Objective To prepare a harmine hydrochloride liposome formulation with high encapsulation efficiency. Methods Preformulation investigation was carried out to obtain the drug physicochemical properties such as solubility and lgD in buffers of different pH value. Harmine hydrochloride was encapsulated into liposomes by active loading method. Encapsulation efficiency of liposomes was determined after the free drug was separated from liposome by ultrafiltration. The influence factors on the encapsulation efficiency including drug-lipid weight ratio, incubation temperature, pH value of external water phase were investigated. Results As the pH value increasing, the solubility of harmine hydrochloride was decreased, while the apparent oil-water distribution coefficient was increased. By active loading method, the encapsulation efficiency could be over 80% when the drug to lipid weight ratio was under 1∶5. The pH gradient between intervesicle and intravesicle obviously influenced the encapsulation efficiency, while incubation temperature had little effect on encapsulation efficiency. Conclusion Active loading is suitable for preparing harmine hydrochloride liposome with high encapsulation efficiency.

Objective\ To investigate the cardiovascular distribution of orphanin FQ (OFQ) and OFQ precursor mRNA in spontaneously hypertensive rat(SHR) and rabbit. Methods\ Reverse transcription polymerase chain reacrtion(RT PCR), and immunohistochemical method were used. Results\ The expression of OFQ precursor mRNA was detected from aorta, pulmonary artery, renal artery and vein of rat at a high level comparable with the amounts of brain, and a weak expression signal could also be observed in the atrium. The positive immunoreactive OFQ was detected in the tissues of aorta, atrium and renal of rabbit, as well as in smooth cells, endothelium and glomerulus. Conclusion\ These observations suggest that orphanin FQ might play a role in regulating the function of cardiovascular system and kidney, but the exact underlying mechanism needs further studying.

Objective: To observe the effect of tolvaptan on treating the patients with intractable heart failure (HF) combining hyponatremia for their clinical conditions and improvements. Methods: A total of 100 relevant patients treated in our hospital from 2014-01 to 2015-01 were studied. Based on conventional treatment as cardiac stimulant, dieresis and correction of electrolyte disturbance, the patients were randomly divided into 2 groups: Tolvaptan group, the patients received tolvaptan15 mg/d for 5 days and Control group, the patients had no tolvaptan administration.n=50 in each group. The improvement of clinical symptoms, changes of cardiac, renal functions and blood levels of electrolyte were compared between 2 groups after treatment. Results:① Compared with Control group, Tolvaptan group had significantly improved dyspnea, reduced lung moist rale and low limb edemaP<0.01; Tolvaptan group showed increased 24 h urine volume (2416.0±771.6 vs 1124.6±215.7) ml,P<0.01, decreased plasma levels of NT-proBNP (2678.04 ± 537.09) pg/ml vs (4051.34 ± 306.07) pg/ml,P<0.01 and increased blood levels of sodium (139.08 ± 6.18) mmol/L vs (129.44 ± 2.20) mmol/L,P<0.01. ②In Tolvaptan group, the above improvements were found in 38 patients, and with 1 day tolvaptan therapy, their blood nitrogen dropped from (10.39 ± 1.23) mmol/L to (7.28 ± 1.53) mmol/L,P<0.01; the other 12 patients had no such effect, and with 1 day tolvaptan therapy, their blood nitrogen elevated from (10.39±1.23) mmol/L to (13.38 ± 0.66) mmol/L,P<0.01. Conclusion: Tolvaptan could effectively improve clinical symptom and cardiac function in patients with intractable HF, it is helpful to increase blood sodium level; the efifcacy of tolvaptan might be evaluated by the changes of blood nitrogen at the early stage of treatment.

The causes of dizziness and vertigo were complex.The traditional diagnostic paradigm was based on symptom quality- what do you mean dizzy? According to this system,a patient with vertigo has a different list of possible causes than those who endorselightheadedness.The new diagnostic paradigm was based on their description of the timing,triggers of symptom strengthened the context of the vertigo medicine.More emergency physicians (EPs) lacked a significant knowledge regarding bedside examination and extensively convinced neuroimaging,resulting in misdiagnosis of serious causes such as stroke,unnecessary use of neuroimaging,and failure to institute specific treatment for many patients with inner ear causes of dizziness.This article focuses on how to use bedside physical examination to more accurately diagnose patients who present with acue dizziness,vertigo,or other similar vestiblar symptoms.This,in turn,could lead to lower rates of misdiagnosis,decrease utilization of expensive imaging studies,and increase in prompt,and correct treatments,thereby to improve patient outcomes.

Objective To investigate the risk factors of upper gastrointestinal injury induced by non-steroidal anti-inflammatory drugs (NSAIDs).Methods A total of 1032 patients which used NSAIDs was selected.Patients were divided into two groups based on the condition of dyspepsia,peptic ulcer or upper gastrointestinal bleeding:the adverse drug reaction group (331 cases) and the control group (701 cases).Data of two groups on clinical presentation,laboratory test,medication and treatment were analyzed.Risk factors for the adverse drug reaction were identified by multivariable Logistic regression.Results The two groups had significant difference in age ＞ 65 years old,Helicobacter pylori (Hp) infection,ulcer history,drug overdose,combination with glucocorticoid,addicted to tobacco and alcohol history,non-specific inhibitor of cyclooxygenase(COX)-2,combination with anticoagulant,concomitant chronic cardiopulmonary disease (P ＜ 0.05).Logistic regression analysis by backward elimination method revealed that following variables retained,such as combination with glucocorticoid (OR =3.104,95％ CI 1.936-4.695),Hp infection (OR =2.768,95％ CI 2.047-3.742),drug overdose (OR =2.411,95％ CI 1.683-3.453),ulcer history (OR =1.781,95％ CI 1.278-2.480),age ＞ 65 years old (OR =1.659,95％ CI 1.237-2.225),non-specific inhibitor of COX-2 (OR =1.470,95％ CI 1.103-2.133),addicted to tobacco and alcohol history (OR =1.459,95％ CI 1.032-2.064),concomitant chronic cardiopulmonary disease (OR =1.357,95％ CI 1.008-2.143),P＜0.05.Conclusion Combination with glucocorticoid,Hp infection,drug overdose,ulcer history,age ＞ 65 years old,non-specific inhibitor of COX-2,addicted to tobacco and alcohol history,concomitant chronic cardiopulmonary disease are risk factors of upper gastrointestinal injury induced bv NSAIDs.

Prednisolone-induced zebrafish osteoporosis model was used to explore the bone-strengthening effect of Jie-Gu-Tang (JGT). Zebrafish larvae of 5 days post fertilization (d.p.f.) were co-exposed with 25 μmol·L-1 pred-nisolone and a series of JGT solutions with a range of concentrations (0.025, 0.25, 2.5, 25 and 100 mg crude herb per liter). The 25 μmol·L-1 prednisolone was selected as the model group. Etidronate disodium (15 and 30 mg·mL-1) with 25 μmol·L-1 prednisolone was used as the positive group. And 0.5% DMSO was used as the vehicle control group. All groups were incubated in 24-well plates (28.5℃) until 10 d.p.f. Zebrafish skeleton at 10 d.p.f. was anes-thetized and fixed for staining with alizarin red. Quantitative analysis of the stained area was performed by microscop-ic inspection and digital imaging methods to reflect the amount of zebrafish head skeleton mineralization. The results showed that prednisolone group at 25 μmol·L-1 concentration can obviously decrease the staining area and the stain-ing optical density values when compared with the vehicle control group (0.5% DMSO). Compared with the model group, both etidronate disodium (15 and 30 mg·mL-1) and JGT (2.5, 25 and 100 mg crude herb per liter) can in-crease the mineralized matrix and integrated optical density (IOD) of zebrafish head skeleton significantly with dose-effect relationship. It was concluded that zebrafish osteoporosis model was successfully used in the evaluation on bone loss prevention and bone formation promotion of JGT, which provided basis for the reliability and reasonability of zebrafish model.

Aim To investigate the expression pattern of secretory clusterin ( sCLU) in lung tissues and plas-ma of rats with pulmonary arterial hypertension ( PAH) induced by monocrotaline ( MCT ) . Methods Thirty male SD rats were randomly divided into control group ( n=6 ) and MCT group ( n=24 ) , and were intraper-itoneally injected 60 mg·kg-1 MCT for MCT group or equal volume normal saline for control group. Real time PCR and Western blot were performed to investi-gate the expression pattern of sCLU mRNA and protein in rat lungs 1 ( n=6 ) , 2 ( n=6 ) , 3 ( n=6 ) and 4 (n=6) weeks after MCT injection, respectively. Im-munohitochemistry was performed to determine the lo-calization of sCLU in rat lungs. Enzyme linked immu-nosorbent assay was performed to detect the concentra-tion of sCLU in rat plasma. Results Expression of
sCLU mRNA and protein elevated significantly in time-dependent manners in rat lungs of MCT group, and sCLU mainly localized in the cytoplasma and extracel-lular matrix of cells in pulmonary arterioles. Further-more, sCLU plasma levels were significantly elevated with the progression of PAH and had positive correla-tions with pulmonary hemodynamic indices and right ventricular hypertrophic index. Conclusion sCLU was significantly elevated in MCT induced PAH rat lungs and plasma, and it may participate in the pulmo-nary vascular remodeling process. Moreover, plasma sCLU may be a potential biomarker for PAH.

Objective To evaluate the methods and predictive values of obstetric conjugata measured by ultrasound.Methods A total of 200 women at 37～42 week's gestation,delivering a singleton infant and having an ultrasound examination within three days before delivery were studied.The obstetric conjugata,fetal biparietal diameter(BPD),fetal clavicula were measured by ultrasound,and compared with the obstetric conjugata measured in operation,newborn BPD,and newborn clavicula.Results The parameters such as obstetric conjugata,BPD and clavicula had no significant difference between ultrasonic measurement and actual measurement.When the obstetric conjugata and BPD difference

OBJECTIVE:To study the cardiac and skeletal toxicity of retinoic acid (RA) in Danio rerio at early life stage. METHODS:Danio rerio embryos of 24 hours post fertilization(hpf)were used as toxicity model and were exposed under medium with various concentrations of RA(0.1,1,10,25,100 μmol/L). The morphology of embryos and larvae hearts were observed 24,48 h after exposed. LC50 was calculated. Danio rerio larvae of 4 days post fertilization (dpf) were used as skeletal deformity model and were exposed with a series of RA at various concentration(0.1,1,10,25,50μmol/L). They were sacrificed 5 d later, and then Danio rerio skeleton were fixed for staining with alizarin red. The microscopic was used to observe the difference of stained skeleton area. RESULTS:RA caused significant adverse effects on hatching capabilities of Danio rerio embryos,and the ob-vious malformation features were produced during the culture process. 1-100 μmol/L RA could cause heart malformation in Danio rerio embryos and larvae,and the main heart malformation characteristics included heart linearization,pericardial edema,yolksa-cedema,hemocytes accumulation incardiac region. 100 μmol/L RA could inhibit the hatching capabilities of Danio rerio embryos, and caused lethal effects on embryos and larvae. The LC50 were 36.44,23.69 μmol/L after exposed for 24,48 h. 0.1-50 μmol/L RA induced vertebral column sclerotization of Danio rerio embryos and larvae in advance,which was positively associated with the con-centration of RA. CONCLUSIONS:RA can cause cardiac and skeletal toxicity in Danio rerio embryo and larvae,which is positive-ly associated with the concentration of RA.

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.