Zebrafish was selected as model animal, and glucocorticoid dexamethasone was used as a model compound to establish a rapid and high efficient osteopenia model. Zebrafish larvae at 4 days post fertilization (dpf) were exposed to a serial concentrations of dexamethasone solutions, and 0.5% DMSO was selected as the vehicle control group. All groups were incubated in 24-well plates (28.5 degrees C) until 9 dpf. In addition, effects of 10 micromol x L(-1) dexamethasone on preventing against osteopenia induced by etidronate disodium were also investigated. Zebrafish bones at 9 dpf were stained with alizarin red. Quantitative analysis of the stained area was performed by microscopic inspection and digital imaging methods to reflect the amount of bone mineralization. Results showed that dexamethasone group at 2.5, 10 and 25 micromol x L(-1) can decrease the staining area and the staining optical density values of zebrafish head bones when compared with the vehicle control group (0.5% DMSO), which suggested that dexamethasone can significantly reduce the zebrafish mineralized bone and the bone mineral density. Results also showed that 15 and 30 microg x mL(-1) etidronate disodium can increase the mineralized matrix of zebrafish head bone and prevent against osteopenia induced by dexamethasone. In conclusion, the study indicated that zebrafish can be an idea osteopenia model induced by dexamethasone.

OBJECTIVE:To evaluate the bioequiavailability of the domestic and the imported paracetamol and oxycodone tablets.METHODS:The blood concentrations of paracetamol and oxycodone in22healthy male volunteers were determined by HPLC-MS after a single dose orally1tablet of domestic or imported oxycodone tablet by a randomized crossover way.RE?SULTS:The main pharmacokinetic parameters of the domestic and the imported oxycodone tablets were as follows:C max were(10.4?2.2),(11.1?3.3)?g/L,respectively;t max were(1.05?0.35),(0.92?0.40)h,respectively;t 1/2 ke were(5.36?0.91),(5.53?1.25)h,respectively;AUC 0～t were(44.2?7.9),(44.5?8.3)(?g?h)/L,respectively;AUC 0～∞ were(49.3?9.4),(51.0?11.6)(?g?h)/L,respectively;the relative bioavailability of the domestic preparation was(102.8?27.4)%.The main pharmacokinetic parameters of the domestic and the imported paracetamol were the following:C max were(4612?696),(4592?825)?g/L,respectively;t max were(0.94?0.28),(0.96?0.23)h,respectively;t 1/2 ke were(3.99?0.77),(4.05?0.83)h,re?spectively;AUC 0～t were(15732?3450),(16265?3858)(?g?h)/L,respectively;AUC 0～∞ were(16618?3545),(17205?4194)(?g?h)/L,respectively;the relative bioavailability of the domestic one was(97.6?10.3)%.CONCLUSIONS:The2preparations are bioequivalent.

Objective To investigate the differences of protein and mRNA expression of matrix metalloproteinase 9 (MMP-9) in osteoclasts (OC) and osteoclast-like cells (OLC) obtained by mechanical and inducement methods. Methods Mechanical separation method was used to separate mature osteoclasts from long bones of SD rats aged one-day;and inducement culture method was applied to induce OLC by using RANKL (100 ng/mL) and M-CSF (100 ng/mL) . The protein expression of MMP-9 was measured by immunocytochemistry and mRNA expression of MMP-9 was assayed by in situ hybridization. Results The integral optical density (IOD) and average optical density (AOD) of positive cells in the visual field were higher in the 12-d group of inducement method as compared with the 3 d-group of mechanical method. Conclusions It is suggested that the protein and mRNA expression of MMP-9 in OLC obtained by 12 d inducement method is much high than in OC obtained by 3 d mechanical method. OLC obtained by inducement method can be applied in the study of osteoporosis.

Objective To evaluate clinical features,therapeutic effects and outcomes of patients with non-human immunodeficiency virus(HIV)-infected cryptococcal meningitis treated with fluconazole or fluconazole and flucytosine.Methods Twenty-four cases of non-HIV-infected cryptococcal meningitis(fluconazole with or without flucytosine as initial therapy)in Huashan Hospital,Fudan University from 1997 to 2007 were retrospectively reviewed.Clinical manifestations,therapeutic effects and outcomes of the patients were collected.Results Fluconazole was administered with median dosage of 400 mg/d,for a median duration of 20.5 days.After fluconazole initial therapy for 2 weeks,16.7% showed partial response,83.3% showed no response,and the overall response rate was 16.7%.After 10 weeks,33.3% showed partial response,29.2% showed complete response,16.7% showed no response,and the overall response rate was 62.5%.Mortality at week 10 was 20.8%.Twenty-two patients who failed to respond to initial therapy were switched to other antifungal drugs(amphotericin B,amphotericin B colloidal dispersion,itraconazole)or other fluconazole containing combined therapy.Eleven out of the 24 patients died during one-year follow-up,8 of whom died of eryptococcal meningitis,and 3 died of other diseases.Conclusions The initial therapy of fluconazole with or without flucytosine is inefficient,and most of the patients need other antifungal drugs because of initial therapy failure.Therefore,fluconazole might not be appropriate for initial therapy in non-HIV-infected cryptococcal meningitis.

Objective To establish a LC-MS-MS method for determining febuxostate in human plasma .Methods Febuxostate added into blank plasma was sedimented by acetonitrile , and the supernatant was determined by LC-MS-MS.Analytical column was Thermo Biobasic-8,5 μm,50 mm ×2.1 mm(ID).The mobile phase consisted of acetonitrile-10 mmol/L ammonium acetate (0.05%acid=70:30 at a flow rate of 0.2 ml/min.Mass spectrum conditions:ESI-was performed in the SRM mode using target ions m/z 315→271 (10 eV)(febuxostate), m/z 360→274 (18 eV)(bezafibrate), SP 3 500 kV, SGP 10 Arb, AGP45 Arb, TEM 270℃.Results The calibration curve was linear over the range of 10-8 000 μg/L.The LLOQ of Febuxostate in plasma was 10 μg/L.The extracted recovery was >85%.The intra-and inter-day RSD were <15%.Conclusion The method was sensitive , simple and accurate to deter-minate febuxostate plasma concentration and to study pharmacokinetics of febuxostate .

Objective To evaluate the effect of oxycodone on function of GABAA receptors in dor-sal root ganglion ( DRG ) neurons of rats with neuropathic pain ( NP ) . Methods Thirty-six adult male Sprague-Dawley rats, weighing 180-220 g, aged 10 weeks, were allocated into 3 groups ( n=12 each) u-sing a random number table method: sham operation group ( group S ) , group NP and oxycodone group ( group O) . The sciatic nerve was only isolated but not ligated in group S. NP was induced by chronic con-striction injury. The sciatic nerve was exposed and 4 loose ligatures were placed on the sciatic nerve at 1 mm intervals with 4-0 chromic catgut. Oxycodone 15μg∕kg was intraperitoneally injected once a day for 14 con-secutive days from ligating the sciatic nerve to satisfaction in group O. The thermal paw withdrawal latency( TWL) was measured at 1 day before establishing the model ( T0 ) and 3, 5, 7, 10 and 14 days after es-tablishing the model ( T1-5 ) . The rats were sacrificed after measurement of pain threshold at T5 , and DRG neurons were acutely isolated for recording the amplitude of GABAA receptors-activated currents using whole-cell patch-clamp technique. Results Compared with group S, the TWL was significantly shortened at T1-5, and the amplitude of GABAA receptors-activated currents in DRG neurons was decreased in NP and O groups (P<0. 05). Compared with group NP, the TWL was significantly prolonged at T1-5, and the ampli-tude of GABAA receptors-activated currents in DRG neurons was increased in group O ( P<0. 05) . Conclu-sion Oxycodone can enhance the function of GABAA receptors-activated currents in DRG neurons and thus enhance GABAA receptors-mediated presynaptic inhibition, which may be related to the mechanism of oxyc-odone-induced reduction of NP in rats.

The causes of primary adrenal insufficiency(PAI) are varying, however, anti-phospholipid syndrome (APS) is a relatively rare one. PAI lacks unique clinical manifestations, so the confirmation of PAI was easily to be neglected by physicians. We report a case with abdominal pain as the first complaint, followed by multiple infections, thrombotic events, and aggravating fatigue. Through a series of the laboratory examination, medical imaging, and pathology examination, this patient was diagnosed as PAI caused by APS. Combining this report with literature review, we aim to raise awareness of the disease and avoid misdiagnosis and missed diagnosis.

Objective:To verify the protective effect of terazosin on cognitive function of rats after whole-brain irradiation (WBI) and to investigate its mechanism.Methods:A total of 64 1-month-old male SD rats were randomly divided into the untreated control group, terazosin group, irradiation group and irradiation plus terazosin group (combination group). WBI was administered at a single dose of 20 Gy in the irradiation and combination groups. The open field test and the Morris water maze (MWM) test were used to evaluate the effect of terazosin on cognitive function after WBI.Starting from the three aspects of juvenile neuron apoptosis, neurogenesis disorderand microglia activation, the possible cellular mechanism wasassayed by double-label immunofluorescence staining for BrdU (bromodeoxyuridine) / NeuN, DCX(Doublecortin) / Caspase-3 and single-label immunofluorescence staining for Iba-1 (ionized calcium binding adaptor molecule-1).Results:Terazosin intervention improved the short-term memory retention of irradiated rats ( P=0.032). After terazosin treatment, the number of DCX + cells in the combination groupwas increased by approximately 35% compared with that in the irradiation group ( P=0.038). The number of BrdU +/NeuN + cells in the combination group was increased by approximately 15% than that in the irradiation group ( P>0.05). The number of Iba-1 + cells in the irradiation plus terazosin group was decreased by 49% compared with that in the irradiation group ( P=0.036). Conclusion:Terazosin may reduce the hippocampal juvenile neuron loss and inhibit neuroinflammation via microglia activation, which can alleviate WBI-induced cognitive dysfunction to a certain extent.

Autoimmune diseases (ADs) are due to the lack ofautoantigen immune tolerance and they are chronic and heterogeneous conditions that affect specific target organs or multiple organ systems.Polyautoimmunity (PA) is defined as the presence of more than one AD in a single patient.It provides a major clinical evidence for autoimmune tautology and emphasizes that different immune phenotypes can coexist in the same individual (i.e.,individual carries a unique genotype).When three or more ADs coexist,this condition is called multiple autoimmune syndrome (MAS).This article will make a summary about the pathogenesis of autoimmune diseases and PA and MAS in several common clinical autoimmune diseases in order to help clinical work and further research.

Chronic obstructive pulmonary disease (COPD) is a heterogeneous lung condition characterized by persistent airflow obstruction caused by long-term airway inflammation or alveolar abnormalities, often manifested as chronic respiratory symptoms and decreased lung function. In recent years, experimental research has shown that mesenchymal stem cells (MSC) have anti-inflammatory, immunomodulatory, and repairing properties of lung epithelial cells, which can be used to treat various diseases including COPD. This article is mainly based on the main findings of in vitro and in vivo animal model experiments and clinical studies of MSC treatment for COPD. It summarizes and discusses the possible mechanisms of action of MSC as a new therapy, and provides new ideas for clinical treatment of COPD.