patients in the treatment group took TWP Tablet (10 mg each time, three times per day), while those in the control group took methotrexate (MTX), 10 mg each time, once per week. The whole course lasted for 24 weeks. Patients' rest pain, tender joint number, swollen joint number, health assessment questionnaire (HAQ), patients' global assessment, physicians' global assessment, erythrocyte sediment rate (ESR), C reactive protein (CRP), rheumatic factor were assessed at week 0, 4, 8, 12, and 24. The curative effect was statistically evaluated by the United States Institute of Rheumatology ACR20, ACR50, and ACR70 improvement criteria. Meanwhile, any adverse event was recorded and evaluated.

RESULTSTotally 41 completed the trial, and 5 dropped off (3 in the treatment group and 2 in the control group). Compared with the control group, there was no statistical difference in ACR20, ACR50, or ACR70 in the treatment group (P > 0.05). Compared with before treatment in the same group, there was some improvement in tender joint number, swollen joint number, visual analogue scale (VAS) for patients' global assessment, VAS for physicians' global assessment, ESR, CRP, and HAQ between the two groups, showing statistical difference (P < 0.05). Compared with the control group in the same phase, there was no statistical difference in the treatment group (P > 0.05). There was no statistical difference in the occurrence of adverse events between the two groups.

CONCLUSIONSEtanercept plus TWP could achieve equivalent therapeutic effect to that of Etanercept plus MTX. The two regimens could improve clinical signs, symptoms, and QOL related to RA. They were well tolerated in the treatment of elderly patients with active RA.

Aged ; Antirheumatic Agents ; therapeutic use ; Arthritis, Rheumatoid ; drug therapy ; Drug Therapy, Combination ; Etanercept ; Female ; Glycosides ; therapeutic use ; Humans ; Immunoglobulin G ; therapeutic use ; Male ; Middle Aged ; Receptors, Tumor Necrosis Factor ; therapeutic use ; Treatment Outcome ; Tripterygium ; chemistry

The shape and structure of granules are controlled by the granulation process, which is one of the main factors to determine the nature of the solid dosage forms. In this article, three kinds of granules of a traditional Chinese medicine for improving appetite and promoting digestion, namely, Jianwei Granules, were prepared using granulation technologies as pendular granulation, high speed stirring granulation, and fluidized bed granulation and the powder properties of them were investigated. Meanwhile, synchrotron radiation X-ray computed micro tomography (SR-µCT) was applied to quantitatively determine the irregular internal structures of the granules. The three-dimensional (3D) structure models were obtained by 3D reconstruction, which were more accurately to characterize the three-dimensional structures of the particles through the quantitative data. The models were also used to quantitatively compare the structural differences of granules prepared by different granulation processes with the same formula, so as to characterize how the production process plays a role in the pharmaceutical behaviors of the granules. To focus on the irregularity of the particle structure, the box counting method was used to calculate the fractal dimensions of the granules. The results showed that the fractal dimension is more sensitive to reflect the minor differences in the structure features than the conventional parameters, and capable to specifically distinct granules in structure. It is proved that the fractal dimension could quantitatively characterize the structural information of irregular granules. It is the first time suggested by our research that the fractal dimension difference (Df,c) between two fractal dimension parameters, namely, the volume matrix fractal dimension and the surface matrix fractal dimension, is a new index to characterize granules with irregular structures and evaluate the effects of production processes on the structures of granules as a new indicator for the granulating process control and optimization.
Drugs, Chinese Herbal ; analysis ; Fractals ; Medicine, Chinese Traditional ; Powders ; Quantitative Structure-Activity Relationship ; Synchrotrons ; Technology, Pharmaceutical ; Tomography, X-Ray Computed

OBJECTIVETo study the effect of Tongluo Xingnao effervescent tablets on learning and memory capacity and expression of Na(+)-K(+)-ATPase in hippocampus of rats with chronic cerebral ischemia-induced learning and memory dysfunction model.

METHODThe 2-VO method was used to establish sd rat model learning and memory dysfunction induced by chronic cerebral ischemia. The 50 rats in the successfully established model were randomly divided into the model control group, the Dihydroergotoxine Mesylate tablets group (0.7 mg x kg(-1), Tongluo Xingnao effervescent tablets high dose (7.56 g x kg(-1)), middle dose (3.78 g x kg(-1)) and low dose (1.59 g x kg(-1)) groups and the sham operation group (n = 10) as the control group. The groups were orally given 10 ml x kg(-1) x d(-1) drugs for consecutively 90 days. On the 86th day, Morris water maze was adopted for them. On the 90th day, a leaning and memory capacity test was held. The brain tissues were fixed with 10% formaldehyde and observed for pathomorphism after routine slide preparation and staining. The expression of hippocampal Na(+)-K(+)-ATPase was detected with immunohistochemistry and image quantitative analysis.

RESULTCompared with the model group, all of Tongluo Xingnao effervescent tablets groups showed significant decrease in the escape latency at the 5th day in the Morris water maze, and notable increase in the frequency of the first quadrant dwell, the frequency passing the escape platform and the frequency entering effective area (p < 0.05). According to the pathomorphological detection, the control group showed a significantly higher pathological score than the sham operation group (p < 0.01), the middle dose group showed a significantly lower pathological score than the model group (p < 0.05). According to the immunohistochemistical detection, the model control group showed a remarkably lower mean OD value of Na(+)-K(+)-ATPase than the sham operation group (p < 0.05), high and middle dose groups showed a significantly higher mean od value than the model control group (p < 0.01).

CONCLUSIONTongluo Xingnao effervescent tablets can improve the learning and memory capacity, reduce pathological changes of hippocampal tissues of rats with chronic cerebral ischemia-induced learning and memory dysfunction model, and promote the expression of Na(+)-K(+)-ATPase in hippocampus.

Animals ; Brain Ischemia ; drug therapy ; enzymology ; genetics ; psychology ; Chronic Disease ; drug therapy ; psychology ; Drugs, Chinese Herbal ; administration & dosage ; Female ; Hippocampus ; drug effects ; enzymology ; Humans ; Learning ; drug effects ; Male ; Memory ; drug effects ; Rats ; Rats, Sprague-Dawley ; Sodium-Potassium-Exchanging ATPase ; genetics ; metabolism ; Tablets ; administration & dosage