OBJECTIVE:To optimize the formulation of indomethacin-loading solid lipid nanoparticle(SLN). METHODS:Us-ing indomethacin as model drug,glyceryl behenate as oil phase,poloxamer 188 and polyethylene glycol-12-hydroxystearic acid as emulsifier,with turbidity,entrapment efficiency and drug loading amount as index,Box-Behnken response surface methodology was used to optimize the amount of oil phase,emulsifier-oil phase ratio,drug-oil phase ratio. The physicochemical properties of SLNs were characterized by SEM and DSC. RESULTS:The optimal formulation was as follows as oil phase of 0.91%,emulsifier-oil ratio of 1∶1,drug-oil phase ratio of 1∶5. The turbidity,entrapment efficiency and drug loading amount of prepared nanoparticle were 1 025-1 030 NTU,98.94%-99.08%,2.43%-2.46%,respectively;particle size and polydispersity index(PDI)were 181.5-182.3 nm and 0.340-0.341(n=3). The results of DSC showed that indomethacin was not present in crystalline state dispersed into SLNs. CONCLUSIONS:The optimal formulation is screened successfully,and indomethacin-loaded SLNs have been prepared.

In this study, daphnetin and its major metabolites in the intestinal wall of rats were identified by liquid chromatography and quatrupole-time of flight mass spectrometry. Perfusion fluid of duodenum, jejunum, ileum and colon were collected separately for 2 hours from the rat intestine following perfusion with daphnetin. The metabolites of daphnetin in the perfusion fluid of different intestine segments were analyzed by the liquid chromatography and quatrupole-time of flight mass spectrometry. It is shown that the parent drug daphnetin and four metabolites were found in the perfusion fluid of duodenum, jejunum and ileum. However, no metabolites were found in the colon. Among the four metabolites, two daphnetin sulfates (m/z 257) were first discovered as the phase II metabolites of daphnetin in rats, which revealed a new way of daphnetin metabolism in rats.
Animals ; Chromatography, High Pressure Liquid ; Colon ; metabolism ; Duodenum ; metabolism ; Ileum ; metabolism ; Intestines ; metabolism ; Jejunum ; metabolism ; Male ; Perfusion ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Spectrometry, Mass, Electrospray Ionization ; Umbelliferones ; metabolism ; pharmacokinetics

OBJECTIVETo study the anti-inflammatory effect of resveratrol in primary cortical astrocyte cultures stimulated by lipopolysaccharide (LPS) and explore the underlying mechanism of this protective effect.

METHODSThe astrocytes were cultured in the presence of resveratrol at different concentrations for 12 h followed by stimulation with lipopolysaccharide (LPS) for another 24 h. Lactate dehydrogenas (LDH) leakage volumes were detected, the cytotoxicity of resveratrol was examined using cell counting kit-8 (CCK-8), the release of NO was measured by Griess reaction, and the expression levels of TNF-α and iNOS were measured using ELISA and Western blotting respectively.

RESULTSThe purity of the astrocytes cultured in vitro was (95.49∓1.86)%. LPS treatment increased LDH leakage and reduced the survival rate of the astrocytes, resulting also in significantly increased NO and TNF-α release and iNOS protein expressions. Within the concentration range of 5-50 µmol/L, resveratrol effectively improved the survival rate of the astrocytes and decreased LDH leakage with a dose-response relationship. Only 25 and 50 µmol/L resveratrol produced obvious inhibitory effect on NO and TNF-α release and iNOS expression, while 5 µmol/L resveratrol had no such effects.

CONCLUSIONHigh concentration of resveratrol can inhibit the release of inflammatory mediators and improve the inflammation injury induced by LPS in astrocytes, the mechanism of which may involve the inhibition of iNOS/NO expression pathway.

Animals ; Animals, Newborn ; Anti-Inflammatory Agents, Non-Steroidal ; pharmacology ; Astrocytes ; cytology ; Cerebral Cortex ; cytology ; Inflammation ; chemically induced ; Lipopolysaccharides ; Nitric Oxide ; metabolism ; Nitric Oxide Synthase Type II ; metabolism ; Primary Cell Culture ; Rats ; Rats, Sprague-Dawley ; Stilbenes ; pharmacology ; Tumor Necrosis Factor-alpha ; metabolism

OBJECTIVETo ascertain whether mouse c-Kit(+)Lin- bone marrow cells have the potential of hepatic stem cells.

METHODSc-Kit(+)lin- bone marrow cells were isolated and purified by magnetic-activated cell sorting (MACS) from BALB/C male donor mice, and immediately transplanted into age-matched BALB/C syngeneic female mice with 35-Gy total liver irradiation. The recipients were sacrificed 1 month after the transplantation for pathological observation of the liver morphology. The presence of Y-chromosome was examined in the liver cells of the recipient by in situ hybridization (ISH), and alpha-fetoprotein (AFP) and albumin in the cells were detected by immunohistochemistry.

RESULTSThe hepatocytes positive for Sry gene on Y-chromosome were identified 1 month after transplantation, and immunohistochemistry for AFP and albumin confirmed that the donor mice-derived cells were hepatocytes.

CONCLUSIONc-Kit(+)lin- bone marrow cells have the potential of hepatic stem cells, which can reside and differentiate into hepatocytes in the liver after transplantation. c-Kit(+)lin- bone marrow cells can be used as the source cells of cell transplantation for liver disease.

Animals ; Bone Marrow Transplantation ; methods ; Cell Differentiation ; Female ; Hepatocytes ; cytology ; metabolism ; Immunohistochemistry ; Male ; Mice ; Mice, Inbred BALB C ; Multipotent Stem Cells ; metabolism ; transplantation ; Proto-Oncogene Proteins c-kit ; metabolism ; Random Allocation ; Whole-Body Irradiation ; alpha-Fetoproteins ; metabolism

Objective To explore the endoscopic characteristics of multidrug-resistant tuberculosis (MDR-TB) combined with tracheobronchial tuberculosis (TBTB). Methods 248 MDR-TB as study group, they hospitalized from October 1st 2008 to June 31st, 2016. 274 cases of non MDR-TB with bacteria positive as control group over 2015, all of them received bronchoscopy, sputum cultured and drug sensitivity tested of Isoniazid and Rifampicin. We analyzed the results of bronchoscopy and demographic data. Results 248 cases of MDR-TB patients, of 175 (70.56%) were diagnosed TBTB by bronchoscopy, of 73 (29.44%) without TBTB. 274 cases of non MDR-TB with bacteria positive patients, of 146 (53.28%) were diagnosed TBTB, of 128 (46.72%) non TBTB, the difference of comparisons was statistically significant (χ2 = 16.42, P = 0.000). MDR-TB combined with TBTB median age was 32 years, non MDR-TB combined with TBTB median age 42 years, the difference was statistically significant (U = 9932.00, P = 0.001). Among the MDR-TB patients, of 75 (42.86%) TBTB in the upper right bronchial, of71 (40.57%) upper left bronchus, while non MDR-TB patients, of 70 (47.95%) and 60 (41.10%), there was no statistically significant difference (χ2 = 2.44, P = 0.786). Among the MDR-TB, of 76 (43.43%) were inflammation infiltration type, of 11 (6.29%) were necrosis type, of 13 cases (7.43%) granulation proliferative type, of 72 (41.14%) were scar stricture type, of 3 (1.71%) tube wall softening type. Among the non MDR-TB, in turn, TBTB type were 50 (34.25%), 41 (28.08%), 9 (6.16%), 40 (27.40%), 5 (3.43%), the difference were statistically significant (χ2 = 30.50, P = 0.000). Conclusions The detection rate of TBTB was higher in MDR-TB patients, that common occur in younger patients. TBTB common infringe on upper right bronchial and upper left bronchus, TBTB type most are inflammatory infiltration type and scar stricture type. More attention should be paid to bronchoscopy among MDR-TB patients.

Objective To survey the prevalence rates of adult carotid atherosclerosis in water-sourceoriginated high iodine area in Shandong province in 2008 and discuss the relationship between water-sourceoriginated high iodine and carotid atherosclerosis occurrence. Methods Yuncheng county was chosen as observation area which included Dachenlou, Weigai, Liuyi and Ershilipu villages. Juye county was chosen as control that included Zhangxi, Bihainan, Xiaguan and Qiji villages. Two hundred and ninety-nine participants aged over 40 from water-source-originated high iodine areas and 323 residents aged over 40 from normal iodine areas were investigated.Portable-type B mode color Doppler was performed to examine the carotid artery of all participants. The adult carotid atherosclerosis was diagnosed and graded through the ultrasonograms. Results The prevalence rates of adult carotid atherosclerosis in the 4 water-source-originated high iodine villages of Dachenlou, Weigai, Liuyi and Ershilipu were 47.1% (33/70) ,62.2% (51/82) ,67.5% (52/77) and 58.6% (41/70), respectively and the prevalence rates of adult carotid atherosclerosis in the 4 normal iodine villages of Zhangxi, Bihainan, Xiaguan and Qiji were 40.7%(35/86),40.8% (31/76),38.2% (34/89) and 37.5% (27/72), respectively. The prevalence rates of adult carotid atherosclerosis standardized by age in the 4 high iodine villages and the 4 normal iodine villages were 45.81% ,58.18% ,61.63%,55.34% and 34.66%,36.25%,43.01% ,41.30%, respectively. The prevalence rates were higher in high iodine villages than that in control villages(T = 26, P ＜ 0.05 ). There were 136 people scored "0", 120 people scored "1 -3",43 people scored "4 - 7", and total 299 people. There were 201 people scored "0", 87 people scored "1 - 3", 35 people scored "4 - 7", and total 323 people. The expected prevalence rates and severity of adult carotid atherosclerosis was significantly different between high iodine area and normal iodine area (x2 = 17.54,18.42, all P ＜ 0.01).Conclusion The prevalence rate and severity of adult atherosclerosis in water-source-originatod high iodine area is higher than that in normal iodine area.

Objective To observe the prevalence and distribution of ideal cardiovascular health behavior.Methods Health examination data between 2008 to 2009 from the employees of Kailuan Group were analyzed.Results A total of 101 333 subjects took part in the health examination,subjects with previous myocardial infarction(n =871),stroke(n =2255),myocardial infarction and stroke(n =162)and subjects with incomplete examination data(n =9311)were excluded and 88 534 subjects were included for final analysis[mean age(50.6 ± 12.3)years,male 69 916].(1)Body mass index(B MI),systolic and diastolic pressure,cholesterol(TC)and triglyceride were significantly higher in males than in females (all P ＜0.05),women's income and the education lever were significantly higher than men(P ＜ 0.05).(2)The distribution of ideal cardiovascular health behavior(smoking,BMI,physical exercise,salt intake)was 55.8％,41.4％,18.9％ and 14.0％ respectively among the population; the ideal cardiovascular factors(fasting blood glucose,TC,blood pressure)was 80.9％,61.8％ and 18.5％,respectively.(3)The subjects with distribution of seven,six,five,four ideal cardiovascular health behavior and factors was 0.1％,1.9％,9.1％,20.3％,respectively.(4)Multiple logistic regression analysis showed that female,age ＜ 55 and high education level were associated with the ideal cardiovascular health status with a RR value (95 ％ CI)of 4.52(4.32-4.72),1.46(1.39-1.53)and 2.23(2.10-2.37),respectively.Conclusion The prevalence of ideal cardiovascular health is extremely low in the study population,most persons were notin the ideal cardiovascular health behavior and factors and female,age ＜ 55 and high education level arelinked with ideal cardiovascular health status.

Objective:To summarize the surgical treatment result in patients with anomalous left coronary artery from pulmonary artery (ALCAPA) combining severe left ventricular dysfunction.Methods:A total of 24 ALCAPA patients combining severe left ventricular dysfunction received coronary reimplantation in our hospital from 2009-02 to 2016-04 were retrospectively studied.The patients' mean age was 7.0 (5.0,17.8)months including 13 male;mean left ventricular ejection fraction (LVEF)＜30％ and the median pre-operative LVEF was 21.0％ (17.3％,26.5％).Results:There were 2/24 (8.3％) in-hospital death,The median cardiopulmonary bypass time was 109 (95,128) min,aorta cross-clamp time 65 (48,87) min,mechanical ventilation time 94.5 (48.3,165.5) h and ICU stay time 176.5 (101.0,305.3) h;2 patients received ECMO support and weaned off successfully and 2 patients received re-intubation.In 22 survival patients,the median discharge LVEF was 26.0％ (20％,35％) which was similar to pre-operative condition,P＞0.05.The mean follow-up time was (15.3±14.9) months at the longest of 63 months,no re-admission,reoperation and death occurred.The patients had NYHA I and the last follow-up LVEF was 60％ (50％,69％) which was increased than discharge level,P＜0.05,4 patients had LVEF＜50％.Conclusion:Surgical treatment had satisfactory short-and mid-term outcomes in ALCAPA patients combining severe left ventricular dysfunction;comprehensive effort should be emphasized in surgery,anesthesia,cardiopulmonary bypass and ICU management at peri-operative period.

Central neurocytomas (CNs), initially asymptomatic, sometimes become huge before detection. We described and analyzed the clinical, radiological, operational and outcome data of 13 cases of huge intraventricular CNs, and discussed the treatment strategies in this study. All huge CNs (n=13) in our study were located in bilateral lateral ventricle with diameter ≥5.0 cm and had a broad-based attachment to at least one side of the ventricle wall. All patients received craniotomy to remove the tumor through transcallosal or transcortical approach and CNs were of typical histologic and immunohistochemical features. Adjuvant therapies including conventional radiation therapy (RT) or gamma knife radiosurgery (GKRS) were also performed postoperatively. Transcallosal and transcortical approaches were used in 8 and 5 patients, respectively. Two patients died within one month after operation and 3 patients with gross total resection (GTR) were additionally given a decompressive craniectomy (DC) and/or ventriculoperitoneal shunt (VPS) as the salvage therapy. Six patients received GTR(+RT) and 7 patients received subtotal resection (STR)(+GKRS). Eight patients suffered serious complications such as hydrocephalus, paralysis and seizure after operation, and patients who underwent GTR showed worse functional outcome [less Karnofsky performance scale (KPS) scores] than those having STR(+GKRS) during the follow-up period. The clinical outcome of huge CNs seemed not to be favorable as that described in previous reports. Surgical resection for huge CNs should be meticulously considered to guarantee the maximum safety. Better results were achieved in STR(+GKRS) compared with GTR(+RT) for huge CNs, suggesting that STR(+GKRS) may be a better treatment choice. The recurrent or residual tumor can be treated with GKRS effectively.
Antineoplastic Agents ; therapeutic use ; Combined Modality Therapy ; Humans ; Neurocytoma ; therapy ; Radiotherapy ; Surgical Procedures, Operative

Objective Throush identify biochemical characteristics and virulence factors of 2 strains suspected Yersinia pestis(Y.pestis)isolated from the dead Marmota himalayana(M.himalayana)to confirm the nature epidemic focus in Dege County,Sichuan Province.Methods Y.pestis was analyzed by specific staining and shape,culturing characteristics,splitting-test by bacteriophage,test of biochemical characteristics and glycolysis ability,virulence factors,virulence,nutritional requirement,plasmid,genetic test and genetic type. Results The tested strains were Gram staining bacilus.The main biochemical characteristics were Arabinose(+)、 Rhamnose(-),Maltose(+),Melibiose(-),Glycerol(+),Denitrification(+).The virulence factors with FI+.VW+, Pgm+,Pst I+;and with the common 6.0×106,45.0×106,65.0×106 plasmids,also with the virulence-relative plasmid gene.Both their absolutely lethal dose(LD100)in mice were 50 bacteria.The nutritional requirement appeared which were depended on Phenylalanine and Methionine.With the Genomovar 5 genotype characteristics of M.himalayana plague foci of Qinghai-Tibet plateau.The difference between tested strains and Yersinia pseudotubercuosis on the 3 different culture medium was obvious.The tested strains had a Y.pestis' specific 3a fragment,Pst I and FI-Ag,at 22 ℃,the strains could be split by bacteriophage completely.Conclusions According to the diagnostic criteria of plague in China,the 2 suspected strains isolated from Dege County,Sichuan Province ale confirmed as Y.pestis.both with powerful virulenceand with the characteristics of the Y.pestis of M.himahtyana in Qinghai-Tibet plateau plague natural focus.