Glycosaminoglycan(GAG) has recently become an important landscape of discovering new mechanisms of apoptosis stressed by oxidative stress.In this review,we focused the signal transduction passways of GAG in lysosome which can inhibit apoptosis induced by oxidative stress.

Objective To measure the leakage rate in the process of expansion in vivo and in normal saline and the over-expansion property of the expander.Methods We chose 17 cases that were treated with the skin expansion.We recorded total injected saline volume intentionally in these cases before the second surgery,and recorded the remainder of the volume of saline postoperatively.We injected normal saline into 8 expanders,respectively,exceeding 50％ of the volume-rating;and subsequently put these expanders into plastic bucket filled with saline.30 days after,we measured the remaining volume of the normal saline.We injected 100 ml normal saline into 4 expanders,respectively,of which nominal volume was 100 ml,and then left these expanders in saline and measured the remainder volume of the saline 30 days later.In the second time,we injected 150 ml and repeated the abovementioned process.It was repeated 7 times until the injection volume reached 400 ml.We processed the data and depicted a curve of effective expansion.Results The results showed that the leakage rate reached (29.0+12.5) ％ in vivo.Experiments in vitro confirmed that 85.0％ (8.0/9.4) of the saline leaked through the injection port and 14.8％ (1.4/9.4) leaked through the membrane of the expander.In addition,over-expansion performance index test confirmed that the over-expansion property of an expander was about twice the nominal volume.Conclusions The expander is not completely sealed structure.Normal saline can leak through the injection part and the membrane of the expander.The over-expansion property of an expander is limited.When the volume injected into the expander exceeds a certain value,the effective expansion performance is not increased with it.

Objective: To reduce the frequency of administration of tamoxifen citrate so as to improve its bioavailability and patients’ compliance. Methods: HPMC K4M was employed as major retarded release controller. The wetting granulation and directly compressing method was used to produce the sustained release tablet. Then the in vitro release profile was applied as main criteria to evaluate six formulations according to the variation of HPMC K4M amount. The concentration of tamoxifen citrate was measured by UV spectrometry. Finally the releasing characteristics of sustained release and conventional tablets were compared to clarify the sustained effect of the former. Result: At 278 nm there was no interaction between tamoxifen citrate and the recipients so that it was adopted as the wavelength of determination. The recovery efficiency of this method ranged from 95%-105%. The final formulation could release 86.40% of its loading amount in 12 h and its releasing profile fitted the Zero order equation well. The percentages of accumulative release in 1 h were 76.81% and 7.08% for sustained release tablet and conventional tablet respectively. Conclusion: The sustained release tablet of tamoxifen citrate could demonstrate a continuous and stable releasing profile and last for over 12 h. It has significant retarded effect in comparison with the conventional one and could be a new choice of regimen in its clinical application.

AIM: Site-specific functional neurons of brains were with different cellular morphology. It has not been fully understood whether the grafted neural stem cells could differentiate into the site-specific neurons. This experiment is to investigate the neuronal differentiation of the neural stem cells derived from a human fetal brain after transplanted into young rats' brains, to study the possibility of cell-replacement therapy for children's brain disorders with neural stem cells. METHODS: Experiments were performed at the Cell Laboratory of Naval General Hospital from April to July 2007. ①Human fetal brain tissues of 16 week gestation were provided by Department of Gynaecology and Obstetrics of Naval Hospital. Pregnant woman and family members signed an informed consent. Experimental intervention was approved by Hospital Ethical Committee. Fourteen clean brood young SD rats aged 10 days, irrespective of gender, were provided by Experimental Animal Center of Medical College of Peking University. Animal intervention met the animal ethical standards. ②The neural stem cell spheres were derived from the fetal brain tissues of 16 week gestation. The differentiation multipotency of the neurosphere was identified when cultured in a child's cerebrospinal fluid (CSF). The neurospheres cultured in vitro for 14 days were injected into the lateral ventricles of young rats of 10 days old. The rats were respectively killed at days 4, 7 and 14 after transplantation. The special immuno-fluorescent assays were performed using anti-human neurofilament (anti-hNF) to show the location and morphology of graft neurons. RESULTS: ①The typical floating neurospheres were obtained, with the potency to differentiate into neurons, astrocytes and oligodendrocytes. ②The neuronal differentiation of grafts was detected with the mixture of three monoclonal antibodies against human neurofilament. Four days after transplantation, the immune response positive cells lied within the granule cell layer of cerebral cortex were shown in the shape of granule cells, or within the pyramid cell layer in the shape of pyramid cells with long processes, and the interneuron-like cells also were seen. The Purkinje cells arranging in a monolayer were detected in the cerebellum. Compared the results at different time points, the location of grafts were the same. The graft cells were less and the processes were longer over time. CONCLUSION: The in vitro cultured neurosphere cells can migrate into brain tissues and differentiate into site-specific neurons in shape after transplanting into the lateral ventricles of young rats. It is suggested that the host brain tissue microenvironment played an important role in guiding the graft differentiation into neurons. The results have an important significance for understanding cell replacement of developing brain disorders.

Objective Subcutaneous transplantation Lewis lung carcinoma model is commonly used in experimental studies.Researchers often choose different transplantation sites to create the models while little attention was paid on the effect of different inoculation sites on the formation of transplanted tumors.The aim of this study was to compare the effect of tumor cell inoculation at different sites on tumor formation in mice.Methods Lewis lung adenocarcinoma (ll2-luc-m38) cells stably expressing luciferase protein were subcutaneously injected into C57 BL/6 mice at the right armpit, right groin, or footpad, respectively.An IVIS spectrum in vivo imaging system was used to observe the tumor and metastasis formation.The survival time and mortality were recorded.H-E stained pathology was performed to examine the histological changes of the lung tissues and tumor metastesis.Results The tumor formation time was earlier in the armpit and groin groups, both with a tumor formation rate of 100%, while the tumors occurred later, with a tumor formation rate of 33% in the footpad group.The pulmonary metastasis rate was 70% in the groin group, 50% in the ampit group, and 0% in the footpad group, at the 21st day after inoculation.The footpad group had a high mortality.The tumors in the groin group and armpit group can be surgically resected, with a postoperative survival rate of 100%.Conclusions In this mouse model of subcutaneously transplanted Lewis adenocarcinoma, the groin and ampit groups have advantages such as a high tumor formation rate, good tolerance of tumor resection, low surgical mortality rate, easy to monitor, simple operation and high reproducibility.The axillary group has an even higher metastasis rate.

Cathepisn D plays a key role in early process of apoptosis before mitochondrion damage and caspases activations, and also involves in Alzheimer's disease (AD). Glycosaminoglycans (GAGs) have been suggested to inhibit the progress of apoptosis. Fucoidan, a nature GAGs mimetic, is shown as a potential candidate for neuroregressive disease. Here we reported PC12 cells response to oxidative stress with clear cathepsin D release, followed by caspase-3 activation. We found that fucoidan treatment can alleviate cathepsin D and caspase-3 activation, and improve cell survival. Furthermore, for the first time, fucoidan was shown to directly inhibit human liver cathepsin D by a dose-dependent way. These results support that cathepsin D involves in early apoptosis, suggest that fucoidan can decrease apoptosis at lysosome-cathepsin D level, which opens a new therapeutic approach to AD.
Alzheimer Disease ; drug therapy ; metabolism ; Animals ; Apoptosis ; drug effects ; Caspase 3 ; metabolism ; Caspase Inhibitors ; Cathepsin D ; antagonists & inhibitors ; metabolism ; Cell Line, Tumor ; Cell Survival ; drug effects ; Humans ; Hydrogen Peroxide ; metabolism ; Oxidative Stress ; drug effects ; PC12 Cells ; Polysaccharides ; pharmacology ; Rats

Objective To investigate whether chemokine CCL2(also known as monocyte chemotactic protein 1 or MCP-1)has a causal relationship with lung cancer.Methods Genetic data of chemokine CCL2 and different pathological subtypes of lung cancer were extracted from genome-wide association studies(GWAS),and inverse-variance weighted(IVW)analysis was used as main analysis,while weighted median,simple model,MR-Egger regression,and weighted model were chosen as supplementary analyses.Sensitivity analyses were performed to verify the reliability of the data.Results The result of IVW analysis on chemokine CCL2 to lung adenocarcinoma was OR = 1.065,95%CI(0.919～1.234),P = 0.401.The result of IVW analysis on chemokine CCL2 to squamous cell lung carcinoma was OR = 1.059,95%CI(0.931～1.205),P = 0.381.The result of IVW analysis on chemokine CCL2 to small cell lung carcinoma was OR = 0.959,95%CI(0.760～1.208),P = 0.720.Conclusions There is no direct causal relationship between chemokine CCL2 and lung cancer.

OBJECTIVEWuji pill is a prescription of traditional Chinese medicine(TCM) and was composed of Rhizoma Coptidis, Fructus Evodiae Rutaecarpae and Radix Paeoniae Alba. The aim of this research is to investigate the effects of Wuji pill compound with different compatibility on the levels of enzymic activity of cytochrome P450 CYP3A1/3A2 in rat liver microsomes in vitro, and to confirm the compatibility mechanism of Wuji pill from the point of relationships between compound prescription of TCM and metabolism.

METHODWith testosterone being a probe, the levels of enzymic activity of CYP3A1/3A2 were detected by HPLC, which were suppressed by Wuji pill with different compatibility in vitro.

RESULTThe IC50 of Rhizoma Coptidis, Fructus Evodiae Rutaecarpae, Radix Paeoniae Alba and 1"-9" of different level Wuji pill is: 38.96, 871.96, 15 519.17, 43.17, 60. 47, 276.12, 133.40, 118.08, 88. 47, 64. 36, 35. 13 and 39. 91 mg x L -', respectively. Rhizoma Coptidis and 1-9" of Wuji pill can suppress the enzymic activity of CYP3A1/3A2 significantly, and the capability of Rhizoma Coptidis in Wuji pill of action on CYP3A1/3A2 can be modified by different composition of Fructus Evodiae Rutaecarpae and Radix Paeoniae in Wuji pill, and there are statistical differences among the IC50 of 1#-9# of Wuji pill. While the ratio of Rhizoma Coptidis raises up in Wuji pill, Wuji pill may suppress the enzymic activity of CYP1A2 largely.

CONCLUSIONThe reason why Wuji pill with different compatibility has different pharmacodynamics and pharmacokinetics characteristics is likely to lie in the difference of the capability of Wuji pill with different compatibility on CYP3A1/3A2. [Key words] Wuji pill; CYP3A1/3A2; testosterone; HPLC; different compatibility prescription of traditional Chinese medi-cine

Animals ; Aryl Hydrocarbon Hydroxylases ; antagonists & inhibitors ; metabolism ; Coptis ; chemistry ; Cytochrome P-450 CYP3A ; Drug Compounding ; Drugs, Chinese Herbal ; adverse effects ; pharmacology ; Enzyme Inhibitors ; adverse effects ; pharmacology ; Evodia ; chemistry ; Inhibitory Concentration 50 ; Male ; Membrane Proteins ; antagonists & inhibitors ; metabolism ; Microsomes, Liver ; drug effects ; enzymology ; Paeonia ; chemistry ; Rats ; Rats, Wistar

In recent years， the incidence of pulmonary nodules has kept rising. To give full play to the advantages of traditional Chinese medicine （TCM） in the treatment of pulmonary nodules and identify the breakthrough points of integrating TCM with Western medicine， the China Association of Chinese Medicine organized medical experts in TCM and western medicine to carry out in-depth discussion regarding this disease. The discussion encompassed the modern medical advances， TCM theories of etiology and pathogenesis， the role and advantages of TCM in the whole course management of pulmonary nodules， contents and methods of research on pulmonary nodules， and science popularization work， aiming to provide a reference for clinical practice and scientific research. After discussion， the experts concluded that the occurrence of pulmonary nodules was rooted in the deficiency of the lung and spleen and triggered by phlegm dampness， blood stasis， and Qi stagnation. TCM can treat pulmonary nodules by controlling and reducing nodules， improving physical constitution， ameliorating multi-system nodular diseases， reducing anxiety and avoiding excessive diagnosis and treatment， and serving as an alternative for patients who are unwilling or unfit for surgical treatment. At present， the optimal diagnosis and treatment strategy for pulmonary nodules has not been formed， which needs to be further studied from multiple perspectives such as clinical epidemiology， biology， and evidence-based medicine. The primary task of current research is to find out the advantages， effective prescriptions， and target populations and determine the effective outcomes of TCM in the treatment of pulmonary nodules. At the same time， basic research should be carried out to explore the etiology and biological behaviors of pulmonary nodules. The expert consensus on the diagnosis and treatment of pulmonary nodules with integrated TCM and Western medicine needs to be continuously revised to guide clinicians to conduct standardized， scientific， and accurate effective diagnosis and treatment.